Research ethics in genomics studies: towards a protocol for returning individual genetic data to research participants.
Steeds vaker wordt er in medisch-wetenschappelijk onderzoek ook (delen van) het genoom van proefpersonen onderzocht. De afgelopen jaren is er een debat ontstaan over de vraag of en in hoeverre genetische resultaten moeten worden teruggekoppeld aan proefpersonen. Door een aantal ontwikkelingen, waaronder de opkomst van biobanken, wordt het steeds urgenter om een goed antwoord te vinden op deze vraag. Door de zich snel ontwikkelingen technologie is het immers mogelijk geworden om ongekend grote hoeveelheden DNA te genereren in steeds kortere tijd.
De uitkomst van dit project is dat er valide ethische argumenten zijn om individuele genetische onderzoeksresultaten terug te koppelen aan proefpersonen. Maar er moet rekening worden gehouden met de voortgang van wetenschappelijk onderzoek en het niet-schaden van proefpersonen. Daarom hebben de onderzoekers een genetisch terugkoppelingbeleid ontwikkeld dat recht doet aan de complexiteit van de problematiek en dat een goede balans biedt tussen de voor- en nadelen van terugkoppeling.
Samenvatting van de aanvraag
An important topic of debate in (clinical) research ethics is whether respect for research participants implies that results should be returned to them. In the context of genetics research, this resulted in the ‘clinical utility standard’: the view that individual genetic data should be disclosed to research participants when these data are of clinical relevance - i.e. preventive or therapeutic measures are available. Genetics research, however, has shifted from Mendelian genetics to genomics research. Genomics research, such as the current genome wide association studies (GWAS) and the impending Whole Genome Sequencing-studies, is focused at identifying risk factors for complex common disease, such as cancer, diabetes and heart disease. A characteristic of genomics research regards its large scale character: large sample sizes, large amounts of genetic data, requiring the participation of large numbers of research participants. Furthermore, as the spotlight in genomics studies is turned on increasingly larger parts of the genome, the chance of unexpected findings pointing at abnormal genetic findings unrelated to the disease(s) under study increases. Although we take the clinical utility standard as our point of departure, the specific characteristics of the current genomics research and the impending Whole Genome Sequencing-studies re-open the debate about this standard. We identify four issues that ask for further elaboration to see whether the clinical utility standard can become useful and applicable for the genomics era. A first issue regards the appropriate scope of the clinical utility standard, ranging from a narrow interpretation (only disclosing data that help to avoid clear and present danger) towards broader interpretations (also disclosing data regarding less immediate threats). A second issue is what we should regard as data of clinical utility: should risk information be included? If so, this evokes new questions regarding the magnitude in risk and the kind of risk information eligible for disclosure. A third issue is who decides about the appropriate procedures of identifying and subsequently disclosing clinically relevant results. Furthermore, as the significance of many genetic variants is currently still unknown, a question that needs to be addressed is how to deal with information that turns out to be clinically relevant in the future. Finally, a fourth issue regards the proper person (or profession) to communicate the results to the research participant. Currently, a lack of clarity exists regarding when and how to disclose individual genetic data to research participants in studies with a genetic component. Although the lack of guidance was signalized some years ago, at present still no uniform guidance for disclosing research results exists. If guidance is already available, then this is not shaped with the current genomics research and the impending Whole Genome Sequencing-studies in mind. As a consequence, researchers and Research Ethics Committees (REC) still struggle with the question as to whether research protocols should adopt provisions about whether to return results, and if so, how this should take shape. Therefore, the aim of this project is twofold. First, we aim to rethink the scope and limits of the clinical utility standard in order to make it appropriate for medical-scientific research involving human subjects in the genomics era. Second, we aim to develop guidelines for researchers and REC’s regarding the disclosure of individual genetic data to research participants in genomics research. We expect these guidelines to be helpful for researchers in designing their study protocols and for REC’s in assessing the ethical acceptability of genomics research. Most importantly, these guidelines will eventually provide research participants with transparency regarding when and under which conditions they may be confronted with genetic (risk) information – which, after all, may have profound psychological, social and economic consequences. Our strategy for implementing our intended guidelines is a two-stage rocket: first we will involve relevant actors and professional organisations in the development of the guidelines, subsequently we will use the existing research infrastructure for implementing the guidelines.