History, Policies, and Laws
This page provides information on selected events, policies and laws related to the development and expansion of ClinicalTrials.gov. It is not intended to be comprehensive.
- 1997: Congress Passes Law (FDAMA) Requiring Trial Registration
- 2000: NIH Releases ClinicalTrials.gov Web Site
- 2000–2004: FDA Issues Guidance for Industry Documents
- 2004: ClinicalTrials.gov Wins the Innovations in American Government Award
- 2005: International Committee of Medical Journal Editors Requires Trial Registration
- 2005: State of Maine Passes Clinical Studies Registration Law (Repealed in 2011)
- 2006: World Health Organization Establishes Trial Registration Policy
- 2007: Congress Passes Law (FDAAA) Expanding ClinicalTrials.gov Submission Requirements
- 2008: ClinicalTrials.gov Releases Results Database
- 2008: Declaration of Helsinki Revision Promotes Trial Registration and Results Dissemination
- 2009: Public Meeting Held at the National Institutes of Health
- 2013: European Medicines Agency Expands Clinical Trial Database to Include Summary Results
- Present: Development of Notice of Proposed Rulemaking
1997: Congress Passes Law (FDAMA) Requiring Trial Registration
The first U.S. Federal law to require trial registration was the Food and Drug Administration Modernization Act of 1997 (FDAMA) (PDF).
Section 113 of FDAMA required that the National Institutes of Health (NIH) create a public information resource on certain clinical trials regulated by the Food and Drug Administration (FDA). Specifically, FDAMA 113 required that the registry include information about federally or privately funded clinical trials conducted under investigational new drug applications (INDs) to test the effectiveness of experimental drugs for patients with serious or life-threatening diseases or conditions.
The information in the registry was intended for a wide audience, including individuals with serious or life-threatening diseases or conditions, members of the public, health care providers, and researchers.
2000: NIH Releases ClinicalTrials.gov Web Site
With input from FDA and others, the NIH National Library of Medicine (NLM) developed ClinicalTrials.gov. The first version of ClinicalTrials.gov was made available to the public on February 29, 2000. At the time, ClinicalTrials.gov primarily included NIH-funded studies.
2000–2004: FDA Issues Guidance for Industry Documents
In 2000 FDA issued a draft Guidance for Industry document, which provided recommendations for researchers submitting information to ClinicalTrials.gov. A final guidance document that incorporated comments from the public was issued in 2002.
- FDA Final Guidance, March 2002: Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions (PDF)
In January 2004 FDA proposed a revised draft Guidance for Industry document that included guidance for researchers submitting information required by the Best Pharmaceuticals for Children Act of 2002 (BPCA).
- FDA Draft Guidance, January 2004: Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions (PDF)
2004: ClinicalTrials.gov Wins the Innovations in American Government Award
ClinicalTrials.gov was cited by the Ash Center for Democratic Governance and Innovation at the Harvard Kennedy School as "a successful model for the creation and maintenance of a system that processes and presents large amounts of specialized information to a wide range of users" and was selected as one of five award winners in 2004. The Innovations in American Government Awards is the nation's preeminent program devoted to recognizing and promoting excellence and creativity in the public sector. The program highlights exemplary models of government innovation and advances efforts to address the nation's most pressing public concerns.
- ClinicalTrials.gov Innovations in American Government Awards Site
- National Institutes of Health's ClinicalTrials.gov Web Site Wins Prestigious Award - National Institutes of Health Press Release, 7/28/04
2005: International Committee of Medical Journal Editors Requires Trial Registration
In 2005 the International Committee of Medical Journal Editors (ICMJE) began to require trial registration as a condition of publication.
- Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals ("ICMJE Recommendations") - Clinical Trial Registration
- ICMJE Frequently Asked Questions about Clinical Trials Registration
2005: State of Maine Passes Clinical Studies Registration Law (Repealed in 2011)
In 2005 the State of Maine passed a law requiring prescription drug manufacturers or labelers to submit clinical study registration and results information to ClinicalTrials.gov. The law applied to FDA-approved prescription drugs that are dispensed, administered, delivered, or promoted in Maine.
In 2011 the law was repealed; it is no longer in effect.
