Since the release of the Notice of Proposed Rulemaking to revise the Common Rule a year ago, I have been thinking about biospecimens research, specifically about the role of public trust in the success of such research, and about some of the tensions that arise between respecting people’s autonomy, and advancing potentially important and beneficial science. This is a complicated cluster of issues that, while particularly salient to biospecimen research, is generalizable to the research enterprise as a whole.
Public trust is clearly important to the ongoing success of research, most obviously because much research is publicly funded. In the context of human subjects research, public trust comes into play in a more immediate way. The ability to carry out human subjects research requires people volunteer to take part in that research, which further requires they trust that the research is worthwhile and important; that they won’t be exposed to unnecessary risk in the service of research; that any benefits of the research will be appropriately shared with them; and that nothing will be done to or with them without their knowledge and permission.
Trust, therefore, undergirds the social contract we create with those involved in human subjects research. Within the contemporary research enterprise, with its growing emphasis on patient-centered research, the levers for fostering trust go beyond appropriate oversight and informed consent, and include efforts to involve subjects, advocates, and communities as full-blown research partners.
Research with biospecimens adds further layers and challenges, in part of because of the way risks and benefits are distributed. Most of the potential benefits of biospecimen research—and I mean here primarily large-scale genomic research that relies on the collection of biological samples from many different individuals to examine associations between genetic variants and disease states—are likely to be realized in the future, and to redound to society as a whole; biospecimen research is particularly unlikely to yield benefits for individual specimen donors. But at the same time, most of the risks of this research, including, predominantly, risks to privacy, fall on individuals donating biological materials. And though it’s generally agreed the risks are low, concerns about risks are exacerbated by the rapid progress of genomic science, wherein what information about a person is “contained” in a biological sample is constantly evolving.
At the same time, research with biospecimens has the best chance of improving human health if there is participation from a broad cross-section of the public; the larger, more diverse, and hence representative a collection of biological samples that can be collected, stored, and made available for future research, the greater the potential to glean information about health, disease, and potential treatment. In order to realize the promise of biospecimen research, many people have to be willing to assume the risks of participating, and that willingness depends on trust.
As noted above, and as history has repeatedly shown us, one basic way we foster public trust in research is by not conducting research on people without their knowledge. Hence the ethical and regulatory requirement that we seek and secure the informed consent of potential research subjects and, more broadly, that we respect those potential subjects as persons who are, among other things, autonomous decision-makers.
Right now, the research community is struggling with the question of how to acknowledge and operationalize this core principle of respect for persons in the context of collecting and using biospecimens for secondary research. I think it’s clear that neither societal norms nor ethics support the regulatory status quo—namely, that a biological specimen stripped of identifiers for secondary use is subject to no ethical oversight or any requirements to notify or get consent from the specimen donor. Public reaction to the story of Henrietta Lacks and the use of her cells without her knowledge; and to the discovery that de-identified residual newborn bloodspots were being used in research without parental permission in Minnesota, Texas, and elsewhere; as well as a growing body of empirical literature examining public attitudes about biospecimen research, all reveal public expectations that they be informed about use of their biological samples in research. As PRIM&R has argued in its comments on the NPRM—and in agreement with the Common Rule agencies—the fact that a researcher can currently use a specimen at will once identifiers are removed seems to controvert the principle of respect for persons.
But having established that, the question of the appropriate way to respect persons in biospecimen research is, to my mind, an open one. The NPRM proposes to redefine all secondary research with biospecimens, whether identified or not, as human subjects research and, for most such research, to require broad consent. A number of commentators, including PRIM&R, have pointed out the many difficulties with this approach, from creating undue obstacles to valuable research, to doubts about whether broad consent meaningfully serves the principle of respect for persons.
I think we as a community have an opportunity to think more creatively about how we show respect for persons who provide samples for biospecimen research, and potentially in other research contexts as well. For too long, we have seen prospective informed consent as the only legitimate way to do this. And for many research contexts, prospective informed consent is clearly the only ethical option. But I can imagine a different approach to showing respect for individuals who contribute to biospecimen research, one that is based on concerted efforts to (1) educate people about research as a public good—how research works, how we have benefited from research and its discoveries, the inevitable risks and uncertainties involved in research, what kinds of protections are in place for those who participate, and the reasons researchers depend on widespread participation; and (2) express gratitude to and for public participation in research.
In my view, such efforts to increase transparency about research—which includes being honest both about its successes, but also about its failures—would ideally be undertaken at both the public or national level and by individual institutions that collect biospecimens for research. That is, rather than trying to obtain broad consent from every patient, as the NPRM proposes, institutions large and small could create highly visible, lay-friendly educational campaigns and materials to notify all those entering their doors that the institution, as a matter of routine, collects biospecimens for research and why, what the risks and benefits and protections are, and the other sort of details I mention above. I imagine this sort of approach would be less costly to institutions than broad consent, especially if the federal agencies provided templates and support. Some might argue that people should have the option to opt out altogether. And perhaps that’s correct. But it seems to me that in an environment that is characterized by transparency and shared understanding of the nature of research, its promise and its risks, the public is already being treated as a respected and valued stakeholder in research.
I imagine this will be controversial, and of course this is only the broadest sketch of an alternative approach to respecting persons in biospecimen research. But I wonder what you think. Would the general approach I suggest here serve the principle of respecting persons? What do you see as the biggest obstacles to implementing such an approach? What would the role of the federal agencies be?