58 AAP Grand Rounds

BIOETHICS

Research on Stored Samples: Ethical IssuesSource: Wendler D. What research with stored samples teaches us about research with human subjects. Bioethics. 2002;16:33-54.

Pediatricians and their patients are increasingly in-volved in research of different types, and the subject’s informed consent for participation in research has

become a cornerstone of research ethics. But what if the re-search is to be done on leftover samples of tissue and blood obtained for some other purpose? Involvement in most re-search includes 3 distinct elements: participants are exposed to risk, they have to perform certain behaviors defi ned by the research project, and their contribution helps answer a research question. In most studies, all 3 factors are present and we rarely consider whether 1 or all of these elements requires the informed consent of participants. In research using biological samples obtained previously for other pur-poses, 1 or more of these factors may be absent. In this paper, the author discusses 3 models of informed consent based on these factors.

The fi rst model, the subject model, identifi es the need to obtain informed consent in the participant’s exposure to risk from the research. In the subject model, consent to use existing tissue specimens is needed only when the samples are linked to personal identifi ers. There is no need to obtain informed consent to use tissue specimens that cannot be linked to the original participant since the absence of a link to the source eliminates any risk to the source. The second model is the experiential model, which fi nds the need for informed consent in research procedures that have some personal effect on the participant—where they interact with the investigators or are asked to do certain things. Un-der this model, research that uses tissue samples obtained for other reasons and that contain no personal identifi ers would not necessarily require consent, since the source of the tissue specimen is unaffected by whether the research is performed or not. A third model, the contribution model, focuses not on risk or interaction, but on whether the indi-vidual makes a contribution to a particular research project. An individual contributes to a research project anytime in-formation about that person is included as data in the proj-ect. This model recognizes that persons have interests in the projects to which they contribute, and, therefore, should provide informed consent for the use of tissue samples in research projects. The author concludes that although the contribution model would argue for obtaining consent for a specifi c project, if such consent would impose a serious burden on researchers the potential value of the research may outweigh the individual’s interest in controlling pre-cisely which research project they contribute to. In other words, individuals can ethically provide a general consent to future research on their biologic samples without know-

ing of and approving of every use of their sample.

Commentary by Brenda Mears, MD, FAAPPediatrics, Medical City Dallas Hospital, Dallas, TX

Researchers have long used stored tissue samples for purposes other than those originally intended. Doing so without obtaining informed consent has recently become less acceptable. Some commentators believe that the doc-trine of informed consent is based on the right of persons to control the course of their lives,1 a right that includes the control of tissue samples taken from them. Even when a per-son is not subjected to risk and is not asked to do anything additional for a research project, that person may wish to make decisions about whether to contribute to a certain research project.

At the present time, federal regulations do not apply to re-search involving stored tissue samples that cannot be linked to an individual either “directly or through identifi ers.”2 The Offi ce of Human Subjects Research has an information sheet available on this subject.3 If any member of the research team can identify the source of the samples, an institutional review board (IRB) must review the research use. If the source of the samples is not identifi able, an exemption from IRB review may be requested. Recommendations for collection of new tissue samples that might be used for research in the future have included informing patients about the possibility of future research, informing patients about the possibility of notifi cation in the event of a clinically important discovery, and warning patients about the possibility of incidental fi ndings.4,5

References1. Veatch R. Theories of Informed Consent: Philosophical Founda-

tions and Policy Implications. In: The Belmont Report. Appen-tions and Policy Implications. In: The Belmont Report. Appen-tions and Policy Implications. In: The Belmont Reportdix II DHEW Publication No. (OS) 78-0014. Washington, DC: United States Government Printing Offi ce; 1978.

2. United States Department of Health and Human Services. Protections of Human Subjects. Title 45 Code of Federal Regulations Part 46: 101 B4. Washington, DC: United States Department of Health and Human Services; 1991. Available at: http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm#46.101.

3. National Institutes of Health, Offi ce of Human Subjects Re-search. Guidance on the Research Use of Stored Samples or Data. 2000. Washington, DC: United States Department of Health and Human Services; 2000. Available at: http://ohsr.od.nih.gov/info/ninfo_14.php3.

4. Steinberg KK. Stat Med. 2001;20:1415-1419. Available at: http://www.cdc.gov/genomics/info/reports/policy/ethical.htm

5. Clayton EW, et al. JAMA. 1995;274:1786-1792.