Focus research on safety

DRUG BUST by Alan Cassels

The people’s briefing note on prescription drugs

Portrait of columnist Alan Cassels• Why is more money going towards drug discovery research than drug safety research? Because that’s what the government of Canada is paying for.

Today’s fortune-tellers, horoscope writers and other modern soothsayers are very compelling figures. They are magnets for attention even though their predictions should be thought of as entertainment and not enlightenment. Yet some predictions do turn out to be right. Julius Caesar was murdered by a conspiring group of senators in Rome, but at least he was warned by his wife and a soothsayer who said the Ides of March – the 15th of the month – could be a very bad day indeed.

This year on the Ides of March, Canada’s federal government chose to announce, with much fanfare, an investment of $150 million over the next five years for pharmaceutical research. The funding seems to be aimed primarily at drug researchers connected to drug companies – because you need matching funds to play in that pool – and at a mere $30 million per year over five years, this doesn’t seem like that much. If, however, we step back from that announcement and gaze into a crystal ball, we can judge with some degree of certainty where the government’s priorities may be taking us. In an era of restraint and worries about the fiscal health of the country, and with the Conservative’s Health Minister Leona Aglukkaq plunking down a big wad of cash to help strengthen “Canada’s position as a preferred location to conduct clinical research,” you tend to pay attention. If you like the idea of Canadians doing clinical research and welcome Canadian patients being the research subjects, you’d welcome such an announcement.

If you have a debilitating disease like MS or Parkinson’s, you might be glad that Canada’s government is prioritizing pharmaceutical research and putting money towards researching products to help our citizens stay healthy. The announcement also noted the new investment will “accelerate the development of new clinical practices and health products, which will have a direct impact on treatment and services provided to patients.”

I know many hardworking researchers who would salivate over even a small portion of the new $150 million, especially the relatively poor lot struggling away doing health services research, investigating drug safety questions or testing different ways to make physicians better aware of adverse drug warnings. But clearly this new funding is not about using the drugs we have more thoughtfully; it’s about developing even more of them. I look into the crystal ball and wonder why it seems important to have drug research done in Canada. Does it matter if a new drug, a new computer program or a new car is designed, tested and built in Mumbai, Melbourne or Montreal? Arguments could be made either way, but the stark reality of globalization is that the global mega-corporations who develop any product nowadays – whether it’s a mobile phone or an osteoporosis drug – are ruled by the laws of the marketplace and will get things done where it is cheapest.

So why would pharmaceutical companies want to develop and test their drugs in Canada if they could do so in Africa, India or China at a fraction of the price? That’s a complex question, but we do know that federal tax incentives and research funding to sweeten the pot will, at least, buy some temporary loyalty. Developing drugs is all about determining effectiveness, learning if a new chemical entity will work in certain diseases and result in improved health outcomes. We absolutely need that kind of research and the drug industry and the Canadian government, including our Health Minister, would argue we need to fund the people and the infrastructure to keep high tech medical research in Canada. All part of the “knowledge economy” they’ll say. Others would argue where a product is developed and tested is irrelevant because the global companies doing the developing will want to sell them wherever they find paying customers. This leads me to conclude that, by necessity, we need more of the kind of research that can only be done here – applied research – which is about taking effective treatments and practices and maximizing their efficient use in a Canadian health system.

Archie Cochrane, a British researcher whose name now brands the internationally esteemed Cochrane Collaboration, one of the best sources of systematic health evidence in the world, wrote a book called Effectiveness and Efficiency: Random Reflections on Health Services. Over 40 years ago, he stressed that governments must actively determine a nation’s research priorities and that “pure” research” can be done and is, in fact, done all over the world.” He said that to improve the effectiveness and efficiency of a health service, governments needed to make considerable investments in applied research.

Applied research asks “real world” questions such as: does health service X or drug Y or diagnostic test Z produce health outcomes in our population that are worth the money we invest in them? And if not, what does produce those desired health outcomes?

One example of applied research could lead to safer and more effective use of pharmaceuticals. We have a Canadian research network called DSEN – the Drug Safety and Effectiveness Network – which was set up a few years ago and funded with $30 million over five years to study the real world safety and effectiveness of drugs. Research to discover rare side effects or adverse effects of drugs already on the market is intensive work that is relatively low-cost, but with potentially high impact. While the DSEN group is studying some vital questions, including the safety of statins (cholesterol-lowering drugs) and antipsychotics (drugs for schizophrenia, but also widely used in the elderly), will it be enough to make much of a dent in the way drugs are used in this country? The crystal ball says no.

Undoubtedly, there are many important drug safety issues that affect millions of Canadians that may never get studied because of insufficient funds and these important research questions might include:

1. Are cholesterol-lowering drugs safe or effective in women and the elderly? (All the data accumulated so far says it’s probably neither.) 2. Should teenagers be prescribed antidepressants, given the known harms of suicide risk? 3. Should pregnant women consume certain prescription drugs when we don’t know their overall risk to the fetus? 4. Should antibiotics be limited to only the most serious, verifiable bacterial infections, which would help stop the deadly onward march of antibiotic resistance? 5. Should the elderly have their blood pressure lowered so vigorously with drugs and could this be contributing to an epidemic of hypotension (low blood pressure) that leads to falls and broken hips? It’s clear the Ides of March announcement of a new $150 million won’t answer important questions like these. The drug companies don’t want to ask questions that might lead to the population taking less of their products.

Will further research in pharmaceutical development make a difference in the lives of Canadians? It might, but that crystal ball is murky. Would it be better to put more money into drug safety and ways to get patients off dangerous drugs to keep people healthier? I can’t read the future, but that’s where I’d invest my money.

A final point: everyone who swallows pills has a golden opportunity to make the world a better place. Have you had an adverse reaction to a drug? Then why not share that experience with others by asking your doctor or pharmacist to file a report with MedEffect Canada, our federal adverse drug reaction reporting system? (Just Google MedEffect Canada.) You could also call the Canada Vigilance hotline at 1-866-234-2345 (toll-free) and file a report with a new website launched in Canada at www.rxrisk.org.

Alan Cassels is a drug policy researcher at the University of Victoria and author of the forthcoming book Seeking Sickness: Medical Screening and the Misguided Hunt for Disease, due out April 2012. Read more of what he’s writing about at www.alancassels.com

The real cost of free samples

A bunch of Prozac capsules spilling out of a bottle

DRUG BUST by Alan Cassels

The people’s briefing note on prescription drugs

• Psst. Hey kid, try one of these. It’s really good stuff.

Thus goes the standard pitch of the schoolyard pusher, selling the benefits of the product – so to speak – and expanding his market. What he seeks is a happy client who will hopefully come back for more. The hook, as any drug peddler knows, is “The first one’s always free.”

And that’s how you build a market.

I shouldn’t be comparing these tactics to those of the world’s major pharmaceutical makers who sell legal and often very valuable products, but there are certain similarities. Drug companies have been using free samples as an essential part of their marketing efforts for decades.

The logic of free samples is quite simple. The manufacturers need to introduce their new product to a market that is usually already crowded. How do you get people to use your product without actually paying doctors to prescribe your drug (which also happens, but more about that later)? Samples, that’s how.

The free sample is ubiquitous in many of our physicians’ offices where large cupboards store the latest offerings, waiting to be dished out to patients.

The appeal of freebies is obvious: everyone loves something for free, especially those patients who feel good about skipping the pharmacy and saving themselves money. Doctors like satisfied patients and helping out someone who maybe can’t afford their drugs probably feels good too.

With all the feel-goodery swirling around drug samples, society seems to act like a kid in a candy store when it comes to applying caution to how they’re used. In my opinion, we need to ban or severely restrict the use of free samples.

Of course, the brand name pharmaceutical industry – generic companies don’t play the free sample game – would howl in protest were such a ban enacted. The industry would object vigorously, saying that free samples are vital for physicians and patients to become aware of new therapies. They would argue that free samples provide important drugs for the poor. They’d claim that a free sample is a central part of free enterprise and you can’t ban businesses from giving away their products. If you start down that road, you’d have to also ban other stuff such as free food samples in grocery store aisles, free wine samples in liquor stores and so on.

That’s what they would argue.

What the companies wouldn’t say is that the law lets them write off the selling price of the samples, which might be several dollars per pill even if it cost them only pennies to make. And because of this, samples cost governments hundreds of millions of dollars a year in lost income while companies get to feel like good corporate citizens by flooding our doctors with tax-deductible freebies.

