Usage of Disease-Specific Patient Reported Outcome Measures (PROMs) for Assessing Quality of Life (QoL) in Industry Sponsored Hemophilia Interventional Trials

Introduction

The World Health Organization (WHO) defines QoL “as an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.” Measurement of QoL is vital to making informed treatment decisions which include patient’s priorities and values. Over the last 20 years, several disease-specific PROMs have been developed and validated to collect QoL data in hemophilia patients. To aid industry sponsors in the design of future hemophilia clinical trials we attempted a comprehensive review of the usage of different QoL instruments in past hemophilia clinical trials.

Objective

Review patterns of usage of different PROMs commonly used to assess QoL in industry sponsored Hemophilia clinical trials in the last 20 years.

Methods

We searched Citeline Trialtrove database, a registry of clinical trials, for sponsor type = industry, patient segment = HemA/B, start years = 2004-2024 and excluded trials that were observational and non-interventional. We also performed a literature search for available associated publications and protocol documents to find patient-reported and health outcomes instruments and added trials referenced. For identified trials, the following data was recorded: therapy tested, clinical development phase, patient segment included, study start date, age range, geographical regions included, and PRO instrument(s) used, if any.

Results

Thirty three industry sponsored hemophilia trials using PROMs to collect QoL data as an endpoint were identified. Of these, 20 targeted HemA, 7 HemB, and 6 HemA and HemB patients. Sixteen trials tested a factor concentrate product, with 13 trials testing 5 unique novel drugs and 4 trials testing 2 unique gene therapies. The most used disease specific PROM was Haemo-A-QoL in patients ≥ 17 years and Haemo-QoL in patients 13-16 years. Other utilized disease specific PROMs in more than1 trial included HEMO-SAT, Hemo-TEM, HAL and CHO-KLAT. In addition, generic instruments were also used to measure health outcomes and included EQ-5D and SF-36 family of questionnaires, PROMIS and Patient Global Impressions (PGI) scales. Eight of the identified trials collecting QoL data in children < 12 years of age using the Haemo-QoL, HEMO-SAT, CHO-KLAT, HEMO-TEM and generic EQ-5D-Y and PROMIS. Of the 21 trials of 9 different agents collecting QoL data starting since 2014, 19 (90%) used the Haemo-QoL family of instruments, with the other 2 studies corresponding to a single sponsor. Although Haemo-QoL-A was not developed for use with gene therapy, this instrument was used in the 4 identified gene therapy studies.

Some reviewed publications describe a lower rate of completion of QoL instruments in the adolescent group, compared to completion rates in adults and children in the same studies. Other observations reported by authors include a lack of significant improvement in pediatric QoL, possibly as a result of a ceiling effect, HAEMO-QoL has age-specific versions further limiting sample sizes in adolescents and children, and analyses of subdomains within PRO instruments indicate pain and physical health mobility as the concepts most sensitive to change with prophylaxis treatment.

Conclusion

This review found the most utilized disease-specific PROMs in hemophilia trials with an industry sponsor, therefore helping the decision process at the time of designing new trials.