Healthy Skepticism Library item: 11062

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Cassels A.
Prescription for a drug disaster
Common Ground 2007 Aug
http://commonground.ca/iss/0708193/cg193_cassels.shtml

Full text:

“It is a very problematic information environment.” Those are the words of a UN spokesman in Afghanistan, recently commenting on the progress on the war there and the incredible difficultly officials had in accurately counting the deaths of civilians.

Very applicable words, I thought, given my world. Whether you are swallowing a war or a prescription drug, there’s much that’s “problematic” about the information we are able to access. Do we ever really know what’s happening on the ground? Do we know how many people suffer injury or death due to the use of new prescription drugs? Not really, and while you could describe the regulation and marketing of prescription drugs as problematic, I think “shock and awe” are more applicable.

One key problem is that as a new chemical entity travels from laboratory bench to your mouth, the information consumers need to use it safely often isn’t available, is biased or is actively kept secret.

For starters, the evidence a company presents to regulators like Health Canada or the US FDA, in order to get approved, is drawn from a relatively small and select sample of patients. We don’t know the actual benefit/harm ratio from the data used to approve the drug because that information is secret and considered “proprietary.” And Health Canada only releases “summary” information often leaving more questions than answers. Even with several rigorous and well-controlled trials behind a new drug, your physician really has no way of knowing how those data apply in real situations with the kinds of patients he will see in the “real world.” And that’s a huge problem.

Many people I talk to ask, quite earnestly, what’s not to trust about the safety of a new drug? After all, it was studied in big trials, approved by a regulator, prescribed by a competent medical doctor and dispensed by a helpful pharmacist. How could we question the safety of it?
A good question, with a simple, succinct answer: Vioxx.

Think back to 1999 at the eve of a new millennium when Vioxx and her sister Celebrex were arriving on the market. The media breathlessly dubbed these two new Cox-2 inhibitors “Super Aspirin” as medical symposia around the world promoted them as less likely to cause gastrointestinal bleeding, a common side effect of non-steroidal, anti-inflammatory drugs.

The manufacturers were spending money like it was 1999 because, well, it was 1999. Thousands of sponsored medical dinners with “thought leader” rheumatologists bedazzled our physicians with the magical properties of these drugs. The intense competition between the two rival drug makers, Merck and Pfizer, created a situation where you could barely find a doctor that hadn’t been wined and dined by those pitching their brand.

But what did the consumers know about these new drugs? Well, if you remember, Vioxx skated into our lives on one of the slickest and most expensive prescription drug ad campaigns every mounted, featuring figure skater Dorothy Hamel who helped expand and reshape an arthritis market which, up to that time, had been the preserve of little, old ladies.

At the same time, arthritis patient groups in Canada, lubricated with pharma largesse, were actively lobbying for public coverage of the drugs because, after all, provincial health plans are the biggest buyers around and if they weren’t going to pay for them, it would severely limit the drugs’ markets. In BC, the Arthritis Society used its website to ask visitors to fill out postcards to their MLA, demanding public coverage of the new drugs, so thoroughly smitten they were.

Seems like the patient advocates either weren’t apprised of the bad news or didn’t care. In 2000, the widely publicized VIGOR study suggested Vioxx may increase risk of heart attacks; the company’s response was to spend $160 million on drug ads to skate around this uncomfortable bit of news. The millions the manufacturers invested in drug ads, rheumatologists, physician education and arthritis patient groups, an enormous investment by any standards, provided a good return. By 2003, Vioxx was the 10th most prescribed drug in Canada, and with worldwide sales in the multiple billions, Celebrex and Vioxx had redefined pharma’s idea of the super blockbuster.

And then, of course, disaster struck.

Vioxx was withdrawn in disgrace in September of 2004 and thousands of lawsuits were launched against Merck amid estimates that its drug may have caused up to 120,000 cases of cardiovascular disease and left 40,000 to 60,000 people dead in the US alone. (The Vietnam War, by comparison, lasted three times as long as Vioxx and killed 58,000. How many died on the Vietnamese side is still open to question as that war, as you might have guessed, also presented a very “problematic” information environment.)

