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About this Author
Derek Lowe
Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 12, 2009

Book Review Department

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Posted by Derek

For those who are interested, I have a review up at Nature Biotechnology of Reasonable Rx: Solving the Drug Price Crisis, a book that proposes an. . .interesting solution for reworking the drug industry.

And as Fate would have it, I also have a review in the latest issue of Nature Chemistry of Drug Truths: Dispelling the Myths About Pharma R & D, from Pfizer's John LaMattina. The only reason these are showing up at the same time is that I took an unconscionably long time to come to grips with Reasonable Rx - it wasn't something that I could just dismiss, but it has (I think) a lot of things wrong with it.

Comments (11) + TrackBacks (0) | Category: Drug Industry History | Drug Prices | Regulatory Affairs

Kumbaya

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Posted by Derek

Time, regrettably, for some politics. In case anyone’s wondering, my take on yesterday’s health care announcement by the Obama administration is perfectly stated here. I could not agree more.

In other words, I see the “historic announcement” as nothing more than political theater. Everyone got together, held hands, and pledged to voluntarily do some not-all-that-painful things to reduce costs, some of which (cost savings through better record keeping?) have already been underway for years. Even so, the chances of all of these being followed through are still low. And even if they were, the amount of money being saved is only a small fraction of what would be needed to pay for the administration’s stated health care goals.

None of this would bother me all that much, under normal circumstances. A lot of what goes on in Washington, at least in front of the cameras, is an elaborately choreographed dance. It’s related to real political dealing in the same way that a synchronized swimming exhibition compares to the 1956 Olympic water polo match between the Hungarians and the Soviet Union. But (like Megan McArdle in the Atlantic link above), I worry that the administration will now pretend that these savings are real. When they turn out to be (gasp!) insufficient, a crisis will be declared (you should never waste one, you know), and more persuasive measures will be used. You know, just as in the recent Chrysler “bailout”, a term I can only put in quotes. (Mickey Kaus perfectly sums up my feelings about that one, in that link and here).

Why should I care? After all, my industry should be more or less in the clear, since prescription drug spending is only about ten per cent of the nation’s health care costs, right? Well, my worry is that we’re a very visible (and often disliked) ten per cent, a nail that sticks up and that may well get hammered down pour encourager les autres. I hope I'm wrong. But I think that the Chrysler deal was just a curtain-raiser for an even bigger one in the same style for General Motors, and I hope I'm wrong about that one, too.

Comments (15) + TrackBacks (0) | Category: Business and Markets | Current Events | Drug Prices

September 3, 2008

Direct To Consumer Ads: Wasted Money?

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Posted by Derek

It’s a truism that half of all advertising dollars are wasted, but that no one buying the ads can be sure which half it is. Advertising from the drug companies is ubiquitous: how much of that is doing them no good?

A recent study suggests that the widely reviled direct-to-consumer (DTC) campaigns may be in that category. A paper in the British Medical Journal looks at the cross-border effect of US-based advertising on English-speaking and French-speaking Canadians, on the reasonable assumption that the former group is more likely to pay attention. They picked products that had been on the market for at least a year before the ad campaigns started, and looked at the number of prescriptions among both groups once the ads started running. What they found was no effect on the prescriptions for Schering-Plough’s Nasonex (mometasone) and Wyeth and Amgen’s Enbrel (etanercept), both of which were heavily advertised. Novartis’s Zelnorm (tegaserod, now off the market) did show a 40% rise, which gradually went back down again.

A reasonable theory to explain these results starts by looking at the respective markets. In the case of the first two drugs, a number of different therapies were already available. But Zelnorm was pretty much the only thing available in Canada for irritable bowel syndrome. It could be that DTC ads are useful in letting patients know that there’s finally something for a disease that previously had few options, but less effective in pushing into a crowded area. There’s also the multiple-step barrier problem – seeing a general practitioner and then a specialist, and so on – which can mitigate the effect of advertising, depending on the drug.

But the people who would know these effects best aren’t talking: the marketing departments of the drug companies themselves. As I’ve pointed out here before, the whole purpose of advertising is to make money: if you don’t increase sales enough to more than cover the cost of the ads, you’re clearly wasting your time. And that’s why I don’t have a lot of patience with outraged comparisons of pharma R&D budgets to marketing budgets, because the latter are there to bring in even more money for the former.

If, though, some of these marketing campaigns really are wasted money, then clearly that spending needs to be redirected. And that’s what makes me wonder. No one keeps a closer eye on prescription trends than the companies that sell the drugs, and they’re in the best position to see if a given ad campaign is doing anything or not. Even allowing for the usual human quota of inertia and incompetence, it would seem that DTC campaigns must be doing something for the companies involved, at least in many cases, or they wouldn’t exist at all. It’s also worth keeping in mind that what they may be doing is not so much boosting the number of prescriptions written as keeping them from falling. In the case of the drugs in the BMJ study, you have to wonder if the normal trend would have been for the number of scripts to have declined, while the ad campaigns held them steady.

That can be hard to prove, of course, and no doubt there are some marketing strategies that have far outlived their usefulness on just that kind of reasoning. But overall, I have trouble believing that DTC campaigns are useless across the board. Some of the marketing folks are weasels, but they’re not dumb ones. (It's also important to remember that DTC ads are only 5 to 10% of the total amount spent on drug promotion, according to the figures I've seen). In the end, I can agree with this statement from the paper:

Until we better understand how direct to consumer advertising modifies prescribing for particular drugs, debates about its positive and negative consequences will continue to be based on conjecture rather than strong evidence.

Comments (20) + TrackBacks (0) | Category: Business and Markets | Drug Prices

March 18, 2008

A Solution, Courtesy of the MIT Faculty

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Posted by Derek

Do drug discovery and drug marketing belong in the same company or not? That question’s been asked in several forms, but two MIT professors are taking it about as far as it can go. Stan Finkelstein and Peter Temin have a book coming out (“Reasonable Rx: Solving the Drug Price Crisis”) which proposes decoupling the two by force.

By analogy to the way the electrical power industry was divided into generation and distribution sectors, they propose splitting up the pharmaceutical business into drug discovery firms and drug marketing firms. But wait, there’s more: they also would like to have an “independent, public, non-profit Drug Development Corporation” formed to act as an intermediary between the two:

“It is a two-level program in which scientists and other experts would recommend to decision-makers which kinds of drugs to fund the most. This would insulate development decisions from the political winds," (Finkelstein) said.

The MIT press release also talks up the other putative benefits of this plan, such as how it would “insulate drug development from the blockbuster mentality, which drives companies to invest in discovering a billion-dollar drug to offset their costs”. There’s a lot to talk about in this idea, but here are some of my first impressions:

1. The electric power analogy is probably specious. Generating electricity is, for the most part, a sure thing. If you build a big coal-fired generating plant, which we most certainly know how to do, it will generate electricity for you. And its output will be proportional to how fast the turbines spin. Research is most profoundly different, as many executives from other industries have found to their sorrow. You can turn the crank like crazy and have hardly anything come out the other end at all – ask Pfizer – and that’s because we do not have a very clear idea of how to discover drugs.

Another problem is that electricity is fungible. The electric power coming from one plant is exactly the same as that coming from another, and can be pooled and distributed in exactly the same way. Every drug, however, is different. The electric power industry would be rather changed in appearance if some kilowatts were ten times as profitable as the others, but only for a few years after the generating plant came on line, or if particular kilowatts were only of benefit to certain homes or businesses and had to be routed there specifically.

2. Where are these experts, exactly? I have an instinctive distrust of plans that call for a board of dispassionate technocrats to step in and do things that the market is supposedly doing by itself. It’s not that such things absolutely can’t work, but my default belief is that they won’t work as well as their planners hope. Finkelstein and Termin’s “DDC” proposal is just the sort of thing I worry about. I can see establishing something to make sure that less immediately profitable diseases get R&D directed to them, but running the whole industry like an NIH grant review board sound like a recipe for disaster.

3. To some extent, the industry is already divided in the manner proposed. But it's not done through review boards, it's done through business dealings. Many small firms don't have the resources to develop their own drug candidates, so they shop them to larger firms who can handle the clinical, regulatory, and marketing aspects of the process. This goes on all the time. It's been proposed (many times) that one or more large companies might shut their own research down completely and serve as a clearinghouse for the smaller ones in just this way, but no one has been willing to take the plunge. My guess is that there aren't enough good ideas out there for sale to keep a company going without having some of its own research in the game; I feel sure that the numbers have been run on this idea more than once.

Of course, these deals are made on the basis of who will make money, rather than how much society will benefit. But you'd be surprised at how often those two can overlap.

Where do the costs go? I suppose I'll have to read the book to get the details, but I'm not sure how money is supposed to be saved here. The cost of developing drugs doesn't look like it'll be changed much, since Temin and Finkelstein aren't coming in with any insights into human biochemistry or any new ways for us to predict efficacy or side effects. Profits, however, would surely be reduced: the the DDC that they propose would seem to exist to recommend that less profitable drugs be developed, for the good of society, rather than the ones that companies believe that they can make the most money from.

I note that the press release makes much of climate change and globalization, probably because in many circles these days you can't be taken seriously unless you mention those somewhere. This is done in the context of tropical diseases possibly making inroads into the US and other industrialized countries. But if that were to happen, research on these diseases would become much more profitable - which I realize is a crude way of looking at it, but the market doesn't have to be pretty to work. And I think the process would be slow enough to fit the timelines for drug discovery as it's practiced today - an example would be the burst of work on avian influenza in the last few years. A sudden epidemic would be bad news indeed, and might well catch the industry flat-footed, but that's going to be hard to avoid under any drug development regime.

Comments (28) + TrackBacks (0) | Category: Business and Markets | Drug Development | Drug Prices | Why Everyone Loves Us

January 31, 2008

Drugs and Money

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Posted by Derek

Over at Megan McArdle's site at The Atlantic Monthly, there's been a run of posts on the pharmaceutical industry - touched off, I think, by this one from over here. Her readers are a diverse bunch, some of whom seem to stop by because they can't stand the posts there but can't seem to help commenting on them. So there are some interesting wrangles going on in the comments to this post on the return on investment for R&D, and the follow-up on why we can't necessarily just fund all of it with that marketing money. The next in the series was on the problem, which may have no solution, of getting other countries to pick up more of that investment than they do, and that was followed by one about why nationalizing the whole drug industry might not work out well, either. And today's entry is about what that return on investment might actually be, with an appropriate warning about survivor bias. (I'll add my two cents to that debate by pointing out the notorious Wall Street Journal article which suggested that the entire biotech industry, net, has lost money so far).

There have been some thought-provoking comments to these, some infuriatingly dense ones, and some from people who clearly have done drug discovery for a living. But perhaps my favorite comment of the bunch, in an otherwordly way, has been this one, from one "Mintun":

"Really, what drugs are there left to develop? I think the state of medicine we have now is pretty good now. If we can guarantee most people a reasonably good shot at 80 or 90 years before they die, what else needs to be done? It seems like we are shoveling resources down a pit to get ever diminishing returns? I'd be happy to live under the status quo of the medical technology for the rest of my life. In fact if it means I pay less for insurance etc. over my lifetime it seems like a good trade."

Other people have already let him have it for that one, which saves the rest of us some work. . .

Comments (0) + TrackBacks (0) | Category: Business and Markets | Drug Prices

January 28, 2008

Laissez-Faire?

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Posted by Derek

Reader B.C. noted this on Ezra Klein’s blog over at The American Prospect, talking about Mark Warner’s Senate candidacy in Virginia. He quotes Warner as saying:

” We need to rationalize drug costs. I won't stand up here and bash pharma. But it's not fair that Americans pay for research and development of the whole world, as other countries all have some pricing constraints."

And Klein then adds:

As readers of this site know, our decision to forgo national bargaining (or even Medicare bargaining) while every other country does use their size to drive down costs has led to a situation in which we pay far more so that Canadians and the French can pay far less. That's what Canadian Drug Reimportation is all about: Buying the same drugs we buy here, but at the prices negotiated by the Canadian government. It's galling, and I'm glad to hear Warner giving voice to it.

It is galling, I have to admit, and Warner’s correct that the US market must be paying for the majority of the R&D expenses of the pharmaceutical industry (since this is where the majority of the money is made, in most cases). My reply was, though, that I was worried that Klein (and Warner?) might think that the solution was to run US prices down to those of the other countries, presenting my industry quite a shortfall on its hands. Here's B.C.’s reply to that (this is him, not Ezra Klein or Mark Warner):

”I disagree with your conclusion. If you have three people bargaining to buy goods and one is willing to pay much more than the others without regard to what the other two will pay, you will sell to him at the higher price and sell excess supply to the others at the lower price, if you are so inclined.

But if all three bidders have the same market clout, then something will have to give. The market will probably reset pricing for all bidders. It might mean reductions in monies available for R&D, it might not. If the bidders are on a more or less even playing field, the market will determine that. I think that is what Klein is saying.

As things stand now, one of the buyers has given the drug companies have a massive put. That's not fair to the (involuntary) stakeholders of that buyer. If that put is removed, there is a much higher likelihood of a more equitable distribution of the burden of R&D. OTOH, as long as that put exists, there is zero likelihood that the current inequitable distribution will be corrected.”

My take on this is that health care spending is in a different category than many other things, for reasons both psychological and political. You’d expect some ordinary economic good to be divided up among three bidders in this way, but I wouldn’t expect medicine to be. It would be politically popular to see prescription drug prices go down here in the US, but it would be (almost certainly) politically impossible to see them go up by the the corresponding amount in Canada, France, Germany, etc.

Of course, I’ve made an assumption there, that the current revenues of the drug companies would remain roughly constant, and just be divided up in a different way. That's probably not how it would work. If you somehow put that idea to a vote across all the countries involved, I’m sure it wouldn’t pass. The majority of consumers, and probably the majority of politicians, would be glad to set the price of drugs by fiat, and that setting would be dialed down to “nice and cheap”. The time lag involved in drug discovery would let you do this and not notice many problems, at least on the pharmacy shelves, for several years.

