Control of Clinical Trials Bill, 1986: Report and Final Stages.

Minister of State at the Department of Health (Mr. Leyden)

I move amendment No. 1:

In page 4, between lines 22 and 23, to insert the following:

"(ii) are satisfied with the composition of a committee appointed to consider the justification for conducting the proposed clinical trial and the circumstances under which the proposed trial is to be conducted, and".

During the discussion on Committee Stage of the Bill in the Dáil, the Minister undertook to re-examine section 2 as drafted. He referred to the need to bear in mind that the protection of the interests of participants in trials was of the utmost importance. To this end it is now proposed in relation to trials specified in subsection 2 of section 2 to include an additional safeguard to the extent that the National Drugs Advisory Board satisfy themselves with the composition of a committee appointed to consider the justification for conducting the proposed clinical trial and the circumstances under which the trial is to be conducted. The committee would in effect be an ethics committee but not one to which the statutory requirements for ethics committees specified in the Bill would apply.

The need to build into the Bill a requirement that a third party would have a vetting role in relation to clinical trials using medicinal products which have a product authorisation has been mentioned by a number of competent organisations and persons and indeed by Deputy Flaherty on a number of occasions. I am happy, therefore, to propose this amendment which will strengthen section 2 (2) further.

Miss Flaherty

Ba mhaith liom buíochas a gábhail don tAire as oth na leasanna atá molta aige. I thank the Minister for the amendments he put forward on Report Stage which meet many of the issues raised on Committee Stage. This amendment is welcomed because it will increase the safeguards in relation to trials where the exceptions under section 2 apply.

Amendment agreed to.

Mr. Leyden

I move amendment No. 2:

In page 4, between lines 30 and 31, to insert the following:

"(3) Where a person proposes to arrange for the conducting of a clinical trial or to conduct a clinical trial, and

(a) there is in force in respect of the substance or preparation concerned a product authorisation granted under the Medical Preparations (Licensing, Advertisement and Sale) Regulations, 1984, and

(b) the purpose of the clinical trial is to determine the effect of a new use for the substance or preparation concerned.

then the provisions of section 3 to 6 and sections 8 to 11 shall not apply where—

(i) the National Drugs Advisory Board have been notified in writing of the proposal and have, not later than 6 weeks after being so notified, made a recommendation to the Minister on the proposal, and

(i) the Minister has granted permission for the proposed trial to be undertaken, and

(iii) in respect of the substance or preparation concerned, the conditions relating to dosage form contained in the product authorisation so granted are complied with when the clinical trial is being conducted and the dosage administered in each case does not exceed that specified in the said authorisation.".

While discussing the provisions of section 2 of the Bill during Committee Stage, the Minister gave an undertaking to Deputy Flaherty to look again at section 2 with a view to safeguarding the interests of participants in trials while at the same time ensuring against unduly impeding legitimate trials on products which have been authorised.

The trials in question are carried out to determine new uses for products which have a product authorisation and which are in extensive use in medical practice. These types of trials are generally undertaken by hospital consultants and are of considerable benefit in determining new and beneficial uses for widely used products, determined on the basis of experience in using the product clinically, In considering how best to develop an appropriate mechanism for clinical trials under section 2 of the Bill, I find it necessary to restrict any deviation from the full requirements of the Bill to certain trials for new uses only.

It is proposed, therefore, to exempt, subject to certain conditions, from the requirements set out in sections 3 to 6 and 8 to 11 of the Bill, trials involving a preparation which has a product authorisation where the purpose of the trial is to determine a new use for the preparation.

The amendment governing the exemption include the following stipulations: where the National Drugs Advisory Board have been notified in writing of the proposal and have not later than six weeks after being so notified, made a recommendation to the Minister on the proposal; the Minister has granted permission for the proposed trial to be undertaken; and in respect of the substance or preparation concerned, the conditions relating to dosage form contained in the product authorisation so granted are complied with when the clinical trial is being conducted and the dosage administered in each case does not exceed that specified in the said authorisation.

