Evaluating Orphan Drugs: Discussion (Resumed)

The purpose of this morning's meeting is to consider the implementation of the recommendations in the committee's report on evaluating orphan drugs, which was published last February. We will hold two sessions on the topic. The first session will involve Rare Diseases Ireland, which is the umbrella body for patients with rare diseases and will present to the committee first. The second session will be with officials from the Department of Health and representatives from the HSE and the National Centre for Pharmacoeconomics.

On behalf of the committee, I welcome Mr. Philip Watt, chair of the Rare Disease Taskforce and CEO of Cystic Fibrosis Ireland; Ms Vicky McGrath, interim CEO of Rare Diseases Ireland; and Dr. Derick Mitchell, CEO of the Irish Platform for Patients, Organisations, Science and Industry.

I draw the attention of witnesses to the fact that by virtue of section 17(2)(l) of the Defamation Act 2009, witnesses are protected by absolute privilege in respect of their evidence to the committee. However, if they are directed by the committee to cease giving evidence on a particular matter and they continue to so do, they are entitled thereafter only to a qualified privilege in respect of their evidence. They are directed that only evidence connected with the subject matter of these proceedings is to be given and they are asked to respect the parliamentary practice to the effect that, where possible, they should not criticise or make charges against any person, persons or entity by name or in such a way as to make him, her or it identifiable. I advise witnesses that any opening statements made to the committee may be published on the committee website after the meeting.

Members are reminded of the long-standing parliamentary practice to the effect that they should not comment on, criticise or make charges against a person outside the House or an official either by name or in such a way as to make him or her identifiable. I invite Ms McGrath to make her opening statement.

Ms Vicky McGrath

My name is Vicky McGrath and I am interim CEO of Rare Diseases Ireland. We are the national alliance for voluntary patient-led organisations for people affected or at risk of developing rare diseases in Ireland. We are committed to the identification, treatment and cure of rare diseases. Today, I am joined by Mr. Philip Watt, chair of the Rare Disease Taskforce and the Medical Research Charities Group and CEO of Cystic Fibrosis and Dr. Derick Mitchell, CEO of the Irish Platform for Patients, Organisations, Science and Industry.

Orphan drugs are defined as medicines that prevent or treat rare diseases. There are an estimated 6,000 to 8,000 rare diseases that we know of with more being described. Collectively, rare diseases may affect up to 8% of the population. It is estimated that rare diseases affect 300,000 people in Ireland during their lifetime. Rare diseases have a significant impact on our citizens and an associated economic impact on our society. A recent survey across Europe revealed that more than 70% of people living with rare diseases have difficulties with daily activities, motor and sensorial functions and social interaction. A total of 30% of carers spend more than six hours per day on illness-related tasks. Over 95% of primary carers are family members with the vast majority being women. A total of 70% of patients and carers had to reduce or stop their professional activity due to the disease. There is a significant mental health burden with rare disease patients and carers being three times more likely to feel depressed compared to the general population.

Orphan drugs provide an opportunity to improve lives considerably or even cure disease. During 2017, the members of this committee met with two Irish rare disease patient organisations - the Alpha One Foundation and Muscular Dystrophy Ireland. During these meetings, members heard about the challenges facing these organisations' patient communities around access to novel and life-saving orphan drugs. These medicines have been found by regulators to be both safe and effective and have been approved for reimbursement by many of our peers across Europe yet they are still not available in this country. Over the intervening 12 months, the committee has, no doubt, encountered many other patients and patient groups with similar stories. Access to life-saving and curative therapies in this country is lagging behind that of our neighbours. This situation must change. The reimbursement system in Ireland continues to fail the patients it is supposed to serve. We must take an innovative approach to reimbursement and design a system that is fit for purpose - a system that is not only suited to so-called "common" diseases but also addresses the needs of rare disease patients. Such a system will ensure that all members of our society can contribute maximally.

There are no comparative therapies for most rare diseases. In most instances, the patient will not transition from one therapy to a better one. Orphan drugs constitute the only game in town and provide the best opportunity to slow disease progression and improved quality of life. As with cancer patients, we are seeking to avail of the best therapies today in the hope of being in a position to avail of new and better therapies in the future. Many rare disease patients are not being afforded this chance at a better and longer life. We must build a reimbursement system that provides that bridge to the next therapy. We must have a system that is robust enough to address challenging decisions. We know curative gene therapies are on their way. These transformative therapies will be expensive.

We all want value for money but how does one define value when one considers the ability of an individual to walk unaided rather than being wheelchair bound for decades or the child who will have have his or her vision restored and can thus integrate normally into classroom life? What type of society do we wish to have ten years hence? Today we are on the cusp of a step change when it comes to rare disease patient care. Access to the European reference networks as a result of the EU's cross-border directive will allow rare disease patients in Ireland access to the best clinical minds across Europe. Our care will be on a par with that of rare disease patients throughout Europe. Our care pathways will be best in class and we will be provided with opportunities to enrol in clinical trials. Innovation will be at the heart of our care. However, if the reimbursement system in Ireland does not change we will fail at the final hurdle and continue to be denied the therapies we need.

We acknowledge that progress has been made over the past 12 months, but it is very slow and just too late for many patients. In recent weeks the rare disease technology review committee began its work. Patients finally have the opportunity to provide real world experience of living with a condition and the impact that a particular drug may have on quality of life for both the patient and his or her carers. We are not there to give a sob story but as experts on our diseases. More significantly, patients are often members of the committee and we finally have a seat at the table as equals. We are no longer viewed simply as stakeholders. We are decision makers within the committee and have an equal say in the recommendations that the committee will provide to the HSE leadership, where the ultimate decision around reimbursement lies.

We understand that these are very early days for the technology review committee and we caution that more time is required to bed down the processes and learn from experience. Nonetheless it has finally been recognised that patients have a valuable contribution to make to the discourse and decision making process. To build on this we seek a seat at all stages of the process, be it horizon scanning, the pre-submission consultation or the HSE's decision making meetings. We have a growing cohort of educated patients who understand the process and the decisions involved. If we do not have a seat at the table, are we just on the menu? We have no interest in recommending treatments that do not work. We do not wish to take medicines that will not work and we do not want to waste money. We believe that innovative approaches to reimbursement decisions are required. Payments based upon defined clinical outcomes, so-called pay for performance, or guaranteed access to future improved therapies should be the norm, not the outlier.

Another development in recent months is Ireland joining the BeNeLuxA initiative, which aims to ensure timely access to, and affordability of, innovative medicines. Disappointingly, since the Minister for Health signed the agreement five months ago there has been no evidence that we have made any progress.

Finally, orphan drugs are at the cutting edge of medicine. We are moving into the realm of personalised or precision medicine. Orphan drugs should only be provided to those who will benefit from them. They are not designed for the wider community or even for every patient who might have a particular rare disease. A genetic diagnosis will be required for many orphan drugs that will come onto the market. Genetic services, by which I mean consultant geneticists, genetic counsellors and genetic testing facilities, fall far short of what we need in Ireland. Waiting lists are growing by the day. Current services are under-resourced and overwhelmed. We must address this basic building block of medicine in the 21st century if we are to have any hope in the future. Genetic diagnosis coupled with patient registries will ensure that only those who will benefit from the drug will be put on the drug. Registries will also allow for post-marketing data collection, enabling the pay for performance reimbursement model to be employed.

In summary, we have three messages to deliver today. First, we must develop an all-inclusive, transparent and accountable reimbursement system that will withstand the challenges that lie ahead. We must think creatively and innovatively. We must build a system that ensures that the needs of every patient in the country are addressed. Just because somebody is the only one with a particular rare disease does not mean we are indifferent to that person's needs.

Second, we must build genetic services capacity that meets the needs of not just the rare disease community today but those of the nation. Personalised or precision medicine is not just a dream. It is knocking on our door and the only way we can take part in this revolution is by ensuring that every patient has the opportunity to know more of his or her genetic composition.

Third, we are not just a voice or even stakeholders, we are decision makers and must be allowed to take on this role in the development of our health service. Of all the interested parties, patients have the most risk. It is our health that is at stake. There is a perception among patients that the health authorities fear our input. We are not to be feared. We are the experts on our diseases and we must be involved in all decisions involving our treatment. Revelations within the health service in Ireland over the last 12 months have shown that patients must be included in all decisions - nothing about us without us. I thank the committee for its time.

We will open the discussion to members. I call Deputy Donnelly.

I thank the witnesses for their time today and, more broadly, for all the work they do. The advocacy work and the pressure and technical expertise they bring to the table are incredibly valuable. I realise they can feel they are ploughing a lonely furrow for much of the time so I wish to acknowledge all the work they do on behalf of many men, women and children throughout the country. They should keep it up and we will support them in any way we can.

I wish to focus on some of the possible solutions. I keep hearing that Ireland is lagging behind. We signed up to the BeNeLuxA initiative. It agrees on a certain orphan drug yet Ireland does not bring introduce it. I saw data recently that showed we are the last or one of the last countries in the EU to introduce drugs that have been approved across the EU. It is probably not always the case but that is what I hear from the parents of sick children, experts such as the witnesses, clinicians and the pharmaceutical companies. Everybody seems to be saying that Ireland is last or close to last with regard to some of the incredible drugs that are coming through. The witnesses referred to that several times in their statements. Why do the witnesses think we appear to be slower than most of the rest of Europe in giving people access to these drugs? What can we do in real terms to speed up the process?

Mr. Philip Watt

That is a fantastic question. My sense, and the committee will probably hear this from the representatives of the National Centre for Pharmacoeconomics and the HSE later, is that some positive things have begun and we welcome those. They include the BeNeLuxA initiative and the rare disease technology review committee. They are moves in the right direction. Professor Michael Barry would probably say that we need to tweak the system rather than reform it. We are saying we need to go a little further than that. What we are asking the Government to do is set out an overall policy position which would cover everything, not just the minute detail of appraising a particular drug, representation on one or two committees and so forth. It would look at the entire process and, indeed, the cost, because we see it from the committee's perspective as well. These drugs are a horrendous price. We would all say that we will put on our Irish jerseys and support the Government to get the best and fairest price it can for these drugs. However, that entails us working together in a more partnership way than has been the case up to now. Certainly, the last thing we want to do is what Cystic Fibrosis Ireland had to do which was protest outside the Oireachtas. We would far prefer to see the system being reformed. It is going in the right direction but it must be far more comprehensive than it has been to date.

Dr. Derick Mitchell

I agree with Mr. Watt. An additional element we would like is probably more transparency in the process. It has been very frustrating to have to go to multiple different sources to get the facts about the delays. A number of studies have been performed but the system does not seem to release information readily. From a patient perspective to know where a particular drug is in the process at any stage would be one thing, but also to know which stakeholder has been holding up the process would be very beneficial as well.

I have a question on that. I was going through the process on this last week and the view I got was that the clinical evaluation is quite open and moves at a decent clip. The National Centre for Pharmacoeconomics, whether one agrees or disagrees with what it decides, arrives at a recommendation quite quickly. It has its €45,000 per year measure, with which we can agree or disagree, but it is there and the centre moves through that quite quickly.

Their recommendation goes into the HSE or the Department and at that point it becomes completely opaque. Does that sound about right to the officials or would they describe it differently?

Mr. Philip Watt

That is part of the problem but we were advised that virtually no rare disease drug will get through the system as it stands because of the way the drug is measured. It is often done through the health technology assessment process which looks at one key outcome for a drug, but science has moved on. These new drugs are treating the underlying cause of the disease, not just the symptoms. The drug must be measured by several outcomes. There must be reform. I expect that Professor Barry would also acknowledge that these discussions are taking place at a European and international level.

The Deputy is absolutely correct about transparency around the second stage of the process, which involves senior people in the HSE and politicians, but in addition, the whole system needs to be looked at in a holistic way to see what reforms need to be introduced.

Specifically on evaluation, one of the issues in passing these rare drugs is that they do not meet this magic number of €45,000 per quality-adjusted life year, QALY, or a disability adjusted life year, that rare drugs are not meeting. This is for several reasons, including the lack of comparator therapies to use, because they are very expensive due to the small numbers of people to whom they apply and partly, we are told, because the State does not have a system of payment by performance. Are the officials in favour of a ring-fenced budget that would say that a certain amount of millions of euro was designated for orphan drugs and the €45,000 would be moved to something else and bring in extra issues?

Professor Barry has repeatedly made the point that in the case of orphan drugs, there must be payment by results. One reason it is so unaffordable is because there could be a phenomenal drug that works on one in 20 people suffering from a rare disease, but because one must pay for all 20, it becomes uneconomical for the one person. I have put that directly to the pharmaceutical companies, including some of those making rare drugs, and they have said that they would be very happy to move to a payment by results or outcomes system, however, the IT systems are not in place. They said that it is nothing to do with the pharmaceutical companies but relates to the inability to cope by IT systems in Irish hospitals. They have cited places such as Scotland and England where they have been introduced. Does that sound correct? Have the pharmaceutical companies told the HSE and the Department that they are willing to move to payment by outcomes?

Ms Vicky McGrath

The general view is that would be a desirable avenue to take. The systems are not currently in place, and we have some hope that they will become available but it has been a very slow process. We need to ramp up investment in the area to ensure that it can happen in the next two to five years, or else we will always lag behind and will never be in a position to identify that one patient who is getting good outcomes, and we will always struggle to reimburse.

A ring-fenced fund is a good idea in theory and it is something that we would like to see in the short to medium term. However, we do not want the ring-fencing to be a limit or barrier where we have a discrete pot of money and we end up arguing among ourselves over which patients we will spend the pot on. There are other areas where the health service can be streamlined so that funds could be taken from one pot and put into another so that it does not become the case that there is only one bloc of money available.

The Deputy spoke of a cost-benefit, the QALY and so on. Mr. Watt has alluded to re-jigging the entire heath technology assessment, HTA, system. We must take account of the burden borne by people in general and by society generally. It is not only the Department of Health budget or the Government, but it is about all the work we do and how better can we invest our money and time into other areas if these therapies were being made available.

Mr. Philip Watt

We also have to deal with a particular mindset. When we are trying to fight for rare disease drugs we are told that they are so expensive that we are denying others services. It is not only that patients are having to live with their disease but they are also being blamed from taking resources from somewhere else. We would counter that it is not a zero-sum game. The Government has been criticised for years for spending far too much on drugs which are much cheaper in other European countries, and that we do not have enough investment into biosimilar and generic drugs which would come at a fraction of the cost of many of these drugs. We still have a long way to go to reducing our drugs cost and using at least some of that money on innovative and new technologies such as those for rare diseases. There is also a lack of recognition that the cost of developing a rare disease drug is recognised internationally as far greater than one for a more common disease. I am not defending drug companies trying to exploit countries but that is an economic reality. If there is only a small number of patients from which a company can make back its money, and it costs $1 billion to develop a drug, there is no doubt that the drug will be expensive.

The witnesses are very welcome and I thank them for their contributions. The committee has written its report and several of us have argued and fought for various different organisations. I and Deputy Brassil and others have worked closely with the Alpha-1 foundation in its fight. In the last week or so, we secured a guarantee on the 19 remaining patients that were on clinical trials. I had a sad situation of my own where someone I knew well, Marion Kelly from Nenagh, who is no relation, unfortunately passed away after being taken off Respreeza. Her family had some satisfaction last week.

Responsibility in clinical trials is a real issue. There are issues around honouring commitments, whereby pharmaceutical companies sign up to these trials but then can withdraw from them. We need protocols around clinical trials in Ireland, but my question is how we do that. It is a very important area and I do not want to see something like this happen again. As far as I am concerned, two people lost their lives after coming off a trial because of how it would be administered. One of those people had been in my office only two weeks earlier.

I am trying not to overlap with the good questions Deputy Donnelly asked. I refer to reimbursement and the whole process surrounding it. There is an issue around jumping between the Department of Health, HSE and the National Contact Points, NCP. Unlike Britain, the NCP here is not aligned with the budget. Therefore, unlike other jurisdictions, those who decide on drugs do not have control over the budget, which is a real issue. How can we change this? We have seen so much jumping around on decision making. The committee found a farcical situation where there were letters going between the Department of Health, the HSE and the NCP; it was insane and it is infuriating. Will the officials give their views on how we can have budgets and decision-making in the one place?

Will the officials comment on the rare disease committee being decision makers and how that might work into the future? I can see that the witnesses are passionate about this but how do they anticipate it will happen?

How do the witnesses envisage they will form part of the team that makes decisions? I ask that because I do not want to see a situation where the witnesses are not part of the team.

Some of us here have had a lot of discussions on biosimilars. How can we move quickly in this area? We must move a lot quicker in this area because it will solve some of the issues. The witnesses referred to the issue, on which I have strong views.

My last question is on genetic services. It is a topical issue because of the revelation about a transcription error in Crumlin. I understand that Ireland is quite behind in terms of genetic services. The HSE has tried to recruit senior people with expertise in this area in order to upgrade services, which hinges on the fact that personalised drugs are the future of medicine. I do not think they can match until genetic services reach the required level from a quality and quantity analysis perspective. In other words, we need a service that is able to review many people pretty quickly. We are nowhere near that stage in Ireland. I would like the witnesses to give their thoughts on that matter.

