Yesterday, the Department of Health and Human Services and the National Institutes of Health (NIH) proposed to “increase the transparency of clinical trials via information submitted to ClinicalTrials.gov.” NIH notes that “[a] major proposed change from current requirements is the expansion of the scope of clinical trials required to submit summary results to include trials of unapproved, unlicensed, and uncleared products.”
NIH also proposed a policy that would extend the similar registration and reporting requirements to all clinical trials funded by NIH, including phase 1 trials of drugs and biological products, small feasibility studies of devices, and clinical trials of behavioral, surgical, and other types of health and medical interventions.
View the full proposed regulation here.
NIH states that registering and reporting results of clinical trials, including both positive and negative findings, will help “researchers prevent unnecessary duplication of trials, particularly when trial results indicate that a product under study may be unsafe or ineffective, and it establishes trust with clinical trial participants that the information from their participation is being put to maximum use to further knowledge about their condition.”
“This proposed rule would close an important gap, making additional information about clinical studies of investigational drugs, medical devices and biological products available to the public,” said FDA Commissioner Margaret A. Hamburg, M.D. “It would help eliminate unnecessary duplicative trials, advance biomedical innovation, and provide the public with a much richer understanding about the clinical trials for these products.”
In addition to requiring the submission of summary results for unapproved products, the proposal clarifies and expands a number of aspects related to ClinicalTrials.gov, including what constitutes an applicable clinical trial for purposes of the proposal, who is responsible for submitting the information, registration information, new compassionate use requirements,
Applicable clinical trial: NIH notes that “[a]pplicable clinical trials include controlled, interventional studies of drugs, biological products, and devices that are regulated by the FDA, but exclude phase 1 studies of drugs and biological products and feasibility studies of devices.” They state that “[i]n general, clinical trials of products regulated by FDA will meet one or more of the following criteria: include one or more sites in the United States; study a drug, biologic, or device that is manufactured in the United States or its territories and is exported for use in a clinical trial outside the United States; or be conducted under an FDA investigational new drug application (IND) or investigational device exemption (IDE).” The proposal specifies an approach for determining whether a particular clinical trial or study is an applicable clinical trial, using information that would be submitted at the time of registration.
Responsible party: The rule indicates that “there must be one (and only one) responsible party for submitting information about an applicable clinical trial,” noting that the “sponsor of an applicable clinical trial would be considered the responsible party, unless and until the sponsor designates a qualified principal investigator as the responsible party.” It includes a discussion of how to determine who is considered the sponsor, among other related issues.
Registration: Under the proposal, responsible parties would have to register an applicable clinical trial within 21 days after enrolling the first participant. The rule specifies a wide variety of data elements to be included upon registration, across four categories: 1) descriptive information, 2) recruitment information, 3) location and contact information, and 4) administrative information.
Expanded access: The rule also proposes that “if a drug studied in an applicable clinical trial is available under expanded access, or compassionate use, the sponsor would also have to submit a separate expanded access record (or link to an existing record) containing details about how to obtain access to the investigational drug.”
Results submission: While implementing the statutory requirement for summary results submission for specified products, the rule also proposes to “extend the requirement for results submission to applicable clinical trials of drugs, biological products, and devices that are not approved, licensed, or cleared by FDA.” Specifically, the rule would “require the submission of tables of data summarizing demographics and baseline characteristics of the enrolled participants and primary and secondary outcomes, including results of any scientifically appropriate statistical tests.”
In terms of timing, NIH proposes that results information must be submitted within one year after the completion date of the applicable clinical trial—the date that the final subject was examined or received an intervention for purposes of data collection for the primary outcome measure. NIH notes that results submission could be delayed for as long as two additional years “if the responsible party submits a certification to ClinicalTrials.gov that either: 1) a drug, biological product, or device studied in the clinical trial is not yet approved, licensed, or cleared for marketing by the FDA and is still under development by the manufacturer; or 2) that the manufacturer is the sponsor of the clinical trial and has sought or will seek within one year approval, licensure, or clearance for a new use of a product studied in the trial. The proposed rule also permits responsible parties to request extensions to the results submission deadline for “good cause.”
Adverse events: As proposed by NIH, responsible parties would have submit “information summarizing the number and frequency of adverse events experienced by participants enrolled in a clinical trial, by arm and organ system.” Two tables would have to be submitted, with one capturing all serious adverse events, and the other “summarizing other adverse events that occurred with a frequency of 5 percent or more in any arm of the clinical trial, regardless of whether such adverse events were anticipated or unanticipated.”
Separate Proposal For NIH-Funded Studies
“Medical advances would not be possible without participants in clinical trials,” said NIH Director Francis S. Collins, M.D., Ph.D. “We owe it to every participant and the public at large to support the maximal use of this knowledge for the greatest benefit to human health. This important commitment from researchers to research participants must always be upheld.”
Collins, along with Kathy Hudson, Deputy Director for Science, Outreach, and Policy, took the clinical trial submissions one step further for NIH-funded studies:
Today, the Department of Health and Human Services (HHS) proposed a rule to require public sharing of key results—the summary data—from certain clinical trials of drugs and devices regulated by the Food and Drug Administration (FDA). While such a mandate has been in place for several years, the proposed rule aims to clarify the requirements. Summary data would include: baseline characteristics of participants, primary and secondary outcome results, and information about adverse events. With a few exceptions, such results must be submitted to ClinicalTrials.gov within one year of the time when the trial completes collection of primary outcome data.
But we at NIH are proposing to go one step further to address this important issue. Today, NIH released a draft policy for public comment to apply these data reporting requirements to all interventional clinical trials that it funds. We are committed to working with NIH-supported researchers and institutions to ensure the new responsibilities in this proposed policy are understood and any unanticipated obstacles are removed.
The proposed NIH Policy would apply to all NIH-funded awardees and investigators conducting clinical trials, funded in whole or in part by NIH, regardless of study phase, type of intervention, or whether they are subject to the rules proposed in the NPRM. It includes phase 1 trials of drugs and biological products, small feasibility studies of devices, and clinical trials of behavioral, surgical, and other types of health and medical interventions.
Comment
Publishing clinical trail results is not always possible, as some trials may not have been completed due to enrollment issues, poor study design, or inconclusive data. Also, journals don’t publish trials for the sake of publishing trials, there has to be new information that the editor deems important. Reporting adverse events (AE’s) also has downsides in that often small phase I or II trials may have AE’s completely unrelated to the study drug or device. It is only with larger trails and multiple trials do we get the full picture for adverse events.
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Comments on the proposal will be accepted for the next 90 days (approximately until February 19, 2015). Written comments should be submitted to docket number NIH-2011-0003 at www.regulations.gov. Commenters are asked to indicate the specific section of the proposed rule to which each comment refers. Written comments on the proposed NIH Policy should be submitted electronically to the Office of Clinical Research and Bioethics Policy, Office of Science Policy, NIH, via email at clinicaltrials.disseminationpolicy@mail.nih.gov, mail at 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, or by fax at 301-496-9839.
Related Documents:
Changes To ClinicalTrials.gov Clinical Trial Submissions