Health
JAMA's Fosamax study funded by Merck
By Martha Rosenberg
Online Journal Contributing Writer


Jan 9, 2007, 00:46

Let no one say the studies in JAMA are funded by hidden drug company money. The funding is right out in the open.

"Effects of Continuing or Stopping Alendronate After 5 Years of Treatment," in the December 27, 2006, issue of JAMA was funded by Merck that manufactures alendronate, a bisphosphonate, under the patent name Fosamax.

Not only was the study "supported by contracts with Merck and Co.," according to JAMA, it "was designed jointly by the non-Merck investigators and Merck employees"  and written "with editorial input from Merck throughout the process."

Want further transparency? "The final version of the manuscript was approved by all coauthors, including Merck authors," says JAMA.

The study's 11 non-Merck authors disclosed 40 research grants, consultancies and other financial relationships with drug companies including Eli Lilly, Pfizer, Roche, SmithGlaxoKline, Wyeth, Novartis, Procter & Gamble and, of course, Merck.

And the three Merck authors disclosed they "potentially own stock and/or stock options" -- as if working for Merck weren't enough of a conflict of interest.

Dr. Cathleen S. Colon-Emeric who wrote an accompanying editorial, "Ten Vs Five Years of Bisphosphonate Treatment for Postmenopausal Osteoporosis," and discloses she has received money from Novartis, even appears on an "Understanding Osteoporosis" Novartis web page.

It's a good thing Editor in Chief Dr. Catherine DeAngelis has cleaned things up since the scandals about JAMA authors taking undisclosed drug company money earlier in 2006.

Of course the osteoporosis market is big -- the malady "grew" from half a million to 3.6 million when bisphosphonates were introduced in the mid 1990s, says the Associated Press with tongue firmly in cheek -- and Fosamax is Merck's second biggest performer.

Merck even presciently went into the bone density measuring equipment business, says Maryann Napoli of the Center for Medical Consumers, so patients wouldn't have to go too far to be told they had osteopenia (which they all had) -- a term that also appeared when bisphosphonates did, meaning low bone mass or low rate of drug sign up, depending on whom you ask.

But there were a few wrinkles in the bone-anza.

Soon after Merck launched Fosamax, it was slapped with an FDA warning that its advertising was misleading and in violation of the Federal Food, Drug and Cosmetic Act.

"The headline on page two, 'Menopause is the single most important cause of osteoporosis' is false," wrote Anne M. Reb, regulatory review officer, in a July 2, 1997 letter, "because although menopause is a factor contributing to the development of osteoporosis, menopause alone does not cause osteoporosis. Further the headline [Are You One of 20 Million Women With Osteoporosis?] is misleading because it overstates the population eligible for therapy with Fosamax by implying that all women develop osteoporosis at menopause."

Two years later Merck was again cited for misleading advertising, this time for failing to include risk information about Fosamax and another pill called Vioxx, used for the treatment of osteoarthritis.

Doctors were also having doubts.

"Many people believe that these drugs are 'bone builders,' but the evidence shows they are actually bone hardeners," wrote Dr. Susan M. Ott in the Annals of Internal Medicine in 2004, pointing out that they depress "the bone resorption rate as well as the bone formation rate" and "bones could become brittle with long-term accumulation."

Indeed, problems from lack of bone formation is exactly what a study in the March 2005 issue of the Journal of Clinical Endocrinology & Metabolism (Severely suppressed bone turnover: a potential complication of alendronate therapy) found.

"We report on nine patients who sustained spontaneous nonspinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months to 2 years during therapy," wrote the authors.

"Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of, nonspinal fractures."

And there were patients themselves.

"I still suspect I have been permanently (or hopefully semi-permanently) altered by Fosamax," wrote one woman on the web site Ask a Patient where over 450 rate the drug. "It is as though my ligaments became crystallized, without elasticity."

"After six years of taking Fosamax, I slipped in ice in my driveway and broke my femur (thigh bone). Two years later, still taking Fosamax, I fell in the snow and my other femur snapped before I hit the ground," wrote another woman.

"My condition is basically the same as rickets," wrote a third after going off Fosamax.

And there was more bad news.

Merck's attempt to bill a once a week version of Fosamax as a new drug protected by a new patent -- yeah, right -- until 2018 was denied by the U.S. Court of Appeals for the Federal Circuit in Washington, D.C., after years of litigation. Generics maker Teva Pharmaceutical Industries is now nipping at Merck's heels and ready to begin marketing alendronate next year.

In its self-funded study, "Effects of Continuing or Stopping Alendronate After 5 Years of Treatment," -- did JAMA charge ad rates? -- Merck concludes the residual effects of Fosamax in women who have taken the drug for five years will last indefinitely. (Just what many feared.) What else will last indefinitely is the effect of Merck's shameless and deceptive marketing.