Contracts Keep Drug Research Out of Reach
Results of Drug Trials Can Mystify Doctors Through Omission
Posted on 12/29/2004 9:21:32 PM PST by neverdem
MEDICINE'S DATA GAP
Across the country, doctors are struggling to decide which pain relievers to prescribe now that they know that popular drugs like Vioxx and Celebrex pose potentially serious heart risks. "We are desperately in need of information," said Stephen Brenner, an internist in New Haven. Yet for at least two years, doctors at the Mayo Clinic, the federal Veterans Affairs Department and the Kaiser Permanente health plan have been sharply limiting their use of Vioxx and Celebrex.
That is because those three institutions, after undertaking separate reviews of test data available on various painkillers, reached the same conclusion: For most patients, Vioxx, Celebrex and a related drug, Bextra, did not work any better than older pain relievers or provide any safety benefits beyond them.
A growing number of health care organizations have in recent years taken rigorous steps to close one of medicine's biggest information gaps. They are scrutinizing findings about all drugs, new and old, available to treat a particular health condition to determine which work best at the lowest cost.
Such evidence-based reviews, as they are known, are an effort to separate scientific wheat from chaff by examining not just the quantity, but also the quality of clinical trials and studies on a given drug. They also seek to determine how a drug's risks and benefits stack up against competing treatments. These reviews have been applied to every major category of medication, from blood pressure treatment to antidepressants.
Practitioners like Dr. Brenner do not typically consult such reviews when deciding which drugs to prescribe, but instead rely on their own experience. But that may change as government agencies and academic centers disseminate drug review research more broadly.
The drive to base medical practice on such reviews is not new, but it is taking on more urgency as health care costs rise and many newer drugs prove to be only marginally better, if that, than older ones.
Eric L. Matteson, a rheumatologist with the Mayo Clinic, said such reviews also help to counterbalance the forces that influence doctors in writing prescriptions, like drug company pitches, medical specialists championing certain medicines and patients eager to get the latest drug advertised on television.
"The pressures to prescribe are enormous," Dr. Matteson said. "You constantly have people at your door."
One of the leading institutions doing drug class reviews is the Evidence-based Practice Center at Oregon Health and Science University in Portland. In recent years, some states have started to use reviews produced by the center to draw up lists for preferred drugs that their Medicaid programs will cover.
Today, about 12 states, including Washington, Oregon and Missouri, use the center's reports to differing degrees.
Earlier this month, the federal government announced that it was planning to spend $15 million in coming years to pay for evidence-based reviews that will compare the effectiveness of various procedures and drugs used to treat 10 of the most common health conditions, including stroke, arthritis, pneumonia, diabetes and ulcers. The studies will be made available to doctors and the public as well as to government and private health plans.
Physicians like Dr. Brenner may welcome the help in deciding which painkillers are appropriate for certain patients. In recent weeks, studies have linked Vioxx, Bextra and Celebrex - all of which are in the class of drugs known as COX-2 inhibitors - to increased heart risks under certain conditions. In late September, Vioxx was withdrawn from the market by its manufacturer, Merck. Pfizer, the maker of Bextra and Celebrex, continues to sell both drugs but has limited marketing.
Another recent study has suggested that an older pain reliever, naproxen, which is sold as Aleve, might also increase heart attacks, though several experts said the Aleve data was less troubling because the numbers appeared too small to be statistically significant. Drug companies say they support the idea of evidence-based medicine. But they also contend that the Oregon center's approach is more about cutting costs than about science.
"What Oregon is doing is hiding a cost-cutting agenda that they are marketing widely under the rubric of evidence-based medicine," said Mark Horn, the medical director for the government relations group at Pfizer. Mark Helfand, the director of the Oregon center, dismissed that suggestion.
And Dr. Matteson said he had heard similar complaints about the Mayo Clinic's work from drug company representatives. "We've had plenty of criticism from the representatives of different companies that market these drugs to us that we are just looking at the bottom line and not to the patient's best interest," he said.
Advocates of evidence-based reviews say they can help make sense of the incomplete and conflicting state of knowledge about different drugs used for the same problem. Newer drugs, for example, are typically tested more extensively than older ones, and not all drugs in the same class are tested against each other. Moreover, the quality of clinical drug trials run on each drug and their relevance to medical practice can also vary sharply.
Those advocates have also long called upon pharmaceutical companies to disclose all clinical trials run on a drug so that all evidence about the drug is available to the public. Legislation to require companies to register their drug trials was recently introduced in Congress.
To do an analysis, researchers try to pull together published and unpublished clinical trials and studies about all drugs in a treatment class by doing extensive literature reviews and asking pharmaceutical companies for data. They analyze the studies to determine their scientific rigor, eliminating those that they believe do not make the cut. Even clinical trials, which are considered the most thorough because they test medications under controlled conditions, can be flawed or misleading because of their design.
"The biggest contribution that we make is in laying out the evidence," Dr. Helfand said.
