Pushing pills

ERIC B. LARSON, M.D.
Last updated: April 27th, 2008 01:27 AM (PDT)

Maybe it’s also human nature that when profits can be made, businesses find more ways to attract consumers.

This dynamic has produced amazing innovations to relieve human suffering. It has also brought the pharmaceutical industry tremendous profits – especially in recent years with more direct-to-consumer marketing. According to the Kaiser Family Foundation, U.S. spending for prescription drugs was $200 billion in 2005, nearly five times as much as in 1990.

In the drug companies’ rush to exploit this expanded market, some companies seem to have ignored established scientific standards for conducting research and reporting results. Now – with Vioxx, Zetia and Vytorin – we have seen evidence that such failures are risking patients’ lives and driving up the cost of care for all.

Under attack this month is Merck, maker of the painkiller Vioxx, which was withdrawn for safety problems in 2004.

A new study published in the April 16 Journal of the American Medical Association shows that Merck may have misrepresented data to the FDA that significantly minimized the drug’s risk of death to patients with Alzheimer’s disease and dementia.

Dr. Bruce M. Psaty, director of the University of Washington Cardiovascular Health Research Unit and a Group Health scientific investigator, conducted the analysis with his colleague, UW biostatics professor Richard Kronmal. This information came to light only when the pair analyzed internal Merck documents uncovered during recent litigation against the company.

This disturbing news comes on the heels of an April 3 report that two blockbuster cholesterol-lowering drugs, made by Merck and Schering-Plough, Zetia and Vytorin, appear to be less effective at preventing heart disease than statins alone.

After these two drugs earned more than $5 billion for their makers in 2007, a two-year randomized and controlled trial published in the New England Journal of Medicine showed that the new drugs failed to slow – and might even have spurred – the growth of plaque in arteries, which can set the stage for heart attacks and strokes.

How could the drug makers have gotten it so wrong? By promoting drugs shown to affect a surrogate endpoint – in this case, reducing “bad” (LDL) cholesterol, a cardiovascular risk factor – without proof that it actually reduces illness or death.

It doesn’t have to be this way. In a different article in JAMA, Psaty contrasts the FDA’s approval of Zetia and Vytorin with its handling of torcetrapib. Another once-promising cholesterol drug, torcetrapib also was shown to affect a surrogate endpoint: boosting “good” (HDL) cholesterol. But further study showed this drug actually increased cardiovascular problems and deaths. So Pfizer stopped developing torcetrapib before asking for FDA approval.

Psaty points out striking differences in the drugs’ histories. Zetia and Vytorin were “approved and marketed aggressively,” he explains, while randomized controlled trials evaluating their effects on heart disease, heart attacks and strokes were “slow to be reported or started.” In contrast, a large, long-term randomized controlled trial evaluating torcetrapib’s link with major cardiovascular problems was well under way before FDA consideration.

That’s the way it should be, according to Psaty. The FDA should consistently work with drug sponsors to ensure that large, long-term randomized controlled trials evaluate medications adequately before any promotion to the public.

That did not happen with Zetia and Vytorin. Instead, early and aggressive marketing by Merck and Schering-Plough have resulted in some 800,000 Americans now taking these questionable drugs. Meanwhile, use of statins has fallen sharply. Yet statins are available in generic form, far less expensive and proven to cut not only cholesterol levels but also deaths from heart attacks and stroke.

A $200 million consumer ad campaign for Zetia and Vytorin fueled the drugs’ success in the U.S. from 2002 to 2006, according to another study. Sales of Zetia and Vytorin during that period were four times lower per capita in Canada, which bars direct-to-consumer drug marketing. And while sales of statins fell in the U.S., they remained stable in Canada.

In the presidential election debates over health care costs, drug prices have become a common target. In addition to proposing that Medicare negotiate with drug companies for lower prices, all three major candidates say they want to encourage more use of generic drugs while introducing restrictions on direct-to-conumer drug marketing. This makes sense.

Unlike in Canada and the rest of the world, lax U.S. policies on DTC marketing have allowed too many ill-advised ads. The drug industry calls DTC advertising “health education” – even suggesting it can “activate” patients. But on balance, the only healthy results I see are in the drug-industry’s profit statements.

I predict that one day soon we’ll look back to see the real impact of aggressive direct-to-consumer marketing of blockbuster drugs, particularly those ultimately proven unsafe, ineffective, or both. That impact? More illness and dramatically higher health care costs.

Dr. Eric B. Larson is executive director of Group Health Center for Health Studies in Seattle.

Originally published: April 27th, 2008 01:27 AM (PDT)