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Seanad Éireann díospóireacht -
Tuesday, 27 May 1986

Vol. 113 No. 1

Control of Clinical Trials Bill, 1986: Second Stage.

Question proposed: "That the Bill be now read a Second Time."

I thank the House for the opportunity to present the Control of Clinical Trials Bill 1986. The purpose of the Bill is to provide a statutory basis for the control of clinical trials involving human participants. The statutory scheme will replace the current informal procedure whereby proposed clinical trials are voluntarily notified to the National Drugs Advisory Board and where such trials are then carried out in accordance with approvals of guidelines issued by the board.

The subject of clinical trials, when raised, is one which is guaranteed to provoke a voluble response, irrespective of the forum in which it is raised. It is generally accepted that there is a continuing need for more effective and safer drugs. However, this general acceptance is not always accompained by a willingness to accept the need for clinical trials in developing these drugs.

The thalidomide tragedy of some 25 years ago brought home very forcibly the need for great care in the study of new medicines before they are licensed for general use. Experience since then has also taught us the lesson that even preparations which appear to have passed stringent tests and are apparently innocuous require to be closely monitored for quite some time after their release into widespread medical use.

Clinical trials form a vital element not only in the process of development of new drugs but in the continued assessment of drugs already on the market to ensure their safety, quality and efficacy. In the pre-marketing stage this process of development is a lengthy one involving various stages of investigation ranging from chemical development to experimentation on animals and finally to testing on man. The tests on man are extensive and include those carried out on healthy volunteers, on patients suffering from the condition for which the substance or preparation is intended to treat and on patients suffering from certain complications which could affect the behaviour of the drug under trial in the body.

The ultimate objective of the process is to ensure the availability of a safe and effective drug for treating a particular illness or condition and which at the same time conforms with safety, quality and efficacy criteria laid down by national regulatory bodies for the marketing of such drugs. In assessing applications for the placing on the market of medicines, stringent regulations apply to ensure the protection of public health and these include the need to supply detailed information in relation to results obtained from clinical trials. There is a regulatory requirement in most countries, including Ireland, that the results of such trials on a particular drug be furnished for evaluation prior to authorising its placing on the market. In Ireland, the detailed assessment is carried out by the National Drugs Advisory Board which then advises the Minister for Health in relation to the issue of a product authorisation or licence to market the product in this country.

However, the question of the involvement of humans in clincial trials has received much public attention in recent years. This has prompted an examination, at both national and international level, of the controls applicable to such trials. At international level, the World Medical Assembly adopted, as far back as 1964, the Declaration of Helsinki which contains recommendations guiding physicians in biomedical research involving human subjects. This declaration has been revised on two occasions since, in 1975 and 1983, and compliance with it is a prerequisite for approval of clinical trials by most drug regulatory agencies. The Council of Europe has also been working on formulating a list of principles on medical research in man.

Unfortunately, in Ireland, there is no provision in existing legislation for a statutory scheme to control the conducting of clinical trials and there has, for some time, been grave public disquiet about the absence of such statutory controls. The current arrangements for the clearance of submissions for trials through the National Drugs Advisory Board have been in existence for a number of years and are in line with accepted international principles. However, they fall short of those required by virtue of the fact that they are carried out on a voluntary and informal basis. I believe that comprehensive controls of all trials must now be guaranteed by a statutory scheme as provided for in this Bill.

The Bill is drafted in a manner which provides wide scope for control and, at the same time, ensures against rigidity in relation to interpretation of the provisions. This form of drafting is vital when one considers the extent, range and nature of clinical trials which must be carried out. I believe that it is most important that we avoid introducing a statutory scheme which would be so rigid as to limit the opportunities of the pharmaceutical industry in this country, including those manufacturing generic products as well as those involved in the research and development of special delivery systems, to complete the drug clinical profiles required by drug regulatory agencies for evaluation prior to market. However, at the same time, it is vital that the new statutory scheme must also safeguard the health and rights of those participating in clinical trials. We must ensure that the interest of medical science and society in general should never take precedence over considerations relating to the well-being of the participants.