And that’s the problem with setting prices that way: the temptation is for whoever is on the thick end of the whip – that is, whoever can determine prices by force of law – to set them and be damned. It’s not just drugs: I’m sure that people would, if they thought they could, vote themselves cheaper cars, not to mention the gasoline that runs them. But oil’s a commodity that trades freely, and there’s a constantly changing market price for it. A new medication, on the other hand, has just one supplier. There's just one neck presenting itself.

That turns negotiations between drug companies and governments into a rough business. Very quickly, things can come down to their ultimate positions: “We won’t let you sell in this country” versus “We won’t let you have this drug”. Note that both of these end up with the citizens involved being denied a chance at medical care. It’s as if rug-merchant transactions tended to escalate into threats to set the bazaar on fire.

Governments have another weapon when things get to that point: compulsory licensing. This has already come up with Brazil and Thailand, and will no doubt be threatened again in other places. And that brings me to my depressing point: this playing field will never be level.

Ideally, I would like to see drugs, and drug companies, compete strictly on price and on effectiveness. And I’d like to see that happen around the world, and let supply and demand sort things out. I think that prescription prices would go down a bit here, and up in many other countries. At the same time, generic drug prices would probably drop outside the US. But it won’t happen. The more I think about it, the more I fear that drugs and other health care will never trade on a free market. The temptations to do otherwise are just too great.

Comments (14) + TrackBacks (0) | Category: Business and Markets | Drug Prices

January 17, 2008

The EU Suspects No One, And Suspects Everyone

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Posted by Derek

Thanks to a longtime reader in Germany, I have the scoop from the EU and the respected Frankfurter Allgemeine Zeitung newspaper. In an article about drug prices and drug approvals, titled “The European Pharmaceutical Industry Under Suspicion”, we find (my translation following):

”Die Kommission betonte, bislang lägen keine konkreten Indizien für wettbewerbswidrige Absprachen zwischen einzelnen Herstellern vor. Es sei aber auffällig, dass die Zahl neu angemeldeter Arzneimittel-Patente von durchschnittlich 40 in den Jahren 1995 bis 1999 auf durchschnittlich 28 im Zeitraum von 2000 bis 2004 zurückgegangen sei.

„Wenn innovative Arzneimittel nicht hergestellt werden und kostengünstige Generika zum Teil erst mit Verzögerung auf den Markt gelangen, dann müssen wir nach den Gründen suchen“, erklärte EU-Wettbewerbskommissarin Neelie Kroes.

The Commission stressed that so far there was no concrete evidence of anti-competitive agreements between individual manfacturers. It was striking, however, that the number of new registered patented medicines declined from an average of 40 in the years 1995 to 1999 to an average of 28 from 2000 to 2004.

"When innovative medicines are not being made and cost-effective generics come first on the market only with delays, then we must search for the reasons," said EU Competition Commissioner Neelie Kroes.“

(Update: Here’s more, in English, on the same story.)

Well, I’m glad they’re on the case. Hey, I’m not proud – I’ll take help from anywhere. If a commission of bureaucrats can figure out how to increase our success rates, I’m willing to listen. Mind you, I’m probably going to find something else to do with my time while I’m waiting for Neelie and the gang to get back to us, but still. I note, though, that their other concern is the “delay” in getting generics to market, and I’d like to address those accusations of shady dealing in there.

Here’s a minor problem with that theory: generics come out, on average, rather quickly over here in the US. I mean, right when those patents expire – and the generic companies are often in court, pitching various theories about how the various patents should be expiring even earlier. “Ah,” but you may be saying, “but that’s because prices in the US are so high – they’re looking to scoop up those profits as soon as they can”.

I’m not one to say bad things about the profit motive, of course, and the size of the US market is a big incentive all its own. But here’s something that a lot of people don’t realize, including perhaps members of EU commissions: generic drugs are cheaper in the US than in Europe. We have more expensive drugs on patent, but once they go generic, competition really slices them down, and the generic companies make it up on volume. The profit margin on generics is, last I heard, higher in Europe.

So that would be mighty crafty of the various drug companies, to hold back on entering a profitable market that way. What, then, could be the reason? Regulatory delays, anyone? Courtesy of the same EU superstructure that’s looking into said delays? Think of how many meetings, committees, and conferences it could take to work that one out. I’ll try to speed things up for them: Here in the US, generic companies are free to work on production and regulatory issues even before the relevant patents expire, thanks to the “research exemption”. This has not generally been the case in Europe. There’s also the problem that in many EU member states, generics account for only a tiny bit of the market, apparently due to decisions by the health insurance carriers themselves – which are either arms of the state, or heavily regulated by it.

There, maybe that will help. Of course, if the process of investigating all these suspicions were to move more quickly, the impact would be felt by various restaurants in Brussels and conference hotels all over the place, so we have to consider the economic factors. Good luck, folks!

Comments (16) + TrackBacks (0) | Category: Drug Development | Drug Prices | Press Coverage

January 10, 2008

Drugs and Money and How It Feels

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Posted by Derek

Imagine that if you wanted to buy a car, you had to first visit a car consultant. This would be an expert who would place your order with a car dealer, after first looking over your transportation needs, financial status, and other factors. No one would be able to order a car on their own. Advertisements for cars would look similar to the ones we have today, except there would be a phrase at the end to “Ask your car consultant”. Much more advertising and promotion, though, would be directed at the consultants themselves, as you’d figure. A steady stream of representatives from the various automakers would come by, extolling the virtues of the latest models and leaving stacks of glossy literature, DVDs, etc., along with offers of free trips to come by for some test-drives.

Let’s move the analogy over to something a bit more realistic: mortgages. Given the current subprime meltdown, it wouldn’t surprise me much if someone, somewhere, has called for the creation of a class of mortgage advisors. Anyone looking to borrow money for a real-estate transaction would be required to go through at least a cursory visit with one. The advisor would look over your finances, explain the different mortgage options out there, and make sure that you understood what you were getting into if you had a particular offer in mind. In fact, the advisor would do more than that – if you didn’t meet certain criteria, they would not put you in touch with a lender. Some advisors would be more lenient than others, but you’d have to see one, and have them sign off on your mortgage, before you could legally borrow money.

Ads for low interest rates and creative refinances would still be around, but they’d always end with an urgent request to call your mortgage advisor immediately, before the great deal evaporated. And the bulk of the promotion money would, again, surely find it way to trying to influence the mortgage advisors themselves. Lenders would come in with figures showing how few people had defaulted with them, what percentage of the loans in a given market they underwrote, and so on. As gatekeepers in an important industry, they’d be much in demand.

Of course, in the world we live in, we trust adult consumers to be able to make decisions about which car to buy. The car companies lose no opportunity to try to make people think about the advantages of a new car, both emotional and tangible, and to suggest that it would be easy to purchase one. The car dealers themselves stress the same points, and add more details about how easy they are to deal with. People do get into bad leases or buy more car than they can really afford, but that’s considered largely the customer’s problem.

And (for now, anyway) we trust adult consumers to be able to decide for themselves if they’re ready to buy a house, which houses they might be interested in purchasing, and how they might wish to do so. This is a harder decision, since it involves a much greater commitment of time and money than purchasing a car, and there are many more options available. The existence of real estate agents and attorneys show that more people feel the need for and are (more or less) willing to pay for outside assistance in buying or selling the property itself, but there are as yet no licensed mortgage agents of the kind I describe above. That’s typically left up to the customer.

So we finally come to prescription drugs. Medical care is even more complicated than real estate – you can obtain licenses to sell properties or mortgages far more easily and with far less schooling than you need to obtain one to practice medicine, and that’s a good thing. You also cannot obtain new medicines, or any drugs for major diseases, without seeing a doctor first, both to make sure of the disease and to advise on its treatment. Consumers – and by this time, we use the word “patients” – are free to follow or not follow this advice, or to shop around until they find a doctor whose opinions they like better (if any), but they are not free to purchase and dose themselves (or others) with prescription drugs.

The difference is, as anyone will tell you, that health is an intensely personal category unto itself. A person’s health affects every aspect of their life, immediately and continuously, in a way that not even the roof over their heads can. Medical issues are unavoidably saturated with thoughts (and fears) of death or grave disability, and always have been. This has receded in places as medical science has reduced the incidence of some causes of death, but overall, this emotional entanglement is very much with us, and will be for a very long time. Look closely, and you’ll see it: as mentioned above, we have a whole special word for “customer of a physician”, because we don’t usually think of the relationship in business terms. “Patient” connotes someone who is in the care of someone else, whose fate rests partly or wholly in another’s hands.

The unusual quality of a medical transaction is understandable for another reason as well, since traditionally the course of a physical ailment has been uncertain, and the ability of medicine to do anything about it has been likewise in doubt. For most of human history, seeing a doctor has been very much like seeing a priest. It has not been looked at as a business interaction, and in most cases it had no hope of ever being one in the usual sense. (See Lewis Thomas’s The Youngest Science for more on that – he points out that almost everything his physician father prescribed in his day was a placebo of one kind or another).

The personal and emotional importance of disease (and of treatment) leads to behavior that is seen less often in other activities. People will spend terrifying amounts of their own money in the hopes of helping themselves or close family members, even in cases where the probability of success is tiny. Huge sums are spent in this country on people who are clearly near death. A person who would never dream of taking their savings to the racetrack and betting it all on a 50-to-1 longshot horse will take the same amount and put it down, with hardly a second thought, on a 500-to-1 chance of a successful medical treatment. This changed attitude extends further: medical personnel are often paid well for their efforts, but they can also give a great deal of themselves in the process, since lives are at stake. There’s an urgency, a justifiable sense of importance, which is hard for people in other professions to feel as often or as intensely.

So medicine, will probably always be special – at least, I don’t see that changing in the lifetime of anyone reading this. That complicates things, though, because (like it or not) money is involved. How could it not be? In fact, I’d say that this is one of the most obvious grinding points of friction between the worlds of private emotion and of commerce. Many people find the whole idea of medicine for profit unappealing and somehow unseemly. Since this is an area where altruism is more common (and more easily recognized) than usual, the contrast between selfless sacrifice and self-interested capitalism is especially disconcerting.

But the value people place on effective medical care, and the difficulties of discovering and providing it, ensures that large amounts of money will always be involved. Medical care works better than it used to, and it has reached that state through vast efforts, which deserve to be compensated. It’s true that when money changes hands, it can be an evil sign, as with charlatans cynically exploiting desperate people with snake-oil cancer treatments and the like. But it doesn’t have to be. We all work for a living; money does not have to stain everything it touches. Physicians deserve to be compensated for their work, proportional to its value and difficulty, and to their skills in performing it. And drug companies should be compensated for their efforts in discovering new drugs, also according to their value.

Not even the harshest critic of the industry would balk at that last statement, but that because we haven’t come down to numbers yet. If you believe that virtually all the work of drug discovery is done through federal funding, with the drug industry stepping in at the end to decide on the price and the packaging, then you will feel that this compensation should be rather minimal. (If you think that, you’re mistaken, but that’s another topic).

How, then, to decide how much a given drug therapy is worth? Any economist will tell you that the price of some good is, finally, what people are willing to pay for it. This principle works silently, for the most part, until someone offers to resell tickets for the big game for five times what they paid for them, or when the price of lumber and gasoline goes up after a hurricane comes through. At such points it stops seeming so reasonable to many observers (although nothing has changed, in terms of supply and demand). It also stops looking so reasonable to many people in the case of pharmaceuticals, but under completely normal conditions – no hurricane is necessary.

My industry realizes this (any fool realizes this). But it’s never known quite what to do about it. Pointing out that drug discovery is expensive has been a traditional argument, and it’s one that I’ve made myself. But that doesn’t address the underlying reasons for the uneasiness. Paying money for health care does not descend to the same mental category as paying money for car repairs just because someone has tried to make a case for the accounting involved. People don’t believe the numbers, anyway, but even the most believable numbers in the world would not do the trick.

Pointing out that these are, in some cases, life-saving therapies (important things, worth the price) is another tactic. That has a better chance of working, because it gets closer to the psychological core of the problem, but in the end it’s not effective, either. The more important, the more involved with matters of life and death something appears to be, the more uneasy people feel about paying market prices. The industry, if it stresses the power and efficacy of its drugs, risks looking like someone charging rent for the use of a fire hydrant.

And another tactic is to put a personal face on things – to show testimonials from people whose lives have been saved, or from researchers working hard to come up with new treatments. This also has a better chance of addressing the psychology of the problem, but also risks heightening the conflict between matters of emotion and matters of commerce. These appeals are a bid for sympathy, on at least one level, which means that they really can’t talk about money. That connection has to be made later, and the mixture is as incompatible as ever.

This is where I should come right out and say that I don’t have a solution to this problem. But I think that it’s worthwhile to consider why it exists, and where (to my mind) it’s coming from.

Comments (28) + TrackBacks (0) | Category: Business and Markets | Drug Prices | Why Everyone Loves Us

January 6, 2008

Dollar, Drugs, and Advertising

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Posted by Derek

Well, it's the first full working week of the year, so let's dive right into some controversy. There's an article on PloS Medicine on the amount that the drug industry spends on marketing. They at least try to avoid the problem of mixed administrative and marketing expenses, but the authors come up higher than the other estimates that have been arrived at. That's because they take the varying figures from the two major sources and decide to take the larger figure every time the two disagree.

