Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jul 18;18(1):333.
doi: 10.1186/s13063-017-2068-3.

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting

Adam T Phillips  1 , Nihar R Desai  2   3 , Harlan M Krumholz  2   3   4   5 , Constance X Zou  6 , Jennifer E Miller  7 , Joseph S Ross  8   9   10   11
Affiliations
Review

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting

Adam T Phillips et al. Trials. .

Abstract

Background: Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry.

Methods: Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation.

Results: Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive.

Conclusions: FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

Keywords: Clinical trials; Drug approval; Publications; United States Food and Drug Administration.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Because our examination of trial publications did not involve human subjects, ethics committee review was not required by the Yale University Human Research Protection Program. Consent to participate not applicable.

Consent for publication

Not applicable.

Competing interests

NRD, HMK, and JSR receive support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Blue Cross Blue Shield Association to better understand medical technology evaluation, and from the Centers of Medicare and Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting. HMK and JSR receive support through Yale University from Medtronic, Inc. and the US FDA to develop methods for postmarket surveillance of medical devices. HMK, JEM, and JSR receive support through Yale University and New York University, respectively, from the Laura and John Arnold Foundation to better understand clinical research integrity and transparency. HMK reports that he chairs a scientific advisory board for UnitedHealthcare. ATP and CXZ declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Sample construction of novel therapeutic agents in cardiovascular disease and diabetes approved by the US Food and Drug Administration between 2005 and 2014
Fig. 2
Fig. 2
FDA reviewer trial interpretation and publication, along with published interpretation of the trial findings, for novel therapeutic agents in cardiovascular disease and diabetes approved by the US FDA between 2005 and 2014, pre and post the Food and Drug Administration Amendment Act (FDAAA). FDA reviewer trial interpretation as positive, equivocal, or negative
Fig. 3
Fig. 3
FDA reviewer trial interpretation and publication, along with published interpretation of the trial findings, for all novel therapeutic agents in cardiovascular disease and diabetes approved by the US Food and Drug Administration (FDA) between 2005 and 2014, characterized based on the number of trials (a) and the number of patients participating in the trials (b). FDA reviewer trial interpretation as positive, equivocal, or negative
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. New Drugs: Grounds for Refusing Application; Approval of Application; “Substantial Evidence” Defined, 21 USC §355d. https://www.gpo.gov/fdsys/pkg/USCODE-2010-title21/html/USCODE-2010-title.... Accessed Aug 2016.
    1. Guidance for Industry: Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati.... Accessed Aug 2016.
    1. Smithy JW, Downing NS, Ross JS. Publication of pivotal efficacy trials for novel therapeutic agents approved between 2005 and 2011: a cross-sectional study. JAMA Intern Med. 2014;174(9):1518–20. doi: 10.1001/jamainternmed.2014.3438. - DOI - PMC - PubMed
    1. Miller JE, Korn D, Ross JS. Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012. BMJ Open. 2015;5:e009758. doi:10.1136/bmjopen-2015-009758. - PMC - PubMed
    1. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358(3):252–60. doi: 10.1056/NEJMsa065779. - DOI - PubMed

MeSH terms