On November 14, Geron, a pioneer in the field of human embryonic stem cell research, announced that it would discontinue its stem cell programs. This abrupt decision, which shocked the science and business communities, raises important ethical questions about clinical trials conducted by for-profit corporations.
Last year, the company started the world’s first clinical trial using cells derived from human embryonic stem cells. The study involved injecting oligodenrocyte progenitor cells, a type of nervous system cell, into the spinal cords of patients with neurologically complete, traumatic spinal cord injuries to assess safety. Previously, Geron funded the work of James Thomson and colleagues that resulted in the first successful derivation of human embryonic stem cells. But now, according to Geron’s press release, “after a strategic review of the costs, value inflection timelines and clinical, manufacturing and regulatory complexities associated with the Company’s research and clinical-stage assets” Geron has decided that its technical and financial resources will be directed exclusively to its oncology programs.
The decision to exit the field of stem cell research and to halt the trial leaves five individuals who had received the experimental stem cell intervention in a kind of twilight zone between patient and research participant. Four patients were injected with the cells between October 2010 and September of this year. A fifth patient received an injection on November 16, two days after Geron announced its decision to quit stem cell research.
Geron has said that it will “continue to follow all enrolled patients, accruing data and updating the Food and Drug Administration and the medical community on their progress.” Moreover, Stephen Kelsey, Geron’s chief medical officer, is reported to have said that the results “will be a fair reflection of what would have happened if we had completed the study.” This statement is deeply problematic, however.
The estimated enrollment for the study was 10 research participants. If Kelsey’s statement (made when there were four participants) is true, and the research findings from four (now five) patients are equivalent to the potential research findings from 10 patients, then there are serious questions to be asked (and answered) about the original sample size. A sine qua non of ethical research involving humans is scientific validity. Key elements of scientific validity include appropriate sample size and the ability to enrol sufficient research participants to generate scientific knowledge.
No clinical trial should involve too few or too many participants. It is important that the trial not be underpowered and thus unable to generate scientific knowledge. It is equally important than no more research participants than necessary be exposed to potential research risks. If only five participants were needed to generate the scientific knowledge, then why would Geron and the F.D.A. have agreed to expose additional persons to the potential harms of trial participation?
On the other hand, if Kelsey’s statement is false, and the findings from five research participants will be underpowered, then they may have been exposed to the potential harms of trial participation without the potential for benefit in the form of scientific knowledge. To quote Ezekiel Emanuel and colleagues on what makes clinical research ethical: “Without validity the research cannot generate the intended knowledge, cannot produce any benefit, and cannot justify exposing subjects to burdens or risks.” Reasoning along similar lines, international research guidelines from the Council for International Organizations of Medical Sciences in collaboration with the World Health Organization, state that “scientifically unsound research involving humans as subjects is ipso facto unethical in that it may expose them to risk or inconvenience to no purpose; even if there is no risk of injury, wasting of subjects’ and researchers’ time in unproductive activities represents loss of a valuable resource.”
It is one thing to close a trial to further enrollment for scientific reasons, such as a problem with trial design, or for ethical reasons, such as an unanticipated serious risk of harm to participants. It is quite another matter to close a trial for business reasons, such as to improve profit margins.
Geron might well argue that its decision was not about increasing profits, but rather was about avoiding bankruptcy. In either case, the scenario forces us to consider what measures should be taken with respect to future trials funded in the private sector so that participants are not left stranded. Perhaps regulators and institutional review boards should critically examine whether a company has both the financial (and other) resources and the will to complete a trial under review before granting regulatory or ethics approval. If there are doubts about this, then either the trial should not be approved, or there should be stringent disclosure requirements so that prospective research participants are aware of the possibility that research may stop mid-trial for financial reasons.
Françoise Baylis, PhD. is a professor and the Canada Research Chair in the departments of philosophy and of obstetrics and gynecology at Dalhousie University in Halifax.