Examining bias in studies of statin treatment and survival in patients with cancer

Abstract

IMPORTANCE Patients with cancer who use statins appear to have a substantially better survival than nonusers in observational studies. However, this inverse association between statin use and mortality may be due to selection bias and immortal-time bias.

OBJECTIVE To emulate a randomized trial of statin therapy initiation that is free of selection bias and immortal-time bias.

DESIGN, SETTING, AND PARTICIPANTS We used observational data on 17 372 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2009) with complete follow-up until 2011. The SEER-Medicare database links 17 US cancer registries and claims files from Medicare and Medicaid in 12 US states. We included individuals with a new diagnosis of colorectal, breast, prostate, or bladder cancer who had not been prescribed statins for at least 6 months before the cancer diagnosis. Individuals were duplicated, and each replicate was assigned to either the strategy "statin therapy initiation within 6 months after diagnosis" or "no statin therapy initiation." Replicates were censored when they stopped following their assigned strategy, and the potential selection bias was adjusted for via inverse-probability weighting. Hazard ratios (HRs), cumulative incidences, and risk differences were calculated for all-cause mortality and cancer-specific mortality. We then compared our estimates with those obtained using the same analytic approaches used in previous observational studies.

EXPOSURES Statin therapy initiation within 6 months after cancer diagnosis.

MAIN OUTCOMES AND MEASURES Cancer-specific and all-cause mortality using SEER-Medicare data and data from previous studies. RESULTS Of the 17 372 patients whose data were analyzed, 8440 (49%) were men, and 8932 (51%) were women (mean [SD] age, 76.4 [7.4] years; range, 66-115 years). The adjusted HR (95% CI) comparing statin therapy initiation vs no initiation was 1.00 (0.88-1.15) for cancer-specific mortality and 1.07 (0.93-1.21) for overall mortality. Cumulative incidence curves for both groups were almost overlapping (the risk difference never exceeded 0.8%). In contrast, the methods used by prior studies resulted in an inverse association between statin use and mortality (pooled hazard ratio 0.69).

CONCLUSION AND RELEVANCE After using methods that are not susceptible to selection bias from prevalent users and to immortal time bias, we found that initiation of therapy with statins within 6 months after cancer diagnosis did not appear to improve 3-year cancer-specific or overall survival.