Basic to the nature of the control regime for clinical trials proposed in the Bill is the requirement that the prior approval of the Minister for Health must be obtained by a person wishing to arrange for the conduct of a clinical trial.

The form of application necessary is outlined in section 2 and the information required to be submitted is such as will enable the Minister to satisfy himself, inter alia,

—that the proposed ethics committee is so constituted so to afford assurance that the justification for the trial is carefully and impartially considered.

—that the doctors or dentists who will be conducting the proposed trial are suitably qualified and competent to do so.

—that the method of recruitment of participants is satisfactory, and

—that the level of rewards to be made to participants is not such as to constitute an excessive inducement.

While formal approval will be a matter for the Minister, he will rely on the expert advice of the National Drugs Advisory Board in arriving at his decisions. It is the intention that all applications will be referred to the board for assessment and for recommendations as to any conditions which should be attached to his approval.

The board have, of course, been operating an informal scheme of this nature on their own initiative for almost 20 years. Section 3 empowers the Minister to apply whatever conditions he considers necessary for the safe conduct of the trial.

The need to have the Minister's prior approval to any change in a subsisting permission and his authority to request information on the progress of the trial, and to intervene when necessary, is recognised. For example, section 4 provides that any proposed variation to a subsisting approval must be subject to agreement by the Minister. The Minister will also have the power, as provided for in section 6, to revoke, at any time, a permission granted.

Section 10 empowers the Minister to require such information as he deems fit about the progress of a trial. It also obliges all persons involved in the conduct of a clinical trial to bring to notice promptly any adverse reactions or suspected adverse reactions which come to light in the course of a trial.

In accordance with internationally recognised standards section 5 of the Bill makes it a requirement that a clinical trial may be conducted only by a registered medical practitioner or a registered dentist. The definition of the phrase "conduct a clinical trial" covers trials with both new and existing drugs and whether they involve healthy volunteers or patients. However, it has been framed in a manner to ensure that it does not interfere with ordinary medical or dental practice. I might add that while the basic purpose of the Bill is to control drug trials it has been thought desirable to provide that a clinical trial may cover investigations of the use of potentially hazardous substances such as cosmetics.

Concern has been expressed that the terms of the Bill as circulated would seriously interfere with or even cause the cessation of certain types of research for which the controls in this legislation are not appropriate and which are of fundamental importance for public health and good medical practice. I have read of these particular concerns and I want to assure the House that they are unfounded.

It has been suggested, for instance, that research involving normal dietary constituents, such as studies of the results of administration of iron supplements or other normal dietary constituents such as vitamins, would be subjected to the full rigours of the new scheme, including the insurance requirement. In fact, the definition of clinical trial in section 5 excludes substances which are deemed not to have a medical or deleterious effect and under our current medicines licensing system we do not regard as a medicine a vitamin or similar dietary constituent which is given at levels within the recommended daily allowance. Neither does the Bill affect arrangements for the exchange or pooling of information by doctors of their observations of the effects of the use of established drugs with which they are treating their patients in the normal course of medical practice.

Similarly, demonstrations of the effects of drugs of a kind in which medical students have traditionally participated in the course of their training do not come within the scope of the Bill. These can hardly be regarded as "investigations", which is part of the proposed description of a clinical trial.

However, I would not be justified in excluding absolutely trials with medicines which are already the subject of a product licence. Investigation of new indications for licensed drugs, including higher dosage levels or different patient groups, for example, also require scrutiny by a national regulatory body. I may say that this is the opinion which emerges for discussion in the Committee on Proprietary Medicines of the EC. In the operation of the scheme there will be sufficient flexibility to take account of existing knowledge of the development and use of a drug but additional uses such as I have mentioned are introducing a new and unknown factor and it would be unwise to neglect their inclusion within the general scope of the Bill.

