Inverse probability weighting to control for censoring in a post hoc analysis of quality-adjusted survival data from a clinical trial of temsirolimus for renal cell carcinoma

Abstract

Objective:

This post hoc analysis evaluated treatment-associated quality-adjusted survival (QAS) in patients randomly assigned to temsirolimus or interferon alfa (IFN-alfa), corrected for censoring using inverse probability weighting (IPW), in the Advanced Renal Cell Carcinoma (ARCC) trial.

Methods:

Follow-up was divided into 11 time intervals; Kaplan–Meier estimates for not being censored were estimated for each interval. The QAS for each interval was weighted by the inverse probability of not being censored in that interval. Overall treatment-associated QAS was calculated as the sum of the weighted QAS across all follow-up intervals. Differences in mean QAS between temsirolimus and IFN-alfa were evaluated with t-statistics at a two-sided α = 0.05.

Results:

In total, 416 patients were randomly assigned to temsirolimus (n = 209) or IFN-alfa (n = 207); 400 patients were included in this analysis. Overall weighted mean (standard deviation) QAS during progression-free survival was 111.9 (5.3) days with temsirolimus (n = 204) and 75.7 (6.3) days with IFN-alfa (n = 196). The mean weighted QAS difference of 36.2 days in favor of temsirolimus was significant (p < 0.05).

Limitations:

One potential limitation is that the weights developed by the Kaplan–Meier estimates did not allow for covariates to be adjusted among treatment arms. Another possible limitation is that the ARCC trial included patients with advanced renal cell carcinoma, and thus it cannot be conclusively determined how our findings would apply to patients with less advanced disease.

Conclusions:

Patients with poor-prognosis advanced renal cell carcinoma treated with temsirolimus had an incremental gain of 48% (36.2 days) in QAS compared with patients treated with IFN-alfa.

Key words::

• Health outcomes research
• Inverse probability weighting
• Quality-adjusted survival
• Renal cell carcinoma

Transparency

Declaration of funding

This study and its report were supported by Pfizer Inc.

Declaration of financial/other relationships

S.R. is an employee of Med Data Analytics, Inc., a paid consultant for Pfizer Inc.; M.J.A. reports no potential conflicts; and all other authors were employees of the study sponsor at the time of the study.

Acknowledgments

Assistance in manuscript preparation was provided by Sara Glickstein, PhD, and Stephen W. Gutkin, Rete Biomedical Communications Corp. (Wyckoff, NJ, USA), with financial support from the study sponsor (Pfizer Inc.).