AUTHOR=Chao Yi-Sheng , Wu Chao-Jung , Wu Hsing-Chien , McGolrick Danielle , Chen Wei-Chih 

TITLE=Interpretable Trials: Is Interpretability a Reason Why Clinical Trials Fail?

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.541405

DOI=10.3389/fmed.2021.541405

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> There are clinical trials using composite measures, indices, or scales as proxy for independent variables or outcomes. Interpretability of derived measures may not be satisfying. Adopting indices of poor interpretability in clinical trials may lead to trial failure. This study aims to understand the impact of using indices of different interpretability in clinical trials.</p><p><bold>Methods:</bold> The interpretability of indices was categorized as: fair-to-poor, good, and unknown. In the literature, frailty indices were considered fair to poor interpretability. Body mass index (BMI) was highly interpretable. The other indices were of unknown interpretability. The trials were searched at <ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">clinicaltrials.gov</ext-link> on October 2, 2018. The use of indices as conditions/diseases or other terms was searched. The trials were grouped as completed, terminated, active, and other status. We tabulated the frequencies of frailty, BMI, and other indices.</p><p><bold>Results:</bold> There were 263,928 clinical trials found and 155,606 were completed or terminated. Among 2,115 trials adopting indices or composite measures as condition or disease, 244 adopted frailty and 487 used BMI without frailty indices. Significantly higher proportions of trials of unknown status used indices as conditions/diseases or other terms, compared to completed and terminated trials. The proportions of active trials using frailty indices were significantly higher than those of completed or terminated trials.</p><p><bold>Discussion:</bold> Clinical trial databases can be used to understand why trials may fail. Based on the findings, we suspect that using indices of poor interpretability may be associated with trial failure. Interpretability has not been conceived as an essential criterion for outcomes or proxy measures in trials. We will continue verifying the findings in other databases or data sources and apply this research method to improve clinical trial design. To prevent patients from experiencing trials likely to fail, we suggest further examining the interpretability of the indices in trials.</p>