Wednesday, July 20, 2005

Neutralizing doctors

In my avocation ham radio, the term "neutralize" refers to applying capacitive or inductive feedback in an amplifier, often a high-power radio transmitting amplifier. The purpose of the neutralization is to prevent unwanted, out-of-control waverings and oscillations that can cause interference with the business of radio operation, or damage the critical and potentially saleable assets of the ham radio operator, i.e., the amplifier itself.

In pharmaceutical marketing to clinicians, however, "neutralization" means providing education, according to the press report below.

Next time your drug rep appears in your office, ask them if you are being neutralized, and if being neutralized carries CME credit.

Merck executive testifies in nation's first Vioxx trial

By KRISTEN HAYS / Associated Press

Merck & Co.'s marketing team targeted doctors viewed as unfriendly toward Vioxx to bring them into the fold, neutralize or discredit them, the plaintiff's lawyer in the nation's first Vioxx-related lawsuit to go to trial alleged Tuesday.

Houston litigator Mark Lanier questioned Nancy Santanello, head of Merck's epidemiology department, about an internal list of 36 doctors identified as "physicians to neutralize" in an e-mail circulated two months after the popular painkiller went on the market in 1999.

"Attached is the complete list of 36 physicians to neutralize with background information and recommended tactics. You will notice that some have already been 'neutralized,'" the e-mail said. It also said a previous e-mail had a subset of the 36 physicians "we would like to get involved in Merck clinical research" and that the e-mail's recipient should "be aware of our most challenging (and also most vocal) national and regional physicians."

Santanello said the term "neutralize" was a marketing strategy to educate doctors about Vioxx.

On another note, some press releases such as this one review issues in FDA warning letters that had been received. For example:

... among those [warning letters] was a letter Merck received in September 2001 — two years after Vioxx was introduced to the market with much fanfare — about Vioxx marketing in the aftermath of a 2000 study dubbed VIGOR. The study found some Vioxx users suffered five times as many heart attacks as people who used the older pain reliever naproxen, sold under the brand name Aleve.

"The [FDA] letter said Merck was engaged in a promotional campaign for Vioxx "that minimizes the potentially serious cardiovascular findings" observed in the 2000 study, and "misrepresents the safety profile for Vioxx."

The letter also said that Merck's campaign discounted the fact that patients on Vioxx "were observed to have a four to five fold increase in myocardial infarctions (MIs)," or heart attacks, compared to patients taking naproxen.

The FDA also challenged Merck's attribution of the disparity to naproxen's cardioprotective qualities, not a defect in Vioxx.

"That is a possible explanation, but you fail to disclose that your explanation is hypothetical, has not been demonstrated by substantial evidence and there is another reasonable explanation, that Vioxx may have pro-thrombotic properties," or the ability to cause blood clots, the letter said. "

Company representatives have repeatedly opined that non-clinical trial data such as from retrospective review is invalid, since it is not based on the gold standard of randomized clinical trials. For example:

... an FDA analysis of a Kaiser Permanente database reportedly showing that 27,785 heart attacks and sudden cardiac deaths might have occurred, and might have been avoided if Celebrex were used instead of VIOXX, was reported by the Wall Street Journal. This conclusion is controversial, however. In an interview in the Boston Globe, Merck CEO Raymond Gilmartin refutes the study's findings because it was based on a review of medical records, not a clinical trial. "You can't take a study like this and take a patient population and extrapolate those kinds of numbers," he said. "It's just not valid to do that."

Yet, the explanation proposed for cardiovascular observations about VIOXX compared to Naproxen - that Naproxen protects the heart - "has not been demonstrated by substantial evidence" and is hypothetical, according to the FDA.

Contradiction alert. It seems it's not quite valid to make hypothetical, unsubstantiated assumptions about pharmacology and drug effects. To do so seems a significantly greater leap of faith compared to making inferences from retrospective review of actual medical data -- such as non-clinical trial data from HMO claims or from an EMR. But what do I know. I'm just a physician-Medical Informatics specialist (who pushed hard to improve provision of scientific information to Merck's research lab scientists), who then got "neutralized" by the non-medical former computer executive who presided over biomedical information provision to the labs. This occurred as part of the non-VIOXX related 4,400 layoffs in Nov. 2003.

-- SS

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