COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov

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.

Contents

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 (FDAMA 113) required the National Institutes of Health (NIH) to 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 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.

To Top

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.

To Top

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In 2000 FDA issued a draft Guidance for Industry document, which provided recommendations for researchers submitting information to ClinicalTrials.gov. A final guidance document that incorporated comments from the public was issued in 2002 and was withdrawn by FDA in September 2017.

  • FDA Final Guidance, March 2002: Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions (Withdrawn by FDA September 2017)

In January 2004 FDA proposed a revised draft Guidance for Industry document that included guidance for researchers submitting information required by the Best Pharmaceuticals for Children Act of 2002. This draft guidance was withdrawn by FDA in September 2017.

  • FDA Draft Guidance, January 2004: Guidance for Industry: Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions (Withdrawn by FDA September 2017)
To Top

2004: ClinicalTrials.gov Wins the Innovations in American Government Award

In 2004 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. 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.

To Top

2005: International Committee of Medical Journal Editors Requires Trial Registration

In 2005 the International Committee of Medical Journal Editors (ICMJE) began requiring trial registration as a condition of publication.

To Top

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.

To Top

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.

To Top

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) required 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.

To Top

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. The submission of adverse event information was optional when the results database was released but was required beginning in September 2009.

To Top

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 the prospective registration and the 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) required 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."

To Top

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 on 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 submissions, for use in the development of draft regulations.

To Top

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.

To Top

2014: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 Issued for Public Comment

In November 2014 the U.S. Department of Health and Human Services issued a notice of proposed rulemaking (NPRM) describing the proposed requirements and procedures for registering and submitting the results, including adverse events, of clinical trials on ClinicalTrials.gov, in accordance with FDAAA 801. It also considers regulations intended to provide more complete results information and enhance patients' access to the results of clinical trials, by proposing to expand the requirement for submission of results information for Applicable Clinical Trials of unapproved products (i.e., drugs, biological products, or devices that have not been approved, licensed, or cleared by FDA). Public comments on the proposed rule were accepted until March 23, 2015. All substantive comments will be carefully reviewed and considered in drafting a final rule.

To Top

2014: NIH Draft Policy on Registration and Results Submission of NIH-Funded Clinical Trials Issued for Public Comment

In November 2014 NIH proposed a policy to ensure that every clinical trial (see the Revised NIH Definition of "Clinical Trial") that receives NIH funding is registered on ClinicalTrials.gov and has summary results submitted and posted in a timely manner, whether subject to FDAAA 801 or not. Public comments on the proposed rule were accepted until March 23, 2015. All substantive comments will be carefully reviewed and considered in drafting a final policy.

To Top

2015: National Cancer Institute Issues Clinical Trial Access Policy

In January 2015 the NIH National Cancer Institute (NCI) issued its Policy Ensuring Public Availability of Results from NCI-supported Clinical Trials. Generally, for "all initiated or commenced NCI-Supported Interventional Clinical Trials whether extramural or intramural" (i.e., Covered Trials), "Final Trial Results are expected to be reported in a publicly accessible manner within twelve (12) months of the Trial's Primary Completion Date regardless of whether the clinical trial was completed as planned or terminated earlier." This policy will be incorporated as a term and condition of any award supporting a Covered Trial.

To Top

2016: Final Rule for FDAAA 801 Issued

In September 2016, the U.S. Department of Health and Human Services issued a Final Rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11) that clarifies and expands the regulatory requirements and procedures for submitting registration and summary results information of clinical trials on ClinicalTrials.gov, in accordance with FDAAA 801. The final rule is intended to make it clear to sponsors, investigators, and the public which trials must be submitted, when they must be submitted, and whether compliance has been achieved. For example, the final rule clarifies the definition of an Applicable Clinical Trial and provides structured criteria for determining which studies are considered to meet the definition. The final rule also expands the FDAAA 801 requirements by requiring the submission of results information for trials of unapproved products. The regulation is effective on January 18, 2017 and responsible parties are expected to be in compliance as of April 18, 2017.

To Top

2016: Final NIH Policy on the Dissemination of NIH-funded Clinical Trial Information Issued

In September 2016, NIH issued a final policy to promote broad and responsible dissemination of information from NIH-funded clinical trials through ClinicalTrials.gov. Under this policy, every clinical trial funded in whole or in part by NIH is expected to be registered on ClinicalTrials.gov and have summary results information submitted and posted in a timely manner, whether subject to FDAAA 801 or not. This policy is effective for applications for funding, including grants, other transactions, and contracts submitted on or after January 18, 2017. For the NIH intramural program, the policy applies to clinical trials initiated on or after January 18, 2017.

To Top

2017: Revised Common Rule (45 CFR 46) Issued

In January 2017, nearly 20 Federal department and agencies issued a revised Federal Policy for the Protection of Human Subjects (also known as subpart A of 45 CFR part 46, or the "Common Rule"). The revisions were designed to modernize, strengthen, and make more effective the Common Rule originally promulgated in 1991. The revised Common Rule is intended to better protect human subjects involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators. It became effective on July 19, 2018, as amended.

The revised Common Rule (45 CFR 46.116(h)) requires that for any clinical trial conducted or supported by a Common Rule department or agency, one consent form used in enrolling participants be posted on a publicly available Federal website within a specific time frame. In an August 2018 announcement, ClinicalTrials.gov and Regulations.gov were identified as the publicly available federal websites that will satisfy the consent form posting requirement.

To Top

2020: Federal Court Decision in Seife et al. v. HHS et al., 18-cv-11462 (NRB) (S.D.N.Y. Feb. 24, 2020)

On February 24, 2020, a Federal court held that Section 801 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (PDF) requires submission of results information for an "applicable clinical trial" ("ACT") that was initiated after September 27, 2007, or that was ongoing as of December 26, 2007, if the ACT studies a product that is approved, licensed, or cleared by the FDA at any time, including after the ACT's primary completion date.

On September 21, 2016, the Department of Health and Human Services ("HHS") published the Final Rule for Clinical Trials Registration and Results Information Submission, 81 Fed. Reg. 64,982 (Sept. 21, 2016) ("Final Rule"). The preamble to the Final Rule states that a responsible party is not required to submit to the ClinicalTrials.gov data bank results information under section 402(j)(3)(C) and section 402(j)(3)(I) of the PHS Act for an ACT that was completed before January 18, 2017, the effective date of the Final Rule, if the ACT studied a product that was not approved, licensed, or cleared until after the ACT's primary completion date. 81 Fed. Reg. at 65,067.

On February 24, 2020, a Federal court rejected this interpretation, holding that FDAAA requires responsible parties to submit to the ClinicalTrials.gov data bank results information required under section 402(j)(3)(C) of the PHS Act, which includes information required under section 402(j)(3)(I) of the PHS Act, for ACTs subject to the registration requirements and with a primary completion date before January 18, 2017, if the ACT studies a product that is approved, licensed, or cleared after the ACT's primary completion date. The Court set aside HHS's contrary interpretation in the preamble to the Final Rule, but did not change the regulations promulgated in 2016. Seife et al. v. HHS, et al., No. 18-cv-11462-NRB, 2020 WL 883478 (S.D.N.Y. February 24, 2020).

This page last reviewed in August 2020