Inclusivity and diversity: Integrating international perspectives on stem cell challenges and potential

Abstract

Summary Regenerative medicine has great potential. The pace of scientific advance is exciting and the medical opportunities for regeneration and repair may be transformative. However, concerns continue to grow, relating to problems caused both by unscrupulous private clinics offering unregulated therapies based on little or no evidence and by premature regulatory approval on the basis of insufficient scientific rationale and clinical evidence. An initiative by the InterAcademy Partnership convened experts worldwide to identify opportunities and challenges, with a focus on stem cells. This was designed to be inclusive and consensus outputs reflected the diversity of the global research population. Among issues addressed for supporting research and innovation while protecting patients were ethical assessment; pre-clinical and clinical research; regulatory authorization and medicines access; and engagement with patients, policy makers, and the public. The InterAcademy Partnership (IAP) identified options for action for sharing good practice and building collaboration within the scientific community and with other stakeholders worldwide.

Early-Phase Clinical Trials of Bio-Artificial Organ Technology: A Systematic Review of Ethical Issues

“…One of the conditions for ethically responsible clinical research is a favorable risk-benefit ratio ( Table 4 ). This means that the risks and burdens of trial participation must be outweighed by the expected scientific or social value and the (potential) benefits for individual participants ( 12 , 16 , 21 , 23 , 24 , 28 , 29 , 32 , 34 , 37 , 45 , 50 , 53 , 57 , 64 , 66 – 69 , 77 , 78 ) ( Figure 3 ). The requirement of a favorable risk-benefit is difficult to meet in early-phase research, because the potential direct benefits to individual research participants in these trials are limited and uncertain ( 69 ).…”

“…When researchers are dealing with uncertain but potentially high risks, they are advised, before undertaking an early-phase clinical trial, to provide preclinical evidence of high internal validity (e.g., through replication) and external validity (e.g. through careful study design) ( 12 , 16 , 23 , 27 – 29 , 31 , 34 – 37 , 43 , 46 , 49 – 51 , 53 , 57 , 59 , 61 , 62 , 64 – 69 , 77 , 79 – 81 , 84 , 85 , 87 – 90 ). Some argue that large animals should be used, because these animals can better imitate the human anatomy and/or pathology than small animals ( 12 81 ).…”

“…To detect health risks associated with potential long-term adverse events, such as genetic instability, undirected or uncontrolled cell growth, research participants must be carefully monitored ( 16 , 19 , 21 , 23 , 24 , 28 , 29 , 32 , 34 , 42 , 46 , 50 , 58 , 64 , 67 – 70 , 81 – 83 , 85 ), with long-term follow-up ( 12 , 19 , 21 , 23 , 27 – 29 , 32 , 34 , 35 , 37 , 38 , 40 , 46 , 50 , 51 , 53 , 62 , 66 – 70 , 73 , 79 , 81 , 85 , 87 , 91 , 92 ). On the one hand, intensive monitoring may be perceived as reassuring or beneficial by research participants ( 50 , 83 , 93 ).…”

“…In the literature, relevant outcome measures for regenerative medicine clinical trials are discussed in 18 papers ( 12 , 16 , 19 , 21 , 24 , 32 , 34 , 37 , 43 , 50 , 61 , 64 , 69 , 77 , 80 , 81 , 87 , 94 ). Both clinical outcome measures (e.g., survival rate or functional status) and patient-reported outcome measures (PROMs) (e.g., quality of life or experienced symptoms) are considered important ( 12 , 21 , 34 , 43 , 69 , 77 , 81 , 87 , 94 ).…”

“…The ethical requirements of clear informed consent is mentioned frequently in the literature ( 12 , 16 , 17 , 20 – 25 , 27 , 29 , 31 – 34 , 37 , 38 , 43 , 45 , 50 – 52 , 59 , 60 , 64 – 69 , 75 – 77 , 79 , 81 , 83 , 85 , 89 , 90 , 92 , 93 , 97 , 98 ). Valid informed consent requires that participants must be adequately informed about relevant aspects of research participation, including the aim of the procedure, duration of the study, their right to withdraw, and the risks and benefits implications of the trial ( Table 7 ).…”