The drug companies won’t tell you that without free samples most doctors would stop seeing the drug reps altogether and without them their most effective method of talking up their wares to doctors would grind to a halt.

From my perspective, after looking at the issue of free samples for years I’d have to conclude that, on the basis of consumer safety, economics and sustainable drug plan spending, free samples have gotta go. It will be one of those things in the history of medicine – like bloodletting – that we’ll look back on with horror at how incompetent we were.

On the basis of safety alone, I think the BC government would be perfectly justified in banning free pharmaceutical samples. In BC, we have an extremely useful computerized database called PharmaNet that helps protect patients from adverse drug reactions.

When you pick up your new drug from a drugstore in BC – it doesn’t matter if you get it from our local Gonzales Bay pharmacy or from a drugstore in Fort St. John – it still gets recorded in PharmaNet. When you go to pick up that drug, your pharmacist – your best friend when it comes to keeping you safe from drug interactions – will enter it into the system. If there is a potential adverse reaction with any other drug in your profile, they will alert the doctor, possibly asking for a change to the prescription. Call it the “sober second thought” on prescribing.

Free samples, on the other hand, never get entered into PharmaNet so any potential interaction between the new drug and the ones you’re already taking is left unexamined. Not good.

But do samples help get drugs to poor or indigent patients? Drug samples are almost always the newer, more expensive patented drugs about which we know the least. Most guidelines and the majority of reputable sources of prescribing information to doctors will say that “first line” recommended treatments – the first choice of a drug for a particular condition – are older, proven treatments and usually generic drugs. You’ll never find generics among the free samples.

Often, the provincial drug programs won’t cover the newest drug you first took as a sample so when you finally have to go to the pharmacy to pay for it, what happens? Sticker shock, that’s what happens. Free samples are a bust on the economic front because there is a good chance you’ll be started on a drug you eventually have to pay for yourself at a vastly inflated price over what is likely recommended therapy.

This same “first one’s free” rule happens in our hospitals too. The drug companies know that people started on drugs while in hospital will often stay on the same ones when they are discharged so the drug companies often give the hospitals super low prices.

A few years ago, a BC hospital pharmacist told me their hospital had the most expensive anti-heartburn drug, in a class called PPIs or Proton Pump Inhibitors, on their formulary. The drug in the community cost about $2.50 per pill, but the company was selling them to the hospital at a penny each. And why not, if the principle of the “first one’s free” still is wonderfully profitable?

Which brings me to the final issue, something people ask me about all the time: Do doctors get paid to prescribe certain drugs? I can say this is typically not public knowledge, but we do know that one of the ways drug companies market their drugs is by carrying out what are called “seeding trials.” They will say to a doctor, “Please prescribe our new drug to the next 10 patients and we’ll pay you $200 per patient.” If your doctor makes an extra $2,000 to be part of a company’s “research team,” does that seem unreasonable?

Maybe not to the doctor, but to the patient who isn’t told their doctor is being paid to prescribe a particular new drug, it might seem a little dodgy.

Let me leave you with a final bit about the PPIs, which include drugs like Losec, Nexium, Pantoloc or Pariet, all very widely used in people with heartburn or ulcers. These powerful drugs have been commonly prescribed for at least 15 years and like any drug class, as time goes on, more and more adverse effects seem to appear. Health Canada recently issued a warning saying that PPIs can cause diarrhea and may lead to more serious intestinal conditions, including increasing your risk of getting a nasty bug known as C. difficile.

PPIs are fabulous at reducing stomach acid, yet like any weapons-grade pharmaceutical they are also capable of causing considerable collateral damage. Last year in the US, the drug watchdog group Worstpills.org, worried about the growing list of dangers associated with PPIs, petitioned the FDA to require black box warnings on the whole class, saying they caused a host of problems including rebound acid hypersecretion – which can cause people to become dependent on the drug – fractures, infections and magnesium deficiency, among other things.

If you’d received a PPI as a free sample, your pharmacist wouldn’t have been able to warn you about any potentially dangerous interaction with dozens of other drugs. And the pharmacist couldn’t have told you that PPIs render some drugs, such as clopidogrel, (Plavix) less potent.

All in all, free samples are bad medicine and they can be a pain in the gut. Avoid them.

