Meds and Machinations

How Merck Rejiggered Diagnostics and Disease to Create Demand for a Drug

How do diseases get defined and diagnosed? Who decides what counts as disease and therefore calls for treatment? It’s not always as clear-cut as you might think. The bone condition called osteopenia provides an interesting case.

It all started in a small hotel meeting room in 1992 Rome, when a group of osteoporosis experts convened under the auspices of the World Health Organization to standardize the diagnostic criteria of osteoporosis. Bone loss after age thirty was normal, especially in women, but at what point should the degree of loss be deemed disease? Professional opinion at the time was all over the map.

After two or three days of poring over research and trying to decide exactly where on the graph of diminishing bone density the line demarcating wellness from disease should be drawn, one of the participants stood up saying, “Well, let's just do this,” and drew a line.

And thus, it was decreed that all patients on one side of the line had osteoporosis. The next question that arose was, how to categorize those patients whose bone density was close to, but not quite over, the line? Someone came up with the term osteopenia. According to Anna Tosteson, a professor of medicine who attended the meeting, the category was created for the sake of public health researchers, since researchers needed categories for their studies. No one intended for osteopenia itself to become a disease.

Yet it did. Here’s how. In 1995, Merck Pharmaceutical released a new drug called Fosamax, a nonhormonal drug that Merck claimed stopped the progress of osteoporosis. But Fosamax wasn’t selling well, so Merck approached pharmaceutical industry consultant Jeremy Allen. Could he provide some outside-the-box thinking?

He could and he did. Allen had Merck create a nonprofit called the Bone Measurement Institute, with him as its sole employee. Next, the Bone Measurement Institute/Allen set about changing the way bone measurement was practiced. At the time, bone density scanners were very large, very expensive machines. Allen discovered that there existed smaller, cheaper bone-scanning machines. They were called peripheral machines, and he wanted to get them into more doctors’ offices, so more patients could get screened. But industry manufacturers objected that the peripheral devices were inadequate for obtaining solid diagnoses. They were concerned that the peripherals could lead to sub-par medicine.

So, Merck bought one of the peripheral manufacturers. (That’s one way to silence your naysayers.) Next, Merck and Allen helped move their peripherals through the FDA approval process by funding trials and assisting with submissions. Merck sales reps educated doctors about the machines, and Merck created a leasing program to make it easier for doctors’ offices to purchase one. In 1997, the Bone Measurement Institute, together with a few other organizations (several of which were also receiving funding from Merck), lobbied Congress to pass the Bone Mass Measurement Act. It passed, making bone densitometry a Medicare-reimbursable procedure, and bone scanning a potentially profitable enterprise.

By 1999, the business of screening for osteoporosis was off and running. Medicare claims for bone scanning leapt to 1.5 million. The new, smaller machines that were beginning to populate doctors’ offices would spit out a reading in one of three colors: Green meant normal, red meant osteoporosis, and yellow meant osteopenia. And with that, osteopenia became a “disease.”

Meanwhile, Merck had also introduced a lower dose version of Fosamax, intended for the treatment of (guess what?) osteopenia. With all the new peripheral scanners “diagnosing” osteopenia and Merck marketing a “treatment” for it, Fosamax became a successful drug, at least from a sales perspective.

Jeremy Allen looks back on it all as a successful venture. “I get a great sense of satisfaction that I was able to rejigger the marketplace so that women could be treated for osteoporosis before it got them,” he said. Others see it differently. Richard Mazess, founder of one of the peripheral manufacturers, said Allen had been “complicit in a plot to misdiagnose American women.” As a result of this market “rejiggering,” millions of women were being exposed to the risks of a medication they may not need.

Alix Spiegel told the whole osteopenia-Fosamax story in an NPR article titled “How A Bone Disease Grew To Fit The Prescription,” but it’s not a unique development. “There are versions of this story about a lot of diseases,” she says. The dynamic is well understood. She quotes Caleb Alexander, a pharmaco-epidemiologist at the University of Chicago:

There’s a powerful economic incentive for pharmaceutical firms to expand the boundaries of the use of different therapies. So whether you consider treatments for osteoporosis or treatments for depression or treatments for high cholesterol — in all of these settings — pharmaceutical firms stand to benefit if the therapies for these diseases are broadly used. Even if they're used among people who have very mild forms of these diseases.

It’s not that Fosamax is always harmful. Indeed, the consensus seems to be that in real cases of osteoporosis, there’s a net benefit to taking it. The concern is in the way Merck set out to change what qualified as disease, basically widening the definition to expand the market for its “treatment.” Treatments often involve tradeoffs, and at some point, the risks of treatment can outweigh the benefits. It is now established that in some cases, Fosamax may cause bone loss and bone breakage, along with other side effects. But those kinds of things can’t be known when a drug is new on the market. Even if they were, we can’t always rely on the manufacturers to be up front about them. It is now known that Merck continued to market Vioxx well after it was known to increase risk of heart attack.

Given conflicts of interest and the arbitrariness of some disease definitions, it’s questionable whether a “mild form” of some diseases is even disease at all. When it comes to prescription drugs, if it’s new on the market, patients are wise to practice a little caveat emptor. And if the disease is newly defined, that probably goes double.