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Comparison of Patients With Head and Neck Cancer in Randomized Clinical Trials and Clinical PracticeA Systematic Review

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Key Points

Question  Are patients with head and neck cancer in randomized clinical trials representative of patients in clinical practice?

Findings  In this systematic review of 87 randomized clinical trials with a total of 34 241 patients, patients with head and neck cancer in randomized clinical trials were much younger than the clinically treated population and had a very good performance status. In more than half of the head and neck trials, the average yearly accrual per participating center was less than 6 patients, suggesting overly restrictive recruitment.

Meaning  Critical appraisal of trial population characteristics is recommended before results are implemented in clinical practice.

Abstract

Importance  When patient populations in randomized clinical trials deviate too much from the general population, it undermines the relevance for daily practice.

Objective  To investigate if patients with head and neck cancer in randomized clinical trials are representative of the clinically treated population.

Evidence Review  A systematic literature search was performed for randomized clinical trials on head and neck cancer evaluating an intervention to improve outcome with total sample size of 100 patients or greater and published between 2009 and 2019. Outcome measures were age, performance status, and recruitment rate. National cancer registries provided reference data. Databases that were searched included MEDLINE and Epub Ahead of Print; Embase; Cochrane Central Register of Controlled Trials; and ClinicalTrials.gov. Abstracts of search results were retrieved to assess selection criteria by 2 reviewers independently. After the selection procedure was completed by both reviewers, the results were compared and reviewed once more to reach consensus. Full articles were downloaded to retrieve general study information and outcome data.

Findings  A total of 16 927 publications were identified, resulting in 87 compliant randomized clinical trials with a total of 34 241 patients. Half of the trials included all major head and neck sites, and one-third were exclusively for nasopharynx cancers. The experimental intervention was systemic treatment in 47 (54%) studies, radiotherapy in 23 (26%), and other in 17 (20%). Median sample size was 332, and median duration of accrual was 4.6 years. Median accrual per center per year for head and neck and nasopharynx trials was 5.4 and 39.7 patients, respectively. Median age of patients in head and neck trials was 57 years, which was 7 years younger than in cancer registries. More than 70% of patients had a World Health Organization performance score of 0 to 1 or a Karnofsky performance status of 90 to 100.

Conclusions and Relevance  In this systematic review, patients in head and neck randomized clinical trials had a very good performance status, and half of them were younger than 57 years, while half of the clinical population was older than 64 years. In more than 50% of the head and neck trials, the yearly accrual per center was less than 6 patients, suggesting overly restrictive recruitment. Critical appraisal of trial population characteristics is recommended before results are implemented in clinical guidelines and general practice.

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Article Information

Accepted for Publication: March 30, 2022.

Published Online: May 19, 2022. doi:10.1001/jamaoto.2022.0890

Corresponding Author: Johannes H. A. M. Kaanders, MD, PhD, Department of Radiation Oncology 874, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, the Netherlands (j.kaanders@radboudumc.nl).

Author Contributions: Drs Kaanders and van den Bosch had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kaanders, Kleijnen.

Acquisition, analysis, or interpretation of data: Kaanders, van den Bosch.

Drafting of the manuscript: Kaanders.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Kaanders, Kleijnen.

Administrative, technical, or material support: Kaanders.

Supervision: Kaanders, Kleijnen.

Conflict of Interest Disclosures: None reported.

Additional Information: The data underlying this article will be shared on reasonable request to the corresponding author. The authors acknowledge the cancer registries of the US (SEER), the UK (NHS, National Cancer Registration and Analysis Service UK), the Netherlands (Netherlands Cancer Registry), Hong Kong (Hong Kong Cancer Registry), and Taiwan (Taiwan Cancer Registry) for providing reference data. This work used data that have been provided by patients and collected by the NHS as part of their care and support. The data are collated, maintained, and quality assured by the National Cancer Registration and Analysis Service, which is part of Public Health England.

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