Alan Cassels is a drug policy researcher at the University of Victoria and author of the forthcoming book Seeking Sickness: Medical Screening and the Misguided Hunt for Disease, due out April 2012. Read more of what he’s writing about at www.alancassels.com

Educating doctors

a big red heart-shaped pillow wrapped in a stethoscope

DRUG BUST

by Alan Cassels

The people’s briefing note on perscription drugs

• A few years ago, I was invited to be the guest on an Ottawa radio talk show, the topic being something I was well familiar with, a book I co-wrote called Selling Sickness. The book explores how the pharmaceutical industry influences regulators, physicians and patients in order to sell its treatments.

On this occasion, Steve, the show’s host, invited the station’s “house doctor” to join us. Barry, a local doctor, had his own program at that station and it soon became startlingly clear I was about to be tag-teamed. After warming me up, Barry came to the point: “How could you possibly insinuate that physicians were under the influence of pharmaceutical sales reps?” These are the salespeople working for drug companies that make personal visits to doctors, dropping off samples and otherwise ‘educating’ our physicians about new drugs. “I’m offended that you think we physicians can be so easily bamboozled by sales reps,” he spat out.

Pinned against the turnbuckles, I turned to the radio host and asked, “Steve do you own any shares in pharmaceutical companies, maybe have pharma stocks in your mutual fund portfolio?”

“Sure I do,” he said. “Well, Steve, you’re wasting your money,” I said. “You know, those companies spend upwards of $2 billion per year marketing their drugs to Canadian doctors; most of that goes to drug reps. So, Steve, if those drug rep visits ain’t having any influence on doctors, then you’ve made a poor investment. If Dr. Barry is right, pharma’s marketing model ain’t working.”

They both sputtered a bit. C’mon guys. Reality check. Does an industry this successful and this powerful invest in things that don’t work? Of course not; pharma has lots of high octane brains to invest its money where it produces the greatest return. Period. If it’s in pizza or pens, delivered by smiling drug reps, then that’s where the money’s going.

Barbara Mintzes, an epidemiologist at UBC’s Department of Anaesthesiology, Pharmacology and Therapeutics knows a thing or two about drug marketing, having studied the advertising and marketing activities of the drug industry for nearly two decades: “We know from the research that sales representatives, also known as ‘drug detailers’, have a big influence on doctors’ prescribing,” she says. “They often have much more influence than doctors realize. If doctors aren’t getting the full story [about a drug], if most of the time they hear nothing about side effects or about rare, more serious harmful effects, how can they make sure they’re prescribing safely?”

When I asked a friend, a former sales rep in Nova Scotia, he said: “Hmm, ‘good safety profile’, is about all we’d say about safety. Basically, unless they [the doctors] ask, we don’t bring up the topic.”

It’s easy to see why drug sales people are effective. Generally, they are polite, engaging and extremely good at reading people, trained to focus on the positive of their products and driven to do whatever is needed to get doctors to write their prescriptions.

Some physicians won’t see drug reps, but a 2006 survey found about two-thirds of doctors in BC see reps at least once a month and 42 percent of BC’s GPs get visited several times a week. Many doctors like the free drug samples. More than one doctor has told me that’s the only reason he sees reps. The samples are always the newest and usually the most expensive drugs on the market.

Worries about how drug reps might be biasing prescribers led researchers to think about providing doctors unbiased or academic sources of information. Thus, the concept of counter-detailing or “academic detailing” was born. The Granddaddy of this movement is Dr. Jerry Avorn, a physician and professor of medicine at Harvard Medical School. His 2004 book Powerful Medicines reflected on the thinking behind it: “If the pharmaceutical industry could change doctors’ prescribing patterns this way to increase sales, why couldn’t the same method be used to improve the appropriateness of drug use?”

That’s a very good question and he and his colleague Steve Soumerai set out to prove academic detailing could do what it purported to do: provide a lifeline to physicians swimming in a sea of pharmaceutical marketing spin. More than 25 years later, academic detailing programs are in place in many parts of North America, but they have hardly any effect on medical practice.

Why? Well, for one, it’s hard to change prescribing. As Dr. Avorn notes, it’s not easy to get “evidence-based, unbiased clinical knowledge” to supplant other types of information based on “tradition, superstition or mainly commercial agendas.”

