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Original Investigation
January 2018

Examining Bias in Studies of Statin Treatment and Survival in Patients With Cancer

Author Affiliations
  • 1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 2Institute of Health and Society, University of Oslo, Oslo, Norway
  • 3Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Sweden
  • 4Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 5Harvard-MIT Division of Health Science and Technology, Boston, Massachusetts
JAMA Oncol. 2018;4(1):63-70. doi:10.1001/jamaoncol.2017.2752
Key Points

Question  Does selection and immortal-time bias influence the findings in studies of use of statin therapy that report reduced early cancer-specific and all-cause mortality in patients with recently diagnosed prostate, breast, colorectal, or bladder cancer?

Findings  In patients with cancer identified through the SEER-Medicare database, the hazard ratios of mortality were 1 in comparisons between those who began statin therapy and those who did not. Strong, apparently beneficial effects of statin therapy use estimated by previous observational studies are likely owing to selection bias and immortal-time bias, biases that can be prevented with an appropriate study design.

Meaning  An explicit target trial emulation helps avoid misleading estimates and found no evidence that initiation of statin therapy improves 3-year 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.

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