Drug Safety

Drug safety—or, more precisely, drug non-safety—is an issue that gets frequent and intense public scrutiny and media coverage. From Vioxx to heparin, the dangers of prescription medications have captured the attention of doctors, patients, journalists, politicians, and lawyers. The Food and Drug Administration (FDA), a convenient and often unfairly maligned scapegoat, is under almost constant attack. And patients, not always trusting the judgment of their physicians, rely on a variety of sources for information about drugs, some of dubious value. For rheumatology, the escalating turmoil about drug safety has been juxtaposed with the rapidly changing approaches to therapy of rheumatic diseases. At a time when our use of pharmaceuticals is evolving at a much faster pace than ever before, rheumatologists and their patients have more questions about drug safety than ever before. What are the elements that have created this crisis? And what is the ACR doing on behalf of its members and their patients to address drug safety issues?

Before commenting further, a disclaimer is needed. I’m not an expert on pharmacology, drug development, or drug safety. The little I know comes from treating patients with rheumatic diseases since 1981 (which includes my fellowship training), reading both the medical literature and the lay press, and whatever my colleagues in the ACR who are real experts in this area have been able to teach me. But one of the perks of being ACR president is that once a month you get to write a column in The Rheumatologist (TR) about a topic of your choice, even if you don’t know that much about it! (And without even having to stay at a Holiday Inn Express.)

So, in no particular order, here are what I see as some of the roots of the drug safety mess:

• The high cost of drug development and the opportunities for blockbuster profit push manufacturers to expand usage of drugs too quickly after approval—both through intensive marketing to physicians and direct advertising to consumers—before enough time has elapsed to get a sufficient understanding of the safety issues.
• The FDA has become seriously understaffed and underfunded in the face of an expanded mandate that now also includes worldwide supervision of pharmaceutical manufacturing practices, a necessity that has been dramatized by the adulterated heparin episode. Only this year, after numerous fatalities from contaminated heparin, are additional funds being appropriated that will allow the FDA to hire more regulatory staff.
• In some cases, pharma has been slow to fully reveal safety concerns, or has manipulated the writing of scientific papers and reviews (as discussed in June’s ”President’s Perspective,” p. 4). Regulatory penalties and lawsuits are the inevitable consequences of such incidents.
• Patient expectations are at times too high. The notion that dangerous diseases can be cured by innocuous remedies, a perception that is fueled by the way that medical advances are often reported in the mass media, is rarely accurate.

But as important and concerning as these issues may be, it seems to me that the more fundamental reason for a drug safety problem is the existence of enormous gaps in our knowledge, due to enormous gaps in the data that is available. An important reason for this has to do with the way that drugs are studied during the drug development and approval process. Patients who are too young or too old, or who have any of a long list of co-morbid conditions, are excluded from clinical trials, yet these groups represent most of the patients whom we treat. And, often, these are the people who experience more frequent, more severe, more diverse, and more unexpected drug toxicities. It’s obvious that either clinical trials need to be designed in a different way and/or post-approval data collection from real-world practice settings needs to improve.

ACR Actions

1. Treatment guidelines: Under the supervision of the ACR Quality of Care Committee (QOC), chaired by Daniel Hal Solomon, MD, (an expert in drug safety and a TR editorial board member), groups of experts are updating treatment guidelines for a variety of rheumatic diseases. The new guidelines for the treatment of rheumatoid arthritis were published in June’s Arthritis Care & Research, together with an editorial commentary. (See p. 1 to read more about the guidelines.) These guidelines provide guidance for clinicians in both disease management and safe use of drugs, while pointing out important safety questions for which sufficient data is simply not yet available. Updated guidelines for management of osteoarthritis and glucocorticoid-induced osteoporosis are due out next year.