3.4.6 Research Subject Follow-up and Trial Monitoring
Recommendation 126.96.36.199: A data-monitoring plan is required for clinical studies. When deemed appropriate, aggregate updates should be provided at predetermined times or on-demand. Such updates should include adverse event reporting and ongoing statistical analyses if appropriate. Data monitoring personnel and committees should be independent from the research team.
The risk/benefit balance can change over the course of clinical research, as safety and response are observed, recruitment wanes, or as new treatments become available. This is especially true for stem cell-based intervention trials, which are characterized by high uncertainty and rapidly evolving science. The welfare of subjects must be carefully monitored throughout the duration of stem cell-based clinical trials, the study interrupted if the risk/benefit balance becomes favorable or unfavorable, and subjects informed of new information about themselves, the trial, or the intervention that might materially affect their continued participation in a study.
Recommendation 188.8.131.52: Given the potential for transplanted cellular products to persist indefinitely and depending on the nature of the experimental stem cell-based intervention, subjects should be advised to undergo long-term health monitoring. Long-term follow-up is mandated in some countries, often for the use of gene therapies or xenotransplants. Additional safeguards for ongoing research subject privacy should be provided. Subject withdrawal from the research should be made in an orderly fashion to promote physical and psychological welfare.
Long-term follow-up provides an opportunity to monitor the emergence of late adverse events and the durability of benefit. Given the practical realities, conducting long-term follow-up may be challenging. Investigators should develop and adopt measures to maintain contact with research subjects. In addition, funding organizations should be encouraged to develop mechanisms for supporting long-term follow-up. Since the length of appropriate follow-up is impossible to specify in the abstract, the decisions about this should be clearly articulated by investigators and reviewed by independent peer-reviewers and oversight bodies. If subjects withdraw from a study after the product has been delivered, investigators should continue long-term follow-up to monitor the emergence of adverse events if subjects concur.
Recommendation 184.108.40.206: To maximize the opportunities for scientific advance, research subjects or surviving next of kin in stem cell-based intervention studies should be asked for consent to a partial or complete autopsy in the event of death to obtain information about cellular implantation and functional consequences at some point in the trial. Requests for an autopsy must consider cultural and familial sensitivities and be conducted in a respectful and compassionate manner. Researchers should strive to incorporate a budget for autopsies in their trials and develop a mechanism to ensure that these funds remain available over long time horizons.
Though a delicate issue, access to post-mortem material substantially augments the information coming out of trials and enables future product or delivery refinements in the treated condition. Since consent for autopsy is typically obtained from the family members of someone who has died, investigators should facilitate discussion of this issue among subjects and appropriate family members well ahead of any anticipated terminal event.