Saturday, August 23, 2008

Fifteen days of blogging for health care reform: Down on the pharm

Guest post by Skylanda...and sorry folks, this is a long one!

A virile sixty-ish male chucks a football through a tire swing, raises a couple of fists in victory, and manhandles his comely wife; the final voiceover lists headache, flushing, dizziness, rash, cognitive dissonance, sudden loss of conscience, and pernicious priapism as possible unintended consequences of the little blue pill that made this moment possible. I might have just made up the side effects, but you’ve seen the ads.

If you’re old enough to remember ten years back or more, you remember a time when pharmaceutical ads did not appear on television. These ads first appeared around 1996, when changes in FDA regulations began allowing direct marketing of pharmaceuticals to consumers, bypassing the expertise of your doctor and asking you as the patient to approach your provider and ask for medication that might benefit you. Pharmaceutical peddlers now go to a lot of trouble to make sure that you know their brand names as you know the brand of your kid’s cereal: they debut ads during Superbowls, they hire ex-presidential candidates to plug drugs for conditions that no one wanted to talk about in public a year earlier (Bob Dole wants you to know that Bob Dole has trouble with his wee wee, says Bob Dole).

Among the most eye-browing raising ads I ever saw for a pharmaceutical product was for Procrit, an extraordinarily expensive injection used to drag red blood cell counts up in anemic chemotherapy patients, those with end-stage renal disease, and those doping for high altitude sports. The former patients are usually managed closely by specialists who keep an eye on issues like this, so unless you are trying to get yourself kicked off the Tour de France, this is probably not something you need to ask your doctor for. Nevertheless, these ads are more or less asking you to call up your doctor and request yourself what roughly amounts to a chemotherapy drug (Patients, ask your doctor if adriamycin is right for you today! …sorry, geek humor…move along…nothing to see here…)

The opening of the advertising for pharmaceuticals was ostensibly done equally in the name of the free market and in the name of full patient education. And indeed, there is some equalizing factor poured into the mix when you as a patient find out that there are six roughly equal allergy medications on the market instead of the one marginally effective one that your doctor has been prescribing you for ten years simply because it is the one that he or she is comfortable with. The concurrent explosion of direct-to-consumer advertising and the arrival of the world wide web have contributed to a double-edged sword for doctors: a generation of patients that is perhaps the best-informed in history, and the enormous headache of trying to sift through the raft of misleading misinformation that is now at every patient’s fingertips.

Aside from direct advertising, pharmaceutical companies have more insidious ways of inserting their buy! buy! buy! message into the public consciousness. Gone are the halcyon days of all-expense-paid golfing trips to the Bahamas to hear a one-hour lecture on the newest heart drug, but pharmaceutical money still pays its way into physicians’ minds in a variety of ways. Drug companies buy their way into trainees’ heads by providing food for required lunchtime lectures in return for a few minutes of air time on their latest product. They sponsor professional conferences, which for small states and less lucrative specialties like mine, could not happen without some commercial support (ironically, in family medicine, these conferences are often the site of ragged ongoing debate about the issues du jour surrounding affordable health care and - always - the role of drug pricing in that affordability). They litter the hallways with cheap pens, clocks, and other products bearing the flashy logo of their expensive wares. You would think that future doctors and practicing doctors wouldn’t sell out quite so cheap, but this is an awful large outlay of funds across the nation for these efforts; something must be working.

Most controversial of all is the provision of free sample drugs to clinics. Ostensibly, this is charity: who can nay-say free drugs? But by providing free drugs as a start-up pack, pharmaceuticals hope to buy patient-doctor loyalty to that brand, and this is often the case - and it is important to note that only patented, on-brand drugs are given out for free (no one runs around in fancy suits with branded pens and clocks pedaling drugs that cost four dollars a month). A patient is started on, for example, a cholesterol medication out of the doctor’s free sample closet, and once the samples run out, the patients transitions to paying for the medication at full price because it works and they are comfortable with it and they know the brand. You can see how this does not work at all as a charity for uninsured patients, it only works as a come-on for insured patients. You’ve probably seen this tactic before; it’s called “First one’s free!” and - not to be too prejudicial or anything - it’s also used by the guy selling heroin a block down the street from your local high school.

