Weill Cornell Medical College of Cornell University : Institute for Clinical Research : Planning

Clinical Trials.gov Registration Requirement

In 2005 The International Committee of Medical Journal Editors (ICMJE) issued a directive stating that all clinical trials (beginning recruitment on or after July 1, 2005) must be registered into a public registry as a requisite for publication. Registration must be completed following IRB approval but prior to any study participant enrollment. Details of this directive are available at the following URL: http://www.icmje.org/clin_trialup.htm

Please read the following information carefully. If you have any further questions, please contact the Institute for Clinical Research at 212-746-3774.

The registration requirement
The definition of a clinical trial according to ICMJE
Exception
The Medical College and the ICR's role in this requirement
Person responsible for posting a trial on clinicaltrials.gov
When to register your trial
How to register a trial
After you have registered a trial
New Requirements under Public Law 110-85
Helpful Links

1) The registration requirement

As described on the ICMJE website (http://www.icmje.org/clin_trialup.htm):

"The purpose of a clinical trials registry is to promote the public good by ensuring that everyone can find key information about every clinical trial whose principal aim is to shape medical decision-making."

"A complete registry of trials would be a fitting way to thank the thousands of participants who have placed themselves at risk by volunteering for clinical trials. They deserve to know that the information that accrues from their altruism is part of the public record, where it is available to guide decisions about patient care, and deserve to know that decisions about their care rest on all of the evidence, not just the trials that authors decided to report and that journal editors decided to publish."

2) The definition of a clinical trial according to 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." By "medical intervention" we mean any intervention used to modify a health outcome. This definition includes drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. We update our 2004 editorial to state that a trial must have at least one prospectively assigned concurrent control or comparison group in order to trigger the requirement for registration."

3) Exception

There is one exception: Purely observational studies, in which the assignment of the medical intervention is not at the discretion of the investigator, are not required to register. In other words, trials dealing primarily with assessing unknown toxicity or determining pharmacokinetics (phase 1 trials) are excluded form the requirement to register. Example: Retrospective chart review. (Please refer to the ICMJE statement: "Is This Clinical Trial Fully Registered?" available at http://www.icmje.org/clin_trialup.htm if you are still unclear about whether your trial should be registered. Authors of unregistered clinical trials will have to convince the editor that they had good reason for not registering their trial.)

4) The Medical College and the ICR's role in this requirement

Clinicaltrials.gov requires that each institution designate a PRS administrator. The PRS Administrator is housed at the Institute for Clinical Research (ICR). The Administrator can be reached at OCTA@med.cornell.edu and 212-746-3774

5) Person responsible for posting a trial on clinicaltrials.gov

Generally, the registration should be done by the funding sponsor of the study.

Industry sponsored trials should be registered by the sponsor.
Investigator-Initiated trials should be registered by the PI.
Multi-Site trials should be registered by the "lead sponsor" so that there are not duplicate registrations for the same trial.

Regardless of whether the sponsor, funding agency or PI registers the trial, it is always the primary responsibility of the PI to be sure that registration requirements have been met. Before enrolling patients in a trial, the PI should ask the sponsor if the clinical trial is fully registered on clinicaltrials.gov. After the trial has been registered, the PI should check back regularly to be sure that the info is current and correct. "It is critical that investigators and sponsors work together to make sure that a trial is registered once and only once."

6) When to register my trial

Your trial must be registered after IRB approval but prior to any patients being enrolled. Please see # 9 for important deadlines related to new requirements under Public Law 110-85

7) How to register a trial

Trials are registered on Clinical Trial.gov through the Protocol Registration System (PRS). "The PRS is a web-based system for submitting information about clinical trials ensuring the protocol records are correct and updated in a timely manner. The system allows users to create, modify, maintain and submit protocol records to clinical trials.gov."

Getting Started:

After you determine that you need to register your study on clinical trials.gov, contact the PRS administrator to obtain a PRS User Account:

Email PRS Administrator at WCMC OCTA@med.cornell.edu containing the name of the person under whom the account should be created and their email address.
You will shortly thereafter receive a response via email containing the User Name and a Temporary Password. Now you can go to http://register.clinicaltrials.gov to register your trial.
Note: Registering your clinical trial may take about an hour or more. It is advisable to set aside a substantial block of uninterrupted time for this process.

