On April 28, 2008, the Vice Dean for Clinical Investigations issued a letter outlining changes in requirements for registering clinical trials. The changes were necessitated by FDA requirements (http://www.fda.gov) and the International Committee of Medical Journal Editors (ICMJE) policy update (http://www.icmje.org).
Accordingly, JHM has revised the “Organization Policy on Registration of Clinical Trials” (Policy No. 103.25). Investigators/sponsors must register clinical trials with a clinical trials registry that is electronically searchable and accessible to the public at no charge. The site for registration is maintained by the National Library of Medicine on www.clinicaltrials.gov. Under the JHM policy, a clinical trial is defined as, "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." Health outcomes include any biomedical or health-related measures, including pharmacokinetic measures and adverse events.
Which Johns Hopkins “clinical trials” must be registered?
As of January 25, 2008, the following new or ongoing trials* need to be registered on http://www.clinicaltrials.gov:
- Trials of Drugs/Biologics: Controlled, clinical investigations of a product subject to FDA regulations. This includes preliminary studies or phase I trials to be published in an ICMJE journal.
- Trials of Devices: Controlled trials with health outcomes, other than small feasibility studies, and pediatric post-market surveillance.
- More data elements are required than under prior federal law, and these new requirements include:
- Primary and secondary outcome measures;
- Start date;
- Target number of subjects; and
- Adverse events.
For trials that are already registered, these new data fields as well as the previous data fields must be updated when there are changes to the study.
(* An “ongoing” trial has enrolled one or more subjects and the final subject has not been examined or received an intervention for the purpose of collecting data on the primary outcome).
Penalties for Failure to Register
There are now penalties for responsible parties who fail to register applicable clinical trials or who submit false or misleading information. Civil monetary penalties are allowed under FDA regulations. Civil penalties for investigator sponsors can range up to $10,000/day (see, Food and Drug Administration Amendments Act of 2007 (FDAAA Law)). For federally-funded trials, the penalties could include withholding or recovery of grant funds.
Who should register a Johns Hopkins clinical trial?
- The sponsor of the clinical trial; OR
- The Principal Investigator (PI)/sponsor of clinical trials that are investigator-initiated has the responsibility of:
(a) Determining whether or not a trial for which he/she is the investigator/sponsor should be registered, AND
(b) Completing and maintaining the information on the registration site – with one exception.
(c) For oncology clinical trials, the Oncology Clinical Research Office is responsible for clinicaltrials.gov user account set-up.
- Most NIH supported clinical trials expect the PIs to register the study but check with the NIH project officer.
Timing of Registration at ClinicalTrials.Gov
For new clinical trials, submission requirements are triggered by enrollment. The PI or sponsor must submit required information no later than 21 days after the first participant is enrolled.
For ongoing clinical trials already registered, new information must be posted. A trial that was enrolling subjects as of September 27, 2007 (even one which does not involve a “serious or life-threatening disease or condition”) must be registered and updated at least annually (see details below).
ICMJE Definition of “Clinical Trials”
The ICMJE policy on registration of clinical trials has been revised to broaden the definition of clinical trials to include preliminary studies or phase I studies (Clinical Trial Registration JAMA 298; 93-4, 2007). The ICMJE has adopted the World Health Organization’s definition of clinical trial as “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.” Health outcomes include any biomedical or health-related measures including pharmacokinetic measures and adverse events. However, the ICMJE states “Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.” The ICMJE’s Frequently Asked Questions about Clinical Trials Registration states, “Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal.”
The ICMJE policy applies to all trials that began enrollment on or after July 1, 2008.
What are the obligations of the Johns Hopkins PI regarding registration if the trial is commercially sponsored?
The Johns Hopkins PI should consult with the commercial sponsor to ensure that posting the clinical trial on the government website is in accord with the terms of the study contract.
What are the requirements for updating clinical trial registrations?
- Unless there have been no changes, registration information must be updated no less than once every 12 months.
- If recruitment status for the study changes (ex., recruitment suspended), the registration must be updated within 30 days.
- If the trial is complete (whether concluded or terminated prior to conclusion), registration must be updated within 30 days.
Requirements for posting basic study results:
The JHU faculty member who is the sponsor/investigator of a clinical trial is responsible for posting basic study results at the conclusion of the study. The following items must be posted on the site:
- DEMOGRAPHIC AND BASELINE CHARACTERISTICS OF PATIENT SAMPLE – A table of the demographic and baseline data collected overall and for each arm of the clinical trial to describe the patients who participated in the clinical trial, including the number of patients who dropped out of the clinical trial and the number of patients excluded from the analysis, if any.
- PRIMARY AND SECONDARY OUTCOMES – The primary and secondary outcome measures, as stated in FDAAA Section 801, and a table of values for each of the primary and secondary outcome measures for each arm of the clinical trial, including the results of scientifically appropriate tests of the statistical significance of such outcome measures.
- POINT OF CONTACT – A point of contact for scientific information about the clinical trial results.
Detailed instructions for submission of “Basic Results” may be obtained on the clinicaltrials.gov Protocol Registration System website at http://prsinfo.clinicaltrials.gov/fdaaa.html.
How do I register my study on Clinicaltrials.gov? (Non-Oncology Research)
- Go to the clinicaltrials.gov website and click the link under “Investigator’s Note”.
- Under Account Application Process, follow the instructions for “Individual Accounts.” The SOM does not have an organization account. The Hopkins PI is the responsible official for initial registration and for keeping the listing updated.
- On the page titled “Getting a PRS Individual Account”, consider the questions listed. Question 6 asks whether your organization already is registered with the PRS. The answer to this question is “No” – and we do not have a PRS administrator. Proceed to apply for an individual account.
The ICTR Research Navigators are available to provide assistance to PIs who must update their ClinicalTrials.gov registration information or post study results. Simply go the ICTR Connection Request page, log in with your JHED ID, then select “Research Questions – Ask an ICTR Navigator” from the list of ICTR services and submit your question. You may also contact the Navigators via email at ICTR_Navigators@jhmi.edu. They will respond to your ClinicalTrials.gov questions promptly.”