Posted on October 1, 2018 at 2:28 AM
by Ann Mongoven, PhD, MPH
Recent controversies at Memorial Sloan Kettering Cancer Center raise ethical questions about medical research that deserve public attention. Jose Baselga, M.D., Ph.D., a famed cancer physician and researcher, resigned as chief medical officer following reports that he failed to disclose millions of dollars received from drug companies. Baselga claimed the lack of disclosure was unintentional. Then the New York Times and Pro Publica published reports raising questions about whether data-sharing between Sloan and biotechnology start-up Paige.AI constitutes a conflict of interest. Paige seeks to develop artificial intelligence programs that will improve pathology diagnostics. Prominent board members and physicians within Sloan, a non-profit hospital and research center, invested in Paige. According to the Times, Paige then negotiated an exclusive deal to use millions of patient tissue samples and associated health data from Sloan’s archives. In exchange, Sloan would receive a percentage of Paige’s profits. Some Sloan pathologists had questioned the ethics of the deal before it became public.
(In the wake of public outcry over the Sloan-Paige deal, Sloan announced that its Vice President, Dr. Gregory Raskin, will be required to donate back to Sloan $1.4 million in profitshe made from stock he received for board service at biotech start-up Y-mABS Thereapeutics. Sloan said it will develop new conflict-of-interest policies.)
Whether laws were violated in the Sloan/Paige deal may turn on whether Sloan fairly assessed the market value of the bio-samples and data to which Paige was given access. However, advocates for patients and the public express broader ethical concerns.
The controversies at Sloan underscore the importance of commonly endorsed ethical ideals and associated practices in medical research. They also raise questions about whether we need to develop new ethical practices as research becomes more technologically, socially, and institutionally complex.
1) Research on human beings ethically requires their consent.
This has been a core bioethical principle since research harms dramatized by the Nuremburg Trials and the Tuskegee Syphilis Experiment sparked regulations and processes to protect human research subjects. In the U.S., the regulations are encapsulated in “the Common Rule,”and the key protective process is review of research proposals by Institutional Review Boards (IRBs). Recent revisions to the Common Ruleunderscored that human tissue samples and personal health data are included within human subjects’ protections when they are “identifiable”– if they have patient-names attached. They also encouraged processes through which researchers could invite patients to participate not only in specific clinical trials, but also in the construction of resources that will enable future research—including “biobanks” of tissue samples that are linked to “big data” systems of de-identified personal health records. Emerging policy and practicerequire IRB approval and patient consent to store biological samples and associated health data for research, but do not require additional by-study consent if the data is de-identified.
A troubling question raised by the Sloan/Paige controversy is whether the patients whose tissue samples and health data were bartered had any idea that could happen. Patients who knowingly gave permission to Sloanto use residual tissue samples in research may never have imagined that their donation could be sold to a commercial entity. Sloan has not publicly released its informed consent document for donors. But its general description of the option for patientsto donate tissue discusses supporting cancer research at Sloan. The commercialization of the tissue might greatly upset some patient-donors, while others might conclude it is acceptable because of the health-related goals of Paige’s research. Critics worry that patients were given no real knowledge or choice over the matter. Sloan’s IRB reviewed and approved the Paige deal, raising questions about how institutional interests other than protecting human research subjects might capture an IRB.
The case reminds us that true informed consent is not a signature but rather a process,one that should result in testable understanding. The Sloan/Paige case may call into question healthcare institutions’ burgeoning practice of wording as broadly as possible consent documents for patient release of bio-samples and health data. “Broad consent” becomes a fraudulent scheme when it is so broad that people who provided samples for research are shocked either to learn that they did so, or to learn how their donated resources are actually used. Researchers and IRBs should consider what information about allowable research goals and research sites should be presented to potential donors. They should also design representation processes that can attend over time the ethical interests of those who donate.
Medical research is evolving in ways that seek to benefit from wider scientific sharing of tissue samples and health data extracted from electronic medical records, in order to support genomic population studies needed for the development of precision medicine. Ethically Informing research recruits now requires informing them about data-sharing practices.
2)Having conflicts of interest is not necessarily bad. Hiding them is.
In both the Baselga resignation and the Sloan/Paige controversy, the retrospective coming to light of major conflicts of interests among prime decision-makers was decried and generated wider suspicion. Conflict-of-interest disclosure practices recognize that complete avoidance of conflicts-of-interest is impossible in modern healthcare. The Sloan missteps underscore the ethical importance of routine conflict-of-interest disclosure: to funders, to IRBs, to publishers, to boards, and to patients recruited to participate in research. Indeed, researchers may be most tempted to hide conflicts of interest when those they have are so large that they intrinsically beg ethical questions.
3) The relationship between public good, private benefit, and non-profit status is complex.
In both of the contentious Sloan cases, physicians and researchers worked across non-profit/for-profit institutional boundaries. Rightful public outcry over the extent of, and lack of transparency about, their conflicts of interest should not be allowed to oversimplify the genuine complexity of how research is currently financed and organized. Although their institutional goal is not to generate profit, non-profit institutions still need ways to raise money because “no money, no mission.” And public benefits may come from research done by commercial for-profit firms that aim to “do well by doing good.” Data-sharing between non-profit and commercial institutions in healthcare is not an intrinsic wrong. But patients recruited to donate tissue or data for health research deserve clear explanations of what kinds of institutional entities, governed by what kinds of ethical policies, will be allowed to use their donations over time. And exclusive deals that commercially monopolize biodata should be viewed with the same public distrust that fueled anti-trust regulations in other areas of economic life.
4) Public trust is a prerequisite resource for health research.
The twin Sloan cases remind us that the most fundamental resource necessary for any large-scale health research is public trust. The diminishment of public trust is both a benefit and a harm of the Sloan controversies. It is a benefit because the cases appropriately warn against prematurely granting trust to an august institutional name or to a white-coated medical priesthood. It is a harm because the necessary foundation of health research is eroded. Patients may be dissuaded from participating in even very low-risk population-based research when those conducting it are perceived as untrustworthy. Researchers should not only follow established practices of informed consent and disclosure of conflicts-of-interest that serve to maintain public trust, but they also should converse with research participants and their representatives, and with the general public, to learn their hopes and concerns about health research in emerging biotechnological cultures and economies. We need to develop new protective practices that treat patient-participants in research not as research “subjects,” but as research partners. Both for- and not-for-profit research centers should develop governance models analogous to institutional trusts, given the preciousness of what is entrusted to them.
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