Scientific Fraud & Corruption on Both sides of Atlantic: Merck / Proctor & Gambl

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[sSRI-Research] Scientific Fraud & Corruption on Both sides

of Atlantic: Merck / Proctor & Gamble

 

 

 

 

Scientific Fraud & Corruption on Both sides of Atlantic: Merck /

Proctor & Gamble

 

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting Openness, Full Disclosure, and Accountability

www.ahrp.org

 

 

FYI

Two major cases of medical research fraud on each side of the Atlantic

involve evidence of fraud and data tampering by pharmaceutical

company giants. Both cases provide insight into the way in which

academics are used by pharmaceutical companies that are desperate to

obtain a stamp of respectability to their drug research. Companies

commission academics to pen their name to published reports in

prestigious journals. But those reports do not reflect the actual

clinical trial data. Both industry and the academics who serve as

their lackeys are destroying the very basis of that respectability.

The positions taken by the scientists involved in these two cases are

a study in contrast.

 

The U.S. press is focused on stunning revelations of fraud and data

tampering that were uncovered during Vioxx court proceedings.

Merck- " once the most esteemed name in the pharmaceutical business " -and

its contracted academic scientists were shown to have deleted data

linking Vioxx to cardiovascular damage from the major VIGOR report

published in The New England Journal of Medicine in 2000. The NEJM is

viewed as the most authoritative scientific journal.

 

Fortune reports (below) that Dr. Gregory Curfman, Executive Editor of

the NEJM said he was " stunned to find out that data linking Vioxx to

cardiovascular risk was deleted from a major study his journal

published five years ago--and that it appears that Merck researchers

may have deleted that data. " The New York Times editorial states:

 

" What aroused the ire of the journal's editors was an internal company

memo revealing that the researchers knowingly suppressed data on three

additional heart attacks among Vioxx users that was available months

before the paper was published. Had that data been included, Vioxx

would have looked five times as risky as naproxen, not four times, and

would have looked potentially dangerous even in patients deemed at low

risk of heart attacks. " See:

http://www.nytimes.com/2005/12/11/opinion/11sun2.html

 

However, Fortune reports that following the withdrawal of Vioxx, NEJM

editors stumbled upon the evidence by examining a disc containing an

earlier version with the cardiovascular data that was subsequently

deleted from the final published version. The Journal editors remained

silent about the evidence of data manipulation in a major report in

its Journal that though they " talked internally " about the deletion of

data they did not alert readers of the Journal who rely on the

Journal's review process to protect the integrity of scientific

reports within its covers: " We did not feel we had sufficient evidence

to act on it. "

 

From Fortune, we learn, that The NEJM editors saw fit to alert readers

only after Dr. Curfman was deposed (on Nov. 21, 2005) in Boston by

lawyers from the firm of Lieff Cabraser Heimann and Bernstein, at

which time he was confronted with " an internal Merck document dated

July 5, 2000--after the VIGOR manuscript was submitted to the journal,

but well before the study went to press. "

 

Merck's defense is that the company had submitted all the data to the

FDA-as is its legal obligation. From that we are left to conclude

that scientists who pen their name to journal articles do not feel

similarly obliged to disclose ALL. The lead author of the VIGOR study,

Dr. Claire Bombardier, (at the University of Toronto) appears to have

been a willing servant of commercially driven misleading presentation

of research. How many other such misleading reports are polluting the

scientific literature?

 

On the other side of the Atlantic, a similarly worrying new and

important case is unfolding at the University of Sheffield in the

United Kingdom. The case involves a collision between a senior

clinician and respected scientist, Dr Aubrey Blumsohn, who was the

lead scientist for a clinical study of a Procter & Gamble

Pharmaceuticals (P & G) drug, Actonel (risedronate). Dr. Blumsohn blew

the whistle on data concealment and ghostwritten journal reports with

his name appended.

 

The case has attracted intensive press coverage: " A war between one

of Britain's most experienced academics and one of the world's most

successful drugs companies. At issue is a highly significant report on

a drug to treat a debilitating disease which the academic says was

published under his name when he had not seen analysis of the research

it was based on. The drugs firm denies anything untoward has

happened. "

http://observer.guardian.co.uk/uk_news/story/0,6903,1657275,00.html

 

After Dr. Blumsohn's data collection efforts for this study, P & G

refused to provide him with randomization codes or to allow an

independent analysis of this data. This, according to Dr. Blumsohn,

was in breach of the company's contract with the institution.

