A study had indicated that Vioxx increased the risk of stroke and heart attacks in some patients who used it for extended periods. After Vioxx’s withdrawal, safety questions arose about Cox-2 inhibitors generally, including Celebrex and Bextra, and certain other approved drugs.
In response to these events, the FDA has begun taking steps to strengthen its safety program for approved drugs, and Congress is likely to consider legislation this year. An effective response will require a multi-faceted approach that involves FDA, pharmaceutical companies, health care providers and Congress. Ideally, these changes will lead to improved monitoring of marketed drugs, more thorough examination of side effects and greater benefit and risk information. If you’re planning to start a pharmaceutical company to develop new drugs, you may work with a firm that provides drug process development services and improve the chances of your products being approved by the FDA.
Monitoring marketed drugs
The FDA should be given clearer legal authority and more resources to monitor approved drugs.
Typically, new drugs are studied in about 3,000 patients before approval. These studies can identify drug-related adverse effects that occur in one-in-500 to one-in-1,000 patients. For widely used drugs, a serious adverse event that occurs in one in 10,000 is substantial. Such rare reactions can be identified only after a drug is widely used.
The FDA’s authority to require manufacturers to conduct post-market studies of approved drugs is unclear. Drug manufacturers must pay user fees when they submit drug approval applications. The FDA must act on those applications in a timely manner. As a result, many more resources are available for drug approval reviews than for adverse event surveillance.
Resources for drug approvals are important, but additional resources for surveillance are needed. With that and clearer authority, the FDA could identify risks with unexpected adverse events sooner and could require manufacturers to conduct studies to resolve questions about adverse event patterns.
The FDA drug review division responsible for approving a drug is also primarily responsible for determining whether it should be withdrawn or have its approved uses limited. The FDA’s Office of Drug Safety should be strengthened and have primary authority for post-market safety issues.
Better tracking of side effects
In the United States, physicians voluntarily report adverse events associated with a drug. This system works best for identifying unusual side effects such as allergic reactions or kidney toxicity. This system is less useful for identifying problems, such as heart attacks, that could have happened without the drug. For such problems, particularly in newer, commonly prescribed drugs, use of patient registries that track patients for benefits and side effects would be a significant improvement. A strengthened Office of Drug Safety could use registry data to identify patterns and evaluate appropriate next steps.
Benefit and risk information
All approved drugs have risks. The FDA’s approval decisions are based on benefit-risk judgments.
The FDA may approve a drug with significant side effects where, for example, adequate treatments do not exist or the drug presents an advantage over existing treatments. Currently, when a severe side effect is identified with an approved drug, it is added to the drug’s labeling, and letters are sent to physicians who may prescribe it. But this approach has only limited impacts on prescribing patterns. Some have suggested severe restrictions on direct-to-consumer advertising as a response to this problem. However, such restrictions will likely have difficulty passing First Amendment scrutiny.
Manufacturers should expand their voluntary efforts to educate physicians and consumers about risks. The FDA should also increase its efforts to publicize safety issues associated with marketed drugs and to better inform the public that all drugs have risks.
What’s next?
A new Secretary of the U.S. Department of Health and Human Services has begun work. The acting commissioner of Food and Drugs is likely to be confirmed as commissioner. Under this leadership, FDA appears on track to continue to strengthen post-marketing surveillance of approved drugs.
Whether, when and how Congress will act is unclear. Congress rarely moves quickly on major changes to FDA authority. Instead, Congress tends to consider proposals over the course of two or more year-long sessions.
The President’s fiscal year 2006 budget – and Congress’ response – will be an important early indicator. Without more resources, FDA will find it difficult to implement meaningful enhancements to its post-marketing program.
Signs already exist that FDA reviewers are becoming more cautious in their approvals of new drugs, and requiring more information. Such shifts will cause drug development and approval to take longer and cost more. That could have a profound impact on patients with life-threatening diseases that have resisted conventional treatments.
To avoid such impacts and to help make the “FDA approved” brand even stronger in the world marketplace, Congress should act effectively and soon.
Patricia J. Kaeding was an associate chief counsel at the U.S.
Food & Drug Administration for 10 years and currently serves as the lead attorney in Godfrey & Kahn’s FDA Practice Group in Milwaukee.
February 18, 2005, Small Business Times, Milwaukee, WI
