Gene Therapy Trials and Pediatric Assent – Is it Time to Re-Think or Align with Organ Transplant?

Clinical trials in children require additional protections compared to trials in adult populations. While parental consent is an absolute requirement in pediatric research, some Institutional Review Boards (IRBs) in the United States also require child participants to assent or agree to participate, in the trial. The age that pediatric assent is required however is discretionary. The past 2 decades have seen a rapid advancement in the number of trials in children with rare diseases due to mutations in a single gene. Some single gene mutations are amenable to potential correction via gene therapy (GT) and gene editing (GE) techniques. The advanced science of GT and GE is complicated and permanent, making the eligibility and decision to participate far more complex than traditional clinical research with small molecule drugs and biologics. The ability to fully withdraw and preserve the option of participating in other, future investigational trials is far more nuanced. Participation in GT trials can also require long commitments to immunosuppressive drugs, and trials may last a decade or longer, during which children may mature into young adults who develop independent agency. Rather than anchoring to rubrics developed for clinical trials of drugs, conventions from pediatric organ transplant may be applicable to GT and GE trials. A new rubric is proposed to allow IRBs to weigh these similarities to transplant, and differences from traditional drug trials, as they determine whether or not, and when, to require pediatric assent for participation in GT and GE trials.