Biomedical subjects
Publications and source records attributed to Marc Buyse.
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PURPOSE: A meta-analysis of randomized trials in advanced ovarian cancer showed a longer survival with cyclophosphamide, doxorubicin, and cisplatin (CAP) than with cyclophosphamide and cisplatin (CP; P =.009). In contrast, the results of the large International Collaborative Ovarian Neoplasm Study (ICON2) showed no survival difference between CAP and carboplatin (P =.98). In this article, we show how these discrepant results can be reconciled through the estimation of expected survival curves. MATERIALS AND METHODS: A proportional hazards model, fitted to the meta-analysis data, was used to construct the expected survival curve for each treatment arm of the ICON2 trial. Expected survival curves were compared with observed survival curves in the ICON2 trial at all time points using a nonparametric test. RESULTS: The prognostic model for survival obtained in the meta-analysis included extent of residual disease, age, histologic grade, and International Federation of Gynecology and Obstetrics stage. When this model was applied to the ICON2 data, there was no difference between the expected and observed curves in the CAP arm. In contrast, the observed survival curve for carboplatin was far superior to the expected survival curve for CP (P <.01). CONCLUSION: These analyses provide indirect evidence that better results are achieved with carboplatin alone at an optimally tolerated dose, compared with the CP combination at a cisplatin dose of 50 to 60 mg/m2. The expected survival may provide valuable insight when direct comparisons between randomized groups yield discrepant results across different studies.
In the three trials that tested screening with biennial fecal occult blood test (FOBT), follow-up of control patients for colorectal cancer (CRC) differed: in the Minnesota (United States) trial, the follow-up was equivalent to patients in the intervention groups, while in the Nottingham (United Kingdom) and Funen (Denmark) trials, control patients just received usual care. In the two latter trials, mortality from colorectal cancer was lower in subjects with interval colorectal cancer than in control subjects, while in the Minnesota trial, survival was equivalent in patients with interval CRC and in control patients. We examined whether better disease awareness of subjects allocated to the intervention group contributed to changes in colorectal cancer mortality observed in the FOBT trials. In the Nottingham and Funen trials, we evaluated the amount of colorectal cancer mortality reduction attributable to better survival of subjects in whom an interval colorectal cancer developed. In the Minnesota trial, we examined whether earlier detection of colorectal cancer in control subjects could explain the small (6%) reduction in colorectal cancer mortality observed with biennial FOBT. In the Nottingham and Funen trials, about one-quarter of the reduction in colorectal cancer mortality could be attributed to better awareness of patients with interval colorectal cancer. After correction for the effects of disease awareness, the absolute reduction in colorectal cancer mortality due to FOBT itself was 12% instead of 16%, and was no longer statistically significant (P>0.05). The results from biennial FOBT in the Minnesota trial published in 1993 would probably have been similar to those obtained in the Nottingham and Funen trials if disease awareness had not influenced the stage at diagnosis of colorectal cancers found in the control group. Better awareness of colorectal cancer contributes to the reduction of colorectal cancer mortality and should be encouraged. Because of a study design effect, the decrease in colorectal cancer mortality attributable to the FOBT itself is about 25% lower than that reported in the Nottingham and Funen trials. Therefore, recommending general population screening with biennial FOBT is still an open question.
Despite recent progress made in screening, prevention and adjuvant treatment of colorectal cancer, a large proportion of patients with this disease develop local recurrences or distant metastases. The management of these patients requires a multidisciplinary approach. Surgery must be performed whenever possible for metastases confined to the liver or lung. However, in most cases, chemotherapy and supportive care are the only feasible treatments. This review describes the research carried out in this field through randomized trials and meta-analyses aimed at optimizing the efficacy of front-line chemotherapy.
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Explore the source record for details and available documents.
The validation of surrogate endpoints has been studied by Prentice, who presented a definition as well as a set of criteria that are equivalent if the surrogate and true endpoints are binary. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs proposed to replace the proportion explained by two quantities: (1). the relative effect, linking the effect of treatment on both endpoints, and (2). the adjusted association, an individual-level measure of agreement between both endpoints. In a multiunit setting, these quantities can be generalized to a trial-level measure of surrogacy and an individual-level measure of surrogacy. In this paper, we argue that such a multiunit approach should be adopted because it overcomes difficulties that necessarily surround validation efforts based on a single trial. These difficulties are highlighted.
In the last decade, the Meta-Analysis Group in Cancer (formerly Advanced Colorectal Cancer Meta-Analysis Project) has systematically used a meta-analytic to reassess the efficacy and toxicity of various fluoropyrimidine regimens in advanced colorectal cancer, as well as to investigate related questions, such as the relation between tumor response and survival. In this paper, the basic methodology of meta-analysis is reviewed and the findings of seven successive meta-analyses conducted between 1989-2000 by the Meta-Analysis Group in Cancer are summarized. The interested reader can refer to the statistical appendix for details on the methodology used for all meta-analyses.
In many therapeutic areas, the identification and validation of surrogate endpoints is of prime interest to reduce the duration and/or size of clinical trials. Buyse et al. [Biostatistics 2000; 1:49-67] proposed a meta-analytic approach to the validation. In this approach, the validity of a surrogate is quantified by the coefficient of determination Rtrial2 obtained from a model, which allows for prediction of the treatment effect on the endpoint of interest ('true' endpoint) from the effect on the surrogate. One problem related to the use of Rtial2 is the difficulty in interpreting its value. To address this difficulty, in this paper we introduce a new concept, the so-called surrogate threshold effect (STE), defined as the minimum treatment effect on the surrogate necessary to predict a non-zero effect on the true endpoint. One of its interesting features, apart from providing information relevant to the practical use of a surrogate endpoint, is its natural interpretation from a clinical point of view.