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Title: | Net benefit in the presence of correlated prioritized outcomes using generalized pairwise comparisons: A simulation study | Authors: | Giai, Joris Maucort-Boulch, Delphine Ozenne, Brice Chiem, Jean-Christophe BUYSE, Marc Peron, Julien |
Issue Date: | 2021 | Publisher: | WILEY | Source: | Statistics in Medicine (print), 40, p. 553-565 | Abstract: | Background The prioritized net benefit (Delta) is a measure of the benefit-risk balance in clinical trials, based on generalized pairwise comparisons (GPC) using several prioritized outcomes. Its estimation requires the classification as Wins or Losses of all possible pairs of patients, one from the experimental treatment (E) group and one from the control treatment (C) group. In this simulation study, we assessed the impact of the correlation between prioritized outcomes on Delta, its estimate, bias, size, and power. Methods The theoretical Delta value was derived for the specific case of two correlated binary outcomes when a normal copula is used. Focusing on one efficacy and one toxicity outcome, two situations frequently met in practice were simulated: binary efficacy outcome with binary toxicity outcome, or time to event efficacy outcome with categorical toxicity outcome. Several scenarios of efficacy and toxicity were generated, with various levels of correlation. Results When E was more effective than C, positive correlations were mainly associated with a decrease in the proportion of Losses, while negative correlations were associated with a decrease in the proportion of Wins on the toxicity outcome. This resulted in an increase of (Delta) over cap with the intensity of the positive correlation without adding any bias. Results were similar whatever the type of outcomes generated but led to power alteration. Conclusion Correlations between outcomes analyzed with GPC led to substantial but predictable modifications of Delta and its estimate. Correlations should be taken into consideration when performing sample size estimations in clinical trials. | Notes: | Giai, J (corresponding author), CHU Albert Michallon, CIC Innovat Technol, Pavillon Taillefer,CS 10217, F-38700 La Tronche, France. joris.giai@chu-lyon.fr |
Other: | Giai, J (corresponding author), CHU Albert Michallon, CIC Innovat Technol, Pavillon Taillefer,CS 10217, F-38700 La Tronche, France. joris.giai@chu-lyon.fr | Keywords: | clinical trial;correlation;generalized pairwise comparisons;multivariate analysis;net benefit | Document URI: | http://hdl.handle.net/1942/32925 | ISSN: | 0277-6715 | e-ISSN: | 1097-0258 | DOI: | 10.1002/sim.8788 | ISI #: | WOS:000583727100001 | Rights: | 2020 John Wiley & Sons, Ltd. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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Statistics in Medicine - 2020 - Giai - Net benefit in the presence of correlated prioritized outcomes using generalized.pdf Restricted Access | Published version | 1.69 MB | Adobe PDF | View/Open Request a copy |
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