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By Matthew Boyd Van Hook
Senior Counsel, Holland & Knight LLP
In the wake of the recent withdrawal of Vioxx, and the U.S. Food & Drug Administration’s (FDA) decision to require “black box” warnings on all antidepressants because of concerns regarding suicidal tendencies in adolescents, the entire health care industry is facing changing regulatory expectations and perhaps growing liability risks as well.
On November 5, Lester Crawford, then Acting FDA Commissioner and now Commissioner, announced a range of initiatives aimed at strengthening the agency’s safety program for marketed drugs, including a review by the Institute of Medicine of the FDA’s current role in overseeing both drug review and approval, and post-approval drug safety (so-called “pharmacovigilance”).
Outlined briefly below is a “pharmacovigilance checklist” with some directional/non-prescriptive suggestions for pharmaceutical, biotech and device companies to consider in reviewing existing policies and programs. The text was derived from a speech, “New Era of Pharmaco(ultra)vigilance? Changing Laws and Product Liability Risks Are Impacting Standards of Care, FDA Role,” given by the author at a Food and Drug Law Institute Conference in November 2004.
1. Support use of accredited Institutional Review Boards (IRBs).
The process of voluntary accreditation can help standardize best practices for the conduct of human clinical trials, assure a proper focus on regulatory compliance, and achieve these and other benefits without increasing regulatory burden. Consider, for example, AAHRPP (the Association for the Accreditation of Human Research Protection Programs, www.aahrpp.org).
2. Timely register of human clinical trials in the federal Data Bank www.clinicaltrials.gov.
Congress intended the data bank to be a resource to facilitate patient enrollment in U.S. trials testing the efficacy of medicines for serious and life-threatening disease. The HHS Office of Inspector General will be studying pharmaceutical industry compliance, and FDA implementation efforts in 2005.
3. Attend to Phase IV study commitments.
There are many legitimate reasons why post-marketing studies are not completed in the timeframe initially agreed to with the FDA. But there can be ramifications for failure to complete studies in a timely fashion; the HHS Office of Inspector General also plans to update its review of industry compliance in this area during 2005.
4. Establish and implement company policy regarding the disclosure of clinical trial results.
New York Attorney General Eliot Spitzer insists that a “new standard of disclosure” has been established for industry to establish an online register containing summaries of all trials conducted since 2000. Regardless of whether there is in fact a “new standard,” companies need to decide whether and what to report, consistent with FDA labeling and promotion obligations, as well as the SEC/FDA procedure that has been established for referring allegedly “false and misleading” statements to the SEC Division of Enforcement.
5. Recognize that there is a growing focus on post-approval review, and a changing role for both private and public payers like the Centers for Medicare & Medicaid Services (CMS).
There are changing concepts of non-routine risks, with implications for maintaining a drug’s approval status in the face of newly available benefit/risk data. Further complicating the picture is the emerging role of CMS in sponsoring outcomes research, and even conditioning Medicare payment for treatment on paying for (in the case of drug sponsors) and participating in (in the case of patients) efficacy/outcome studies.
6. Anticipate the impact of negative trial results on indications, labeling and approval status.
Too much is at stake to begin planning what actions to take only after negative human clinical trial results become available. Complicating sound planning is the fact that any statements, e-mails and memos concerning emerging information will surely be viewed, and judged, in hindsight. Even the introduction of a later-generation drug can have implications for the continued viability of the first drug in a given therapeutic class (as was the case with the withdrawal of Seldane following FDA approval of a “safer” alternative, Allegra). There are also growing stakes for both innovators, and generics, in the FDA’s determination of the reasons for withdrawal under 21 C.F.R. Â§314.161.
7. Prepare Direct-To-Consumer (DTC) advertising programs to withstand further heightened scrutiny.
Recent FDA guidances have noted the pro-patient benefits of DTC (to stimulate doctor visits and patient awareness, and reveal previously undiagnosed conditions). However, some have long questioned the propriety of such ads and other promotional activities, which now will be under renewed pressure (e.g., whether ads can exacerbate product liability exposure, particularly where the FDA may have found them to be false, lacking in balance, or misleading).
8. Stay current on evolving preemption law and policy.
The FDA has been increasingly vocal in urging that federal approval and labeling decisions preempt state courts and juries, a trend likely to continue during the second Bush term.
9. Continually update employees on changing standards, and the implications for your business.
Changing expectations at the FDA, and at other state and federal enforcement agencies, necessitate stepped-up continuing education at regulated companies. Employees need to appreciate the importance of their roles for public health (e.g., signal detection as adverse event and other information comes in), and for maintaining corporate compliance (the growing array of post-approval obligations, and the need to recognize that any communication whether paper or electronic must be taken seriously and may last virtually forever).
For more information, e-mail Matthew B. Van Hook at email@example.com or call toll free, 1-888-688-8500.