Steven Nissen Gives Obama an Rx for FDA Reform

[Pharma Newshound]

Cleveland Clinic cardiologist Steven Nissen wants the FDA to make more data from clinical trials public.

Here's Nissen's Letter, which was published in Nature:

Steven E. Nissen

Chairman of the department of cardiovascular medicine, Cleveland Clinic, Ohio, USA.
An end to secrecy will revive the Food and Drug Administration.

After an unprecedented series of revelations about drug and device safety issues, many observers consider the Food and Drug Administration (FDA) a failed agency. The Obama administration has the opportunity to reinvigorate the FDA, but only through major restructuring and policy changes that are designed to protect the agency from undue influence, and to promote transparency.

The next FDA commissioner should serve a fixed six-year term to insulate the agency from political influence. Moreover, the system by which pharmaceutical companies fund a major portion of the FDA's budget through user fees requires re-evaluation.

Secrecy is antithetical to both science and good government, but much of what the FDA knows about drugs, it never publicly discloses. The agency must cease to regard clinical-trial data as proprietary and provide access to all available information on safety and efficacy. This policy should apply to information gathered during approval for drugs, and to post-approval surveillance. The agency needs better harmonization between its Office of Surveillance and Epidemiology, which monitors post-marketing safety, and its Office of New Drugs, which is responsible for post-marketing regulatory decisions.

The current voluntary mechanism for adverse-event reporting is relatively ineffective, because only 1%–10% of events are actually reported. Partnerships with large health-care providers, such as health maintenance organizations that supply care through hospitals, doctors and other providers, are needed to prospectively assess drug safety.

The approaches used to approve drugs need attention. Drug approvals are often based on placebo-controlled clinical trials. However, appropriate use of therapies requires understanding comparative effectiveness. The FDA has increasingly used 'non-inferiority' study designs to support efficacy. In these, a treatment is considered 'approvable' if it retains 50% or more of the effectiveness of a comparable product, which may represent too lenient a standard. The agency has also increasingly used 'surrogate endpoints' (biomarkers or laboratory measures) to support approvals without subsequently requiring more informative clinical-outcome studies.

For medical devices, the agency has authority to clear a product for market if it is deemed 'substantially equivalent' to devices already being sold. This rule has become the principal approach used to approve medical devices. However, even small changes to a device can affect safety, which has resulted in major safety recalls, such as for defective pacemaker leads.

Stronger enforcement capabilities are required throughout the agency. The Division of Drug Marketing, Advertising, and Communications needs the right to restrict direct-to-consumer advertising during the first two years a drug is marketed and to preview advertising to ensure it is not misleading. An FDA policy introduced in 2008 unwisely allows off-label promotion of drugs and devices through distribution of article reprints, an approach that may encourage unsafe use for unapproved indications and discourage appropriate clinical trials to establish new indications.

Currently, about 1,600 facilities in China manufacture drugs or components of drugs marketed in the United States. Recent high-profile cases — such as contaminated heparin — poignantly illustrate the risks inherent in globalization. The FDA must increase inspections and foreign governments must be held accountable for setting regulatory and safety standards for local manufacturing. All of these initiatives require more robust funding of the FDA, which currently has a budget of $2.3 billion with which the Agency must regulate $1 trillion worth of food, drugs, cosmetics and medical devices. The agency's budget is quarter that of the Centers for Disease Control and Prevention, which has a significantly more limited mission. Congress must re-evaluate priorities and recognize that ensuring the safety of food and drugs is a crucial national priority.

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