A Systematic Review of NHLBI-funded Cardiovascular Clinical Trials and the Impact of the NIH Revitalization Act on the Enrollment of Women and Reporting of Sex-Specific Outcomes in Primary Findings Publications Open Access

Abstract

The establishment of new laws and policies that address public health issues can serve as a powerful tool to initiate change in public health practice. The NIH Revitalization Act of 1993, was implemented to ensure the inclusion of women and underrepresented minorities in NIH funded clinical trials. In the United States, cardiovascular disease (CVD) is the leading cause of death among women (T. Shah, Palaskas, & Ahmed, 2016). Historically the overriding belief in the biomedical community was the inclusion of women in clinical trials caused inconsistencies and invalid findings. Progress has been made in the inclusion of women in clinical trials since the passage of the 1993 NIH Revitalization Act, yet these changes have not translated to equity in the inclusion of women in cardiovascular clinical trials according to disease prevalence or the reporting of sex-specific outcomes in primary results publications. In this systematic review, Clinical Trials.gov was accessed to identify NHLBI funded CVD clinical trials and the unique "NCT" Clinical trial.gov identification numbers were used to retrieve primary results publications in PUBMED. The primary result publications that were located were used to assess the enrollment of women in CVD clinical trials, whether there were outcomes by CVD area, prevention type, and if the clinical trials addressed sex-specific outcomes in the primary results papers. Results showed a higher proportion of men (59.5%) enrolled in the NHLBI funded CVD clinical trials that were included in this systematic, compared to women (40.5%) (95% CI: 40.17%, 40.63%). Only 20 of the 142 CVD trials (14.1%) reported on sex-specific outcomes in the results, discussion and/or conclusion sections and 122 (85.9%) of the 142 CVD trials with published primary results papers did not address sex outcomes in the results, discussion or conclusion sections. The results suggest that improvements have been made with regards to the inclusion of women in CVD trials when compared to previously published systematic reviews, however the reporting of sex-specific outcomes in primary results papers still demonstrate that few publications report on sex-specific outcomes in CVD trials.

Table of Contents

Chapter 1: Introduction

Introduction ........................................................................................................................1

Background Regarding Inclusion of Women in NIH Funded Research

and the 1993 NIH Revitalization Act ......................................................................................3

The NIH Revitalization Act and NHLBI Inclusion Policy...........................................................5

Problem Statement ..............................................................................................................6

Theoretical Framework .........................................................................................................7

Purpose Statement ...............................................................................................................8

Research Questions ...............................................................................................................8

Significance Statement ..........................................................................................................9

Terms and Definitions and Abbreviations ..............................................................................11

Chapter 2: Literature Review

Introduction ........................................................................................................................16

Cardiovascular Disease in Women: Prevalence and Sex Dfferences ..........................................16

Underrepresentation of Women in Clinical Trials ..................................................................18

Criticisms Regarding the 1993 NIH Revitalization Act ............................................................21

Systematic Reviews Evaluating the 1993 NIH Revitalization Act .............................................24

Summary of Current Problem and Study Relevance................................................................28

Chapter 3: Methodology

Introduction........................................................................................................................29

Background of ClinicalTrials.gov...........................................................................................29

Population and Sample.........................................................................................................30

Research Design and Procedures ...........................................................................................30

Data Analysis Methodology...................................................................................................33

Study Limitations and Delimitations .....................................................................................34

Chapter 4: Results

Introduction .......................................................................................................................37

Key Findings .......................................................................................................................38

Inclusion of Women in CVD Trials by CVD Area ....................................................................39

Acute Coronary Syndrome & Myocardial Infarction ..............................................................41

Cardiac Arrest & Resuscitation ............................................................................................41

Cardiac Surgery ...................................................................................................................42

Coronary Heart Disease .......................................................................................................43

Heart Failure .......................................................................................................................44

Pediatric and Congenital Heart Disease .................................................................................45

Primary Prevention of Cardiovascular Disease .......................................................................46

Secondary Prevention of Cardiovascular Disease ....................................................................47

Vascular Diseases ................................................................................................................48

Enrollment of Women in CVD Clinical Trials by Prevention Type ............................................49

Enrollment of Women in CVD Clinical Trials by Primary Publications Year...............................50

Primary Publications Papers Repoirting on Sex-Specific Outcomes .........................................52

CVD Clinical Trials with Subsequent Paper Published After Primary

Findings and Sex-Specific Outcomes .....................................................................................53

Summary ............................................................................................................................53

Chaper 5: Discussion

Introduction .......................................................................................................................55

Summary of Study ...............................................................................................................55

Limitations .........................................................................................................................57

Implications .......................................................................................................................58

Conclusion and Recommendations .......................................................................................59

References ..........................................................................................................................62

List of Figures and Tables

Fig 1: Systematic Review Flow Chart ......................................................................................36

Table 1: Overall Enrollment in CVD Clinical Trials by Sex .......................................................38

Table 2: Breakdown of the Enrollment by Sex for Nine Cardiovascular

Disease Area Categories .......................................................................................................40

Table 3: Total Enrollment by Sex for Primary Prevention CVD Trials.........................................49

Table 4: Total Enrollment by Sex for Secondary Prevention CVD Trials.....................................50

Table 5: Primary Results Publication Dates of CVD Trials

and Enrollment by Sex..........................................................................................................51

Table 6: Publication Year Groupings for CVD Trials and Enrollment by Sex...............................52

About this Master's Thesis

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School	Rollins School of Public Health
Department	Executive Masters of Public Health
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health
Keyword	Cardiovascular Women Outcomes
Committee Chair / Thesis Advisor	O'Connor, Jean, Emory University
Committee Members	Desvigne-Nickens, Patrice, NHLBI
Partnering Agencies	US (Federal) agency other than CDC

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