Calendar time as an instrumental variable in assessing the risk of heart failure with antihyperglycemic drugs. Issue 8 (26th June 2018)

• Record Type: Journal Article
• Authors: Gokhale, Mugdha; Buse, John B.; DeFilippo Mack, Christina; Jonsson Funk, Michele; Lund, Jennifer; Simpson, Ross J.; Stürmer, Til
• Is Part Of: Pharmacoepidemiology and drug safety. Volume 27:Issue 8(2018)
• Page Start: 857
• Page End: 866
• Publication Date: 2018-06-26
• Subjects: calendar time -- instrumental variables -- pharmacoepidemiology; Pharmacoepidemiology -- Periodicals; Chemotherapy -- Periodicals; Epidemiology -- Periodicals; 615.705
• DOI: 10.1002/pds.4578
• Languages: English
• ISSNs: 1053-8569

Abstract

Abstract: Objective: In recent years, second‐line diabetes treatment with dipeptidyl peptidase–4 inhibitors (DPP‐4i) increased with a corresponding decrease in thiazolidinediones (TZDs). Using hospitalization for heart failure (HF) as a positive control outcome, we explored the use of calendar time as an instrumental variable (IV) and compared this approach to an active comparator new‐user study. Methods: We identified DPP‐4i or TZD initiators after a 6‐month washout using Medicare claims 2006–2013. The IV was defined as a binary variable comparing initiators during October 2010 to December 2013 (postperiod) versus January 2008 to May 2010 (preperiod). We examined IV strength and estimated risk differences (RDs) for HF using Kaplan‐Meier curves, which were compared with propensity score (PS)–weighted RD for DPP‐4i versus TZD. Results: The IV compared 22 696 initiators (78% DPP‐4i) in the postperiod versus 20 283 initiators (38% DPP‐4i) in the preperiod, resulting in 40% compliance. The active‐comparator (PS‐weighted) approach compared 26 198 DPP‐4i and 18 842 TZD initiators. Covariate balance across IV levels was slightly better than across treatments (standardized difference, 3% vs 4.5%). The 1‐ and 2‐year local average treatment effects of RD of HF per 100 patients in the "compliers" (95% confidence intervals) were −0.62 (−0.99 to −0.25) and −0.88 (−1.46 to −0.25). Corresponding PS‐weighted results were −0.20 (−0.33 to −0.05) and −0.18 (−0.30 to 0.03). Conclusion: Both approaches indicated lesser risk of HF hospitalizations among DPP‐4i vs TZD initiators. The magnitude of the estimated effects may differ due to differences in the target populations and assumptions. Calendar time can be leveraged as an IV when market dynamics lead to profound changes in treatments.