The final tally? About $57.5 billion spent in 2004. Most of that is in detailing to physicians and the cost of free samples. Direct-to-consumer ads, although they get a lot of attention and collect a lot of flak, account for only 7% of the total. The authors lose no opportunity to point out that this figure is not only larger than the industry's own statements, but is just shy of twice the estimated industrial R&D expenditures for that year. And, of course:

". . .These numbers clearly show how promotion predominates over R&D in the pharmaceutical industry, contrary to the industry's claim. . .it confirms the public image of a marketing-driven industry and provides an important argument to petition in favor of transforming the workings of the industry in the direction of more research and less promotion."

Well, we do spend a lot on marketing, that's for sure. US pharmaceutical sales in 2004 were about $235 billion. If these latest figures are correct, then promotion was about 24% of sales. I don't know how that compares to other industries, but it wouldn't surprise me if it ran high. Several things lead to that - the drug industry is quite fragmented, for one thing, with even the largest companies having a fairly small market share. And patent terms mean that the bulk of the profits on new drugs have to be earned back relatively quickly before they go generic. The distribution channels in the prescription drug business lead to a concentration on the gatekeepers (physicians) as well.

But the authors of this paper have missed an important concept. As I've pointed out here before, the idea of spending money on marketing is that it brings in more money in return. If it didn't, why bother? Marketing campaigns are supposed to pay for themselves, and more besides. That doesn't always work, of course - Prizer sure didn't make back the money spent promoting Exubera - but the failures are made up for by the successes, or at least they'd better be.

So it's not like we have this huge pile of money (X) and choose to divide it up so that we spend 0.65X buying ads and 0.35X on research. Those ads are responsible for the size of the pile in the first place. If they didn't exist, X would be smaller. If the advertising is working, that whole 0.65X is being paid for by increased sales: why on earth would you spend more on advertising than you make in return for it, year after year? And some of that 0.35X comes from those increased sales, too: why on earth would you spend that huge amount on advertising and get only that same amount back in revenues, year after year?

No, as far as I can see, most of the "why don't you spend some of that money on research" question is founded on a misconception. It breaks down when you look at where "that money" comes from. I freely admit that it's not an aesthetically pleasing state of affairs. And maybe that's the root of the problem.

My industry would apparently prefer not to put it in such crude terms, but drug research involves money, and plenty of it. Advertising brings in more money, which is why it exists. The nature of our industry probably allows a higher profitable level of advertising, which is why we do so much of it. My industry may, in the long run, be doing itself no favors by avoiding this topic and encouraging the saintly-white-coated-researcher picture instead. We do help sick people, and we are glad of that (and I do have a white lab coat hanging in my lab across the hall). But helping sick people by discovering new drugs takes big piles of cash. That's how the world is.

Comments (24) + TrackBacks (0) | Category: Business and Markets | Drug Prices | Why Everyone Loves Us

September 9, 2007

Guess That Market

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Posted by Derek

When a drug company starts off a new project, a lot of things go into the decision. Most of them are scientific decisions, but a big one that isn't is the projected market size. It's a business, and if you keep developing things that don't earn out their costs (and plenty more), you won't be part of the business for long.

These market numbers aren't the most reliable in the world - Pfizer, for example, appears to have been surprised by how well Viagra did, and Bayer and Lilly were likewise surprised that their follow-ups didn't repeat. For a more recent example, try Pfizer's Exubera. Its potential as a big winner was already much eroded by the time it finally made it to market, but surely it's selling even below their worst projections.

But underserved markets give you something you can depend on. A safe, effective anti-obesity drug would clearly reap billions - not that I'm expecting to see one. An effective HDL-raising therapy would do the same in the cardiovascular market (but hold on tight if you're trying to develop one of those, too). And CNS is full of opportunities, like Alzheimer's. Mind you, those opportunities are there because people keep trying and failing to do much for the diseases, but there's definitely a fortune waiting for the first thing that does.

As you can see, the risk-reward curve is pretty similar to what you see in finance. If you want the big returns, you have to take the big risks. "Big risk" is a relative term around here, though, since even the plainest of vanilla rip-off me-toos can implode on you, taking all its costs with it. But in general, it's the same no-free-lunch graph as everywhere else in the world.

There are some exceptions, but the problem (as always) is that it's usually impossible to see them coming. Lipitor is the first example that comes to mind - Warner-Lambert just about killed it because it was going to be the umpteenth statin, and they didn't think its market share would justify the development costs. (I should have mentioned that one back in the first paragraph, when I was talking about shaky market projections!) It was only after the drug got well into the clinic that its potential began to show itself, just as Exubera was far along before its deficiencies became clear.

On a macro level, one of the big problems is the disconnect between underserved markets and underserved populations. Tropical diseases like malaria are an instant example. An effective antimalarial would be taken by huge numbers of people, but many of them still couldn't begin to afford the cheapest pharmaceuticals in the world, which is a real dilemma. (Of course, there's also the possibility that the sudden introduction of such a drug might help precipitate a Malthusian crisis in countries with traditionally high death rates, but better to deal with that than have the current situation, I'd say).

There are several methods that have been tried to bring things in line. The Orphan Drug Act is an example from inside the US (making diseases with smaller numbers of patients more financially attractive), and there's perennial talk of something similar for tropical diseases through prizes and other incentives. A different world would do things still differently, but we don't, to the best of my ability to see, live in one.

Comments (8) + TrackBacks (0) | Category: Business and Markets | Drug Development | Drug Industry History | Drug Prices

July 24, 2007

Godzilla vs. Mothra? Relman vs. Epstein!

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Posted by Derek

Arnold Relman is back. The co-author, with Marcia Angell, of The Truth About The Drug Companies, has a long review in The New Republic of Richard Epstein's new book on the industry, Overdose.

Not everything in Epstein's book is right, and not everything in Relman's review of it is wrong. But when Relman misses, he misses big. Take, for example, this:

"Indeed, the industry's greatest enemy is itself. Innovation by the major pharmaceutical firms has certainly fallen off sharply in recent years, but there is good evidence that the cause lies with the industry's own policies rather than with government regulation. The drug companies are being driven more by financial ambition and marketing considerations than by scientific or public health objectives, and that is the root of their current problems."

That must be why we plowed all that money into genomics, among other technologies: marketing made us do it. I knew we'd track down the culprits eventually! OK, Relman's targets here are the "me-too" drugs, which I've written about many times on this site. I get the strong impression that he underestimates the cost and difficulty of developing these - he seems to think that it's pretty much a breeze once the first drug in a class has hit the market. Actually, to my mind, one of the main advantages companies are seeking in a me-too is that the first drug has proven that a market exists, and that its mechanism actually works. The development costs for the later drugs, though, aren't hugely cheaper than for the first one. And, I might add, they still don't always work.

Inside the industry, people spend a lot of time talking about why productivity has gone down (we're in agreement on that point). But you don't hear many people advancing Relman's pet thesis, that we're spending too much time chasing each other. That's because I think he's confusing cause and effect a bit: we're not unproductive because of the me-too drugs - we're making me-too drugs because a lot of our other stuff doesn't work.

Believe me, companies would love to come up with new therapies for underserved markets - Alzheimer's, say - or to come up with anticancer compounds that would do for the many what the likes of Gleevec do for the few. And we'd certainly make money at these, too - if we could find a way to do them. Saying that it's for lack of trying just doesn't ring true.

That mention of making money brings up another favorite part of Relman's review:

"Regardless of the disease it targets, and whatever the benefit, no one has ever adequately explained exactly how the "value" of any new drug can be translated into dollars. It seems more likely that the price of newly approved patented drugs is simply set at whatever the manufacturer believes the market will bear. "

Good Lord! Where will it end, if companies price things according to what they think that people will pay for them? I look forward to the establishment of the Relman Board, which will determine, by means doubtless beyond my abilities to understand, the True Price (trademark applied for) of all drugs. Problem is, Relman himself probably looks forward to that, too. . .

Comments (23) + TrackBacks (0) | Category: "Me Too" Drugs | Drug Industry History | Drug Prices

July 16, 2007

European Drugs, American Drugs

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Posted by Derek

I don't know how many people here in the US have noticed, but the European Community is getting worried about how well its member countries are doing in drug research. Their Pharmaceutical Forum group has met twice so far, trying to recommend changes in drug pricing, rewards for innovation, information transfer to patients, and other areas.

I'll let one of the co-chairmen, Guenter Verheugen, explain the problem:

". . .The time has passed that Europe was the pharmacy of the world. True, our industry still has an inherent strength. But we are losing competitive ground to the United States and, increasingly, to China, India, Singapore and others. There are many worrying signals. Let me mention just two:

First, the widening gap in pharmaceutical research: Over the last 15 years investment in pharmaceutical R&D has been growing in the US significantly and consistently faster than in Europe.

Second, the development of key medicines: In the past, Europe was leading in developing the most successful breakthrough pharmaceuticals. This trend has reversed. In 2004, two thirds of the 30 top selling medicines in the world were developed in the USA."

All of the things the group is looking at seem worthwhile. But I wonder how many of them will do anything to actually change that trend? Phrases like "fair reward for innovation" and "alternative pricing and reimbursement mechanisms" point to one that might. These seem to be carefully worded calls to let the drug companies make a bit more money, in the hopes that they might find it worthwhile to make some more drugs.

That's bound to help. It's true that the United States market is where the money is made in this business, and it can't be a coincidence that this is where a lot of the innovation is coming from. But you can always develop a drug in Europe and sell it in the US, right? No, I think that there are other factors at work, cultural ones that no high-level multinational task force is going to pin down.

Perhaps I think this way because I used to work for a European company, and now work in Cambridge (home of a zillion startups). But I've long thought that there's a different attitude to research and development in this country, a greater willingness to try odd ideas and to put money behind them. I'm not saying that you don't find innovation in Europe, because you certainly can. But I think that innovators have, on the average, an easier time getting funded and being taken seriously over here. It's not a huge difference, but it's a steady one, and it's been compounding over time.

Comments (20) + TrackBacks (0) | Category: Business and Markets | Drug Prices | Who Discovers and Why

May 7, 2007

Brazil Raises The Pirate Flag

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Posted by Derek

Back in 2005, the government of Brazil threatened to break the patent on Abbott's HIV medication Kaletra if the price didn't come down (see here and here). But after a lot of arm-wrestling, a deal was reached. Now it's Merck's turn, with their efavirenz, and this time things went all the way: on Friday, Brazil's president issued a compulsory license to produce the drug outside Merck's patent.

My problem with this, other than the obvious problem I have with expropriation of someone else's property, is that Brazil is trying to have things both ways. The government spends much of its time talking about how the country is an emerging power, with the 12th-largest economy in the world, huge natural resources, its own successful aircraft industry and space program, and so on. But when it comes time to pay for HIV medications, which are important both medically and politically, suddenly they're a poor third-world country being exploited by the evil multinational drugmakers. A look back at the second blog link above, with its quotes from Brazil's Minister of Health on how nationalizing drug patents would help the country's industry, shows that this issue probably has more to do with the first worldview than the second one.

During the Kaletra dispute, I asked a question:

I've known some pretty good Brazilian scientists, but the country isn't up to being able to discover and develop its own new ones. (Very few countries are; you can count them on your fingers.) So I've saved my usual justification for last: if Brazil decides to grab an HIV medication that other people discovered, tested, and won approval for, who's going to make the next one for them?

And now Merck is basically asking Brazil the same thing:

"Research and development-based pharmaceutical companies like Merck simply cannot sustain a situation in which the developed countries alone are expected to bear the cost for essential drugs in both least-developed countries and emerging markets. As such, we believe it is essential to price our medicines according to a country's level of development and HIV burden, thereby ensuring equitable access as well as our ability to invest in future innovative medicines. As the world's 12th largest economy, Brazil has a greater capacity to pay for HIV medicines than countries that are poorer or harder hit by the disease.

This decision by the Government of Brazil will have a negative impact on Brazil's reputation as an industrialized country seeking to attract inward investment, and thus its ability to build world-class research and development."

It should have, anyway. Look, intellectual property law is not pretty, and doesn't give anyone a warm feeling. It's not meant to. But the alternative Jolly-Roger world is even worse, and anything that takes us toward that is a bad move.

Comments (44) + TrackBacks (0) | Category: Drug Prices | Infectious Diseases | Patents and IP

July 19, 2006

Fuzeon's Fallout

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Posted by Derek

I wrote some time ago (Ay! Four years ago - have I been doing this for that long?) about the Roche/Trimeris HIV drug Fuzeon (T-20, enfuvirtide), and its costly manufacturing process. Roche built a factory in Colorado just to make the drug, which is a 26-amino acid peptide. And instead of doing it recombinantly, they're producing it the good old chemical way, by peptide coupling. (Here's a not incredibly competent collection of whiz-bang photos of the place, which at least have no purple spotlights in them)

Back in 2002, I had some thought that Roche had perhaps lost its corporate mind. But as this article from Chemical and Engineering News points out (subscriber-only, I think), they've actually done everyone a favor, whether by losing their minds or not. Their decision to go fully synthetic, and the massive investment that followed, has lowered the cost of all sorts of peptide synthesis reagents, starting materials, and equipment, to the point that it's now become enough of an industry to attract a lot more production interest. (And one of the big players in the contract business is. . .Roche's Colorado facility!)

As the article points out, recombinant technology (producing the peptide in engineered cells) is a wonderful thing, but only when it's working perfectly. And getting it to that point can be a long, expensive task. There are a lot of potential cell lines to choose from, each with its own advantages and disadvantages, and uncountable ways to engineer them and culture them. Even then, the purification of the target protein can be a whole new nightmare - as one chemist interviewed by C&EN says, at least synthesis doesn't give you back ten times as many different things as you put into it.

Peptides still aren't anyone's first choice for development when there's a small-molecule alternative. But for the targets that no small molecule is going to hit, they're worth looking at. Recent years have seen improvements in metabolic stability and duration of action, as people come up with all sorts of nifty delivery systems and conjugate polymers. You could do a lot worse.

