Defining Study Outcomes That Better Reflect Individual Response to Treatment

Defining Study Outcomes That Better Reflect Individual Response to Treatment Background: Most clinical trials comparing treatments evaluate the separate effects on each of several efficacy and toxicity outcomes. However, population-averaged summary measures of treatment differences may not accurately reflect individual responses to treatment, and drawing conclusions about which treatment is “best” is straightforward if one treatment is superior across all outcomes, but challenging when this is not the case. Methods: We created a study outcome based on expert opinion, which captures the risk/benefit profile of response to a treatment. Treatments were compared using this ordered outcome with standard statistical techniques. To illustrate the approach, we used as an example a study designed to evaluate initial antiretroviral therapy (ART) in human immunodeficiency virus-1–infected infants, in which results were contradictory across the study’s primary and secondary efficacy and toxicity outcomes. The proposed risk/benefit outcome was evaluated retrospectively in each participant. Results: In the International Maternal Pediatric Adolescent AIDS Clinical Trials P1060 study, one treatment regimen (lopinavir/ritonavir-based ART) was superior to the other (nevirapine-based ART) in reducing viral load (primary outcome) but inferior for immunologic and growth outcomes (important secondary outcomes in resource-limited settings). Treatment comparisons using the risk/benefit outcome indicated that the lopinavir/ritonavir-based ART regimen had a higher proportion of participants with the best overall response to treatment. Comparisons focusing on individual-level responses for the secondary outcomes also favored lopinavir/ritonavir-based ART, results that differed from the original population-averaged analyses ones. Conclusions: Designing studies prospectively using risk/benefit outcomes focusing on an individual’s responses to treatment more closely matches the needs of clinicians making decisions about how best to treat patients in clinical settings. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pediatric Infectious Disease Journal Wolters Kluwer Health

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
0891-3668
eISSN
1532-0987
D.O.I.
10.1097/INF.0000000000001766
Publisher site
See Article on Publisher Site

Abstract

Background: Most clinical trials comparing treatments evaluate the separate effects on each of several efficacy and toxicity outcomes. However, population-averaged summary measures of treatment differences may not accurately reflect individual responses to treatment, and drawing conclusions about which treatment is “best” is straightforward if one treatment is superior across all outcomes, but challenging when this is not the case. Methods: We created a study outcome based on expert opinion, which captures the risk/benefit profile of response to a treatment. Treatments were compared using this ordered outcome with standard statistical techniques. To illustrate the approach, we used as an example a study designed to evaluate initial antiretroviral therapy (ART) in human immunodeficiency virus-1–infected infants, in which results were contradictory across the study’s primary and secondary efficacy and toxicity outcomes. The proposed risk/benefit outcome was evaluated retrospectively in each participant. Results: In the International Maternal Pediatric Adolescent AIDS Clinical Trials P1060 study, one treatment regimen (lopinavir/ritonavir-based ART) was superior to the other (nevirapine-based ART) in reducing viral load (primary outcome) but inferior for immunologic and growth outcomes (important secondary outcomes in resource-limited settings). Treatment comparisons using the risk/benefit outcome indicated that the lopinavir/ritonavir-based ART regimen had a higher proportion of participants with the best overall response to treatment. Comparisons focusing on individual-level responses for the secondary outcomes also favored lopinavir/ritonavir-based ART, results that differed from the original population-averaged analyses ones. Conclusions: Designing studies prospectively using risk/benefit outcomes focusing on an individual’s responses to treatment more closely matches the needs of clinicians making decisions about how best to treat patients in clinical settings.

Journal

Pediatric Infectious Disease JournalWolters Kluwer Health

Published: Mar 1, 2018

References

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