Dr. Derick Mitchell

The Deputy has asked comprehensive questions and I will start with his first question. In terms of compassionate access to innovative drugs that have not received marketing approval or been approved by the European Medicines Agency, that has been a grey area for us. The Deputy is right that protocols should be put in place. It is something we have included as part of our joint work on our Drug Iceberg reports where we feel that any patient who is on trial, as part of a compassionate programme, should have access to that drug for their life. When we talked to other stakeholders in the area there seems to be a reluctance to adhere to that aim for a number of different reasons. Let us consider the environment for clinical trials. A new clinical EU directive is coming down the tracks that will detail how clinical trials will, potentially, be harmonised. The Department of Health is doing a lot of work into research ethics in terms of creating a single committee. The Helsinki Protocol governs how patients should gain access to clinical trials. The area of compassionate access has not been structured in a satisfactory way for patients. Recently the European rare diseases organisation, EURODIS, has compiled a report on trying to get a consistent approach to compassionate access and made a number of recommendations. We could consider those recommendations in order to move the issue forward in Ireland. If there is a potential that Irish patients would get compassionate access, then we should ensure that the company that allows a drug to be available for free adheres to a set of guidelines.

The next issue is biosimilars. In the absence of a national policy on biosimilars, from a patient perspective it makes sense to use these drugs. However, we should do so on the basis that the savings accrued to the system would be reinvested in innovation or similar types of drugs. We have had some discussions on substituting an existing innovative drug for a biosimilar, and who might be involved in that instance. We would like to see greater interaction between clinical and pharmacy communities on those decisions because we feel that pharmacists have a role to play maybe not as the decision-makers but, certainly in terms of the decision itself, there should be more collegiality between the two communities on that aspect.

Ms Vicky McGrath

I will address the issue of rare diseases and the technology review committee. I would caution against the use of the phrase "decision-making" because we do not want people to believe that the group makes decisions on reimbursement. It does not. It is making a decision about a recommendation for reimbursement. We need to be very clear that the committee is not the decision-maker.

Ms Vicky McGrath

That still lies with the HSE leadership team, I guess.

My point is this is beyond a stakeholder.

Ms Vicky McGrath

Yes. In terms of the make up and operation of the group, it looks at everything outside of pricing, the economic reimbursement or the economic models that the National Contact Points, NCP, would traditionally consider. It considers clinical trials and the impact the results would truly have on somebody's life, and quality of life. The group's role is far more objective. It is not that it is unsupported by evidence and research but it is much more based on the patient. The group aggregates the data and the data produced by the clinicians around members' own experiences dealing with these patients, and the effect that they feel the drugs would have on them. It is not an economic conversation; it is about how will this truly impact on the life of the patient. The group makes recommendations on the basis of that information, and not on economic information.

Mr. Philip Watt

On whether the same body should be responsible for assessing and considering the price of drugs, that happens by default. There should be a scientific analysis of the particular drugs using a hospital treatment insight, HTI, system that we can all agree with, and then that assessment is done. It is slightly odd to see the person responsible for making those judgments talking on RTÉ the next day arguing about the price. I greatly admire Professor Michael Barry. To me, it is a conflict of interest when he, as the Chief Medical Officer decides whether a drug is good enough, goes on radio the next day and says that the drug is not worth the price that has been offered. Naturally, when one is on the airwaves one will use any argument to support one's reason to deny a drug and one quickly starts talking spin whether one likes it or not. The NCP should be given the task of making judgments and somebody from the corporate pharmaceutical unit, CPU, of the HSE should be the person discussing the price on the airwaves. The squeezing of the margins is part of the problem.

In terms of genetics, Professor Smyth compiled a report on the future of genetic services in Ireland five years ago. Virtually nothing has been done but the HSE is recruiting a couple of people to work in this area, which is positive. I was not surprised by what was said earlier concerning genetic services because they are completely understaffed. The staff are fantastic, do their best and provide great support to patients. The current situation is a national outcome of a decade where clinical genetic services have been underfunded.

We considered the HSE's service plan from two years ago. We noted that clinical genetic services were not mentioned and not even the word "genetics". The HSE is playing catch up. Genetics and the human genome are the way forward in terms of personalised medicine. It is only now that we are getting our heads around that aspect.

That is why there must be an overall Government strategy that recognises all of these new developments.

This is an area to which we might return. The issue of genetics is very interesting.

I thank Deputy Kelly. Deputy O'Reilly is next.

I thank the witnesses for coming in this morning. We have talked a little about bringing transparency into the process but we keep coming up against the barrier of commercial sensitivity. Is there any country that does it better? Could we look to Scotland or replicate what is being done in any other country? Do we need to reinvent the wheel if another country has gone to the trouble of working out the process well?

The process here is flawed and those who are central to it very often seem to be furthest away from it. The witnesses will be aware of my views on this issue as I have discussed it with them previously. Recently there was interaction between massive pharmaceutical companies, the Government, patient advocates and politicians and we ended up being used as pawns in a game being played by the companies and part of that was because of the process. The companies were putting pressure on us to put pressure on the Government. People came to the Dáil waving pieces of paper around, screaming and asking "What price for a life?". All of this is extremely emotive and is a really poor way for us to have to make decisions. There has to be a better way. At the end of the process, if it does not work, how can we reasonably say "No"? Is there evidence from other countries that suggest that we can do so? At the moment, what happens is that if the drug is over a certain price, that is it. The answer is going to be "No" and then we get into a long, drawn out process. That is clearly not working and is not satisfying anybody. In the event that we go through the process but there is just not sufficient evidence in terms of positive outcomes to justify the expense, what happens? I do not mean to sound cold but are there countries where this works? Is there anywhere where patients and patient advocates are so centrally involved in the process that they understand that a drug might not be for them? That seems to be the hardest part. Patients say that if the answer is "No", they will accept it. If they are told that it does not work, they will accept that but the "No" is always on price. It does not seem that sufficient evidence is being presented back but when one turns on the radio, one hears people who are central to the process saying that a drug is not good value for money. Then we are back on the merry-go-round, shouting at the Minister and so forth and it all keeps coming back to the same place. There has to be a better way to do it. There also has to be a way to do it better if the evidence is not there to support a drug. Do other countries get it right? If so, I ask the witnesses to elaborate on that.

How many times has the technology assessment review group met? Is there a hope that it will review and improve the process, particularly in the context of the patient and advocate involvement? My last question relates to overall costs and the issues that are not really taken into consideration. I refer here to the additional burden on the health service. Perhaps burden is the wrong word but if drugs are not made available then presumably the everyday crises in the health service like trolley waits, waiting lists and so on will have a more profound impact on the people the witnesses are representing. Like everyone, they clearly want to be able to stay out of hospital. Is there evidence of higher incidence of hospital presentation for the groups that the witnesses are representing? Is there any way of identifying what the consequent savings to the health service might be? I know that is not considered here but it is considered elsewhere. Part of any assessment process is to weigh one factor against another. It is hard to quantify in some instances but it is something that should be taken into consideration and offset against the cost. While I do not agree that cost is the only factor, it would be silly to pretend that it is not an important one.

I invite Mr. Mitchell to respond.

Dr. Derick Mitchell

In terms of the first question on what countries get it right, for comparative purposes it is useful to look to Scotland because of its similar size, population and genetic make up. Scotland has successfully incorporated both patient and clinician perspectives in parallel. They have managed to do it from a health care improvement perspective, which has led to the new processes within the Scottish Medicine Consortium. We would look very favourably on what it has managed to achieve in terms of incorporating more qualitative evidence and also developing a process that is far more welcoming. We had the privilege of being observers at a recent Patient and Clinician Engagement, PACE, meeting. It is similar to the rare disease technology review group but at a level up in terms of the decision making process.

As Mr. Watt suggested, there is a reluctance in the system to systematically engage with patients due to media coverage and public policy coverage. What we have been doing in more recent years is structuring the way that patients are educated and informed around this particular area in medicines research and development. We now have a growing cohort of educated Irish patients who are more than willing to engage with what we would determine as meaningful opportunities. Rather than simply plucking an individual patient from out of the blue and putting him or her on a committee, we would support a much more systematic process whereby if the opportunity for a patient perspective as part of a committee has been identified, then the patient should be supported and educated to a certain degree. As a minimum the patient should feel that it is an opportunity to be embraced. Once we get that process in place then the point about accepting that sometimes "No" means "No" for very good reasons is relevant. At the same time, there is a challenge on the patient side for any citizen in Ireland. If one's brother, mother or other family member is suffering from a rare disease, one has a right to stand up for one's relative.

There are a number of responsibilities attached to this too, particularly with regard to the way things are reported in the media. A lot of positive things are happening in this area and there are lots of new developments but if everything ends up being commented on negatively, how exactly are patients going to view our system?

The challenge is to bring the voices in and to recognise that when the answer is "No" it is because the drug is not going to work and not because the system is just giving a blanket "No". Patients feel they are not involved in the process.

Mr. Philip Watt

Absolutely and what struck us about the Scottish system is the involvement of both patients and clinicians. This committee has invited us here as patient advocates.

However, the committee should also bring before it the clinicians because they feel equally outside the system as often they are not asked for their opinion in a systematic way. They are our doctors and many of them are involved in the clinical trials on these drugs. The Scottish system was very good from this perspective. Certainly the day we were there, there was no disagreement between what the patients' representatives said and the assessment. Obviously there was a greater sense of trust in the system.

I understand Deputy O'Reilly's point on interaction with the drugs companies and I suspect she was thinking about cystic fibrosis when she mentioned it.

I did not mention any company but it was high-profile-----

Mr. Philip Watt

I certainly think that if we have a system that everybody can trust it would reduce the amount of advocacy. Fundamentally, what we are saying is the system needs to be more than tweaked, which is the standard response from the National Centre for Pharmacoeconomics and the Government. The change needs to be more fundamental with regard to the health technology assessment process and afterwards. This is the point Deputy Donnelly raised with regard to transparency after the process. When we drew up our documents we tried to find a flowchart of the drug approval system in Ireland but we could not find one. There is none on the HSE website. We had to make it up based on what we guessed.

It looked like a map of an underground from somewhere.

Mr. Philip Watt

Exactly.

It was very convoluted.

Mr. Philip Watt

At the very least, things like this should be made absolutely transparent.

With regard to cost, one of the things we saw with regard to cystic fibrosis drugs, which is something not put much credence was put on, is that they reduce by 30% to 40% the need for people to go into hospital. Their lung function did not increase that much but their need to go into hospital reduced by more that 30%. This was proved in the clinical trials. Obviously massive savings will be made. It also means that patients are living longer, which is why we are fighting for the 20-bed unit in Beaumont Hospital. Our patients now live into their 30s, 40s and 50s whereas 20 years ago they died at the age of 16 or 17. This is the difference the care has made and we acknowledge the Irish health system in terms of these changes. We speak about all the bad things but when we see how things have moved on for our patients we realise that if the will is there massive positive changes can be made.

Mr. Watt said he observed one of the PACE meetings in Scotland. Would it be fair to say be advocates were there on an equal footing and their contribution was-----

Mr. Philip Watt

Those meetings are filmed now and people can sign in online to watch them. We asked them afterwards whether the meetings changed after they began to be filmed and we were told they did change for approximately six months and everybody was so much more polite but after that it went back to the way it was. It was probably a bit like that when the Oireachtas was first filmed.

Dr. Derick Mitchell

With regard to transparency, we have been wondering why information is not more readily available. We are told there is legislation that must be abided by on the release of information. We have looked at Ireland and other jurisdictions in terms of the information that gets redacted. More redaction seems to happen in Ireland than in other jurisdictions. We are curious as to why this is the case. There seems to be more black marker used in Ireland than other jurisdictions with regard to commercial confidentiality and the public arena. We are curious as to why this is.

There is probably more said by what is left out than what is in the public domain.

The committee's report made a recommendation that there would be a review of the 2013 Act to see whether there was any legislative barrier to the process. Have the witnesses been able to identify any legislative barrier in the Act that inhibits the provision of orphan drugs?

Dr. Derick Mitchell

In terms of the Act itself, to be honest when it came out it was a surprise.

Mr. Philip Watt

We did not know about it. We were not consulted about it. We were not asked to go before any committee. All of sudden it appeared. It was surprising because so many other health legislative measures have sat on the books for years, including the health information Bill and the human tissue Bill that still have not been enacted. They first came to the Dáil in 2009. It is surprising that something can be passed beneath the radar that nobody knows about. A review needs to take place but we certainly have not been approached about it and our opinion on it has not been asked.

Dr. Derick Mitchell

To come back to Deputy O'Reilly's question on other jurisdictions, under the health Act a number of criteria are defined against which the reimbursement and assessment processes are measured. The nine criteria offer a degree of flexibility. In particular, in terms of what we are speaking about today, there are other countries that have managed to put in another level of criteria for orphan drugs that greatly recognises the specific unmet need with regard to more rare conditions. I am thinking in particular of Sweden. It comes back to the other question that was asked. Sweden was able to put in place these principles because it had a degree of public trust in the system's ability to assess, evaluate and make decisions. It also has a very well-recognised national registry system. It has a health information system that is able to monitor effectiveness in a much better way than we have in Ireland. It comes back to Deputy Donnelly's point that an IT system and a national electronic health record for individual patients with individual identifiers definitely need to be part of a national strategy on what we are speaking about, in terms of personalised medicine and precision medicine. The patient registries have a very important role to play. They have been doing phenomenal work for a number of years with very little resources. They are approaching a tipping point in terms of their ability to sustain this. At the same time, they are being very innovative in bringing in new solutions for how patients can be effectively monitored, whereby they take their medication and, ultimately, we are able to show the improvement in outcomes.

At a previous hearing, a recommendation or suggestion was made that orphan drugs need to be dealt with differently to standard drugs but the legislation does not allow for a distinction between a standard or common drug and an orphan drug. A recommendation was made that the legislation would be reviewed to see whether amendments to the legislation were necessary to allow a different process to be undertaken for orphan drugs. Do the witnesses believe that the legislation in its present form can accommodate orphan drugs or does it need to be amended?

Dr. Derick Mitchell

To a certain extent changes can be incorporated under the Act but it is very clear the process is not sufficiently flexible to incorporate the specific needs of orphan drugs.

When Mr. Shaun Flanagan came before the committee he was asked that question.

His response was that the HSE has pushed the legislation as far as it can. He was basically saying that what is in place and what it is doing with it is the reason for the decisions it is making. As the witnesses know, I have tabled an amendment to the Bill, which I am trying to get to Second Stage; I will give a copy the witnesses a copy of it. It lists nine criteria but I have extended that to 12 to include three small additions, which the witnesses spoke about previously, taking into account patient advocacy groups and giving orphan drugs a specific criteria, namely, if they are not quantitatively assessed that they would be so assessed.

I will allow the Deputy back in to expand on that in a few minutes. I thank the witnesses for those responses.

I thank the witnesses for their presentation. Regarding orphan drugs, Ireland is at a disadvantage because of the size of the country and our population. A country with a large population like Germany is able to make progress at a faster rate. I refer to recommendation 13 in our report. We had done an agreement in the past five months and the witnesses are saying there is no evidence that working closer with other countries has come into effect. Ireland's approach seems to be to deal with countries with smaller populations. Would we be better off aligning with a country with a bigger population in that we would be in a better position both in terms of assessment and trying to deal with the price issue? I am aware of a drug coming onto the market which would have benefited only ten people in the Thirty-two Counties. Of the ten, six would have had a real benefit from it, which is a very small core group of people. However, if we were dealing with a country with a larger population, more people would benefit from a particular drug. Should we examine that in a more comprehensive manner?

Regarding assessment, we seem to be going through a long process of assessment when the European Medicines Agency may have approved the drug already. There was a recommendation in our report on working with other countries in doing the assessment rather than having a team here devoting all its time to doing it when three or four countries are doing the exact same assessment. There is a duplication in that regard. I recall speaking to a pharmaceutical company that had presented more than 300 pages of documentation on its research and development of a drug here. The process seems to be drawn out. We are in the European Union. The idea was that we would work together to ensure there would be benefits for everyone thereby removing all the duplication.

My next question is on rare diseases. I dealt with a particular case of someone with epidermolysis bullosa, EB. Debra Ireland raised a simple point with me five years ago, namely, that even if patients with EB had medical cards, the cost of bandages was not covered by the medical card. I arranged a meeting with the medical card service to ensure that bandages could be made available to those on the medical card scheme. I am sure there are small areas that are being ignored because that is the regulation and we cannot bend that rule. Could we be doing much to assist patients with rare diseases that do not fit into the criteria provided in regulation or legislation because we do not have a system within the health service to help them get access to an improved level of care? It is one of the problems that tend to arise for people with rare diseases.

