STUDY DESIGN

In order to answer the questions above, a research group at Goettingen University designed an empirical study to assess the decisions of chairpersons of German research ethics committees in cases of non-therapeutic research with minors. In accordance with Kopelman,⁸ by non-therapeutic research we understand study elements performed to seek “generalisable knowledge and not intended as therapy to benefit the individual directly”. Forty nine REC chairpersons were contacted and asked to complete a questionnaire. In the questionnaire we asked for an evaluation of five realistic research scenarios, all examples of non-therapeutic research in paediatrics or child psychiatry with no direct benefit for the children concerned (see box). The risk and burden involved for the study participants gradually increased from scenario 1 to 5 (see box). We recorded 35 reactions (71.4%); 29 questionnaires were filled out and sent back (59.2%). Ninety per cent of those who answered were men, 51.7% were older than 60 years, and 41.4% were between 41 and 60 years old.

Eighty nine point seven per cent of the respondents were medical doctors, and 20.7% worked in the field of paediatrics. 72.4% of the respondents had extensive experience in the field of decision making in RECs—that is, they had taken part in more than 50 committee meetings; another 24.1% had participated in at least 10 to 50 meetings. Ninety three point one per cent of the respondents had children of their own.

We asked whether the research scenarios depicted would be evaluated positively by the chairperson (“Do you think the study is justifiable and would you support a positive decision of the research ethics committee?”). The respondents had four options: “Yes, without restrictions”, “Yes, with restrictions (please explain)”, “I don’t know/I have no opinion”, and “No, under no circumstances”.

RESULTS

The answers of the respondents are shown in the figure. From the respondents’ point of view, there was a significant difference between the appraisals of studies 1 and 2, and studies 3, 4, and 5. While research scenarios 1 and 2 would have been approved by all REC chairpersons (although sometimes with slight restrictions), trials 3 to 5 were strongly rejected by a number of participants. In our view, this division of opinion is caused by the far more invasive character of the latter research projects. While the study design of research projects 1 and 2 involved only a very small risk for the participants’ health, the medical interventions in studies 3 to 5 were far riskier and could have caused severe side effects.

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Figure 1

Evaluation of five different studies by chairpersons of German research ethics committees (n = 29).

The design of study 1 had the highest acceptance (28/96.6%). It included the use of an additional 5 ml blood from a blood sample for diagnostic reasons from children with a non-specific mental retardation. Although the study design as far as risks are concerned strongly resembled the German “Eisingen case” (see above), it seemed quite acceptable to chairpersons. The respondents could add comments to their evaluation of the respective research projects. Most of the comments on the evaluation of study 1 correctly referred to the necessity of obtaining the parents’ or children’s informed consent or assent.

The proposal for study 4 received the highest number of rejections. Children at the age of 6–11 suffering from acute lymphatic leukaemia were supposed to participate in a randomised, two armed study. Its purpose was to compare the outcome of a new chemotherapy with standard therapy. In the course of the study, weekly bone marrow biopsies were to be performed in both study groups. Six out of 10 bone marrow biopsies were intended for purely scientific purposes, without direct benefit for the participant involved. Most of the respondents (17/58.6%) refused approval of the study. The most frequent comment on the study design was the rejection of additional, non-therapeutic bone marrow biopsies. Other frequent comments were critical of the high burden it put on the study participants, and of the treatment plan for the biopsies. One respondent referred to the additional biopsies as “a kind of child abuse”. However, six chairpersons (20.7%) saw no problem to approve the study without further restrictions.

Scenario 5 also elicited a wide range of reactions. The aim of the study was the treatment of children aged 2–5 with congenital cardiac defect. These patients have an increased risk of myocardial inflammation caused by respiratory syncytial viruses. The research programme proposed a randomised, two armed, placebo controlled study to prove the prophylactic effect of immunoglobin against heart muscle inflammation. The children in the placebo group were to receive intramuscular injections of sodium chloride solution. In the course of the study, cases of myocarditis in each group would be counted. Study participants with myocardial inflammation were to receive standard treatment. As the chart in the figure shows, the placebo controlled study (5) was more easily accepted by chairpersons than study 4. Seven of the respondents (24.1%) would have approved the study without further restrictions, while 12 (41.4%) would have rejected it.

CONCLUSION

The results of our study show that in the case of non-therapeutic research with minors involving a higher than minimal risk, decisions of chairpersons of German RECs vary to a disturbingly high degree. In contrast to widespread public criticism, chairpersons do not object on principle to non-therapeutic research with only minimal risk or burden (for a critical discussion of the notion “minimal risk” see Kopelman⁹ and Maio¹⁰). There seems to be a kind of consensus among chairpersons with regard to the evaluation of less invasive interventions for non-therapeutic research, as the undisputedly positive evaluation of studies 1 and 2 has shown. More invasive interventions like those involved in studies 3 to 5, however, are seen as more controversial. This reflects the ethical discussion about non-therapeutic research with minors in Germany. From our point of view, it is disturbing that RECs in Germany seem to arrive at widely differing decisions where more invasive interventions are concerned. Whereas four out of 29 committees, according to the vote of their chairpersons, would probably have refused the approval for at least three of the five studies, two committees might have approved all studies without any restrictions.

We believe this situation is not acceptable. We are aware of the fact that the opinion of chairpersons cannot simply be equated with the decision of the committees as such. However, chairpersons are usually experienced and well informed members of ethics committees as far as ethical and legal regulations are concerned. Their interpretation of what is legally and ethically acceptable on the basis of current German regulations should, where more than minor risks are at stake, at least not differ to such a wide extent. The European Convention on Human Rights and Biomedicine, for example, strictly rules out this type of research. That the opinions of German chairpersons on these issues vary to such a high degree reveals significant uncertainty as to the ethical standards in non-therapeutic research. This creates problems for study participants, researchers, and the public, who are left uncertain about the standards of protection of research participants and in risk benefit analyses. This problem is particularly prominent in multicentre research projects where several local RECs are involved. Our conclusion is that there is an urgent need for a more detailed, comprehensive, and unambiguous regulation of research with the non-competent in Germany that does not permit such a wide range of interpretation. Meanwhile, the ratification of the European Convention on Human Rights and Biomedicine seems to be a good way to guarantee at least minimal ethical standards in these cases in Germany.