It is for all these reasons that some institutions - often at the behest of medical students and residents - have started to boot the pharmaceutical companies out of their clinics, their mailbox, their lunchrooms, and their drug closets. The integrity of education is at stake, they argue, as is the integrity of their ability to treat patients without this ultimately costly interference. The American Medical Student Association’s Pharm Free campaign has successfully spearheaded the movement to drive the pharmaceutical companies out of several major university hospitals, and is gunning for more. (Of note, some community-oriented providers have made interesting compromises with pharmaceuticals to continue providing expensive drugs without compromising patient priorities. Both community clinics I have worked in within New Mexico have had a policy of allowing pharmaceutical companies to hawk their wares and leave samples, but only those with whom the clinic has established means of continuing uninsured patients on those expensive drugs through corporate-sponsored patient assistance programs, which give a certain number of prescriptions out for free each year as a charity write-off for the drug company. Why the pharmaceutical companies even bother with these clinics, I cannot imagine - perhaps the hope that one day these patients will receive paying Medicare benefits? - but nevertheless, there it is.)

So the move is afoot to boot the pharm companies from places they should not be sticking their noses, to reclaim a less biased territory for training new doctors, and to control costs. This is a universal good, yes?

Well, it may be more complicated than that. Drug innovation is a mighty expensive enterprise. It depends who you ask (and what their motivation is for cooking the numbers in any given direction), but from the moment a drug is first thought up to the time the first commercial batch is sold off the assembly line, the total cost of developing a new drug is somewhere between $75 million and $800 million dollars. This can include versions of the drug that are canned early on because of safety or efficacy failures - expenses which biotech companies routinely swallow as a cost of doing business, which is part of why it is so hard to say exactly how much a new drug costs to get to market. And every drug that does reach the market risks being yanked later (amidst a raft of lawsuits) due to unforeseen safety problems…even a blockbuster like Vioxx. With that kind of up-front investment required of pharm companies to keep the conveyor belt of innovation moving, it requires some powerful motivation to keep the pipeline open. That motivation is known as profit. There is a danger to impinging too deeply on pharm profit, and that danger is that we slow the pipeline for innovation into advances that may be life-altering or life-saving down the road. What is the use in inventing drugs that no one can afford?, you might ask, and that is indeed the balance that has to be struck: keeping the pipeline open, but in a means that at least a useful critical mass of people can afford.

It is also useful at this point to widen out the scope of this discussion to a more global scale, to understand the role of the US market in the drug trade (the legal drug trade, that is) around the world. And for that, we have to go back in history a few years, to a very different time and place.

That place is New Hampshire, around 1944, in a town called Bretton Woods. The Allied victory was starting to look like a sure thing, and the representatives of the future victors gathered quietly to start planning for what that victory would look like. Galvanized with the understanding that punitive measures against the loser nations (especially Germany) after World War I largely sparked the disastrous build-up toward World War II in Europe, these planners sought to employ the lessons of the 1920s and 1930s toward building a better world. You’ve probably never heard of Bretton Woods, but you’ve certainly heard of at least one of the global institutions that were born or consolidated that summer in New Hampshire: the International Bank for Reconstruction & Development (later the World Bank), the International Monetary Fund, the General Agreement on Tariffs and Trade (GATT), and the United Nations, which had its roots in the post-WWI League of Nations and was formalized in the spring of the following year. Together these formed the logistical underpinning of the Marshall Plan, perhaps the most ambitious (and arguably the most successful) program ever undertaken to promote peace and prosperity in the world to date; in a couple of decades, western Europe was transformed from a zone of constant conflict and cyclical spasms of poverty into the wealthy and relatively peaceable place we know it as today.

Among these institutions, the one you are least likely to have heard of is GATT. The GATT treaty was designed to create a forum for breaking down trade barriers that had both hindered free movement of goods and people and also encouraged the kind of regional Balkanization that historically sparked wars throughout Europe. When GATT was originated, its founders probably had no idea the sort of contentiousness and riots would one day be fomented in its name wherever its representatives gathered, for what started as GATT eventually morphed into its heir child, the World Trade Organzation.

A full discussion of the WTO and its controversies is entirely beyond the scope of this post, but the role of pharmaceuticals in that morass serves as both an example and a parable of globalization and its complications. And the best place to go to study the globalization of the pharmaceutical industry is the Indian subcontinent. In 1970, India’s populist government passed a law that no pharmaceutical compound could be patented within its borders (patents, incidentally, are nation-by-nation protection; the WTO tries to enforce world-wide patents, but has no legal authority to do so, and can only attempt to wangle compliance through economic pressure on member nations); a nascent industry was born in generic knock-offs of costly medicines patented in industrial nations, unhindered by any legal ramifications of this sort of intellectual piracy. But in 1995, India joined the WTO and was given 10 years to comply with intellectual property rules (known as TRIPS - “Trade Related Aspects of Intellectual Property Rights” in one of the clumsiest excuses for an acronymn ever invented) and cut out the business of knocking off expensive drugs invented in other countries. The intervening ten years saw some profound advances in the treatment of cancer, AIDS, and other devastating diseases, and the dust is still settling on the nuances of which patents are enforceable in the massive Indian pharmaceutical business (some drugs were patented before 1995 but not marketed til later; others receive exemptions from WTO patent rules for their life-saving public health properties; the gritty details go on and on).