My final point is on cross-Border healthcare. As someone who was involved in that issue in Brussels in 2008 and 2009, the directive has now been transposed. Could we work with other countries on cross-Border healthcare and remove some of the hurdles here to getting access to care? We are doing that in many other areas. Why can we not do it much more in healthcare? We seem to be unable to do that.

Mr. Phillip Watt

Those were excellent questions. To start with the one on cross-Border healthcare, we work with the rare diseases group in the North. Members can tell from my accent that I am from Belfast. That group feels utterly abandoned. There is no administration, and they are dealing with Brexit as well. They are very concerned about the cross-Border services that will be affected by Brexit. They are distraught; that is the only word I can use. We need to extend a hand to them much more often than we do currently in terms of making sure they are included.

We still have backs to the Border. Everybody in the South looks at Dublin and everybody in the North looks at Belfast. It is far too small an island to do that. We need to pool all our resources, and there are some fantastic services in the North. They are developing genetic services of which we can avail. Some retina operations are done in the North. Likewise, patients with heart conditions are treated in the South. As the chief medical officer in Northern Ireland stated, we just have to get on with it and try to ignore Brexit and the fact that there is no Administration in the North and make sure those services work for our patients. I believe we should not stop that but enhance those services. I take that point fully on board.

Ms Vicky McGrath

I will go back to the Senator's first question and then move on to the cross-Border directive. In terms of the BeNeLuxA initiative, it is five months in. We need to give them a little time to do some work but it comes down to transparency. Have they made any progress? What have they done? None of us seems to know. The initiative has been signed. That is great. We had all the fanfare but we do not know whether anything has happened in the intervening period. I would not throw it out as being a case of wanting to go with a larger country. We need to let it bed down.

That rolls very well into the cross-Border directive and what we refer to as the European reference networks. The Commission has decreed that Europe needs to work as one when it comes to rare diseases. There is no longer an Irish rare disease healthcare system; it is a European rare disease healthcare system. In so doing, I would expect the likes of BeNeLuxA to work with the German and the French authorities. They will start to work together and then to do reimbursement for drugs across Europe. The chances are that some of these therapies will be made available, as in administered, in only one or two countries because the diseases are so rare. There are so few patients they will end up having to travel, and that is how we will get access to it. We will get access to it because Ireland is signed up to these reference networks. We are still in the very early stages. There are 24 networks. Some countries have representations in all 24. Currently, we have representations in two, but we understand at least 21 applications are due to be submitted by the next deadline. The deadline has not been set, so it is not that we are behind the ball in that regard. By the middle of next year, we expect to have the applications in and, hopefully, they will be processed by the end of the year to ensure Ireland is well represented in the European realm in terms of these reference networks. They will provide many solutions. The will provide some of the infrastructure we want around the registries and ensuring we have the best care pathways. It is a major burden to put on the European reference networks, but the pharmaceutical sector is calling for it.

The challenge we face is that the pharmaceutical industry will stop coming to Ireland seeking to get drugs reimbursed because our population is too small. If the industry is dealing with Europe, there is some hope that it will end up coming across. It will be a challenge for our health system to equate to Germany's, but we have to address that in the years ahead. There are positives, but in the intervening period, we need to readdress the existing system and make sure that we do not fall behind. We must also consider the other drugs and diseases that are not termed "rare".

Dr. Derick Mitchell

To complement that, and to emphasise the point Ms McGrath is making, there is a certain perception that the European Reference Networks are just about service delivery. The vision for the European Reference Networks is also about data collection. It is about harnessing the power of Europe to work for patients in individual countries. In Ireland in particular, part of the development of a new national rare disease plan would be more emphasis and much more supports for the clinical leaders. However, patients are playing leading roles in several of the European Reference Networks, and such a plan should also allow for greater Irish leadership in those reference networks. We believe they will become one of the major solutions for things like pricing, reimbursement and ultimately better assessment processes.

I refer also to the joint clinical assessment initiatives that are going through the European Legislature at the moment. The Commission's proposal for joint clinical assessments is something we have been looking at and of which we are highly supportive. While there are differences in opinion in various member states as to how it affects their assessment processes, joint clinical assessments applicable across jurisdictions certainly make sense from a patient perspective and with regard to duplication. Some 14 patient umbrella groups at European level recently released a statement about the consensus on patient involvement in that proposal. Patient involvement needs to be a greater consideration in the overall co-ordination of efforts in joint clinical assessments.

I wish to make a final point about the supports that should be made available to patients with rare diseases. they have no-one to turn to in many cases. Could there be a better structure for supporting people who could be provided with care but who do not know how to access it? Does more need to be done to provide information to people who are identified as having rare diseases?

Mr. Philip Watt

The conditions are so diverse. The Senator's point is correct. In some cases, more visibility is needed. To get back to the point about epidermolysis bullosa, EB, it is ridiculous that people have to pay for bandages when that is a core part of their medical treatment. There is a kind of grey area between what is a drug or medication and what is not which definitely needs to be resolved. Moreover, without a universal healthcare system, we just have the long-term illness scheme which was introduced in 1971. That names about 43 conditions for which there is basically a universal healthcare system. We are very lucky that cystic fibrosis, CF, is one of them. However, many other conditions, including many rare diseases, are not named in the scheme but should be equivalents. I do not advocate getting rid of the scheme but it should be expanded to cover many more conditions until we have a universal healthcare system. That is crucial as well.

I thank the witnesses for their presentation. I refer where we are as a country with regard to orphan drugs. The European Medicines Agency has designated 148 medicines as orphan drugs for rare diseases. Currently we reimburse 53 of those or 35%. The UK reimburses 68, Spain reimburses 75, Italy reimburses 84, France reimburses 116 and Germany reimburses 133. We are at 35%. Germany is best at 90%. Spain, a country whose economy is not going as well as ours, is at 50%. We are at the lower end for reimbursement for orphan drugs and drugs for rare diseases. The NCPE is aware of this. We have been fighting individual battles, over Respreeza for alpha-1 proteinase inhibitor deficiency, as Deputy Kelly mentioned, and Orkambi for CF. It seems that if the lobby is strong enough, or given the unfortunate and tragic deaths of two patients, the HSE takes notice.

As a result of my work as spokesperson on primary care I have tried to modify the Bill. This committee has stated that it needs to be modified. It is being resisted at all ends. That is the context of our dealings with the NCPE and the HSE in trying to establish a better model to reimburse more drugs and to give patients with rare diseases, who are as deserving of proper care as anyone else, some chance of either dealing with their symptoms or in some cases dramatically changing their lives.

The rare disease technical review committee was referenced. That is a welcome addition. The key point, which the witnesses have recognised, is that this group is reviewing the decision, not making it. Because it is reviewing a decision based on a flawed process, it will find it difficult to come up with a different decision. The 2013 Act needs to be amended. That is my focus and it should be that of the witnesses as well. Unless we amend the process by which these drugs are reviewed, we will be fighting an uphill battle.

Dr. Mitchell made reference to Sweden. Sweden's model is a based on quality-adjusted life year, QALYs, but it does not have an upper limit. The Swedish model allows for situations where maybe half a dozen patients are suffering from one condition, where one could not possibly get the type of data that is needed and meet the threshold of 45,000. Interestingly, in 2015, the proportion of health expenditure on medical goods was greater in Ireland than it was in Sweden.

Deputy Donnelly raised the issue of biosimilars. The IPU has identified a potential saving of €307 million on biosimilars alone over three years. I have met children suffering from spinal muscular atrophy. A drug called Spinraza has revolutionised treatment. Its total cost to the system would be approximately €9 million. Multiples of that cost are available.

We need to amend the Act to give some hope of orphan drugs being reviewed. If we do not do so, the companies will just stop applying, as Ms McGrath pointed out. They know the answer will be "No", so why would they waste time and resources applying for something when they are going to be refused? That will have a knock-on effect.

I met officials from Vertex, the company that makes Orkambi, recently. After all the battling, arguments, protests, marches and so on, that drug was reimbursed, including future iterations. I believe the next Orkambi, whatever it is called, is coming on-stream shortly without any debate. Vertex told me it is looking for other countries to consider reimbursement in the way the agreement was made in Ireland.

Mr. Philip Watt

That has happened. Sweden and Denmark copied Ireland.

It can be done. Orkambi was not reimbursed because the NCPE suddenly saw the light, however. Massive political pressure and patient-centred demonstration and focus made officials realise they could no longer ignore it or make the decisions they were making without being challenged. When they were challenged, they made the decision. I do not know if I had any question there; it was more of a statement. I would appreciate if the witnesses' organisations could look at the Bill I am-----

Mr. Philip Watt

We need to use that power responsibly. I give an assurance that my organisation would never campaign for a drug we did not believe in or see the scientific evidence for. Our point was that the system was flawed so that no orphan drug would get past. That was fundamentally why we were protesting. It is great to see some reforms being put in place, partly as a legacy of that but also as a result of the work of all the patient groups. Our key point is that the reforms need to be broader. A broader strategy needs to be put in place which considers issues such as cost and where the money is going to come from, rather than simply tweaking things by putting a couple of patient representatives here and there. All that is welcome and great but it must be part of a broader change. There is also an issue in respect of how patient representatives are picked. We want to set down a marker that we should elect our own representatives and not have them hand-picked by the HSE and the Department of Health. There was an election for the rare diseases committee, which was welcome, but other processes are happening daily whereby the HSE simply picks a patient or an organisation. Those days are gone and the structures need to be much fairer and more transparent.

On the budget for orphan drugs, I have consistently sought a figure but cannot get it. Deputy Donnelly raised this earlier as well. Unless we have a specific budget it is difficult to make comparisons, decide how much we should spend or know how much of those savings will be reinvested in orphan drugs. That is something else we should insist on. Although I know they have the data, the companies keep coming back saying they do not. In the application process for any company, one of the questions is whether there are orphan drugs ratifications. It is in their applications so they know what is an orphan drug and what is not and, therefore, they can tell us how much they are spending on orphan drugs. They just do not want to do so.

Dr. Derick Mitchell

I reiterate that there is a specific recommendation in the national plan for a budget. It does not specify the total amount and certainly is not viewed as a target but as a way in which we can effectively measure the spend. It has not been touched as part of the current plan, however. We certainly hope that as the new plan is being developed, it will be re-examined in that context.

I am sympathetic to the issue of orphan drugs, particularly where it has been shown that they work and that a patient cohort will benefit from them. The problem, which the committee has discussed many times, is where the determination as to their benefit and safety comes from. Is it made at EU level? There is a vetting system at EU level but, as we found out in this committee a year or so ago, we have an internal system that vets them again. I do not see the purpose of that exercise at all. We appear to have, and to contribute to, two systems, as the vetting system we have here is also replicated at European level. When it comes down to it, the EU is in the best position to command a price. If someone is negotiating on behalf of 500 million people, the case is an awful lot stronger than on behalf of three or four. Despite the good cause, it comes down to the power of the market but we do not use that argument in this country at all. An average of 14 member states are involved in these processes. The Bill referred to by Deputy Brassil is a classic example. Why could it not be the entire EU 27? It could have been 28 member states up to recently but could still be 27 from here on in. Whoever is vetting and dictating the going rate to individual states, no individual state can have the same power, except perhaps the larger states. We should get to that point as early as possible. I spoke about this issue 20 or 30 years ago in another capacity. It has not changed over the years. We are still engaged in procurement standing alone on our own two feet and it is not working. It does not, and cannot, work. Having a duplicate system where we have one system operating at EU level and another one superimposed on it here is daft and stupid in the extreme.

I acknowledge the benefit of patient representative groups but I would also balance that benefit against the points raised by Deputy O'Reilly. We could find ourselves in an awkward position. We have the telling tales of the patients and lobby groups on the one hand, while, on the other, we have this amorphous system, which we do not know how to deal with and cannot manage. Everything comes down to cost in the final analysis. Deputy Brassil makes a useful point about the 2013 Act. It was framed and passed in the midst of the worst economic crisis this country or any other European country ever had the misfortune to experience. It might be a good idea to examine it again in a different light. However, as a note of caution, before the economic crash we believed we were one of the wealthiest countries in the world but that was a figment of our imaginations. We were not and we are not. There is no use pretending we are. Wealth is made up of series of factors of which housing, goods, services and trade are a part. They tend to float with the market and can leave us high and dry when the tide goes out. We need to be cautious that we do not walk ourselves into trouble, not necessarily in respect of pharmaceuticals and health only but in other respects as well.

Diagnosis is an important issue, particularly for rare diseases. For example, Guillain-Barré syndrome is a rare disease. I know five people who have been unfortunate enough to wake up and find themselves paralysed. There is no answer to it at all and they spent considerable time in hospital while their cases were examined before diagnosis eventually happened, sometimes on a haphazard basis. That needs to be examined. Modern communication should make it much easier to compare cases across the country and the continent. This condition is curable. The same people were walking around six months after being diagnosed. They had to go a long route to learn to walk again and needed rehabilitation but it happens. Early diagnosis is of considerable economic benefit in that area.

I would be one of those strongly in favour of utilising it as much as possible.

I have already referred to my final point. We need a single system of adjudication. It is either in Europe or it is here. We do it one way or the other; there is no use doing it twice because there is a cost involved in that. From a safety point of view, utilising new drugs on the market is of paramount importance. Years ago, there was considerable anxiety and questions were raised about the manner and methodology used to test the drugs and those on whom the tests were carried out. Considerable controversy arose at the time and people remain concerned. It must be one of the issues we consider. We need to move on. We need to remove the emotional situation that arises on a daily basis where it requires a significant amount of publicity or attention to be drawn to a particular condition before there is a response but that response must be tempered by the ability of the State. We return to the question of how much a life costs, a point raised by Deputy O'Reilly.

I am conscious of the fact that we have the HSE and the NCPE outside. Was there a specific question in that?

It was more of a comment.

Mr. Philip Watt

The EMA makes the decision and it goes to individual countries. The Deputy is right. There is considerable inefficiency in that process. It is about whether the Government is willing to put its trust in the EMA. The question is whether it becomes a economic burden the Government is unwilling to shoulder. It makes so much more sense. The EMA makes the decision on a drug and all European countries can negotiate at once with the drug companies so they have far better leverage when it comes to getting a better price. I do not think the HSE is ready for that but it is a principle worth working towards.

I thank our guests for the work they do. I am following two drugs in particular, namely, Translarna and Spinraza. These drugs are what led me to the issue of rare diseases. I am not a permanent member of this committee. What has shocked me is the lack of transparency, which has been mentioned. Where there is no transparency, there is no trust. That is the real issue we need to tackle. The issues involve transparency, the delays and blockages in the system and how quickly we can get to a European situation where the BeNeLuxA benefits kick in and people really benefit from them. Are there specific actions we can take to bring transparency to the process?

Dr. Derick Mitchell

This comes back to my previous point about what is done in Scotland and the rest of the UK. A point was made earlier about comparing the NCPE to what other jurisdictions use to assess. There is great value in having that independent scientific assessment process-----

My time is limited because other witnesses are waiting outside. How long does it take, on average, for approval in Scotland?

Dr. Derick Mitchell

I would not be privy to that information. The NCPE carried out an analysis of the assessment process recently, which is quite transparent to everybody here. In respect of the reasons and steps along the process where there was a stop clock or a gap, that has only recently been done through a manual process in the NCPE. We do not have an equivalent on the reimbursement side in Ireland. As far as I am aware, they do not have that kind of breakdown in Scotland. This is something we would like to see more of in terms of the reasons that the clock stops.

That is exactly what I am trying to get at. Is it due to a human blockage or lack of resources? What is it?

Dr. Derick Mitchell

Getting a real-time analysis of that is very difficult because it is a confidential negotiation so we would only get that information in retrospect once a negotiation has been completed.

It is obscure. Is Dr. Mitchell clear on the cost-benefit analysis that is used in the context of how many negative or positive externalities are taken into account or how the decision is arrived at? Is it long, short or medium term?

Mr. Philip Watt

They generally tend to look at one particular aspect of a disease and ask how the drug impacts on that. The reason there is a need for a bigger review is that these new drugs are impacting in a much more holistic way so they need to be measured in terms of four or five different end points rather than one. Quality of life is vital in terms of that and must be taken very seriously. We can have all the processes in place - and the Scottish system is very good - but the point Senator Conway-Walsh is making relates to the outcomes. We would remain suspicious if all these new processes are put in place and we still find that Ireland is the only country in Europe that does not approve a particular drug. One's suspicions would definitely be aroused if such a drug was available in most other European countries.

That is the point. Is the EMA worth anything? Is it of any value at all or are its standards lower than the ones we have here? These treatments are often for children. Does a child in another country differ from one here? Why do we not take the EMA's decisions and say "Now we are here, what is the other part we need to get in order to get it approved in our country?" I cannot understand why we keep-----

Ms Vicky McGrath

To clarify, the EMA says whether a drug is safe and effective.

Ms Vicky McGrath

The EMA assesses whether the drug does what it says on the tin. It does nothing in respect of pricing.

I understand that.

