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. 2023 Oct 31;7(6):pkad100.
doi: 10.1093/jncics/pkad100.

Characteristics of post hoc subgroup analyses of oncology clinical trials: a systematic review

Jawad Alrawabdeh  1 , Marah Alzu'bi  1 , Muntaser Alzyoud  1 , Nada Odeh  1 , Yazan Hamadneh  1 , Hira Mian  2 , Ghulam Rehman Mohyuddin  3 , Amar H Kelkar  4   5 , Aaron M Goodman  6 , Rajshekhar Chakraborty  7 , David A Russler-Germain  8 , Nikita Mehra  9 , Diva Baggio  10 , Edward R Scheffer Cliff  5   11 , Samer Al Hadidi  12
Affiliations

Characteristics of post hoc subgroup analyses of oncology clinical trials: a systematic review

Jawad Alrawabdeh et al. JNCI Cancer Spectr. .

Abstract

Background: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology.

Methods: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding.

Results: Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%).

Conclusions: This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies.

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Conflict of interest statement

Medical writers were involved in the preparation of 31% of the articles, and COI was reported in 58%. The remaining 44% either did not report COI or reported no COI. The most recent period, 2019-2022, had a considerably higher proportion of articles reporting any kind of funding compared to other periods (P < .001). However, there was no significant change in the rate of funding from pharmaceutical companies over the years (P = .065), in the context of a far greater number of published subgroup analyses. The reporting of medical writer usage varied significantly between time periods, increasing from 25% from 2000 to 2014 to 37% from 2015 to 2018, and then down to 30% from 2019 to 2022 (P < .001, Cramer’s V = 0.1) (Figure 3). The reporting of COI increased significantly across all time periods, with the more recent periods having the highest rates of reporting (P < .001). Both the 2014-2018 and 2019-2022 periods exhibited significantly higher average percentages (approximately 40% for both) of COI compared to the earliest period (30%) (P < .001).

Interventional drug trials reported the highest percentages of funding, pharmaceutical company funding, COIs, and usage of medical writers compared to other types of trials (P < .001 for all). Subgroup analyses of hematological malignancies compared to solid and mixed cancer trials, respectively, showed higher percentages of studies that reported funding (89.4% vs 78.1% vs 86.9%), pharmaceutical company funding (68.8% vs 44.8% vs 22.3%), reporting of COIs (80.9% vs 58% vs 35.4%), and usage of medical writers (50% vs 30.7% vs 16.2%) compared to solid and mixed cancer trials (P < .001 for all.).

J.A., M.A., M.A., N.O., Y.H., H.M., G.R.M., A.H.K, A.M.G, D.A.R. H.M., and D.B. reported no conflict of interests. R.C. reported consulting for Janssen, Sanofi Pasteur, and Adaptive Biotechnologies. S.A. received honoraria from Jansen and Sanofi. E.R.S.C receives research funding from Arnold Ventures.

Figures

Figure 1.
Figure 1.
PRISMA 2020 flow diagram for the article screening and selection process.
Figure 2.
Figure 2.
(A) Cumulative frequency of subgroup analysis according to publication year. (B) Number of subgroup analyses per year.
Figure 3.
Figure 3.
Usage of medical writing and pharmaceutical industry funding in subgroup analysis.
See this image and copyright information in PMC

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