Risks, Benefits Need Continual Analysis

Posted June 17, 2007 at 11:00pm

It seems like every day there is a new crisis about the Food and Drug Administration or one of the products it regulates. One of the latest incidents, contamination of toothpaste and cough medicine with diethylene glycol, ironically centered on the very same chemical contaminating medicines that led to the creation of the Food, Drug and Cosmetic Act, and the FDA as we know it, in 1938. As we come full circle, it is becoming increasingly clear that we need to give the FDA more tools to evaluate and monitor the safety and effectiveness of drugs.

Some suggest the FDA needs a separate office to evaluate the safety of drugs after approval. These proposals would turn back the FDA’s regulation of drugs toward its original, and less functional, form. After passage of the FDCA in 1938, for the first time a manufacturer had to show a drug to be safe before it could sell the drug. It became apparent, however, that considering the safety of a drug without considering its benefits was not sufficient. So, in 1962, Congress amended the FDCA so that a manufacturer must demonstrate both safety and effectiveness before marketing a drug.

Risks and benefits are inextricably linked: You can’t consider one without the other. For example, although no one would accept nausea, hair loss and anemia in a drug for headache, patients do accept such risks to treat cancers. A focus solely on risks will deny treatments to suffering patients. A focus solely on benefits may mean a drug causes more harm than good.

When allowing a drug to be studied in humans, approving the drug, or assessing new information first available after drug approval, the FDA must assess risk and benefit together, and it must actively reassess the risk and benefit of a drug over its entire life span. The FDA must have teams with experts who can assess the safety and effectiveness of drugs based on pre-approval clinical trials and who can identify and manage risks post-approval, and these teams must closely evaluate drugs before approving them and more actively follow them after approval. Only such an integrated, life-cycle approach to drug regulation, one that considers both risks and benefits at every step, can ensure patients the promise of this century of the life sciences: a large choice of treatments for diseases that are now untreatable and the information necessary to make an informed decision about which to use.

We have spent the past two years developing a bill that takes this approach to drug safety and moves the FDA drug safety evaluation process into the 21st century. The Food and Drug Administration Revitalization Act strengthens the concurrent evaluation of risk and benefit information and requires close collaboration between the offices of the FDA charged with evaluating the safety and effectiveness of drugs. The Senate recently spent nearly two weeks debating our FDA reform bill, and we achieved a monumental victory when the Senate passed it by a 93-1 vote.

The weighing of risk and benefit information together is vital to determine how drugs, including the miracle products many of us take every day, get into the marketplace. This legislation, for the first time, gives the FDA the tools to take advantage of the rapid developments in science and technology and will allow it to evaluate the risks and benefits of new drugs with greater certainty and to monitor these drugs more actively once they are on the market and with a clearer purpose.

Most people would agree that knowledge is power. However, our current approach to gathering drug safety knowledge is largely passive. We rely on manufacturer reports, and doctors and patients recognizing a drug’s side effects, and taking the time to report it to learn about other possible side effects. In contrast, actively seeking safety information would better support science-based decision making about the drugs we take.

Take as an example Avandia, a diabetes drug that has been making news over the past couple of weeks. It still is not clear whether there is an increased cardiovascular risk with this drug, how big that risk might be, and what patients ought to do about it. But one thing is clear: With an active safety surveillance system, we could collect the information to figure it out and get patients and providers the information they need to make decisions about treatment because of new tools being provided to the FDA to make the surveillance effective.

The FDA does not currently have a mechanism for active, automated surveillance for potential safety problems. The agency, therefore, cannot detect safety problems as quickly and robustly as we would like after a drug has been put on the market. Observational studies or clinical trials are very good at answering certain questions, but they take time and are costly.

That is why our legislation calls for the creation of a routine, active safety monitoring system using large linked databases — what we call “health IT for drug safety.” These databases include existing sources such as the Medicare Part D database, which contains claims information for more than 40 million beneficiaries. Imagine the wealth of safety information just sitting there, waiting to be harvested and understood so that it can help the very people who contributed to it. This system is a critical tool for the FDA to ask the right questions and get answers in a reliable and rapid manner. However, there are some questions this system cannot answer, and our bill gives the FDA the authority to require the necessary clinical trials or studies.

Passage of the Food and Drug Administration Revitalization Act through the Senate is a big step, but our work is not yet done. We must ensure that the funding for these initiatives is secured through the appropriations process and that other mission areas in the FDA, such as food safety, are not given short shrift. The House also must move its version of the legislation.

This year marks the 70th anniversary of the first diethylene glycol contamination and a new focus on safety and protection of the public health. As we work to enhance drug safety, Congress needs to focus reform efforts on the emerging horizon of the life science century and resist the temptation to fall back into old methods and old ways of thinking about drug safety.

Sens. Edward Kennedy (D-Mass.) and Mike Enzi (R-Wyo.) are chairman and ranking member, respectively, of the Health, Education, Labor and Pensions Committee.