On January 18, 2017, the final rule from the Department of Health and Human Services (HHS) and the National Institute of Health (NIH)’s corresponding policy on reporting to ClinicalTrials.gov will take effect. ClinicalTrials.gov, which is run by NIH, is a searchable registry of clinical trials. It is a federal requirement that sponsors of certain clinical studies that either have one American research site or are conducted under an investigational device exemption (IDE) or an investigational new drug (IND) application register and report the summary results on ClinicalTrials.gov. However, currently very few pharmaceutical companies, academic institutions, and government agencies are complying with the requirement. The regulatory changes taking effect will only have a meaningful impact if the incoming Administration chooses to enforce them.
The final HHS rule came in at a whopping 126 pages. Much of the rule consists of the agency’s legal justification for the new changes and a survey of the hundreds of comments it received in response to its 2014 Notice of Proposed Rulemaking announcing the proposed changes. Under the new regulations, most drug, biological, and device clinical trials regulated by the FDA will need to be reported to ClinicalTrials.gov; this includes trials for products that were never approved by FDA.
The complementary NIH policy “sets the same reporting expectations for all NIH-funded clinical trials whether or not they are subject to the regulation.” As a result, NIH-funded phase 1 trials of FDA regulated products and NIH-funded studies of interventions not regulated by FDA will have to be reported to ClinicalTrials.gov. In its new policy, NIH argues that publicly displaying results information helps both institutional review boards and investigators by giving them the opportunity to review proposed studies’ benefits and risks against a more detailed evidence base than exists in the scientific literature.
The ClinicalTrials.gov results database currently includes study outcomes and adverse events that were reported during the course of a trial. The final HHS rule expands the submission requirements, including how adverse events are to be publicly reported. More specifically, reporting of the time frame during which adverse event information was recorded and how adverse events were collected are no longer discretionary, but rather must be reported. Researchers will be able to identify on ClinicalTrials.gov whether a “systematic assessment” or a “non-systematic assessment” was used to collect adverse event information. Systematic assessments are methods such as checklists or laboratory tests at regular intervals while non-systematic assessments involve adverse events that are spontaneously reported, for example, when there is “unprompted self-reporting” from a human research subject.
Furthermore, the final rule mandates that the serious adverse events table for a registered trial state the number of deaths from any cause by comparison group, if that data was recorded.
The Director of ClinicalTrials.gov, Dr. Deborah A. Zarin, noted that this requirement will allow NIH “to address deficiencies in the ability to determine the total number of deaths during each trial.” However, without adequate enforcement it is unlikely that there will be full compliance with these important requirements.
HHS’ final rule states that ClinicalTrials.gov will identify noncompliant parties, that parties receiving federal funds may see their grant funds withheld if they do not comply with the reporting requirements, and that there may be civil monetary penalties of up $10,000 a day for non-compliance, with the amount to be adjusted going forward.
The new NIH policy, in turn, states that noncompliance may result in suspension or termination of NIH grant or contract funding. NIH will also consider past instances of noncompliance when making future funding decisions and, like HHS, will identify noncompliant parties on ClinicalTrials.gov. However, public health advocates are concerned that the consequences for noncompliance remain weak and are unlikely to be enforced. Advocates pointed out that the federal government for years has had the ability to levy a $10,000 fine on noncompliant parties, but no one has ever been held accountable, costing the United States billions in lost fines.
In response to the new regulations and policy, Dr. Ben Goldacre, a co-founder of the AllTrials campaign, said “We have waited a decade to hear how the law will be enforced. We now need to know who will be monitoring compliance; how they will share details of their deliberations and work; [and] what principles and policies they will be following in making their decisions on whether to apply a fine, or any other form of censure.” In its summary of the comments it received on the proposed rule regarding the legal consequences for noncompliance, HHS noted that commenters called for harsh penalties for those who were intentionally violating the federal requirements.
Members of Congress have also expressed concern about NIH’s lack of enforcement. In December 2015, STAT ran a well-received article on researchers’ failure to comply with the ClinicalTrials.gov requirements, after which there was a spike in results reporting. However, Senator Charles Grassley (R-IA), who co-sponsored the legislation on reporting clinical trial findings to ClinicalTrials.gov, pointed out that the media should not have to enforce federal requirements: “It’s good news that media disclosure encouraged more reporting of clinical trial results…. But NIH shouldn’t rely on media coverage to do its job here. Media coverage comes and goes, while NIH’s obligation to ensure compliance with reporting requirements is constant.”
In response to the STAT article, Senator Grassley asked NIH about enforcement of the ClinicalTrials.gov requirements and what penalties had been issued to noncompliant parties over the last five years. It is worth nothing that four years ago, three members of the House of Representatives also asked NIH if it had adequate resources and authority to enforce the reporting requirements. NIH responded that it did.
In order to ensure that research dollars are not squandered on unnecessarily duplicative research, the new Administration should ensure that HHS and NIH enforce these important new federal requirements. In response to the aforementioned letter from Senator Grassley, the director of NIH acknowledged that publicly posting clinical trial information shows the public which trials they may be able to enroll in, facilitates the design of better studies, and prevents “duplication of unsafe or unsuccessful trials.” The millions of people who volunteer for trials and the patients that rely on such research are counting on institutions to comply with the new regulations and for the government to enforce them.