Registration, publication, and outcome reporting among pivotal clinical trials that supported FDA approval of high-risk cardiovascular devices before and after FDAAA

Matthew J Swanson,Joseph S Ross,James L Johnston

doi:10.1186/s13063-021-05790-9

Abstract

BackgroundSelective registration, publication, and outcome reporting of clinical trials distort the primary clinical evidence that is available to patients and clinicians regarding the safety and efficacy of US Food and Drug Administration (FDA)-approved medical devices. The purpose of this study is to compare registration, publication, and outcome reporting among pivotal clinical trials that supported FDA approval of high-risk (class III) cardiovascular devices before and after the FDA Amendment Act (FDAAA) was enacted in 2007.MethodsUsing publicly available data from ClinicalTrials.gov, FDA summaries, and PubMed, we determined registration, publication, and reporting of findings for all pivotal clinical studies supporting FDA approval of new high-risk cardiovascular devices between 2005 and 2020, before and after FDAAA. For published studies, we compared both the primary efficacy outcome with the FDA’s Premarket Approval (PMA) primary efficacy outcome and the published interpretation of findings with the FDA reviewer’s interpretation (positive, equivocal, or negative).ResultsBetween 2005 and 2020, the FDA approved 156 high-risk cardiovascular devices on the basis of 165 pivotal trials, 48 (29%) of which were categorized as pre-FDAAA and 117 (71%) as post-FDAAA. Post-FDAAA, pivotal clinical trials were more likely to be registered (115 of 117 (98%) vs 24 of 48 (50%); p < 0.001), to report results (98 of 117 (87%) vs 7 of 48 (15%); p < 0.001) on ClinicalTrials.gov, and to be published (100 or 117 (85%) vs 28 of 48 (58%); p < 0.001) in peer-reviewed literature when compared to pre-FDAAA. Among published trials, rates of concordant primary efficacy outcome reporting were not significantly different between pre-FDAAA trials and post-FDAAA trials (24 of 28 (86%) vs 96 of 100 (96%); p = 0.07), nor were rates of concordant trial interpretation (27 of 28 (96%) vs 93 of 100 (93%); p = 0.44).ConclusionsFDAAA was associated with increased registration, result reporting, and publication for trials supporting FDA approval of high-risk medical devices. Among published trials, rates of accurate primary efficacy outcome reporting and trial interpretation were high and no different post-FDAAA.

Highlights

Selective registration, publication, and outcome reporting of clinical trials distort the primary clinical evidence that is available to patients and clinicians regarding the safety and efficacy of US Food and Drug Administration (FDA)-approved medical devices
FDA Amendment Act (FDAAA) was associated with increased registration, result reporting, and publication for trials supporting FDA approval of high-risk medical devices
We excluded Automated External Defibrillator (AED) because FDA published a final order on January 29, 2015, stating that AED clinical study information can be leveraged from both published studies and clinical data previously submitted under the 510(k) process instead of requiring the conduct of a pivotal trial to support FDA approval [17]

Summary

Introduction

Publication, and outcome reporting of clinical trials distort the primary clinical evidence that is available to patients and clinicians regarding the safety and efficacy of US Food and Drug Administration (FDA)-approved medical devices. The purpose of this study is to compare registration, publication, and outcome reporting among pivotal clinical trials that supported FDA approval of high-risk (class III) cardiovascular devices before and after the FDA Amendment Act (FDAAA) was enacted in 2007. Pivotal clinical studies are generally the primary clinical evidence on which the FDA bases its approval decisions because they are designed to meet the aforementioned regulatory requirements, demonstrating both the safety and efficacy of the device for the intended use [4]. Given the widespread use of high-risk medical devices in clinical practice, the quality and transparency of clinical data supporting their approval are of paramount importance to patient health and wellbeing [5]

Objectives

Methods

Results