When assessing the application for the trial, the National Drugs Advisory Board would have to be satisfied with the arrangements made by the applicant. These would include an independent committee to vet the trial. I feel that this amendment will go a long way towards meeting the legitimate demands of individual researchers conducting clinical trials while, at the same time, protecting those participants in such trials.

Miss Flaherty

I thank the Minister for his efforts in this area. This amendment goes a long way towards dealing with some of the problems outlined by many doctors and consultants working in our hospitals. The amendment is sufficiently tight to ensure maximum safeguards but allows the two major practices, to which the doctors referred, which are commonly used at present in clinical practice. Perhaps the utilisation, in consultation with the National Drugs Advisory Board, of a medicine for a new medical purpose and trials with lower doses of the medicine are to be welcomed. I also welcome the fact that the question of exceeding the dosage has been dealt with very clearly, and that it will not be possible to exceed the dosage. The fact that slow release doses may now be possible is also to be welcomed.

This amendment successfuly balances the need to protect participants, particularly in the context of amendment No. 1 which has just been passed, and will allow current clinical practices in hospitals, which might have been interfered with by the Bill as originally drafted, to continue. We are happy to accept this amendment.

Amendment agreed to.

An Ceann Comhairle

Amendments Nos. 3 and 6 are related and amendment No. 7 is consequential on amendment No. 6. I suggest, therefore, that we take amendments Nos. 3, 6 and 7 together by agreement. Is that agreed? Agreed.

Miss Flaherty

I move amendment No. 3:

In page 4, line 41, after "committee", to insert "which shall have regard to regulations governing composition of ethics committee made under section 17 (1) of this Act".

While the Minister has gone a long way in dealing with the major issues raised on Committee Stage, I am still unhappy — and I am sure this unhappiness is shared by others — that there have been no changes in relation to the way in which ethics committees are appointed. The only safeguard in relation to ethics committees are the broad terms of reference and the fact that they will need ministerial approval. Given that ethics committees are central to the success of the Bill in terms of protecting the participants and supervising the trials, the requirements within the Bill are inadequate to achieve that to public satisfaction.

We have every reason to have confidence in the assessment of Departmental officials and that of the Minister but it would be desirable to have some further elements of public accountability. My three amendments seek to achieve that and on Committee Stage I referred to the possibility of requiring that statutory regulations should be made in relation to the composition of ethics committees. Such informal guidelines are currently available from the National Drugs Advisory Board for persons conducting trials and these could set down at least minimum regulations which would have to be observed. If there was any query in future that would be the yardstick by which the performance of their duty by the Minister and the National Drugs Advisory Board in relation to the requirements under the various sections was met.

As it stands, in section 3 the person proposing the trial names the committee and I have been unhappy with that provision from the beginning. Perhaps we must accept that but if there was a requirement to publish regulations and guidelines for the composition of this committee, minimum requirements could be set down. Section 17 gives the Minister power to make regulations in relation to what he may consider expedient for the implementation of the provisions of the Bill. The power is there but I am anxious that this should not depend on any one Minister. It should be contained in the Bill as well as the minimum requirements which the Minister expects from any person naming the committee before the Minister, his Department or the National Drugs Advisory Board would be happy with the ethics committee.

I ask the Minister to accept this amendment. It is not a major change but it ties in with a series of amendments on Committee Stage, none of which was successful in relation to having the appointment of the ethics committee being made in a more publicly accountable fashion. This aspect of the Bill is not satisfactory and I ask the Minister to accept this amendment which would meet, to some degree at least, the concerns expressed by many people on Committee Stage. It is the only remaining area of concern as far as Fine Gael are concerned in relation to the Bill.

