FDA needs to Reevaluate Fosamax Safety

Evelyn Pringle November 10, 2006

The FDA is facing mounting accusations that it puts more effort into protecting drug company profits than protecting American consumers from unsafe drugs and Merck’s Fosamax is but the latest example of this unhealthy allegiance.

According to the 2003 report by the Office of Inspector General of the Department of Health and Human Services, a survey of FDA’s own drug reviewers revealed that 66% of the lacked confidence in the FDA’s safety monitoring of marketed drugs, and 18% said that they had felt pressure to approve a drug despite reservations about its quality, efficacy, or safety.

A March 2006 report to Congress on an investigation of the FDA’s ability to monitor drug safety by the Government Accountability Office found that the “FDA lacks clear and effective processes for making decisions about, and providing management oversight of, postmarket safety issues.”

The GAO also said that the FDA’s performance was undermined by infighting between drug evaluation administrators whose allegiance is with industry, and the Office of Drug Safety.

Most recently, five experts who are past and current members of FDA Drug Safety Advisory Panels say the FDA’s safety studies often miss serious problems with drugs, both before and after a drug is approved.

Critics contend that the problem stems from the fact that the FDA does not have the authority to remove drugs from the market, or force a company to change a drug’s warning label, or issue sanctions against drug companies that do not properly monitor their products.

The group of experts, who published a critique of the agency in the Archives of Internal Medicine, includes current panel members Curt Furberg, Robyn Shapiro and Arthur Levin, and former panel members Peter Gross and Brian Strom.

They recommend that Congress take steps to improve the FDA’s monitoring of drug safety to include:

1. Providing the FDA with more legal authority to pursue safety violations;
2. Creating a “conditional” drug approval policy for certain types of drugs;
3. Providing the FDA with additional funding to improve safety-monitoring operations and require that it do so;
4. Mandating a broader representation of safety experts with fewer conflicts of interest on advisory panels; and
5. Banning consumer advertising of newly approved drugs until they have been on the market long enough to detect safety issues.

In addition, the group recommends that a new agency, the Center for Drug Safety, be created outside of the FDA’s Center for Drug Evaluation and Research.

The Institute of Medicine also recently suggested a ban on consumer advertising for newly approved drugs until a drug has been on the market long enough to gauge whether any serious problems are likely to occur.

Many experts say that in recent years the mass marketing of newly approved drugs in many instances has proven to be disastrous.

On October 31, 2006, Ronald Brown, a professor of oral diagnosis at the Howard University College of Dentistry, wrote an editorial in the Washington Post to say that he found it especially troubling to see television ads for bisphosphonates such as Boniva and Fosamax.

“Certainly,” he wrote, “these medications appear to be useful in treating osteoporosis, but they also appear to have serious risks in an as-yet-unknown percentage of patients.”

“Jawbone infections known as bisphosphonate-associated osteonecrosis (BON),” he said, “have serious morbidity and mortality issues and are difficult to treat.”

“It is scandalous to allow these drugs to be advertised on television,” he states.

Merck has spent a fortune on promoting Fosamax and it has paid off well. In fact, for 2005, it was announced that Fosamax was the highest scoring medical journal ad at The Doctors’ Choice awards luncheon on October 19, 2006, in New York City, with a 3-page Fosamax ad from FCB HealthCare in the generalist physician category. The ad appeared in both general practice and OB/GYN medical journals.

The Doctors’ Choice annual study is conducted by the Association of Medical Publications, and researches physicians’ attitudes toward product advertising via a web-based study of 315 ads from the 200 most widely advertised products. More than 6,250 practitioners responded with their preferences in medical advertising messages.

Fosamax was hailed as a miracle drug when it came on the market a decade ago.

However, a study published in the October 2006, Journal of Bone & Mineral Research, Fracture Incidence & Characterization in Patients on Osteoporosis Treatment: The ICARO Study, found that the clinical trials Merck touts as proof that Fosamax is effective, actually overstate the benefits of Fosamax in both the clinical and practical setting.

The study found that unless patients were taking Vitamin D and calcium supplements along with Fosamax, there was a poor bone fracture reduction leading medical experts to wonder whether the positive results in the studies were indeed due to Fosamax or the supplements alone.

The drug has come under fire recently after an Annals of Internal Medicine study linked the use of bisphosphonate drugs to osteonecrosis of the jaw (ONJ), often referred to as dead jaw.

ONJ is an irreversible, disfiguring condition in which bone tissue dies and fails to regenerate and most often becomes known when patients have dental extractions or implants and oral surgery. Symptoms of the condition include excruciating pain, swelling, exposed bone, and loose teeth.

This Fosamax side effect directly contradicts its intended purpose, which is to strengthen bones and prevent bone loss in people with osteoporosis. There also have been reports that Fosamax does indeed increases bone density, but the new bone that develops is too brittle and more prone to fracture.

Although studies have shown that intravenous use of bisphosphonates is more likely to cause ONJ, pill form is also a big concern due to the heavy promotion of Fosamax for life-long treatment, and the high number of prescriptions written each year for younger patients, especially women.

Critics point out that once a patient takes Fosamax for several years, the damage can occur long after a patient stops taking the drug.

According to Dr Mark Steinberg, an oral surgeon at Loyola University Medical Center, “These drugs stay in your body for 10 years, maybe even more.”

“So, just by stopping it, it doesn’t mean it’s going to go away right away,” Dr Steinberg said during an interview CBS News.

According to a study in the November 2006, journal Expert Opinion on Drug Safety, scientists are considering two theories on exactly how the drugs cause of ONJ.

The first is that bisphosphonates cause cell death within the jaw bone and make it more prone to chronic infection. The other theory is that the bone is alive until it is injured and infected and the bisphosponates hinder the formation of fresh bone surface for reestablishment of bone cell coverage due to a reduced resorptive ability.

The study’s author, Professor Per Aspenberg, from Linkoping University in Sweden, notes that the theories are compared based on recent but scarce literature. “None of them can be completely refuted,” he writes, “but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis.”

The American Association of Oral and Maxillofacial Surgeons has said that its members are reporting as many as 5,000 cases of ONJ related to bisphosphonates.

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