Results Summary

What was the project about?

A randomized controlled trial, or RCT, is the best way to compare how well different treatments work to improve patients’ health. In RCTs, researchers assign patients to treatment groups by chance. But RCTs aren’t always an option due to high costs or ethical concerns. In these cases, researchers use other types of study designs such as

  • Cohort studies, which look at patients’ data over time to see how a treatment affects the risk of a certain health event, such as a heart attack
  • Case-control studies, which compare data from patients who did and didn’t have a certain health event

These designs often use data from health records to compare treatment results. In these studies, researchers use statistical methods to make results more like results from RCTs. Current methods work well for cohort studies but not for case-control studies.

In this study, the research team created and tested new methods and a guide to analyze case-control studies so that results would be more like results from an RCT.

What did the research team do?

The research team talked with researchers who do case-control studies. The team used what they learned to create the new methods and a guide. The guide explained how to use the new methods for case-control studies. The team then asked the researchers for feedback to improve the guide.

To test the guide and new methods, the research team used health records from patients receiving care at health systems in Washington State. The team did a case-control and cohort study to look at whether statins, a medicine to lower cholesterol, helped prevent heart attacks. Next, the team compared the results from previous RCTs of statins to results from

  • The new methods for case-control studies
  • Current methods for case-control studies
  • Current methods for cohort studies

What were the results?

The guide had information on how to mimic an RCT with case-control data and how to set up data for analysis. The research team also created a computer program to analyze case-control data.

Compared with current methods for case-control and cohort studies, the new methods for case-control studies got more accurate results.

What were the limits of the project?

The new methods only work when researchers collect data at multiple time points. The research team tested the new methods using data for one treatment for heart attacks.

Future research could test if the new methods work for other health problems or treatments.

How can people use the results?

Researchers can use the guide and computer program when designing case-control studies.

Final Research Report

View this project's final research report.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

  • The reviewers lauded the strengths of this report and requested minor changes, focusing largely on the investigators providing more information on the similarities and differences of cohort and case-control observational research designs. The researchers added language to describe the similarities and differences in these two approaches, as well as provided previously published explanations of the theoretical background behind the approaches the researchers evaluated in this study.
  • The reviewers noted that there were demographic differences in patient characteristics between the cohort and case-control samples and wondered if these differences could lead to bias that would make the results of the cohort and case-control comparison different from results of similar analyses between either of these designs and a randomized trial design.  The researchers acknowledged that there were differences in prevalence of hypertension and use of antihypertensives between the cohort and case-control study design results. However, the researchers stated that they did not expect the same demographic factors to affect the comparison of these two study designs because previous meta-analyses have not demonstrated that these factors led to differences in other studies of antihypertensives and myocardial infarction.

Conflict of Interest Disclosures

Project Information

Goodarz Danaei, MD, MS, DSc
Harvard T.H. Chan School of Public Health
Causal Analyses of Nested Case-Control Studies for Comparative Effectiveness Research

Key Dates

August 2017
March 2021

Study Registration Information


Has Results
Award Type
Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: April 11, 2024