Ms Vicky McGrath

The question is then whether we should add that to the EMA and whether it should be the next stage of the EMA where Europe comes together. With the reference networks, it will slowly move in that direction but in the intervening period, we need to do something to cover ourselves.

As Ms McGrath knows, in many of these cases, time is the one thing we do not have. I have significant issues with the cost because it is not negotiated. We are taking a headline cost and working out the cost-benefit analysis on that basis but we cannot hope to do so when the drug company is giving a cost expecting it to be negotiated, and rightly so - it would happen in any business negotiation - but it is not being negotiated by the HSE. How can we hope to have an outcome that would be positive in that situation?

Mr. Philip Watt

I would defend that somewhat. Even in terms of our experience around Orkambi, it got a significant reduction in terms of what was offered originally. I cannot reveal the price. It brought in an innovative system whereby if better drugs come along in the future, we will automatically get them. That is being copied by other countries so there are occasions when it can get it right. We need to build on that good practice.

We need to get it right all the time because it was not the case with of Translarna.

Mr. Philip Watt

Absolutely.

A total of 22 countries have approved that drug.

Mr. Philip Watt

I went to the annual conference concerning children with Duchenne muscular dystrophy. They have a window of two or three years and if they do not get the medication, they will go into a wheelchair straight away. They will not be able to walk. Those medications are broadly available in the rest of Europe. Cost seems to be the reason why they are not being brought-----

With regard to the impact of delays in the BeNeLuxA countries, we know the situation regarding Spinraza in all of the BeNeLuxA countries. Surely we can use that as a lever.

The children are being admitted to ICU. Even taking out the inhumane aspect and the distress caused, the additional costs are building up in trying to-----

Ms Vicky McGrath

It comes down to whether we are willing to even pay the price BeNeLuxA has negotiated. I do not know. In the very short term, as patients and patient organisations, the big thing we would like to see happen is an opening up of the relationship between pharma and the HSE. Things go into the black box - I think "opaque" is a nice word to use - but there is no visibility and one, two or three years could pass by. We hear anecdotally from the industry which is far more willing to discuss this issue than not that it has had a meeting, or not as the case may be, or a phone call, or that an email was sent in the intervening period. That there is no visibility is one of the biggest challenges we face in the short term and it would be easy to address, to at least say in broad terms that there was communication, or that a meeting was held and that people promised to come back in three months' time. That would help us a lot in the short term. We would then look at rebuilding the systems and stuff like that.

It is a shame that the clinicians are not involved in the decision-making. We are lucky, in a country of this size, that we have well qualified clinicians, yet their opinions are just dismissed. There is protectionism within the system that certainly does not serve either the clinicians or the families and those who need the solutions and treatment.

Mr. Philip Watt

There is also cynicism. Recently I talked to people involved in pharmacoeconomics across Europe and they all seemed to have the sense that somehow patient groups were in the pockets of pharma companies. To be honest, it is really insulting. As patient groups, we would be betraying patients if we ever advocated for use of a drug which was not effective. That would be disgusting and we need to be more robust in showing that is the case. Clinicians are accused of the same because they are involved in clinical trials and so on. It is so simplistic and wrong and needs to be challenged.

The Minister needs to challenge it.

On behalf of the committee, I thank Mr. Watt, Ms McGrath and Mr. Mitchell for coming to give their evidence. Of course, they can wait and observe the next session.

Sitting suspended at 11.13 a.m. and resumed at 11.17 a.m.

The committee will now continue its consideration of the implementation of the recommendations contained in the report on the evaluation of orphan drugs which was published last February. On its behalf, from the HSE I welcome Professor Michael Barry, clinical director of the National Centre for Pharmacoeconomics; Mr. John Hennessy, national director of acute strategy and planning; and Mr. Shaun Flanagan, chief pharmacist in the corporate pharmaceutical unit. From the Department of Health I welcome Mr. Finian Judge, principal officer in the community pharmacy, dental oral and aural policy unit.

By virtue of section 17(2)(l) of the Defamation Act 2009, witnesses are protected by absolute privilege in respect of the evidence they are to give to the committee. If, however, they are directed by it to cease giving evidence on a particular matter and continue to so do, they are entitled thereafter only to qualified privilege in respect of their evidence. They are directed that only evidence connected with the subject matter of these proceedings is to be given and asked to respect the parliamentary practice to the effect that, where possible, they should not criticise or make charges against any person or entity by name or in such a way as to make him, her or it identifiable. I advise that any submission or opening statement made to the committee may be published on its website after the meeting.

Members are reminded of the long-standing parliamentary practice to the effect that they should not comment on, criticise or make charges against a person outside the Houses or an official, either by name or in such a way as to make him or her identifiable.

I ask Mr. Judge to make his opening statement.

Mr. Finian Judge

I thank the Chairman and committee members for the invitation to discuss the report on evaluating orphan drugs. I am accompanied by Mr. John Hennessy, national director of acute strategy and planning; Mr. Shaun Flanagan, chief pharmacist in the corporate pharmaceutical unit; and Professor Michael Barry, clinical director of the National Centre for Pharmacoeconomics.

In March the Department of Health received the committee's report on evaluating orphan drugs. The report included a number of significant recommendations related to the assessment and reimbursement process for orphan drugs. Some of the recommendations concerned the policy and statutory framework underpinning the process, with the remainder focused on the evaluation and reimbursement process, including the clinical criteria deployed in that evaluation.

I note that the 2013 Act is very comprehensive and provides for a range of important matters, including the criteria to which the HSE must have regard when making reimbursement decisions on new medicines. The Act includes provisions on interchangeable products, rules for the establishment and maintenance of reimbursement lists and provisions on reference pricing. In its report the committee focused on that part of the Act which provided for the evaluation process for new medicines proposed for inclusion in the reimbursement list.

Since the publication of the committee's report, the Department has been engaging with the HSE and the NCPE to address the recommendations contained in it on the framework and process for assessing orphan drugs. In this contribution I will address those recommendations directed to the Minister for Health or the Department. My colleagues from the HSE and the NCPE will address the recommendations on the evaluation and reimbursement process, including the clinical criteria pertaining to evaluation. Under statute that function is vested in the HSE.

The Minister is satisfied that the Oireachtas has put in place a robust legal framework in the Health (Pricing and Supply of Medical Goods) Act 2013 for the assessment and reimbursement of medical goods. The Act provides the HSE with full statutory powers to assess and make decisions on the reimbursement of all medicines and includes detailed criteria to which the HSE is required to have regard when making those decisions. The Act puts in place a clear statutory framework by which new products must be assessed by the HSE and ensures decisions are made on an objective and scientific basis. It provides for a fair, transparent and rigorous process for the assessment of all drugs and has delivered tangible results for patients. The Minister is satisfied that there are no legislative barriers to the reimbursement of orphan drugs, as distinct from any other drug, and is further satisfied that the rules pertaining to the assessment of all drugs do not discriminate against orphan drugs. In fact, the criteria which apply to the evaluation process contained in Schedule 3 to the 2013 Act provide sufficient scope for the HSE to take on board the particular circumstances of orphan drugs. My colleagues from the HSE and the NCPE can elaborate further on that matter.

In its report the committee, rightly, identified that drugs were increasingly being developed to target very rare conditions and that these drugs often came with a very high list price. Under the Act, the HSE is required to have regard to the funding challenges these drugs represent. It does so by drawing on the criteria contained in the Act, including the potential or actual budget impact of the drug in question and the cost-effectiveness of meeting health needs by supplying a particular item, rather than by providing other health services. These are difficult decisions, but they recognise the core challenge presented by the availability of finite resources in the face of ever-competing demands.

The committee recommended the appointment of an independent person to conduct a review of the current process and its role in orphan drug availability. The Department is preparing to undertake a review of the governance arrangements applying to the internal HSE process. The review will examine the systems, structures and resources which support the decision-making process for reimbursement.

In its report the committee also expressed support for collaboration with other EU member states. The Minister is very much in agreement with that notion. In fact, the challenge of accessing innovative medicines at an affordable price is one shared by most, if not all, developed countries. Demographic change will have to be managed, with a continually growing pipeline of new and innovative medicines, many of which will come with asking prices that risk making them unaffordable or unsustainable. It is estimated that approximately 45 new molecules are due to receive market authorisation in Europe in each of the next five years. It is in this high technology space which includes orphan drugs that the greatest challenges will arise in the years ahead.

Already, expenditure under the high technology arrangements through which the majority of new high cost medicines, including orphan drugs, are funded has increased, from approximately €400 million in 2012 to close to €700 million this year. That level of growth is a major challenge for the Government and the HSE and a reason Ireland is working with other countries in Europe to develop common solutions to a universal problem. A significant development since the publication of the committee's report has been Ireland joining the BeNeLuxa initiative on pharmaceutical policy in June. This collaboration will support the Minister's objective of co-operation with other EU member states to identify workable solutions in an increasingly challenging environment. As the committee acknowledged in its report, this is a long-term strategy. However, it is one we expect will complement existing domestic policy in this area.

While the Department has not undertaken a formal review of the Act in its entirety, it has, in conjunction with the HSE and the NCPE, considered in detail the committee's report and the recommendations contained therein. There has been substantial engagement between the Department, the HSE and the NCPE on each of the recommendations. I am pleased to note, as well as the policy developments I have outlined, that a number of significant changes have been made within the confines of the Act at operational level in the assessment and reimbursement process to address a number of the recommendations made in the report.

I will hand over to my colleagues from the HSE and the NCPE to elaborate on the operational developments.

Mr. John Hennessy

I thank the joint committee for the invitation to discuss orphan drugs. As Mr. Judge said, I am joined by my colleagues, Professor Michael Barry, Mr. Shaun Flanagan and Mr. Ray Mitchell from our parliamentary affairs unit. Our preparations focused on the committee's report of February 2018 and the measures taken or under way to address the recommendations contained in it. Mr. Judge has covered the main policy and legislative elements. I will focus on the operational aspects.

On recommendation No. 4, I confirm that discussions have commenced with the pharmaceutical sector to provide clarity on pricing and measures to speed up the negotiating process. The discussions have also explored the issues of risk sharing and post-approval review to ensure ongoing expenditure is justified by evidence of clinical effectiveness.

On recommendations Nos. 6 and 7, there is already a high degree of communication between the HSE and the pharmaceutical sector, as well as, of course, with patient advocacy groups. However, steps have been taken to strengthen this engagement through the provision of additional resources at both NCPE level and within the corporate pharmaceutical unit. This is intended to enable representations to be considered at both the HTA and negotiation stages. There is also routine engagement with the pharmaceutical industry, while the composition of the drugs group has been expanded to include patient representatives and more clinical expertise in the area of rare diseases. Enhancements have also been made regarding medicines for older persons and medical ethics.

The HSE has written to hospital groups setting out the importance of having a clear understanding and informed consent arrangements in place prior to the commencement of clinical trials and compassionate access programmes. The establishment of a specific budget for high technology and orphan drugs is also being examined. This was also a recommendation made in the report. To a large extent, it is already something we have in place in that high technology and orphan drugs are, by and large, funded centrally, rather than from individual hospital budgets.

The measures now under way to strengthen the representation of rare diseases in the assessment process and to involve patient representation and medical ethics should also refine the process of assessing medicines in the manner intended and recommended by the committee. The issues highlighted in recommendation No. 10 are being pursued further with the HRB, which appears to be the most obvious route to influence research in collaboration with the university sector. With regard to recommendation No. 12, the HSE has established a national rare disease technology review committee. The role of the committee is to enable clinicians and other stakeholders to input into the assessment process and in the post-health technology assessment phase to review proposals, prescribing guidelines etc. for consideration by the drugs group. This is designed to operate similarly to the National Cancer Control Programme therapeutic review committee, which has been operating successfully. Such guidelines will, where appropriate, include recommendations relating to the prescribers who should be enabled to access orphan medicines. I will ask my colleague, Professor Barry, to elaborate on the work of this group. A model of care has also been prepared by the HSE’s clinical programme for rare diseases, which aims to improve access to care for patients with rare conditions and improve value and quality in this area.

As the process for evaluating applications was covered in detail at our meetings with the committee in 2017, I will not repeat this other than to emphasise again that the criteria for assessment are as detailed by the legislation, the Health (Pricing and Supply of Medical Goods) Act 2013, and as set out specifically in section 19(4) of the Act. The important point to bear in mind is that the legislation requires the HSE to have regard to the cost-effectiveness and the clinical benefits of the product being applied for. The particular features that relate to orphan conditions are obviously considered during the assessment process and factors such as clinical effectiveness and the number of potential patients affected are clearly set out in the reports compiled. As members are aware, the HSE currently spends in excess of €2 billion per year on drugs and medicines, and on a per capita basis the Irish health service continues to be one of the highest spenders on medicines in the OECD area, with expenditure still increasing annually. I will now hand over to Professor Barry for further detail on the rare diseases technology review group.

Professor Michael Barry

I thank the committee for inviting me here today. With regard to access to medicines and technologies for people with rare diseases, recommendation No. 30 on page 54 from the National Rare Disease Plan for Ireland 2014-2018 suggested the establishment of an assessment system similar to that for cancer therapies established under the national cancer control programme. The HSE has implemented this recommendation in setting up the rare diseases technology review committee, RDTRC. The aim of the committee is to facilitate the incorporation of the patient and clinician perspectives into an agreed statement, which will be presented to the HSE drugs group to aid the group's reimbursement recommendations. It is important to remember the rare diseases technology review committee, is not a voting or decision-making forum but it merely provides advice to the drugs group.

I was asked by the HSE to help establish and to chair the rare diseases technology review committee and I was very happy to take on that task. Membership of the committee includes the chair, the clinical lead for the HSE rare diseases programme, five consultant physicians with expertise in rare diseases, two pharmacists, one health technology assessor, one representative from the Health Information and Quality Authority and two patient representatives. It is a total of 13 members. The first meeting of the committee was held on 15 October 2018 and a second meeting was held on 8 November 2018. Meetings were also held with patient representatives on 8 November and 30 October. We also held a meeting with the manufacturer of nusinersen on 30 October 2018.

Have we a copy of this? None of us has a copy of this.

Was this submitted?

Professor Michael Barry

Yes.

When was that?

Professor Michael Barry

We can arrange for a copy to be sent.

I do not want to hold up the meeting but I just wanted to ensure I was not the only person who has not seen it.

Professor Michael Barry

Sure. We can certainly arrange for a copy to be sent.

Was it submitted this morning?

Professor Michael Barry

No, it was a few days ago. I just wanted to give the committee a flavour of what is going on. There were five meetings in 24 days and it is testimony to the significant work done by committee members, who do such work on their own time and in an unpaid capacity.

The committee has focused on two medicines to date, which are sapropterin or Kuvan for phenylketonuria, and nusinersen or Spinraza for the treatment of spinal muscular atrophy, SMA. As an example, the committee recommended to the HSE drugs group that access to sapropterin be considered under a managed access programme. In other words it would occur where clinical criteria were laid down for starting and stopping the medication if it was not working. It was taken by the HSE drugs group, which made a positive recommendation with regard to Kuvan, which is good news. The funding issue must be decided on by leadership. Currently we are preparing a rare diseases technology review committee recommendation for nusinersen for spinal muscular atrophy and we hope to submit it to the drugs group shortly. That is a flavour of how the new committee is working.

I thank everybody for coming before the committee this morning. It is very much appreciated. I thank them for all the work they do and this is clearly a very sensitive and important area. I have various process questions as to how things are being improved. I will first ask about both Spinraza and Translarna. With Translarna, an application was received in September and yesterday we got a letter saying the application is now reaching the concluding stages and will be tabled for discussion at the December HSE leadership meeting. Mr. Hennessy said he would revert on the matter. I thank him for that. This does not affect a large number of children but for those who are waiting, time is critical. When is it expected to have a decision one way or another? For those parents and the children, is the decision we are awaiting a therapeutic and clinical decision or is it a funding decision? Is it both?

Mr. John Hennessy

The Translarna application has concluded the assessment process through the drugs group and is listed for the December leadership meeting. I would expect the decision to be immediate after the December meeting but there are affordability issues currently being dealt with as part of the service plan preparation for 2019. There are aspects of that still outstanding. The service plan will also be concluded by then, I hope, and it should clear up matters relating to affordability.

I thank Mr. Hennessy. On the affordability side, the question for the parents and children is when they can expect to get a "Yes" or "No" or a half-yes or any answer on this in order that they might be able to access the drug.

Mr. John Hennessy

It will certainly be by the end of the year.

That is by the end of this year.

Mr. John Hennessy

Yes.

It will be in the next six weeks.

Mr. John Hennessy

Yes.

I thank Mr. Hennessy. The Spinraza process has been ongoing for some time. In May 2017 it was approved by the European Medicines Agency and an application was received in October last year. In December last year we were told the National Centre for Pharmacoeconomics, NCPE, completed its health technology assessment and said "No" at the current price. My understanding is we have a "Yes" on the impact of the drug at a clinical level but a "No" on the price based on the analysis of the NCPE. Responses to parliamentary questions from October - we are getting the same response now - was that it is now with the rare diseases review committee, the HSE drugs group and the HSE leadership. I have the same question as earlier, as a number of men, women and children are desperately waiting for an answer and hoping for a positive reply on this. When will they expect to hear either way from all the different groups? If it is a "Yes", when can they expect access to the drug?

