Ethical management in the constitution of a European database for leukodystrophies rare diseases.

BACKGROUND: The EU LeukoTreat program aims to connect, enlarge and improve existing national databases for leukodystrophies (LDs) and other genetic diseases affecting the white matter of the brain. Ethical issues have been placed high on the agenda by pairing the participating LD expert research teams with experts in medical ethics and LD patient families and associations. The overarching goal is to apply core ethics principles to specific project needs and ensure patient rights and protection in research addressing the context of these rare diseases. AIM: This paper looks at how ethical issues were identified and handled at project management level when setting up an ethics committee. METHODS: Through a work performed as a co-construction between health professionals, ethics experts, and patient representatives, we expose the major ethical issues identified. RESULTS: The committee acts as the forum for tackling specific issues tied to data sharing and patient participation: the thin line between care and research, the need for a charter establishing the commitments binding health professionals and the information items to be delivered. Ongoing feedback on the database, including delivering global results in a broad-audience format, emerged as a key recommendation. Information should be available to all patients in the partner countries developing the database and should be scaled to different patient profiles. CONCLUSION: This work led to a number of recommendations for ensuring transparency and optimizing the partnership between scientists and patients.

Evaluation of biobank constitution and use: multicentre analysis in France and propositions for formalising the activities of research ethics committees.

Biobanks are collections of biological material and related files gathered and stored for clinical or research purposes. Here, we investigated the questions raised during the evaluation of biobanks by biomedical Research Ethics Committees (RECs), particularly in the context of genetic research. We sent a questionnaire to all RECs in France to survey their concerns and the ethical criteria used when evaluating research involving the storage of biological samples. Most of the RECs think that they should be consulted to evaluate the constitution of biobanks. The proportion of RECs of this opinion depended on whether the biobank is being constituted in the absence of an associated research project (initially created for clinical purposes or for undefined research) (14/28), whether the biobank is being constituted for research use (21/28) or whether an existing research biobank is being re-used (19/28). Views diverged concerning the way ethics principles are applied, showing that REC evaluations of biobanks might be formalised at each of the following steps: constitution, use and re-use. In this paper, we suggest concrete elements that could be integrated into the application of the new French law concerning the protection of the human beings participating in research as well as into international recommendations.

[Study over 10 years of 622 protocols receiving unfavourable reports from 19 research ethics committees]. / Etude sur 10 ans de 622 avis non favorables rendus par 19 comités consultatifs de protection des personnes se prêtant à la recherche biomédicale (CCPPRB).

OBJECTIVE: The aim of this study was to analyse the nature of applications and the criteria for their negative evaluation by 19 ethics committees for the protection of human subjects participating in biomedical research, the French CCPPRB. METHODOLOGY: The committees distinguished between negative opinions that were given from the start of the applications or after amendments were made, and between lost protocols (no answer within more than 1 year) or protocols that were outside of the framework of the Huriet-Sérusclat law. The opinions were analysed by an independent observer over a period of 10 years. RESULTS: Few protocols (1.3% of the total number of files) are rejected on the basis of scientific and ethical criteria. Traceability is a significant problem, which obstructed the study of lost protocols and amendments. For protocols not covered by the law, the committees already work in accordance with the European directive recommending the exclusion of studies consisting only of routine medical procedures.

Communication of pharmacogenetic research results to HIV-infected treated patients: standpoints of professionals and patients.

The aim of pharmacogenetic studies is to adapt therapeutic strategies to individual genetic profiles, thus maximising their efficacy and minimising the likelihood of adverse side effects. Since the advent of personalised medicine, the issue of communicating research results to participants has become increasingly important. We addressed this question in the context of HIV infection, as patients and associations are particularly concerned by research and therapeutic advances. We explored the standpoints of both research professionals and participants involved in a pharmacogenetic study conducted in a cohort of HIV-infected patients. The setting of the research protocol was followed over a 2-year period. Participants' standpoints were collected through a questionnaire and interviews were conducted with research professionals. Of 125 participants, 76% wished to receive individual results and 71% wished to receive collective results; 39% did not know when results might be expected. Communication of global research results is a principle that is generally accepted by professionals. Concerning individual feedback, the professionals felt that it was necessary if it could be of direct benefit to the participant, but they expressed doubts for situations with no recognised benefit. Our results highlight the necessity to consider this issue in greater detail. We suggest the need to anticipate the debates concerning individual feedback, to differentiate between situations and the importance of further investigations on the opportunities and modalities of communication. Finally, our work emphasised the opposite pressures between the pursuit of scientific knowledge and the therapeutic orientation of clinical trials.

Decisions concerning potentially life-sustaining treatments in paediatric nephrology: a multicentre study in French-speaking countries.

BACKGROUND: Few studies have looked at how decisions are made to withhold or to withdraw potentially life-sustaining treatments (LST) in paediatric nephrology. The aim of this work was to evaluate such practices in all nephrology centres in French-speaking European countries, so that guidelines could be discussed and drawn up by professionals. METHODS: We used semi-directed interviews to question health care professionals prospectively. We also retrospectively analysed the medical files of all children (n = 50) for whom a decision to withhold or to withdraw LST had been made in the last 5 years. The doctors (n = 31) who had been involved in the decision-making process were interviewed. RESULTS: All 31 of the French-speaking paediatric nephrology centres in Europe were included in this study. Of these, 18 had made decisions in the previous 5 years about withholding or withdrawing LST. Resultant quality of life, based on long-term living conditions, was the principal criterion used to make the decisions. Relational aspects of life and the child's prognosis were also considered. The decision-making processes were not always collective, even though interactions between doctors and the rest of the medical team seemed to be key elements to them. The parents' involvement in the decision-making process differed between centres. CONCLUSIONS: The criteria used to decide whether to withhold or to withdraw LST are not standardized, and no specific guidelines exist.