Healthy Skepticism Library item: 14149

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Johnson LA.
Researchers: Merck Vioxx study was for marketing
Associated Press 2008 Aug 18

Abstract:

Researchers: Merck Vioxx study was designed to market
the painkiller; company disputes that

Full text:

A 1999 Merck & Co. study of its since-withdrawn
painkiller Vioxx, touted to participating doctors and patients as meant to
show whether Vioxx caused fewer stomach problems than another drug, was
primarily a stealth marketing strategy, researchers report.
The true purpose was to get lots of doctors and patients in the habit of using
Vioxx just in time for its launch, according to doctors who uncovered internal
Merck memos discussing the strategy behind the study, called ADVANTAGE.
They did so while reviewing roughly a million Merck documents for plaintiffs’
lawyers preparing for trials in Vioxx lawsuits.
Drug companies are widely suspected of doing many such “seeding,” or
marketing studies, but there’s been no “smoking gun” proving it before,
according to the Annals of Internal Medicine, which published Merck’s original
report on ADVANTAGE in 2003 and will publish the new report Tuesday.
An accompanying editorial, co-authored by Annals editor Dr. Harold C. Sox,
states the journal was not told the true purpose of ADVANTAGE, which
compared Vioxx with an older, cheaper pain reliever, naproxen, when it
published results indicating Vioxx was better tolerated.
Dr. Jonathan Edelman, head of scientific affairs at Merck Research
Laboratories, said Monday “the ADVANTAGE study was primarily a scientific
study” designed and executed by the company’s clinical research unit and
that any later use of data for marketing was a separate operation.
But Dr. Kevin P. Hill said he and colleagues, while working as paid
consultants for lawyers representing plaintiffs who claimed Vioxx caused
heart attacks or other harm, stumbled on documents indicating Merck’s
marketing division designed ADVANTAGE and handled the data collection and
analysis.
Using funding from the Robert Wood Johnson Foundation’s clinical scholars
program, they searched further, uncovering items such as a memo from two
top Merck executives nominating the study for an internal marketing award.
“The objectives were to provide product trial among a key physician group to
accelerate uptake of Vioxx as the second entrant in a highly competitive new
class,” the memo states.
ADVANTAGE used about 600 family doctors new to clinical research, with
each getting a stipend plus fees for recruiting a handful of patients each.
Most clinical trials are run by a limited number of specialists at major
teaching hospitals that each recruit hundreds of patients.
Vioxx came on the market in June 1999, after rival Pfizer Inc.‘s Celebrex.
Both makers claimed their drug caused less cramping, diarrhea and dangerous
gastrointestinal bleeding than other pain relievers. Merck battled hard for
market share, and Vioxx at its peak brought in about $2.5 billion a year.
Hill, now a staff psychiatrist at McLean Hospital in Massachusetts, said he and
his colleagues found documents indicating “ADVANTAGE was marketing
framed as scientific research,” with an emphasis on how much Vioxx doctors
in the study later prescribed.
“I don’t think people would be willing to (risk side effects) if they knew that
the aim of a clinical trial was to boost profits for a pharmaceutical company,”
Hill said.
The study’s name implied it had a scientific purpose: ADVANTAGE, or
Assessment of Differences between Vioxx And Naproxen To Ascertain
Gastrointestinal Tolerability and Effectiveness.
But Hill said doctors participating in ADVANTAGE got a kit telling them how to
talk to other doctors about Vioxx, and another Merck study running at the
same time, called VIGOR, also examined how safe Vioxx was for people with
gastrointestinal problems, so ADVANTAGE wasn’t needed. VIGOR’s results
were published in 2000.
Merck spokesman Ron Rogers said Hill and his colleagues have been critics of
Merck and just cherrypicked “some documents to support their thesis.”
The director of the Food and Drug Administration’s Office of Medical Policy,
Dr. Robert Temple, said that if a study follows a research protocol, asks a
legitimate question and “uses garden-variety physicians” instead of academic
experts but has a marketing purpose, “I’m not sure that’s a sin.” He said
doctors have been clamoring for studies that compare one drug to another,
as ADVANTAGE did.
Temple said the agency has no explicit rule that every motive in a clinical
study has to be revealed. However, that is the case with the ClinicalTrials.gov
site run by the National Library of Medicine, where mid- and late-stage tests
on people must be registered, according to the site’s director, Dr. Deborah
Zarin. But the ADVANTAGE study started the year before that site began
operating.
Dr. Bruce Psaty, a University of Washington epidemiologist, said Hill and his
colleagues had disclosed their conflict of interest in their report but that the
ADVANTAGE trial wasn’t transparent about its purpose.
“I would think that at some level this is standard practice,” he said of seeding
studies, but they don’t come to light except during the discovery phase of
litigation.
Dr. Ross McKinney, director of Duke University’s bioethics center, said
seeding studies have been around for decades and usually are called
postmarketing studies, meaning they’re for drugs approved for sale. He said
most never get published, but this one did because it addressed an important
scientific question, stomach tolerability, even though it was a seeding trial.
But McKinney said seeding studies make the public skeptical about enrolling
in clinical studies.
“It’s a serious violation of research ethics” and prevents patients from
figuring out the risks and benefits of participating in the study, said Arthur
Caplan, who heads University of Pennsylvania’s medical ethics department.
Whitehouse Station, N.J.-based Merck pulled Vioxx off the market on Sept.
30, 2004, after its own research showed the then-blockbuster arthritis
treatment doubled risk of heart attack and stroke. It has since reached a
$4.85 billion settlement to end the bulk of personal injury suits over Vioxx,
and the first payment checks are slated to go out later this month.
Sox, the Annals editor, and Dr. Drummond Rennie, the Journal of the
American Medical Association’s deputy editor, wrote that the institutional
review boards required to protect patients in clinical studies should ask
whether an experiment is a seeding study, particularly when there are
obvious clues. “Simply shining a bright light on their existence may have
already sown the seeds of their destruction,” they write.