In the midst of heightened allegations regarding the suppression of unfavorable results by pharmaceutical and biotechnology companies, in September 2007, Congress significantly expanded the obligations of clinical trial sponsors to submit information regarding their trials to the federal data bank. Some of these new requirements have already become effective, while others will be imposed incrementally over the next several years. Particularly in light of the addition of civil penalties for noncompliance, sponsors must make proper registration a priority.
In 1997, Congress required National Institutes of Health (NIH) to establish a repository of clinical trials information, housed at www.ClinicalTrials.gov, to serve as a tool for patients seeking access to investigational drugs.1 However, this initial foray of the federal government into clinical trials registration imposed obligations only on sponsors of trials for drugs intended to treat serious or life threatening diseases. It also lacked an enforcement mechanism for failure to submit information, and it did not require the submission of information regarding trial results.
At the state level, only Maine has been successful in imposing unique clinical trial registration requirements of its own, although several state legislatures have introduced proposals to do the same. Importantly, Maine’s law is more onerous than the 1997 federal law, and it does not overlap entirely with the new federal legislation. For jurisdictional reasons, however, Maine’s requirements apply only to approved drugs dispensed, administered, delivered, or promoted in that state.2
Finally, since 2004, the International Committee of Medical Journal Editors (ICMJE) has also played a significant role in this area.3 Publications such as the New England Journal of Medicine, the Journal of the American Medical Association, and many other non-member journals that have adopted the ICMJE policy, now categorically refuse to publish articles regarding trials that were not properly registered at or before initiation.
The New Law
Title VIII of the Food and Drug Administration Amendments Act of 2007, expands the federal registry in several important ways. First, it is no longer limited to trials of drugs intended to treat serious or life-threatening diseases, but rather requires registration of all clinical trials, other than Phase I, and requires significantly more content. As of December 26, new data points for initial registration became required, even reaching back to include some clinical investigations that began before the law was passed.4 NIH has also been directed to expand ClinicalTrials.gov to include trial results.5 By this fall, sponsors will have to submit results information about approved products, and soon thereafter, adverse event data will be required on the site.
Additionally, the law directs the promulgation of regulations by September 2010, further expanding the results database “to provide more complete results information and to enhance patient access to and understanding of the results of clinical trials.” 6 These regulations are mandated to require certain additions to ClinicalTrials.gov, and must also determine whether results requirements should be extended to unapproved products. However, their most important impact will be that states may no longer establish or continue in effect any requirement for the registration of clinical trials or the inclusion of results information upon the regulatory expansion of the federal data bank.
While preemption of state law will certainly streamline the registration burden, sponsors must recognize that the federal registration requirements now have teeth. Not only will failure to submit the required information in a timely fashion be posted on ClinicalTrials.gov, but sponsors may also face civil fines up to $10,000 for all violations adjudicated in a single proceeding. If noncompliance continues thirty days after notice, the fine may be increased $10,000 each day until the matter is resolved.
For the time being, Maine also imposes a $10,000 fine for each day its law is violated, and even states without specific trial disclosure laws of their own have shown activism in this area. New York, for example, has relied on consumer protection and fraud statutes to reach substantial settlements with pharmaceutical companies and medical device manufacturers for failure to disclose information gathered in clinical studies. Whether application of these state laws would be preempted by compliance with the new federal disclosure requirements is yet to be seen.
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Transparency with regard to clinical trials and their results is essential for all sponsors, and Congress has reasserted that message through its 2007 law. Going forward, trial sponsors must ask themselves the following questions:
- Which of the company’s trials fall under the scope of federal registration requirements?
- Have all of the company’s trials subject to the December 26, 2007 deadline been appropriately registered with ClinicalTrials.gov?
- Will all other company trials not yet required to register be appropriately registered by the applicable deadline?
- Will results information be required for the company’s trials and by what date?
- Who within the company will be responsible for ensuring compliance and serve as the point of contact for information on the company’s registered trials?
- Will any registration responsibilities be delegated to Principal Investigators?
- What are the most important issues concerning the posting of results information that the company would like to see addressed in the required federal regulations implementing the new law?
- Are the company’s trials subject to Maine’s requirements, prior to preemption?
- Will the company be impacted by the ICMJE requirements?
Now is the time for pharmaceutical companies to establish or reevaluate their clinical trial disclosure policies, ensuring that their trials are in compliance with each requirement and deadline set by statute, as well as those imposed by medical journals and regulations yet to come.