Lost in Transmission — FDA Drug Information That Never Reaches Clinicians

[supernova]

I saw this article from the New England Journal of Medicine referenced over on The People's Pharmacy website and thought I'd bring it over here for discussion too. The article discusses benefits and harms of prescription drugs. For the purposes of the article, a "harm" is a bad effect. They also cover the phenomenon of newer drugs or bigger doses being not necessarily better theraputically, but they sure do rake in the bucks. The article goes on to discuss Lunesta as an example, which I believe we have discussed in this space before.

Lost in Transmission — FDA Drug Information That Never Reaches Clinicians

Lisa M. Schwartz, M.D., and Steven Woloshin, M.D.

The 2009 federal stimulus package included $1.1 billion to support comparative-effectiveness research about medical treatments. No money has been allocated — and relatively little would be needed — to disseminate existing but practically inaccessible information about the benefits and harms of prescription drugs. Much critical information that the Food and Drug Administration (FDA) has at the time of approval may fail to make its way into the drug label and relevant journal articles.

....

When companies apply for drug approval, they submit the results of preclinical studies and usually at least two phase 3 studies — randomized clinical trials in patients with a particular condition. FDA reviewers with clinical, epidemiologic, statistical, and pharmacologic expertise spend as long as a year evaluating the evidence. FDA review documents (posted at www.accessdata.fda.gov/scripts/cder/drugsatfda/) record the reasoning behind approval decisions. Unfortunately, review documents are lengthy, inconsistently organized, and weakly summarized. But they can be fascinating, providing a sense of how reviewers struggled to decide whether benefits exceed harms. Yet in many cases, information gets lost between FDA review and the approved label.

Sometimes what gets lost is data on harms. For example, in 2001, Zometa (zoledronic acid, Novartis) was approved for use in patients with hypercalcemia of malignancy. Approval was based on the results of two trials,1 in which 287 patients with cancer were randomly assigned to receive either 4-mg or 8-mg doses of Zometa or Aredia (pamidronate), the standard of care. According to the label, 8 mg of Zometa was no more effective than 4 mg in reducing calcium levels but had greater renal toxicity (see box on Zometa data). The numbers quantifying the renal-toxicity data for the 8-mg dose did not appear in the label, as they did for the 4-mg dose. But they did appear in the 98 pages of FDA medical and statistical reviews. Surprisingly, the reviews also noted that the 8-mg dose was associated with a higher rate of death from any cause than the 4-mg dose (P=0.03). These mortality data also did not appear in the label. Nor did they appear in the journal article reporting on these studies,2 which actually recommended the 8-mg dose for refractory cases. In 2008, the FDA approved an updated Zometa label with an explicit warning statement: “Renal toxicity may be greater in patients with renal impairment. Do not use doses greater than 4 mg.” Yet the mortality data are still missing from the label.



The People's Pharmacy: http://www.peoplespharmacy.com/2009/10/24/can-you-trust-prescription-drug-information/

Full article: http://healthcarereform.nejm.org/?p=2126&query=home

Moral: Always research any meds you are proscribed and discuss it with your doc. Your doc may not have all the information either.

[Name removed]

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[supernova]

2. Meaning?

:shrug: