(204) The Current Use of Single Arm Trials (SAT): A Targeted Literature Review

Background: Single arm trials (SATs) are an important research design, in the appropriate context, to provide robust efficacy and safety evidence for transformative therapies, allowing expeditious regulatory approval and availability to patients in need. However, SAT design has several limitations that require careful consideration. Recently, leveraging real-world data has drawn particular attention in recent years for facilitating oncology clinical development and regulatory decision-making through external control arms (ECA). Understanding key contextual factors and characteristics of SATs may be useful to gauge potential for ECA opportunities.

Objectives: To provide a description of key characteristics of SATs carried out from 2018 to 2023 as presented in the scientific literature.

Methods: A targeted search on MEDLINE was conducted in January 2024 to identify published studies reporting a SAT design from January 2018 to December 2023. The search aimed for high specificity and included free-text keywords aimed at the target study design. Abstracts of the search output were screened for appropriate study design and inclusion. For each included study, a unique trial registration number was identified. In case of multiple articles referencing the same trial number, one entry was kept. Therapeutic area (TA), funding source, and type of intervention product (pharmaceutical or medical) were extracted and summarized descriptively.

Results: 510 SAT publications dating from 2018 to 2023 were identified and screened. After screening, 360 unique SATs were included. A steady increase (105%) in the number of published SAT per year was observed over the review period; 60 publications in 2018; more than 120 in 2023.
Approximately 57% (n=204) of SATs evaluated pharmacologic interventions developed by bio-pharmaceutical or bio-technology industry, while the rest involved non-pharmacologic interventions such as educational or dietary programs. 141 studies (39%) utilized products developed by large pharmaceutical companies. The most frequent therapeutic area was oncology (25%) followed by cardiology (9%) and infectious diseases, neurology, and psychiatry/mental health (each at 5%). The number of new publications for these TAs remained steady during the study period, the overall increase in publications to be attributed to an increase in SATs in new TAs (11 different TAs in 2018; 18 in 2023).

Conclusions: An accelerated use of SATs was demonstrated. Notably, in addition to the widely established, traditional domain of oncology, several other TAs show an upward trend. There is a demonstrable imperative for high-quality ECAs, built using real-world data, to reduce uncertainties arising from SAT limitations.