Because responses to pain relievers varies among individuals, a drug that works for one patient might not work for another. But after reviewing all relevant data, the Oregon group and others doing similar studies decided that Vioxx, Celebrex and Bextra did not relieve pain any better than other drugs they had been tested against, like ibuprofen, which is also a nonsteroidal anti-inflammatory drug, or Nsaid.
In terms of safety, Vioxx showed the strongest evidence of reducing the incidence of stomach bleeding associated with older Nsaids. Stomach bleeding is a problem that is generally limited to older patients or those with a history of gastrointestinal problems. So even as the prescribing of COX-2 drugs by doctors in general was increasing, the use of these drugs by doctors working for organizations doing evidence-based studies was falling.
Doctors working for the Veterans Affairs Department have been curtailing their use of COX-2 drugs since late 2001. The Mayo Clinic decided two years ago to cut down its use of the medications by 50 percent.
Those groups and Kaiser Permanente, which also sharply limited its COX-2 prescriptions, saved money. Their actions may have also saved lives. A study conducted by an F.D.A. researcher that was released in September found that Kaiser patients relied on high doses of Vioxx, which can increase the risk of heart attacks, less than half as often as the general population.
In undertaking its drug review, Veterans Affairs also re-examined the value of a lesser-known pain reliever, etodolac, and began using it more. The drug was first sold in 1991 as Lodine by a company that is now part of GlaxoSmithKline. Like many older medications, however, it was not extensively tested.
A study based on a review of V.A. patient records that was published last month in a medical journal, Gastroenterology, found that the rate of stomach bleeding caused by etodolac was substantially lower than that caused by naproxen and comparable to that of Vioxx.
Byron Cryer, a researcher at the University of Texas Southwestern Medical School in Dallas who led the study, said his group was reviewing those same patient records in effort to determine whether etodolac increased heart risks. Dr. Cryer said that analysis should be completed in about a month.
David Campen, a medical director at Kaiser, said that his organization had not yet changed its prescribing guidelines for Celebrex, which was reported to pose heart risks during a trial of the drug as a cancer treatment.
The Mayo system, which operates hospitals and clinics in several states, meanwhile, has decided to reduce its use of the COX-2 drug even further.
Previously, any patient over 60 qualified for Celebrex, Dr. Matteson said. But earlier this month, a group of Mayo Clinic doctors, epidemiologists and pharmacists, after reviewing old and new test data, decided to limit the drug's use to patients at risk of stomach bleeding or to others with highly specific conditions.
Contracts Keep Drug Research Out of Reach
Results of Drug Trials Can Mystify Doctors Through Omission
bump for later read!
FReepmail me if you want on or off my health and science ping list.
Recently a doctor prescribed Bextra for my shoulder. When I went to fill the prescript, the pharmacist said my drug insurer said the doctor would have to contact them and explain why he prescribed it. This had never happened before but I was in a hurry and paid the full price - $50 something. Next day I did a google on the Bextra and found plenty of headlines about it along with Celebrex and Vioxx. I called my regular doctor and raised 'ell with her (she wasn't in that day) and they are putting a $50 credit on my account.
OK - gabby signing off on this one :o)
But do you still drive a car? Talk about risk taker. Your chances of dying in a car crash are much, much greater than dying from a med.Did you also call Ford?
This is all new news to the medical community and with junk science that is presented as fact, its gonna take some time t sort it out .
Doubt your doc was lazy or out to get you.
Cut her some slack. She's only trying to help.
this is simply the consequence of the Clinton administration FDA.....Billary is the gift that keeps on giving.....
First, the pharma industry is imperfect; we have failed in marketing and in research and development compared to what was expected back in the '80s. Billions spent on R&D by the big companies with precious little to show for it. And, there has always been contention between the medical/regulatory side and the marketing types, in terms of strategies and tactics.
In terms of finding the risks, this is actually less the fault of the industry and FDA than would appear. If 5,000 patients are studied, but a toxicity only occurs in one of 20,000, what can we do?? There is a certain amount of risk always...and the risk for an anticancer drug would be unacceptable for a pain medication.
Although a small government and industry guy, the FDA does a pretty good job. They are torn between releasing new meds and pritecting the public against risk: not always easy. They always try to use evidence-based medicine.
Finally, all disease is based on an interaction between the genes you were dealt and the environment that you grew up in and currently exist in: different for all. Our predictive powers will be better once the science of pharmacogenetics develops into a usable form (that is, testing people for their susceptibility to the good and bad that a drug offers based on their genes).
My problem is every time I go see my doctor; I have to wait for long periods while drug sales representatives get right in to see him. It seems to be a two to one ratio of sales representatives to every patient.
What does he get out of it? Well, a few things: a chance to learn some new data (and the docs are smart enough to know that it is not always "pure"); and, SAMPLES with which to help his indigent patients with.
There are other things, but I won't boor you...
Cheaper to go to the healthfood store and get Boswella Herb with Curcimum..... or online order AR-Encap... Boswella is a natural anti-inflammatory and has no side-effects. It works miracles on pain and inflammation.
Thanks Arizona - have written this down and will see about finding it tomorrow and have it on hand for the next time.
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