FDA reform continues in new programs to track drug safety and share data with the public.

The FDA has a three part mission but has been criticized in focusing on only one of these.  The missions of the FDA are:

1) To promote and protect the public health by helping safe and effective products reach the market in a timely way (however this is the focus of what they do now- new drug approval). 
2) To monitor products for continued safety after they are in use (new programs are to focus on this)
3) To help the public get the accurate, science-based information needed to improve health (new programs are to focus on this)

Why is post-approval FDA drug safety monitoring important for the US population? A September 2006 Institute of Medicine report recommended 25 changes to ensure the safety of prescription drugs. FDA has responded with an announcement that it will establish a pilot program that will publish a “report card” that reviews the side effects, use and latest research on two or three new drugs 18 months after they reach the market.  The IOM report’s major recommendations are:

• A requirement that packages for new prescription drugs for two years include a symbol to inform patients that the safety profile of the medication is not fully established
• A restriction on direct-to-consumer advertisements for new prescription drugs for the first two years
• A requirement that FDA reevaluate the safety and effectiveness of new prescription drugs within five years of approval
• Additional authority for FDA to impose fines on pharmaceutical companies
• A requirement that pharmaceutical companies register all clinical trials they sponsor in a federal database accessible by patients and health care professionals
• A requirement that most FDA advisory committees members have no potential conflicts of interest with the pharmaceutical industry
• A six-year term of office for the FDA commissioner.

kaisernetwork.org further comments on the FDA deficiencies leading to the recommendations:

Committee Chair Sheila Burke, said “We found an imbalance in the regulatory attention and resources available before and after approval. Staff and resources devoted to pre-approval functions are substantially greater. Regulatory authority that is well-defined and robust before approval diminishes after a drug is introduced to the market” (Bridges, AP/Chicago Sun-Times, 9/24).

Post marketing approval is vital since the clinical trials that lead to drug approval are so tightly constructed that they often have limited applicability to the general real-world population.  As a clinician and investigator I see this every day.  This was one of the reasons why in years past so few drug trials included women and minorities - whose different genetics and metabolism led to unexpected results and side-effects when they took the drugs as patients. 

Committee member R. Alta Charo, a bioethicist at the University of Wisconsin-Madison, said that clinical trials conducted prior to the approval of new prescription drugs might not provide an accurate safety profile for the general population. “A drug tested in a few hundred or thousand people is very different when used by millions, especially over long periods of time and in conjunction with other supplements,” Charo said. Charo also said that FDA has “a lack of collaboration among divisions, tensions (and) inappropriate management” (Washington Post, 9/23).

FDA picks three areas to focus upon out of the 25 IOM recommendations.

1. Strengthening the science used during product reviews and finding new tools to detect safety issues from preclinical testing through postmarketing.

2. Improving communications, especially about risk, to patients, physicians, and other interested parties.

3. Improving management practices.

Funding to come from new fees on drug makers Under the Prescription Drug User Fee Act the FDA aims to collect $29 million from drug makers over 5 years specifically for postmarketing safety programs.

New Drug Report Card reports ognews

Key among the new initiatives announced in late January is a “report card” on the postmarketing safety of new molecular entities. FDA has proposed a pilot feasibility study this year. These periodic, regularly scheduled reports would encompass data from the Adverse Events Reporting System (AERS), epidemiologic studies, postmarketing clinical trials, and from “mining” of various other databases. The first report would come 18 months after a drug’s launch. The goal of this effort is “to identify potential safety concerns early in the product life cycle,” according to the FDA.

Hearings to look into public safety reporting system

The FDA also said it would hold a public meeting in early March to explore the creation of a nationwide public-private medical product safety network. The agency envisions a network that would let both health care providers and regulators rapidly collect and exchange information about adverse events—and would do so at the point of care to help providers make better-informed treatment decisions

Senators want to go even further

Sen. Christopher J. Dodd (D-Conn.) Sen. Chuck Grassley (R-Iowa) are introducing a bill that would “revamp and prioritize the postmarket surveillance process within the Food and Drug Administration.”  The Food and Drug Administration Safety Act, would establish a Center for Postmarket Evaluation and Research for Drugs and Biologics. The Center would report directly to the FDA commissioner.

