Abstract
BackgroundRandomization 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.MethodsWe 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.ResultsWe 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.ConclusionsPS-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 registrationClinicalTrials.gov: NCT01134484 May 28, 2010 (retrospectively registered)EudraCT: 2005-003723-39 December 17, 2008 (retrospectively registered)
Highlights
Randomization procedure in randomized controlled trials (RCTs) permits an unbiased estimation of causal effects
The evaluation of a specific phase is complicated because it may be biased by different compliance to the previous phases
The aim of this article was to evaluate the effect of the consolidation therapy, the last phase of a complex therapeutic strategy composed by two arms of induction therapy randomly administered to prepare patients to receive at least one autologous stem cell transplantation (ASCT), in patients with previously untreated multiple myeloma
Summary
Randomization procedure in randomized controlled trials (RCTs) permits an unbiased estimation of causal effects. 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. It is possible that some patients are more likely to be treated than others (possibly depending on prognostic factors) in which case treatment may erroneously appear more efficacious [3,4,5]. Another important issue is that RCTs usually compare the entire therapeutic strategy without any detailed evaluation of each singular therapeutic phase. During the course of a trial, especially when the study protocol is complex and the disease is severe, randomization balance may be lost right from the earliest phases due to selective patient withdrawal between one phase and another
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
