Drugs: Effective for the Few, Prescribed to the Many

Every time you walk into a physician's office, you run the risk of overtreatment: Tests you don't need, medications that are ineffective (or dangerous), procedures that cause more problems than they solve. Here, we look at the problems of ineffective drugs and their side effects. 

Most of us trust, or at any rate hope, that the benefits of a drug our doctor prescribes will outweigh the side effects. Why else would we take it? We would probably be shocked to learn that most drugs don't do anything good for the majority of the people who use them. That's probably because we picture a simple cause-and-effect relationship, like antibiotics curing an infection. "But most chronic diseases involve a complex chain of biochemical interactions," says Dr. Jonathan St. George, assistant professor of emergency medicine at Weill Cornell Medical College. "The idea that you're going to take one drug that affects one pathway and dramatically change the course of the illness is just pie in the sky." The statistical measure that crystallizes this inconvenient truth is the NNT, or "number needed to treat" – that is, the number of people who have to take a drug in order for one person to benefit. There are plenty of popular drugs with NNTs over 50, and a drug with an NNT of five or fewer might fairly be considered a wonder drug – for instance, sumatriptan for migraines or steroids for kids with croup. "But if I told my patients that the drug I was prescribing them had only a 20 percent chance of working," St. George says, "they'd look at me like I was crazy."

The reason you've probably never heard of the NNT is that the pharmaceutical industry ignores it when marketing its wares to the public. According to Newman's website, thennt.com, which crunches the best available research data to arrive at NNTs for common tests and therapies, statins have an NNT of 60 – meaning 60 people would have to take a statin drug for five years to prevent one person from having a nonfatal heart attack. Not one heart attack death would be prevented. Picture a similar effect this way: a study in which a control group of 1,000 people taking no heart medication suffered 24 heart attacks over a five-year period, while the group on statins suffered 16. Because these numbers are small, even relatively minor differences between the incidence of heart attacks translate into an impressive-sounding difference, when you measure it as a percentage – the so-called relative risk. Now you've got the makings of a pharmaceutical ad campaign: "Statins reduce heart attacks by 33 percent."

It gets worse. Stanford epidemiologist John Ioannidis got the medical world's attention in 2005 with a journal article titled "Why Most Published Research Findings Are False." In it he notes that 80 percent of published drug studies are funded by the drug industry, and that some 30 percent of all drug studies are never published, presumably mostly the negative results that never enter into the final cost-benefit reckoning.

But, Hadler says, even if we were to take the research at face value – that a given drug has a statistically significant benefit when the NNT is, say, 50 or higher – the benefit is so small it's clinically meaningless. But fortunes are made from such microscopic benefits. The pharmaceutical companies can create blockbuster drugs by promoting meds that have shown benefit in a smaller, targeted population – say, statins for people who've already suffered a heart attack – to a larger, relatively healthier population, with the hope that the medication might be good for them, too. "Blockbuster drugs demand overtreatment," Hadler says. Beyond the side effects that the overtreated may suffer for no offsetting gain is what Newman calls the culture of the pill. "It's destructive to physicians," he says, "and to patients who believe, 'I can forget all the lifestyle stuff because I can take a pill and I'll be good.' "

Statins

Introduced in the States in the late 1980s, statins inhibit an enzyme that the liver uses to make cholesterol, in most people dropping that LDL number by between 30 and 50 percent. At a cost. Newman crunches the research figures and calculates that for every 50 people on statins, one will develop type 2 diabetes who otherwise would not have. The statistic that tells you what you need to know about the severity of a drug's side effect is the "number needed to harm." So if we're talking about diabetes risk, the NNH for statins is 50 – dose 50 people with a statin and you can expect to see one extra case of type 2 diabetes turn up.

The most common side effect of statins is muscle pain and weakness and, in severe cases, muscle breakdown. Here the NNH is 10 – 10 to treat, one to harm. Mental "fuzziness" and forgetfulness haven't been rigorously studied enough to generate an NNH, but enough anecdotal reports have come in that two years ago the FDA slapped statins with a cognitive safety alert.

So this past November, when a panel convened by the American Heart Association released its new guidelines on statins, you might have expected it would take a more conservative line on prescribing – that, given the possible side effects, they would want to prescribe the drug only to a more select group of patients for whom the benefits clearly outweigh the harms. But with statins you'd be wrong.

http://www.mensjournal.com/

Graham