Report raps drug firms' 'post-approval' studies

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Report raps drug firms' 'post-approval' studies

By Alice Dembner, Globe Staff, 6/25/2002

CHICAGO - Drug manufacturers spent $1.5 billion in 2000 to test medicines

already approved by the Food and Drug Administration primarily so they could

make new marketing claims to sell their products, industry specialists said

this week. Critics say the trend inflates health care costs while

undercutting the integrity of research.

Spending on these ''post-approval'' drug studies tripled in the last half of

the 1990s, growing faster than any other clinical drug research, according

to CenterWatch, a Boston-based firm that presented the data at the national

meeting of the Drug Information Association. CenterWatch, which monitors the

pharmaceutical industry, said approximately 700,000 patients completed

post-approval studies last year.

''What used to be a scientific purpose - clarifying effectiveness and safety

in a larger population - has turned into a commercial purpose,'' said

conference speaker Nayan Nanavati, a vice president at Parexel, an

international company based in Waltham that conducts studies for drug firms.

''However, it must still be supported by a scientific need.''

These studies can yield important new information on safety and uses of

drugs, such as a 2000 study that found the hypertension drug Ramipril could

reduce the risk of heart attacks. But regulators and consumer advocates say

the studies are helping increase health care costs, can put some patients at

risk, and may taint the public's view of safety testing necessary to get new

drugs on the market.

''If studies are done primarily for marketing purposes, are they serving the

interests of the public?'' asked Dr. Greg Koski, director of the federal

Office for Human Research Protections. ''It could undermine the integrity of

the scientific enterprise.''

Before medicines can be marketed, they must be extensively tested in people

to ensure that they are safe and effective. Pre-market studies are closely

regulated by the FDA and tend to involve fewer than 1,000 patients per

study. When the FDA has further questions about a drug's safety, the agency

requires more testing after approval.

But the bulk of testing after FDA approval is being done so companies can

differentiate their drugs from competitors' and generate more demand, the

conference panelists said. The panelists, speaking in two separate sessions,

mentioned studies of drugs for Alzheimer's disease, hypertension, arthritis,

and heart disease as examples of marketing-driven research.

Some studies are also used to hint at a new use for a drug - and encourage

doctors to prescribe it for that purpose - without going through a lengthy

FDA review, the speakers said. Nonetheless, the studies must have some valid

scientific purpose or they may be halted by federal regulators.

''It's a crowded market, so it's critical to position your drug,'' said

Nanavati, adding that most drug companies will not acknowledge the major

role marketing plays in their studies.

In most post-approval studies, hundreds of doctors are paid to prescribe new

medications to thousands of patients, who receive the drugs for free. While

many of these patients might get the drug anyway outside the study, others

may get a more expensive drug than their doctor would otherwise prescribe.

The studies themselves typically cost between $10 million and $40 million,

the speakers said.

It's unclear whether drug makers directly pass these costs on to consumers.

However, advocates say the studies do inflate overall health care costs.

''This is a high-class version of free samples, and like free samples it

gets people hooked on a drug,'' said Dr. Sidney Wolfe, director of the

Health Research Group of Public Citizen, who did not attend the conference.

''It's good for the companies, but often not for the individual patients,

who can't afford to pay for the drugs or can't afford to pay for their

insurance premiums because they're being driven up by drug expenditures.''

In addition, the studies are designed to get hundreds of doctors in the

habit of prescribing a certain drug, said another panelist,

Deininger, executive vice president of AAI International of Natick, which

also conducts these trials for drug companies. ''It's also a platform for

direct-to-consumer advertising.''

Deininger said the most effective studies from a marketing perspective are

typically those backed by the best science. As a result, he said, he

believes companies have little incentive to lower research standards in the

post-approval trials despite their commercial motives.

Post-approval studies are being driven by economic pressures on the

companies, the speakers said. Major drug companies stand to lose billions of

dollars in sales in the next five years as patents expire and they face

generic competition. At the same time, development costs are rising and

fewer new drugs are being approved. ''Companies need to double or triple

their revenue to maintain the profit margin that Wall Street is demanding,''

said Joan Kroll, director of marketing and sales for CenterWatch.

For example, Merck and Pharmacia did extensive post-approval studies to show

that their arthritis pain medications, Vioxx and Celebrex, were easier on

the stomach than older, cheaper painkillers. Merck's study, involving more

than 8,000 adults, showed Vioxx causes fewer stomach complications than the

painkiller naproxen, but also found it increases the risk of heart attacks.

Both facts were widely reported in medical journals and the media, and the

company has stepped up promotion of the drug's safety since the FDA added

that information to the drug's label.

Likewise, Pharmacia circulated preliminary results suggesting that its study

of more than 8,000 patients showed that Celebrex was easier on the stomach

than ibuprofen. But, in the end, the FDA ruled that the study showed no such

benefit and the British Medical Journal criticized the company for

''distributing overoptimistic short term data'' from its study.

Officials from both Merck and Pharmacia said the primary purpose of the

studies was to answer important scientific questions. And Pharmacia

officials still maintain their drug is safer than ibuprofen.

The risks to patients are generally low if the studies are conducted

carefully, because many side effects are known from pre-approval testing.

Like pre-approval studies, the trials must be reviewed by oversight

committees and must include only patients who agree to participate,the

speakers said. The studies are typically not monitored as carefully by

either the FDA or by the companies themselves, they said. In addition, the

speakers said companies can probably get away with not fully collecting and

reporting to the FDA the occurrence of side effects already listed on the

drug's label, a tactic that others suggest could keep important information

from the public.

But the studies are not risk-free. Some serious side effects only come to

light after approval when a drug is used more widely. This has led some

doctors to shy away from prescribing new drugs in the first few years

they're on the market. However, CenterWatch found that doctors who test

drugs post-approval are nearly 60 percent more likely to prescribe them to

their other patients than doctors not involved in the studies.