Mr. Michael Barry

The rare diseases technology review committee first met on 15 October, when it was high on our agenda. We met again on 8 November. We also met patients and families, who presented well to the group and demonstrated what living with SMA is like. The committee is putting together a report which will be sent to the drugs group within weeks and it will outline how one might decide on the prescribing areas, who would be prescribed for, what the criteria to start prescribing nusinersen would be and whether there would be criteria to discontinue it if it did not work, as some of the trials show that up to 50% of people will not respond. That is the kind of document that is being prepared. I anticipate that a draft will be sent to the drugs group in the next two or three weeks, and that is the task of the rare diseases committee.

Mr. Flanagan might comment further on the drugs group. I imagine it will be taken into consideration before the end of the year.

Mr. Shaun Flanagan

The question the Deputy is asking about Spinraza is not one on which we can give a time limit or make any guarantee. Our responsibility while appearing before the committee is to give honest testimony. As context, the drugs group has reviewed Spinraza on five separate occasions to date and has not been able to accept it at the proposed cost, which is a commercially improved offer from that which was originally approved. I am not a member of the group but rather a secretary, and I am non-voting. As I am involved in the commercial negotiations, it is clear it is better to separate me from the vote. It is hard to put a time limit on it because the difference is that Translarna has gone past the drugs group and is under consideration by the senior leadership team. There is a step where the drugs group must make a deliberation, and that drugs group has a responsibility under the Act to give HSE advice but it has not yet given that advice and I cannot guarantee it will be positive, although I would not say it will be negative either. We cannot make a comment on it. The Deputy is asking us to make a guarantee on something that is in an ongoing process.

Mr. Shaun Flanagan

In terms of giving a time limit-----

I am not asking for a guarantee on the approval of the drug. I hope the HSE can negotiate a price where it is approved, and we all hope that happens soon. As we are all acutely aware, because we are all trying to achieve the same thing, SMA is a degenerative disease and every week and month matters. I am cognisant that the NCPE refused the price that was offered 11 months ago. Some 11 months have passed, therefore, and representatives from the HSE are before the committee. While I accept that Mr. Flanagan cannot give any guarantees, it has been 11 months since the NCPE refused the price and it is not acceptable that he would say he cannot even give a broad timeline.

Mr. Shaun Flanagan

For the record, in that period of 11 months there were six or seven meetings with the pharmaceutical company about commercial negotiations. The commercial negotiations have finished and, to the best of our knowledge, the company has made it clear it has made its best offer and it will not move any further. The drugs group has considered the drug. In committee meetings like this, it is difficult to explain the complexity. There is not one decision to be made but rather three separate decisions: SMA type 1, SMA type 2 and SMA type 3. There is considerable variation in the level of evidence for each of those. As has been communicated, the drugs group strongly want access for type 1 on the basis of the evidence, which is robust. It made an offer to Biogen but the offer was not acceptable. Biogen made a counter offer to the State but that offer for type 1 has not been acceptable to date. On type 2 and type 3, it is a far more challenging issue because the evidence is far less robust.

That is helpful. If we assume the best and final offer was made by the pharmaceutical company, although that can change, can the HSE not give the parents a broad outline? It sounds as though the negotiations have concluded and it is now a question for the State. Surely we should then be able to indicate how long the State will take to make these decisions.

Mr. Shaun Flanagan

I can give a timeline. We can assume that the rare diseases technology review committee will provide a report relatively imminently, and there is a drugs group meeting in December which already has five items on the agenda because multiple medicines are going through the process, including multiple orphan drugs. In the past 12 weeks, for example, there were three meetings of the drugs group and 18 drugs were assessed and reviewed at the meetings, which means that we can process approximately six per meeting. At the moment, there are four items on the agenda. If it can be put on that agenda, it will be dealt with on that agenda but there are steps in the process and we have multiple other drugs and patients who also deserve responsibility.

To give context for the challenges the State faces, in 2018 to date the drugs group has made positive recommendations for medicines that will cost the State €300 million over the next five years. A significant amount of money, therefore, is flushing through in positive recommendations through that process. It is a very challenging position for the State to have to try to fund, and many orphan drugs with positive recommendations are included in that. From an evidence point of view, notwithstanding that SMA is an horrific disease and everyone recognises the unmet need of the patients, not least the type 1 patients, it is very challenging due to the lack of evidence evidence and maintaining cost effectiveness, even at the commercial offer.

It is public money and I would love to be able to put what the offer is into the public domain, but I am constrained by the company's constraints.

I am not asking Mr. Flanagan to do that; I am just looking for timelines. If it is discussed, and if it gets onto the December agenda, is the drugs group the deciding body or does it go back to another body?

Mr. Shaun Flanagan

The drugs group is put in place to make recommendations to the senior leadership team of the HSE. From a statutory point of view, the senior leadership team of the HSE must sign the cheque. The sequence is such that if drugs that are in the drugs group in October receive a positive or negative recommendation, they go onto the agenda of the next leadership team meeting.

The meetings are held every month.

Mr. Shaun Flanagan

Yes, every month.

It could be that it is on the agenda for-----

Who is on the review group that meets every month?

Mr. Shaun Flanagan

It is not a problem for us to provide a list of the membership for the committee. There are clinicians and representatives from each of the divisions, as was outlined in answers to parliamentary questions. The information has been provided to the Oireachtas but we can provide a list to the committee.

If it is put on the agenda for the drugs group for December, a recommendation one way or the other, or potentially somewhere between, will go-----

Mr. Shaun Flanagan

The recommendation will more than likely be type 1, type 2 or type 3.

Yes. That recommendation would then be sent to the HSE leadership team, which would discuss it at a January meeting. Is that how it works?

Mr. John Hennessy

Yes, it normally follows the next available leadership meeting. Realistically, it will be an early 2019 referral to the leadership team, subject to the outcome of deliberations with the technology review committee.

Whenever the recommendation is sent to the HSE leadership team, is that team the final stamp to say "Yes", "No" or somewhere in between?

Mr. Shaun Flanagan

Yes, but to clarify, that is if there is a budget impact. If money is being spent, it is the director general, the directorate and the HSE senior leadership team that must sign off on it. There are some medicines, however, for which the net cost is not additional, and we accelerate the process for them.

I turn now to the process. Professor Barry made a point, on which I fully agree with him, that the State should pay on an outcomes basis for orphan drugs. If there is a drug, be it Spinraza or something else, which works on, say, one in five people, and if it is not cost effective to provide ongoing treatments for all five, we can identify and pay for the one for whom it works while stopping the treatment for those for whom it does not work, although that is not always easy and it can be politically and administratively difficult but it must be done. I have put Professor Barry's point to several of the bigger pharmaceutical companies which provide some of these fantastic drugs and they were positive.

They said they want to do it as well and they gave me examples of other countries in which they are doing this. The impression I got was that pharmacoeconomics here is not up for it. I am not suggesting that is what I was told, rather it is what I had assumed. However, what they said is that the problem in Ireland is that we do not have the necessary IT systems in place to track the patients and, therefore, be able to do this. Is that the witnesses's understanding? Is the barrier to the payment by outcomes, which hopefully would allow for more of these wonderful drugs, that we do not have in place the IT systems to do it?

Professor Michael Barry

What the Deputy is referring to is what we call managed access programmes with specific starting and finishing criteria, or stopping criteria if the system is not working. I do not think there are IT barriers to it. For example, in the case of Nusinersen we are not talking about a lot of patients so it should be relatively easy to track patients and their outcomes. The focus on managed access programmes came on stream with the rare diseases technology review committee, the focus of which is not on cost effectiveness or money but clinical outcomes from the point of view of patients and patient representatives. It is a question of the system focusing on managed access programmes. I think they can be delivered but I take the Deputy's point that for the conditions in respect of which the patient numbers are larger there would be a challenge. For the conditions about which we are speaking, the patient numbers are not large and it should be eminently possible to do it. The idea of a managed access programme is that we know from the trials that, say, 50% of patients may not respond to the drug. I do not think anybody wants to be funding expensive drugs like Spinraza at a cost of €500,000 in the first year and €250,000 per patient in the second year. It is about trying to do the best we can and to ensure that people who respond to the drugs get them.

I would like to discuss the alleged delay in Ireland in getting some of these drugs onto the market. The witnesses may disagree but it has been put to me by patients, patient advocacy groups, clinicians and the pharmaceutical companies that relative to other EU countries Ireland is very slow in getting the drugs to market. For example, in the case of Translarna, 22 other countries-----

Mr. Shaun Flanagan

My apologies for cutting across the Deputy but I would question the figure of 22.

That is fine. It has been put to me by a number of people that Ireland is slower than other countries at getting drugs to the market, for whatever reason. What is being put to me, fairly or unfairly, is that the NCPE moves pretty quickly and is transparent in what it does - whether one agrees or not with the full process that is what happens - and that the EMA at a European level is pretty good and is tipping along but when it comes to the Department of Health and the HSE the process slows. I am not making that allegation. It has been represented to me by numerous groups that at Department of Health and HSE level the process becomes opaque and there is not the level of interaction that people are looking for. Is it fair or accurate that the process slows once it reaches Ireland and, if so, what three actions can we take to make it more transparent and quicker?

Mr. Finian Judge

The Deputy mentioned the HSE and the Department in terms of where the bottlenecks may occur. As I said in my opening statement, statutory responsibility for decision making in terms of reimbursement rests solely with the HSE. The Department is out of loop in terms of the decision making process.

On the substantive issue of the perceived delay in Ireland, there are various lists of where Ireland sits in regard to other European countries. We have no idea how these lists are put together and what is regarded as reimbursement in one country in comparison with another. Over the last number of years a lot of medicines have been reimbursed. Practically none has been refused.

It is the timing of the process that is in question.

Mr. Finian Judge

I will ask Mr. Flanagan to respond on the timing issue because it is a matter for the HSE but the timing issue cannot be looked at separately from the pricing and funding issues.

Mr. Shaun Flanagan

I cannot remember a year of my career when the HSE was under spend on drugs. There is clearly a funding challenge for every country around the globe. Many countries are trying to get into multilateral type arrangements, whether BeNeLuxA or Valletta, such that Ireland is not the only country struggling in that regard. I would not argue that we are slower than other countries. In my view, the challenge is around the availability of sufficient resources and trying to match the resources we have with the demand.

On the issue of resources, is Mr. Flanagan speaking about drug budget resources or human resources?

Mr. Shaun Flanagan

It is drug budget resources. The NCPE and the pharmaceutical unit did have a challenge around human resources but that is no longer an excuse as over the last 18 months the HSE has given us substantial resources. I will give a practical example, which might better explain the delay. Commercial negotiations can take a long time. It can be hard to get a company to the point of an offer that will be acceptable to the State. The system is broken internationally from a pricing point of view in that we have a system whereby companies come with lists prices of, say, €100, and they get involved with one country in non-transparent negotiations and reduce the price to, say, €90; they then move on to the next country for which they reduce the price to €80 and then for a third country they reduce it to €70. If Ireland is the first country it pays €100. It is unfortunate but true that the further down the line a country is, the better the offer it gets. It is not possible for me to put particular information into the public domain but I will try to illustrate what happens in the case of a non-orphan drug. The drug Pablociclib - Ibrance - is used to treat breast cancer. It was approved by the EMA in 2016. At the time of the pricing and reimbursement application the company in question applied for a price of €3,800 per pack. This would have resulted in a budget impact of €66 million. This was in commercial negotiation for over a year. Eventually, a pricing decision was made in a different country. The price offering given to us at that point was €2,190 per pack. Within three months the HSE had completed all processes and had reimbursed it. The net difference is €28 million over five years. If we go early, we pay more which means we can reimburse fewer drugs. The challenge is getting the balance right in terms of the right amount to be spend at a premium over other prices versus fighting as hard as we can for reduced prices.

I thank the witnesses for being here. We respect and appreciate the job the witnesses do and we acknowledge that very often they are portrayed as the bad guys but sometimes they do not help their own cause. Patients come to us because they want to know the status of their approvals. They should not have to contact their local public representatives to get that information. It should be readily available to them but clearly it is not because if it was patients would not be making representations to us. Patients are awaiting the approval of drugs that they believe will be effective for them but are unable to find out the status of the approval of those drugs.

What I am hearing from the Department of Health is that it is out of the loop with regard to the process. I understand there are various meetings and so on. Is it possible to bring transparency to this while respecting commercial sensitivity? I fully appreciate that the Department must uphold commercial sensitivity. Is it possible to put in place a system that keeps the families informed? Everyone seems to be waiting. The clock is ticking and people are told another meeting will take place. Yet, the Department does not know if the matter will get onto the agenda of the meeting. If it does, the Department does not know what is to happen at the next meeting. It seems that no matter who I talk to, that person is never the person who is responsible. It seems it is always a matter for another person.

I found it curious for Mr. Judge to say that the Department was out of the loop with regard to the process. I would have thought the Department would have been central to or involved more in the process. Do the officials have any suggestions on how we might be able to improve transparency?

I will bank the questions. It will be easier in terms of time and I know others wish to come in. Has the rare disease technology review group published a work programme? If so, I have not seen it. If there is a work programme, perhaps it can be shared with us. If there is none I would be a little concerned.

The question of reviews and expected timelines is relevant. We know that we are not dealing with things that necessarily move in a straight line but the possibility of expected timelines and sharing that information is important.

The patient and clinical engagement system in Scotland is a relevant model. Scotland has a similar population size, profile and so on in terms of health. It seems there are far fewer problems in Scotland and the system it has appears to work. Has consideration been given to replicating the best aspects of what they are doing in Scotland? It appears to be working. Central to the system there is the involvement of the patients. That is important.

Will the officials give us an update on or idea of what progress, if any, has been made on the BeNeLuxA group? I apologise if the question was already asked - I may have missed it.

There are problems at the moment relating to clinician and patient input into any new assessment programme. Will this take place before or after the health technology assessment will be completed? I am referring to the opportunity for clinicians and patients to have input. I am trying to understand how it works with the various committees. The officials will know this better than I do but the problem with the HTA and orphan drugs is the low level of information available. Often families say to us that they cannot satisfy the necessary numbers – they simply do not have them. Some assessments may set the bar higher in terms of numbers but if they are not there, they are simply not there. Often that leads people to believe they are excluded from the process and it seems to them as if they are not being listened to. That is why they come back through their local representatives.

Both clinicians and patients are involved in the health technology assessment. Is there an opportunity at that point for patients to have an input and influence over the process so that they will be there and will be able to discuss their experience? Often we are not dealing with big groups and we do not have a large population from which to gather the information. It seems sometimes that the information is not gathered from the people who are there because there are not enough of them.

Mr. John Hennessy

The issue of transparency was central to the committee report in February 2018. We have been attempting to address it in several ways. I believe we have made progress but if there is more to be done we would be happy to engage with members on how we can strengthen the transparency factor.

I wish to remind members that the National Centre for Pharmacoeconomics reports are published on the website once they are concluded. The deliberations of the drugs group are notified to the particular companies involved. There can be commercial sensitivities around what goes into the public domain. However, we are particularly keen to be as transparent as possible and to report publicly the outcome of the drugs group deliberations.

My question was about moving along through the process.

Mr. John Hennessy

I am getting there. The recommendations of the drugs group come to the leadership team. The deliberations of the HSE as a public body are available as well. The items on the agenda are public knowledge and the decisions taken at those meetings are publicly available and reported on the HSE website. If there are ways to put more transparency around it, we would be happy to explore those and deliberate on them.

Deputy O'Reilly's point goes to the issue of delay or the perception of delay. There is no deliberate slowing down or delay factor coming through the process at our end. What we see and hear about is access in different jurisdictions but, as Mr. Flanagan mentioned, access can mean different things from one jurisdiction to another and it is not always easily comparable.

We aim for a two-fold agenda. We want to ensure access to medicines for Irish patients and to ensure as much value as we can get throughout the process. We have been exploring ways to speed up the processing with the pharmaceutical sector. Those discussions are productive and proactive in fairness to the industry. We have ongoing discussions on the matter. We have put additional resourcing into the process so that we can handle the additional numbers of applications coming through now for reimbursement. It is a two-way process. Getting to the final price is one of the issues we tend to struggle with in dealing with the pharmaceutical sector. We are trying to resolve that as well. Mr. Flanagan mentioned that the list price and the final price can often differ substantially. It is important we get access to drugs. It is also important that we can get value and demonstrate that as well.

Deputy O'Reilly asked about the rare diseases review group and publishing the work programme. I will ask Professor Barry to speak to that point. Deputy O'Reilly also asked about the Scottish experience. We have been examining that closely and we see opportunities there. Some of the steps that have been taken so far this year in response to the committee report are modelled on the Scottish model of transparency and patient involvement. We hope to go further on that as well. Mr. Judge will talk about the BeNeLuxA question and I will bring in Professor Barry on the health technology assessment and patient involvement aspect.

