Operational complexity predicts selective non-dissemination within pharmaceutical sponsor portfolios: a retrospective cohort study

BackgroundIncomplete dissemination of clinical trial results remains an important challenge for research transparency and evidence synthesis. Although prior studies have quantified the overall extent of non-dissemination, less is known about whether trial characteristics observable at registration are associated with subsequent dissemination within sponsor portfolios. Methods and findingsWe conducted a retrospective cohort study of 17,537 completed interventional clinical trials registered on ClinicalTrials.gov between 2007 and 2024 across the 20 largest global pharmaceutical companies. We developed the Operational Complexity Index (OCI), a composite measure derived from planned enrollment, facility count, and geographic scope, and examined its association with trial dissemination using multivariable logistic regression and time-to-event analyses. Higher OCI was associated with greater odds of dissemination (adjusted odds ratio [aOR] = 2.40, 95% CI 2.23-2.60; p < 0.001), with dissemination increasing from 47% in the lowest OCI decile to 95% in the highest. Higher operational complexity was also associated with earlier dissemination; over a 1,095-day horizon, high-OCI trials were disseminated a mean of 310.88 days earlier than low-OCI trials (RMST difference, 310.88 days; 95% CI 300.59-320.96; p < 0.001). This pattern was observed across sponsors, clinical phases, and therapeutic areas. In predictive analyses using registration-time variables, the structural model achieved a cross- validated AUC of 0.816 and a holdout AUC of 0.814, whereas the full model, including sponsor identity, achieved a cross-validated AUC of 0.858 and a holdout AUC of 0.857. Using benchmark phase-based costing assumptions, the 5,019 non-disseminated trials corresponded to an estimated US$10.94-15.26 billion in sunk research investment. ConclusionsAmong trials conducted by the 20 largest pharmaceutical sponsors, greater operational complexity at registration was associated with a higher likelihood of dissemination and earlier dissemination. These findings suggest that aggregate sponsor-level transparency metrics may mask important heterogeneity within sponsor portfolios. Future work should assess whether registration-time trial characteristics can help identify trial subgroups at higher risk of non-dissemination. AUTHOR SUMMARYO_ST_ABSWhy was this study done?C_ST_ABSO_LIIncomplete dissemination of clinical trial results reduces the completeness of the medical evidence base and the public value of research participation. C_LIO_LIPrevious studies have described overall rates of trial non-dissemination, but less is known about whether dissemination varies systematically across different types of trials within sponsor portfolios. C_LIO_LIWe examined whether trial characteristics available at registration were associated with later dissemination of results among large pharmaceutical sponsors. C_LI What did the researchers do and find?O_LIWe analyzed 17,537 completed interventional clinical trials sponsored by the 20 largest pharmaceutical companies and registered on ClinicalTrials.gov between 2007 and 2024. C_LIO_LIWe developed an Operational Complexity Index (OCI) based on planned enrollment, number of facilities, and geographic scope to measure trial operational scale at registration. C_LIO_LIHigher OCI was associated with a greater likelihood of dissemination and earlier dissemination. Dissemination ranged from 47% in the lowest OCI decile to 95% in the highest. C_LIO_LIThis pattern was observed across sponsor portfolios, clinical phases, and therapeutic areas, with an average within-sponsor dissemination gap of 40 percentage points between lower- and higher-complexity trials. C_LIO_LIIn manual validation of 344 sampled trials, the automated dissemination-classification pipeline achieved 92.1% accuracy. C_LIO_LIUsing benchmark phase-based costing assumptions, the 5,019 non-disseminated trials corresponded to an estimated US$10.9-15.3 billion in sunk research investment. C_LI What do these findings mean?O_LIDissemination was not uniform across trial types within sponsor portfolios; trials with lower operational complexity were less likely to be disseminated than trials with higher operational complexity. C_LIO_LIAggregate sponsor-level transparency measures may therefore miss important differences within portfolios. C_LIO_LIRegistration-time trial characteristics showed predictive signal for non-dissemination, but whether such information could support monitoring strategies would require prospective validation. C_LIO_LIMore complete dissemination of trial results would strengthen the scientific record and improve the public value of clinical research. C_LI