The sister Cox-2 drugs didn’t fare much better. Bextra was yanked from the market shortly afterward and Celebrex, the sole Cox-2 remaining, wears a “black box,” the most serious warning placed on a marketed drug product. What is problematic in the whole sordid Cox-2 saga is that nobody, including the regulators, the doctors and the arthritis advocates sending postcards to their MLAs, knew exactly what would happen when a drug tested on a few thousand select people is then used by millions.

Post-Vioxx, everyone asked how this could be prevented from happening again and we’ve heard many calls for restricting drug advertising, stopping drug companies from wining and dining our doctors and better post-market surveillance systems (i.e. monitoring a drug’s behaviour once it enters the market). These measures don’t, however, address the real problem: uncertainty.

The best approach to uncertainty when billions of dollars and thousands of lives are at stake is to collect more data. As the case of Vioxx soundly illustrated, what we need is what a group of Canadian academics have labelled “Real World Safety and Effectiveness” research (RWS&E). There are a number of ways to get this data before putting new drugs on the market, but one way is to involve drug insurers to make sure that RWS&E data are being collected and analyzed.

I remember the hullabaloo when the Cox-2s came to BC; some researchers proposed that Pharmacare conduct a policy trial to determine the “real world” effects of Celebrex and Vioxx. The specialists, doctors and especially the arthritis advocates in Canada were so overwhelmingly infatuated with the Cox-2s, they wouldn’t want another pesky “study” to find what would happen to these drugs in the real world. The researchers’ wishes to gather additional data were dismissed. And that’s a pity. A properly controlled trial in the real population in the province could have discovered in a year what it took the company four years to admit: that for many patients, the harm of these widely-used drugs exceeded their benefits.

Like many, the industry-funded, patient arthritis advocates in Canada wanted access, access, access, and they pushed every provincial government in the country to pay for the drugs, with varying degrees of success, but that’s another story. In Canada, the “access” mantra comes loudest from a group that calls itself the Best Medicines Coalition, an umbrella group largely consisting of pharma-funded advocacy groups. Check out the coalition’s website at www.bestmedicines.org and see if you can see how and where safety and “real world” drug information fits in its list of priorities.

At the end of the day, when you look in the mirror and take your drug out of the medicine cabinet, you want to know two things: will it work and is it safe? Despite our confidence in the regulator, the Vioxx debacle has rudely reminded us that good data from Real World Safety and Effectiveness research is about the most important safeguard we consumers need when new drugs arrive, all breathless and full of promise.

If the Canadian government needs more proof before it puts serious money behind Real World Safety and Effectiveness, it can look further into the past, before Vioxx, and recall other drug disasters: Tambocor, Baycol, Rezulin and Prepulsid all looked good out of the research pipeline.
They were promoted with great fanfare, pushed by the advocates and used by millions of people, then withdrawn in disgrace when the body count got too high.

Will we see those patient advocates who proclaim to be providing consumers with a voice, promoting Real World Safety and Effectiveness Research? Don’t count on it; the pharmaceutical companies aren’t in the charity business.

They fund groups to pump governments to open access to every new drug coming out of the pipeline. Real World Safety and Effectiveness research sounds like a speed bump to the market.

Dear reader, when your doctor offers you a free sample for the newest drug on the block, ask yourself if you want to be part of an uncontrolled experiment, for which the “data” on how the drug actually works for you may never be collected?

Until “real world” data on the effects of drugs are required, and systematically collected, like Afghanistan, the information environment will continue to be “problematic.”

Sadly, we will only be able to venture a guess at the body count.

Alan Cassels is co-author of Selling Sickness: How the World’s Biggest Pharmaceutical Companies Are Turning Us All Into Patients and a drug policy researcher at the University of Victoria. His new book, The ABC’s of Disease Mongering: A Guide to Drugs and Disorders (Emdash Book Publishing), will launch in October.