1. Interpreting the proposed consent requirement
One of the most discussed and controversial aspects of the Department of Health and Human Services’ recent notice of proposed rule-making (NPRM), which stands to change the federal regulations governing research with human beings, is a new consent requirement for secondary research on bio-specimens. ‘Secondary research’ involves leftover blood or tissue samples that are re-purposed for research after their original use as clinical samples or in prior research studies has been served. Whereas the current regulations permit re-purposed samples to be used in research without consent so long as the samples are anonymized or de-identified, the new rule would require individuals to be notified that their samples will be used in research, and to give broad permission or consent for such use, before research using them is permitted.
One possible justification for the new consent requirement is what I will call the ‘rights-violation’ interpretation. The rights-violation approach maintains that consent for research with biospecimens is ethically required to avoid a rights-violation—which is what, the view claims, using someone’s samples without their consent amounts to.
Defenders of this view face the challenge of saying precisely which right is violated by research with re-purposed specimens. One idea is that the samples still count as part of the individual’s body, even if they are no longer spatially continuous with it, so that using them without consent infringes a bodily right. A second possibility is that, even if donated specimens are not part of one’s body in the relevant sense, we yet have ownership interests in and claims to our biological materials, so that something closer to a property right at stake. A third view focuses on the personal health information that can be garnered from certain sorts of research with bio-specimens (e.g., research involving whole genome sequencing), claiming that privacy rights stand to be infringed when specimens are used without consent. Each of these views raises complex ethical (and indeed in some cases metaphysical) issues that defenders of the rights-violation interpretation must work out.
Even putting aside these philosophical challenges, however, the NPRM taken in its entirety fits poorly with the idea that bio-specimen research without consent violates a right. We can see this by focusing on what the NPRM has to say about research with samples that have already been collected and stored (or which will be collected and stored) before the proposed new rule takes effect. The NPRM does not extend the new consent requirement to these samples; rather, it continues to apply the current rule. (See the NPRM at §ll.101(k)(2), here). So long as bio-specimens collected before the new rule takes effect are de-identified, consent is not required for research with them.
On the rights-violation interpretation, this is puzzling. If what motivates the NPRM’s new consent requirement is avoidance of a rights-violation, this same concern should demand re-contacting individuals and obtaining their consent for previously collected samples. After all, conducting research on previously collected samples without consent presumably violates rights no less than conducting research on newly obtained samples without consent. If the rights-violation is the same in both cases, we deserve an explanation for why consent would be required in one case but not the other.
2. Can differential treatment of the cases be justified?
Defenders of the rights-violation approach might to try to justify differential treatment of the cases by pointing to a difference in the degree of practical difficulty or impracticability involved with obtaining consent in each case. Re-contacting individuals and obtaining consent for previously collected samples may be quite time-consuming and difficult. Obtaining consent at the time the sample is given, on the other hand, does not involve the same costs of locating and re-contacting anyone, since individuals must be physically present to give the sample.
It is doubtful, however, that mere practical difficulty in obtaining consent is the right kind of consideration to justify a rights-violation. An investigator would not be permitted to forego consent for a research blood draw, thereby violating an individual’s right against bodily trespass, on the grounds that obtaining consent would be practically burdensome (because, say, it would require going to great lengths to find a language interpreter to communicate effectively, or to track down an authorized surrogate). Indeed part of the very function of moral rights is their ability to defeat considerations of expedience, putting pressure on us to abide by ethical imperatives that it would be easier or more advantageous for us to ignore. It is much more plausible to conclude that a rights-violation is not present when research is conducted on previously collected specimens without consent than that it is to conclude that it is present but can be outweighed so easily by considerations of expedience.
