Dataset Information

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

ABSTRACT: 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.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.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.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.ClinicalTrials.gov: NCT01134484 May 28, 2010 (retrospectively registered) EudraCT: 2005-003723-39 December 17, 2008 (retrospectively registered).

SUBMITTER: Pezzi A

PROVIDER: S-EPMC5103416 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Pezzi Annalisa A Cavo Michele M Biggeri Annibale A Zamagni Elena E Nanni Oriana O

BMC medical research methodology 20161109 1

<h4>Background</h4>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 t ...[more]

PMID: 27829371

Similar Datasets

Project description:Aim: The phase III randomized controlled trial (RCT) CARTITUDE-4 (NCT04181827) demonstrated superiority of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) over daratumumab, pomalidomide and dexamethasone (DPd) and pomalidomide, bortezomib and dexamethasone (PVd) for relapsed/refractory multiple myeloma (RRMM) patients who have received one to three prior line(s) of therapy (LOT[s]) including an immunomodulatory agent and a proteasome inhibitor, and are refractory to lenalidomide. These analyses estimate the relative efficacy between cilta-cel and other common treatment regimens, for which no direct comparative evidence is available. Materials & methods: Patient data were available from the CARTITUDE-4, CASTOR, CANDOR and APOLLO RCTs. Imbalances between cohorts on key patient characteristics were adjusted for using inverse probability of treatment weighting (IPTW). Relative efficacies were estimated with response rate ratios (RRs) and 95% confidence intervals (CIs) for overall response rate (ORR), very good partial response or better rate (≥VGPR) and complete response or better rate (≥CR), and with hazard ratios (HRs) and 95% CIs for progression-free survival (PFS). Sensitivity analyses using different analytical methods and additional covariates were explored. Results: Key characteristics were well balanced across cohorts after IPTW. Cilta-cel showed statistically significant benefit in PFS (HRs: 0.11-0.51), ≥VGPR (RRs: 1.51-5.13) and ≥CR (RRs: 2.90-35.24) versus all comparators, and statistically significant improvements in ORR over most comparator regimens (RRs: 1.22-1.90). Results were consistent across sensitivity analyses. Conclusion: Cilta-cel demonstrated benefit over other common treatment regimens, highlighting its potential to become a new standard of care option for lenalidomide-refractory RRMM patients with one to three prior LOT(s). These comparisons help to demonstrate the improved efficacy of cilta-cel in countries where the standard of care may differ from DPd/PVd.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets