Informed consent in the era of biobanks
© BioMed Central Ltd. 2013
Published: 25 January 2013
Biorepositories collecting human specimens and health information have proliferated in recentyears. Efforts to set a range of policies related to biorepositories, including those related toprocedures for obtaining informed consent and recontacting participants, have been hindered by apaucity of data on the diverse forms biorepositories take and the variety of institutional settingswhere they are established. A recent survey demonstrates in detail, for the first time, thediversity of biorepositories in the USA.
See research article: http://genomemedicine.com/content/5/1/3
The 'scaling-up' of research
Approaches to the way investigators obtain consent and later recontact research participants areregulated in the USA under a set of policies focused on protecting research subjects, often referredto as the Common Rule, that were published in 1991 . In recent years, however, the development of novel research approaches has caused someto raise questions over the practicability of traditional procedures for obtaining consent andrecontacting participants. For example, biorepositories can include very large numbers of biosamplescollected from large populations of individuals. Traditional procedures used to obtain informedconsent to participation in research, such as enrollment visits that can last over an hour, seembetter suited to studies with participants who number in the hundreds, rather than tobiorepositories whose participants can number in the hundreds of thousands.
The 'scaling-up' of research approaches has led to increased interest in identifying the bestways for investigators to engage with research participants when the number of participants becomesvery large . In fact, a recent proposal for revisions to the Common Rule included a suggestion thatpermission to collect biosamples might be obtained using a brief permission form rather than adetailed informed consent process . This and other proposed reforms to the Common Rule may be intended, in part, to addressthe concerns that have arisen in building biorepositories. Until now, however, our understanding ofthe scale of the problem of balancing adequate engagement with practicability in the development ofbiorepositories has been based on an incomplete picture of the biorepository landscape. Arebiorepositories with hundreds of thousands of biosamples really that common? Where do they obtaintheir samples and with what consent approach? Which stakeholders are involved in developing andcarrying out governance and oversight for these collections? In this issue of GenomeMedicine, Henderson et al. for the first time provide data and analysis on thediversity of biorepositories in the USA . The findings in this report are wide-ranging and will help move a number of ongoingpolicy debates forward.
The two core ethical aims for informed consent encounters are: (1) to ensure that potentialparticipants are adequately informed about the risks and benefits associated with researchparticipation, and (2) to obtain participants' voluntary agreement to participate in research. Inpractice, the approaches that can be taken to achieve these aims in the setting of biorepositoriesare numerous. In the procedures adopted by many biorepositories, participants are informed of thegeneral scope of planned research and asked to consent en bloc (that is, provide 'blanket'consent) to all future research. The alternative is to recontact participants periodically torequest consent for use of stored biosamples in newly developed research projects.
Even though the findings reported in Henderson et al.  do not address the consent approach adopted by biorepositories, they do help place thischoice into context across the range of biorepositories currently in operation in the USA. Fifteenpercent of biorepositories report having fewer than 500 samples. For these biorepositories that aresimilar in size to more traditional types of medical research studies, a 'blanket' consent approachmay not be necessary.
However, a number of biorepositories are extremely large. Over 20% of biorepositories containmore than 100,000 specimens, and at least one biorepository reported collecting biosamples from morethan 10 million individuals! Since the majority of biobanks (75%) obtain samples directly from theindividuals donating them, we can begin to see the scale of the effort needed to obtain consent fromparticipants on just one occasion. Despite the many salutary features of the periodic recontactmodel, the data from this study indicate that this model may not be feasible for a significantpercentage of biorepositories.
The passage of time poses another challenge to the recontact approach. Henderson et al.  found that 17% of biorepositories were established prior to 1990. Although we do not knowwhether samples collected prior to that time are still in use, it is daunting to consider theoperational challenge of recontacting participants over a 20 year period!