- Maine State Public Law, Chapter 461 (PDF): "An Act To Make Certain Prescription Drug Disclosure Laws Consistent with Federal Law" (Enacted on 7/8/11)
2006: World Health Organization Establishes Trial Registration Policy
In 2006 the World Health Organization (WHO) stated that all clinical trials should be registered, and it identified a minimum trial registration dataset of 20 items. In 2007 WHO launched the International Clinical Trials Registry Platform (ICTRP), which includes a search portal providing a single point of access to studies registered in various international registries. The ICTRP Search Portal includes data available on ClinicalTrials.gov.
- WHO ICTRP Web site: WHO International Clinical Trials Registry Platform
2007: Congress Passes Law (FDAAA) Expanding ClinicalTrials.gov Submission Requirements
In 2007 the requirements for submission to ClinicalTrials.gov were expanded after Congress passed the Food and Drug Administration Amendments Act of 2007 (FDAAA) (PDF) Section 801 of FDAAA (FDAAA 801) requires more types of trials to be registered; additional trial registration information; and the submission of summary results, including adverse events, for certain trials. The law also included penalties for noncompliance, such as the withholding of NIH grant funding and civil monetary penalties of up to $10,000 a day.
- ClinicalTrials.gov: See the FDAAA 801 Requirements page
- NIH Office of Extramural Research: Frequently Asked Questions: FDAAA - Further Resources for NIH Grantees
2008: ClinicalTrials.gov Releases Results Database
In September 2008, as required by FDAAA 801, ClinicalTrials.gov began allowing sponsors and principal investigators to submit the results of clinical studies. Submission of adverse event information was optional when the results database was released and became required in September 2009.
- NLM Technical Bulletin: ClinicalTrials.gov to Include Basic Results Data
2008: Declaration of Helsinki Revision Promotes Trial Registration and Results Dissemination
In October 2008, the 59th World Medical Association (WMA) General Assembly amended the Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Two newly added principles (paragraphs 19 and 30) considered prospective registration and public disclosure of study results to be ethical obligations.
In October 2013, the 64th WMA General Assembly modified these two principles. In particular, paragraph 35 (formerly 19) requires prospective registration, as follows: "Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject."
Paragraph 36 (formerly 30) promotes the public disclosure of study results as an ethical obligation and states, in part, "Researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports. All parties [i.e., researchers, authors, sponsors, editors and publishers] should adhere to accepted guidelines for ethical reporting. Negative and inconclusive as well as positive results should be published or otherwise made publicly available."
- WMA: 2013 Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects
- WMA: 2008 Declaration of Helsinki (PDF)
2009: Public Meeting Held at the National Institutes of Health
In accordance with FDAAA 801, NIH held a public meeting in April 2009 to solicit input from interested individuals about future regulations that will expand the information contained in ClinicalTrials.gov.
NIH gathered input on a range of issues, including the submission of adverse events information and the addition of narrative summaries to results submission. Comments on these issues will be used in the development of draft regulations.
- Videocast and podcast of the public meeting
- The meeting transcript, final meeting agenda, list of speakers for public statements, presentations, and public submissions are available at: Regulations.gov under Docket ID: NIH-2009-0002
2013: European Medicines Agency Expands Clinical Trial Database to Include Summary Results
In October 2013, the European Medicines Agency (EMA) released a new version of the European Clinical Trials Database (EudraCT), marking "the initial step of a process through which summary clinical trial results will be made publicly available through the EU Clinical Trials Register (EU CTR) ." Notably, the EudraCT summary results data requirements are "substantially aligned" with those of the ClinicalTrials.gov Results Database.
- EMA Press Release: European Medicines Agency launches a new version of EudraCT: Summary results of clinical trials soon to be available to the public
Present: Development of Notice of Proposed Rulemaking
In the future, NIH will issue regulations on procedures for registering and submitting the results, including adverse events, of clinical trials on ClinicalTrials.gov, in accordance with FDAAA 801. A notice of proposed rulemaking (NPRM) and request for comments from the public on the development of the final rule (regulations) will be issued before the final regulations are written. The rulemaking process will also consider regulations intended to provide more complete results information and enhance patient access to and understanding of the results of clinical trials, including:
- Whether results information should be required to be submitted for applicable clinical trials of drugs, biological products, or devices that have not been approved, licensed, or cleared by FDA
- Whether narrative summaries of clinical trials and their results can be included in the data bank without being misleading or promotional
- Whether the full protocol should be submitted to help evaluate the results of the trial
RegInfo.gov: EO 12866 Regulatory Review. The Office of Management and Budget, Office of Information and Regulatory Affairs (OIRA), received the NPRM on 3/11/2014 for regulatory review.