Osteoporosis - drug companies interfering with research

[Guest guest]

I found this article on Slate interesting. Shows how Procter and Gamble didn't

allow research to be carried out properly and let people think its drug was

better than it was. As someone with osteoporosis who took this drug (Actonel), I

am wondering what we can believe and why these companies think we can trust

them.

 

Jan

 

Artcle to be found at http://www.slate.com/id/2133061/

 

Rent-a-Researcher

Did a British university sell out to Procter & Gamble?

By Jennifer Washburn

Posted Thursday, Dec. 22, 2005, at 2:38 PM ET

 

Earlier this month, Sheffield University in Britain offered $252,000 to one of

its senior medical professors, Aubrey Blumsohn. According to a copy of a

proposed settlement released by Blumsohn, the university promised to pay him if

he would agree to leave his post and not make " any detrimental or derogatory

statements " about Sheffield or its employees. For several years, Blumsohn had

been complaining of scientific misconduct. His concerns primarily revolved

around a $250,000 research contract between Sheffield and the Ohio-based Procter

& Gamble Pharmaceuticals. Blumsohn claimed that the company had denied him

access to key data and then tried to ghostwrite his analysis of it. He further

alleged that P & G had engaged in such practices before.

Why did Sheffield, a top-flight research university, try to silence and get

rid of Blumsohn? The answer appears to lie in the complex and increasingly

compromised relationships that have grown up between some research universities

and the pharmaceutical industry. In 2001, the editors of nearly a dozen

prominent medical journals warned that growing industry interference with

academic research (from study design to data analysis and publication) was

threatening the objectivity and trustworthiness of medical research. The editors

issued new guidelines requiring all authors publishing in the journals to verify

that they " had full access to all of the data " related to their studies and that

they took " complete responsibility " for " the accuracy of the data analysis. "

But in the years since, universities with medical schools have become

dependent on drug companies for an ever-larger share of their research

budgets—roughly 80 percent of clinical research is now privately funded. And

drug companies, in turn, have pressed for greater control over the research

process, making it easier for them to obscure or delete negative results from

published academic papers. Earlier this month, the New England Journal of

Medicine accused Merck of failing to report three patient deaths in the trial

that led to FDA approval of the painkiller Vioxx, which was pulled from the

market last year because of its association with heart attacks and strokes. The

careful record Blumsohn kept of his dealings with Procter & Gamble and Sheffield

suggests that P & G didn't control academic research on its own. It needed

Sheffield University to permit incursions on scholarly independence.

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In the summer of 2002, Blumsohn, a senior lecturer and bone metabolism

specialist, and Dr. Richard Eastell, Sheffield's research dean, signed a

$250,000 research contract with Procter & Gamble. Blumsohn and Eastell were to

evaluate the effectiveness of P & G's osteoporosis drug, Actonel. The goal was not

to win FDA approval; Actonel was already being widely prescribed. Instead, the

Sheffield study would shed further light on how Actonel affects women's bones

and their susceptibility to fractures. According to Blumsohn, Eastell had

already reviewed blood and urine samples from two previous P & G clinical trials

of Actonel. Now Blumsohn was supposed to evaluate a third trial, with the aim of

providing a final analysis of all three.

But in the past, it seemed, P & G had not allowed Eastell to perform his own

data analysis. In an e-mail that Eastell wrote to P & G and copied Blumsohn on, he

confessed that while presenting a paper at the International Osteoporosis

Foundation, he had been unable to respond to questions about his own research

posed by a fellow academic. " I think that to avoid criticism in the future it

would be good if we could say that we had done the analyses independently, "

Eastell wrote in the e-mail. He suggested that Blumsohn be entrusted with the

independent analysis, so he could vouch for results that would be published

under both their names.

Blumsohn and his staff reviewed thousands of blood and urine samples from

women with osteoporosis. At this stage, they were " blinded " from knowing which

patients had taken Actonel and which had taken a placebo. This helped to ensure

objectivity. But when he finished examining the samples in December 2002,

Blumsohn says he asked P & G to release the codes for the raw data so he could

independently interpret the results.

Blumsohn requested the data access codes for 18 months, as numerous e-mails

and other records document (here's one). P & G officials wrote back refusing to

permit independent access to the data. However, in a written statement, the

company denied that it withheld necessary data. " We have appropriately shared

our clinical data with both investigators and regulatory authorities, and have

conducted our business with the highest of standards. "

Meanwhile, Blumsohn says P & G began to analyze his Actonel data and write up

the final results for him to present at the American Society of Bone and Mineral

Research in Minneapolis in fall 2003. The previous April, P & G statistician Ian

Barton informed Blumsohn and Eastell by e-mail that Mary Royer, the company's

medical ghostwriter, would help write up the Actonel manuscripts for

publication. Blumsohn and Eastell would both be listed as authors. Barton

emphasized that the ghostwriter was " familiar with … our key messages. "

