Business Week: Do drugmakers have too much control over lab data?

June 22, 2004

Again, a medical article from the business media.

My favorite line:

" Drug companies can design trials in ways that give their products an

edge. Dr. Cary P. Gross, assistant professor of medicine at the Yale

School of Medicine, says drugmakers may, among other things, select

dosages that are likely to show their product in a positive light. "

We've seen a lot of that lately.

http://www.businessweek.

com/print/magazine/content/04_26/b3889080_mz018.htm?tc

Business Week Online

JUNE 28, 2004

SCIENCE & TECHNOLOGY

Commentary: When Medicine And Money Don't Mix

Do drugmakers have too much control over lab data?

GlaxoKline PLC is the drugmaker in the hot seat this month. New

York State Attorney General Eliot Spitzer sued the company on June 2,

alleging that Glaxo fraudulently concealed data suggesting that its

antidepressant Paxil might trigger suicidal thoughts and acts in kids

under 18. British regulators, meanwhile, have been investigating

whether Glaxo improperly withheld similar data on how the drug affects

children. Glaxo says it has acted responsibly in conducting studies on

pediatric patients and in disseminating that data. On June 14, Glaxo

posted full pediatric study data on Paxil on its Web site.

The Paxil case, unfortunately, highlights a growing problem: Over the

past two decades big drugmakers have exerted increasing control over

medical research. Now they face broad criticism that they often spin

the resulting data for commercial gain.

In some cases, drug companies downplay or delay the release of

negative data. Critics also accuse drugmakers of designing their

studies to improve the odds that their drugs will outshine competing

products. And to spread the word, some pharma companies have hired

consultants to write positive reviews of trials and paid doctors to

sign on as authors.

Even the revered National Institutes of Health has drawn congressional

scrutiny into financial ties between its researchers and companies.

" The threat is to the objectivity of scientific research, " says

Sheldon Krimsky, a science policy expert at Tufts University and

author of Science in the Private Interest. " It is reaching crisis

proportions. "

Pharmaceutical companies don't bury all unfavorable data. In early

March, for example, Bristol-Myers Squibb announced that a study

comparing its cholesterol-lowering drug to Pfizer's had shown the

rival's product to be superior.

But such moves are all too rare. Take the case of the arthritis

treatment Celebrex. A big product for Pharmacia in the 1990s, the drug

is a $3 billion blockbuster. It got a boost in 2000 when a trial

showed that it was linked to fewer ulcers than two older nonsteroidal

anti-inflammatory drugs (NSAIDS). The problem was, Pharmacia's

published data showed how patients fared after just six months, even

though the company had gathered data for 12. The figures for the full

year revealed less of a safety advantage for Celebrex -- and the Food

& Drug Administration continues to require that Celebrex' label carry

the same warning about stomach side effects as older NSAIDS.

A spokesman at Pfizer Inc. (PFE ), which bought Pharmacia in 2003,

says a committee of medical experts determined that the 6-month data

was more meaningful because a large number of patients dropped out of

the study at the half-year mark. In any case, he says, the full

results were presented at scientific meetings. But critics argue that

all that data should be publicized, so that doctors can reach their

own conclusions. " The information prescribing physicians get on the

safety and efficacy of drugs is grossly inadequate, " contends Dr.

Sidney Wolfe, director of the health research group at Ralph Nader's

watchdog body, Public Citizen.

Yet even if all trial information is made public -- a step being

pushed by a variety of groups, including the International Committee

of Medical Journal Editors and the American Medical Assn. -- other

problems will persist. That is because corporate funding now permeates

most drug-related research. One Yale University study notes that in

1980, 32% of biomedical research and development in the U.S. was

funded by industry. By 2000, the figure had soared to 62%.

As the industry has tightened its grip on research, the traditional

emphasis on independence and ethics in medical science seems to have

eroded. The Yale study found that in industry-funded research the odds

are 3.6 times higher that the results will buttress the sponsor's

product than in studies by independent groups such as the NIH and

various foundations.

The reason: Drug companies can design trials in ways that give their

products an edge. Dr. Cary P. Gross, assistant professor of medicine

at the Yale School of Medicine, says drugmakers may, among other

things, select dosages that are likely to show their product in a

positive light.

PAID ENDORSERS

Independent researchers are supposed to provide a counterbalance,

thwarting the drug industry's tendency to turn research studies into

marketing grist. But some drugmakers appear to have found ways around

that. A lawsuit brought by a whistle-blower against Warner-Lambert in

1996 alleged that the company brought in consulting firms to

" ghostwrite " articles on its epilepsy drug Neurontin, and then paid

physicians to sign on as the authors. Pfizer, which bought Warner in

2000, agreed to pay $430 million to settle a government suit triggered

by the whistle-blower allegations. A spokesman for Pfizer says the

company did not admit to the allegations in its settlement, and points

out that all the activities at issue in the case occurred before

Pfizer bought Warner.

It's impossible to know how prevalent ghostwriting is. But Dr.

Drummond Rennie, professor of medicine at the University of California

San Francisco and deputy editor of the Journal of the American Medical

Assn., believes it is " pervasive, deceptive, and disgraceful. "

In fact, Big Pharma's money and influence touch almost every corner of

the medical industry. Consider that the NIH was compelled to set up a

commission to look into conflicts of interest at the agency last

February. An NIH spokesman now concedes that 118 employees at the

Institutes have 196 ongoing consulting deals with corporations,

primarily pharmaceutical and biotech companies.

So what's the right prescription for the questionable practices that

have infected medical research? The first logical step is to establish

a public registry that would carefully archive the results of all

clinical trials. Drug companies have not supported such a move to

date. And even if they bend, it won't be enough simply to disclose

results as they are analyzed by the trial sponsors. Independent

scientists -- enlisted by citizen groups, medical journals, or the

government -- must have access to the raw data to ensure that

conclusions are fair and accurate.

At the same time, the federal government should make more money

available for follow-up trials on drugs that are already on the

market. Such tests, uncontaminated by corporate funding, would provide

valuable comparative data on how well drugs work -- especially in

" off-label " treatments that don't involve FDA approval. Why bring in

the government? Because drugmakers may resist doing expensive trials

if they believe the drug may fare poorly.

The discouraging fact is that for many pharmaceutical companies, the

current system is working beautifully. Few will acknowledge that major

reforms are necessary. Of course, Wall Street analysts took exactly

the same stance when they first came under legal fire. Big Pharma

would do well to take their traumatic experiences to heart.

By Amy BarrettWith Kerry Capell in London and n Rutledge in New

York

reserved.

June 22, 2004