Mr. Finian Judge

A couple of questions were directed to the Department. Deputy O'Reilly referred to the Department being out of the loop. That was a decision taken by the Oireachtas when it passed the 2013 Act. The idea was that responsibility would be solely vested in the HSE. The Minister has no role in the final decision-making process. That is contained in statute in the 2013 Act.

There was a question about BeNeLuxA. As committee members probably know, the whole concept of regional collaboration is in its infancy. There are a few regional collaboration groups across Europe. We signed up to BeNeLuxA in June of this year. The BeNeLuxA grouping envisages collaboration in four domains. The idea is to collaborate around information exchange, HTA, horizon scanning and joint price negotiations. At this point our involvement is in its early stages, as committee members will appreciate. The win so far for us is really around information exchange. In fact, some of my colleagues today are at a meeting in Vienna on BeNeLuxA. We are merely getting into the process at this stage.

We intend to work on the other domains as the initiative develops.

Does Mr. Flanagan wish to contribute?

Mr. Shaun Flanagan

Professor Barry will address the work programmes.

Professor Michael Barry

The National Centre for Pharmacoeconomics, NCPE, details on its website exactly where in the process is each drug and the dates in that regard. When the process is completed, a report is published on the website.

The NCPE is not the only organisation involved.

Professor Michael Barry

I can only answer for the NCPE.

I acknowledge that but the witnesses are collectively representing the Department and the HSE. The progress is being tracked through all committees.

Professor Michael Barry

That is so, but I can only reply for NCPE and the rare diseases group and I hope to try to do so. We have made many developments in regard to patient involvement with the health technology assessment, HTA, process. There is a patient area on the website through which one can get a summary of the process and submit online. There is also information in regard to interpreting our recommendations and a plain English explanation of them. We hold educational sessions with groups such as the Irish Platform for Patient Organisations, Science and Industry, IPPOSI. We are quite active in the area of patient engagement. Using the website, people email us on a regular basis with all sorts of questions which we are very happy to answer within 24 hours.

On the rare diseases technology review committee, Deputy O'Reilly mentioned Scotland. I agree that the Scottish system is a good model, but £1 million sterling was invested in it. We can improve things. We have been up and running for less than two months, so it is early days, but I would like to think that patient groups and representatives are seeing how this group will make a difference. I agree that it would be nice to have our publications and timelines on the website as well. We do not currently have a website. It would be nice to have that in order that people would know the stage at which a particular drug is and what are our recommendations. That is a great suggestion and certainly something that we should consider.

Are there any other points to be addressed?

In order to make a submission, patients submit an online form rather than participate in a one-to-one meeting.

Professor Michael Barry

The rare diseases group meets those making a submission. For example, we met children with spinal muscular atrophy and their families in regard to Spinraza. They made a very detailed presentation involving videos of what it is like to live with spinal muscular atrophy. Particularly in regard to drugs for rare diseases, the new rare diseases committee considers that dimension which had not previously been looked at in such detail. That is a positive development.

Do the witnesses accept that there is a problem with the current system? Do they accept that notwithstanding the work that has been done to bring families into the process to some degree, the families are still experiencing difficulty with the process and their level of involvement in it? I am not saying that the people in this room do not work hard; I fully appreciate that they do. However, do they think the system is okay and working in spite of the views of patients and their families that it is not working? The problems do not solely involve access, but also that the process is not working for patients and they feel left outside it. Do the witnesses accept that improvements must be made and that there is work to be done? If they do not, I would be concerned.

Professor Michael Barry

Absolutely, there is work to be done. The establishment of the rare diseases committee speaks to and acknowledges that. I was struck by the fact that in our first meeting with patient representatives they wanted basic information on how the system works. When one works in the system, one takes such knowledge for granted. The meeting was very helpful and we spent quite a lot of time explaining how the system works. They came back a week later to present on their particular area, namely, spinal muscular atrophy. The Deputy is correct that we need to engage in more such work and we will do so.

Mr. John Hennessy

What we have done so far this year acknowledges that there was an issue in regard to transparency and patient involvement. However, measures have been taken to address that, such as the expansion of the membership of the drugs group and the formal inclusion of patient representation on the group referred to by Professor Barry. Those are genuine attempts to address that issue. Ultimately, whether people experience a problem with the process probably relies more on the outcome of the process than the process itself. However, if there are further steps that we can take, such as the development of websites and greater transparency, we would be happy to explore those.

I thank Mr Hennessy. I will now move to Deputy Kelly.

I asked the question of all the witnesses. I have not taken much time.

Mr. Shaun Flanagan

We acknowledge that it is a very difficult and challenging area. My team enters every commercial negotiation in the hope of being able to get something over the line. We could improve the processes. The challenge around transparency is underestimated because it is impossible to understand the decision making unless one knows the pricing. The problem is the lack of transparency in pricing in the industry. It is impossible to give a coherent explanation of how a negative decision is made. My experience is that people who have significant challenges with the process often go away when the decision is "Yes". The key challenge is for the State to get access to as many medicines as it can. That is what will solve this issue. Even the fabulous Scottish patient and clinician engagement, PACE, system is experiencing a significant ongoing problem in regard to not having funded Orkambi. Members may think there is silence around that, but there is not.

With regard to the point------

The Deputy should conclude her questioning.

I ask the Chair to allow me to finish as Mr. Flanagan's reply was not particularly fair.

Mr. Shaun Flanagan

I did not mean it in a bad way. People want access to the drugs.

Mr. Flanagan stated that once people get the "Yes" answer, they go away. With respect, such people go back to looking after their loved ones who are struggling with an illness. It is not very fair to say they would not want to------

Mr. Shaun Flanagan

I apologise and unreservedly withdraw that comment.

It might be more correct to state that the HSE does not follow up with such persons and ask what were their experiences of the system.

Mr. Shaun Flanagan

I unreservedly apologise for any offence caused. It was my intention to try to explain the challenges and so on. I apologise unreservedly if my wording was inappropriate or callous. That was not my intention and I sincerely apologise for it.

That is fine. I thank Mr. Flanagan.

It is obvious that we need an extensive national medicines policy to be driven at departmental level. It is to be hoped that will happen in the next Government. Mr. Judge stated that the Minister cannot get involved in drug reimbursement decisions. If that is so, what happened in the case of Orkambi? Did the Minister become involved contrary to the Act referred to by Mr. Judge or did he have no involvement? Is there a clause in the deal with the Irish Pharmaceutical Healthcare Association, IPHA, whereby drug cases may be referred to the Department in certain instances?

There was a case in Crumlin last week, and we heard earlier from the witnesses that genetic services in this country, which are intertwined with decision-making, are simply not up to the standard required. Is this accurate? I have spoken to people in the HSE who have said they have been trying to employ people for a number of years. The case last week has caused alarm. Is it the case that genetic services are not up to the standard required? That is my second question to Mr. Judge.

My next questions are probably a mix for the other three witnesses. The first concerns affordability, which is an issue in the case of orphan drugs. What is the HSE's position on biosimilars and biosimilar penetration? What are the expected savings in this regard for 2019? I presume that with the budget and projections, the HSE must put in something.

Fourth, what is the typical weighting price for tenders on drugs? How do we compare with other countries, such as Germany and the UK? I understand that in many cases the weighting they have on price in their tenders could be up to 80% while we are generally very low at 25%. Are we not losing money as a result of this?

My last question concerns pembrolizumab, the drug Vicky Phelan is on. I do not expect any of the four witnesses to criticise Government policy, but has any of them ever seen a similar case in which a decision was made to give a drug such as this, which is off licence, free of charge to one cohort of women or men outside of the normal Health Products Regulatory Authority, HPRA, procedure, which is to go two years? Would this be in any way normal? How can it be that Áine Morgan in Loughrea - this is all in the public domain, by the way - is fundraising to go on pembrolizumab? Ms Morgan has cervical cancer but is not one of the 221 women, yet Vicky Phelan, to whom I have spoken in depth about this and who is one of the 221 women, is getting the drug for free from the State. One cohort is getting it for free. Women in another cohort must get a clinician to say they need it, but they do not get it for free. The drug costs €8,500 every three weeks.

I put the following questions to each and every one of the witnesses. Do they believe this is equitable and fair or discriminatory? Do they believe it is legal? I certainly have issues with it. I cannot in any way justify how one can distinguish between two women who have cervical cancer such that one gets a treatment free of charge because of a decision made at Government level and another does not. I would like to hear the witnesses' views on this. I am aware this drug is used to treat other conditions and other cancers but I want to know specifically how within our drug administration policy this is equitable or fair. Have the witnesses ever seen this done before? I have spoken to many of their colleagues from different walks of life and there is deep unease in the HSE and other parts of the health service about this. Something will have to be done about it.

There are five questions to be answered.

Mr. John Hennessy

I will start some of the answers and my colleague, Mr. Judge, may be able to help with others. What happens in the case of Orkambi is that the HSE operates within the scope of its service plan for drug applications for reimbursement brought before it. If we can provide within the scope of our service plan for the applications that present, that is where the decision begins and ends. If an application comes before the HSE that goes beyond our scope and capacity in the service plan, there is a route, as the Deputy said, to escalate the matter to the Department and the Minister.

That is what happened with Orkambi.

Mr. John Hennessy

To the best of my memory, that is what happened in the case of Orkambi, but Mr. Judge may have a little more information on that.

I might ask Professor Barry to deal with the question about genetic services and the issues concerning biosimilars the Deputy has raised. There is a lot of information available on both, but on biosimilars in particular.

To respond to the question the Deputy raised about weighting and drug tenders, outside of the normal reimbursement process I am not aware of too many drugs in respect of which we embark on a tendering process with a competitive supplier. I am aware of one or two but I will have to check further the weighting of the price within that. The Deputy has indicated it is 25% here as opposed to 80% elsewhere.

That is so in one case I am aware of.

Mr. Shaun Flanagan

I must qualify that our responsibility is for reimbursement, which is not a purchasing model, and this should be remembered. The one case of which I have recent experience is the hepatitis C tender. Clearly, before one goes into any tender, one must figure out the criteria. If the drugs are very alike, it will be almost entirely price, but if the drugs have significant variations there will be more for the other advantages in terms of convenience, perhaps, or whatever else. I can tell the Deputy that the hepatitis C tender was almost substantially based on price, and that delivered about-----

About what percentage?

Mr. Shaun Flanagan

I cannot recall the percentage off the top of my head but it is in the 80s or 90s. It is of that kind of scale. I can double-check to be absolutely sure, but it was-----

To save time, because this is very statistics-orientated, I might supply a list and the witnesses might come back to me. Would that be okay?

Mr. Shaun Flanagan

As I said, a reimbursement model generally does not involve tenders. Tenders happen in the hospital system, and I am not-----

That is what I am asking about.

Mr. Shaun Flanagan

Yes, but I cannot answer that question here today. I am not the chief pharmacist of the HSE or the chief pharmacist of the reimbursement section.

Mr. Shaun Flanagan

Within the tender process, however, when I worked as a hospital pharmacist, we would try to design our tenders in such a way that we had fairly comparable items in order that we had a high weighting on price so that, in turn, we drove value as opposed to allowing people to compete on differences, unless there were substantial differences. I am not aware of a tender in my experience for 25% but I could be wrong. I would have to-----

That needs to be looked at.

Mr. John Hennessy

As for the question of drugs funded outside of the process, I have seen it happen. It is very rare but it does occur from time to time. Usually, it involves life-threatening situations. Most systems and processes would contain the capacity to respond in a life-threatening situation. The process, which has developed and evolved over a considerable time, is designed to ensure that all the checks and balances that are required are dealt with. As I said, though, situations can arise from time to time when an emergency response is required.

I am not leaving here until we get an answer to my last question. What Mr. Hennessy has just said is of no comfort. This is going to explode in everyone's face. The witnesses all know what I am talking about. One cannot discriminate between two people on the basis that one got cancer at one point and another got cancer a year later. There was a crisis in this country and the Government made a decision.

That is fine. I am not criticising the Government, but there are consequences because a precedent has been set.

Mr. Shaun Flanagan

In terms of answering that, I am not sure what the Deputy expects. It did not come through a reimbursement process. A standard reimbursement process involves, at the start, the EMA reviewing a medicine for a particular use to decide if the quality, safety and efficacy is appropriate to support market authorisation. After that, we have an assessment process regarding cost-----

I know the whole process. It takes a couple of years but all of that was skipped in this instance.

Mr. Shaun Flanagan

As far as I am aware, there will not be a market authorisation in Europe for cervical cancer for pembrolizumab or any other immunotherapy before 2021 at the earliest.

I understand that and I agree that it will be across Europe. In terms of the women affected, it will work for some but not for others. I am not saying that this is a miracle drug in any way, shape or form but it seems to be helping Vicky Phelan, with whom I am in contact a lot. In other cases, it may not help but all of these women will do anything they can, regardless of whether they are in the cohort of 221, to get a chance at life. The drug is made in Ireland. How can we collectively justify the fact that it is outside the process outlined by Mr. Flanagan? I agree with him and yet we have a decision to give it free to some women who are part of the cohort of 221 . No one can stand over that; it is impossible to justify. We cannot distinguish between a lady in Loughrea who is crowd-funding in an effort to raise money to get this drug and to get a chance at life and those in the cohort of 221. I would like to hear the opinions of all of the witnesses on that.

I invite Professor Barry to respond first.

Professor Michael Barry

As the Deputy has pointed out, these are very expensive medications. My feeling is that all medication should be assessed from a value-for-money perspective.

I thank Professor Barry for his honesty.

Professor Michael Barry

That is my feeling and that should be done without exception.

I appreciate the Professor's honesty.

Professor Michael Barry

If the medication provides value for money for the taxpayer and there is a clinical benefit, that is fair enough. That is my view on that issue.

That did not happen in this case.

Professor Michael Barry

No, it did not.

Mr. Shaun Flanagan

In case the Deputy misinterpreted what I was saying, I am pretty clear in my view that the only way we can provide guarantees to the population on quality, safety and efficacy is by following the processes that are set out. However, I can understand how, in extremis and in cases where it is thought that the State may have had a role in something, exceptions may be made. Historically, it has always been possible for clinicians to set out individual circumstances of patients under exempt medicinal products legislation, where drugs were not licensed. There are, in exceptional individual circumstances-----

I am aware of that and Dr. Fennelly and Professor Crown have written about it. I understand that it can be done off-licence. The issue here is that it costs €8,500 every three weeks and the State is paying for it. I invite Mr. Judge to respond.

Mr. Finian Judge

I will address a number of the issues raised by the Deputy-----

I am interested in Mr. Judge's view on that specific point.

Mr. Finian Judge

On that point, I cannot comment on the merits of a Government decision relating to Cervical Check. That is the situation that pertains. On the role of the Minister in the context of the reimbursement process, the Deputy is correct that there is a clause in the IPHA agreement whereby if it has been identified that a medicine cannot be funded within existing resources, the HSE may inform the Department and, obviously, it gets into the Department and is brought to the attention of the Minister at that stage. The Minister may decide, if he or she wishes, to bring a memorandum to Government on that funding challenge in respect of a particular product.

Did that happen with Orkambi?

Mr. Finian Judge

I was not around at the time but my understanding is that it may have happened in the case of Orkambi.

The Minister intervened in the process by way of the clause to which Mr. Judge referred.

Mr. Finian Judge

Yes, if he did intervene, he did it in that way.

The Minister can have a role here.

Mr. Finian Judge

The clause refers to cases where the HSE cannot fund from within existing resources. The HSE is assigned a pot of money every year for the primary care reimbursement services for all drugs and all community schemes. The HSE has a statutory responsibility to assign that money across all schemes, including new drugs. It is only in the event that it identifies a problem from within existing resources that it can inform the Department.

In fairness to Mr. Judge, I know he is in a difficult situation as a representative of the Department but, in a roundabout way, that means that the Minister intervened in this scenario. As many of my colleagues have said, most notably Deputy Brassil, political pressure creates the conditions which allow the Minister to intervene. That is just reality. Professor Barry has been very open and honest about the issue. He believes that everything should go through the same process and, in fairness, Mr. Flanagan made exactly the same point. We have a situation whereby a Minister can intervene and that is something we must consider further.

I have a question for Mr. Hennessy. He was clear in what he said but what is going to happen in the context of pembrolizumab? What is going to happen to the women who will ask why they are different to Vicky Phelan? For the sake of clarity, I have spoken with Vicky Phelan in detail about this and her views are similar to mine.

We will have a brief answer from Mr. Hennessy and then we will have to move on.

What is going to happen? How can we distinguish between two sets of women? There is a woman in Galway-----

Mr. John Hennessy

I appreciate the sensitivity of the point the Deputy is making. I simply cannot address or answer it. In terms of the specific question as to whether I have ever seen a situation like this before, the answer is yes, I have. Would I prefer that the process would operate in the manner in which it is designed? Yes, I would. Of course, the process is designed to deal with all of the checks and balances that are necessary regarding medicines but everybody also appreciates that emergency situations arise from time to time and the system has to be able to respond and react to that too. That is as far as I can go with it, I am afraid.

