Historical Perspective of Landmark Trials in Head and Neck Cancers.

[OBJECTIVE] Understanding the historical perspective, including the evolution, conceptualization, and the issues in implementation of clinical trials, is crucial in developing future clinical trials.

[DATA SOURCES] A literature search included the following databases: MEDLINE; Embase; Cochrane Central Register of Controlled Trials; and ClinicalTrials.gov for clinical trials on head and neck cancer.

[REVIEW METHODS] Six principal investigators/senior authors of major landmark trials in head and neck cancers conducted over the past 30 years were interviewed. The goal was to get their insight on factors including conceptualization, writing, conducting, and reporting a clinical trial.

[RESULTS] Several roadblocks were identified during our interviews and review of relevant literature. These included methodological and ethical dilemmas of surgical trials, standardization of surgical interventions, lack of exposure to clinical epidemiology for surgeons, and issues with the logistics of conducting clinical trials outside a comprehensive cancer center or an academic medical center. The interviewees and literature review provided insight into how these issues could be mitigated. The strategies included standardized surgical credentialing to provide quality assurance and expertise-based surgical trials, involvement of surgeons early in clinical trials, and collaboration with medical oncology colleagues, decentralization of clinical trials, and a private-public partnership to increase clinical trial enrollment.

[CONCLUSION] Insight from investigators who have spearheaded landmark clinical trials gave us the opportunity to apply their experience with possible regulatory challenges to methodological issues and to consider practical considerations while conducting clinical trials.