OBJECTIVES: Evidence generated from systematic literature reviews (SLRs) and meta-analyses can play a crucial role in informing trial design and statistical analyses. This is particularly the case for rare/orphan diseases where there is often limited trial data available to guide trial design. However, these methodologies are often used too late in the market access pathway and to a limited degree—typically only to fulfil health technology assessment (HTA) submission requirements. Our objective was to investigate and describe the potential utility of adopting evidence synthesis approaches earlier in drug development.

METHODS: We reviewed company submissions and evidence review group (ERG) reports from all NICE highly specialised technology (HST) assessments published from inception to March 2024 to identify instances where evidence synthesis approaches could have been used to generate supporting evidence.

RESULTS: We identified three areas where SLRs and meta-analyses could have been used to strengthen company submissions beyond the standard approach of compiling clinical, economic, and quality-of-life data: (1) to investigate the impact of individual and social factors on illness burden and/or healthcare access in specific patient subpopulations, thereby highlighting health inequities that could be accounted for in trial recruitment, statistical analyses, and/or economic models; (2) to examine associations between short-term/novel endpoints and gold-standard outcomes to support the use of these endpoints in trials; and (3) to establish and quantify the effect of patient factors on treatment response in order to identify specific patient subgroups who are likely to benefit more from treatment and/or indicate which subgroups should be included in clinical trial data stratification.

CONCLUSIONS: Evidence synthesis approaches have utility beyond late-stage preparation for HTA submission. Manufacturers should consider using these methodologies at an earlier stage in drug development to capitalise on benefits, such as identifying health inequalities, justifying short-term or novel endpoints in trials, and supporting personalised medicine approaches.