The moral right of Indian generic pharmaceutical producers to knock off patent medicines is a tricky one. On one hand, India has a burgeoning population to take care of, and its pharmaceutical industry has traditionally also been a prime source of drugs for developing nations that do not have infrastructure to produce their own nor the cash to buy them on the global market from legitimate producers. On the other hand, lopping a billion or so of the increasingly wealthy Indian people out of the profit-making market for any given drug is liable to put such a crimp on expected revenues that it may hinder motivation for new drugs to be sent down the pipeline in first world countries, when corporations know that these drugs can be knocked off the moment they start coming down the production line. Patent rights may still to this day be threatened on newly marketed drugs because many compounds are patented years before they are proven to be at all useful; this was the driving logic behind the Gleevec decision (which allowed generic versions of a very expensive cancer drug in India), of which I wrote extensively two years ago in this very forum.

Which brings us back to the role of the US market in global drug development. We all know that Americans pay more for the same drugs, no matter how many variables you adjust, than any other nation in the world. Sometimes on an exponential scale. While pricing out drugs in a number of nations for the masters thesis I wrote on TB pharmaceuticals, I stumbled across a policy paper out of the British National Health Service that unequivocably declared that the antibiotic Avelox - at some two pounds per pill - was far too expensive to consider as a first-line drug for any known condition. In translating that number through the exchange rate, I generously doubled two pounds to four dollars (to account for our ghastly exchange rate at the moment) and looked up the price per pill at Walgreen’s: ten bucks a pill. Two and a half times a number that the British medical authorities had deemed too ridiculously expensive to consider for routine use. Avelox is on formulary at the hospital where I work now; not a day goes that we don’t have someone on the inpatient service taking this drug. The mind does boggle.

We pay for prescription drugs at a rate that would impress your local cocaine pusher. We do it because we can, we do it because we’ve been pushed into it, we do it because we have such an obscured system that the only people who actually know the true retail price of a drug are those who are paying out of pocket without insurance coverage. And when we get fed up with it, we get sneaky and order our prescriptions from Canada or India or Mexico and feel like we’ve just got the deal of the century over it (and on that note, here’s today’s PSA: order drugs from Canada, fine, that’s a developed nation with drug standards similar to our own; but caveat emptor if you order medications from developing nations, including India - serious questions of purity, efficacy, and even content have arisen, especially in batches sent abroad to unsuspecting and well-paying foreign buyers). But if you start to strand out the threads of the story, you’ll find that it is not only the pharmaceutical companies that are parasiting off the American consumer; in a very real way, drug consumers in other nations aren’t just getting a better deal than American patients, they are quite literally freeloading off Americans who pay full price for medication. And here’s why:

When a multinational pharmaceutical corporation looks at a promising compound and calculates the plausible return on investment if they take that compound into trials, part of that profit projection comes from bloated, high-roller drug costs in the good ol’ USofA. A large part. If you removed the American portion of that profit margin (or just tightened its belt by a good notch), you would be looking at a far thinner profile. Investment into patent drugs sits heavily on the American consumer; you may eat your shirt every time you pay a hundred bucks for a month’s worth of one drug, but come on, revel in it: you’re ensuring the next generation of cancer cures, blood pressure controllers, and cholesterol fighters in a way that consumers throughout the rest of the world are not contributing so much.

If only the truth were so clear-cut as that murky road home, eh? But of course there is one more twist. And that twist is that the pharmaceutical pipeline is not necessarily as responsive to consumer needs - even the very American consumer that feeds it money-hungry maw - as we might like it to be. You would like to see a safer, more effective treatment for cancer this year; what you get instead is yet another cholesterol drug, in the same class as a half dozen other cholesterol drugs, that is one atom different and costs ten times more than those that have gone generic for no provable increased benefit. You want to a new class of antiretrovirals - AIDS drugs - to see the market this decade; what you get is a blood pressure drug in the same class as ten other blood pressure drugs…again, for an increased price, with little increased benefit. How on earth do you get anyone to buy this stuff - same product, higher price - you might ask? Well, go back to the beginning of this wordy diatribe…advertising, accessing young doctors at their places of training, building brand loyalty through free sampling, obscuring the true cost by filtering it through the insurance industry. The cycle is vicious indeed.

