Endpoints in cancer clinical trials.
Endpoints are measurable clinical and biological findings that are used for the development and assessment of treatment options. In the treatment of cancer, endpoints can be classified into two categories: "patient-centered clinical endpoints" including overall survival (OS) and health-related quality of life (QoL), and "tumor-centered clinical endpoints" such as progression-free survival. Surrogate endpoints are tumor-centered clinical endpoints that can be used as substitutes for patient-centered clinical endpoints, particularly OS. The choice of endpoints in oncology trials is a major problem. The published Consolidated Standards of Reporting Trials (CONSORT) best-practice guidelines encourage the reporting of clearly defined primary and secondary outcome measures. OS is the gold standard of endpoints but as increasing numbers of effective salvage treatments become available for many types of cancer, much larger numbers of patients are included; this requires a longer follow-up period and increases the cost of clinical trials. Thus, tumor-centered clinical endpoints that can be assessed earlier and used as surrogates for overall survival are increasingly studied, but most of them currently lack standardized definitions to enable cross comparison of results among different clinical trials and they have not been validated as surrogate endpoints. In addition, the variability of their definition can strongly impact the trial's conclusions by affecting both statistical power and estimation. In this context, QoL constitutes an available and useful surrogate endpoint for trials to ensure treatment benefit from both the patient and public health points of view. Methodological research should be pursued to develop standard outcome definitions for use in cancer clinical trials and to define a standardized longitudinal analysis of QoL data.
University Hospital of Besançon, Department of Medical Oncology, 3, boulevard Fleming, 25000 Besançon, France.
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Fiteni
University Hospital of Besançon, Chest disease Department, Besançon, France.
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Westeel
University Hospital of Besançon, Department of Medical Oncology, 3, boulevard Fleming, 25000 Besançon, France.
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Pivot
University Hospital of Besançon, Department of Medical Oncology, 3, boulevard Fleming, 25000 Besançon, France.
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Borg
Methodology and quality of Life in Oncology unit (EA 3181) & quality of Life and cancer clinical research plateform, CHU de Besançon, 2, place Saint-Jacques, 25000 Besançon, France.
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Vernerey
Methodology and quality of Life in Oncology unit (EA 3181) & quality of Life and cancer clinical research plateform, CHU de Besançon, 2, place Saint-Jacques, 25000 Besançon, France. Electronic address: franck.bonnetain@univ-fcomte.fr.
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Bonnetain
D002986:Clinical Trials as Topic / Q000379:methods*; D018572:Disease-Free Survival; D006801:Humans; D009369:Neoplasms / Q000401:mortality / Q000628:therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011788:Quality of Life; D012107:Research Design; D015996:Survival Rate; D016896:Treatment Outcome
Cancer clinical trials; Disease-free survival; Endpoint definitions; Health-related Quality of life; Methodological researches; Overall survival; Progression-free survival; Surrogate endpoints