Evidence generation and reproducibility in cell and gene therapy research: A call to action

The emergence of new cell and gene-based therapies (CGTs) utilizing innovative technologies has recently intensi fi ed. Long-standing efforts in publicly funded biomedical research have resulted in break-through therapeutic approaches for patients with devastating and life-threatening diseases. Transformative gene-based therapeutic tools include human genome editing technologies, re fi ned transposon systems, and synthetic immunoreceptors, such as chimeric antigen receptor (CAR) T cell and natural killer cell engineered immunother-apies. Cancer has been a leading disease target, with the treatment of B cell malignancies yielding compelling clinical outcomes, resulting in the regulatory approval of several CAR T cell therapies. 1 Concur-rently, intensive research on solid tumor indications is underway. 2 Similarly, rare diseases are prominent targets for gene therapy and gene editing technologies. 3 Founded on these scienti fi c advances, next-generation CGTs are expected to transform into treatment options for a wider spectrum of conditions. 4,5 Moreover, while these treatments, to-date, target mostly patients with advanced illnesses, future therapies may be introduced at earlier disease stages, even as primary therapeutic options. Here, we highlight some of the obstacles inherent in CGT evidence generation and research reproducibility and recommend concerted actions on how they can be overcome. Developers, regulators, funders and payers involved the development and next-generation CGTs robust evidence bene fi ts decision making 6 and ensure their translation from promising discoveries effective therapeutics. 7 Inadequate on their comparative ef fi cacy has led several CGTs be withdrawn from the European Union (EU) require-ments. 8 This is in certain attributes of CGTs such as in treatment and toxicities, targeting rare diseases with low patient accrual and lack suitable comparators need long-term and ef fi