But perhaps Roche could have done better. There were all sorts of glowing forecasts about Fuzeon when it was first approved, and all sorts of grumbling from people who took the optimistic numbers and calculated that Roche would be making its money back in two or three years at the prices they'd set. Well, that hasn't happened yet, since the drug isn't selling nearly as well as had been hoped.

Another two or three years should do it, if nothing better comes along to cut into Fuzeon sales. And stipulating that (which is no sure bet) Roche might be selling it for a long time to come, since the barrier to generic manufacture is going to be rather high. So, even after that wild factory in Colorado, they're still probably going to go into the black on Fuzeon, but it does make you wonder how the return compares to some of the other drugs in Roche's portfolio.

But that's their problem. In the meantime, it looks like they've helped everyone else in the business by making industrial peptide synthesis more affordable. Adam Smith's invisible hand strikes again. . .

Comments (10) + TrackBacks (0) | Category: Drug Development | Drug Prices | Infectious Diseases

March 16, 2006

Price Gouging or Not?

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Posted by Derek

Update: More on this issue from Jim Hu here.

The New York Times ran a pretty heavy-duty article the other day on drug pricing. But for once, it wasn't the big companies that were getting pummelled. No, this time it was Ovation Pharmaceuticals getting the treatment, and I'd have to guess that most readers will have the same reaction I did: who they?

Well, they're sort of a specialty generic company. Their business model seems to be taking on ancient medications, which other companies are giving up on, but which still have a small patient population to serve. Their business model is also apparently to raise the price of said drugs, and that's what got them into the papers:

"Last August, Merck, which makes Mustargen, sold the rights to manufacture and market it and Cosmegen, another cancer drug, to Ovation Pharmaceuticals, a six-year-old company in Deerfield, Ill., that buys slow-selling medicines from big pharmaceutical companies.

The two drugs are used by fewer than 5,000 patients a year and had combined sales of about $1 million in 2004.

Now Ovation has raised the wholesale price of Mustargen roughly tenfold and that of Cosmegen even more, according to several pharmacists and patients."

Mustargen is better known to chemists as nitrogen mustard, which was basically the first chemotherapy agent ever used. Cosmegen, for its part, is the brand name for actinomycin D, which goes back almost that far itself. (To give you the idea, the first person to try it out for cancer was Sidney Farber, whose last name still turns up in cancer therapy circles.

These are drugs from the caveman days, that's for sure, and many references (that Wikipedia link to nitrogen mustards, for example, unless it's been fixed by now) will tell you that they aren't used at all any more because of their toxicity. But they're each still useful for the small group of patients the Times article mentions, generally those with very particular forms of cancer that respond well to these agents above all others. To give you the idea, five thousand patients is one fortieth the market size for what the FDA considers an orphan drug, and it's not clear if that's the patient population for both drugs put together. These are orphaned orphans.

This article is of a piece with the recent one on the price of Avastin, which I spoke about here:

The increase has stunned doctors, who say it starkly illustrates two trends in the pharmaceutical industry: the soaring price of cancer medicines and the tendency for those prices to have little relation to the cost of developing or making the drugs. . .people who analyze drug pricing say they see the Mustargen situation as emblematic of an industry trend of basing drug prices on something other than the underlying costs. After years of defending high prices as necessary to cover the cost of research or production, industry executives increasingly point to the intrinsic value of their medicines as justification for prices."

Now we're down to the real question: is this price justified, or not? Ovation is in business to make money, like any drug company, and charging a high price is about the only way to do that when you're talking about a few thousand patients. A company like Merck could carry these things on its books without much harm being done to its bottom line, because the costs of its other medicines would make up for them (not that the Times is too crazy about those other prices, either). But when a small company like Ovation takes them over, they're going to try to make them into profit centers. Over at Blogs for Industry, Jim Hu asks: "I wonder what (the Times) would be writing if Merck just dropped Mustargen and these patients weren't able to get it at all." He's got a point.

For the most part, Ovation seems to be getting the prices that they're asking. One problem is that they're selling injectable Mustagen, which is the approved form, but there's one set of patients that uses the stuff as a topical lotion (which is formulated for them by local pharmacies). It's harder to get insurance to pay for that, since it's not an approved use. (And it's hard to imagine who would be able to go to the expense of getting it approved, either, considering the subset-of-a-fraction-of-an-orphan size of the market). These people are really feeling the price increase, and the Times article accordingly spends most of its space on them. Ovation is apparently lobbying for increased insurance coverage - which is, after all, in their financial interest - but for now, things don't seem to have changed.

The downside, for Ovation and for the industry, is that this kind of thing makes it very easy to write the heartless-price-jackers article. And this is why I think the ban on Medicare using prices as a consideration is a mistake. I know that my industry lobbied hard for it, and it's no mystery why. But I'd rather have Medicare responding to (and giving out) pricing signals, and I think that (for their part) private insurance companies should do so at every opportunity. Says the Times article:

And once a company sets a price, government agencies, private insurers and patients have little choice but to pay it. The Food & Drug Administration does not regulate prices, and Medicare is banned from considering price in deciding whether to cover treatments.

While private insurers can negotiate prices, they have limited leeway to exclude drugs from coverage based on price, said C. Lee Blansett, a partner at DaVinci Healthcare Partners, which works with drug makers on pricing and marketing.

"Price is simply not included in whether or not to cover a drug," Mr. Blansett said.

But why not? It's included as a factor in decisions to pay for all sorts of other things. If that quote were talking about anything other than pharmaceuticals, it would sound weirdly obvious. The same goes for that earlier excerpt: all sorts of things are priced considering factors other than their intrinsic costs. (What the market will pay, for example). Competing on price sounds heartless at first, but consider: if Ovation's raising their prices too high, that should open the door for someone else to step in and undercut them. Pricing signals go both ways. . .

Comments (9) + TrackBacks (1) | Category: Cancer | Drug Prices

February 16, 2006

What's It Worth to You?

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Posted by Derek

So now we come (again) to the topic of cancer drug pricing. The New York Times ran an article on this the other day which has gotten a lot of attention. In it, Alex Berenson points out that prescriptions for the antibody therapies like Avastin and Erbitux cost a huge amount of money.

This isn't news, unfortunately. See this 2004 article by Matthew Herper in Forbes, for example, or see my posts from around that time here and here. What the NYT article makes much of, though, is what it says is a new rationale for the costs:

"Until now, drug makers have typically defended high prices by noting the cost of developing new medicines. But executives at Genentech and its majority owner, Roche, are now using a separate argument — citing the inherent value of life-sustaining therapies.

If society wants the benefits, they say, it must be ready to spend more for treatments like Avastin and another of the company's cancer drugs, Herceptin, which sells for $40,000 a year. . ."

You won't catch me disagreeing about the value of pharmaceuticals. But this argument can only be taken so far, because (as those links from two years ago make clear) drugs like Avastin really only add a few months of life. That's nothing to make light of, but I fear that it's also not much of a basis for Genentech and Roche to talk about how society should be willing to pay for such outcomes. Can you fix a price for two extra months of life? We're going to have to.

The NYT article has an excellent example of someone who's done the calculation for himself:

"Ellis Minrath, who has pancreatic cancer, said he had chosen not to take Tarceva, a drug from Genentech that is approved for lung cancer and has shown promise in pancreatic cancer. He did so after learning that it would cost him about $1,000 a month in co-payments, even though he is covered by Medicare.

"If anybody came out and said, 'By God, this is the stuff. You want to get well, find a way to buy it,' that would be one thing," said Mr. Minrath, who is 87. "But that isn't the case. The forecast of how much it's going to do is not that wonderful. . .

I agree with Mr. Minrath's decision, and I strongly endorse his right to make it. As an 87-year-old with pancreatic cancer, he seems to have studied his situation objectively and realized the odds he faces. He is very, very likely to die within the next few months, and (although we've never met) I'll be sorry to see him go, because he sounds extremely sensible. Personally - and I hope I never have to work this decision out for real - I would lean toward a similar "leave more for my heirs" position. Other patients in different situations may well come to different conclusions, and that's up to them (and in the real world, up to their insurance companies) as well.

What we need, of course, is some cancer drugs that don't make us put prices on months. I'd rather be working out the value of whole years or decades. Therapies which can do that will be the place to make the "society should suck it up" argument, but making it for Avastin and the like seems rather premature. What will we do when we find something that's good?

Comments (29) + TrackBacks (1) | Category: Cancer | Drug Prices

February 15, 2006

Pfizer Takes a Deep Breath

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Posted by Derek

I haven't mentioned Pfizer's inhaled insulin project in a while, but a few weeks ago they got the stuff approved, at (very) long last. The development of Exubera, which is certainly a cheerful brand name, has been anything but uplifting, though Here's a piece I did three years ago, when the story already seemed to have been going on for a long time.

Insulin, of course, is the very definition of a well-established drug, but that's only if you inject it. Slowing things down have been problems which are unique to inhaled powders: the effect on lung function over time, the changes in dosage under suboptimal conditions (allergy, flu, etc.), and the reproducibility of the dose. These are particularly worrisome for insulin, which is a tough situation: it's vital to its users, and it has a lower margin for error (both under- and over-dosing) than most other drugs. As I put it in that 2003 post, if you take twice as much aspirin as you should, it'll be rough on your stomach. If you take twice as much insulin, you're going to end up on the floor (and there had better be someone around with a candy bar).

You can see this troubled history in the drug's labeling, which Frederick Cohen at Crownstone has been going over. To pick one interesting detail, patients will be required to have a baseline pulmonary function test before starting the drug, with monitoring thereafter. And this brings up the current worry: how much will Exubera (and its baggage) cost, and who's going to pay for it? The product won't be launched until mid-year, and no one knows quite what its price will be. Pfizer's just saying that it will be "competitive", an answer which is synonymous with "Go away", but you can find estimates of up to four times the cost of injectable insulin (my guess is 2.5x). Call it a convenience premium. Will it fly?

Well, here's a piece in Business Week that's enough to make you wonder. It's written by a pair of consultants from the Bruckner Group, an outfit that's very big on outcome-based medicine, and from that perspective they think Exubera's in trouble even before it launches:

". . . Based on our analyses and interviews with major managed-care decision-makers, we expect that payers will either dramatically limit Exubera's availability to patients, impose very high co-payments, or reject coverage of it outright. . .For Exubera to achieve widespread preferential formulary status, payers will need to see a credible and compelling value proposition rather than an argument centered on patient convenience. The crux of the issue is whether an inhaled therapy will improve compliance and lead to significant improvements in patient health."

As they point out, the data on other inhaled therapies isn't too reassuring. Studies have indicated that asthma inhalers, for example, are often misused, both quantitatively and qualitatively. The Flumist inhaled flu vaccine has also been a disappointment compared to its injectable competition.

Pfizer may be counting on its (justly) famous marketing powers to put Exubera over. If the landscape, though, really is changing to more rigorous cost/benefit calculations, that might not do the trick. I realize that the BW authors have an interest in promoting this viewpoint, but I hope that they're on to something. I'd rather see more of the competition between drug companies taking place over medical evidence and financial benefit, rather than the size of the sales forces. Salesmanship alone can't put over a lousy drug. But it can take away from the issues that really should be decisive.

Tomorrow we'll take a look at how this applies to oncology, where things are getting really interesting. . .

Comments (18) + TrackBacks (0) | Category: Diabetes and Obesity | Drug Prices

January 5, 2006

Ugly, But Effective

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Posted by Derek

There are plenty of links around the blog world to the Edge.org "Dangerous Ideas" symposium, and much of it makes for good reading. But there are some clinkers. I was going to take some time to disassemble this one from biologist Paul Ewald, but that effort has already been made for me.

Put briefly, Ewald is a believer in the more extravagant reaches of the "New Germ Theory", the idea that many more diseases than we now think are actually caused by infectious agents. But he also seems to believe that even if vaccines were possible for things like cardiovacular disease that no drug company would develop them. Y'know, so we could keep selling our regular drugs instead of curing diseases. But it never seems to occur to people who advance ideas like this that such a vaccine would make an overwhelming amount of money, and that we'd be very interested in it indeed. Think about how much people are willing to pay for, say, medication to lower their cholesterol or keep their blood pressure down. Think how much people pay yearly for insulin or for asthma medication - whole companies are founded on these kinds of franchises, even with fierce competition between drugs.

Now imagine how much people would pay to never have to do that again. Quite a bit, I'd guess, since you no longer have the disease and no longer have to take any drugs for it. And here's the real kicker: the company that comes up with this wonder cure would scoop up the revenue from the entire therapeutic area, because there would be nothing that could compete. No, I think that we'd be quite intrigued.

Now, I have to say that such treatments probably aren't going to turn out to be possible in most cases. I like a lot of the New Germ Theory stuff, but I'm not sure if it can be pushed this far - although I'd love to be proven wrong about that. But the best way to make sure that they don't happen is to remove that gigantic incentive. Any company that makes a serious try at something like this will be taking a very large, very expensive risk, and if they know that there's a patent seizure waiting at the end of it they may decide that the money is better spent elsewhere. It would get done, eventually, but the fastest way - if there is a way at all - is to let profit-minded companies scramble for it.

Comments (17) + TrackBacks (1) | Category: Drug Prices

October 12, 2005

The Undefeated Brazilian Team

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Posted by Derek

I wrote earlier this year about the showdown between Abbott and the Brazilian government over the price of the antiretroviral Kaletra. After several weeks of rumors, the deal has been struck. And as far as I can see, Abbott did most of the caving in.

Kaletra will now be down to 63 cents a dose in Brazil, down from the previous $1.17. It's interesting to note that back in the summer, press reports had the Brazilian government asking for a price of 68 cents. I don't know if the latest figure reflects a further price break or inaccurate earlier reporting. The new price is less than the American one by a factor of four or five, and this deal sure isn't going to send the price here any lower. In the end, money will be transferred from Abbott's existing customers to the government of Brazil.

