Study Identifies Sponsor Decisions and Recruitment as Leading Causes of HNSCC Trial Failure
A retrospective study of 692 matched HNSCC trials found that sponsor-driven decisions and poor recruitment were the leading causes of early termination. The analysis also identified enrollment, funding source, trial phase, and inclusion of procedures or surgery as factors associated with failure.
Clinical trials evaluating treatments for patients with head and neck squamous cell carcinoma (HNSCC) are often terminated early due to strategic decisions or poor recruitment, according to findings from a retrospective study published in JAMA Otolaryngology–Head & Neck Surgery. Of 692 matched trials that were analyzed, 346 failed and 346 were completed, with sponsor-driven decisions accounting for 29.5% of failures and poor recruitment accounting for 26.0%.
The cross-sectional case-control study identified interventional clinical trials for the treatment of patients with HNSCC conducted between January 1, 2000, and December 31, 2024, via ClinicalTrials.gov. Failed studies were defined as those with terminated or withdrawn status, and failed trials were matched with completed study controls via a 1:1 nearest-neighbor propensity score method based on trial phase.
Strategic decisions were the most common reason for failed phase 1 studies, accounting for 47 of 111 failures, or 42.3%. Poor recruitment was the most common reason for failure for phase 2 trials, at 57 of 190, or 30.0%; phase 3 trials, at 9 of 41, or 22.0%; and phase 4 trials, at 4 of 4, or 100%.
Further data from the retrospective study showed that the most common reason for study failure moderately differentiated by treatment type. Strategic decisions were the most common reason for failure in immunotherapy trials, accounting for 46 of 84, or 54.8%, and in targeted therapy trials, accounting for 17 of 62, or 27.4%; recruitment was the most commonly cited reason for the failure of other studies.
Findings from a multivariable logistic regression analysis identified some independent factors that were predictive of early trial failure in HNSCC. Increased log-transformed enrollment had a protective effect on study termination and withdrawal, with an odds ratio of 0.36 and a 95% confidence interval of 0.30 to 0.42. Industry-funded trials displayed a higher risk of termination compared with those funded by the government, with an odds ratio of 2.84 and a 95% confidence interval of 1.16 to 7.17. Each progression of trial phase increased the odds of termination, with an odds ratio of 1.81 and a 95% confidence interval of 1.35 to 2.45, and the inclusion of a procedure or surgery was a predictor of failure, with an odds ratio of 1.98 and a 95% confidence interval of 1.12 to 3.54.
The study authors noted that funding from nongovernmental sources and inclusion of drug, device, biological/vaccine, or radiation were protective of study termination, although the width of the 95% confidence interval did not allow for precise estimates. The research team said updated recruitment schema, improved data monitoring practices, adaptive trial designs, and other interventions should be employed to improve HNSCC trial failure.