Furthermore, P & G wrote meeting abstracts, draft publications and

statistical reports on behalf of the University academics while

denying them access to data upon which those reports were based. Data

was required by the academics to verify scientific reports,

statistical analyses, meeting abstracts, and draft publications " ghost

written " in their names.

 

Refusal of access to data under such circumstances is unprecedented,

and violates all norms of proper conduct and procedure in science. It

interfered with the ability of academics to discharge their duties as

responsible scientists and clinicians, and prevented proper

publication and correction of the scientific literature. It appeared

that " fair " analysis of the data might not have yielded findings

desired by the sponsor. The company violated the norms of science

under whose banner they claim to sell their products.

 

Repeated attempts to obtain the required data were not successful, and

information emerged that the data analysis had been misleading.

Blumsohn eventually made his concerns known about his inability to

access the data to several senior officials at his university but was

apparently repeatedly ignored. Because, however, the University

charged that he did not go through proper channels, and eventually

talked to the news

 

media, the University of Sheffield suspended him.

 

Victimization of academics raising such difficult issues is sadly only

too familiar.

Particularly important was the UK Observer report of a taped

conversation Blumsohn had with Professor Richard Eastell, head of the

university's bone and metabolism unit and also Research Dean of his

Medical School about his attempts to get the data from P & G. Eastell said:

 

" The only thing that we have to watch all the time is our relationship

with P & G. Because we are... we have the big Sheffield Centre Grant

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

the reason why I worry is the network within P & G is like lightning. So

if Ian [barton] is unhappy it goes to Arkadi [Chines, global medical

director of P & G Pharmaceuticals] and before we know it, there is an

issue, there is a problem. "

 

The matter was discussed extensively in the House of Commons (UK

Parliament) on 8th of December 2005.

 

Different aspects of the Sheffield case are reported in the UK

including: Times Higher Education Supplement (a UK academic

newspaper), and the Observer (a UK Sunday paper). It has also been the

focus of discussion in Parliament.

 

When access to data is a real bone of contention

http://www.thes.co.uk/search/story.aspx?story_id= 26307

 

How the drugs giant and a lone academic went to war

http://observer.guardian.co.uk/uk_news/story/0,6903,1657275,00.html

 

Doctor accuses drugs giant of 'unethical' secrecy

http://observer.guardian.co.uk/uk_news/story/0,6903,1657302,00.html

The Observer, UK - Dec 3, 2005

 

 

 

Contact: Vera Hassner Sharav

212-595-8974

veracare

 

 

 

FORBES

http://www.forbes.com/home/sciencesandmedicine/2005/12/08/merck-vioxx-

lawsuits_cx_mh_1208vioxx.html

 

Sciences and Medicine

Merck's Deleted Data

Robert Langreth and Matthew Herper, 12.08.05, 8:10 PM ET

 

NEW YORK - A top editor of The New England Journal of Medicine says

that he was stunned to find out that data linking Vioxx to

cardiovascular risk was deleted from a major study his journal

 

published five years ago--and that it appears that Merck researchers

may have deleted that data.

 

" I was somewhere between surprised and stunned, " Dr. Gregory Curfman,

executive editor of The Journal, says. " They allowed us to publish an

 

article that was just incomplete and inaccurate in some respects and

was misleading and may have contributed to the detriment to the

public health. "

 

The discovery (see: " Merck's Slanted Study? " ) comes as the company

faces a flood of lawsuits following its decision to pull the drug

from the market in September 2004. Merck recalled Vioxx after its own

study linked long-term use of the drug to an increased risk of heart

attacks and strokes. Now, the question is if that alarm should have

been sounded much earlier.

 

Just days after Merck recalled Vioxx from the market, editors at The

Journal discovered a diskette containing earlier versions of a

manuscript for a crucial Vioxx clinical trial called VIGOR that they

 

had published in November 2000.

 

The early versions of the manuscript contained a blank table entitled

" CV events " --which is standard jargon for cardiovascular events. Time

stamps in the software indicated that the table was deleted two days

before the manuscript was submitted to The New England Journal on May

18, 2000. " When you hover the cursor over the editing changes, the

identity of the editor pops up, and it just says 'Merck,' " Curfman says.