While these findings put a number of claims into their empirical context, they can provide nodirect resolution of the debate. For example, although a significant number of biorepositories areeither very large or have been in operation for a long time, Henderson et al. have notreported whether any face both challenges. And going beyond these findings, it is clear that underexceptional circumstances, large, long-term research projects can maintain meaningful engagementwith participants . Finally, even biorepositories that have adopted a one-time, 'blanket' consent model maylater find that they need to recontact participants, such as when the scope of planned researchchanges or when plans to share data are developed .
Return of results
Just as the size and duration of biorepositories can pose challenges to recontacting participantsfor the purpose of expanding consent, they can also create barriers to returning research results toparticipants. If we imaginatively combine the findings provided by Henderson et al. withrecent studies that demonstrate that incidental findings generated through DNA-based tests arerelatively common , we may conclude that returning incidental findings to 100,000 or 500,000 participantsincluded in a genomic biorepository could represent a remarkably expensive and time-consumingeffort. This is of particular interest, since 41% of biorepositories already consider long-termsustainability to be a major concern.
The scope of this challenge is mitigated significantly, however, if we assume that only thoseresults expected to provide significant and timely clinical utility should be returned. Taken inthis light, DNA-based biorepositories may not pose the most significant challenge in terms of returnof results, since we may expect them only infrequently to generate findings that are both urgent anddiagnostic. But as scientific knowledge increases in coming years, a great number of RNA andprotein-based biomarkers are likely to emerge as both highly predictive and timely markers fordisease. Although nearly 50% of biorepositories currently focus on DNA research, the findings ofHenderson et al.  raise our awareness that 24% of biorepositories are focused primarily on RNA and 7% arefocused primarily on protein. In this way, these findings direct our attention beyond return ofgenomic results toward results that we may soon find are far more convincing - and urgent -candidates for return to participants.
In this brief article, I have addressed only one narrow area of interest in ethics and policyissues related to biorepositories. My aim has been to demonstrate how the new empirical findingsreported by Gail Henderson and her colleagues can serve as a starting point for grounding discourseon a range of issues related to biorepository design, oversight and governance.
At the same time, these findings direct our attention toward emerging challenges. As the trendsrevealed in this report indicate, widespread innovation in approaches to research is likely tocontinue. With this innovation will come a continuing need to evaluate the advances that are takingplace in all quarters, especially since they are likely to bring new challenges to efforts to enactethical, legal and societal commitments into practicable policies.
- US Department of Health and Human Services: Protection of human subjects. Title 45 Code of Federal Regulations, part 46. 2009, Washington, DC: HHSGoogle Scholar
- Trinidad S, Fullerton S, Ludman E, Jarvik G, Larson E, Burke W: Research practice and participant preferences: the growing gulf. Science. 2011, 331: 287-10.1126/science.1199000.PubMed CentralView ArticlePubMedGoogle Scholar
- Department of Health and Human Services: Human subjects research protections: enhancing protections for research subjects and reducingburden, delay, and ambiguity for investigators. Federal Register. 2011, 76: 44512-44531.Google Scholar
- Henderson GE, Cadigan RJ, Edwards TP, Conlon I, Nelson AG, Evans JP, Davis AM, Zimmer C, Weiner BJ: Characterizing biobank organizations in the U.S.: results from a national survey. Genome Med. 5: 3-
- Levy D, Brink S: A Change of Heart: How the Framingham Heart Study Helped Unravel the Mysteries ofCardiovascular Disease. 2005, New York: Knopf,Google Scholar
- Ludman EJ, Fullerton SM, Spangler L, Trinidad SB, Fujii MM, Jarvik GP, Larson EB, Burke W: Glad you asked: participants' opinions of re-consent for dbGap data submission. J Empir Res Hum Res Ethics. 2010, 5: 9-16. 10.1525/jer.2010.5.3.9.PubMed CentralView ArticlePubMedGoogle Scholar
- Westbrook MJ, Wright MF, Van Driest SL, McGregor TL, Denny JC, Zuvich RL, Clayton EW, Brothers KB: Mapping the incidentalome: estimating incidental findings generated through clinicalpharmacogenomics testing. Genet Med. 2012, doi: 10.1038/gim.2012.147,Google Scholar