This looks like another victory for the "Lower your price or we'll break your patent" strategy that Brazil has used before. They've never gone through with the threat, but it's clearly a real one. Abbott has apparently decided that it's better to make 63 cents a pill in Brazil than to make nothing, and (worse yet) to have Brazilian generic drug makers cranking Kaletra out for the rest of the world. And they've got a point there, of course, even after assuming that this deal could set off more price negotiations in other countries.

But this is worth thinking about next time you hear about the evils of pharmaceutical patents - you know, licenses to print money and all that. There is a trump card, and it's just been played again. Back into the deck it goes until it's needed

(Much, much more on drug pricing can be found in the blog archive here. This very point about national health plans and price-setting came up, for example, in this post from February of 2004.)

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July 6, 2005

Brazil Pulls Out the Pin

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Posted by Derek

Just how much should an anti-HIV drug cost? What if you're selling it in a place where most of the patients can't afford it? These questions have been fought out in Africa and other parts of the developing world over the last few years (and the stagnating world, too, unfortunately.) Now Brazil may be making good on a threat of outright patent confiscation.

The Brazilian government is unhappy with the price of Abbott's combination therapy, Kaletra (PDF), which they already pay just over $100 million per year for. Mind you, that's the lowest price in the world outside Africa. Online pharmacies claim that the average US retail for Kaletra tablets is about $4.06 each, and they offer it at about $3.60. Brazil's paying $1.17, and they're saying that they'll issue a compulsory license if the price doesn't come down to 68 cents.

They've threatened to do this before, but have never come this close to following through. The worry for Abbott is that once the Brazilian generic companies start making the stuff, it'll end up all over the rest of the world at a base of $0.68/tablet. And where do you think demand for it will be strongest? In the countries where it's already the most expensive, which Abbott is counting on for their profits.

Opinions vary a bit, as you'd figure. You can find no shortage of activists cheering the Brazilians on. To wit, from the AP article linked above:

"We are the hostages of these companies, and compulsory licensing is a defense against the abuse of monopolies," said Jorge Beloqui, the leader of a Sao Paulo-based AIDS support group.
Beloqui, a university math professor, has taken 30,000 anti-AIDS pills provided free by the government since 1991. If Brazil breaks the patent, he says, activists will pressure Brazilian politicians to go a step further and let its generic drug makers produce much more of Abbott's drug so it can be shipped around the world to needy patients.
"These medicines are essential to the world, and I think Brazil should sell them," he said.

Actually, Prof. Beloqui is the hostage of a retrovirus, but his comments seem pretty representative of the "stick it to The Man!" point of view. Well, speaking for The Man (to crib a line from Tom Wolfe), I have to say that Brazil seems to be playing to the galleries here. There are accusations that the country is spending less on anti-HIV medications than it did five years ago, and they turned down $40 million in US money not so long ago. There's another problem, too. Brazil is acting according to WTO language about breaking patents in case of a public health crisis. But you have to wonder

Allowing Brazil to use the "public health crisis" justification creates a dangerous and perverse incentive for governments of the developing world: if you as a government are responsible and work hard to uphold a fiscally manageable public health program, then you will be punished by having to pay for expensive drugs, but if you fail or simply ignore the problem and cry "crisis," then you will be rewarded with permission to trample on intellectual property rights.

I've known some pretty good Brazilian scientists, but the country isn't up to being able to discover and develop its own new ones. (Very few countries are; you can count them on your fingers.) So I've saved my usual justification for last: if Brazil decides to grab an HIV medication that other people discovered, tested, and won approval for, who's going to make the next one for them?

Comments (43) + TrackBacks (0) | Category: Drug Prices | Infectious Diseases | Patents and IP

December 7, 2004

Check, Please

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Posted by Derek

Here's a post from back in the spring which goes into why I think that the cancer drug market is in the process of changing. As we figure out which patients will respond to which drug - which will happen, albeit slowly - the standard industry assumptions about market size will have to be rethought.

For now, we in the business can continue to assume that everyone will be given most everything for most everything. That's why Gleevec sells at the level it does - it's really an orphan drug which has benefited from the let's-give-it-a-shot mentalily more than anyone thought possible. The thing is, most of the people who've received the drug (and the other new agents) for totally different kinds of cancer than they're known to treat have wasted their time and hopes, and their insurance companies have wasted their money. It's true that this kind of clinical practice can lead to new treatments (there are always some surprises), but it leads to a lot of lost effort, too.

But as we move into the world where we know more about what we're doing, that's going to change (see that post linked above for details.) Cancer is going to slowly turn into a constellation of hundreds (thousands?) of orphan diseases, each of which will have its own particular preferred therapy. We won't need new drugs for all of them - many of these will be particular combinations of known agents - but we'll need a lot more than we have now. And the market size for each of them might be at least an order of magnitude smaller than we'd like.

That, naturally enough, will mean that the prices of these drugs will go up, because they're probably not going to be any cheaper to develop. So we'll have a lot of drugs, each of which can do great things for a small set of patients, and each of which will cost a heap. Doctors will have no problems with this, and patients will adapt to this world without many complaints. We'll adapt to it in the drug industry. But think about how this is going to look to an insurance company or HMO. . .

All of their cancer-patient customers will be taking highly expensive medications - different ones, true, but the bottom line will be the same. And they'll all have to stay on them for a long time, since we still don't know how to make cancer reliably go away very well - we can just keep it in check. How's that sound over on the insurance side of the street, guys? Guys?

(For those who are interested, I wrote a few other posts on the issue of cancer therapies (and their prices) back in the summer - try here and here if you haven't seen them.)

Comments (6) + TrackBacks (0) | Category: Cancer | Drug Prices

November 10, 2004

Cui Bono?

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Posted by Derek

Holman Jenkins has an interesting "Business World" column in today's Wall Street Journal. Writing about Merck and Vioxx, he wonders:

"Did CEO Ray Gilmartin blunder in withdrawing Vioxx from the market? Merck executives yanked the prescription pain reliever, amid much backpatting, when a study revealed that long-term users were at somewhat elevated risk for heart attacks and strokes.

Merck was evidently bidding for public admiration in sacking its biggest revenue spinner. If so, the tactic seems to have failed catastrophically. And contrary to the tone of much recent coverage, doctors had long understood that patients taking Vioxx would suffer more heart attacks than patients taking conventional pain relievers."

I didn't think that Merck was looking for good-conduct points, actually - what changed was that there was finally a large-scale study that showed irrefutable evidence that there was a cardiovascular problem. Jenkins goes into this a bit, but I think that it's clear that if Merck wasn't going to act, then the FDA would have forced them. Perhaps that's the only good PR that they might have been hoping to salvage. He goes on to make a very useful point:

"Merck chose to withdraw the drug, although honesty would have been equally well-served by a big informational campaign saying: "Don't prescribe this for patients not at risk for stomach bleeding. Don't let patients become chronic users."

Given that market surveys show that two-thirds of Cox-2 users don't need them, Merck's revenue hit would have been devastating in either case. But it would have made the point that Vioxx is not a defective product -- all drugs have risks that have to be weighed against their benefits -- but a seriously overprescribed one.

The Vioxx debacle is symptomatic of a system that shields consumers from price signals and sometimes actually discourages them from making the right health-care choices. . .Big Pharma is well along in being corrupted by third-party payership, just like the rest of the health-care industry. Drug makers increasingly aim their development efforts at the aches, pains, insecurities, heartburn and erectile dysfunction of price-insensitive, over-insured baby boomers because that's where the money is.

The problem is compounded by a regulatory system that drives the cost of developing a new drug to a billion or more, then forces companies to recoup all their costs in a few short years before the patent expires. This basically forecloses a great deal of investment in drugs that don't fit the above description, such as vaccines or antibiotics."

Unfortunately, there's an awful lot of truth in that. Since we're a business, we are always going to look for where the most money can be made. Other things being equal, underserved markets would be some of those places. But with the increasing difficulty of finding drugs and getting them to market, the pressure to get your few, rare shots to land right has increased. Thus the situation that Jenkins describes - and this is where I part company with the Marcia Angells and Merrill Goozners of the world.

They see the current situation and say "See! The big drug companies are just going for the big profitable diseases! That's why pharmaceuticals are in the shape they're in!" And from our end, it looks more like "Things are in such bad shape that we'd better stick to the big, profitable diseases. If we spend all our time targeting the others, we'll go under!" It's a cause-and-effect argument.

And the larger point stands as well: I think that companies should, in fact, shoulder blame for promoting Cox-2 inhibitors as if they were the right choice for everyone, and for pushing things like Nexium over Prilosec (and Prilosec over the older drugs in the category, for that matter.) But there's plenty of blame to go around.

Physicians have to write prescriptions for these things for us to sell them. Have the doctors been stampeded by our marketing departments, bribed by our piles of loot, or are they worried that if they don't write for these drugs then the next doctor will? And what about the insurance companies who are paying for all this stuff? To me, those are the people whose actions make the least sense.

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October 17, 2004

Preach It, Brother

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Posted by Derek

Saturday's New York Times had an astonishingly sensible article about the drug reimportation issue. (You can go ahead and insert the phrase ". . .especially for the New York Times") Some highlights:

"It may make political sense to point to Canada as a solution to high prescription drug prices in the United States. But many economists and health care experts say that importing drugs from countries that control their prices would do little to solve the problem of expensive drugs in the United States, where companies are free to set their own prices. Even the nonpartisan Congressional Budget Office estimated that allowing Canadian drug imports would have a "negligible" impact on drug spending. To begin with, there are not enough Canadians, or drugs in Canada, to make much of a dent in the United States. There are 16 million American patients on Lipitor, for instance - more than half the entire Canadian population."

Quite so, and as the article goes on to point out, we in the drug industry have no incentive to ship Canadian pharmacies ten times as much stock as they need for their own country. It's not going to be pretty, but cutting things off at the supply end is what's going to happen - unless, of course, Congress manages to make that particular business decision illegal, as they're threatened to do. Here's some more:

". . .the measures proposed so far would do little to change the fundamental economics of the drug industry as it exists today. Prescription drugs cost a lot to invent, but once invented cost little to manufacture. That is why patents are granted to drug companies - to prevent other companies from copying their inventions long enough for the inventors to set prices high enough to recover their investment and make a profit. But price controls short-circuit this system."

That's absolutely correct in every detail, and such is the state of journalism today that I could not believe my eyes when I read it. I starting waving the paper around, clutching my chest and calling out to my wife: "It's the big one! I can feel it!" She's used to me. And one last quote:

"But the United States market is hard to compare with any other. It represented more than half of the global drug industry's sales of $410 billion last year and was the country in which drug companies make the bulk of their profits. Whatever one thinks of the pricing disparity, efforts to force down American prices to Canadian or European levels could radically change the economics of the pharmaceutical industry - which effectively depends on United States profits for all of its activities, including a substantial portion of its spending on research and development.

American consumers are "subsidizing everyone's R&D,'' said Mr. Love, the consumer advocate. "We're paying way more than everyone else. Others should pay more.''

This article is bylined Eduardo Porter, and I wish to publicly salute the man. I'll think of this every time I'm about to get the vapors about reimportation and remind myself that good sense can break out.

Comments (8) + TrackBacks (0) | Category: Drug Prices | Press Coverage

October 11, 2004

Prices and Innovation

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Posted by Derek

Alex Tabarrok over at Marginal Revolution has called attention to a very interesting study on the financial aspects of drug discovery. Price reductions could have a disproportionate effect on R&D, the authors say, which fits in with my personal industry experience. If you cut everything by, say, 20%, you're not going to have just 20% fewer drugs to show for it. It isn't linear (not much is, as far as I'm concerned. . .) (Note his correction, though, which makes the effect less drastic, but also see Tyler Cowen's post just above the original post.)

That inspired this post over at Asymmetrical Information. Jane Galt finds the prospect "frankly terrifying". There are 80 comments so far - it's quite a discussion, and I encourage anyone interested in the issue to have a look.

Comments (6) + TrackBacks (0) | Category: Drug Prices

September 29, 2004

Peter Rost, Oddity

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Posted by Derek

After mentioning my cheerful outlook on drug reimportation, I should bring up the interesting case of a Pfizer executive, Peter Rost, who also thinks that the drug safety argument is a loser and is willing to say so. (But he's saying it because he thinks that Canadian reimportation would be a really great idea. This is, to put it gently, a most unusual position for a pharmaceutical executive to take.) Rost has been all over the news and in front of Congress, telling everyone with a microphone what he thinks.

He lays it right out about the ridiculous drug safety tactics, saying that he's "never, not once, heard the drug industry, regulatory agencies, the government or anyone express any concern related to safety" and that ". . .companies are testifying that imported drugs are unsafe. Nothing could be further from the truth." Hey, open up! It's good for the soul!

How is Pfizer taking this? Not too well. One of their other executives, one Chuck Hardwick, sent a letter to members of Congress saying "Dr. Rost has no qualifications to speak on importation, no responsibilities in this area at Pfizer, no knowledge of the information and analysis Pfizer has provided to the government on this issue and no substantive grasp of how importation may impact the safety of this nation's drug supply." Safety first, Chuck, never forget. We're going to go down with this one eventually, but at least we'll go down as a team, eh? Another Pfizerite, Paul Fitzhenry, says that Rost's comments "impugn the integrity" of people inside the drug industry who've made the safety argument. Well, I'd hate to impugn anyone's integrity. How about their intelligence?

Now, I don't think that the drug-safety firewall is going to crumble tomorrow (not with things like this going on. But these findings are a direct consequence of one of the only weapons my industry has in the reimportation battle: limiting the supply of drugs to Canada. The Canadian pharmacies are turning to other countries, not all of them reliable.

This will work, for a while - but is it a weapon we want to be seen using? There's a real possibility that this will create shortages of some medicines in other countries as the supply problem cascades along. Do we want everyone to watch as we turn the spigot?