 

The editors weren't sure what to make of the finding, so they kept

quiet. It wasn't clear that the information that had been in the

table would have changed the conclusions of the study. The published

 

version of the study noted a higher heart attack rate in patients who

took Vioxx compared with those who took naproxen, an older painkiller

that is sold over the counter as Aleve. But the report provided

relatively few details.

 

" We talked internally. Should some action be taken? We did not feel

we had sufficient evidence to act on it, " Curfman says.

 

But on Nov. 21, 2005, Curfman was deposed in Boston by lawyers from

the firm of Lieff Cabraser Heimann and Bernstein, who represent

plaintiffs in one of the Vioxx suits. During the deposition, which

also included attorneys for the drugmaker, they showed Curfman an

internal Merck document dated July 5, 2000--after the VIGOR

manuscript was submitted to the journal, but well before the study

went to press.

 

It indicated that two Merck authors on the VIGOR study knew of three

additional heart attacks among Vioxx patients in the study, which had

not been disclosed to The New England Journal of Medicine. The heart

attacks occurred in the final five weeks of the trial and in patients

at low risk for heart problems.

 

The plaintiff's lawyers also showed him early versions of the

manuscript containing the original version of the deleted table, he

says. This version also revealed more cardiovascular problems

 

potentially connected to Vioxx than those had been discussed in the

published study.

 

Curfman says the editors had assumed that the VIGOR manuscript only

included limited data on heart attacks because that was all that was

available at the time. " It turns out that they had quite a bit more

already worked up, " he says. He raced back to the office and spent

the next few weeks analyzing all the VIGOR drafts, raw data and

correspondence.

 

At 3:00 P.M. today, Curfman and two other editors released an

editorial on The New England Journal's Web site entitled " _Expression

of Concern, " which calls on the VIGOR authors to submit a correction

of the 2000 manuscript. " Taken together, these inaccuracies and

deletions call into question the integrity of the data on adverse

cardiovascular events in this article, " it read.

 

Curfman says he called lead author Claire Bombardier of the

University of Toronto, on Monday, indicating that the statement would

be published. She told him that she would begin working on a

 

correction. However, in an e-mail to Forbes.com, Bombardier said that

the VIGOR paper appropriately disclosed the data and that the authors

were working on finalizing a response to the editorial.

 

Catharine Whiteside, dean of medicine at the University of Toronto,

said today that she has yet to talk to Dr. Bombardier. " In the event

that information is brought to light in which we would need to

 

investigate Dr. Bombardier, we would initiate due process, " Whiteside

says.

 

Hints that Vioxx might cause heart attacks had existed for years, as

basic research pointed to a mechanism by which the drug might cause

more clots. When VIGOR was published in The New England Journal of

Medicine, there were already questions among scientists about the

potential of Vioxx and related drugs made by Pfizer (nyse: PFE - news

 

- people ) to cause heart attacks. Later on, the data about the VIGOR

manuscript led researchers at the Cleveland Clinic to sound the alarm

about Vioxx's heart risk.

 

Some analysts have estimated Merck's potential liability in the tens

of billions of dollars. Others say that the risk to the drugmaker,

once the most esteemed name in the pharmaceutical business, is

 

impossible to know. The news that the once-popular arthritis drug may

have caused thousands of heart attacks led to a firestorm about drug

safety.

 

In a statement, Merck disputed The New England Journal analysis. " The

VIGOR publication, which was peer-reviewed, fairly and accurately

described the results of the study as of the prespecified cutoff for

analysis. The additional events referred to in the editorial were

events that were reported after the prespecified cutoff date and,

therefore, these were not included in the primary analysis reported

in the article.

 

" Nevertheless, the additional events were disclosed to the FDA in

2000, presented publicly to the FDA's Advisory Committee in February

2001 and included in numerous press releases subsequently issued by

Merck. We also note that these additional events did not materially

change any of the conclusions in the article. "

 

Curfman responded, " We're not buying into that. "

 

