What is ClincialTrials.gov?
ClinicalTrials.gov is a publicly accessible online database of clinical trials, with registration of certain trials required as per many US regulations and policies, including FDA policy, Medical Journal Editors Policy and National Institute of Health Trial Dissemination Policy. Registering and updating the information on the platform is the job of a designated responsible party, who may be a clinical trial sponsor or investigator. The information available is accessed and used by patients, healthcare professionals, and other researchers for the purposes of advancing scientific discovery and protecting public health. Trials are registered by the responsible party on the protocol registration and results system (PRS), with trial information then passing through automated validation and manual quality control review before being posted publicly. As required information and trial documentation varies according to the type of trial, it is important for responsible parties to check the specific required information according to their study.
Requirements
Patient Information Sheet
The patient information sheet given to the patient at the time of informed consent must include a the following word-for-word statement regarding the registration of the trial on ClinicalTrials.gov:
“A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”
This directs potential patients to a full description of the trial, for the purpose of full transparency and public availability.
Pre-trial Registration
There are various FDA requirements for the registration of trials on ClinicalTrials.gov PRS prior to enrolling the first study participant. Importantly, all submissions must be completed no later than 21 days after enrolling the first human subject, with all trial information and documentation in English. Required trial information includes study identification, design, eligibility criteria, conditions and interventions being investigated, contact details and outcome measures. Required documentation typically includes full protocol and statistical analysis plan, although this may vary depending on the type of study. Additionally, the FDA 3674 form is a certification of compliance required for certain studies and submissions, including investigational new drug applications, and biologics license applications. This form is a formal certification of compliance with legal requirements for trial registration and results publishing. To check whether this is required for their trial, responsible parties should check the full list of application types requiring the FDA 3674 form.
Ongoing Review and Updates
The FDA requirements specify that clinical trial information must be updated at least every 12 months throughout the trial. Any changes to key data elements throughout the duration of the trial, such as responsible party, study start and completion date, and recruitment status, must be changed in the PRS within 30 days of update. The status of a medical device product under investigation, when not FDA approved, must also be updated within 15 days of the update. It is therefore important for responsible parties to be aware of these timelines in order to remain compliant.
Results Reporting
The FDA policy also specifies specific requirements for reporting the results of the trial within the PRS. After the study has been completed, results information should be made available on the platform within 1 year after primary completion date. The guidelines also specify specific formatting of information, including tables of participant flow, demographics and baseline characteristics, and primary and secondary outcome measures. The full study protocol, adverse event information and statistical analysis plan should also be made available, as this is required for the quality control review.
Following the automatic validation and manual quality control review, responsible parties may receive major comments, which require mandatory action, and advisory comments, which are optional suggestions or recommendations. If a noncompliance issue, such as missing or incorrect trial information, is noted by the reviewer, the responsible party may receive an official FDA preliminary notice of noncompliance letter. Potential noncompliance issues must be addressed within 30 days in order to achieve voluntary compliance. If, however, the issue is not resolved within 30 days, the responsible party will receive an official FDA notice of noncompliance, which acts as a formal notification of the identified noncompliance. Responsible parties will then be given another 30 days to resolve this in order to reach compliance. Failure to address the official notice may result in further consequences such as fines, withholding of grant funding, or even criminal prosecution may be actioned by the FDA.
It is therefore important for all researchers undertaking clinical trials of products seeking FDA approval to designate an appropriate responsible party who can ensure accurate and timely submission and updating of trial information and documentation to the PRS at all required study timepoints. This is important for maintaining the reliability of publicly available trial information on the ClinicalTrials.gov platform so that that research findings are available for the benefit of patients, healthcare professionals and the wider scientific community.
Source: https://www.youtube.com/watch?v=0fLHm0YmH3w
Author: Lydia Ainsworth, Senior Clinical Data Quality Manager
