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NIH Guide Notice: NOT-OD-08-023 and NOT-OD-09-030
Initial Posting: December 21, 2007
Last Updated: December 17, 2008
- What is Public Law 110-85, (also known as the FDA Amendments Act) and how does it relate to ClinicalTrials.gov and NIH-funded clinical trials?
On September 27, 2007, the President signed Public Law 110-85 http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110.pdf (PDF - 424 KB). The law includes a section on clinical trial databases (Title VIII) that expands the types of clinical trials that must be registered in ClinicalTrials.gov, increases the number of data elements that must be submitted, and also requires submission of certain results data.
- What trials are affected by this law?
Under the statute, the “applicable clinical trials” trials generally include:
- Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation; and
- Trials of Devices: Controlled trials with health outcomes, other than small feasibility studies, and pediatric postmarket surveillance.
- Who is responsible for registering the trial? (designated the “responsible party” in the law)
The sponsor of the clinical trial; - OR - The principal investigator (PI) of such clinical trial if so designated by a sponsor, contractor, grantee, or awardee, so long as the PI is responsible for conducting the trial and has sufficient data rights.
For NIH-funded clinical trials where there is an IND holder, consistent with FDA regulations, the IND holder is the sponsor, and will be considered the responsible party unless this obligation is delegated to the principal investigator. For NIH-funded clinical trials where there is no IND holder, the funding recipient will be considered the responsible party.
- When must the trials be registered?
- Trials initiated after 9/27/2007 must be registered in full not later than 21 days after the first patient is enrolled, or by 12/26/2007, whichever is later.
- Trials that were initiated on or before 9/27/2007 and “ongoing” as of 12/26/2007 and do involve a “serious or life threatening disease or condition” must be registered in full by 12/26/2007.
- Trials that were “ongoing” as of 9/27/2007 and do not involve a “serious or life threatening disease or condition” must be registered in full by 9/27/2008.
- Trials that were “ongoing” as of 9/27/2007, 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 registration requirements.
(“Ongoing” in this context means a trial had one or more patients enrolled, but had not examined the final subject or provided the final subject an intervention for the purposes of final collection of data for the primary outcome.)
- What is a “serious or life threatening disease or condition”?
Consistent with current FDA and ClinicalTrials.gov guidance, the NIH interprets ”serious and life-threatening disease or condition” to mean: (1) diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and (2) diseases or conditions with potentially fatal outcomes, where the endpoint of clinical trial analysis is survival.
The seriousness of a disease is a matter of judgment, but generally is based on such factors as survival, day-to-day functioning, and the likelihood that the disease, if left untreated, will progress from a less severe condition to a more serious one. For example, acquired immunodeficiency syndrome (AIDS), all other stages of human immunodeficiency virus (HIV) infection, Alzheimer's disease, angina pectoris, heart failure, cancer, and many other diseases are clearly serious in their full manifestations. Furthermore, many chronic illnesses that are generally well managed by available therapy can have serious outcomes. For example, inflammatory bowel disease, asthma, rheumatoid arthritis, diabetes mellitus, systemic lupus erythematosus, depression, psychoses, and many other diseases can be serious in some or all of their phases or for certain populations.
Any investigational drug that has received fast track designation by the FDA is considered a drug to treat a serious disease or condition.
- What needs to 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 ClinicalTrials.gov “Registration” Data Element Definitions), 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 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 ClinicalTrials.gov “Registration” Data Element Definitions), and the identity of the responsible party (or parties) are to be included in the Human Subjects section of the progress report.
- When does the requirement to report trial registration go into effect?
- 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.
- Where do I find which elements need to be included in registration of new trials?
A list of all the elements that are required by the law can be found on the ClinicalTrials.gov “Registration” Data Element Definitions webpage.
- What new elements need to be added to trials that have already been registered?
There are a number of completely new elements and other elements that were previously optional that are now required according to the law. All applicable clinical trials need to be updated accordingly. For details of the new and newly mandatory elements please see the ClinicalTrials.gov “Registration” Data Element Definitions webpage.
- Who submits updated/new information of ongoing trials?
The current processes for registering trials at ClinicalTrials.gov have not changed so updated/new information should be submitted as before.
- Will the application instructions change?
We anticipate that there will be some changes in the application process and will provide details as soon as they become available.
- What about trials that are funded through NIH grants but may not be subject to the sections of Public Law 110-85, cited in the definition of "Applicable Clinical Trial”?
Although registration of these trials is not mandated by Public Law 110-85, we encourage registration of all clinical research studies funded by the NIH in ClinicalTrials.gov.
- Does this apply to intramural investigators?
Yes, it does.
- What about the results database?
The results database is to be created by September 27, 2008. Further details will be provided as they become available.
- Who do I contact if I have additional questions?
Additional information can be found on the ClinicalTrials.gov website (http://prsinfo.clinicaltrials.gov/fdaaa.html) and in the appropriate NIH Guide Notices (NOT-OD-08-014, NOT-OD-08-023, and NOT-OD-09-030).
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