1. Assessing the benefit–risk of new treatments using generalised pairwise comparisons: the case of erlotinib in pancreatic cancer
- Author
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W. R. Parulekar, Julien Péron, Pascal Roy, Marc Buyse, Ke Ding, Laurent Roche, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], and Hospices Civils de Lyon (HCL)
- Subjects
Oncology ,erlotinib ,Cancer Research ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,pancreatic cancer ,Pharmacology ,Placebo ,Deoxycytidine ,Risk Assessment ,Disease-Free Survival ,law.invention ,Erlotinib Hydrochloride ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Overall survival ,Humans ,030212 general & internal medicine ,Protein Kinase Inhibitors ,Analgesics ,business.industry ,Outcome measures ,medicine.disease ,Gemcitabine ,3. Good health ,Pancreatic Neoplasms ,Treatment Outcome ,030220 oncology & carcinogenesis ,statistics as topic ,Quinazolines ,Clinical Study ,Pairwise comparison ,Erlotinib ,business ,randomised controlled trial ,medicine.drug - Abstract
International audience; Background: Efficacy and safety are the two considerations when characterising the effects of a new therapy. We sought to apply an innovative method of assessing the benefit-risk balance using data from a completed randomised controlled trial that compared erlotinib vs placebo added to gemcitabine in patients with advanced pancreatic cancer (NCIC CTG PA.3).Methods: We applied generalised pairwise comparisons with several prioritised outcome measures (e.g., one or more benefit outcomes and one or more risk outcomes). Here, the first priority outcome was overall survival (OS) time. Differences in OS that exceeded 2 months were considered clinically meaningful. The second priority outcome was toxicity. The overall treatment effect was quantified using the proportion in favour of erlotinib, which can be interpreted as the net proportion of patients who have a better overall outcome with erlotinib as compared with placebo. Sensitivity analyses were performed.Results: In this trial 569 patients were randomly assigned in a 1 : 1 ratio to receive gemcitabine plus either erlotinib or a matched placebo. Overall, the method indicated no statistically significant overall treatment effect in favour of erlotinib; if anything, the point estimate of the net proportion leaned in favour of the placebo group (overall proportion in favour of erlotinib = - 3.6%, 95% CI, - 14.2-7.1%; P = 0.51). The net proportion was never in favour of the erlotinib group throughout all sensitivity analyses.Conclusions: Generalised pairwise comparisons make it possible to assess the benefit-risk balance of new treatments using a single statistical test for any number of prioritised outcomes. The benefit-risk assessment was not in favour of adding erlotinib to gemcitabine for the treatment of patients with advanced pancreatic cancer.
- Published
- 2015