Topic
Surrogate endpoint
About: Surrogate endpoint is a research topic. Over the lifetime, 2078 publications have been published within this topic receiving 79715 citations.
Papers published on a yearly basis
Papers
More filters
Food and Drug Administration1, Université Bordeaux Segalen2, Edinburgh Cancer Research Centre3, MedStar Washington Hospital Center4, European Organisation for Research and Treatment of Cancer5, Memorial Sloan Kettering Cancer Center6, University of North Carolina at Chapel Hill7, University of Texas MD Anderson Cancer Center8, Virginia Commonwealth University9, Ludwig Maximilian University of Munich10
TL;DR: In this paper, the authors compared the three most commonly used definitions of pathological complete response (ypT0 ypN0, ypT0/is ypNs0, and ypTsN0/IsYPN0) for their association with EFS and overall survival in clinical trials of neoadjuvant treatment of breast cancer.
2,793 citations
TL;DR: A rather restrictive criterion is proposed for use of the adjective 'surrogate' - it is proposed that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response.
Abstract: I discuss the idea of using surrogate endpoints in the context of clinical trials to compare two or more treatments or interventions in respect to some 'true' endpoint, typically a disease occurrence. In order that treatment comparison based on a surrogate response variable have a meaningful implication for the corresponding true endpoint treatment comparison, a rather restrictive criterion is proposed for use of the adjective 'surrogate'. Specifically, I propose that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response. This criterion essentially requires the surrogate variable to 'capture' any relationship between the treatment and the true endpoint, a notion that can be operationalized by requiring the true endpoint rate at any follow-up time to be independent of treatment, given the preceding history of the surrogate variable. I then discuss this operational criterion in the examples of the accompanying papers and in the setting of trials aimed at the primary and secondary prevention of cancer.
1,816 citations
TL;DR: Surrogate end points are rarely, if ever, adequate substitutes for the definitive clinical outcome in phase 3 trials and proper justification for such replacement requires that the effect of the intervention on the surrogate end point predicts the effect on the clinical outcome.
Abstract: Phase 3 clinical trials, which evaluate the effect that new interventions have on the clinical outcomes of particular relevance to the patient (such as death, loss of vision, or other major symptom...
1,510 citations
TL;DR: These guidelines provide a common framework for designing trials to facilitate comparability of results, and randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC.
Abstract: The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.
1,472 citations
TL;DR: Recanalization is strongly associated with improved functional outcomes and reduced mortality and is an appropriate biomarker of therapeutic activity in early phase trials of thrombolytic treatment in acute ischemic stroke.
Abstract: Background and Purpose— For a biomarker to serve as an auxiliary or surrogate outcome measure, it must be tightly correlated with and causally related to functional clinical outcome. Vessel recanalization is a potential surrogate outcome marker for functional outcome in trials of thrombolytic and mechanical recanalization therapies in acute stroke, but the correlation of recanalization and clinical outcome has not been previously systematically reviewed. Methods— Through Medline search, we identified and abstracted recanalization and outcome data from all articles published between 1985 and 2002 that assessed vessel recanalization, either spontaneous or therapeutically induced, in acute ischemic stroke. Results— Fifty-three studies encompassing 2066 patients reported recanalization rates. Recanalization rates categorized according to intervention were: spontaneous (24.1%), intravenous fibrinolytic (46.2%), intra-arterial fibrinolytic (63.2%), combined intravenous–intra-arterial (67.5%), and mechanical (83...
1,385 citations