Mr. Leyden

I wish to thank the Deputy for her contribution on this amendment. During the course of the Committee Stage debate on the Bill, the question of the need for statutory regulations in relation to the composition of ethics committees and the matters to be considered by such ethics committees under section 8 of the Bill was raised by Deputy Flaherty.

Following further consideration of the issue, I am still of the view that all interests are best served in this matter by means of guidelines as opposed to statutory regulations. Statutory regulations require to be precise and definite and, for those reasons, lack the necessary flexibility which is possible under guidelines. Because we are breaking new ground with this Bill, it would not be prudent to set down rules which could prove so rigid as to render the provisions of the Bill ineffective. For this reason, it might prove beneficial to proceed on the basis of guidelines and, should it prove necessary in the light of experience, to consider the need for statutory regulations at some future date. I appreciate Deputy Flaherty's concern and her request to have the amendment included. We have examined it very carefully in the Department and, because of the fact that this is a new Bill and that many trials will be arising in the future, it would strengthen the Bill to have flexibility to appoint special ethics committees for particular trials. In the circumstances, and after very careful consideration, we cannot accept the amendment.

Proinsias De Rossa

Ba mhaith liomsa cúpla focal a rá faoin cheist seo. I also spoke on Committee Stage in relation to the question of ethics committees and I am still not satisfied that the method of having ethics committees appointed by the institution or the individual carrying out the trial is the correct and proper way of doing it. However, that proposition was defeated on Committee Stage. In the circumstances, the Minister should accept Deputy Flaherty's amendments because the House should err on the side of caution in relation to the protection of individuals undergoing these trials rather than erring on the side of flexibility in relation to ethics committees. Therefore, I strongly support Deputy Flaherty's amendments and I urge the Minister to accept them.

Miss Flaherty

The Minister indicated that he is anxious to have maximum flexibility in the Bill. I accept that different trials may require different types of committees and different supervision. The people in the Bills Office altered it slightly but I had a reference to "minimum regulations". It should be possible to frame the Bill in such a way that the Minister and his Department would have sufficient wisdom and experience to frame minimum regulations which would not prevent the specialist knowledge required in relation to any particular trial but would ensure that certain minimum requirements are met. Obviously, I would anticipate requirements such as having a representative of lay groups whose main interest would be in the trial and an independent medical person.

Based on some of the guidelines laid down by the National Drugs Advisory Board for persons proposing to conduct trials, it is possible to have minimum requirements. As Deputy De Rossa said, we have erred on the side of flexibility by leaving the nomination of the ethics committee in the hands of the trialist. This is a very strong power to give to the trialist without any supervision other than ministerial approval. The Bill does not specify on what basis approval would be given. The Bill does not refer to the composition of the committees at all. Given that the committee are nominated by the trialist and that the question of whether the committee are acceptable is considered in the realms of the Department of Health on the basis of rules and regulations which the Minister indicated on Committee Stage but which are not written into the Bill, the Bill is too open ended. I would ask the Minister to consider these relatively minor amendments.

While the Department up to this were not statutorily responsible for clinical trials they have been involved in the voluntary control of clinical trials for a long time through the National Drugs Advisory Board. I find it strange that the Minister is not willing to give some statutory basis to the guidelines used by the National Drugs Advisory Board over the years. The National Drugs Advisory Board are committed to providing protection and to ensuring that research goes on. The Minister should reconsider these amendments given that this is the one area in which there was substantial concern on Committee Stage and that that concern has not been met in any of the Minister's amendments. If an amendment such as that proposed on section 2 was proposed in relation to a relevant section of the Bill it would have met our concern. It is important to have some further safeguard, some further element of public judgment on ethics committees which are central to this Bill, the aim of which is to give greater protection to volunteers and to ensure the proper conduct of clinical trials so as not to put future research at risk. Both of these aims will be seriously affected if there are further serious incidents similar to that which gave impetus to this legislation.