© Fortune

~~~~~~~~~~

How the drugs giant and a lone academic went to war

 

Worrying power games are at the heart of Procter and Gamble's

relationship with academics, alleges the scientist investigating its

billlion-dollar osteoporosis treatment, reports Jo Revill

 

Sunday December 4, 2005

The Observer

Every medicine prescribed in Britain is offered to patients only after

years collecting data from clinical trials to show a drug's safety and

effectiveness.

 

Increasingly, medical research in the UK is a collaborative effort

between big pharmaceutical companies and universities. Although there

will be a commercial contract between the two, much of that

relationship is built on trust.

 

For patients everywhere it is essential that the way research is

conducted is open and transparent. This is an account of what happens

when the relationships break down, when academics believe they have

not been given access to the data and when the relationship between

universities and the drugs companies which provide much of their

funding for research becomes mired in controversy. This issue - and

the influence of the pharmaceutical industry - will be debated in

parliament this week.

 

At its heart is the practice of 'ghost writing', pharmaceutical

companies hiring writers to produce reports which academics give

permission for their name to be put to.It is rare for tensions in the

highly sensitive world of scientific drugs research to break into the

open. But an Observer investigation has uncovered a story of a war

between one of Britain's most experienced academics and one of the

world's most successful drugs companies. At issue is a highly

significant report on a drug to treat a debilitating disease which the

academic says was published under his name when he had not seen

analysis of the research it was based on. The drugs firm denies

anything untoward has happened.

 

In the summer of 2002, Dr Aubrey Blumsohn, a senior lecturer and

honorary consultant in metabolic bone disease at Sheffield University,

was preparing to lead a major research project. One of the world's

largest pharmaceutical firms, Procter and Gamble, had just signed a

£180,000 deal for his research team to carry out a study on one of

their drugs, Actonel.

 

Actonel is a highly successful medication prescribed by doctors to

nearly one million women around the world every year to treat

osteoporosis. Also known as risedronate, it has been licensed as a

treatment in the UK since 2002, and is known to be safe, with a good

record of reducing the risk of broken hips, spines and wrists.

 

Blumsohn, who was born in South Africa, joined the Sheffield centre

for bone metabolism research five years ago. He was to lead a third

thorough investigation into the drug to look at how it was affecting

the bones of thousands of women. To do the study, thousands of blood

and urine samples, taken from women in more than 100 research centres

around the world, were analysed in Blumsohn's laboratory in September

2002.

 

More than 3,000 pages of laboratory data and electronic records had to

be put together by the researchers. Their aim was to look at the

samples collected over a period of three years from women who were on

Actonel, to determine which patients suffered fractures, and match

that to changes in their bone turnover and bone density with their

treatment. Bone turnover, the rate at which the body replaces its own

bone material, is an important factor in osteoporosis.

 

The data was sent off in December 2002 to be analysed by statisticians

at Procter and Gamble's headquarters in Egham, Surrey. Blumsohn's

colleague, Richard Eastell, professor of bone metabolism at Sheffield,

had worked on previous collaborations with the company, and had

published data prepared by them.

 

A great deal was at stake for Procter and Gamble, a US company with

headquarters in Cincinnati, Ohio. Its fortune was built on soap and

candles made by the Englishman, William Procter, and the Irishman,

James Gamble, more than 170 years ago. With shrewd investment and its

ownership of leading brands in washing powders and disposable nappies,

it has become a major player in pharmaceuticals.

 

Actonel is one of P & G's 16 'billion-dollar brands', making the company

between $500m and $1bn each year. But there is intense competition

with its main rival, the drug Fosamax, manufactured by another

pharmaceuticals giant, New Jersey-based Merck.

 

There has been much debate over how these drugs actually work. It is

known that they do two things: increase the mineral content of the

bone, known as bone mineral density (BMD), and reduce the rate of bone

turnover. Bone is a living tissue which constantly regenerates itself,

by losing and gaining calcium and protein. Bones are always developing

tiny holes which are filled in as new material grows, but as women

grow older the holes are not filled in properly and the bones are

weakened. Both Fosamax and Actonel are 'anti-resorptive agents' - they

prevent the bones from losing material too fast.

 

Blumsohn asked at an early stage if he could see the way in which the

analysis of his research was being carried out by P & G. The contract he

and Eastell had signed with the company stipulated that their final

written report would include all data, and any interpretation

necessary for analysis.

 

Although the two experts were providing the raw data from their

laboratory, the numbers were meaningless in themselves because they

were coded. As in all cases of this type of work, the researcher is

'blind' to the details of the data because they might be 'influenced'

by that knowledge. The results cannot be understood until they are

decoded - and P & G possessed the key. xxxxxxxxx cut xxxxx

 

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