Economics. Drug reimportation is an economic issue, not a safety issue. We've allowed ourselves to get price-controlled into a corner, and we need to find a graceful way out of it. But instead, we're helping to saw through the floor. . .

Comments (4) + TrackBacks (0) | Category: Drug Prices

September 28, 2004

Kicking the Dinosaur's Tail - Again

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Posted by Derek

Economist Mark Kleiman, in a clearheaded post on drug reimportation, says:

"No doubt, the politicians who are campaigning to permit pharmaceutical arbitrage are demagoging the issue by failing to mention the impact on innovation. But at least the argument they make – that allowing arbitrage would reduce prices to consumers – is more or less correct, and actually expresses their goal. The politicians who oppose arbitrage, by contrast -- including the Bush Administration -- largely try to hide behind the “safety” fig-leaf. That’s an insult to the intelligence of the voters."

Oh, yes indeed. My readers know that I've been banging on that particular washtub for a long time now, much good has it done. Here we go again, once more with feeling, from someone who works right here in the drug industry:

Canadian pharmaceuticals are safe. They're just as safe as ours. The reasons that reimporting them is a bad idea are economic ones. We need the money, and we've turned the US into the only place we can make it.

A more, um, detailed presentation of that point of view (from a passel of economists) can be found here. But the politics of the problem aren't in need of expert explication. Opponents of drug reimporation are trying to beat something (cheap drugs!) with nothing (no cheap drugs!) That's always a tough sell, so they - I can't bring myself to use the pronoun "we" - are trying to use irrelevant scare tactics instead. People are catching on

I think you can win a few short-term battles that way, at the cost of most surely losing the war. As I keep saying, the safety argument is one that can be addressed. As it will be, and where will my industry be then? Left wiping sweat from its forehead, stammering "But. . .but. . .there's actually another reason why this won't work. . ."

It'll be too late. The industry whose efforts I have devoted my adult working life to, the one that feeds my kids and keeps a roof over my head, is happily strapping itself to a barrel. It's making double-sure that the knots are firm and the cords are tight. The waterfall makes an awful, awful noise. . .

Comments (3) + TrackBacks (0) | Category: Drug Prices

August 31, 2004

Me Too, Part Two

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Posted by Derek

As came up in the comments to the previous post, there's not as much price competition inside a given drug category as you'd think. That's not because we're Evil Price Gougers, at least not necessarily. As I was pointed out yesterday, "me-too" type drugs aren't as equivalent as some people think. The main reason we go ahead with a drug in a category where there's already competition is because we think we have some advantage that we can use to gain market share.

This is a constant worry in every drug development effort where there's already a compound out there. I've personally, many times, been in drug project meetings where we've looked at the best competing compound (one that's either already marketed or well into clinical trials) and said "We haven't beaten them yet. We're not going to make it without some kind of unique selling point." The best of those, naturally, would be superior efficacy or a superior safety profile. Then you have easier dosing, fewer interactions with other drugs, and so on. I need to emphasize this: I have seen drug projects killed because no case for an advantage could be made.

Now, there's room to argue about how much better efficacy a drug needs to be a real advance in the field, or at least a bigger seller. You can argue about any of those possible advantages I listed, and it's true that drug companies push some compounds that aren't exactly huge leaps over the previous state of the art. (You see more of that when there's a case of shriveled pipeline in progress.) But there has to be something, and the bigger the difference, the better it is for us. We're motivated, by market forces, to come up with the biggest advances we can. The sales force would much, much rather be out there with data to show that the new drug beats the competition in a clean fight, as opposed to saying that it beats the old one on points, in a subset of patients, if you massage the data enough and squint hard, and besides it tastes better, too. . .

And as I've pointed out before, we often find out things about compounds long after they've reached the market. Lipitor, as discussed yesterday, is a case in point. I have not been a Lipitor fan in the past. The statin field seemed already pretty well served to me (as it did to a number of people inside Warner-Lambert during the drug's development, frankly.) The drug made its way forward based on efficacy in the clinic: it seemed to do a better job lowering cholesterol and improving the LDL/HDL ratio. How much advantage that is in the long term is another question, but those are the best markers we have.

The whole antiinflammatory c-reactive-protein story about the drug only came up after it was already on the market. The marked differences between it and the other statins, which I have to assume at this point are real, are a pleasant surprise to everyone involved. Warner-Lambert (and then Pfizer) thought it was a better compound, but not to this degree or for these reasons, I'l bet. I'd say that this is another argument for having multiple drugs in the same category. We don't, and can't, know everything that they'll do.

Comments (2) + TrackBacks (0) | Category: "Me Too" Drugs | Cardiovascular Disease | Clinical Trials | Drug Development | Drug Prices

August 24, 2004

I'll Have the Price They're Having

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Posted by Derek

Thanks to Arnold Kling, I found this piece on the economics of the drug industry. It comes from the remarks at a recent industry conference, and it's worth reading (even if it does make an approving reference to Marcia Angell near the end) - an excerpt:

If the prosperous flow of innovations was to be sustained (he said), either the industry would have to find a way to dramatically alter its cost structure, or else "we are going to have to figure out collectively some way across political parties and countries to construct and maintain a structure of global price differentials."
With the promise that changes in the cost structure would be addressed in another meeting later in the fall, attention turned to various schemes for differential pricing.

Berndt skimmed quickly over the traditional argument for differential pricing. Many industries had high fixed costs and relatively low marginal costs, he said -- electricity, telecommunications, software, database services, movies, and so forth.

But none was the same class as pharmaceuticals, where the difference in incremental cost between the first tablet of a new medicine and the second is on the order of $800 million for an average medicine --$800 million to "get the science right" and make certain that the treatment works in some degree, 25 cents to make the second copy, and the third and as many more tablets as can be sold.

Not being an economist, I'd never thought of it in quite that way. It's a familiar illustration of the problem of software piracy, though, or file-sharing of copyrighted work. We don't have as much of a piracy problem in pharmaceuticals (although it's certainly there), since it's harder for a third party to run off further copies of our pills.

The focus on differential pricing is justified. That's what the whole drug reimportation debate comes down to, and it's the corner my industry has painted itself into. This meeting seems to have mostly tried to find ways to maintain the existing system, which is at least better than suddenly yanking it down. That is, it's better for all of us who would be suddenly pitched onto the street, and it's better for our customers, who in a few years might wonder why there haven't been any new drugs to treat their diseases for a while.

But I'll really be interested in the next conference mentioned above. I think that eventually we're going to have to move to a new pricing structure, and I don't know what it's going to look like. The article itself has a suggestion, which I'll address separately - Arnold Kling has a follow-up on it here. Whatever it is, we're going to need some time to get ready for it.

Comments (5) + TrackBacks (0) | Category: Drug Prices

July 30, 2004

John Kerry on Drug Prices

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Posted by Derek

I didn't watch John Kerry's speech tonight. I'll watch a political speech made to a potentially hostile or sceptical audience (like the State of the Union) but not one made to an adoring throng, either throng. Life is too short.

But I've had some e-mail pointing out that Kerry whipped out a line about drug prices, which I presume was an applause-getter:

"Under our plan, Medicare will negotiate lower drug prices for seniors. And all Americans will be able to buy less expensive prescription drugs from countries like Canada."

Of course, the law as it stands forbids any drug company from offering anyone a lower price than they offer Medicare. Ask Schering-Plough how that one works. But what Kerry is talking about is modifying the latest Medicare drug benefit, to allow the federal government to directly negotiate drug prices. My industry put up a serious battle to keep that from happening, and it's no secret why. This is a direct route to Federally mandated drug price controls. If you think that those are a good thing, then you like that idea - if not, you don't.

And as for importing drugs from Canada, well, I'll resist the temptation to start turning purple again. But I took Kerry's suggestion to go to his campaign website for more details:

"The Kerry-Edwards plan will reduce prescription drug prices by allowing the re-importation of safe prescription drugs from Canada, overhauling the Medicare drug plan, ensuring low-cost drugs, and ending artificial barriers to generic drug competition."

Now that word "safe" is an interesting one to drop in there. As many readers know, Congress has already passed a law making it legal to reimport drugs from Canada - but only if the FDA certifies their safety. And that the agency has refused to do, saying they don't have the resources to make such a guarantee. Is Kerry planning to give the FDA whatever it might need to go ahead and make the call? Or is this an escape clause to allow the status quo to prevail?

Well, if that Medicare idea comes true, it could be a moot point. There won't be much need to import drugs from Canada if we become Canada, will there?

Comments (10) + TrackBacks (0) | Category: Drug Prices

July 25, 2004

Costs and Benefits, Risks and Rewards

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Posted by Derek

Continuing on the latest issue of the New England Journal of Medicine and its articles on cancer therapies, there's the Perspective article, from Deborah Schrag at Sloan-Kettering, which points out that:

"In the wake of the optimism generated by recent trial results, patients experience sticker shock when they encounter the prices of chemotherapy drugs. Physicians find themselves in the undesirable position of having to help patients make decisions about whether the potential clinical benefits warrant the financial strain that even the copayments for these medications may create."

I don't doubt it. She has a chart for a typical patient's eight-week therapy on various regimes. Drug costs for the classic fluorouracil-based therapies will run from $60 to $300 for that period. Throw in irinotecan, the standard since the mid-1990s, and you're looking at about $10,000 for the same eight weeks. An Avastin-based treatment will double that, and an Erbitux-based one will triple it. And those are just wholesale drug costs; they neglect support, labor, wastage, and so on. Avastin and Erbitux are harder to store and administer, so their costs will be still higher. And even if you take the statistics in the latest paper at face value, median survival is increased by less than two months with Erbitux. That brings us to a terrible question: how much are those two extra months worth, and who should pay for them? Everyone's trying to offload that decision onto someone else, and I don't blame them a bit.

We're back to where I was discussing this issue a few weeks ago. As I said then, I think that the solution is that many people won't (and shouldn't) take these therapies, because they're just not worth it. But that's a hard thing to convince someone of, and I'm glad that I don't have to try. My attempt to pass the buck is to point out that none of us in the industry is trying to develop a hugely expensive drug that only prolongs survival by a couple of months - that's just how the damn things come out after we've already spent the time and money. We're trying to hit home runs over here, but the pitching is too strong for us.

The article gets its shots in at the drug industry, though:

"Early scientific work that led to the discovery of bevacizumab (Avastin) and cetuximab (Erbitux) was financed with federal dollars. The pharmaceutical industry translated these fundamental insights into the development of commercial products. The rising stock prices of the publicly traded companies that manufacture these drugs reveal that, development costs notwithstanding, the risk-adjusted return on pharmaceutical products is very high indeed. The drug costs that support these stock prices threaten to overwhelm our ability to pay for health care."

Well. . .let's dispose of those in order, then. The first part is the old drug-companies-rip-off-NIH canard. Allow me to point out that no academic labs were attempting to turn antibodies against the growth factors receptors into new drugs, so why is industry to blame for trying? "Translating fundamental insights into the development of commercial products" is exactly what the drug industry does. It's very hard to do, it's very risky, and it costs a hell of a lot of money. You have a problem with that? If Dr. Schrag believes that she can do it more cheaply and efficiently, I invite her to raise the money and come on down and try it. Many people have done just that, and it's an education, all right.

And as for drug costs overwhelming "our ability to pay for health care", has Dr. Schrag considered that the total contibution of drug costs to health care is below 20%? Isn't there any overwhelming being down by the rest of the business, or are they just standing around in awe of our mighty powers?

And let's see. . .the rising price of the stocks, yes. Please note that I think that Imclone's stock is already too high. As high as Erbitux's cost is, I still don't think it can support Imclone's current price. I think that Bristol-Meyers Squibb overpaid for their share of the drug, and I'm not sure they're going to end up with much of a return. Note also this post about the amount of money that the biotechs have lost over the years - on average, biotech investors have lost money and they continue to lose it. For some years now, anyone investing in the stocks of companies I've worked for has been taking a bracing bath indeed. Believe me, although there are some good investment opportunities, the drug industry only looks like a money machine to the unwary.

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July 1, 2004

So What's Wrong With A Little Money Changing Hands?

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Posted by Derek

The marketing practices mentioned in the last posting sound a lot like radio-station payola - paying to get a song on the air. There was an interesting defense of this practice mounted recently over at Marginal Revolution (see the first three postings here.

Is there a difference in this case? (I mean, short of the "we're-talking-about-people's-lives-here" argument, which can be valid but ends things before you have a chance to do any potentially useful thinking.) I think there is, and it has to do with market efficiency.

Whether a song becomes a hit or not is based on a relatively quick aesthetic call by a large audience: "I like that." The pro-payola argument (or at least the non-anti-payola one!) is that you can't force a song to be a hit by paying for airplay - all you can do is pay enough to give it a chance to become one. There are historical examples of songs and artists that likely wouldn't have had a chance without someone opening their wallets.

But paying doctors to prescribe certain drugs is a different sort of market perturbation. For one thing, there's not such a good feedback mechanism as there is with listener choice. It takes a while before you can tell if most medications are working or not, days or weeks. And even then, it may not be apparent to the patient. Blood pressure therapies don't make you feel much different at all, even when they're lowering life-threatening hypertension. And most chemotherapy (to pick an extreme case) makes you feel absolutely worse, immediately and continuously, even if it's managing to put your cancer into remission.

And songs are more clearly differentiable, making their market more efficient. Listeners can pick out a new song by an established artist quickly, and if it's someone they've never heard before, they'll notice that, too. But the differences between, say, the different statins are more subtle. You won't feel your HDL increasing a bit more with one of them versus the other - heck, unless they look at a large statistical sample, physicians won't notice that, either. And there's the large question, in this case and others, of whether that real difference is enough to have a real clinical effect. No one's in doubt for very long about whether a song has accomplished what it's trying to do.

