Robust Preclinical Evidence in Somatic Cell Genome Editing: A Key Driver of Responsible and Efficient Therapeutic Innovations

Abstract

Somatic cell genome editing (SCGE) is highly promising for therapeutic innovation. Multifold financial and academic incentives exist for the quickest possible translation from preclinical to clinical studies. This study demonstrates that the majority of 46 preclinical SCGE studies discussed in expert reviews as particularly promising for clinical translation do not report on seven key elements for robust and confirmatory research practices: (1) randomization, (2) blinding, (3) sample size calculation, (4) data handling, (5) pre-registration, (6) multi-centric study design, and (7) independent confirmation. Against the background of the high incentives for clinical translation and recent concerns about the reproducibility of published preclinical evidence, we present the here examined reporting standards (1-4) and the new NIH funding criteria for SCGE research (6-7) as a viable solution to protect this promising field from backlashes. We argue that the implementation of the novel methodological standards, e.g. "confirmation" and "pre-registration", is promising for preclinical SCGE research and provides an opportunity to become a lighthouse example for trust-worthy and useful translational research.