Master protocols in low- and middle-income countries: a review of current use, limitations and opportunities for precision medicine

Abstract

Background: Master protocols-umbrella, basket and platform trials, study multiple therapies, multiple diseases or both, offering many advantages, most profoundly that they answer multiple treatment-related questions, which would otherwise take multiple trials. We conducted a review of clinical trial registries to characterise their use in advancing precision medicine in low and middle-income countries (LMICs).

Methods: We searched trial records available in 20 trial registries globally, including ClinicalTrials.gov and WHO ICTRP, to identify umbrella, basket and platform trials launched until 30 September 2023.

Results: We identified 102 master protocols-29 umbrella trials, 31 basket trials, 36 platform trials, as well as six other designs that partially aligned with the working definition of master protocols, run in 54 different LMICs. Most trials were pharmaceutical industry-sponsored studies (60/102, 58.8%), conducted in oncology settings (56/102, 54.9%), currently ongoing (69/102, 67.6%) in early phase (phase I and II) settings (70/102, 68.6%) and have been planned or launched in the last 5 years (93/102, 91.2%), mainly with international collaborations in high-income countries. China was a site to more than half of all master protocols (53/102, 52%), and only a small proportion of trials (5/102, 4.9%) launched exclusively in LMICs excluding China and European middle-income countries. For most studies, aspects of trial design and trial documentation (including study protocols and analysis plans) were not publicly accessible.

Conclusion: Unlike high-income countries, where several hundreds of master protocols are ongoing or completed, there is limited use of master protocols in LMICs, partly owing to low penetration of precision medicine research and limited clinical trial infrastructure in most LMICs. The evidence presented here creates a case for supporting precision medicine initiatives in LMICs (especially Africa) and training and capacity building initiatives focused on innovative clinical trial designs like master protocols, especially in therapeutic areas outside oncology.

Keywords: Clinical trial; Global Health; Randomised control trial; Review.

Figure 1. Trends and descriptive characteristics of master protocols in LMICs. (A) Trends of master protocols in LMICs over time. The statistics here show new trial registrations within a particular year. (B) Summary of novel treatments, modules, sample size and study duration of the master protocols in LMICs. LMICs, low- and middle-income countries.

Figure 2. Geographical representation of master protocols in LMICs. The map is generated from data in our review. Dense colours represent a higher number of master protocols in those regions. LMICs, low- and middle-income countries.