Katja Stoppenbrink: Clinical Research in Vulnerable Populations, Berlin, 3-4 April 2008

On 26 January 2007 a regulation and amending regulation on medicinal products for paediatric use came into force in the EU, which requires that medicines are ethically researched and made available for children aged 0-17 years. During the legislative process, Europe’s pharmaceutical industry was lamenting the complex, time consuming, and therefore expensive research in children required as a consequence and opposed the legislative changes. After a year it is time for a first assessment: The ongoing lack of specialised and targeted research in pharmaceuticals for paediatric use is due to the historically deeply held views that children can be seen as “small adults,” who can simply be administered smaller dosages of medicines adapted according to age and weight, and that research in incapacitated populations is ethically strictly unacceptable. Both views are wrong. This was proved on April 3 and 4 2008 at the Berlin-Brandenburgische Akademie der Wissenschaften (BBAW) where the issues involved in the new regulation were controversially discussed.
The main concern of researchers from both universities and industry remains finding sufficient numbers of minor test persons. Often parents simply do not like the idea that their offspring take part in clinical research and are not susceptible even to good arguments. The consensus was that this is not simply a question of adequate, comprehensive and comprehensible informed consent and the risk-benefit ratio, but also of establishing a personal and trustful relationship with risk averse parents or guardians. In countries providing universal health care, parent consent will be less susceptible to external incentives, such as access to treatment. It is well known that many studies conducted in the European population actually take place in eastern countries such as Romania, Bulgaria, and Ukraine. However, empirical studies on the differences of research participation of children between universal and non-universal healthcare systems are not available. The worry is that the trial requirements for market authorisation of pharmaceuticals imposed by the paediatric regulation will give rise to new “research imperialism.” Research on research is needed to refute this grave accusation.
After one year and two months after the entry into force of the paediatric regulation it seems too early to assess whether the incentives given by the new regulation (six months of patent extension) do their work properly. However, Benedetto Vitiello, of the US National Institute of Mental Health in Bethesda, showed in his talk on publicly funded versus industry funded research strategies in paediatric pharmacology that the US experience with financial incentives for more than a decade Starting point was the FDA Modernization Act of 1997; in 2002 the Best Pharmaceuticals for Children Act was passed, followed by the 2003 Pediatric Research Equity Act. Reauthorizations were enacted with the Food and Drug Administration Amendments Act of 2007, has in general been a success story since the quality of studies improved and the market exclusivity programme was re-authorized (Cf. the assessment by J S Li et al., Economic Return of Clinical Trials Performed Under the Pediatric Exclusivity Program, JAMA, February 7, 2007; 297: 480 – 488) and extended in 2007.
Birka Lehmann of the German Federal Institute for Drugs and Medical Devices explained the details of the new legislative framework for the submission of applications for marketing authorisation of medicinal products. A paediatric investigation plan has to be submitted before in the end the drug industry may receive the coveted paediatric-use marketing authorisation. The pivotal role in the new approval regime is with the paediatric committee (PDCO), which has to assess the compliance of the submitted PIPs and can either approve of or refuse, give a waiver or a deferral. Experts in paediatric pharmacy are needed to do this responsible, burdensome, time consuming, and bureaucratic task, and it is up to national bodies to introduce a reimbursement of expenses incurred. Germany has so far decided to regard the PDCO’s work as an honorary appointment. No wonder there wasn’t any German university professor available to sit on this committee. Neither have enough representatives of healthcare professionals or patient associations been recruited. If you’re interested you might still have a chance.
A final remark: the conference was entitled “Clinical Research in Vulnerable Populations. I have learnt a lot about the new paediatric regulation and the pharmaceutical industry’s indecisiveness to welcome the paradigm shift in clinical research of medicines for use in minors. However, if there had not been an interjection from the audience and a hint en passant by the Oxford child and adolescent psychiatrist and ethicist Jacinta Tan, in her presentation on the salient ethical issues of informed consent and competence (e. g. on group consent by parents and children), I would not have been in a position to tell whether vulnerable populations meant any groups apart from children. My proposal therefore is: How about another conference resuming the debate on targeted medicines for female patients and old age patients, on research in developing countries and other non-universal health care countries and in populations from cultural minorities or with immigrant background? I would be happy to receive an invitation.
Katja Stoppenbrink is a PhD student in bioethics in Cologne, Germany.

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  • Trisha B

    Vulnerable populations is one topic I examine from time to time. In economics and in ethics there seems to be one eye open and seeing and the other eye closed and confused. As you read between the lines in research studies I do notice the missing populations more than those that are in the research. So too, the selection of some populations is a curious procedure. Whether there is informed consent or not is a valid question. The selection and the use of the population requires professionalism and an eye to more than the study on the printed page.