It is pretty clear that we have an issue here that must be addressed.

I appreciate that. The Deputy has made it very clear. Deputy Brassil is next.

I thank our guests for attending. I seek clarification from Professor Barry to begin. He referred to two specific drugs, namely, Kuvan and Spinraza. He said that following two recent meetings, he recommended to the HSE drug group that access to Kuvan be considered under a managed access programme, with a starting, stopping criteria which I am sure will delight the PKU society. The recommendation on Spinraza is expected shortly. Why is the Spinraza recommendation not public? If Professor Barry can tell us about Kuvan, why can he not tell us about Spinraza?

Professor Michael Barry

It is simply because of timing and the point at which they were presented to us. Kuvan was dealt with first and then we moved on to Spinraza. There is no reason other than that. It is just a question of-----

Is there a plan to assess Spinraza further?

Professor Michael Barry

No, there was a series of meetings in respect of it. There were five meetings within 24 days, most of them focusing on Spinraza or nusinersen. We are now at the stage where a document is being prepared which I understand will be including starting and stopping criteria prepared in conjunction with clinicians and also having listened to patients and their relatives. Our task then is to get this recommendation document to the HSE drugs group so that it is not just cost effectiveness that is considered but also the other aspects. The committee, in fairness, has done a lot of work in a short time and we are mindful of the time issue here. That is why I am saying that I am hopeful that the document will be with the HSE drugs group within weeks.

I think Professor Barry can appreciate that all of us have met with the families affected and that is why we are raising this.

Professor Michael Barry

Yes.

I will now turn to Mr. Judge's opening statement.

We have had much debate around the Act, its suitability and what it covers. The committee is really focusing in on orphan drugs, and drugs for rare and ultra-rare diseases. Having had two previous meetings with this group, the committee recommended that the 2013 Act should be reviewed. That was a recommendation of this committee.

In a debate in the Dáil on the drug Ocrevus, which is used to treat multiple sclerosis, MS, the Minister stated that if people in this House think that the current system is broken, we could start hearing what people want to replace it with. He stated on the record of the Dáil that also he thinks it is broken and that the conundrum is how to come up with a better model. I add to that the fact that, in 2017, of the 148 medicines that were designated orphan and subsequently received marketing authorisation by the EMA, 53 are available in Ireland, which equates to 35.8%. That is very much on the lower side compared to Germany, which has 133 of the 148 approved. We are right down on the lower side of things. We have an issue around reimbursement on orphan drugs. Earlier, Mr. Judge stated, "The Act provides for a fair, transparent and rigorous process of assessment [and] the Minister is satisfied that there are no legislative barriers to the reimbursement of orphan drugs." What has changed?

Mr. Finian Judge

The first thing I would say is that the Act has only been in place since 2013. The Minister has stood over the robustness of that Act on numerous occasions. Since the committee's report calling for a review of the entire Act was published, and because the Act contains so many different provisions, we have concentrated on addressing the recommendations regarding the reimbursement process because it was that element of the Act the committee focused on in its report. Obviously, if, down the line, the Minister decides that there should be a review of the 2013 Act, it is in his gift to decide to bring forward proposals on that Act. I am letting the committee know that, since the publication of its report, we have, with the NCPE, been concentrating on what were essentially process issues which the committee pointed out in its report. As my colleagues have said today, the HSE has done a lot in terms of the process to address any barriers that the committee pointed out in its report, or any areas where orphan drugs may have a problem in the process. I think the big development is Professor Barry's new committee which, more or less, adds another layer to the process because of the special situation around orphan drugs.

I want to put on record that I disagree with Mr. Judge's opening statement and the Minister quite clearly disagrees as well. He says there are no legislative barriers to the reimbursement of orphan drugs. I ask why then would the Minister make the statement he thinks the system is broken too? They are two directly opposing views from the same Department.

Moving on to trying to get the best value, Mr. Flanagan gave a very good example of getting in there and batting and waiting for a particular drug that went from €3,800 per unit to €2,100 per unit. I have pointed out, on numerous occasions since I was elected, that there are potential savings of multiple millions in biosimilar products. The IPU has done a report which outlines savings of €320 million over three years. The HSE is anxious to hold out for the best price, and I agree with that approach on orphan drugs. Why is the HSE not banging down the door for the savings it can achieve in the context of biosimilars?

Mr. Shaun Flanagan

I think that is an unfair comment. I am quite happy to put on the record that we absolutely need biosimilars. Deputy Brassil is a pharmacist, as am I. We both know they are not substitutable. We both know they actually have to be prescribed by physicians as the biosimilar, as opposed to as the biologic. Professor Barry's team is working very hard to get what is called a best-value biosimilar document out for early in the new year to try and drive biosimilar uptake. I am quite happy to put on the record and avail of any publicity we might get out of today to say that we need the support of gastroenterologists, dermatologists and rheumatologists to write biosimilar prescriptions. They are less expensive to us and will deliver savings, but we need them to engage with their patient groups and get the patients to accept that a biosimilar will be used.

The HSE was engaged in a drive in respect of generic products. It had absolutely no difficulty with generics being prescribed.

Mr. Shaun Flanagan

To be clear again, Deputy Brassil and I are both pharmacists and we both know that the legal position is that generics were substitutable. They were set out in legislation as being substitutable. The HPRA was given the power to designate them as interchangeable. That power is not available to us and Deputy Brassil and I both know that.

I am well aware of the position. I dispense products every month. I refer, for example, to Humira and Enbrel. I am aware of the biosimilars available at significantly less cost and I have yet to see a prescription for one.

Mr. Shaun Flanagan

I agree with the Deputy.

I do not want to be argumentative, but I am seeking solutions for specific families who have contacted me regarding specific drugs and it always comes down to cost. There are savings out there and we are not availing of them.

Mr. Shaun Flanagan

I am flagging to the Deputy that we agree with him, absolutely and fundamentally. Professor Barry's team is working, as we speak, on a best-value biosimilar paper to try to deliver that. That is out to public consultation, is it not, Professor Barry?

Professor Michael Barry

The Deputy is absolutely right. That is an area where we can make substantial savings and, in the medicines management programme, we have taken this on. Consultation finished on Friday last. The anti-tumour necrosis factor drugs which the Deputy mentioned account for approximately €250 million. Adalimumab, or Humira, and etanercept, or Enbrel, are the two leadings ones and are not far off €200 million. We will publish what, in our view, is the best biologic value of choice for the health service in this country. We hope to do that in early 2019. That will afford the HSE the opportunity then to highlight that this is the best value product and we should be using it.

I agree with what Mr. Flanagan is saying, that it is down to prescribers as well, but we will be issuing that guidance very early in 2019. I agree that there are lots of potential savings. It is about creating space in order that we can afford the other drugs that we are discussing.

I welcome that. I would love to see a budget for orphan drugs. I have asked, again on several occasions, for a specific breakdown and I keep getting the reply that there is nothing in the Act to differentiate orphan drugs from any other drug. That needs to be changed. That is why I have submitted a Bill to change the legislative position in order to allow for orphan drugs to be treated separately. If they were treated separately and there was a separate budget for them, then the savings that were made on one side could be looked at towards providing on the other.

With my last contribution, I want the witnesses to look at the Swedish model. They, ironically, have the same proportion of health expenditure and medical goods as we do, yet they use a qualitative analysis in their orphan drugs reimbursement but do not set a threshold. They take the types of things we have been talking about - patient advocacy, human value and cost-effectiveness - over a very small patient group.

When one is looking for data, particularly for an ultra-rare disease, it is almost impossible to get because there might only be half a dozen patients and the type of assessment that is being undertaken will not facilitate this.

Professor Michael Barry

I get the Deputy's point. We are aware that none of the drugs for rare diseases will reach the €45,000 per QALY. However, the assessment process is valuable in that it highlights the issues, areas and clinical evidence and the pricing issue. What price would be necessary to get to a better place? Mr. Flanagan uses the results of our assessments to enable a better deal to be secured on these. The fact that it underwent assessment provides the HSE with a lot more information on it rather than simply reimbursing it straight-up.

The new committee speaks to the additional aspect of this such as unmet clinical need and physicians' and patients' viewpoints which is valuable. Drugs for rare diseases are reimbursed, such as Orkambi. There is no way that Orkambi would ever reach €45,000 per QALY yet it is reimbursed nonetheless. The HSE can use the reports to try to improve the offer on the table but the €45,000 per QALY threshold is not an absolute and is not used in that way.

On Orkambi, I must give credit where it is due. Vertex are now looking to have the HSE model replicated in other countries, including Sweden, because they regard it as a good model, which has been successful and delivered value for money. It has been agreed that down the line, iterations of Orkambi will become available. However, was that a result of the unending political pressure and the demonstrations that went with it or the HSE process? I suspect it is a combination of the two but not every group has the support of the people in such as with Orkambi. We are dealing with five or eight families who do not have that political clout or do not have the ability to protest. I would like them to get the same treatment without the controversy.

Professor Michael Barry

I take the Deputy's point, but we were steadfast. We never believed that Orkambi was value for money, nor do we believe that now. Our position is unchanged. However, there is a real world out there, so negotiations take place and the drug is made available. That is how our reports are used. We do the best we can and Mr. Flanagan and his group do their best in negotiations and get drugs available.

Mr. John Hennessy

The switch to biosimilars is a high priority in the Department and HSE. The agreement in place between the State and the pharmaceutical industry provides for value on the launch of the biosimilar. Regardless of what is prescribed after the launch of the biosimilar, we get the discount.

Mr. John Hennessy

Yes.

There is 70% available.

Mr. John Hennessy

We know there is more and we are anxious to get there. However, the success in the area of generics was due to the enabling legislation that allowed substitution, which is not there for biosimilars. That relies on prescriber behaviour, which is an influencing factor rather than a directing matter. It would be interesting to have legislation on that to enable it to happen more quickly but altering prescribing behaviour is a slow process.

Mr. Shaun Flanagan

I will add two brief points. I agree with the Deputy about biosimilars. There are schemes and hospitals. There is a large poster promoting biosimilar uptake in the outpatients department of St. Vincent's hospital. Work is ongoing in the area and some of it has been successful. There are also tenders in the hospital for hospital-related drugs. The community primary care side is more challenging.

I reiterate what Professor Barry said. The €45,000 per QALY is not a binary decision. If something costs less than €45,000 per QALY, the HSE will always say "Yes". No cost-effective medicine has ever been denied. As the cost per QALY increases, the probability reduces a little but that is offset by the magnitude of the unmet need and the magnitude of the clinical efficacy. The drugs groups try all the time to arrive at a judgement on that. It is honorifically challenging stuff for them, for which I do not envy them. The €45,000 per QALY threshold is not a binary "Yes" or "No".

Mr. Hennessy referred to the possibility of legislation for biosimilars similar to that for generics 15 years ago. That needs to be examined further than at a meeting of a health committee. That is not substitutable and I cannot imagine a situation where we would introduce legislation to force a consultant dealing with a complex condition to change medication based on a direction by the Oireachtas.

In his opening statement, Mr. Judge said there would be a governance review. Has this been sparked by anything?

I am very much on the same side as the witnesses. I understand the challenge of a pharmacist or a medic trying to balance budgetary constraints.

Following Deputy Brassil's contribution, it is of great concern, particularly in the case of Orkambi, that when there is a well-organised group, it can result in a situation where he who shouts the loudest gets what he wants. That makes me uncomfortable, both as a legislator and a healthcare professional. In light of Deputy Kelly's comments, while acknowledging the autonomy of prescribers to make decisions as they always have, it is not fair to say that a decision to jump over certain regulations can be equated to the use of exempt medicines in the normal scheme of things. There is much talk about conscience these days, but some of us might want to examine our consciences if we were answering those who shout loudest over those with no voice.

When pharma and economics blend, some of the language might come across as crass. However, ultimately, if €500,000 is being spent annually on a patient, someone else is not receiving something and that must be remembered. If we have given something to a particular group, does this committee suggest that we should give it do everybody or we take it away from those we did have given it to? It is easy for members to come here and throw out loose statements but, ultimately, it is a question of whether we take a medication away from somebody or whether we have a free for all.

I must leave now. I am in favour of there always being a level playing field, where if there must be a decision that goes outside the parameters, it should not be made in these Houses or by a Minister for Health but by a professional at the top of his or her game, namely a consultant operating in his or her specialism. Members who make representations have a responsibility when throwing out terms such as "life-saving" and "people are being denied a chance". Leaving aside QALY and health technology assessment, the reason many of these drugs are not mainstream is because the evidence base is not there.

People in these rooms and elsewhere talk about money for this and money for that, but there is a limited pot. This is difficult for the families affected and they are entitled to fight for themselves and what they want, but we have a responsibility and we must be reminded of it every so often.

I must leave as I have an engagement at 1 p.m. but I will read the replies if the witnesses wish to comment. I apologise for leaving.

Perhaps the witnesses will bank those questions while Senator Colm Burke makes his contribution.

Recommendation No. 13 in the committee's report of February 2018 was to work with other countries on the assessment process. It recommended that the HSE works with other European countries on dealing with assessments to expedite that process. Has anything been done on using the assessment process in other countries to help people arrive at a decision? Has there been co-operation with other countries in that area? There is a great deal of duplication in assessments. If something is passed by European Medicines Agency then each country examines it individually. The idea behind co-operation is that to speed up the process in dealing with that. Has anything been done on that area?

We hear every year that the cost of pharmaceuticals is approximately €2 billion but we do not get a breakdown of that. Are the figures available? The healthcare budget for the coming year is more than €17 billion. Is there a breakdown of what amounts are being spent on generic drugs, patent drugs and orphan drugs?

The other issue that arises is whether there is variation in the use of generic drugs from one part of the country to another. If we can save money in one area, it means more money could be available for another area. Perhaps there is an analysis of that but I have not seen it. We must examine that issue of value for money as well as value for money in the HSE. It is fine to say more money is being poured into healthcare but unless there are efficiencies or value for money, there will not be a benefit.

Can Mr. Hennessy provide a detailed breakdown in each area? Have savings been made since the legislation relating to generic drugs was introduced and, if so, where have those savings been made? Does a great deal more need to be done to make savings in order that more money is available for orphan drugs, accommodating the needs of people who have rare diseases and so forth and ensuring they can get the treatment they require? Mr. Hennessy probably does not have the information with him but can we get that detailed breakdown from the HSE at some stage? For example, last week I received a breakdown of staffing numbers in each area. There is a significant cost because an additional 13,500 staff have been recruited. Likewise, new drugs are being taken on as well so there is an added cost, but are savings being made in other areas?

Mr. Finian Judge

Deputy O'Connell asked about the proposed governance review. That proposal has been around for a couple of years to appoint somebody to examine the internal structures in the HSE in respect of systems, processes and procedures. It was never intended to be a review of the 2013 Act. It is now an action point in Sláintecare so my colleagues are in the process of working with the Office of Government Procurement in preparing a tender for that review. We anticipate that the review will get under way in the new year.

Does that refer to committee recommendation No. 5 to appoint of an independent academic with knowledge of pricing and reimbursement to conduct a review of the current process and the role of orphan drug availability in Ireland? Is that the review to which Mr. Judge is referring to?

Mr. Finian Judge

Yes, it will certainly go some way towards addressing that recommendation.

That recommendation was that it would be an independent academic, but what is being proposed by Mr. Judge is an internal review within the Department.

Mr. Finian Judge

No, we are working on a tender to go externally for that review.

Senator Colm Burke asked about working with other countries. As I said earlier, we are in the infancy of working with our new colleagues on the BeNeLuxA arrangement. We only signed the arrangement in June and, to date, our focus has been around sharing information. However, as time progresses, we will certainly work with them on the other domains, which are HTA, horizon scanning and ultimately joint assessments. Some of my colleagues are in Vienna today with their BeNeLuxA colleagues to try and progress that work. We will work with other countries to see what we can do better together. As I said, we are all struggling with the same issues of affordability and sustainability. It is a universal problem.

Mr. John Hennessy

I will comment briefly on Deputy O'Connell's points first, many of which I agree with. The biosimilar and substitution point is fair enough but we have also seen dramatic levels of biosimilar penetration across different jurisdictions and states. While in Ireland it is quite low at present, other countries appear to have moved ahead on substitution. That is where we aim to go as well.

Mr. Judge covered the governance point. The trigger for that governance review is probably the volume of applications coming through, particularly in the cancer and rare diseases space. It has dramatically increased on what it was five and ten years ago.

On the point about who shouts loudest, we cannot control that. At all points we try to ensure that our systems and processes are fair, transparent and equitable and, in particular, that they are evidence-based so decisions are taken on the basis of evidence rather than who is shouting loudest at any point in time.

