Individual rights and autonomy in clinical research

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This editorial refers to ‘Adherence to the medical regime in patients with heart failure’ by S. Muzzarelli et al., on page 389. As stated under the ‘guide for authors’ section on our web site, European Journal of Heart Failure participates in the HEART network, a network of editors from most cardiovascular journals who exchange information and have a common ethics standard as outlined in our mission statement.1 This standard addresses conflicts of interest, scientific fraud, confidentiality and embargos, authorship criteria, claims of ownership and priority with regard to previously published data, claims of benefits of products or techniques, and compliance with institutional review board (IRB) requirements and the ethical standards of the Declaration of Helsinki, The Geneva Declaration, The Belmont Report, and Good Clinical Practices (GCP) from the US Food and Drug Administration.1 Central to these guidelines are that participation in research must be voluntary, informed, and agreed to by voluntary informed consent. In addition, a study must have a research protocol and this protocol must be approved by an Ethics Committee before the study begins. Furthermore, the boundaries between research and clinical practice must be recognized, and finally, the well-being of the individual research subject must take precedence over all other interests.1,2 We publish an article by Muzzarelli et al.3 that examines the adherence to medical therapy in heart failure. Patients were treated with digoxin, completed questionnaires, and had serum digoxin measured. Patients were informed that the aim of the study was to assess adherence, that the blood test assessed electrolytes and kidney function, and that digoxin was prescribed on clinical indication (all true). But they were not informed that a second aim of digoxin was to assess adherence by measuring serum digoxin levels. The authors argued, and the editors agreed, that informing patients of this purpose of digoxin may hinder interpretation of the results, and that the potential harm from digoxin was negligible in this setting. The study had IRB approval and patients completed written informed consents. But the patients were not informed of the second aim of digoxin. Therefore, we must ask whether the rights of the individual research subjects and their autonomy were violated. Would we ourselves be offended or feel violated if we had been participants? The concept of inviolable individual rights and autonomy is central to contemporary Western thought and a mainstay of medical ethics since World War II and the Nűrnberg trials. Fifty years ago, both clinical and research decisions were made without open discussion, much less participation, of the patient. Since Nűrnberg, medical ethics has become central to clinical medicine and research, and today, the pendulum has swung away from paternalism towards patient rights and autonomy. Poor adherence limits the effectiveness of proven medical treatments and about 50% of patients with chronic conditions are considered not adherent. Although better adherence is strongly associated with improved survival and lower risk of hospitalization, the extent and nature of adherence itself and those factors which are associated with it remain unclear. Self-reports and pill counts are available methods in adherence research but these measures are highly dependent upon patients' honesty and accuracy in self-reporting. Therefore, this study and its controversial design could contribute considerably to our understanding of adherence and in its extension provide benefits for other patients and society. These are laudable goals but do they justify withholding information regarding the purpose of digoxin even if this is not physically harmful? There is some precedent in research both with regard to consent, risk to the research subject and individual autonomy. Sham surgery vs. dopaminergic neuron implantation for Parkinson's disease is associated with considerable risk but was considered justified to avoid the placebo effect.4 Thrombolysis for stroke was permitted without individual patient consent after a local community group was consulted,5 which certainly made exception to the patient autonomy rule. As editors, we were humbled by the difficult ethical questions posed by this paper and by the great complexity posed by research questions involving humans and their behaviour.2 We had considerable disagreement within the editorial board, recognized that either decision would be considered controversial, and admit that we do not know what is right, but we eventually decided to publish the paper. Our mission as editors is to disseminate new knowledge while at the same time respecting the rights of research subjects. This is a difficult balance but it is clear that even with both formal guidelines and common sense, clinical research will continue to provide challenging ethical dilemmas where researchers, ethical review boards, and journal editors will disagree. Conflict of interest: none declared.