Results Summary

What was the research about?

Research studies called clinical trials test treatments to see if they are safe and effective for patients. When designing clinical trials, researchers must plan to include enough patients with different traits for the study to have accurate results. Once the study starts, researchers must follow the plan. Sometimes, early results from a trial show that a group of patients with a certain trait may have more benefits or harms from the treatment than other groups. For example, the treatment may not work for patients with a history of heart disease. In the standard trial design, researchers can’t change the plan to stop enrolling these patients once the trial starts.

In this study, the research team compared the standard trial design with more flexible approaches known as adaptive enrichment designs. These designs set up rules that allow researchers to change the study plan. For example, if early results show a treatment doesn’t work for patients with heart disease, researchers can stop enrolling these patients in the trial. The team compared the trial designs using data from four completed trials.

What were the results?

Compared with the standard designs used in the example trials, the adaptive enrichment designs

  • Had more accurate results
  • Needed fewer patients in the overall trial
  • Needed more patients to show that a treatment had a benefit or harm for a specific group

What did the research team do?

The research team developed different methods for designing clinical trials. To test these methods, the team used information from the four completed studies. Then the team created a computer program to help researchers choose a study design for future clinical trials. The program compares the standard and adaptive enrichment designs to predict

  • How many patients would need to take part in a clinical trial to have accurate results
  • How many patients with a specific trait would need to take part in the trial to show that the treatment has a benefit or harm for that group

What were the limits of the study?

The study tested the methods with only four example trials. The adaptive enrichment designs allowed researchers to look at the effect of treatment on only one specific group of patients in the clinical trial.

Future research could develop study designs that focus on the benefits or harms for more than one group of patients.

How can people use the results?

Researchers can use the computer program to choose a trial design and plan for the number of patients needed to take part in the trial.

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:

  • Reviewers noted that in adaptive enrichment trial designs, researchers had many design decisions to make. Those decisions could have affected the validity of the study, such as when to include interim analyses and how many, and researchers could have provided in the report additional, useful guidance about how to approach such decisions. The researchers responded that they would prefer not to provide general guidance on these study-specific choices. Instead, the software the researchers created provides a range of options that clinical investigators can explore as part of designing an adaptive enrichment trial.
  • Reviewers asked whether the results of the sensitivity analyses could be presented in a table with quantitative findings clearly provided. The researchers explained that this might require substantial space to explain the simulation step, and that a qualitative presentation through plots, would be more useful to the report overall. 

Conflict of Interest Disclosures

Project Information

Michael Rosenblum, PhD
Johns Hopkins Bloomberg School of Public Health
$1,069,177 *
Innovative Randomized Trial Designs to Generate Stronger Evidence about Subpopulation Benefits and Harms

Key Dates

December 2013
September 2018

Study Registration Information

Final Research Report

View this project's final research report.

Journal Articles


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
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: January 20, 2023