On Senator Colm Burke's question about cost breakdown, we have a large volume of information on cost and the breakdown of what is happening in pharmaceuticals. By and large, it reveals stabilisation and even cost reduction in the generic and high volume spaces. For example, expenditure on the drugs payment and the long-term illness schemes is currently running at levels similar to those in 2000 on a cost per item basis. We are experiencing a significant increase in the high tech, cancer, orphan drugs and rare disease areas. There are two graph lines. One is stable while the other is increasing. We will be happy to share that data with the committee. I will need to check further about local variation and uptake as I am not sure if we can get that information easily, but we will certainly look for it.

On the Senator's final point on whether we can do more, I believe we can do more to drive value. It is related to the points about biosimilars and substitution. However, it is useful to remember as well that it is difficult to move patients off a drug or product they have been on for some time and sometimes the claims of products are not necessarily that they are curative but that they prevent or reduce deterioration. That is difficult to measure objectively in a manner that would result in the withdrawal of a drug from a patient.

I appreciate the difficulties prescribers have in that regard.

Can we have a breakdown of the cost of pharmaceuticals on a year-on-year basis by the different areas, whether they are patent, generic or orphan drugs, and if there is variation in different parts of the country? It may not be possible.

Mr. Shaun Flanagan

The hospital system is manual so it is difficult to get good data from it, but the vast majority of our spend occurs in the primary care and that is fully electronic. Getting that type of data to the Senator is possible with one constraint which is the databases as currently constructed do not capture orphan status. It is a data field that will have to be added in. In gross terms concerning generic uptake and cost, it is possible to get that figure, as it is for what is on patent and not on patent. Patents are very complicated. We have proxies in our databases that we can use as a proxy for a patent. A patent is not a single thing. For an individual drug, there could be 17 or 25 different patents. We have proxies for monopoly suppliers. We have markers for what is generic. We can link those in our databases and give the committee data on uptake.

Generic uptake throughout the country runs at about 75%. It is important to remember that within reference pricing legislation, which Deputy Brassil and Deputy O'Connell would be aware of from their previous roles as pharmacists, patients can choose to get the brand and pay a surplus or clinicians can say that on an exceptional basis a patient can be provided with a brand. There are reasons we use brands. In one instance it does not cost us anything but where a prescriber says there is an exceptional reason a patient should get the brand, it costs us. I hope I have made myself clear.

Why is Mr. Flanagan saying the hospitals are on a manual system? Surely their information gathering is computerised.

Mr. Shaun Flanagan

No. It is part of a big financial investment programme as I understand it. I do not work in the acute division. St. James's was the first hospital to go electronic about six weeks ago.

I presume part of each hospital budget is the cost of pharmaceuticals for the year.

Mr. Shaun Flanagan

Yes. I am talking about looking for granularity and getting into the depth of it.

I am talking about the overall cost of pharmaceuticals for the entire country for the year, including hospitals. Surely we get a breakdown from the hospitals. They may not have a breakdown of what they are spending it on but they may have an overall cost for pharmaceuticals.

Mr. Shaun Flanagan

I do not work in the acute hospital division so I cannot really answer that. We can give the Senator the vast majority of what he is asking for on the primary care side of things. We will have to engage with our hospital colleagues.

Mr. John Hennessy

We can do that and get the information the Senator is looking for. It is easier to do that in the community sector because-----

I accept that.

Mr. John Hennessy

-----it is a single system. It is more difficult in hospitals because there are individual hospital-based systems and the information has to be gathered from all that.

The reason I am asking is because it is about getting information out to people. We can all work towards making a savings in one area so another area can benefit. The HSE will not be able to do that unless it can get the information. People are shocked when they hear the figure of €2 billion because it is not information that is known generally. It is important we get that information out there. I would appreciate it if I could get some of that information over the next week or two.

Mr. John Hennessy

We will take that as the take-away task for today.

With regard to the rare disease technology review group, are there terms of reference for the group that can be sent to the committee?

Professor Michael Barry

Yes.

It is a review group. Does it make decisions or does it just review decisions?

Professor Michael Barry

It makes a recommendation on each specific product that is referred to it. The examples I gave were sapropterin or Kuvan and shortly nusinersen or Spinraza, so it will make a recommendation incorporating the clinician viewpoint and the viewpoint of patients and their families.

It goes to the drugs group.

Professor Michael Barry

It goes to the drugs group.

The representatives who appeared before the committee this morning spoke about the patients' representatives on that committee. They felt they were hand-picked rather than elected. What is the process of choosing the patient representative?

Professor Michael Barry

That is not a fair representation. We invited people to express whether they would like to be involved or not.

Ms Vicky McGrath

If I could add-----

Ms McGrath may not speak.

Professor Michael Barry

People were invited to take part. People were not just hand-picked. In addition, where patients' relatives are specifically involved in an area, they are invited along to meetings in addition to the representatives. There is good patient representation.

They were chosen by invitation.

Professor Michael Barry

There was a formal invitation.

How is the representative chosen from among those who respond?

Professor Michael Barry

Not very many responded, which was quite interesting.

I thank Deputy Durkan for his patience.

It is unlimited. This issue was mentioned in passing at a meeting I attended in Vienna yesterday. I am aware it is coming up today in another context. There are two things I want to deal with. First is the emotional element and the life-or-death situation. As Deputy O'Connell said, it is down to whoever can exert the most influence or shout loudest. The problem is that individual patients who find themselves confronted with a particular condition see no way out if they cannot access treatment. They find it particularly upsetting if the treatment is available selectively. It is also unconstitutional. That is the reality of life. It is unconstitutional to prescribe something for a group of people, assuming there are no other barriers, clinical or otherwise, and not to approve it for another. It is as simple as that. I hope it is being borne in mind because not only is it unfair, it is subject to there being no other medical reason as to why they should not avail of it or have it made available to them. They are entitled to it under the laws of the land. It should be borne in mind.

The job this group does is a very difficult one. I have no doubt about it. It is torn in all directions. There is one thing missing. I have spoken about it many times. Everybody else has spoken about it today. If I were asked to find out what impact the cost of a particular drug will be on the budget, which is an issue, I would like to find out from the people who know. I would presume I could press a button and find out where the drugs were being used throughout Europe and what the cost was in each case.

I do not agree with the principle of lying downwind in the negotiating process until other countries have gone ahead. That is not the way to do it at all. The market of 500 million people in the European Union should be used. It should negotiate a first and last point. We should use the weight of the 500 million people the European Union represents. The European Union is there to back that up. I cannot understand why it is not the first port of call. It should be the first reference. It should not be to the country that has negotiated successfully individually. There is an institution for doing it so why does it not happen? Why does it not happen in a way that is most beneficial to the patients and the cost of the delivery of the services? The only way it can happen is by reference to the biggest single market of which we are but one. We are only 4 million out of 500 million. We discussed this 25 and 30 years ago and arrived at this conclusion before the European Union was what it is now. To what extent do we now use that reference when coming to a conclusion on the suitability of the drug for all patients, the cost of the drug and recognising there may be variations in patient reactions?

I would like some clarification about biosimilar and generic drugs. I was around at the time when this discussion initially took place. Many patients reported that generic drugs did not have the same impact, but the clinical experts told them that they were wrong and that it was just their imagination. Does the Chairman remember that? As legislators, we were in a difficult position. We did not know who was telling us what they thought was the truth and what was accurate. Legislators can only work based on the information they are given. As such, I would like a clear indication of the extent to which those two thought processes have been merged to give us some idea as to what we should be doing in future while also keeping costs in mind.

I cannot believe that we are still using 14 reference countries. It is all nonsense. It gives an average, but we know how averages are determined, so we will not go into that. For God's sake, can someone somewhere initiate a method whereby we can have a reference to the best possible people in the drug-buying business? The drug companies will, of course, give drugs to some people for free to prove they are effective and to make a bargaining position when dealing with people like the witnesses. That is what they do and that is the commercial world in which we live. There is no use in pretending that it does not exist when it does. It is up to the HSE to set up a structure whereby it can determine which drug is the safest and most effective and appropriate and what is the best value at which it can be purchased so that patients in Ireland pay at least the same as they would in other European countries.

I have many further questions, but I will finish shortly. How does the cost of Orkambi compare across Europe? It is a simple question. I know that the cost varies, but by how much? Why does the Irish patient not have the same access to it as everyone else? I cannot understand that.

In recent weeks, eight drugs were approved at a cost of €300 million over five years, or approximately €60 million per year. Out of interest, how does that compare with the drugs that were reviewed five years ago, two years ago and now in terms of their efficacy and cost? What is the cost per patient of Orkambi? What is the European opinion on its efficacy, that is, its ability to treat all cases, most cases or specific cases? Do situations arise wherein it is possible to determine, based on the analysis of the patient and his or her condition, the drugs that are most likely to work, given the patient's metabolism? I would like to think it is possible. Two patients with the same condition may have metabolisms that are at variance with the norm.

My final question is a general one. I am not a medical expert, but I know of patients whose screenings for cancer have been deemed clear or not clear, whichever the case may be, but whose diagnoses have changed over a period for reasons that are not readily explicable. Is it possible to shed some light on this? The cervical smear test is not diagnostic, but a screening process and its accuracy can vary dramatically. The claim that it is 80% accurate is very misleading from the point of view of the patient because the patient will always believe-----

The Deputy might be straying off topic.

It was referred to earlier, so I am not straying off topic. I am reasonably good at that. If something has been mentioned, I tend to remember it before the end of the meeting, strange as that may seem.

I thank the Deputy.

Mr. John Hennessy

I will need help from my colleagues on some of those issues. Regarding the European Union, I agree with Deputy Durkan that it represents an opportunity as a purchasing bloc. The only two points I would make-----

What is the HSE going to do about it, though?

Mr. John Hennessy

There is the small matter of Irish legislation. The 2013 Act governs the process of assessing new drugs in Ireland. We operate to legislation on that front.

I am sorry, but that is not correct.

Mr. John Hennessy

If the legislation changes and we have to operate to a different rule set, then-----

That is avoiding the issue. I will tell the committee why what Mr. Hennessy said is not correct. The existence of the 2013 Act is a separate issue. When the HSE has achieved best practice in pricing and efficacy in Europe, we can then revert to the Act.

Mr. John Hennessy

I was going to agree with the Deputy in the second part of my answer. Work has commenced on a Europe-wide collaboration, which Mr. Judge mentioned in terms of the BeNeLuxA arrangement. Be it a €300 million bloc or a €50 million bloc is the question. Our experience is that larger member states are less keen to be involved in such a collaboration-----

There are reasons for that.

Mr. John Hennessy

-----whereas smaller member states are keen. We would be in that bloc.

Is Mr. Hennessy saying that the 2013 legislation would have to be amended to allow for collective bargaining?

Mr. John Hennessy

I am open to correction, but I imagine it would.

That is what Mr. Hennessy is suggesting.

Mr. John Hennessy

Yes.

Mr. Shaun Flanagan

The challenge is more about us having to align our Acts and processes with those of other countries so that we are all doing things roughly at the same time and in the same way. Different countries do things slightly differently. Alignment is the challenge.

The reason for the legislation is to ensure that other countries do not run way ahead of us and obtain more beneficial conclusions than us, yet we are waiting for the situation to improve elsewhere instead of going to the top, availing of the best possible price for the most effective drugs and working from there.

Mr. Finian Judge

On the EU issue, Mr. Hennessy is correct. We are a new member of the BeNeLuxA collaboration, and all members recognise that, if we are to progress down the road to joint negotiations, we will have to align our domestic legislative processes with the new structure. Our current process is enshrined in the 2013 Act.

Deputy Durkan asked about taking the collective route. There are 500 million people in Europe. As Mr. Flanagan has outlined, drug companies insist on negotiating with individual countries.

Of course they do.

Mr. Finian Judge

The European Union, as a collective, is starting to move into that space. Since the Deputy has given an opinion on it, he must be familiar with the EU's proposal on common procedures for health technology assessments, HTAs. That proposal is making its way slowly through the Council of Ministers. It could be seen as the start of the EU getting into this space.

Are we pushing that?

Mr. Finian Judge

At the moment-----

Mr. Finian Judge

I am aware that this committee made a positive contribution in favour of the proposal in principle. I am informed that it is going through the constructive dialogue process at the Council. Progress is being made, but one of the sticking points is the mandatory uptake of any HTA that would come out of the process. Some countries are reluctant to go down that route.

Mr. John Hennessy

To continue with Deputy Durkan's questions, his point about access schemes and participation in clinical trials was a good one.

I reinforce the point that steps have been taken to ensure patients are not vulnerable when they participate in such schemes. These steps include putting in place very transparent consent arrangements and very transparent and clear aftercare arrangements at the outset so that it is clear what happens when these access schemes and trials conclude. We have been in formal contact with our respective hospitals and hospital groups over the course of this year.

I was asked about Orkambi and the variance in cost. The Irish deal is regarded as the probably the best around or certainly one of them. Mr. Flanagan might be able to comment on that. Professor Barry may be able to help on the efficacy and evidence questions arising.

Mr. Shaun Flanagan

The Orkambi deal is a complicated one which involves a portfolio and what drug prices will be in future with further lines. It is very difficult to describe it in simple cost terms. Our understanding is that the Australian Government took the exact same deal as we negotiated first and we understand the UK's NHS is engaged currently in a similar portfolio deal. The cost per patient of Orkambi is approximately €12,000 per month.

The Australian Government represents 22 million people. The European Union, of which we are a member state, represents 500 million people. If I were a drug manufacturer selling into a market, I would want to do a deal with the one containing 500 million people at all costs.

Mr. Shaun Flanagan

It is important to recognise that within the EU, not every country has said yes to Orkambi. The NHS has not and Scotland has not.

I asked that question also.

Mr. Shaun Flanagan

That is the reality. Not every country has said yes to Orkambi. There is no point going back to the discussions on the challenges around it and the evidence. The Deputy asked a general question on efficacy and cost over a timeline. It is very hard to comment on that in any scientific way because we have not done a review. In my professional opinion, over the course of my career and in particular over the past ten years, there has been a move for new medicines to come to the market at an earlier stage than they would have previously following smaller trials. Some of that may be a result of the fact that the low-hanging fruit is gone as the major clinical disease areas have been addressed. Once one gets into orphan drugs, it is harder to design trials with patients. Mr. Judge probably started a little before me, but around the time we started our careers, one would expect to have two randomised phase 3, placebo-controlled trials, namely, one big one followed by a conformity trial. It is only then one would like to see a medicine get to market. We have gone way beyond that now, however. What come before the drugs group now are single-arm trials. That means there is no comparison arm within the trial and the group is faced, like any assessment body internationally, with significant challenges. Against that, those drugs would never get to market if a phase 3 trial were expected because those are impossible to design. There are challenges that have to be weighed up around evidence. The straight answer is that the evidence is less robust than it was for medicines coming to market a decade ago. That is the nature of being into orphan diseases and smaller areas. The cost per patient has inflated significantly. The industry argues that it is because it has to harvest its research and development costs across a smaller cohort. The cost has gone up for every assessment and, it is fair to say, cost-effectiveness has worsened over the decade.

I will be brief as it has been a long session and I do not want or expect answers now. The witnesses may be able to respond in writing. As I said in my opening remarks, the committee stated that the 2013 Act needed to be reviewed. Clearly, the opening statement from the Department contravened that. I ask that the committee looks at that and furnishes a response. The Act still needs to be reviewed. I asked how much was spent on orphan drugs. The legislation does not make separate provision for those. The National Centre for Pharmacoeconomics, NCPE, published a report recently, which was prepared by its deputy head and which set out a review from 2012 to 2017 of rapid reviews submitted. I ask for a consideration of that to extract the orphan drugs from the data to inform the committee as to how much is being spent there. The last time Professor Barry was before the committee, his organisation was very understaffed, with only 11 out of 23 posts filled. I am glad to see that, following my representations, it now has 18 out of 23. I will submit a further parliamentary question looking for the remaining five.

Professor Michael Barry

We are very grateful for the Deputy's help.

As a matter of clarification, recommendation No. 2 of the committee last year did not recommend a review of the entire Act. It recommended a review of the Act to identify potential legislative barriers to the reimbursement of orphan drugs and corresponding legislative amendments. It was not asking for an entire review of the Act. It honed in specifically on that aspect. Mr. Judge seemed to think we asked for a review of the entire Act, but that is not the case.

Mr. Finian Judge

I will take that point away in our discussions with the Minister.

Mr. John Hennessy

I have a final comment to finish up with Deputy Durkan's list. It is difficult to be precise about this year compared with five years ago. This year, we have dealt with more than 30 new applications with a cost impact or implication in excess of €300 million over five years. That indicates the scale of this year's activity. We will have a look back at the position five years ago, although I suspect it was a fraction of that in terms of volume and numbers.

That concludes our business. I thank Professor Michael Barry, Mr. John Hennessy, Mr. Shaun Flanagan and Mr. Finian Judge for spending so much time with us this morning.

The joint committee adjourned at 1.40 p.m. until 9 a.m. on Wednesday, 28 November 2018.