The second reason is size: there are probably 100 drug sales reps for every one academic detailer in Canada. The academic side of things is simply outgunned. Despite good research that academic detailing can improve prescribing, there is little public investment in it. The first program started in Canada was here in BC, a single detailer based out of Lions Gate Hospital in North Vancouver. That program has grown to about 10 academic detailers covering the whole province and there are also well-established programs in Nova Scotia and Saskatchewan. However, the big provinces of Ontario and Quebec aren’t even in the game, with the exception of a program in Hamilton. Alberta had a program but it was cut. Manitoba’s program is on life support.

The third reason, and this is my own conclusion, is that no one has made a powerful enough business case for academic detailing.

A duo of ex-pharma detailers in Atlantic Canada, who call their company Prescribed Solutions have an answer. They know the selling game well and their pragmatic approach is to visit doctors armed with drug cost-effectiveness information and teach doctors how to improve generic prescribing so that both patients and drug plans can get good drug therapy and save money.

These Atlantic Canada entrepreneurs understand that one of the most important bits of information doctors need (other than drug safety information) is comparative cost information of the drugs they prescribe. Basically, if there are 10 drugs in a class that all do the same thing, why would a doctor prescribe the most expensive brand, which could be three times the price of the proven generic? A major gap in our physicians’ knowledge is the price of drugs and prescribing an affordable drug can have huge implications on whether a person gets a script filled.

A study out last month by UBC researchers shows patients will avoid a trip to the pharmacy if they don’t think they can afford them. And for many essential drugs, that can be decidedly bad for your health.

If drug reps schmoozing in doctors’ offices are trying to get new customers through free samples and evidence exists that academic detailing is effective, leading to safer, more cost-effective use of drugs, why haven’t governments or employers – who pay for your private drug benefits – embraced it?

Because they haven’t done the math. For every one percent increase in the generic use of drugs in Canada, the private payers – those with drug coverage through the employer – save over $100 million. If Canadians used generics at the same rate as Americans, it is estimated we’d shave about $2 billion per year off our drug bill. This is not small potatoes.

Is any kind of counter-detailing even on the radar of most politicians or union executives? As far as I can tell, the only politician I’ve heard asking for more investments in academic detailing is BC’s NDP leader Adrian Dix. I think he might be on to something.

If provincial governments are all about creating jobs, let’s provide jobs to the many pharma reps out of work due to the recent economic slowdown. Let’s put them on the public payroll and get them to spread the word about drug safety and cost effectiveness to our physicians.

It is time to undo the love affair between drug companies and doctors and start building some new relationships where patients can all benefit.

Alan Cassels is a drug policy researcher at the University of Victoria and author of the forthcoming book Seeking Sickness: Medical Screening and the Misguided Hunt for Disease, due out April 2012. Read more of what he’s writing about at www.alancassels.com

 

A deadly rush to market

The people's briefing note on prescription drugs

DRUG BUST by Alan Cassels

I was interviewing a hospital physician in Ontario and we were discussing a drug that had recently been approved in Canada to prevent strokes and its potential to cause excessive bleeding. I knew something was wrong with this new drug, but I didn’t know how wrong until I was halfway through my interview. It was her mention of the experience of emergency room physicians that caught me off guard.

“Everyone knows of a patient who has drained the blood bank,” she said.

I was floored. What was she talking about? It took me a while to figure out the side effects of the new drug, an anticoagulant called dabigatran – Pradax in Canada and Pradaxa in the US – was capable of some serious stuff, particularly uncontrollable bleeding.

Anticoagulants work to stop blood from clotting and because blood clots can cause strokes, taking drugs to prevent clots can be very helpful. Dabigatran, which was approved in Canada to prevent strokes in November 2010, is the first of a number of new drugs poised to replace warfarin or Coumadin, a standby that doctors have used for decades. Some call it rat poison, as it is also used for that purpose.

The problem is not that this new drug causes unwanted bleeding, which warfarin can do as well, just ask the rats, but it can be extremely difficult to stop the bleeding once started. While Warfarin’s action can be effectively reversed with an antidote of vitamin K, with dabigatran, sometimes there is no easy way to stop an unwanted bleed.

Bleeding to death is not pretty; nor are cerebrovascular accidents also known as strokes. If there is a disruption to the blood supply to your brain, you can rapidly lose brain function. Such disruption is usually due to a blockage, (about 80% of strokes involve a blocked blood supply to the brain) or leakage (where blood leaks out), which also disrupts brain function.

