the protection of patients’ rights in clinical trials
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Science and Engineering Ethics (2006) 12, 131-138
Science and Engineering Ethics, Volume 12, Issue 1, 2006 131
Keywords: protection of patients rights, clinical trials, ethic committees ABSTRACT: The Helsinki Declaration is a very important document regarding the protection of patients rights in clinical trials and one of the fundamental sources of operational principles for every ethics committee. Although they have been updated, the international guidelines for ethics committees continually fail to address certain issues pertaining to the protection of patients rights in clinical trials. These issues include, most significantly, the method of electing ethics committees (a free, secret ballot should be preferred to direct appointment), the avoidance of conflict of interest during the election of ethics committee members, and the necessary insurance coverage for the participants of clinical trials. Polish law should, on the other hand, be developed in such way as to not limit the effectiveness of ethics committees in protecting patients rights in clinical trials. The ideal solution would be to draft a uniform law concerning not only clinical trials, but all medical experiments. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. The past few decades have brought about significant advances in the protection of patients rights in clinical trials. The publishing of several international guidelines and recommendations, most notably the Helsinki Declaration,1 has been beneficial to this field. The Helsinki Declaration was drafted in June 1964 by the World Medical Association and subsequently updated several times. The most recent amendments led to the addition of commentary to articles 29 (Washington 2002) and 30 (Tokyo 2004).
The Protection of Patients Rights in Clinical Trials Marek Czarkowski Medical University of Warsaw, Poland
This paper was presented at the 6th International Bioethics Conference on the subject of TheResponsible Conduct of Basic and Clinical Research, held in Warsaw, Poland, 3-4 June 2005. Address for correspondence: Marek Czarkowski, MD, Department of Internal Medicine andEndocrinology, Medical University of Warsaw, ul. Banacha 1A, 02-097 Warsaw, Poland: email:firstname.lastname@example.org. The author is Chairman, Bioethics Committee of the Warsaw Regional Chamber of Physicians andDentists. 1353-3452 2006 Opragen Publications, POB 54, Guildford GU1 2YF, UK. http://www.opragen.co.uk
132 Science and Engineering Ethics, Volume 12, Issue 1, 2006
The guidelines regarding the use of placebo, detailed in art. 29,a were the subject of intense criticism from circles representing the interests of pharmaceutical companies. This was undoubtedly the result of a conflict between the will to ensure the best possible protection for the participants of clinical trials (trial subjects) and the economic interests of the pharmaceutical companies. Placebo-controlled trials of new medications are more likely to lead to market success than trials in which the effectiveness and safety of a new drug are compared to a widely-known, and usually cheaper, reference drug. Demonstrating the efficacy of a new drug, compared to placebo, allows for its registration as an effective treatment for a given condition. Requiring that the new drug be compared to an older one always creates the risk that the studied drug may prove to be less effective. Thus, from the study sponsors point of view, a placebo-controlled trial of a new drug creates a greater probability of economic success than a trial in which it is compared to other existing, effective, and usually cheaper drugs. Pressure from circles representing the interests of pharmaceutical companies has led to the addition of commentaryb to art. 29 which, instead of clarifying art. 29 and stating it more precisely, created a series of ambiguities and is, in my opinion, insufficient in protecting the rights of the participants of clinical trials.
Art. 30 of the Helsinki Declaration,c on the other hand, and the commentary added in Tokyo in 2004,d are examples of well-written guidelines regarding the protection of patients rights in clinical trials. Art. 30 and the commentary concern the protection of study participants from the scenario in which an effective treatment is ceased at the end of the trial. It is worth noting that some clinical trials, especially those designed in accordance with the rules of Evidence-Based Medicine, deal with potentially fatal conditions, in which withdrawal of effective treatment may pose a direct hazard to not only the patients health, but also their lives. Thus, if patients are offered participation in a clinical trial, it is the study designers responsibility to foresee the possible
a. The benefits, risks, burdens and effectiveness of a new method should be tested against those of
the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic, or therapeutic method exists.
b. The WMA hereby reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances:
- Where for compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or
- Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm.
All other provisions of the Helsinki Declaration must be adhered to, especially the need for appropriate ethical and scientific review.
c. At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study.
d. The WMA hereby reaffirms its position that it is necessary during the study planning process to identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review.
The Protection of Patients Rights in Clinical Trials
Science and Engineering Ethics, Volume 12, Issue 1, 2006 133
consequences, as well as to ensure appropriate therapy following the completion of the trial, especially if the studied method proves to be the only effective treatment for a given condition. In such a situation, the continuation of effective treatment may only be possible if the participants are assured of free access to a new, unregistered drug. New products are usually expensive and study participants cannot afford to purchase them. The national health care system cannot, however, refund the cost of such treatment prior to the official registration of the new drug. Assuring the trial participants of access to the studied drug following completion of the trial can significantly increase the cost of such a study. It simultaneously creates the possibility for patients to participate in a long-term open phase of the study, which can yield interesting clinical observations concerning, among other things, the safety of the treatment and how well it is tolerated by the patients. The alternative to the approach outlined in the Helsinki Declaration is the ethically unacceptable scenario in which study participants are placed in a potentially life-threatening situation after the trial is completed and treatment is withdrawn.
Other important international documents, besides the Helsinki Declaration, include the guidelines for ethical committees developed by the World Health Organization2 and European Forum for Good Clinical Practice.3 Certain significant aspects of the protection of patients rights in clinical trials were, however, omitted in these documents.
First of all, it was assumed that the elections of ethics committee members by ballot and by direct appointment are equivalent. I disagree with this opinion. Polish bioethics committees (the name given to ethics committees in our country) are elected both by appointment and by free ballot. The first method is used for committees at medical universities and scientific research institutions, the latter for bioethics committees of regional chamber of physicians and dentists. Members of the bioethics committees of regional chamber of physicians and dentists are elected by the doctors of the regional medical council. In the case of the Bioethics Committee of the Warsaw Regional Chamber of Physicians and Dentists, for example, the elections may only commence once at least two candidates have been nominated for each position. The ballot is secret, and members of the committee can only be dismissed if they fail to take part in its activities. The members of the bioethics committees of medical universities and scientific research institutions, on the other hand, are both nominated and elected by arbitrary appointment. Direct appointment is still widely used as a method of electing ethics committee members in the European Union and USA. It does not, however, guarantee the true independence of the committee members, and, furthermore, creates a high probability of