By now, Blumsohn thought he knew what those " key messages " were. In 2004,

P & G's main rival, Merck, was due to publish a head-to-head study comparing its

osteoporosis drug, Fosamax, with Actonel. Many doctors considered Fosamax more

effective at increasing bone density and decreasing the rate at which bones

degenerate—and thus probably also more effective in preventing fractures, the

biggest concern for women with osteoporosis. Fosamax's global sales were $3

billion a year, compared to about $1 billion for Actonel. In the summer of 2003,

Blumsohn received a copy of P & G's proposed " statistical plan " for analyzing his

data. It stated that the purpose of his research was to bring about an

" Osteoporosis Paradigm Shift. "

Eastell's earlier research asserting P & G's claims about the effectiveness of

Actonel appeared in June in the prestigious Journal of Bone and Mineral

Research. Eastell and his co-investigators stated that " all authors had full

access to the data and analyses. " Based on Eastell's earlier e-mail, Blumsohn

knew that wasn't true and that Eastell had most likely violated the new

safeguards that medical journal editors had put in place in 2001. Blumsohn says

he warned Eastell they could both be accused of scientific fraud if they kept

authoring papers without seeing the underlying data. A few days later, P & G's

Barton sent an e-mail reiterating that Blumsohn could not perform his own

independent analysis of his data but could come to P & G's offices to look at it.

When Blumsohn sat down with Barton at the company's Surrey headquarters in

late July, he says he spotted something peculiar. In one critical graph showing

how Actonel affects fracture rates, Blumsohn noticed that 40 percent of the

patient data was missing. Inclusion of the data, he thought, would have

disproved P & G's " key message " about Actonel's effectiveness in reducing bone

fractures. Several months later, Blumsohn recorded a meeting in which Barton

expressed concern that if P & G included the missing 40 percent of the data, Merck

would exploit the results. " Because that is contradicting our original

manuscript, " he said. " I just know what Merck are like. I think they are going

to use it. "

P & G denies that it skewed data to achieve desired results, saying that

Blumsohn " was given access to all of the data related to his research. " But the

company's previous written statements seem to contradict this assertion. When

Blumsohn's lawyer filed a formal data request on his behalf, P & G responded: " It

is not the standard practice of P & G to allow unlimited access to raw data from

clinical trials to individual investigators, as these data are proprietary. "

In November, Blumsohn won a few concessions. He says P & G agreed to remove the

graph he'd objected to from an oral presentation and to delete some text from a

paper appearing in his name. But P & G's educational materials and other writings

continued to make assertions about Actonel's effectiveness, which Blumsohn

believed the data he'd seen did not support.

Increasingly, Blumsohn felt he was doing battle not only with P & G but with his

university. Shortly after Blumsohn complained about the apparent manipulation of

his Actonel data, he recorded a conversation in which Eastell warned, " The only

thing we have to watch all the time is our relationship with P & G. " The P & G money

" is a good source of income, we have got to really watch it. "

Over the next 22 months, Blumsohn wrote formal complaint letters to various

Sheffield officials. The university didn't investigate his claims, according to

an article in the British Times Higher Education Supplement. In July, Blumsohn

announced that he would go public with his concerns. Sheffield suspended him in

September, citing, among other things, his " refusal to comply with a reasonable

management instruction by briefing journalists. " Sheffield then offered him the

$300,000. Sheffield states that it repeatedly asked Blumsohn to provide evidence

supporting his allegations and urged him to bring that evidence " through the

proper channels. " The university says legal negotiations were initiated " at

Blumsohn's request " and " undertaken in good faith by the University. "

Universities have long accepted funding from pharmaceutical companies to

conduct clinical drug trials. But in the past, their professors insisted on

running those trials independently of the sponsor. As the Blumsohn case makes

clear, this arm's-length relationship appears to be breaking down. Earlier this

month, the Wall Street Journal reported on the growing willingness of some

academics to sign their names—and lend their prestige—to articles and editorials

penned by drug-company ghostwriters. In addition to the Vioxx episode, recent

reports indicate that published academic studies related to the drugs Celebrex,

Paxil, and Zoloft appear to have been skewed when their authors permitted the

suppression of negative results.

The British Parliament has promised to investigate Blumsohn's allegations. And

in January, medical journal editors will be gathering once again to discuss what

can be done to restore the integrity of the research they publish. One idea

that's been floated in the United States is a new arm of the National Institutes

of Health that could serve as a repository for complete clinical trial data

while also monitoring trials and verifying the accuracy of published results.

Whatever the solution, something needs to be done soon. Scholarly independence

has already taken too many hits.

 

Jennifer Washburn is a fellow at the New America Foundation and author of

University, Inc.: The Corporate Corruption of Higher Education.

 

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Jan

 

 

 

 

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