Trends in collecting health-related quality-of-life measures among hematology gene therapy clinical trials Free

Background:

Health-related quality-of-life (HRQOL) is increasingly recognized as a key, patient-centered clinical trial outcome in hematology, with a recent study of malignant conditions showing that 73% of phase III trials collected HRQOL data (Patel, JAMA Netw Open, 2024). Gene therapies (GT) promise to transform traditional clinical endpoints and HRQOL for many hematologic conditions. Despite 2020 Food and Drug Administration (FDA) guidance encouraging the collection of patient experience data in GT studies, the extent to which HRQOL data are collected during these trials is unclear.

Methods:

The primary objective was to determine trial-level predictors of HRQOL data collection for hematology GT trials. The secondary objective was to determine the association between FDA guidance publication and HRQOL data collection. GT was defined as a therapy utilizing the modification, transfer, or regulation of genetic material through genome editing or cell engineering. ClinicalTrials.gov was the data source. Trials were reviewed and included if they were interventional therapeutic trials, used GT as the therapeutic modality, included a phase II or III component, and were being used to treat hematologic condition(s); there were no time window restrictions. Data were extracted independently by two authors using a standardized collection form; discrepancies and discordant codes were resolved via consensus. HRQOL collection assessment was based on the use of HRQOL study endpoint(s). Non-parametric statistics were used to describe trial characteristics, with Fisher's exact testing used for bivariate comparisons. Multivariable logistic regression analysis assessed associations between HRQOL collection and trial characteristics (year of registration, phase, age group, country, GT type, primary sponsor type), with odds ratios (OR) and 95% confidence intervals (CI) reported. The regression was repeated with pre-2020 and 2021-2025 categories (with 2020 as a washout period) to assess for changes in collection practices associated with the FDA guidance.

Results:

There were 207 trials that met inclusion criteria, of which 166 (80.2%) were for malignant hematologic conditions and 41 (19.8%) for classical hematologic conditions. A majority of trials (149; 72.0%) were phase I/II while 58 (28.0%) were phase II, II/III, or III; most studies were conducted outside the US (132; 63.7%). Half the trials exclusively studied adult participants (110; 53.1%) and the remainder pediatric or all ages (97; 46.9%). Chimeric antigen T-cell therapy (CAR-T) was used in 135 trials (65.2%), and 71 (34.3%) used DNA/RNA-based therapies. Academic institutions and governments sponsored 107 (51.7%) trials while 99 (47.8%) had industry/private sponsors.

Only 35 trials (16.9%) collected HRQOL data related to a trial endpoint. No trial collected HRQOL data for a primary endpoint; 23 (11.1%) and 15 (7.2%) trials collected these data for secondary or exploratory endpoints, respectively (not mutually exclusive). In multivariable analysis, decreased odds of HRQOL data collection was associated with later year of trial registration (OR 0.89; CI 0.80-0.99; p=0.03), pediatric-including vs adult trials (OR 0.28; CI 0.09, 0.88; p=0.03), trials of malignant vs classical hematologic conditions (OR 0.03; CI 0.01, 0.23; p<0.001), trials of DNA/RNA-based therapies vs CAR-T (OR 0.09; CI 0.01, 0.64; p=0.02), primary industry/private vs government/academic institution sponsorship (OR 0.34; CI 0.12, 0.96; p=0.04), and non-US-based vs US-based trials (OR 0.13; CI 0.04, 0.40; p<0.001); later trial phase, as defined above, was not associated with HRQOL collection (OR 0.62; CI 0.21, 1.87; p=0.40). No collinearity or significant interactions between covariates were observed. There were 33 trials registered after 2021; these trials were less likely to collect HRQOL data than trials registered before 2019 (p<0.01, Fisher's exact test), which was redemonstrated in repeat multivariable regression using pre-2020 versus 2021-2025 categories (OR 0.26; CI 0.08, 0.79; p=0.01).

Conclusion:

Few GT trials collect HRQOL data, and multiple trial-level factors are associated with lower rates of collection. Despite 2020 FDA guidance encouraging the collection of patient experience data, fewer trials registered after the guidance collected HRQOL data. This analysis highlights a key gap in the development of GT as well as which types of studies are most in need of HRQOL data collection.