About 15% of all strokes are caused by atrial fibrillation (AF), an irregular heartbeat that is very common in the elderly, who are usually treated with warfarin. With over five million warfarin prescriptions written every year in Canada, it is a major drug market.

In addition to dabigatran, several other anticoagulants are trying to get a toehold on that atrial fibrillation market including apixaban (Eliquis) and rivaroxaban (Xarelto). Since dabigatran is the first warfarin replacement out of the starting gates, it has undergone the most scrutiny.

The drive to find a drug to replace warfarin focuses not on effectiveness, but on convenience. Warfarin is effective, but a royal hassle for many patients. It has a “narrow therapeutic window,” sometimes delivering too much or too little of its blood-thinning effect. It requires frequent monitoring, lots of needles, trips to the clinic and the lab, drug dose adjustments, etc. It also reacts with some foods and many other drugs causing some patients such aggravation they forgo it altogether. Thus a market is created.

Like any new drug, there are pros and cons to dabigatran versus warfarin. Both will reduce your risk of a stroke by about the same margin, yet the key study of dabigatran, the RE-LY trial, found patients on dabigatran had a 1% lower rate of intracranial haemorrhage (bleeding within the skull) compared to those taking warfarin. Compared to warfarin, dabigatran increased heart attacks by about 0.4% and gastrointestinal bleeding by 0.6%. About 1% more dabigatran patients stopped their drug because of a serious adverse effect. The bottom line: dabigatran, at about 10 times the price ($1.70 per day vs. 18 cents per day for warfarin), does not save any additional lives.

The cost implication of people switching their anticoagulant is huge. If BC patients currently on warfarin are switched to dabigatran, it would cost BC patients and drug plans about $50 million more per year. Is it worth it?

Before answering that, you have to consider the cost of treating patients who experience things like unstoppable bleeding. It’s hard to quantify how often patients bleed excessively on dabigatran but a recent report from Quarterwatch, which analyzes adverse drug reaction reports in the US, noted that, after dabigatran was approved in the US (in October 2010), it “moved to near the top of our adverse event rankings, with more reports than 98.7% of the drugs we regularly monitor.” The Quarterwatch analysis found the problems mostly centred on the drug’s clotting mechanism, finding both excessive bleeding (not enough clotting) and blood clots in the legs or lungs (too much clotting). Hmm, maybe the regular monitoring of warfarin doesn’t seem like a bad idea after all?

The canary in this coalmine is the experience in New Zealand. Last July, in a twist no one can explain, dabigatran was rapidly given full, unrestricted coverage by the New Zealand’s Pharmac, the national drug plan. Pharmac has an international reputation of playing hardball with the drug companies on prices and it often severely restricts the coverage for new drugs. So what was it thinking with such a hasty decision in favour of coverage for dabigatran, a budget-busting treatment with minimal advantages over warfarin and very real safety concerns?

It’s almost certain New Zealand haggled and got a very cheap price. Maybe the manufacturer, Boehringer Ingelheim (BI), gave them additional sweetheart deals. We won’t ever know this, as those deals are secret. Maybe the NZ government is striving to entice the US into opening up better bilateral trade relations and it plans to do so by impressing the drug industry. In a press release last June, Pharmac’s medical director stated, “Funding dabigatran is an exciting step forward for anticoagulation treatment in this country. It is literally a game-changer and demonstrates Pharmac’s desire to move relatively swiftly to fund genuinely innovative medicines.”

Yet Pharmac has come under fire for being a little too swift. Within two months of being on the market, the New Zealand’s Centre for Adverse Reactions Monitoring had amassed around 50 reports of people bleeding, linked to dabigatran. And there were some deaths. One newspaper reported, “Critics are alarmed at the way it has been rushed on to the market,” also noting Pharmac’s deal with BI was worth upwards of $100 million.

By November 2011, BI announced there were now up to 260 cases of fatal bleeding linked to dabigatran, while maintaining the number was smaller than if the patients had been taking warfarin.

Back here in Canada, early reports suggest how much we love this new drug. For example, dabigatran was awarded the 2011 Prix Galien Canada award, the “most prestigious award in Canadian pharmaceutical research and innovation.” Accepting the award, the president of the Canadian arm of BI said, “We believe our innovation will transform the way patients with atrial fibrillation are managed in Canada.”

