International Stakeholder Guidance for Improving Informativeness of Randomized Clinical Trials.

Importance: Many randomized clinical trials are poorly designed, address unimportant questions, or are conducted and reported in ways that limit their usefulness and contribute to research waste. Gaining insight into the perspectives of stakeholders is essential for understanding why issues affecting trial informativeness persist. Objective: To explore global perspectives on enhancing trial informativeness using a 5-point framework including trial importance, design, feasibility, integrity, and reporting. Design, Setting, and Participants: This qualitative study used semistructured, one-on-one interviews conducted via an online video conferencing platform between October 2024 and March 2025. Participants included professionals involved in the funding, design, sponsorship, and regulatory and ethical overview of randomized clinical trials. Demographic characteristics of the 55 participants were analyzed using descriptive statistics. Main Outcomes and Measures: The primary outcome was participants' views on how the informativeness of randomized clinical trials is assessed, why uninformative trials persist, and potential approaches to reduce design and conduct flaws. Data were analyzed thematically, beginning with a deductive coding framework informed by insight from an earlier global rapid review and further refined through inductive coding to capture new themes. Results: This qualitative study included 55 individuals from 16 countries across 5 continents, primarily from the US (12 [21.8%]) and the United Kingdom (11 [20.0%]), and included investigators (21 [38.2%]), funders (12 [21.8%]), and a range of other stakeholders in randomized clinical trials. Design yielded the greatest number of insights, including further scientific design review after peer review but prior to funding commitment and the need for qualified trial statisticians. Other key insights included building trust through early and meaningful patient partnership (importance) and the need for additional skills-based training beyond good clinical practice to ensure the quality conduct of trials (integrity). Feasibility, often overlooked, was deemed an important factor, with participants stressing the need for compelling, evidence-based plans for recruitment and retention to ensure that research questions are answered reliably. Conclusions and Relevance: In this qualitative study of 55 international stakeholders in randomized clinical trials, interviews offered context and evidence to guide potential improvements in prefunding and peer review processes, as well as in trial design and best practices. Further action is needed to ensure that randomized clinical trials will consistently produce reliable evidence that improves health and strengthens public trust in science.