Clinical Trial Registration FAQ
What is the requirement?
The recently enacted U.S. Public Law 110-85 (Food and Drug Administration Amendments Act of 2007), Title VIII- Section 801 now has mandates that effect the NIH-maintained data bank of all clinical trials which qualify for registration at ClinicalTrials.gov. Previously, the data bank only required registration of trials of drugs for serious or life-threatening diseases, and those which were to be considered for publication by the International Committee of Medical Journal Editors (ICMJE). The Food and Drug Amendments Act (Title VIII. Sec. 801) significantly expanded the scope of clinical trials that must be registered and set civil monetary penalties for failing to register "applicable trials." In 2004, the International Committee of Medical Journal Editors (ICMJE) defined trials that must be registered in order to be considered for publication in journals that adhere to ICMJE standards. In 2007 the ICMJE expanded the definition of trials that must be registered. Scores of journals (not limited to medical journals) have adopted the registration policy.
How is "clinical trial" defined for registration purposes?
According to the International Committee of Medical Journal Editors (ICMJE):
"Any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome. The trial must have at least one prospectively assigned concurrent control or comparison group in order to trigger the requirement for registration." 2005 statement
"Any research study that prospectively assigns human participants or groups of humans to one or more health- related interventions to evaluate the effects on health outcomes." 2007 Statement
According to the FDA and the NIH:
The Food and Drug Amendments Act (Title VIII. Sec. 801) requires registration for all "applicable clinical trials," including Federal, industry-sponsored, and investigator-initiated that are:
1) Trials of drugs and biologics: Controlled, clinical investigations, other than Phase I investigations, of a product subject to FDA regulation, and
2) Trials of devices: Prospective clinical studies of health outcomes comparing an intervention with a device against a control in human subjects (other than small clinical trials to determine the feasibility of a device, or clinical trials to test prototype devices where the primary outcome measure relates to feasibility and not to health outcomes; and pediatric postmarket surveillance studies, as required under the Federal Food, Drug and Cosmetic Act.
What are the registration deadlines?
The ICMJE follows its 2005 definition. The ICMJE will start to implement the expanded (2007) definition for all trials that begin enrollment on or after July 1, 2008. The ICMJE will not strictly impose this expanded definition until the stated date.
The Food and Drug Amendments Act of 2007 requires that all trials, regardless of sponsor, initiated after 9/27/07 or ongoing as of 12/26/07 must be registered in full by the later of 12/26/07 or 21 days after the first patient is enrolled.
All trials that were ongoing as of 9/27/07 and do not involve serious or life-threatening conditions must be registered by 9/27/08.
What are the penalties for failing to register?
According to the ICMJE:
Unregistered trials will not be considered for publication in journals that adhere to ICMJE standards. This penalty has not changed over time.
According to the FDA/NIH (Food and Drug Amendments Act of 2007):
Penalties may include civil monetary penalties up to $10,000 fine for failing to submit or for submitting fraudulent information to ClinicalTrials.gov. After notification of noncompliance, the fine may go up to $10,000 per day until resolved. For federally funded grants, penalties may include the withholding or recovery of grant funds.
The terms "health-related interventions" and "health outcomes" suggest that this requirement applies only to biomedical clinical trials. Is that correct?
No. According to the ICMJE, "health-related" interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events.
Are there any exceptions?
Yes. Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.
What if I am uncertain about whether to register my trial?
According to the ICMJE:
Those who are uncertain whether their trial meets the ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal.
According to the FDA and the NIH:
Both agencies encourage the registration of ALL trials, whether or not required under the FDA Amendments Act of 2007. For further assistance in determination of registration, please contact the HSRR Office.
Where and what are the registries?
ClinicalTrials.gov has become the registry of choice and is now the registry required by the FDA Amendments Act of 2007. ClinicalTrials.gov is a service of the NIH, developed by the National Library of Medicine.
How is Binghamton University involved?
Binghamton University is already registered as an institution at ClinicalTrials.gov, and we have already registered trials at this site. ClinicalTrials.gov asks each institution to identify a Protocol Registration System (PRS) Administrator. At Binghamton University, the administrator is Anne Casella in the Office of Human Subjects Research.
How do PIs register their trials?
If after reading this information, you determine that you need to register your clinical trial at ClinicalTrials.gov, contact Anne Casella at 607-777-3918 or email email@example.com for further assistance.
Is more information available?
Yes. For more information about the ICMJE registration requirement, see: The 2007 ICMJE editorial entitled "Clinical Trials Registration: Looking Back and Moving Ahead." For more information abut the FDA Amendments Act of 2007, see: Guidance from the NIH Office of Extramural Research.