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Review
. 2021 Feb;96(2):420-426.
doi: 10.1016/j.mayocp.2020.08.015.

Detecting the Dark Matter of Unpublished Clinical Cancer Studies: An Analysis of Phase 3 Randomized Controlled Trials

Dario Pasalic  1 , C David Fuller  2 , Walker Mainwaring  3 , Timothy A Lin  4 , Austin B Miller  5 , Amit Jethanandani  6 , Andres F Espinoza  3 , Aaron J Grossberg  7 , Reshma Jagsi  8 , Prajnan Das  2 , Albert C Koong  2 , Claus Rödel  9 , Emmanouil Fokas  9 , Charles R Thomas Jr  7 , Bruce D Minsky  2 , Ethan B Ludmir  10
Affiliations
Review

Detecting the Dark Matter of Unpublished Clinical Cancer Studies: An Analysis of Phase 3 Randomized Controlled Trials

Dario Pasalic et al. Mayo Clin Proc. 2021 Feb.

Abstract

Unpublished randomized controlled trial (RCT) frequency, correlates, and financial impact are not well understood. We sought to characterize the nonpublication of peer-reviewed manuscripts among interventional, therapeutic, multi-arm, phase 3 oncology RCTs. Trials were identified by searching ClinicalTrials.gov, while publications and abstracts were identified through PubMed and Google Scholar. Trial data were extracted from ClinicalTrials.gov and individual publications. Publication was defined as a peer-reviewed manuscript addressing the primary endpoint. Patient accrual cost was extrapolated from experimental data; investigators/sponsors were contacted to determine nonpublication reasons. Six hundred eighty-four completed RCTs met inclusion criteria, which accrued 434,610 patients from 1994 to 2015; 638 were published (93.3%) and 46 were unpublished (6.7%). Among the unpublished trials, the time difference from primary endpoint maturity to data abstraction was a median of 6 years (interquartile range, 4 to 8 years). On multiple binary logistic regression analysis, factors associated with unpublished trials included lack of cooperative group sponsorship (odds ratio, 5.91, 95% CI, 1.35 to 25.97; P=.019) and supportive care investigation (odds ratio, 2.90; 95% CI, 1.13 to 7.41; P=.027). The estimated inflation-adjusted average cost of patient accrual for all unpublished trials was $113,937,849 (range, $41,136,883 to $320,201,063). Direct contact with sponsors/investigators led to a 50.0% response rate (n=23 of 46); manuscript in preparation and/or in submission (n=10 of 23) was the most commonly cited reason for nonpublication. In conclusion, approximately 1 in 15 clinical oncology RCTs are unpublished and this has a profound impact on the research enterprise. The cooperative group infrastructure may serve as a blueprint to reduce nonpublication.

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Conflict of interest statement

Potential Competing Interests: Dr Koong reports stock ownership in Aravive. Dr Das reports personal fees from Adlai Nortye. Dr Jagsi reports stock ownership and a board advisory role in Equity Quotient; personal fees from Amgen and Vizient; and grants from the National Institutes of Health, the Debbie’s Dream Foundation, the Greenwall Foundation, and Blue Cross Blue Shield of Michigan. Dr Fuller reports honoraria from the University of Texas Health Science Center San Antonio and Elekta AB; royalties from Demos Medical Publishing; travel expenses/accomodations from Oregon Health and Science University, Great Baltimore Medical Center, University of Illinois Chicago, Elekta AB, and the Translational Research Institute of Australia; and grants from the National Science Foundation and National Institutes of Health. The remaining authors report no competing interests.

Figures

FIGURE.
FIGURE.
Flowchart of trial screening and inclusion. Of 1239 trials that were identified, 475 were deemed ineligible. The final cohort included 764 phase 3, randomized controlled trials (RCTs) with a therapeutic and interventional intent. Of those, 80 were excluded to generate 638 published trials and 46 unpublished trials.
See this image and copyright information in PMC

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