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 original principal investigator of this project did not work on the Final Research Report.  Another investigator, Michelle Denburg, MD, MSCE, completed the project and prepared the Final Research Report for peer review. For this reason, peer reviewers focused their comments on aim 3 of the project. The methods and results from aim 1 of this project have been published.
  • The reviewers commented that the analyses used in aim 3 of the project did not in fact involve an adaptation of the prior event rate ratio (PERR) as originally described. The statistical methods were in fact conventional methods to account for measured confounders only. The researchers conceded that they did not use an adaptation of PERR for this aim to account for unmeasured confounders in the analyses because the outcome involved a change over time rather than a single event. However, the researchers stated that they applied the key PERR assumption that the ratio between outcome event rates in the treatment-exposed group compared to the treatment-unexposed group prior to the start of the exposure interval should incorporate the effect of all confounders. Similarly, although the researchers did not directly use the posttreatment event rate ratio (PTERR) that they developed in the aim 3 analyses of composite renal outcome, they stated that they applied PTERR assumptions to their analyses. They applied these assumptions in that they contrasted the drug exposure periods with the unexposed periods and use those contrasts to estimate the effect of unmeasured confounders. They revised the description of aim 3 to align with these peer-reviewer observations.
  • The reviewers noted that the original PERR adjustment method is biased and asked why the researchers did not use the revised PERR-alt method, which they considered unbiased, in their aim 1 analyses. The researchers explained that the PERR-alt method cannot be directly applied to the outcome of death because death can only happen once, and the PERR-alt method requires that an outcome can occur in both time periods assessed. Instead, the researchers applied the PTERR method in this study.
  • The reviewers noted that the study considered event rates before treatment when adjusting for baseline differences between treatment groups. However, many epidemiological studies exclude people with previous occurrences of an outcome so they can focus on new-onset disease and because patients with new-onset disease often have different risk factors than patients who have a subsequent event, rather than a new one. The researchers acknowledged that PERR may not be the best analytic strategy for studying new-onset disease. However, they said that mixing the concepts of new-onset disease and secondary prevention allows results to be generalizable to a broader population.

Conflict of Interest Disclosures

Project Information

Richard L. Tannen, MD
University of Pennsylvania
$1,105,535
10.25302/09.2020.ME.131006601
New Analytic Approach for Valid Comparative Effectiveness Research

Key Dates

July 2014
February 2020
2014
2020

Study Registration Information

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Last updated: March 4, 2022