Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.

<h4>Context</h4>Establishing the long-term benefit of therapy in chronic diseases has been challenging. Long-term studies require non-randomized designs and, thus, are often confounded by biases. For example, although disease-modifying therapy in MS has a convincing benefit on several sh...

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Autores principales:	Douglas S Goodin, Jason Jones, David Li, Anthony Traboulsee, Anthony T Reder, Karola Beckmann, Andreas Konieczny, Volker Knappertz, 16-Year Long-Term Follow-up Study Investigators
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6716c7c5b20943f18ef7c85912b553ed
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spelling	oai:doaj.org-article:6716c7c5b20943f18ef7c85912b553ed2021-11-18T07:33:25ZEstablishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.1932-620310.1371/journal.pone.0022444https://doaj.org/article/6716c7c5b20943f18ef7c85912b553ed2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22140424/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Context</h4>Establishing the long-term benefit of therapy in chronic diseases has been challenging. Long-term studies require non-randomized designs and, thus, are often confounded by biases. For example, although disease-modifying therapy in MS has a convincing benefit on several short-term outcome-measures in randomized trials, its impact on long-term function remains uncertain.<h4>Objective</h4>Data from the 16-year Long-Term Follow-up study of interferon-beta-1b is used to assess the relationship between drug-exposure and long-term disability in MS patients.<h4>Design/setting</h4>To mitigate the bias of outcome-dependent exposure variation in non-randomized long-term studies, drug-exposure was measured as the medication-possession-ratio, adjusted up or down according to multiple different weighting-schemes based on MS severity and MS duration at treatment initiation. A recursive-partitioning algorithm assessed whether exposure (using any weighing scheme) affected long-term outcome. The optimal cut-point that was used to define "high" or "low" exposure-groups was chosen by the algorithm. Subsequent to verification of an exposure-impact that included all predictor variables, the two groups were compared using a weighted propensity-stratified analysis in order to mitigate any treatment-selection bias that may have been present. Finally, multiple sensitivity-analyses were undertaken using different definitions of long-term outcome and different assumptions about the data.<h4>Main outcome measure</h4>Long-Term Disability.<h4>Results</h4>In these analyses, the same weighting-scheme was consistently selected by the recursive-partitioning algorithm. This scheme reduced (down-weighted) the effectiveness of drug exposure as either disease duration or disability at treatment-onset increased. Applying this scheme and using propensity-stratification to further mitigate bias, high-exposure had a consistently better clinical outcome compared to low-exposure (Cox proportional hazard ratio = 0.30-0.42; p<0.0001).<h4>Conclusions</h4>Early initiation and sustained use of interferon-beta-1b has a beneficial impact on long-term outcome in MS. Our analysis strategy provides a methodological framework for bias-mitigation in the analysis of non-randomized clinical data.<h4>Trial registration</h4>Clinicaltrials.govNCT00206635.Douglas S GoodinJason JonesDavid LiAnthony TraboulseeAnthony T RederKarola BeckmannAndreas KoniecznyVolker Knappertz16-Year Long-Term Follow-up Study InvestigatorsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e22444 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Douglas S Goodin Jason Jones David Li Anthony Traboulsee Anthony T Reder Karola Beckmann Andreas Konieczny Volker Knappertz 16-Year Long-Term Follow-up Study Investigators Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.
description	<h4>Context</h4>Establishing the long-term benefit of therapy in chronic diseases has been challenging. Long-term studies require non-randomized designs and, thus, are often confounded by biases. For example, although disease-modifying therapy in MS has a convincing benefit on several short-term outcome-measures in randomized trials, its impact on long-term function remains uncertain.<h4>Objective</h4>Data from the 16-year Long-Term Follow-up study of interferon-beta-1b is used to assess the relationship between drug-exposure and long-term disability in MS patients.<h4>Design/setting</h4>To mitigate the bias of outcome-dependent exposure variation in non-randomized long-term studies, drug-exposure was measured as the medication-possession-ratio, adjusted up or down according to multiple different weighting-schemes based on MS severity and MS duration at treatment initiation. A recursive-partitioning algorithm assessed whether exposure (using any weighing scheme) affected long-term outcome. The optimal cut-point that was used to define "high" or "low" exposure-groups was chosen by the algorithm. Subsequent to verification of an exposure-impact that included all predictor variables, the two groups were compared using a weighted propensity-stratified analysis in order to mitigate any treatment-selection bias that may have been present. Finally, multiple sensitivity-analyses were undertaken using different definitions of long-term outcome and different assumptions about the data.<h4>Main outcome measure</h4>Long-Term Disability.<h4>Results</h4>In these analyses, the same weighting-scheme was consistently selected by the recursive-partitioning algorithm. This scheme reduced (down-weighted) the effectiveness of drug exposure as either disease duration or disability at treatment-onset increased. Applying this scheme and using propensity-stratification to further mitigate bias, high-exposure had a consistently better clinical outcome compared to low-exposure (Cox proportional hazard ratio = 0.30-0.42; p<0.0001).<h4>Conclusions</h4>Early initiation and sustained use of interferon-beta-1b has a beneficial impact on long-term outcome in MS. Our analysis strategy provides a methodological framework for bias-mitigation in the analysis of non-randomized clinical data.<h4>Trial registration</h4>Clinicaltrials.govNCT00206635.
format	article
author	Douglas S Goodin Jason Jones David Li Anthony Traboulsee Anthony T Reder Karola Beckmann Andreas Konieczny Volker Knappertz 16-Year Long-Term Follow-up Study Investigators
author_facet	Douglas S Goodin Jason Jones David Li Anthony Traboulsee Anthony T Reder Karola Beckmann Andreas Konieczny Volker Knappertz 16-Year Long-Term Follow-up Study Investigators
author_sort	Douglas S Goodin
title	Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.
title_short	Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.
title_full	Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.
title_fullStr	Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.
title_full_unstemmed	Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.
title_sort	establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in ms.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/6716c7c5b20943f18ef7c85912b553ed
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Establishing long-term efficacy in chronic disease: use of recursive partitioning and propensity score adjustment to estimate outcome in MS.

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