A “perception of crisis” is harming the credibility of both the US Food and Drug Administration and the pharmaceutical industry, and they are failing to communicate drug safety concerns to the public in a timely, effective manner, says a damning new report.

Chronic underfunding, a lack of clear regulatory authority, a significant tail-off of FDA resources devoted to new products once they are marketed and inadequate post-approval data are harming the agency’s ability to monitor newly-marketed drugs, says the study, which was conducted at the FDA’s request by the Institute of Medicine, a component of the National Academy of Sciences.

The report calls for a newly-launched drug’s label to carry, for two years, a symbol stating that it is new and there may be uncertainties about its risks and benefits. The IoM also favours a moratorium on direct-to-consumer advertising for the drug during this period, although it acknowledges the “legal uncertainties” involved. Nevertheless, it says, DTC ads should at least note clearly that evidence for the product’s risks and benefit are less-developed than for older drugs and urge consumers to talk with their physicians about alternatives.

Five years after a product is approved, the agency should formally review all the risk/benefit information that has accumulated, the report adds.

The IoM also calls for clear authority and appropriate enforcement tools for the FDA, such as fines and injunctions, to ensure that drugmakers comply with label changes and conditions imposed on new products. Moreover, to improve public access to drugs’ safety and effectiveness information, registration of trial data should not longer be voluntary - Congress should legislate to require drugmakers to register all Phase II-Phase IV clinical trials, regardless of their outcomes, on the federal website (www.ClinicalTrials.gov) if data from the studies is to be submitted to the FDA.

On the current policy of allowing waivers for experts to serve on FDA advisory committees despite having financial ties to pharmaceutical companies, the IoM report says at least 60% of panel members should be free of such involvements, while waivers for other members should be issued “very sparingly.”

To implement these and other recommendations, it calls on Congress to authorize an increase in FDA staff and financial resources. This money should come from general revenues, as “all Americans have an interest in a robust drug safety system,” while boosting FDA post-approval activities should not be at the expense of its pre-approval responsibilities. Alternatively, Congress could lift most of the restrictions on how the FDA can apply the fees paid by drug sponsors, which are currently mostly used only for pre-approval work, the study suggests.

The FDA’s ability to assure the safety of marketed drugs has been under attack since the controversies over the withdrawal of Merck & Co’s blockbuster arthritis treatment, the COX-2 inhibitor Vioxx (rofecoxib), in September 2004.

Earlier this year, the Government Accountability Office reported on these issues at the request of Senator Chuck Grassley, chairman of the Senate Committee and Finance, and was equally critical*. Commenting on the new report, Sen Grassley said the Vioxx case had been “like a dead canary in a coal mine – a warning that worse may yet come.”

The IoM study “should be a watershed for FDA reform,” he said, adding: “today, there’s no question left that we need to strengthen post-market surveillance in order to improve drug safety and save lives. Consumers shouldn’t have to second-guess what’s in their medicine cabinets. Access to life-saving, life-enhancing drugs doesn’t have to come at the expense of safety.”

In his response, Health and Human Services Secretary Mike Leavitt said two steps could be taken quickly to help boost drug safety. First, he urged the Senate to speedily confirm Acting FDA Commissioner Andrew von Eschenbach permanently to the post, and, second, he called on Congress for health information technology legislation which stresses the importance of health records that are able to work together (interoperable). Without this, “we will lose many opportunities to improve drug safety,” he said.

Pharmaceutical Research and Manufacturers of America senior vice president Caroline Loew said it would be a mistake to accept the notion that the FDA drug safety system is seriously flawed; “after all, fewer than 3% of approved prescription drugs have been withdrawn from the American market for safety reasons over the last 20 years.” Efforts to improve the system must not harm patient access to medicines, she warned, adding: ‘it is also important to remember that all drugs have risks and the FDA has an effective system that weighs benefits and risks throughout the lifecycle of medicines.”

Jim Greenwood, president of the Biotechnology Industry Organization (BIO), also cautioned: “when considering enhancements to the US system, we must be cognizant that implementing undue hurdles in the drug review process will harm patients by delaying access to life-enhancing and life-saving products.”

BIO is a founder-member of the Coalition for a Stronger FDA, formed on September 25 by a group of industry, consumer and patient advocacy organisations to seek increased public support for the agency. The Coalition’s co-chairs are the three most recent HHS Secretaries - Tommy Thompson, Donna Shalala and Louis Sullivan. Said Dr Thompson: “our Coalition believes the FDA must be given the resources it needs to maintain and build on its position as the world’s premier consumer protection organisation.”

The Coalition has also released a poll which shows that, while the vast majority of Americans believe the FDA does vital work, they are unsure whether it can adequately ensure the products which it regulates are safe and effective.

* Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight Process - March 2006 - www.gao.gov