Stem cell-based clinical interventions are increasingly advancing through preclinical testing and approaching clinical trials. The complexity and diversity of these approaches, and the confusion created by unproven and untested stem cell-based “therapies,” create a growing need for a more comprehensive review of these early-stage human trials to ensure they place the patients at minimal risk of adverse events but are also based on solid evidence of preclinical efficacy with a clear scientific rationale for that effect. To address this issue and supplement the independent review process, especially that of the ethics and institutional review boards who may not be experts in stem cell biology, the International Society for Stem Cell Research (ISSCR) has developed a set of practical questions to cover the major issues for which clear evidence-based answers need to be obtained before approving a stem cell-based trial.
Main Text
In recent years, the number of clinical trials and range of medical conditions being tested with stem cell-derived interventions has expanded. The complexity and diversity of these putative therapies, and their use in early-stage human trials, pose unique review challenges relative to those required for pharmacological agents, which includes the delivery of the therapy and the possible mode of function. Unfortunately, the field has become increasingly confounded by the desire to rapidly move some stem cell-derived interventions to the clinic without sufficient scientific rationale to support this approach, including growing numbers of direct-to-consumer, incompletely tested, or even untested, “cell therapies.” The latter, untested, putative therapies are often described as trials even though the patient is required to pay for the experimental treatment, an atypical approach that raises ethical concerns. In addition, these “trials” are often registered on a clinical trials website, such as clinicaltrials.gov, a common tactic to convey legitimacy, even though simply being listed on such sites offers no guarantees about the level of scientific scrutiny that they have undergone. Consequently, institutional review and ethics boards, physicians, scientists, and especially patients, struggle to understand which of these interventions has sufficient merit to justify clinical evaluation. By their very nature, cell-based interventions require more comprehensive evaluation to ensure they have a justified level of risk for the recipient, are based on solid preclinical evidence of efficacy, and a clear scientific rationale for that effect. This call for a greater emphasis on preclinical data and rationale has been echoed by others for early human trials (Kimmelman and Federico, 2017). This need for a comprehensive, independent review is likely to become more of an issue as the number of trials and conditions that could be treated with stem cell-derived interventions increases. Indeed, the volume of trials could dramatically expand if, and when, regulatory agencies require that direct-to-consumer interventions undergo a formal regulatory review. This welcome change would further increase the need for ethics and institutional review boards to be highly engaged and informed.
