For 14 years, UBC internal-medicine and pharmacology professor Dr. Jim Wright has been challenging the claims of the world's largest pharmaceutical manufacturers. This hasn't endeared him to drug-company executives.
Wright is managing director of the UBC–based Therapeutics Initiative, which provides physicians and pharmacists with unbiased, evidence-based information about drug therapies. Want to know about the effectiveness of treatments for erectile dysfunction, diabetes, or hypertension? Chances are there is a one- to four-page "Therapeutics Letter" on the topic at www.ti.ubc.ca/.
These letters are sometimes an antidote to the marketing bumf issued to doctors and pharmacists. For instance, a letter from 2005 on treatments for Alzheimer's disease stated that the drug donepezil "has not been demonstrated to improve outcomes of importance to patients and caregivers". The same letter stated there was "no evidence" that stopping use of another drug, AChE-I, would be harmful.
A separate 2005 letter stated that two drugs used to treat an overactive bladder, oxybutynin and tolterodine, had not been tested in randomized controlled trials beyond 12 weeks, and not at all with elderly patients. A letter on treatments for diabetes concluded that there was no evidence of a reduction in total morbidity or mortality with insulin lispro–a short-acting insulin analogue–compared with other forms of insulin.
In a phone interview with the Georgia Straight, Wright said that consumers should always ask physicians for evidence that drug treatments are effective. "Nobody should take anything unless they've been adequately [convinced]”¦that the benefits outweigh the harms," he said.
Wright and the former head of UBC's department of pharmacology and therapeutics, Dr. Casey van Breemen, persuaded the former NDP government to fund the Therapeutics Initiative in 1994. UBC researchers provide up-to-date, practical information independent of government, the pharmaceutical industry, and other vested interests. The Therapeutics Initiative distributes the research to doctors in the form of the letters, which are edited by Wright.
He proudly stated that the Web site generates more than 10,000 hits a day. "We get feedback from people all over the world," he said.
Wright noted that prior to 1994, the provincial PharmaCare program "basically just approved every drug that came onto the market". Now, he said, PharmaCare heeds the advice of a drug-assessment working group, which meets with the Therapeutics Initiative's scientific advisory committee. "What I can say is they tend to use our evidence," Wright said.
A letter issued last year noted that annual spending per person on prescription drugs in B.C. more than doubled between 1996 and 2003, rising from $141 to $316. The letter noted that so-called me-too drugs accounted for 80 percent of rising costs over that period. The authors of a British Columbia Medical Journal article on this topic, Wright and UBC researchers Steve Morgan and Ken Bassett, define me-too drugs as those that demonstrate no evidence of "any substantial therapeutic advantage over existing drugs".
Wright, who was trained as a clinical pharmacologist, said he has learned a lot since he began this work. "When we first started, I think we were pretty naive, actually," he confessed. "We've discovered so much. We used to believe what was published in [medical] journals."
This was most apparent with the so-called COX-2 inhibitors, a class of nonsteroidal anti-inflammatory drugs released in the late 1990s to treat osteoarthritis. They were sold under such brand names as Celebrex, Vioxx, and Bextra, with the promise that they were less likely than traditional pain relievers to cause stomach problems.
Back in 1999, the Therapeutics Initiative released a letter asking if one such treatment, Celebrex, was truly a "breakthrough drug". Even though it had been approved by Health Canada, UBC researchers could find "no published trial reports" comparing the drug with a placebo, acetaminophen, or other nonsteroidal anti-inflammatory drugs. The only available information was in the abstracts and promotional material distributed by the manufacturer, Pfizer.
"Since almost all clinical data about celecoxib [Celebrex] remains unpublished and is therefore unavailable for critical appraisal and assessment, it is impossible for the TI to provide timely unbiased information to you and other health professionals," the 1999 letter stated.
In early 2001, the Therapeutics Initiative issued another letter stating that patients on COX-2 inhibitors had "less complicated and symptomatic ulcers but more myocardial infarctions [heart attacks]" than patients on naproxen. Later that year, a third letter on COX-2 inhibitors boldly stated: "In the interest of public safety, serious adverse event rates from all trials must be published."
In a July–October 2004 letter, the Therapeutics Initiative issued a much more damning report. In this letter, it stated that the drug companies' product monographs provided "insufficient information as to whether or not those drugs increase myocardial infarction or total cardiovascular thrombotic events".
"We found that the publications didn't really reflect what the trials really showed," Wright said. "It was quite shocking."
In October 2004, Merck pulled Vioxx off the market. In December of that year, Pfizer revealed that a long-term study had shown that taking Celebrex increased the risk of a heart attack. Since then, many lawsuits have been filed by patients and their families, and Wright said he has been asked to testify in some of these cases.
In the meantime, the Therapeutics Letters appear to be having an impact on physicians and pharmacists in this province. According to a Therapeutics Initiative survey of randomly chosen B.C. doctors and pharmacists, 95 percent of general practitioners and 96 percent of pharmacists stated that the group's letters "serve my educational needs"; 95 percent of physicians and 92 percent of pharmacists stated that the letters had led to changes in the way they prescribe or recommend drugs.
Vancouver resident Colleen Fuller, chair of the health-consumer group PharmaWatch, told the Straight that Wright and the Therapeutics Initiative probably saved hundreds of lives by not recommending Vioxx as a first-line treatment under the provincial PharmaCare program. "That's very important," Fuller said.