Suppose, however, we waive these concerns and agree that impracticability can in principle justify rights-violations and outweigh the need to obtain consent. This approach still falters, since it is by no means clear that the practical burdens of the new consent requirement will be any less significant than the burdens of re-contact. The burdens imposed by the new consent requirement are, it is true, not the same as the burdens of re-contact—but that does not mean they are any less significant. Assessing the burdens of the new consent requirement (the costs of obtaining, documenting, and tracking consent, etc.) are beyond my scope here. But if, like me, you suspect that these burdens will be just as onerous as the burdens of re-contact, you should conclude that in both cases consent may be waived. Indeed the burdens of the new consent requirement need not even be equal to the burdens of re-contact to yield this conclusion. All we would need to show is that in both cases the burdens are sufficiently onerous for consent to be waived. As I said above, I do not think appeals to impracticability are typically capable of justifying rights-violations. But if I did accept this, it would not seem at all implausible to me that the burdens of implementing the new consent requirement would meet any plausible threshold to justify waiving consent.
A second possible way to defend the differential treatment of the cases is to claim that a rights-violation is involved in the collection of biological samples but that merely using them involves no such rights-violation. Specifically, if individuals are not informed about the intent to re-purpose their samples for research, their consent to have the specimen collected may, by virtue of being insufficiently informed, fail to waive the right against bodily trespass that prohibits clinicians and researchers from entering their personal space and obtaining the sample (i.e., drawing blood without consent, taking a biopsy without consent, etc.). If so, consent would be needed to avoid a rights-violation at the time of collection but may not be needed for using previously collected samples, since merely using them does not involve infringing anyone’s personal space.
It is not clear that this approach locates the rights-violation in the correct place. To see why, imagine a situation where a hospital intends to store leftover clinical samples and eventually re-purpose them for research, and collects samples without disclosing this intent to patients, but then subsequently changes its mind, choosing instead to discard the samples before research with them is performed. If the rights-violation consists in specimens being collected without the institution disclosing its intent to re-purpose, not in samples being used in research per se, we should conclude that the patients in this scenario have been wronged. But it seems open to debate whether individuals whose samples are never in fact used in research are wronged under these circumstances. To the extent that our intuitions are uncertain on this point, we should also be uncertain that merely collecting samples without informing patients of an intent to re-purpose suffices for a rights-violation.
Suppose, however, we waive this concern and grant that merely collecting samples without informing patients of an intent to re-purpose them suffices for a rights-violation. The NPRM would still be in an awkward position. On the one hand, it would acknowledge that the donors of previously collected samples have been wronged; at the same time, it would permit researchers to use the samples that have resulted from this wrong while doing nothing to acknowledge the wrong or take steps to repair it. By licensing researchers to use and benefit from this wrong, without acknowledging or addressing it in meaningful ways, the NPRM would be implemented and complicit in the wrong—and indeed would give the appearance of condoning it. By licensing complicity in a wrong the NPRM would, by any reckoning, condone an ethically unsavory result that we have strong ethical reasons to avoid.
3. If not rights-violations, what?
If this is the best the rights-violation approach has to offer, those who wish to affirm the NPRM’s overall approach to bio-specimens are probably best served by forsaking the rights-violation interpretation altogether. A more promising path forward may be to rest the NPRM’s approach to specimens and consent entirely on consent’s role in promoting public trust in bio-specimen research. Such a view would make it easier to reconcile the NPRM’s differential treatment of the cases. Since trust is a matter of degree, and since we may not need to maximize public trust to adequately address the risks of inadequate public trust, requiring consent for previously collected samples may not be necessary; requiring consent moving forward may well suffice for an adequate level of trust.
Regardless of its ability to bring internal coherence to the NPRM, the idea that the new consent requirement can be grounded entirely by appeal to considerations of trust would need to be judged on its own merits. In particular, it would need to be shown that requiring consent rather than other measures—say, conducting a public education campaign about bio-specimen research, and/or requiring institutions to notify patients that their clinical samples will be re-purposed for research and giving them the ability to opt-out (to name just two salient alternatives)—would in fact be optimal: the best way to promote public trust while minimizing the burdens on research. This is a question that deserves very careful scrutiny before the NPRM is enshrined as law.
Luke Gelinas is the Petrie-Flom Center/Harvard Catalyst Fellow in Clinical Research Ethics.