Ten Rules for Conducting Retrospective Pharmacoepidemiological Analyses: Example COVID-19 Study

Michael Powell, Allison Koenecke, James Brian Byrd, Akihiko Nishimura, Maximilian F. Konig, Ruoxuan Xiong, Sadiqa Mahmood, Vera Mucaj, Chetan Bettegowda, Liam Rose, Suzanne Tamang, Adam Sacarny, Brian Caffo, Susan Athey, Elizabeth A. Stuart, Joshua T. Vogelstein

Research output: Contribution to journalArticlepeer-review


Since the beginning of the COVID-19 pandemic, pharmaceutical treatment hypotheses have abounded, each requiring careful evaluation. A randomized controlled trial generally provides the most credible evaluation of a treatment, but the efficiency and effectiveness of the trial depend on the existing evidence supporting the treatment. The researcher must therefore compile a body of evidence justifying the use of time and resources to further investigate a treatment hypothesis in a trial. An observational study can provide this evidence, but the lack of randomized exposure and the researcher’s inability to control treatment administration and data collection introduce significant challenges. A proper analysis of observational health care data thus requires contributions from experts in a diverse set of topics ranging from epidemiology and causal analysis to relevant medical specialties and data sources. Here we summarize these contributions as 10 rules that serve as an end-to-end introduction to retrospective pharmacoepidemiological analyses of observational health care data using a running example of a hypothetical COVID-19 study. A detailed supplement presents a practical how-to guide for following each rule. When carefully designed and properly executed, a retrospective pharmacoepidemiological analysis framed around these rules will inform the decisions of whether and how to investigate a treatment hypothesis in a randomized controlled trial. This work has important implications for any future pandemic by prescribing what we can and should do while the world waits for global vaccine distribution.

Original languageEnglish (US)
Article number700776
JournalFrontiers in Pharmacology
StatePublished - Jul 28 2021


  • COVID-19
  • drug repurposing
  • observational study
  • pharmacoepidemiology
  • retrospective analyses

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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