Personal Views: Pitfalls on the road to drug safety
Authors: Carl Schoenberger
Journal: BMJ (2004)

The recent withdrawal of rofecoxib (Vioxx) from the worldwide market has focused intense public scrutiny on drug safety. Although the US Food and Drug Administration monitors drug safety after product approval, some have raised concerns about whether this system, which relies primarily upon voluntary reporting of adverse drug effects, is adequate to protect the public from unsafe pharmaceuticals.

In his televised appearance before the US Senate finance committee on 18 November, Dr David Graham, associate director in the FDA's Office of Drug Safety, claimed his own agency was “incapable of protecting [the public]” from other dangerous pharmaceuticals (BMJ 2004;329: 1253. [PubMed]). He then listed five drugs that he considered potentially unsafe—the acne drug isotretinoin (Roaccutane), the weight loss drug sibutramine (sold as Reductil in Britain and Meridia in the United States), the cyclooxygenase-2 inhibitor valdecoxib (Bextra), the lipid lowering drug rosuvastatin (Crestor), and the asthma drug salmeterol (Serevent).


I am all for drug safety, but I am also for patient safety


As a pulmonologist, I can only comment on the one drug on Dr Graham's list that I use frequently—salmeterol. I have kept abreast of the literature on this agent and am aware of two potential problems with it: the use of salmeterol as opposed to a rapid onset bronchodilator (such as salbutamol, or albuterol, as it is known in the United States) to treat acutely deteriorating asthma; and the increased death rate observed in the SMART (salmeterol multi-center asthma research trial) and SNS (salmeterol nationwide surveillance (BMJ 1993;306: 1034-7 [PubMed])) studies, in which salmeterol was given for maintenance without an accompanying inhaled steroid (such as fluticasone—the accompanying ingredient in Advair). In both of these instances, an excess of deaths has been reported, although the absolute increase in risk was rather small. Both of these precautions are listed in a “black box” on the package insert and should be well known to doctors using this drug.

The total number of patients currently taking salmeterol worldwide is more than 24 million, and my own experience as well as that of my many colleagues who treat asthma has been overwhelmingly positive with this agent. Shortly after the news of Dr Graham's “list” was broadcast, I started receiving calls from asthmatic patients who stopped taking this drug in response to the television reports and, predictably, noted their asthmatic symptoms increasing. A similar phenomenon occurred about eight years ago when news reports highlighted risks associated with calcium channel blockers in the treatment of coronary artery disease. Predictably, many patients stopped their calcium blockers, resulting in a number of acute coronary and cerebrovascular events that would not otherwise have occurred because of rises in (previously well controlled) blood pressure.

I am all for drug safety, but I am also for patient safety. Media treatment of these types of stories tends to glorify the whistleblower as a crusader for public safety, and usually ignores the fine print of what is well known by professionals in the relevant field. Many members of the lay public respond by acting impulsively—stopping their drugs—rather than discussing their individual circumstances with their doctors to see whether the alleged risks outweigh potential benefits in their particular case.

I am no fan of the big drug companies and have always opposed direct to consumer advertising of prescription drugs and direct to physician drug marketing. Both of these activities are aimed at marketing, rather than education. Overall the drug companies spend more on marketing annually than they do on research and development, and that is outrageous in my opinion. The 15% annual rate of increase in drug costs (including yearly price increases for well established prescription drugs, not just new “miracle” drugs), which makes pharmaceuticals the single most profitable sector in the US economy, is a major driver of higher health costs and higher health insurance premiums. This needs to be changed if we are to bring health costs into a more reasonable range.

But at the same time, we need to be cautious about taking at face value the statements made by Dr Graham and others who appear to be champions of the vulnerable patient. In their efforts to promote patient safety, they may sometimes be causing more harm than good, and there may be better ways to achieve the goals of patient safety than making what I consider irresponsible statements on nationally televised hearings.