[e-drug] Words and how they are used ..

[e-drug@healthnet.org]

E-DRUG: Words and how they are used ..
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Downside for Pharma Companies but "Upside" for Health ?

Copied as Fair Use (Warning - Long Post)

http://www.nytimes.com/2007/05/23/business/23drug.html?_r=1&oref=slogin

An article from New York Times that has many aspects.

It is about the risk of cardiovascular problems with rosigliatazone. See
the recent article in the New England Journal of Medicine.

http://content.nejm.org/cgi/content/full/NEJMoa072761

How does the newspaper headline it - "Downside for Pharma ...." How
about a headline of "Success for Health when Full Information is known".

Is it Bad News that makes Good Newspaper copy or How much does Pharma spend
for advertising ?

Getting the data for this study was possible as Glaxo (under court
order) promised to publish the results of all their clinical trials. The
principles of The Clinical Trial Registry Platform of WHO are similar,
though more details of the trial required. (The commercial break or the
Public Service Announcement! - see http://www.who.int/ictrp/en/)

This full information allowed a balanced assessment of the benefits and
risks of the drug and not the selective data that is put out.

Also full disclosure - posted by WHO Staff Member.

May 23, 2007

For Drug Makers, a Downside to Full Disclosure

By BARRY MEIER

When GlaxoSmithKline settled a lawsuit three years ago with the
State of New York over the antidepressant medication Paxil, the company
agreed to take an unusual step: publicly disclosing the results of its
clinical trials for Paxil and other drugs.

The company, which was criticized at the time for failing to publicize
all pediatric trials of Paxil, not just the positive ones, made good on
its promise. The first posting on a new Web site was about 65 studies
involving its popular diabetes drug, Avandia [rosiglitazone maleate].

This week, GlaxoSmithKline learned what that greater disclosure could
mean.  A cardiologist at the Cleveland Clinic, Dr. Steven Nissen, stumbled onto
the Glaxo Web site while researching Avandia last April. He and a
colleague quickly analyzed the data, and on Monday, The New England
Journal of Medicine released its finding that Avandia posed a heightened
cardiac risk.

"It was a treasure trove," Dr. Nissen said about the Web site.

GlaxoSmithKline has disputed the journal's interpretation. Officials
with the Food and Drug Administration said they were reviewing whether
to take any action on Avandia.

Whatever the drug's fate, the episode is likely to fuel efforts by some
medical experts, including Dr. Nissen, to persuade lawmakers to require
makers of drugs and medical devices to disclose study results publicly.
Currently, producers are not required to do so, but Congress is
considering legislating a requirement.

Many companies besides GlaxoSmithKline already post results from some
studies or trials on their Web sites, or one operated by the
Pharmaceutical Research and Manufacturers Association, a trade group in
Washington.

Dr. Bruce M. Psaty, a cardiologist at the University of Washington, said
that having such information can play a critical role, as the case of
Avandia suggests, in spotting signals of a drug's possible dangers.
Other experts have argued that the relative efficacy or cost of
competing drugs can be compared only when all study results, rather
simply those that a company chooses to publicize, are available.

Studies have found that the vast majority of drug and medical device
studies are never published in medical journals.

"The more information, the better," Dr. Psaty said.

Dr. Ronald L. Krall, chief medical officer for Glaxo, said his company
sharply disputed the methodology of Dr. Nissen's study, and a top F.D.A.
official said that the agency had previously informed doctors about
Avandia's heart risks.

Dr. Krall said his company was aware when it created its database of
study results a few years ago that it might lead to controversy. Other
scientists might look at its data or choose to analyze it differently
than company officials did, he said.

"We are committed to the principle of transparency," Dr. Krall added.
"But we knew that when starting this, by putting the data in the public,
many things could happen, some of which could be trouble."

Some experts also believe that releasing the results of hundreds of
studies involving drugs or medical devices might create confusion and
anxiety for patients who are typically not well prepared to understand
the studies or to put them in context.

"I would be very concerned about wholesale posting of thousands of
clinical trials leading to mass confusion," said Dr. Steven Galson, the
director for the Center for Drug Evaluation and Research at the F.D.A.

Roughly a decade ago, some experts raised concerns that doctors were not
getting the full picture about a drug's risks and benefits because they
tended to hear or read about only those trials in which the medication
showed a benefit.

Companies and researchers typically did not seek publication of studies
that showed that a drug had little benefit or might even cause harm. In
some cases, trials that were started and stopped before completion were
not disclosed.

As a result, outside researchers could not learn what trials of a drug
had been performed so they could put findings in context or compare
studies of competing drugs.

That issue caught the public's attention after it was disclosed that
Glaxo had not publicized trials of Paxil [paroxetine Hydrochloride] in children in which the drug
showed little, if any, benefit. The company was subsequently sued by Eliot Spitzer, who was then the attorney general and who is now the governor of New York. The drug maker, as part of the lawsuit's settlement, created a public Web site for trial results. Glaxo was by no means the only drug company that came under scrutiny. In late 2004, a group of leading medical journals, including The New England Journal of Medicine, said that they would no longer publish articles about study results unless producers publicly registered the tests on Web sites like
ClinicalTrials.gov, which is run by the National Library of Medicine.

As a result, the number of drug trials registered on that site has
sharply increased, said Dr. Deborah Zarin, its director. (Currently,
drug manufacturers are required to register trials of new drugs for
serious or life-threatening conditions).

But even before the recent Avandia episode, advocates for greater study
transparency like Dr. Nissen were pushing lawmakers to take the next
step by requiring that producers of drugs and makers of devices not only
register trials but also publicly disclose study findings.

"It is critical, but this raises the question of how many other drug
safety issues are out there," Dr. Nissen said. Recently, the Senate
passed an F.D.A.-related bill that would set up a process for developing
a mechanism that experts expect would result in a government-run
database where companies and others would post the results of clinical
trials. The House is currently considering a bill that has somewhat
different provisions.

Dr. Alan Goldhammer, a senior executive at the Pharmaceutical Research
and Manufacturers Association, said the organization supported the
disclosure provision in the Senate bill that had passed.

He said the group, however, was concerned that some states may be trying
to get ahead of the federal government on the issue; for instance, Maine
recently passed a bill that mandates the release of study findings.
"We want to make sure it is done in a reasonable way," Dr. Goldhammer
said.

Recently, a report issued by the Institute of Medicine, a part of the
National Academy of Sciences, recommended that the F.D.A. release all
summaries of study data it had collected in the process of approving new
drugs as well as all post-marketing studies of those products.
The F.D.A. rejected the first recommendation as overly burdensome and
Dr. Galson, the director of the F.D.A.'s drug evaluation and research,
said that the agency already released much of this information. "It is
not that we are philosophically opposed to it, but the work would be
enormous," he said.

Even those supporting mandatory results disclosure acknowledge that
finding uniform ways to disclose complex scientific information would
prove difficult and time-consuming. For example, Dr. Zarin of
ClinicalTrials.gov said that reviewing a study's results to make sure
that it was free of any biases interjected by researchers involved in a
study or by its sponsor was a major undertaking.

Then, there is also the question of who the audience for such
information should be - scientists, consumers or both?

Dr. Zarin said that there had been significant discussion among experts
over the last year about that issue. Most have agreed that data is best
understood by experts, a view that might not prove popular with
patients.

Dr. Krall of Glaxo agreed, saying the drug maker had considered
providing summaries of its studies for patients, but then dropped the
efforts after deciding it would require making subjective decisions
about trial results.

"There is not a uniform view about how to interpret results," he said.
"It is quite problematic to go that next step."