Clinical Trials Protocol Registration
Updated 3/3/2009
On July 1, 2008, the International Committee of Medical Journal Editors (ICMJE) adopted the World Health Organization’s (WHO) definition of a “clinical trial”; thereby expanding the current scope of trials which are required to be pre-registered, to include Phase I studies. http://content.nejm.org/cgi/content/full/NEJMe078110?query=TOC
The ICMJE proposed publication policies in 1978 which the Committee has periodically updated since that time. Over 500 biomedical journals use the ICMJE policy as a publication requirement. Over three years ago, the ICMJE instituted a requirement that clinical trials beginning on or after July 1, 2005 must be registered on a publicly accessible internet site prior to patient enrollment as a condition for publication in any journal subscribing to the ICMJE publication policy. In addition, any clinical trial initiated prior to July 1, 2005 had to be registered prior to acceptance for publication. (For more information, go to http://www.icmje.org/clin_trialup.htm).
In large part, this policy facilitates the peer review of submitted manuscripts to journals using the ICMJE publication policy. Referees will be able to view on-line a description of the clinical trial being reported, and reconcile the data presented with the plan of the study.
Since the inception of the initial ICMJE requirement, The Food and Drug
Administration (FDA) Amendments Act of 2007 or the FDAAA (U.S. Public Law 110-85) was enacted on September 27, 2007. Title VIII, Section 801 of the FDAAA mandates the registration and reporting of basic results by the “responsible party” for all controlled studies involving drugs and biologics regulated by the FDA and controlled studies of health outcomes involving devices regulated by the FDA.
Failure to comply with this law may incur serious civil penalties as well as loss of federal funding. Additional information regarding registration and submission of summary results of applicable trials can be found at: http://prsinfo.clinicaltrials.gov/fdaaa.html
In addition to complying with the FDA Amendments Act, The VCU Office of Research continues to endorse the ICMJE requirement for clinical trial registration prior to the enrollment of the first patient, and their expanded requirement of registration of Phase I studies. VCU continues to promote this standard for the following reasons:
- The broad reach of the ICMJE Policy continues to set a national standard which will eventually be adopted by most, if not all biomedical journals. The concept of clinical trial registration of all studies makes sense and is meritorious. Click here for a list of the current subscribing biomedical journals. http://www.icmje.org/jrnlist.html
- Public access to clinical trial protocols will provide a novel and effective educational tool for human subject volunteers.
- Clinical trials registration ensures continuity in VCU’s research enterprise. If a principal investigator directing a trial were to leave the institution, the trial could be continued under a new investigator without concerns about having precluded options for publication of the results.
Frequently Asked Questions
Why is clinical trial registration necessary? For information on the American Medical Association’s position on clinical trial registration, see the attached commentary, “Trial Registration, A Great Idea Switches from Ignored to Irresistible.”
What types of studies must be registered and when should they be registered?
The ICMJE requires that all clinical trials beginning on or after July 1, 2005 must be registered prior to enrollment of the first patient. On July 1, 2008, this definition was expanded to include Phase I studies. For further details on registration deadlines, see the Frequently Asked Questions on the ICMJE web site at www.icmje.org/faq.pdf
In accordance with Public Law 110-85, trials beginning 9/27/07 involving a serious or life threatening disease must be registered no later than 21 days after the first patient is enrolled. Trials that are ongoing as of 9/27/07 which do not involve a serious or life threatening disease must be registered by 9/27/08.
Additionally, NIH requires registration information be included with all competing and non-competing applications.
For further details regarding NIH and Public Law registration deadlines and other pertinent registration information, see the Frequently Asked Questions on the DHHS website at http://grants.nih.gov/grants/policy/hs/faqs_aps_clinical_trials.htm#q9
How is “clinical trial” defined? For the purposes of the ICMJE requirement and this policy, the current definition of a clinical trial is: “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.” http://www.who.int/ictrp/en/
- This applies to clinical trials sponsored internally, by a private foundation, federal funding agency, or by pharmaceutical/biotechnology companies.
- Health-related intervention is defined as any intervention used to modify a biomedical or health-related outcome, including drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes.
- Health outcomes are defined as any biomedical or health-related measures obtained in patients or participants, which include pharmacokinetic measures and adverse events.
Who is the “responsible party” for registering and reporting results for applicable clinical trials? Under the law, a “responsible party” is generally defined as the sponsor of an applicable clinical trial, as that term is used under 21 CFR 50.3.
In general, responsibility for registration is shared between the organization coordinating trial implementation and the lead sponsor. In a drug/device study, the lead sponsor is the entity or person holding the Investigational New Drug (IND)/Investigational Device Exemption (IDE) applications. For multi-site or multi-sponsor trials, the lead investigator or the lead sponsor is considered the responsible party for registering a protocol and reporting basic results. For investigator-initiated studies, the principal investigator is usually considered the responsible party.
When do results need to be reported? Under the FDAAA, a summary of basic results need to be reported on ClinicalTrials.gov under the Basic Results Database within 12 months of the expected or actual completion date of the clinical trial, whichever is earlier.
What are my responsibilities as the Principal Investigator? The Principal Investigator (PI) is responsible for ensuring that registration and, as applicable, reporting requirements are met.
- NIH-funded clinical trials will generally be registered by the PI through the funding institute. The funding institute may allow or require the PI to register the study directly. The Principal Investigator is responsible for contacting the funding institute and providing the following information for determination of registration requirements:
PI’s full name
PI’s contact information
Grant name
Grant number
- If the Principal Investigator is funded, or seeks funding, either internally or externally from an entity other than the NIH, then the Principal Investigator is responsible for registering the clinical trial. To begin the registration process, the full name, email address and telephone number of the Principal Investigator, or person designated by the PI, should be sent to mwiggins@vcu.edu (Melanie Wiggins; 7-4992 or 7-4991) who will set up a user account.
- In all instances, the Principal Investigator is responsible for ensuring that the clinical trial is registered and updated as required by the ICMJE and Public Law 110-85.
- It is essential that all current protocol registration records are updated to include information for the responsible party so that ClinicalTrials.gov may send out automated reminders regarding the need to report results data.
Where should a clinical trial be registered? The ICMJE has established the characteristics of an acceptable registry and the required minimal data for each trial. The FDA Amendments Act of 2007 expanded the criteria for required data elements.
ClinicalTrials.gov, a service of the NIH, meets the ICMJE criteria and registration on this registry is required the FDA Amendments Act of 2007.
- VCU has established an organizational account with ClinicalTrails.gov. The Principal Investigator does not need to establish an individual account.
Does the IRB need to approve the information posted on the registration site? The VCU IRB panel Chairs and Western IRB have decided that they do not need to review or approve these types of postings, i.e., postings intended to meet the ICMJE requirement and not intended to recruit study subjects. |