Ethics committees have a key role to play in deciding on the legitimacy of proposals for clinical trials and in the supervision of the manner in which such trials are carried out. Section 7 of the Bill requires that there shall be an ethics committee to consider and report on the justification for each particular clinical trial before it commences. Central to the area of concern to an ethics committee would be the matter of ensuring that the risks to the participant do not outweigh the objectives of the trial. Guidelines will be drawn up for the information of applicants so that they will know what the Minister might be expected to approve of in terms of the composition of such committees.

I am sure that all involved in the conduct of clinical trials will accept that the public have a right to feel satisfied not only in regard to the competence but also the independence of these committees.

Also of particular concern to the ethics committee would be the matter of consent to participation in a clinical trial. It is of fundamental importance that a proposed participant be given sufficient information, in a comprehensible form, to enable him to make a proper judgment whether to participate or not. This matter is dealt with in section 8 which also requires the participant's written consent and specifies his right to withdraw his consent at any stage. Special provisions are also included in order to protect patients who are unable to give written consent or to understand the nature of the consent. A further protection in the case of a patient is that such patient may only be used in a clinical trial if the drug under trial is to treat his condition.

It has become quite clear that the question of payments to participants is a contentious one. Representations have been made to me that socially disadvantaged groups, such as the homeless and unemployed, are exploited and influenced in their decision to participate in a clinical trial by the expectation of significant financial gain.

To allay concern in this regard, the payments to be made to participants must be in accordance with those specified in the permission of the Minister, as provided for in section 8 (7). It is envisaged that such payments will be confined to a level which would not provide undue inducement to persons to participate in a clinical trial.

A further safeguard in relation to persons undergoing drug experiments is provided in section 9. This requires that the person arranging for the conduct of a clinical trial must see to it that there is in force a policy of insurance, issued by an authorised insurer, which would be sufficient to provide appropriate compensation in the event of the participant suffering injury or loss.

There are several offences created in this Bill. Section 11 makes it an offence for any person to provide, or cause to be provided, to another person incorrect or misleading information etc. either for the purpose of an application or in relation to the trial itself. This should ensure that the information which accompanies the application or which is reported in accordance with section 10 is accurate and unambiguous. Section 12 specifies the other wide-ranging offences which will apply. This section also includes a "good defence" which would apply in a situation where the substance was administered in the case of emergency medical or dental treatment.

Where a person is prosecuted for failure to apply for permission to carry out a trial section 13 stipulates that the onus of proof will be on that person to show that the substance or preparation administered may not have a medical or harmful effect and that, therefore, the activity in which he was engaged did not constitute a clinical trial. Section 14 provides that penalties up to a maximum of a £10,000 fine or imprisonment for a term not exceeding three years, or both, will apply in the case of conviction on indictment.

Section 15 empowers the Minister to charge fees in respect of applications made. In accordance with general policy in these matters, the scale of fees will be geared to provide that this statutory scheme will be self-financing.

In conclusion, I trust that the description and general philosophy of the Bill which I have outlined will satisfy the House both as to the need for a statutory mechanism to control clinical trials and the reasonable nature of the provisions proposed.

I should say that, during the drafting of the Bill, — and I would stress that it was a particularly difficult exercise — and indeed since its publication, a wide range of views on the form which the statutory arrangements should take was conveyed to my Department. However, there was no disagreement with the principle of statutory control.

Bodies consulted prior to the publication of the Bill included the National Drugs Advisory Board, the Federation of Irish Chemical Industries, the Federated Dublin Voluntary Hospitals, the Medical Research Council, the Irish Medical Organisation, the National Health Council and the Social Policy Action Group. I also considered carefully the statement published after the Bill was circulated by the Royal College of Physicians on the text of the Bill and I hope I will have reassured them in relation to a number of aspects on which they expressed concern.

I hope that the explanation I have given of the background to the provisions in the Bill and the impact they are intended to have will be accepted as a fair balance of the need for protection of individual health and welfare and of the legitimate and necessary requirements of medical research.

I look forward to the help and cooperation of Members in the enactment of this Bill and I commend the Bill to the House.

Debate adjourned.
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