Pharmaceutical research, but at whose expense?

How can participants in pharmaceutical studies be protected and ethical standards be effectively enforced in the global context? How can research quality be ensured in a global context? Are ethics committees suited to and necessary for the protection of test subjects? What ethical standards should European research projects take into account? It was to questions such as these and others that the German Ethics Council sought answers at its 2013 annual meeting in Berlin last Thursday, in the course of which it held discussions with around 300 delegates.

“We all want to see medical progress”, said Christiane Woopen, Chair of the German Ethics Council in her opening statement, “but such progress requires research and there is no such thing as research without risk to the test subjects. There is always a price to pay for research.” In this respect, she went on to say, it is about issues of test subject protection and the just distribution of the benefits and burdens of research, whereby the increasing internationalisation in pharmaceutical research involving differing moral paradigms and cultural identities makes it necessary to ensure high ethical standards.

Ignaz Wessler, Executive Physician of the Ethics Committee at the Rhineland-Palatinate State Chamber of Physicians, presented a draft regulation of the European Commission concerning pharmaceutical research on human beings, on the basis of which new rules for clinical tests are to be applied in future and which is designed to harmonise the previously very different approaches and procedures in all 27 Member States. The idea behind this is to ensure that Europe continues to be an attractive location for research and to enable more rapid access to innovative technologies. According to Wessler, both the Working Group of Medical Ethics Committees and the German Medical Association as well as the German Federal Parliament and the Federal Council of Germany are all critical of any such new regulation, because in some respects the new regulation fails to meet the currently applicable ethical and legal standards for pharmaceutical research.

In the following presentation Andreas Spickhoff of the University of Göttingen subjected the planned EU regulation to a critical review with reference to the current legal situation. Spickhoff is particularly apprehensive about lowering existing standards within Europe, which would have far-reaching ramifications for developing countries and emerging economies. In particular he addressed the ethics committees’ essential duties and their significance for the safety of test subjects. In his summary he called for “thoroughness before rapidity”. During the ensuing public discussion Siegfried Throm of the Association of Research-Based Pharmaceutical Companies also backed calls for the retention of the ethics committees.

Jochen Vollmann of the University of Bochum was also critical of the fact that the planned EU regulation does not include ethics committees as mandatory monitoring and certification authorities. One of the reasons he identified for the EU regulation is the reduction of clinical studies in Europe. However, he went on to say, this is not due to our higher standards, but rather it has to do with socio-economic considerations. So rather than lowering ethical standards we should be tackling the problem of funding. He pointed out that the European Commission’s draft regulation endangers “important cultural attainments such as respect for self determination, the protection of test subjects against third-party interests and an ethical research culture”, which is specifically promoted by local ethics committees.

Monika Bobbert of Heidelberg University explained how important the work of clinical ethics committees is, particularly at the local level. However she did remind the assembled delegates of the need to introduce consistent legal regulations throughout Germany. According to Bobbert at least half the members of ethics committees should be drawn from non-medical professions, in order to ensure an impartial consideration of relevant interests. The precise nature of the members' ethical expertise still needs to be agreed, she said. Bobbert also proposed that ethics committees should not only take an independent and qualified stance on ethical issues relating to a given planned study, but that they should also monitor its progress and assess its results. This, she points out, would be extremely beneficial in terms of test subject protections and the advancement of scientific knowledge.

Inder Sen Gandhi of the Vimta Labs in Hyderabad and Amar Jesani from the Center for Studies in Ethics and Rights in Mumbai, India, presented  practice and ethical standards in pharmaceutical research in India. They explained the major challenges faced by clinical ethics committees in India, which involve the role of doctors as researchers, risk-benefit considerations, the informed consent of test subjects, issues of responsibility and the equitable sharing of benefits as well as financial compensation for study participants. A fundamental assumption in both presenters’ talks is the particular vulnerability of many Indian test subjects, and both suggested some concrete steps that are necessary to bring about a responsible research culture in India. Jesani in particular emphasised the fact that ethical guidelines not only need to be developed but also implemented.

With his philosophical musings Ludwig Siep of the University of Münster brought the days’ discussions full circle to the theoretical underpinnings of existing ethical standards. These involve human rights issues as well as generic principles of morality and considerations of justice. The question was briefly touched upon as to the extent to which arguments of personal autonomy, apparently informed by the western conception of mankind, can be reconciled at all with the kind of group-oriented paradigms more strongly represented in other cultures.

In the following plenary session Wolfgang Huber, a member of the Council, and the two guests from India as well as Council member Silja Vöneky explored the question of state obligations vis-à-vis globally active pharmaceutical enterprises, which are increasingly carrying out their pharmaceutical studies in developing countries and emerging economies. From a human rights perspective Vöneky emphasised the fact that it would be possible for industrial countries to impose far more stringent rules for the protection of test subjects on corporate enterprises based within their territorial jurisdiction than has hitherto been the case, which would then apply indirectly to subsidiaries and service providers in developing countries and emerging economies. But also those countries in which research is being carried out have an obligation to establish or negotiate binding conditions for research organisations designed to protect test subjects and that are consistent with human rights. One thing in particular that is required in this context is to restrict the admissibility of placebo studies in situations in which a standard therapy already exists in the research organisation’s home country. He also went on to say that the ethical guidelines, such as the GCP Guideline, to which the draft EU regulation makes reference, should be checked for consistency with human rights and concomitant obligations in terms of test subject protection.

In his summary speech Council member Wolf-Michael Catenhusen reiterated the global dimension of the topic and said that the impressive examples from India provide a positive model for other countries in terms of the restructuring process involved in creating a modern health system. He emphasised the fact “that the establishment of global standards for ethically responsible management of the introduction of certain titles and structures is not automatically being carried out in the spirit of basic ethical principles, which we have come to adopt starting with the Declaration of Helsinki”, and addressed the need to keep a close watch on the discrepancy between aspirations and reality.

The programme for the annual meeting as well as the presentations and contributions to the discussions are available here (in German).