OBJECTIVES: To characterise emerging gene therapies (GTs) clinical trials.

METHODS: The databases of ClinicalTrials.gov have been downloaded on June 1, 2019 and underwent automatized analysis using R algorithms for data mining. The databases were searched for records related to GTs using key words related to gene therapy, gene transfer and adeno-associated vectors. Relevant records were transferred to Excel-based data-extraction table for further descriptive analysis, focusing on study phase, design and population.

RESULTS: The overall number of 911 records were retrieved, of which 86% were interventional trials and 14% were observational studies. Of the interventional studies, 23% were described as randomised controlled trials (RCTs), of which 68% were blinded and 32% were open label trials. The remaining interventional trials adopted single-arm (SAT) (56%), parallel (8%), sequential (5%) or factorial (<1%) assignment strategy; the information regarding patients’ assignment was not provided for remaining records (7%). Of the experimental trials, 44%, 30%, 16%, 2%, 6% and 2% were phase 1, 1/2, 2, 2/3, 3 and phase 4 studies, respectively. Identified 131 observational evidence were cohort (66%), case series (13%), and case-control (9%) studies; with no methodological description for the remaining 12% studies. A total of 70% of all studies assess clinical efficacy, of which 52% adopted patient relevant primary endpoints, and 48% a surrogate end point. A total of 37% records related to malignant diseases, 2/3 solid tumours, followed by non-cancer haematological disorders (12%), metabolic diseases (9%), immune disorders (9%), ophthalmological diseases (5%) and diseases of circulatory system (5%).

CONCLUSIONS: GT clinical trial design are predominantly SAT, targeting primarily oncology indication, half used a surrogate primary end point. This will pose a challenge for future HTA assessment. New guidelines for assessing SAT using surrogate end point are needed.