Research
Ethical Issues in Research with Human Biological Samples
Summary: This project attempts to identify an approach to consent for research with biological samples that balances respecting and protecting the individuals who provide samples with the social importance of allowing appropriate research to proceed.
| Section: | Genetics | ||||||||||||||
| Principal Investigator: | David Wendler, Ph.D. | ||||||||||||||
| Collaborators: |
|
Background: Research with human biological samples holds enormous scientific potential. To realize this potential, it is vital to determine when investigators need to obtain informed consent for research with biological samples. Overly stringent requirements on informed consent could thwart this potential, reducing the scientific value of some studies, and precluding others altogether. Failure to obtain individuals’ informed consent when appropriate would represent an important failure of respect for individuals. Such a failure also might reduce public support for research with biological samples and undermine individuals' willingness to provide samples for research purposes.
Departmental Research Initiative: Most commentators support prospective consent for research with human biological samples, but disagree on what information should be provided, and what choices individuals should be asked to make. Some commentators endorse allowing individuals to choose which diseases will be studied using their samples; others argue individuals should be asked to decide which investigators may use their samples. Our research indicates that IRBs are inconsistent in how they approach consent for research with samples, leading to significant variability in the content of consent forms covering such research (Hull et al. 2004).
Theoretical analysis alone appears insufficient to identify a best practice among the existing approaches. Respect for individual autonomy, for example, implies individuals should be able to control whether their samples are used for research purposes, but does not seem to determine which choices they should be offered. We have argued that, in this setting, where a number of different approaches are consistent with the relevant moral principles, empirical data can be useful for identifying a best practice. Empirical data, if it is sufficiently comprehensive, can help to determine which approach is best supported by the widely endorsed “reasonable person” standard for informed consent. Empirical data also can help to determine which approach is most likely to be acceptable to individuals and receive broad societal support, important considerations if research with biological samples is to remain viable and attain its promise.
In our first empirical study (Wendler, Emanuel 2002), we assessed participants’ views on consent for research with biological samples when presented with hypothetical scenarios. These data suggested individuals want to control whether their samples are used for research purposes, but are willing to have their samples used for research on any disease. To assess whether these findings might be influenced the use of hypothetical scenarios, we next assessed (Chen 2005) the actual choices made by research participants when given the option of donating samples for research purposes. The findings from this study support the view that the vast majority of individuals are willing to contribute samples and are willing to have their samples used for research on any disease. These data also highlighted that a small number of individuals, including those who had already agreed to participate in research, are unwilling to have their samples used for research purposes. This finding underscores the importance of allowing individuals to decide for themselves whether their samples are placed in the research pool in the first place.
Our first two studies, conducted at the NIH, were restricted largely to non-Hispanic whites who had already agreed to participate in research. These studies also focused on non-stigmatizing diseases, such as arthritis and diabetes. Recognizing these limitations, we next designed two studies to assess whether are findings were consistent in other groups. The first was carried out with a largely African American patient population in Atlanta, Georgia (Pentz, Billot, Wendler 2006), while the second involved individuals in Uganda (Wendler 2005). These studies provide further evidence that the vast majority of individuals are willing to contribute samples for research on any disease, including potentially stigmatizing diseases. For example, in the Uganda study, respondents were as willing to have their samples used for research on HIV disease as research on arthritis. In these two studies, we found that the vast majority of individuals are willing to rely on IRBs to determine when their samples are used for future research purposes.
Taken together, these studies provide support for what we have called “one-time general” consent for research with biological samples. This approach involves obtaining consent to collect and use samples for future research in general, with the stipulation that future uses must be approved by an IRB. To evaluate the appropriateness and potential acceptability of this approach, we conducted a systematic search of the literature for studies published in English which provide empirical data on individuals’ views regarding informed consent for research on biological samples. This search identified over 20 studies which assessed the views of more than 33,000 individuals around the world, including patients, research participants and members of the general public. These studies provide compelling support for the use of one-time general consent (Wendler 2006). To facilitate adoption of one-time general consent, this publication also provided a description of the elements of this process, and included sample consent wording.
