A novel approach for identifying and addressing case-mix heterogeneity in individual participant data meta-analysis

Res Synth Methods. 2019 Dec;10(4):582-596. doi: 10.1002/jrsm.1382. Epub 2019 Dec 2.

Abstract

Case-mix heterogeneity across studies complicates meta-analyses. As a result of this, treatments that are equally effective on patient subgroups may appear to have different effectiveness on patient populations with different case mix. It is therefore important that meta-analyses be explicit for what patient population they describe the treatment effect. To achieve this, we develop a new approach for meta-analysis of randomized clinical trials, which use individual patient data (IPD) from all trials to infer the treatment effect for the patient population in a given trial, based on direct standardization using either outcome regression (OCR) or inverse probability weighting (IPW). Accompanying random-effect meta-analysis models are developed. The new approach enables disentangling heterogeneity due to case mix from that due to beyond case-mix reasons.

Keywords: causal inference; direct standardization; inverse probability weighting; meta-analysis; outcome regression; transportability.

MeSH terms

  • Adolescent
  • Clinical Trials as Topic
  • Comparative Effectiveness Research
  • Computer Simulation
  • Diagnosis-Related Groups*
  • Dietary Supplements*
  • Humans
  • Male
  • Meta-Analysis as Topic*
  • Observational Studies as Topic
  • Outcome Assessment, Health Care*
  • Predictive Value of Tests
  • Probability
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Regression Analysis
  • Research Design
  • Respiratory Tract Infections / therapy*
  • Treatment Outcome
  • Vitamin D / therapeutic use*
  • Young Adult

Substances

  • Vitamin D