Transform indeed. But in what way? By cutting secret deals with drug plans to cover a drug that is 10 times more expensive than its alternative, even as safety warnings pile up and patients in emergency rooms drain blood banks?

Early in 2012, BC and other provinces will decide whether to list dabigatran for public coverage. After recently replacing its drug benefits committee with a new model (and sidelining UBC’s Therapeutics Initiative), BC’s decision will be a bit of a test. Will BC follow New Zealand’s example and cover dabigatran without conditions? Has anyone on the new committee read the Therapeutics Initiative’s analysis on dabigatran, in which it cited the drug as “premature, pharmacologically irrational and unsafe for many patients?”

With the air of revolt swirling worldwide, maybe in 2012 we will see a revolt by emergency room physicians and surgeons who are tired of seeing our public blood banks being drained away due to this new drug?

Or will the patients themselves, tired of being part of some drug company’s “game-changing” strategy, revolt and say “no thank you” to the chance of substituting one kind of disease for another?

It’s a new year and time will tell.

Alan Cassels is a drug policy researcher at the University of Victoria and author of the forthcoming book Seeking Sickness: Medical Screening and the Misguided Hunt for Disease, due out April 2012. Read more of what he’s writing about at www.alancassels.com

Health Canada takes baby steps toward drug safety

DRUG BUST Alan Cassels

If you thought we could get through these lazy days of summer without another major drug warning from Health Canada for a class of drugs taken by thousands of Canadians, think again.

The most recent advisory is among the more mystifying of the “adverse drug reactions” warnings I’ve seen lately; it warns of tendonitis and even tendon rupture linked to a commonly prescribed, relatively new class of antibiotics. And while the warning threatens to make me riff, for the umpteenth time, on the variety of ways in which drug regulators around the world – Health Canada not excepted – seem to go through the motions of monitoring and ensuring drug safety, there was also some good news. In a separate announcement, Health Canada advised it would provide some new seed money to help establish a drug safety research network in Canada.

This is very good news, but first, about the warning. The fluoroquinolone antibiotics, which include ciprofloxacin (Cipro) and other drugs whose generic names end in floxacin, have been under a dark cloud for a while now. More than two years ago, the drug watchdog group Public Citizen petitioned the US FDA to strengthen the warnings, stating, “…tendon ruptures associated with these drugs continue to occur at a disturbing rate, but could be prevented if doctors and patients were more aware of early warning signals.”

Last month, Health Canada was seemingly spurred into action by the US FDA’s ruling that makers of fluoroquinolone drugs had to issue a “black box” warning – the FDA’s strongest safety warning – on these drugs. Black box warnings don’t come along all that frequently and they usually emerge after much negotiation between the manufacturers and the regulator. A “black box” often precedes the removal of a drug from the market and it is a serious signal that the regulators are concerned about the drug’s toxicity.

For all you active individuals out enjoying the summer sunshine, the phrase “tendon rupture” is likely to strike fear in your heart. Tendon damage and perhaps a torn Achilles tendon could wreck anyone’s day. And this due to a drug you took for a simple infection? While the potential effects on your tendons from these drugs have been known for some time, what isn’t entirely clear is why any physician would prescribe the drug, being fully aware of the risk it carries when other antibiotics carry no such risk. As far as I can tell, there is no valid evidence that the fluoroquinolones are any better at treating most infections compared to the alternatives, such as older penicillin-type antibiotics.

My knee-jerk reaction is to suspect that the fluoroquinolone antibiotics have been widely prescribed – both mis-prescribed and over-prescribed – and only a little research confirms those suspicions. There is that perennial, but misapplied, axiom “newer equals better,” which has likely driven much of the marketing and subsequent prescribing of these drugs, and as with any newer treatment, the drug roars onto the scene with bells and whistles while the vital safety signals are spoken in whispers years later.

It is obvious to me that these drugs are marketed as being useful for indications for which they would, at best, be someone’s second choice. At least one manufacturer of this type of antibiotic has been slapped on the wrist by the US FDA for “…making false and misleading statements regarding the safety and efficacy” of the treatment in its advertising.

