DRUG BUST Alan Cassels

“Drastic action is essential to preserve the integrity of medical science and practice and to justify public trust.”

– Journal of the American Medical Association

You can learn a lot about the effects of drugs and the actions of drug manufacturers by peering into a courtroom. When you hear what the companies themselves have to say, in sworn testimony, about their drugs or their marketing tactics, you realize that we in the general public really only have an iceberg tip’s worth of information about any drug on the market.

You can’t deny that courts of law can get at a certain purity of truth, which emerges from the wringer of the legal system.

Exhibit A to support this argument is a major lawsuit settled last month in the US against drug giant Eli Lilly. The company was ordered to pay $1.42-billion (US) to settle criminal and civil investigations. These charges stem from the way the drug manufacturer marketed its antipsychotic drug Zyprexa, (generic name olanzapine). Lilly executives explained that the key charge centred on how Lilly was advertising Zyprexa for ailments for which it was not approved.

A company trying to license its drug will come to the regulator with a series of claims of what its drug can do. It is only those claims deemed to be supported by sufficient evidence that get approved by the FDA or Health Canada. However, while drugs are licensed only to treat certain specific conditions, our doctors are free to prescribe any drug for any patient for whatever reason they see fit, approved or not approved. The issue of “approval” is important because a company can only market its drug for “approved” uses. In other words, if your drug is approved to treat toenail fungus, the sales reps can’t go pushing the drug for erectile dysfunction. That’s against the law.

Zyprexa belongs to a relatively new class of antipsychotic drugs approved to treat people suffering from schizophrenia and bipolar disorder. I thought, OK, there can’t be that many schizophrenics or people with bipolar out in society so antipsychotic drugs like Zyprexa wouldn’t have much of a market. I was wrong. Lilly has sold nearly $40 billion (US) worth of Zyprexa since it was approved in 1996, making it, in fact, one of the biggest-selling drugs in the world.

Many of us had sensed there had to be something illegal about the way the drug was being marketed, but we had to wait until the court documents revealed what was actually happening.

A huge blockbuster drug, approved only for the treatment of relatively uncommon diseases, was obviously being taken by millions of people – despite its known and fearful side effects (mainly weight gain and diabetes) and its documented life-threatening severe adverse effects, (heart attacks and strokes). So why was an antipsychotic like Zyprexa so widely used?

The answer is what we call “off-label promotion.” According to documents filed in U.S. District Court in Philadelphia, Lilly said it promoted Zyprexa for elderly people in the treatment of dementia, which is a use strictly not approved by Health Canada or the US Food and Drug Administration. The US attorney handling the case told a press conference, “Lilly completely ignored the law,” making “hundred of millions of dollars” from illegally promoting Zyprexa.

Here’s the main kicker: not only is the drug not approved to treat dementia in the elderly, but Health Canada has said that prescribing this drug to elderly people is something that should emphatically not be done due to the risk of strokes. Yet if you were to wander the halls of the average seniors home in Canada, you’d find as many as a quarter of the residents taking these drugs.

Exhibit B in my argument that the law courts are great places to look to expand our knowledge about drugs is the drug Neurontin (gabapentin). This drug will go down in the history books as being off the scale in terms of its off-label promotion. Neurontin was approved in the mid-1990s as an “add-on” therapy for what they call “partial complex seizures.” A small market, right? I mean, how many people suffer seizures and would therefore need drugs like Neurontin? Seems like a lot. By 2004, nearly $3 billion worth of the drug was being sold.

David Franklin, a whistleblower from Parke-Davis (later bought out by Pfizer, which marketed the drug), set the wheels in motion for a huge lawsuit that followed. The result was public access to some of the most complete court documents ever assembled around the aggressive, off-label marketing of a drug. In the passage below, Franklin relates what a Parke-Davis executive said to him and his fellow sales people:

“I want you out there every day selling Neurontin… We all know Neurontin’s not growing for adjunctive therapy, besides that’s not where the money is. Pain management, now that’s money. Monotherapy [for epilepsy], that’s money… We can’t wait for [physicians] to ask, we need [to] get out there and tell them up front. Dinner programs, CME [continuing medical education] programs, consultantships all work great but don’t forget the one-on-one. That’s where we need to be, holding their hand and whispering in their ear, Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar, Neurontin for everything. I don’t want to see a single patient coming off Neurontin before they’ve been up to at least 4800 mg/day. I don’t want to hear that safety crap either, have you tried Neurontin, every one of you should take one just to see there is nothing, it’s a great drug.” (From The Neurontin Legacy: Marketing through Misinformation and Manipulation by C. Seth Landefeld, M.D. and Michael A. Steinman, M.D., published in the New England Journal of Medicine, Jan. 9, 2009.)

It would become the mother of all court actions against illegal marketing by a company; the payouts were almost a billion dollars, at that time the biggest legal action ever taken against a drug company. The court documents reveal the whole gamut of tricks used to manipulate information: suppressing publications, training and using local doctors to serve as paid speakers for the drug, cultivating “thought leaders,” influencing academics with research grants, appointing people to “advisory boards” that worked to launder payments to physicians and lots and lots of “unrestricted educational grants” to do what was needed to sell this drug.

In an article in December’s New England Journal of Medicine, it was noted that the marketing of Neurontin was based on “the systematic use of deception and misinformation to create a biased evidence base and manipulate physicians’ beliefs and prescribing behaviours.”

The 8,000 pages of corporate documents now in the public domain reveal the tactics used by a company to create a multibillion-dollar blockbuster out of a drug that should have gone nowhere. These documents are available in a searchable digital library at the University of California in San Francisco. (www.dida.library.ucsf.edu). The class-action suit which followed also generated detailed testimony, searchable through the US Federal Judiciary’s Public Access to Court Electronic Records Service Center.

How much off-label prescribing happens? About 20 percent of drugs in the US are written to treat a condition for which the drug was not approved, according to a 2006 study published in the Archives of Internal Medicine.

What’s a patient to do in all of this? For starters, ask your doctor, “Is this drug you are about to prescribe me actually “approved” for the condition or disease for which I would take it? It might be best to first try the proven, standard and “approved” therapies.”

Clearly, we shouldn’t have to wait for the courts to tell us what is happening behind the scenes about how drugs are being used. Better research and regulation on how drugs are actually being used in the market (and what kinds of effects they have) are needed.

In Canada, a group of academics and health policymakers have been trying for several years to make the case that Canada needed better ways to research and assess the safety and effectiveness of drugs as they are used in the “real world.” In mid-January, Canada’s new Health Minister Leona Aglukkaq announced that the government was committing $32 million over four years to create a research network to “enhance national capacity for research on the safety and effectiveness of drugs used by Canadians.” This is about the best news on the drug safety front we’ve seen in a long time.

We shouldn’t have to rely on the courts to provide independent, unbiased evidence to help answer important questions about the drugs we take every day. Publicly funded research that is free from pharmaceutical industry influences will help a lot. The new $32 million is hardly what you’d call drastic action on the drug safety front, seeing as this represents about 1/1,000th of Canada’s annual drug bill, but it could be a step in the right direction. There is no doubt that the time has come to start creating systems to ensure safe and effective use of drugs in Canada.

There is no use waiting until the courts have their say.

Alan Cassels is a drug policy researcher at the University of Victoria.

He uncovers the world of cancer screening in a two-part radio documentary, You are Pre-Diseased, airing on CBC IDEAS at 9:05 pm, February 12 and 19. Mark your calendars.

cassels@uivic.ca