In radio payola, you're trying to seed a large market and hope that something will then take off through the free choice of the consumers. But who are the consumers in the prescription drug market? There are areas where direct-to-patient marketing works, in which case it's clear that the patients are regarded as the real consumer. The hope is that they'll storm their doctors offices clamoring for the latest therapy (much to the irritation of the doctors involved, I think!)

But in many other fields, it's the physician that's clearly the consumer and the target of advertising. Schering-Plough appears to have been paying for their interferon to be prescribed for hepatitis patients, among other things, and there's never been much (any?) direct-to-patient advertising there. One physician can write for a large number of patients, so the temptation for well-targeted payola is strong. And wrong.

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June 23, 2004

It'll Cost You

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Posted by Derek

Over at Slate, NBC's Robert Bazell takes on the drug pricing issue, focusing on the newer oncology therapies. There's no denying that some of them are really costly, and that this is a situation that probably can't continue under the current system (which, to exaggerate only slightly, works like this: every cancer patient gets to try everything, and insurance/Medicare pays for it no matter what.) But the problem with Bazell's article is that it bungles enough other points that his main ones are obscured. One of them goes like this:

"Why are these drugs so expensive? It's hard to know exactly, since drug pricing is a sacred prerogative protected by acts of Congress and the details remain shrouded in trade secrets. But the simplest answer is that drug companies can charge whatever price they want. "

Ahem. That's as opposed to the perfectly transparent pricing mechanisms for, say, cars, toothpaste, and fish sandwiches, I guess. And those aren't even "sacred prerogatives"! Imagine what those things would cost if the businesses that provided them could charge whatever prices they wanted to! Good thing we don't let them. (And yes, I know that cancer drugs aren't exactly discretionary purchases - we'll come back to that one.) Bazell goes on:

"Erbitux and Avastin are both laboratory-produced antibodies (Erbitux blocks a chemical signal that tells cells to grow; Avastin cuts off blood supply to tumors). True, these antibodies are more expensive to produce than most pills, but only slightly-the technology can be replicated in any college biology lab. Production costs amount to few dollars a dose at most."

I hate to put myself in the position of defending Imclone and Erbitux, but this argument is exaggerated to the point of nonsense. I know what he's trying to say - that making monoclonal antibodies is an established technology - and up to a point, it is. But Bazell makes it sound like a bunch of undergraduates could whip up a batch of Erbitux for fifty bucks or so, and that is, to use a term of the pharmaceutical art, complete bullshit. Antibodies are actually a lot more expensive to produce than small molecules. Getting reproducible purity and performance from them is a completely different problem than with small synthetic molecules, and once made, they're significantly harder to formulate, store, and handle. (That's one reason why Iressa, for example, is cheaper by a factor of ten than Erbitux.)

Here's a challenge for Robert Bazell: Let's pick a random college biology lab or two by riffling through a directory, and see if they could produce a steady supply of GMP-grade doses of Erbitux (or any other antibody therapy). Let's just call them up and ask them! Anyone want to put some money down on the results? Bazell goes on:

". . .Like all pharmaceutical companies, BMS and Genentech cite research costs and the huge risks involved in drug development (many drugs fail; clinical trials are expensive ... but haven't we heard it all?) as explanations for the high prices of their drugs. But the real reason is that market forces do not apply to drugs."

I'm sorry that we're boring him. Unfortunately, those explanations get trotted out over and over again because they're true.

"Few individuals purchase these drugs as they would a head of lettuce, say, or a refrigerator. In the case of cancer drugs, health-insurance companies are the consumers. For those lucky enough to have insurance, their plan might pay; and indeed, oncologists say that, surprisingly, so far few have balked."

Now we're down to that nondiscretionary spending issue. It's a real one, and it applies not just to pharmaceuticals, but to every sort of health care. People value their health very highly, as they should. And it's not that market forces don't apply to drugs, it's that no one seems to want them to. If they did so more directly, insurance companies would indeed start to balk, and drug companies would have to decide if they could lower the prices of their new therapies coming through the research pipeline. And if they couldn't, they would have to decide not to take them through clinical trials at all. We would end up with fewer therapeutic options than we have now.

But a therapy that no one can afford is arguably about the same as no therapy at all, so that's not as much of a tragedy as it sounds. And it's certainly true, as the article goes on to point out, that many of these new cancer treatments aren't as effective as everyone would like. Unfortunately, the only way to find that out was to go ahead and spend the money and time to develop them, and take them all the way through clinical trials and regulatory approval. That's when you find out that your wonder drug isn't as wonderful as you'd hoped. But I'll stop right there; I can hear Robert Bazell starting to yawn. Here he comes again:

"But even the current meager benefit will encourage all cancer patients to seek (these drugs), and those who cannot get them, because they lack health insurance or their plan won't pay, to feel cheated. And a marketplace with absolutely no price control will only propel the drug companies to charge even more for future drugs, some of which may offer even less benefit."

Why, exactly, would we enter the market with something that's demonstrably worse than what's already out there? I know that the industry gets hammered for me-too drugs, but those work at least as well as the existing therapies, and they need some selling point that lets you argue that they're even better. I can testify, from personal experience, that projects get killed all the time in the drug industry because we can't beat the competition, either what's already on the market or in clinical trials. I've helped kill them. This hasn't been as big an issue in oncology, but it does happen, and it's going to be happening more often.

And the answer to all this, presumably, is price controls. Hard to say, since that's where Bazell's article ends, but that seems to be the prescription. I can just imagine what kind of price a group of elected officials will decide what is fair. We'll be tied up, top to bottom. It's not clear to me - it never has been - how forcing companies to earn less money from their drugs will cause them to produce better ones. (Think how much Imclone could charge if Erbitux actually worked better than it does.)

If you want a more detailed take on the cancer drug pricing issue, go back a couple of weeks to Matthew Herper's article in Forbes. It covers the same ground, but in a clearer fashion. Ultimately, I think what's going to happen is that there will be patients who will not get some of these drugs, largely because they won't do very much good - or none at all. If we get past the treat-everyone-with-everything style in oncology, it'll force us in the drug industry to modify our projections of market size, and we'll have to come up with a way to deal with it. Pushback from the insurance companies and physicans is a better check on the drug industry, to my mind, than a Central Office of Pharmaceutical Pricing could ever be.

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June 17, 2004

You'd Think It Was An Election Year or Something

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Posted by Derek

There are several Canadian drug reimportation bills floating around in the House and Senate, and it's anyone's guess whether one of them will come up for a vote this session. The AARP has just weighed in in favor of S. 2328, sponsored by Bill Dorgan and Olympia Snowe - and if you're an elected official, the AARP is not to be taken lightly. Of course, neither is the drug industry, so we're set up for a fine Godzilla-versus-Rodan spectacle if the bill ever gets to the floor.

You can see the maneuvering going on. In addition to the AARP's statement, the General Accounting Office has released a study where they tried out dozens of online pharmacies. This one can be spun both ways, depending on where you stand: "US, Canadian Web Pharmacies Generally Safe" or "Many Online Drugs Fake, Study Says." Both headlines are accurate, as far as I can see. The GAO was ordering from as far afield as Turkey, which requires (no offense to the Turkish pharmacy distributors in the audience) a bit of a leap of faith.

I continue to think that the drug-safety argument is a long-term loser for the industry, because it's a problem that can be addressed. The Dorgan-Snowe bill has plenty of provisions to do just that, along with some to prevent drug companies from cutting down supplies to non-US pharmacies. The bill can be summarized as: We have ways of making you sell at the prices we like.

But do they have ways of making us discover and market drugs more cheaply? Or is that going to be our department? I realize that we in the drug business need faster, cheaper methods of finding new therapies - but you know, it's not like we lack incentives - green folding ones - to do that already. And we've been throwing substantial sums at those problems, without all that much to show for it. Would price controls have helped us, do you think?

No, the real arguments against reimportation are economic, and if you don't believe me on that one, believe an economist, Alex Tabarrok over at Marginal Revolution:

Price controls or other such plans such as reimportation may bring cheaper pharmaceuticals for a short period but we will then have a much smaller supply of new drugs forever. Only the shortsighted would buy that prescription.

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May 5, 2004

Price Hydraulics

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Posted by Derek

Just enough time to point out a rarity: a clear-headed article in the popular press about drug prices. Business Week has it, and it's worth a look. (Thanks to reader and colleague Joe C.) I'm glad to see the author acknowledge that efforts to control prices in one area often make them squirt upwards somewhere else.

Of course, the biggest example of that in drug prices is The Rest of the World versus the US. Holman Jenkins ran an article in the Wall Street Journal last week titled "Why Not Import Drugs From Fantasyland?", in which he, with gritted teeth, proposed the reimportation reducio ad absurdum: just take all US pharmaceuticals, toss them over the border into Canada, and reimport the lot. Ta-daa! Lower prices for everyone!

Mind you, many people would read that and say "Yeah! That's it! Under our noses, all along, the answer at last!" I just hope that there aren't a majority of this type in the Senate. . .

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March 23, 2004

Getting the Word Out, For Once

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Posted by Derek

Here comes a fine snapshot of the shape that my industry is in with the public. The Sunday-supplement magazine Parade did a cover story last weekend on medical research, and they commissioned a survey to go along with it. Here's the PDF of the results, obtained in a collaboration with ResearchAmerica, an academic/industrial advocacy group.

One question that particularly caught my eye was "Who do you think pays for most of the medical research done in this country?" 59% answered that the government does (and thus the taxpayers), and 9% said that the pharmaceutical companies do. The Parade article correctly pointed out, though, that industry actually does over half of the research by itself. Looking at that response, I can't help but see the footprint of the idea that I was dealing with here a couple of weeks ago, that NIH does all the drug discovery and we drug companies just swoop down, flap away with the swag in our talons, and feast on the profits.

Another answer that I found grimly enjoyable was to the question "How long do you think it takes, on average, to bring a new drug to market?" 29% of the sample answered 1 to 4 years, and 40% answered 5 to 9. Would that it were so! The record in my experience is just short of 11 years from discovery to regulatory approval. I know it's occasionally done faster, in special cases, but it sure runs slower a lot of the time, too. Makes me wish that they'd asked people to ballpark how much it costs, too. . .

I should note that the responses, overall, were very favorable toward medical research. People want more money spent on it, they support tax and regulatory reforms which would make it easier to perform, and so on. They just have no idea of who does it, or how long it takes.

So, what would it take to get the word out? I can just about sketch out a commercial in my head, just sitting here at home. No smiling senior citizens, no dogs, no athletes or running children. Just something like this:

CLOSEUP of some solution stirring in a round-bottom flask: "John Doe had an idea in his lab for a new medicine. . ."
MONTAGE of white-coated researchers pouring, pipetting, wheeling carts, etc.: ". . .and for once, this one seemed to work. His company got interested, and they made more of it. . .
PAN past a pilot-plant reactor sluicing out product: ". . .a lot more. His compound was tested over and over. Tested for how well it could treat its disease, tested for safety a dozen different ways to see if it could really be a drug. . ."
DISSOLVE to a physician dispensing a service formulation to a volunteer: ". . .and for the first time in John's career, something he invented made it all the way into patients."
TIME-LAPSE DISSOLVES of roomfuls of people fading in and out: "Then the real work started. Small groups of people, then hundreds, then thousands tried his compound in different ways, at different doses. It took years, and it took hundreds of millions of dollars. . ."
CLOSEUP of a pill rattling out of a container in slow-motion: ". . .to find out - that this wasn't going to be the one. Not quite."
DISSOLVE to head shot of researcher slowly flashing wry, determined smile: ". . .but John was still in his lab. Still working. And one day he had an idea. . ."
SUPERIMPOSE a closeup of another solution stirring in a flask, and fade to lettering: America's Pharmaceutical Companies: Where the Drugs Come From. "America's Pharmaceutical Companies. We'll never stop. We promise."

OK, I'm a professional chemist, not a professional PR man. But tell me, would an ad like that really do a worse job of informing people than the stuff we're already doing?

Comments (0) | Category: Drug Prices | Why Everyone Loves Us

March 4, 2004

Welding the Steering Wheel

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Posted by Derek

Steve Postrel of SMU sent along an interesting comment (which he mentions he hasn't fully worked through), one which takes us right back to drug pricing. Yep, to the cheers of some readers and the winces of others. He believes that my reply in the Feb. 22 "Reimportation's Just the Beginning" post doesn't quite add up:

Your correspondent argued that if the US Congress 1) forbade pharmas from price discriminating and 2) defended pharma IP against Canadian infringement then the Canadian government(s) would find themselves paying a higher price and American prices would be slightly lower. You disagreed, on the grounds that:

"The situation in Canada is: would you rather make a little off your drug up there, or make nothing at all? Companies choose the former - there's no way out. Duane's right that in a more rational situation, the balance between the need for profit and the need for the drug would allow things to reach some sort of equilibrium, but I'm not sure that the warm, windless political conditions needed for that state are ever going to exist."

This argument is incorrect given the reader's premise. If price discrimination were illegal, then the pharma's incentives would be transformed--it would have to set ONE price for both countries. Since Canada is so much smaller than the US, the marginal revenue from lowering the price to grab additional Canadian customers would quickly be more than cancelled by the lost revenue due to Americans paying lower prices. Result: The single drug price for both countries is a little bit lower than the old US price if the Canadians are willing to bargain, and the same as the old US price if the Canadians are not willing to bargain (they simply don't get access to these drugs).

The pharmas gain incremental revenue in the first case and lose incremental revenue in the second case. By prohibiting price discrimination, the US would be improving the pharma's bargaining position vs. Canada by credibly committing them not to cut a special deal. It's like visibly welding your steering wheel in a game of Chicken. The only variable here is whether the Canadian authorities would feel politically safe in just refusing their citizens access to new US drugs.