Mr. Leyden

Section 17 (1) of the Bill really covers Deputy Flaherty's amendment because it gives the Minister full powers to make such regulations as appear to him to be necessary or expedient to implement the provisions of the Bill. Initially it would be appropriate to have guidelines which would enable the Minister and the National Drugs Advisory Board to tailor the composition of the ethics committee to suit the trial.

With regard to the powers of the trialist to appoint an ethics committee, the Minister has power to disapprove of the trial if he is not happy with the composition of the ethics committee. Because Deputy Flaherty's amendment is already covered by the Bill I request her to withdraw it. We are very anxious to encompass Deputy Flaherty's requirements in this section as well as the point made by Deputy De Rossa and under section 17 (1) the Minister has the powers to make regulations when required. The Bill gives the Minister adequate power to safeguard those participating in the trials. The officials in my Department who were familiar with the guidelines prior to the introduction of the Bill feel that the provisions are adequate and the Minister and I agree that adequate protection is in the Bill to provide for the proper composition of ethics committees to supervise trials.

As we have facilitated the Opposition by way of amendments and as there are adequate safeguards, this amendment should not be proceeded with.

An Ceann Comhairle

Deputy Flaherty will appreciate that we are on Report Stage. Strictly speaking, when Deputy Flaherty last spoke she replied to the debate. I permitted the Minister to respond to her appeal at that stage. Deputies will appreciate that I cannot allow something tantamount to a Committee Stage to operate now on Report Stage. I will allow Deputy Flaherty a brief comment.

Miss Flaherty

This is the first time I have been through a Bill in such detail so I was not really aware of what was allowed on Report Stage.

The Minister indicated that the Opposition should be grateful. The Minister is not doing the Opposition a favour. We are working on legislation and trying to produce the best legislation possible. Gratitude because the Minister accepted certain valid points should not prevent us from pursuing other points a little further.

The Minister said he had the option to make regulations under the Bill. The Minister has also indicated to the House that he intends to operate from guidelines rather than regulations in the initial stages. The National Drugs Advisory Board have outlined what they consider to be a minimum desirable requirement. The Minister indicated during Committee Stage that this is the line he will follow in relation to the guidelines. Because ethics committees are so central, it is desirable for Members of this House, before this Bill comes into operation, to have an opportunity to look at the kind of regulations the Minister proposes to make in relation to the composition of ethics committees.

The Minister will have to make guidelines available and he will have to explain them so that from the passing of this Bill people will know what is or is not acceptable. Before a trial can take place the Minister will have to approve of an ethics committee, so he will have to make his position clear. I do not see why the Minister could not give statutory basis to minimal requirements for the makeup of these committees. While I welcome the genuine improvements made on Report Stage, this is an issue that will have to be pressed.

An Ceann Comhairle

By allowing amendments Nos. 3, 6 and 7 to be discussed together I have given some discretion to the House but I cannot allow a departure from the normal procedure which should apply on Report Stage. I must now ask Deputy Flaherty if she is pressing amendment No. 3.

Miss Flaherty

I am pressing the amendment.

Amendment put.

The Dáil divided: Tá, 70; Níl, 75.