So where do we go from here? We can’t single-handedly redirect corporate funds to socially worthy drugs over yet another branded me-too blood pressure drug, or reform the WTO stance on patent medications (although throwing rocks at WTO conventions seems popular enough world-wide to make an Olympic sport of it). But remarkably, this is an area where patients as individuals do have a marked bit of control. You buy this stuff, you are a market force. Here’s how you can use your dollars to effect this issue.

First of all, the next time a doctor prescribes you a medication, you have the right (you might get a little annoyance in return - but still, you have the right) to ask these questions: Is this the cheapest effective drug for my condition? Are there generic alternatives that are equally effective? If I am being prescribed an expensive medication in a class where there are cheaper alternatives, why is that? You may get a legitimate answer to this last question: because you had side effects to the cheaper alternatives that we tried, remember?; because your condition is severe enough that we go for broke with the absolute best in the class; because the expensive medication happens to be on your insurance provider’s formulary, while a less expensive one is not; because there is no cheaper effective alternative. But many times, there is no good answer, and the next right answer is: There is no good reason why; let’s try a cheaper alternative instead.

Second, you can understand that pharmacies are a market like any other, and that drug prices vary wildly between them. Call around next time you get a prescription and ask how much it will cost before you fill it, even if your insurance will cover it; the answer may surprise you (when I was between insurance plans once, I paid $18 for prescription eye drops that I later found out I could get for $4 down the street…I‘m not talking about fifty cents, I‘m talking about a four-fold price difference). Part (but not all) of this variation is wrapped up in the four-dollar prescription programs at Walmart, Target, K-Mart, and a few chain groceries like Smiths. Far be it for me to gives props to the vortex of social ills that is Walmart, but credit where credit is due: Walmart initiated the four-dollar pharmaceutical plan a couple years ago to provide a month‘s worth of certain generic prescription drugs at a fixed price (a couple hundred different medications at last count), and the others scrambled to follow suit. Walmart surely crunched some heavy numbers before establishing this policy, some numbers that ensure market share and profitability and competitive edge over the mom-and-pop pharmacies that you would love to support instead of the globe-eating big-box chain, but still: gotta give some credit for affordability, transparency of cost, and ease of accessing their list.

Third, you can refuse (unless there is good reason to do otherwise) to buy expensive, new-generation medications for which there is an older, cheaper equivalent. Market forces allow the continued arrival of me-too drugs, and as consumers, we can just refuse to buy them unless there is some pressing reason to do so. Your single purchase won’t re-shape the market, but if as a whole nation we start refusing to buy me-too drugs at inflated prices, the incentive to continue investing in them (instead of in truly innovative and necessary classes of drugs) will dry up.

But eventually we have to tackle the core idea of the how much we are willing to pay for truly spectacular new drugs - cancer cures, HIV treatments, and the like. These will continue to filter down the pipeline to us if we are willing to pay for them - but the price is steep. The top tag I’ve seen cited on a medication is a whomping $100,000 per year for Avastin, a drug which chokes off the blood supply to breast and colon cancers. These drugs arrive because of market forces, and it is entirely possible that we have other priorities that are more important - such as covering all diabetics with drugs that we already know to save lives. Maybe we don’t need a pipeline of new drugs bad enough to pay what we are being asked to pay for them. Maybe innovation should slow a bit to accommodate a market that cannot handle this kind of expense. Maybe the inflated pharmaceutical market needs to accept a slow-down before it hits the kind of skids the similarly inflated mortgage market just took in the gut.

Or perhaps we can work collectively to cap prices while maintaining incentive, by means like trading government or university funding for caps on prices (the former is already in effect, the latter has not generally been demanded yet), or allowing increased patent times in return for limits on prices or guaranteed supplies to patients who cannot pay.

There is no one answer, no victorious football-through-the-tireswing to mark a successful remedy to the question of balancing drugs and prices in America and throughout the world. What we have is a big, snarly, expensive problem. What we need are thoughtful, balanced, comprehensive solutions. And those are never easy to come by.

Cross-posted at my blog, Loose Chicks Sink Ships. Please note that all references to patients have been altered and/or fictionalized to protect the identity of those individuals.