On "register.clinicaltrials.gov":

Complete the Log In fields. In the "Organization" field, enter "WeillMC". Enter your username and password you received from the ICR via email.
On the Main Menu page, under Protocol Record, hit "Create" to begin creating your record.
There are 12 components to the online registration process. They are in the following sequence: Title, Oversight, Sponsor, Summary, Status, Design, Interventions, Conditions, Eligibility, Locations, Citations and Links.
Each component has its own separate page that links to the next page in the sequence. You are given the option on each page to either "continue" or "quit".
One each page, on the left hand side are links that lead to pop-up menus that give specific definitions of each section of required information for further clarification.

The following list explains some fields that may be confusing:

Organization's Unique Protocol ID: Use the IRB Protocol Number.
Oversight authorities: The name of each national or international health organization with authority over the protocol. If this is not an FDA-regulated protocol, enter "United States IRB".
Sponsor: Be sure to enter sponsor information. Otherwise, the database will default back to "WEILL MC" although WCMC may not be the trial's sponsor.
Collaborators: Although this sub-section refers to additional funding sources, if this is an investigator-initiated trial and you (the PI) hold the IND/IDE, list yourself as a "collaborator".
Record Verification Date: Enter the date upon which you complete and submit the record.
Last Follow-up Date: Specify the anticipated last follow-up date for the study.
"Conditions" & "Keywords": For these sections, ClinicalTrials.gov provides a list from the National Library of Medicine's Medical Subject's Headings (MeSH). If you do not select terms from the list provided, ClinicalTrials.gov will likely delete your term and choose their own. Be sure to make a selection from the MeSH list.
If the person who completed the template is not the PI, send the draft template to him or her for review and approval. This is a key step.
For the complete list of definitions of required data elements for registration: http://prsinfo.clinicaltrials.gov/definitions.html

8) After I have created a record for my trial

After a new record has been created, and associated with the WCMC research profile, the Office of Clinical Trials Administration (OCTA) at the ICR will receive a notification from clinicaltrials.gov
Once a notification has been received the record is reviewed to ensure that all necessary information has been approved by the Institutional Review Board.
If all necessary information is completed and the IRB approval has been confirmed, the trial listing is approved and released to clinicaltrials.gov. If all necessary information is not received and/or the approval has not been confirmed, the PRS user who created the record will be notified of the necessary steps to obtain the records release.
The PI is responsible to update the study record as needed. Updates must be made to the record for study-specific information such as protocol status, revisions to the protocol, updates to enrollment status, changes to contact information, adding new links to the record, etc.
Required verification of study record:

While study is open: every six months.
After study has been closed to enrollment: annually.

9) New Requirements under Public Law 110-85

PLEASE CAREFULLY REVIEW THE FACT SHEET REGARDING THESE NEW REQUIREMENTS: Available at http://prsinfo.clinicaltrials.gov

On September 27th, 2007 a law was enacted that:

Expands the types of clinical trials that must be registered in ClinicalTrials.gov.

Trials of Drugs & Biologics: controlled clinical investigations other than Phase 1 investigations of a product subject to FDA regulations
Trials of Devices: Controlled trials with health outcomes of devices subject to FDA regulation.

Increases the number of data elements that must be submitted.

The following were previously "Optional", but are now "Required" Fields:

Primary Purpose
Intervention Type
Study Start Date
Completion Date
Enrollment (Target Number of Subjects)
Primary & Secondary Outcome Measures
Accepts Healthy Volunteers?
Has Expanded Access?
Expanded Access Status
Secondary IDs
IRB Approval (Yes/No/Other)
Oversight Authority

The following are completely new data elements that are now required:

Safety Issue? (Yes/No)
Responsible Party
Applicable Clinical Trial
FDA Product Status

Requires submission of Results data.

Requirements for Submission of Results Data:

Public Law 110-85 requires Investigators to submit specified study results for all registered clinical trials. Results must be submitted for clinical trials investigating FDA-approved/cleared interventions and non-FDA approved/cleared interventions (drugs or devices).

These requirements take effect on September 27, 2008.

For which studies do I need to submit results?

As of 9/27/2008, results from all clinical trials studying FDA-approved drugs and biologics and FDA-approved or cleared devices must be submitted within 1 year of the study completion date
As of 9/27/2008, results from all clinical trials studying drugs, biologics, and devices not yet initially approved or cleared by the FDA must be submitted no later than later than 30 days after FDA-approval or clearance.

What types of result data will need to be submitted?

By 9/27/2008, investigators will responsible for submitting specific results from his/her clinical trial data (these results may include both published and unpublished data).