Tá

Allen, Bernard.
Barnes, Monica.
Barrett, Seán.
Barry, Peter.
Begley, Michael.
Boland, John.
Boylan, Andrew.
Bruton, John.
Bruton, Richard.
Carey, Donal.
Clohessy, Peadar.
Colley, Anne.
Cooney, Patrick Mark.
Cosgrave, Michael Joe.
Creed, Donal.
Crotty, Kieran.
Cullen, Martin.
Deasy, Austin.
Deenihan, Jimmy.
De Rossa, Proinsias.
Desmond, Barry.
Donnellan, John.
Doyle, Avril.
Dukes, Alan.
Durkan, Bernard.
Enright, Thomas.
Farrelly, John V.
Fitzpatrick, Tom.
Flaherty, Mary.
Flanagan, Charles.
Gibbons, Martin Patrick.
Griffin, Brendan.
Harney, Mary.
Harte, Paddy.
Hegarty, Paddy.
Higgins, Jim.
Howlin, Brendan.
Hussey, Gemma.
Keating, Michael.
Kelly, John.
Kemmy, Jim.
Kennedy, Geraldine.
Kenny, Enda.
Lowry, Michael.
McCartan, Pat.
McCoy, John S.
McDowell, Michael.
McGahon, Brendan.
McGinley, Tomás.
Mac Giolla, Tomás.
Mitchell, Gay.
Mitchell, Jim.
Molloy, Robert.
Naughten, Liam.
Nealon, Ted.
Noonan, Michael (Limerick East).
O'Brien, Fergus.
O'Keeffe, Jim.
O'Malley, Desmond J.
O'Malley, Pat.
Quinn, Ruairí.
Shatter, Alan.
Sheehan, P.J.
Sherlock, Joe.
Spring, Dick.
Stagg, Emmet.
Taylor, Mervyn.
Taylor-Quinn, Madeline.
Wyse, Pearse.
Yates, Ivan.

Níl

Abbott, Henry.
Ahern, Bertie.
Ahern, Dermot.
Ahern, Michael.
Aylward, Liam.
Barrett, Michael.
Brady, Gerard.
Brady, Vincent.
Brennan, Matthew.
Brennan, Séamus.
Briscoe, Ben.
Browne, John.
Burke, Ray.
Byrne, Hugh.
Collins, Gerard.
Conaghan, Hugh.
Connolly, Ger.
Coughlan, Mary T.
Cowen, Brian.
Daly, Brendan.
Davern, Noel.
Dempsey, Noel.
Dennehy, John.
de Valera, Síle.
Doherty, Seán.
Ellis, John.
Fahey, Jackie.
Fitzgerald, Liam.
Fitzpatrick, Dermott.
Flood, Chris.
Flynn, Pádraig.
Foley, Denis.
Gallagher, Denis.
Gallagher, Pat the Cope.
Geoghegan-Quinn, Máire.
Haughey, Charles J.
Hyland, Liam.
Jacob, Joe.
Kirk, Séamus.
Kitt, Michael P.
Kitt, Tom.
Lawlor, Liam.
Lenihan, Brian.
Leonard, Jimmy.
Leyden, Terry.
Lynch, Michael.
Lyons, Denis.
McCarthy, Seán.
McCreevy, Charlie.
MacSharry, Ray.
Mooney, Mary.
Morley, P.J.
Moynihan, Donal.
Nolan, M.J.
Noonan, Michael J.
(Limerick West).
O'Dea, William Gerard.
O'Donoghue, John.
O'Hanlon, Rory.
O'Keeffe, Batt.
O'Keeffe, Ned.
O'Leary, John.
O'Rourke, Mary.
Power, Paddy.
Reynolds, Albert.
Roche, Dick.
Smith, Michael.
Stafford, John.
Swift, Brian.
Treacy, Noel.
Tunney, Jim.
Walsh, Joe.
Walsh, Seán.
Wilson, John P.
Woods, Michael.
Wright, G.V.

Tellers: Tá, Deputies O'Brien and Flanagan; Níl, Deputies V. Brady and Briscoe.

Amendment declared lost.

An Ceann Comhairle

Amendments Nos. 6 and 7 fall also as they were consequential on amendment No. 3. We now proceed to amendment No. 4 in the name of the Minister. Amendments Nos. 4 and 5 are related.

Mr. Leyden

I move amendment No. 4:

In page 8, to delete line 4.

