Comparison of Patients With Head and Neck Cancer in Randomized Clinical Trials and Clinical Practice: A Systematic Review

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.