Further FDA Initiatives for this new surveillance reported by medical news today

• Collaborate with the Department of Veterans Affairs, CMS and private insurers to collect data on any problems that physicians and patients encounter with medications
• Increase transparency in the process of how the agency selects advisory panel members (Vedantam, Washington Post, 1/31)
• Create a new advisory panel that will recommend ways for the agency to improve how it communicates with the public about potential drug risks (New York Times, 1/31)
• Publish periodic newsletters on its Web site to update the public on post-market reviews of medications
• Implement organizational changes to improve communication between agency employees who monitor drug approvals and those who monitor post-market safety (Rubin, USA Today, 1/31)
• Modernize the “adverse events” database so that potential problems are easier to recognize (Alonso-Zaldivar, Los Angeles Times, 1/31)
• Renew the agency’s focus on scientific endeavors, including the creation of a database of genetic codes associated with poor drug outcomes and developing screening tests to identify patients at highest risk for adverse events (New York Times, 1/31)
• Appoint a chief medical officer to oversee scientific operations (Pugh, Miami Herald, 1/31)

They also report FDA claims inadequate funds or authority to enact all IOM recommendations

FDA’s proposals did not address a number of the IOM report’s recommendations, some of which would require congressional action, the Times reports (New York Times, 1/31). For example, FDA did not say it would restrict direct-to-consumer advertising of new prescription drugs or require label changes that would alert consumers if treatments had been on the market for less than two years (Miami Herald, 1/31). FDA Commissioner Andrew von Eschenbach said the agency considers the IOM report “a substantial amount of advice” but not a “rigid blueprint” (USA Today, 1/31). In its response to the IOM report, FDA said it “believes it has the statutory and regulatory authority needed to carry out its commitment to ensure drug safety,” although it added that it needs more funding to do so (Wall Street Journal, 1/31).

Last Minute Update Today From Washington Post: Experts recommend that FDA not allow drug companies to keep drug research study results secret. 

I have seen this happen too many times!  I can recall being involved or hearing about studies of both drugs and devices for FDA approval that did not go as expected and did not show the results the manufacturer expected.  Unfortunately, all too often the compnay contract with the physician researcher or university stipulates that the doc is not free to publish the data on his own.  In effect a virtual gag order on the negative results.  I quickly learned at Yale that for intellectual and academic integrity the University would insist we not have these clauses.  Washington Post reports:

Changes need to be made to the U.S. Food and Drug Administration’s policy regarding the confidentiality of drug safety data from clinical trials, say researchers at the Harvard School of Public Health and Brigham and Women’s Hospital in Boston. 

Current rules allow drug companies to keep data secret, which prevents the public from learning about dangerous side effects of drugs, the researchers said. Allowing greater public access to this data would enable outside experts to independently evaluate the data and perhaps detect risks sooner.

They report that FDA supports blocking access to the information

The FDA and the drug companies say drug information needs to be protected so that competing manufacturers can’t use the data to produce competing versions of drugs. However, the commentary authors argue that making drug safety data public rarely poses a risk to a company’s confidential research and development programs.

“The legal question is whether the information will give other drug companies an unfair competitive advantage. But it is strange to argue that evidence that a drug is harmful will enable others to develop similar drugs,” noted co-author Michelle Mello, an associate professor of health policy and law at the Harvard School of Public Health.

and the authors recommend:

A heavier burden of proof be placed on companies to show competitive harm if safety data are released.The FDA replace the current Summary Basis of Approval with a more comprehensive public document that includes all safety data.Congress passes a law that requires public disclosure of safety data if the FDA fails to take action.

“Safety data from drug clinical trials have important ramifications for public health. The government should do as much as it can to ensure full disclosure of the information,” Kesselheim said