In section 10 of the Bill a policy of insurance is required to ensure that adequate funds are available to provide appropriate compensation for each participant who may suffer injury or loss as a result of a trial. Before a person can conduct a clinical trial under section 8 (4) (a) the ethics committee must have regard to the insurance arrangements entered into. The requirement of a policy of insurance does not reflect the de facto position as regards the availability of various forms of financial compensation and security which are currently available to compensate persons who suffer injury or loss as a result of a clinical trial. Persons who conduct clinical trials at present have available to them arrangements which vary from policies of insurance to bonds and other financial guarantees from financial institutions and insurance companies. It is necessary to recognise in the Bill that these arrangements exist and it would not be appropriate to include a restriction provision in the Bill which has as one of its objectives the facilities of legitimate research projects.

I propose therefore that section 10 be amended to require that a person conducting a clinical trial must establish to the satisfaction of the ethics committee that he can provide sufficient security to ensure that adequate funds are available to provide appropriate compensation for each participant who may suffer injury or loss as a result of the trial.

Section 8 (4) (e) would be redundant as a result and I propose that it be deleted. I might add that it is my intention to include in guidelines for ethics committees the need for the availability of expertise in the areas of compensation for personal injuries to the ethics committee.

Miss Flaherty

Can the Minister say what he suggests will be deleted?

Mr. Leyden

Section 8 (4) (e) would be redundant as a result of the proposed amendment I am making.

Miss Flaherty

Then I would like to welcome the changes the Minister has here in that they do deal with the problems raised on Committee Stage and should allow for research to go on, covered by the various forms of security that would be available. I am satisfied that they adequately protect the individual participants in trials and allow the variety of arrangements that the Minister has referred to to be acknowledged in this Bill and hence to allow the maximum amount of research possible to continue. There was a danger that as it was narrowly defined before the ultimate effect of the Bill would have been to confine research to the large commercial companies who could affored a limited amount of international insurance which is available in this area. The wider drafting of this section allows the other forms of security to be acknowledged and accepted by an ethics committee as providing security for the participants.

I would just like to ask the Minister, given that he has now drafted this section in such a way that it would allow for it in the future, to consider the system that operates in England allowing research to continue within hospitals by providing a fund for which ex gratia payments might be made arising out of claims within the hospitals. This would ensure that desirable research which might still not be able to be covered under any of the other available methods of insurance to continue. Will the Minister indicate if he is willing, in terms of reviewing the impact of this Act, to at least keep this proposal in mind and perhaps next year seek funds from the Minister for Finance to allow such a fund to exist. I welcome this amendment and hope that the Minister might keep this other matter in mind, given that the wider drafting here would make such a fund operable and relevant under the Bill.

Amendment agreed to.

Mr. Leyden

I move amendment No. 5:

In page 10, line 7, to delete "there is in force a policy of insurance sufficient", and substitute "such person establishes to the satisfaction of the ethics committee that he can provide sufficient security".

Amendment agreed to.

Amendments Nos. 6 and 7 not moved.

Mr. Leyden

I move amendment No. 8:

In page 12, line 25, to delete "17 as is", and substitute "15 as are".

Section 19 (2) provides for the coming into force of the provision of the Act. The amendment is basically a technical amendment which arises from the incorrect reference in section 19 (2) to sections of the Bill. The amendment provides that section 19 (2) reads as follows:

This Act, other than sections 16 to 18 and this section and so much of sections 1 to 15 as are necessary to give effect to section 3 (3), shall come into operation on such day as the Minister shall by order appoint.

Miss Flaherty

I would make one minor inquiry. I gather the grammatical change was made by the parliamentary draftsman or the Attorney General's office. Could the Minister confirm that it is as grammatically correct to have "much ...as are necessary""as it is to have "much...as is necessary". "Much" is singular so "is" would seem to be more correct. But the parliamentary draftsmen are proposing we should have it plural. Maybe we should send for the Minister for Education. Is the Minister happy with it?

Question, "That the Bill as amended, do now pass" put and agreed to.

An Ceann Comhairle

As the Bill is considered by virtue of Article 20.2.2º of the Constitution to be a Bill initiated in the Dáil, it is sent to the Seanad.

Dáil Éireann díospóireacht -
Wednesday, 25 Nov 1987