Submission data will include:

Demographic and baseline characteristics of patient sample (including patient flow, number of patients dropped and number excluded from analysis)
Primary and secondary outcomes
Point of contact
Information relating to any agreement between the sponsor and PI that restricts the ability of PI to discuss or publish results after the trial completion date.

More information about the submission of clinical trial results is forthcoming (mid-2008).

Please Note: PENALTIES FOR FAILURE TO REGISTER

Penalties for responsible parties who fail to register applicable clinical trials are significant and may include civil monetary penalties [10] and, for federally-funded trials, the withholding or recovery of grant funds [11]. Starting December 26, 2007, any application or report submitted to FDA under sections 505, 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic Act or under section 351 of the Public Health Service Act will need to include certification of compliance with any applicable provisions [12].

Deadlines for registration requirement under Public Law 110-85:

Trials initiated after 9/27/2007, or trials initiated before that date and ongoing on 12/26/2007 that involve a "serious or life threatening disease or condition," must be registered in full by: the later of 12/26/2007 or 21 days after the first patient is enrolled.
Trials that were initiated before 9/27/07 that are "ongoing" as of 12/26/2007, and which do not involve a "serious or life threatening disease or condition," must be registered by 9/27/2008.
Trials that were initiated before 9/27/07 and are "ongoing" as of 12/26/2007, which do involve a "serious or life threatening disease or condition," and are completed (meaning, not "ongoing") by 12/26/2007 are not subject to these requirements, though they may be subject to pre-existing registering requirements. ("Ongoing" in this context means a trial had one or more patients enrolled, but had not reached its "completion date," meaning, examined the final subject or provided the final subject an intervention for the purposes of final collection of data for the primary outcome as of 9/27/2007.)

Notice to NIH Applicants and Grantees

NIH Grant Applications and Progress Reports now require certification that clinicaltrials.gov requirements have been met.

The following info must be included in Grant Applications and Progress Reports to Provide Certification:

For competing applications (new and renewal) that include applicable clinical trials:
the NCT number/s, Brief Title/s (as defined by ClinicalTrials.gov, see http://prsinfo.clinicaltrials.gov/s801-new-requirements.pdf), and the identity of the responsible party (or parties) must be provided in the Human Subjects Section of the Research Plan. If a new applicable clinical trial is proposed, the human subjects section of the research plan should include a statement that the application includes a trial which requires registration in ClinicalTrials.gov. The signature on the application of the Authorized Organizational Representative will now also assure compliance for the registration of any such trial.

When submitting a non-competing progress report that includes applicable trial/s:
NCT number/s, Brief Title/s (as defined by ClinicalTrials.gov, see http://prsinfo.clinicaltrials.gov/s801-new-requirements.pdf), and the identity of the responsible party (or parties) are to be included in the Human Subjects section of the progress report.

The registration requirement goes into effect as follows:

Competing applications: All applications submitted to the NIH on or after January 25, 2008, which incorporate an applicable clinical trial in their proposed project, are required to provide the information as detailed above.
Non-competing progress reports: All progress reports for grants which include an applicable clinical trial with budget start dates of April 1, 2008 or later are required to provide the information as detailed above.
Please visit this site for more information: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-023.html

Penalties For Failing To Register An "Applicable Clinical Trial":
Penalties for responsible parties who fail to register, or provide the assurance described above to the NIH, or who submit false or misleading information in connection with "applicable clinical trials" are significant, and may include civil monetary penalties and, for federally-funded trials, the withholding or recovery of grant funds. See PL 110-85, Sections 801(a), (b), (adding new 42 U.S.C. 282(j), and new 21 U.S.C. 331(jj)). NIH will verify that each "applicable clinical trial" for which the grantee is the responsible party has been registered in ClinicalTrials.gov.

Obtaining Assistance from NIH:
You may register your trial directly by following the procedures outlined at http://prsinfo.clinicaltrials.gov.

Alternatively, you may request registration assistance from an NIH Institute or Center (IC), in which case you are responsible for ensuring that all necessary information is provided to the IC in sufficient time to review and coordinate before the statutory deadlines described above for submission to ClinicalTrials.gov are triggered. You will need to stay in contact with the IC liaison to ensure that your information has been registered properly. Submission of registration information to an IC is not sufficient to satisfy the statutory obligations for submission to ClinicalTrials.gov. You remain legally responsible for submission of information to ClinicalTrials.gov in accord with all applicable legal mandates.

For additional information please see FAQ: http://grants.nih.gov/grants/policy/hs/faqs_aps_clinical_trials.htm