Strong instrumental variables biased propensity scores in comparative effectiveness research: A case study in oncology

J Clin Epidemiol. 2023 Mar:155:31-38. doi: 10.1016/j.jclinepi.2023.01.002. Epub 2023 Jan 16.

Abstract

Background and objectives: Some medications require specific medical procedures in the weeks before their start. Such procedures may meet the definition of instrumental variables (IVs). We examined how they may influence treatment effect estimation in propensity score (PS)-adjusted comparative studies, and how to remedy.

Study design and setting: Different covariate assessment periods (CAPs) did and did not include the month preceding treatment start were used to compute PS in the French claims database (Sytème National des Données de Santé-SNDS), and 1:1 match patients with metastatic castration resistant prostate cancer initiating abiraterone acetate or docetaxel. The 36-month survival was assessed.

Results: Among 1, 213 docetaxel and 2, 442 abiraterone initiators, the PS distribution resulting from the CAP [-12; 0 months] distinctly separated populations (c = 0.93; 273 matched pairs). The CAPs [-12;-1 months] identified 765 pairs (c = 0.81). Strong docetaxel treatment predictors during the month before treatment start were implantable delivery systems (1% vs. 59%), which fulfilled IV conditions. The 36-month survival was not meaningfully different under the [-12; 0 months] CAP but differed by 10% points (38% vs. 28%) after excluding month -1.

Conclusion: In the setting of highly predictive pretreatment procedures, excluding the immediate pre-exposure time from the CAP will reduce the risk of including potential IVs in PS models and may reduce bias.

Keywords: Bias; Instrumental variables; Matching; Propensity score; Prostate cancer; SNDS.

MeSH terms

  • Comparative Effectiveness Research
  • Docetaxel / therapeutic use
  • Humans
  • Male
  • Propensity Score
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Retrospective Studies
  • Taxoids / therapeutic use
  • Treatment Outcome

Substances

  • Docetaxel
  • Taxoids