Inadequate reporting quality of registered genome editing trials: an observational study

Abstract

Background: To assess registration completeness and safety data of trials on human genome editing (HGE) reported in primary registries and published in journals, as HGE has safety and ethical problems, including the risk of undesirable and unpredictable outcomes. Registration transparency has not been evaluated for clinical trials using these novel and revolutionary techniques in human participants. Methods: Observational study of trials involving engineered site-specific nucleases and long-term follow-up observations, identified from the WHO ICTRP HGE Registry in November 2020 and two comprehensive reviews published in the same year. Registration and adverse events (AEs) information were collected from public registries and matching publications. Published data were extracted in May 2021. Results: Among 81 eligible trials, most were recruiting (51.9%) phase 1 trials (45.7%). Five trials were withdrawn. Most trials investigated CAR T cells therapies (45.7%) and used CRISPR/Cas9 (35.8%) ex vivo (88.9%). Among 12 trials with protocols both registered and published, eligibility criteria, sample size, and secondary outcome measures were consistently reported for less than a half. Three trials posted results in ClinicalTrials.gov, and one reported serious AEs. Conclusions: Incomplete registration and published data give emphasis to the need to increase the transparency of HGE trials. Further improvements in registration requirements, including phase 1 trials, and a more controlled publication procedure, are needed to augment the implementation of this promising technology.