In terms of how well the drugs are being prescribed, one study involving 100 patients in two academic medical centres in the US found that 81 percent of the patients taking fluoroquinolone antibiotics had been given them for an inappropriate indication. In that same study, 43 percent of the patients received these antibiotics as a first-line treatment and 27 percent of recipients had no evidence of an infection. If this study, which was small and perhaps not applicable to the wider population, comes even close to representing the actual use of these drugs in the “real world,” it is a damning indictment of a serious failure in prescribing, made all the more serious because the drugs have the inconvenient capacity to cause “tendon rupture.”

Should we not expect Health Canada, as our drug regulator, to ensure that proper and timely prescribing information, especially safety information, is made available to guide our physicians? Sadly “too little and too late” seems to characterize the safety signals reaching physicians. After a new drug is approved, the marketers jump into action putting the new drug front and centre of our doctors, our hospitals and health clinics, plying them with free samples and glowing literature.

So what can we do to ensure that new drugs are used properly, rather than inadvertently inflicting tendon damage on the population?

Essentially, we need better “real world” data. It is slowly being recognized that Canada lacks the capacity to properly ensure that “real world” data is generated for new drugs, and that vital safety information about how drugs work in the world in which you and I live must be delivered to physicians in a timely manner. We hope that our physicians are acting in the most prudent manner possible when it comes to treating our infections. We also hope they will reserve newer drugs for patients for whom the older, more established classes of drugs clearly don’t work. Although hope is a pretty frail framework upon which to build a drug safety system.

The demand for “Real World Safety and Effectiveness” research around pharmaceuticals is a topic I’ve written about in the past (Common Ground, August, 2007). This need was initially enshrined in the National Pharmaceutical Strategy (NPS), a federal-provincial initiative boldly launched in September 2004, with the goal of providing Canadians with more equitable, sustainable and safer access to new drugs.

Almost four years later, I’m not the only one to notice that the NPS is largely a dud. Some have said that the “new” Conservative government’s mighty tendency to jettison those Liberal initiatives sounded the death knell for the NPS. Others have noted that provincial-federal wrangling over drug issues – the provinces want help to stanch the bleeding of red ink on the provincial drug file while the feds want to please the drug industry – means the NPS is going nowhere fast.

One of the things buried in the NPS’s objectives was a desire to “strengthen evaluation of real-world drug safety and effectiveness” and this recent announcement seems like it’s about to happen, albeit with baby steps.

With prescription drug spending now in excess of $22 billion per year, and a strong public appetite for more rigorous drug safety in Canada, Health Canada announced in mid-July it would provide the seed money needed to set up an independent research network to study the real world safety and effectiveness of prescription drugs in Canada. The business plan behind this network called for about $20 million per year, but Health Canada announced an immediate five percent of that ($1 million dollars) to get things up and running.

The hope is that the provinces will jump in with their own money and make the network a reality, a network that will likely link researchers in Canada, who are already doing “post-market” surveillance work, and allow them to cooperate in tracking real world drug use issues across the country.

No one can argue that Canadians must be protected from the unanticipated, adverse effects of prescription drugs, as the recent drug safety warning related to the fluoroquinolones has highlighted. Some, however, are insulted with the measly five percent Health Canada is kicking in, as it barely represents a down payment on the initiative.

Some have said that regardless of what form Bill C-51 ultimately takes, if it even survives, any promise of a “cradle-to-grave” surveillance of drugs in Canada will have to be bankrolled by “real world” drug data, and this money will ensure that Canadian researchers are organized and funded to use those data.

I say we give credit where credit is due. Health Canada has anted up so let’s wait and see if the provinces will come on board. Only time will tell if they will do their part to make this network fly. Or perhaps this initiative, like so many other important initiatives in the past, is destined to die from the lack of political will.

My strategy? I’m going to say a little prayer for those who are suffering needless Achilles damage this summer and I’ll feel a little guilty as I continue to enjoy running, jumping, hiking and walking. Because of our collective ignorance about a particular class of drugs, many Canadians won’t be enjoying the summer as I will.

It doesn’t have to be this way. Let’s make drug safety a priority this year and put the money behind that decision.

Alan Cassels is a pharmaceutical policy researcher at the University of Victoria and can be reached at; cassels@uivic.ca

If you think you have been injured by a prescription drug, you should call the Canada Vigilance Program at 1-866-234-2345. You can also submit an adverse reaction report on the Med Effect Canada website (www.hc-sc.gc.ca/dhp-mps/medeff/index_e.html).