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Comparator choice in clinical trials of cancer drugs and recommendation categories in National Comprehensive Cancer Network (NCCN) guidelines: a retrospective cohort analysis

Year: 2026

Type: article

Abstract: Background Comparative evidence is important to determine whether new drugs provide added benefit over existing treatments. Ideally, such evidence is generated using appropriate comparators reflecting the standard of care. The National Comprehensive Cancer Network (NCCN) guidelines classify recommendations according to the level of evidence and panel consensus. Category 1 reflects high-level of evidence and categories 2A, 2B and 3 lower-levels of evidence. Objective We evaluated how the choice of a comparator was reflected in the NCCN recommendations. Methods We conducted a retrospective cohort analysis of cancer drugs approved by the US Food and Drug Administration between 2010 and 2024. For each indication, we identified all populations and assessed whether their corresponding efficacy trials used appropriate, inappropriate or no comparators. We extracted NCCN recommendation categories and compared them across comparator groups. We conducted statistical inference via bootstrap CIs. Results Our cohort included 110 indications comprising 176 populations. 56/110 (51%) indications had at least one population tested with an appropriate comparator, 35/110 (32%) had at least one population using an inappropriate comparator, 30/110 (27%) had at least one population based on a single-arm trial and 7/110 (6%) had at least one population for which no data was available. The average proportion of populations classified in NCCN category 1 was 6 percentage points higher with an appropriate than with an inappropriate comparator (95% CI −11 to 25), and 43 percentage points higher than with single-arm trials (95% CI 28 to 58). Conclusion Approximately half of the indications recommended in the NCCN guidelines had at least one population tested with an appropriate comparator. The average proportion of NCCN category 1 recommendations did not differ significantly between populations tested with an appropriate and inappropriate comparator but was significantly lower for populations supported by single-arm trials. Greater transparency regarding comparator choice could improve clinical decision-making.

Source: BMJ Open

DOI: 10.1136/bmjopen-2026-122939

Authors: Camille E G Glaus, Cyrill Meier, Simon Hediger, Lara Welti, Kerstin Noelle Vokinger

Institutions: University of Zurich, ETH Zurich

Language: English

Topic: Clinical practice guidelines implementation

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,839