While one-time general consent for research with biological samples is consistent with relevant ethical considerations and supported by existing empirical data, it appears to be inconsistent with the HIPAA Privacy Rule, which requires individuals to provide study specific authorization for the research use of their protected health information. Since most researchers are employed by covered entities, and most research with biological samples includes protected health information, this requirement appears to block implementation of one-time general consent for a good deal of research on biological samples. To assess this concern, we conducted a comprehensive analysis of the Privacy Rule’s authorization requirements (Wendler 2006).
This analysis revealed that a two-step decision procedure provides a way to reconcile one-time general consent with both the letter and the spirit of HIPAA. This approach stipulates that new research uses of biological samples must be approved by an IRB, and must be consistent with individuals’ original consent for future research.
Finally, data suggest many institutions comply with HIPAA by adding long amounts of texts to already complex consent forms. This approach, while satisfying HIPAA, likely undermines participants’ understanding of the studies in which they participate. We showed that the vast majority of this added text is not necessary (Shalowitz, Garrett-Meyer, Wendler 2006). Specifically, we showed that consent forms which satisfy the common rule's requirements for informed consent need add only minimal additional text to also satisfy the authorization requirements under the Privacy Rule. To facilitate implementation of this approach, we described the specific elements that consent forms which satisfy the Common Rule need add to also satisfy the authorization requirements under HIPAA.
Impact of Research: A number of institutions have expressed interest in adopting our approach of one-time general consent and several IRBs are using our method for reconciling HIPAA with the Common Rule. In addition, the Office for Civil Rights, the agency responsible for enforcing the Privacy Rule, has stated that “our approach addresses an important gap in understanding of the Privacy Rule,” and they intend to develop national guidance based on our approach.
Current and Future Initiatives: Debate over the magnitude of the risks of research with biological samples is difficult to resolve because the risks are largely unknown, leading to disparate judgements regarding when such research poses greater than minimal risk. The Department's previous work on understanding and implementing the minimal risk standard puts us in a unique position to address this question. Second, there is debate over whether IRB review should be required for research with stored biological samples. This debate is largely between Europe and the United States. The Europeans tend to require IRB review. Previously, the OHRP interpreted the U.S. federal regulations as requiring IRB review unless the samples were existing and had been completely annoymized. More recently, OHRP has ruled that research with stored samples does not constitute human subjects research, hence, does not require IRB review, if there is an agreement between the investigators and holders of the samples which precludes the investigators from obtaining identities of the individuals who provided the samples. We plan to assess the appropriateness of this approach to research with stored biological samples. Third, we are currently analyzing data from a survey of 1,193 patients that examines whether they distinguish between research with anonymous vs. identifiable samples and data, and whether this distinction affects their attitudes regarding consent for such research.
Publications
Wendler D. One-time general consent for research on biological samples: is it compatible with the Health Insurance Portability and Accountability Act? Archives of Internal Medicine. 2006;166:1449-1452.
Wendler D. One-time general consent for research on biological samples. British Medical Journal. 2006; 332:544-547.
Shalowitz D, Wendler D. Informed consent for research and authorization under the health insurance portability and accountability act privacy rule: an integrated approach. Annals of Internal Medicine. 2006;144:685-688.
Pentz RD, Billot L, Wendler D. Research on stored biological samples: views of African American and White American cancer patients. American Journal of Medical Genetics. 2006;140:733-739.
Wendler D, Pace C, Talisuna A, Maiso F, Grady C, Emanuel EJ. Research on stored biological samples: the views of Ugandans. IRB: Ethics and Human Research. 2005;27:1-5.
Chen DT, Rosenstein DL, Muthappan PG, Hilsenbeck SG, Miller FG, Emanuel EJ, Wendler D. Research with stored biological samples: what do research participants want? Archives of Internal Medicine. 2005;165:652-655.
Hull SC, Gooding H, Klein AP, Warshauer-Baker E, Metosky S, Wilfond BS. Genetics Research Involving Human Biological Materials: A Need to Tailor Consent Forms. IRB. 2004;26:1-7.
Wendler D, Prasad K, Wilfond B. Does the current consent process minimize the risks of genetics research? American Journal of Medical Genetics. 2002;113:258-262.
Wendler D, Emanuel EJ. The debate over research on stored biological samples: What do sources think? Archives of Internal Medicine. 2002;162:1457-1462.
Wendler D. What research with stored samples teaches us about research with human subjects. Bioethics. 2002;16:33-54.
