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BMC Medical Research Methodology
Published in: BMC Medical Research Methodology 1/2016

Open Access 01-12-2016 | Research article

Inverse probability weighting to estimate causal effect of a singular phase in a multiphase randomized clinical trial for multiple myeloma

Authors: Annalisa Pezzi, Michele Cavo, Annibale Biggeri, Elena Zamagni, Oriana Nanni

Published in: BMC Medical Research Methodology | Issue 1/2016

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Abstract

Background

Randomization procedure in randomized controlled trials (RCTs) permits an unbiased estimation of causal effects. However, in clinical practice, differential compliance between arms may cause a strong violation of randomization balance and biased treatment effect among those who comply. We evaluated the effect of the consolidation phase on disease-free survival of patients with multiple myeloma in an RCT designed for another purpose, adjusting for potential selection bias due to different compliance to previous treatment phases.

Methods

We computed two propensity scores (PS) to model two different selection processes: the first to undergo autologous stem cell transplantation, the second to begin consolidation therapy. Combined stabilized inverse probability treatment weights were then introduced in the Cox model to estimate the causal effect of consolidation therapy miming an ad hoc RCT protocol.

Results

We found that the effect of consolidation therapy was restricted to the first 18 months of the phase (HR: 0.40, robust 95 % CI: 0.17-0.96), after which it disappeared.

Conclusions

PS-based methods could be a complementary approach within an RCT context to evaluate the effect of the last phase of a complex therapeutic strategy, adjusting for potential selection bias caused by different compliance to the previous phases of the therapeutic scheme, in order to simulate an ad hoc randomization procedure.

Trial registration

ClinicalTrials.gov: NCT01134484 May 28, 2010 (retrospectively registered)
EudraCT: 2005-003723-39 December 17, 2008 (retrospectively registered)
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Metadata
Title
Inverse probability weighting to estimate causal effect of a singular phase in a multiphase randomized clinical trial for multiple myeloma
Authors
Annalisa Pezzi
Michele Cavo
Annibale Biggeri
Elena Zamagni
Oriana Nanni
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medical Research Methodology / Issue 1/2016
Electronic ISSN: 1471-2288
DOI
https://doi.org/10.1186/s12874-016-0253-9

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