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?
I don’t see your proposal as being in any way controversial, matter of fact it seems modest to me – and this is not a bad thing. So can it be said that, in essence, what you are proposing for in (1) is increased transparency of research institutions for the sake of public trust? If so I’d say that form of argument makes sense overall. It seems intuitive that informing a participant of how her physical contribution (specimen) will be used would help mitigate any fear that the contribution might be used in way that runs counter to her interests.
To broaden this, as I feel you were doing, the question then becomes: will increased efforts at educating people about both the importance of scientific research and the principles of biomedical research ethics build public trust in the scientific community? This one, in my opinion, is a bit trickier. I feel that, though the scientific community ought to do whatever they can reasonably do to foster trust from the public, they would need to do this in a way that genuinely represents their interests and plans. It should go without saying that they ought not sugarcoat anything or intentionally mislead the public (impl. participants) in any way. More than this, however, they ought to explain the scientifically, technologically, legally, and institutionally imposed limits on specimen usage. It is often hard to discern what is science from what is science-fiction, even for bioethicists — scientific progress has brought and likely will continue to bring to reality what was once only fiction. This in mind, the public should be assured that what is supposed to be going on in biomedical research laboratories is not faithfully depicted through sci-fi horror stories. That being said, there is some truth in fiction: we are well aware of history’s atrocious missteps, missteps which in no small way catalyzed the bioethics movement. So yes, particular researchers and the general scientific community need to do some PR work in order to gain the trust of participants and the public.
On (2), I’d say that it depends on your conception of ‘gratitude’ and to what that word extends. We’ve seen problems in the past which have arisen from providing resource benefits to people for their biomedical contributions, though maybe that inference may not necessarily be sound nowadays. Side note: in “The Plague”, Camus had some interesting thoughts on how gratitude may actually be deleterious to efforts at popularizing altruism. Anyway, the key for me is that what is important, aside from gratitude, is to consider that people feel an intrinsic, genuine sense of “pleasure” (contentious word, I know) from doing altruistic things. Researchers would do well to better understand what compels altruists to do good, and then design their calls so as to maximize the likelihood that people would want to participate on such feelings, regardless of extrinsic benefits. If people 1) don’t see themselves going out of their way or subjecting themselves to undue risk and 2) can somehow actually enjoy the participatory experience itself (not simply the cookies or some such thing) then I’d figure that more would participate. This feeling is probably what drives some prolific “bioaltruists” such as frequent blood product donors. It would be good if people were not compelled to fear (biomedical) science from lack of information. It would be even better if then by way of consequence more people actually wanted to participate.
Adam, thank you for your thoughtful comments.
I think you hit the nail on the head that part of what needs to happen to gain public trust is some public relations work on the part of the scientific community – though I prefer to think of it as education, rather than PR. There is some empirical literature suggesting that the public’s understanding of especially biospecimen research is very mixed. The problem, of course, is that scientists themselves may not the best at educating the public about their work – that is not what they are trained to do. The media isn’t a good source either, given the tendency toward science hype (a tendency that may be fostered by the current incentive and funding structures for scientific research). Thinking further about an infrastructure or system that would support a shift in focus to education, transparency, and trust and away from informed consent processes would involve, I think, determining who should be doing this educating – do institutions who conduct research with biospecimens need community educators on staff? Is this a function the IRB could play or oversee? Can we imagine a system whereby scientific funding could include funding for a community educator to translate the research to the lay public in the interest of fostering trust and buy-in, and ultimately, participation?
On the issue of gratitude, we shouldn’t confuse remuneration with gratitude. I was thinking more along the lines of acknowledgment and recognition that those who make their tissues available are important to the endeavor, that they and their contribution’s aren’t take for granted. Simply sharing results of the trials in a way subjects can understand and digest – even if the research failed or was inconclusive – is a way to show gratitude for participation. Acknowledging that time, effort, and risk were expended or borne on the part of the subjects likewise shows gratitude.
Thanks again for commenting. It’s clear that this is an area for wider discussion within the scientific and bioethics communities.
Elisa,
I wholeheartedly agree with what you are saying here. Coincidentally, considerations such as yours have recently caused me to shift my main focus (in grad school) from active participation in bioethical discourse to the communication of bioethics and relevant subject matter. While it is important to have open discussions through outlets such as this, I think that it is just as important that the scientific community communicates with the public in an interesting yet realistic way. You yourself had hit the nail on the head when you wrote: “the problem, of course, is that scientists themselves may not the best at educating the public about their work – that is not what they are trained to do. ” As a person whose background can be considered at once technical, scientific, and medical, and whose current pursuit in higher education resides in the humanities, I can (anecdotally) attest to the notion that skills in effective communication are not necessarily stressed in STEM programs. Apparently being aware of this problem, the university I attend offers a sequence of journalism courses which have been specifically designed to cultivate and improve scientists’ communication skills. We can hope to see more effective science communication come about as a result of such efforts.
One theme in many of the comments on the NPRM from the public, and echoed by the PRIM&R keynote speaker last year, was not wanting pharmaceutical companies to make money from specimens they got for free. Compensating people for their specimens has many drawbacks, but possibly trust in pharmaceutical companies could be increased if they pledged to set aside some portion of profits attributable to the use of anonymous specimens for a charitable purpose – giving to disease advocate groups, supporting university research, noncommercial public education about research, etc.
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