He's right that I didn't fully take in the premise from Duane's original letter, that price discrimination would be made illegal. I've had a couple of other readers suggest something like this, too. I guess my brain refused to process that one, since (from my prespective) right now we're living in a world where price discrimination has been made mandatory (by the countries getting the cheaper end.) It's quite a stretch. But once past that, I think that this argument follows. In an open market, I think that Canadian (and European) prices would come up, and US prices would come down. Steve goes on to say:

There is the potential for a loss of social welfare here, since some transactions benefitting both parties may not happen under the no-price-discrimination policy (if the Canadians are intransigent). This problem is even more severe in poorer countries where prices now are low not because of government bargaining tactics but because of low incomes. Forcing one price for Boston and Benin is going to eliminate transactions in Benin that mutually benefit the pharma and the Beninese patient.

Yeah, that's the flip side of price discrimination, all right. One of my correspondents in the industry once wrote me that we were heading for a world with two kinds of customers, those who won't pay and those who can't. Obviously you'd have to treat those two groups differently. Postrel's suggestion:

Ideally, then, I'd support a policy that made it illegal to price discriminate between Canada and the US, but legal between the US and Mexico or the US and Benin, and that cracked down on reimportation from the latter nations only. The Canadians aren't that poor; they're just using their collective-purchase mechanism to screw the US consumer (and taxpayer) by not paying as much of the research cost of drugs. The same goes for the rest of the OECD. It's time to weld the steering wheel.

I like this idea, as you'd figure. Practical difficulties exist - for example, there's already a problem with the discounted HIV medications going to sub-Saharan Africa. They're being diverted to the grey market in some cases. The incentive to do that will always exist, naturally, as long as there are multiple pricing tiers. But here's a bigger question: would such outlawing of price discrimination be enforcable under US law? And would it be acceptable under the WTO?

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February 29, 2004

More From the Me-Too Front

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Posted by Derek

Some interesting mail has come in after last week's post on comparative clinical trials. Reader C.B. that I spoke about here some time ago, but should have raised again:

"It seems to me that something else is being left out: not all patients respond the same way to any particular drug. . . Suppose that drugs X and Y are equally efficacious when given to the appropriate patient, but the population more responsive to X is smaller than that benefiting from Y. A simple comparative trial would suggest that Y was more effective because it assumes a single type of patient. On the basis of the results, people who should get X would only be allowed Y. . ."


It's true, there are a number of cases like this, and this is one of the traditional arguments for multiple drugs in a given class. I've made it myself. Given the state of the art, it's nearly impossible to untangle these things. In almost all cases, we have no idea why some people respond better to a particular therapy; it's trial and error. Clinically, these things are bottomless pits, so I think that comparative trials are going to be most useful in areas where a large number of patients respond to both drugs under study.


But we're in the process of inventing ourselves out of this situation. That's why all that money is being poured into pharmacogenomics - and quite rightly, although the end result is that many drugs are going to have their potential market size whacked into a rather more compact shape. The great thing about pharmacogenomics is that we're finally going to know who should take our latest drug, and we'll be able to find them and sell it to them. The terrifying thing, from the marketing standpoint, is that we're simultaneously going to find another group of patients, a potentially larger group with the same disease, who will never take that drug at all. It's going to be a better world, but one in which some business models (cancer therapy!) are going to have to change.


And in a similar vein, reader R. D. writes:

"I have yet to see someone make a rational case for why me-toos are bad. At most, the argument seems to be that if pharma would just stop spending all its time coming up with me-toos, we could get around to curing cancer and parkinsons and stuff. I think that's bunk. You and I both know that any pharma that could come up with cures for things like cancer or parkinsons could start their own mint. The reason they haven't is because it's HARD, not because they prefer to make less money by painting their old pills purple and trying to convince everyone that they're new and improved."


Purple? What on earth can you be talking about? No, the argument he's talking about is one that (in this form) I don't have too much time for, either. The me-too drugs are there to keep the coffers full to pay for the research that doesn't work out, and to tide companies over the dry spells. I can see the objections to the areas where there are six and eight therapies all piled up on top of each other (for example, does the world really need Crestor?) But if Crestor makes money, some of that's going to pay for something new.


And the reason for that touches on another favorite whipping boy: marketing and promotion costs. Keep in mind the inverse relationships between advertising costs, novelty, and the chances of success. A new drug that does something no one's ever seen for a major disease previously thought untreatable - isn't that what makes everyone happy? How much, comparatively, would have to be spent to market such a therapy? There's no competition - it would sell itself! But what are the chances that any of us are going to find and develop such a wonder?


(OK, some of you are saying "Viagra! First on the market, first in the category, promotion out the wazoo!" But keep in mind: no one was sure that men would actually go to their doctor and admit their symptoms - thus the advertising blitz. And Prizer knew, with all the other companies working on PDE subtypes, that competition would be coming soon. They needed all the brand recognition that they could buy.)


Meanwhile, contrast a first-ever wonder drug with, say, the umpteenth statin. It's a crowded field, and you have to spend like crazy to make headway. The thing was a bit lower-risk to develop, since you knew that the rationale was there. But your cost-of-sales figures are going to be uglier, and nothing's ever going to help them.


My point is that a company needs both of these kinds of drugs. You can't hope to live only on the first kind, because they happen so seldom and so unpredictably. And no one's trying to live only on the second kind, either, because you've traded higher costs their for relative security. Everybody developing one of the first class wishes they had some of the second to tide them over. And everyone with drugs in the second class is looking for one from the first.

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February 26, 2004

Putting A Price on Proving It

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Posted by Derek

I've already had some reader mail (see here) about this article in today's New York Times. It starts out looking like a real pharma-bashing exercise. Up to a point, it is - and up to a point, it's deserved, too. But in the end it's a more subtle piece, not that you'd guess that from the opening paragraphs. (I have my own solution to the problem the article raises, and it will bring joy to no one. Read on.)


The issue is comparability of drugs, especially drugs with the same broad mechanism of action. Look at all the statins or antiinflammatories on the market: is there one that's better than the others? Of course, if you listen to the companies that make them and promote them, the answer is clear. Their product is best! But, as in any other industry, that's not the most reliable guide.


The article uses the example of two marketed forms of the protein erythropoetin, one from Amgen, and one from Johnson and Johnson. J&J's product is about one-third the cost of Amgen's. Is there any reason to pay for the more expensive option? Medicare has asked the National Cancer Institute to run a study to answer that question, but (as the Times points out early and often) there is a provision in the latest Medicare legislation that keeps the program from even using such evidence of functional equivalance in its payment decisions. As you'd imagine, Amgen is arguing that this provision makes the planned Medicare/NCI comparison study a moot point. Why compare?


This would seem like an easy call: the drug companies are slamming the door on something that might cut into profits. Hey, I work here, and I'm sure that that was the motivation, too. But I should add the standard comparisons to other industries at this point, though, and note that car makers are not required to prove that their latest models actually work better than the older ones, or better than the competition's. Nikon doesn't have to run head-to-head trials with Canon, nor Gateway with Dell.


I like those examples, but I realize that there are some other considerations. For one thing, we're talking about public funds here, right? Partly, yes, although the managed-care corporations have a big interest in this, too. I'd add that the government spends a lot of money on goods and services that are not required to be comparison tested (but are selected on the basis of lowest bid.) We'll get back to that topic in a couple of paragraphs. The other big factor is that my car and computer comparisons are discretionary purchases. Health care is treated differently. It's an emotional issue, a life-and-death issue, and it's always going to be held to a different standard than other businesses.


So, let's test! But as the article makes clear, it's not as easy to test these things as you'd think:


. . .Rarely are such studies able to answer all the most important questions. The National Cancer Institute has been mulling the appropriate design for the Aranesp-Procrit trial for nearly two years and will probably need another year before starting the test. . . In the end, more than one trial may be needed, Dr. Feigal (of NCI) said.


Dr. Feigal declined to estimate the cost or size of the eventual trial or trials, but similar tests have cost millions of dollars. Indeed, for comparative trials to be the size needed to measure true differences between drugs, they generally need to be large, lengthy and expensive.


Indeed they do. The article goes on to talk about the hypertension drug comparison study that got such play in the media a few months ago - not least from the New York Times itself. It hasn't settled the question, though. There are still real doubts about which therapy is most effective (for one thing, because patients in the study didn't take more than one type of drug, although in the real world this is a common mode of treatment.) This was a huge study already, and adding arms to assess combination therapies would have bulked it up considerably.


Still, I'm in favor of doing some head-to-head tests, because I think that there are several therapies out there that don't offer much for their price. (I'm looking at you, Nexium!) Here's my proposal - and yes, I'm going to go ahead and treat the drug industry unlike any other. If a company wants to bring out a me-too therapy, it will be required to show evidence of whatever factor differentiates it from the existing agents. The company gets to choose the battlefield: more efficacy? Quicker onset? Fewer follow-up visits to the doctor? Whatever. Pick a reason you're going to promote the drug, and come up with data to back it up. I think we'd end up with fewer me-toos on the market, but we'd lose fewer of them than many critics might think. Many times, drugs that look the same can indeed act differently. Admittedly, it would take some careful clinical work to bring some of the differences out, though.


This change would require a major shift at the FDA. For existing therapeutic modes, you'd need to switch at some point from placebo-controlled trials to competition-controlled trials. Perhaps you could run an initial test-the-water placebo control (after all, these are drugs that have a high chance of working), and from then on you run versus the competition. There are complications - which competitor, for example. But it's possible to do, and it's an idea that has been talked about for a long time.


And who's going to pay for all this? Well, you are (if you're a patient, that is.) Believe me, we're going to pass those costs on, and pronto. Raise the regulatory barrier, pay more money: it's a law of nature. And the lost revenue from the me-too drugs, which have higher chances of success (but still aren't sure things!) will be passed on, too. I think that there are still savings to be realized here - but they're not going to be as big as they seem.

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February 23, 2004

One Of Us Is Hallucinating

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Posted by Derek

I've been involved in the comments section of another blog, a discussion of pharmaceutical prices which took off from the posts over here. Things have taken a turn that I didn't expect, so I thought I'd run it past the readers of this site. There's a specific misapprehension that I'm running into, one that I've never quite seen before. Am I right to be puzzled? Read on.


Things got underway when the blogger Prometheus 6 picked up a link to my recent drug and research cost pieces from Sebastian Holsclaw's site. (There are a number of comments over there, which are rather easier to deal with than the ones we're coming to.) P6 started off with a blast at the concept of using imputed interest rates to calculate drug costs. We both reference Marginal Revolution on that one, but he's not buying it.


The discussion then split up into a couple of issues. The first was the whole imputed interest / opportunity cost issue, which ended up in another post. Sebastian Holsclaw reappeared to take P6 to task in the comments section, but I don't think that anyone is going to convince anyone else on this issue. This part is worth reading if you want to see some of the difficulties people can have when discussing economics (no doubt my fellow Corantean Arnold Kling gets this kind of thing all the time.)


The other issue arose from P6's final contention in that initial post above. He finished up his take on research costs by saying that "Most of the money spent was federal money." That, as you can imagine, set me off pretty quickly in his comments section. Here's some of what I wrote:


"As for your second question, there are a lot of people claiming that most new drugs are really straight from the NIH, or some such. This is not true. Even if you get an idea for a drug target right out of a paper in the Journal of Biological Chemistry, from an academic lab funded 100% by government grants. . .even then, you're still looking at, on average, that 800 million dollar figure to find a drug and develop it. The amount spent in grant money pales, imputed interest rate and all.


To pick a recent example, the University of Rochester did not develop a COX-2 inhibitor, although they discovered the COX-2 enzyme. Drug companies did - and a majority of companies that tried to make one failed, and all the money they spent to do it is gone.


Academic labs rarely, if ever, come up with a compound that is ready to go to clinical trials. They're doing academic research, as they should: broad fundamental studies that point the direction you should go in to spend your 800 million.


When a drug company does the fundamental research part as well, the costs are even higher."


This spilled over into yet another post, and here's where I've come to realize that I'm not making any headway. P6 seems to believe that most pharmaceuticals should be in the public domain, unless every single bit of every idea along the way was generated inside a drug company. Here's some of his take:


"Let corporations have process patents on the ways they've developed to mass produce the drug, but if it was developed in government funded research the drug itself should be in the public domain."


"My reasoning is, the risk pharmaceutical companies undertake is in creating the processes whereby the drug is produced, packaged and distributed safely (I include testing in this). They are entitled to a process patent. But in most cases the company neither discovered the compound nor ascertained its primary effects."


What's happening here, I thought, is that he's assuming that academic labs produce drugs. And drug companies, it seems, just test them some more and find ways to manufacture them. What a life we'd lead then! So off I went again, in his comments section:


"Unfortunately, you are wrong. In the huge majority of cases (well over 95%, off the top of my head), the compound was discovered by the drug company. Academic labs do not, as a rule, discover drugs. They are not in that business. They discover biological pathways, new behaviors of known proteins, interesting biochemical regulatory mechanisms. Interesting stuff, valuable stuff. But they do not discover drugs. I can think of almost no exceptions. . .


That's how we can patent the compounds, you know. If anyone else has made a compound before and described it in any way, we cannot own the chemical matter by a patent. And we will almost never go ahead with a project unless we're absolutely sure that we own the chemical matter.


Whoever told you otherwise is gravely misinformed. You would do your source a favor by correcting them."


P6's most recent reply to all this begins:


"Sadly, I have no source. I just know what is done in academic research and give it more weight than you."


Well, we can finally agree on something: that's sad, all right. My first impulse was to have him show me some of this academic research that lead right to a new drug, but I wanted to take this over to my readers first, for either irritation or entertainment value as the case may be. As I mentioned, I haven't come across this delusion - that drug companies don't actually discover drugs - at quite this level of virulence before. Is this something widespread? And if it is, how did we in the industry let things get to this state?

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February 22, 2004

Reimportation's Just the Beginning

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Posted by Derek

Here are some interesting points raised by reader Duane Oyen, from e-mail and quoted by permission


"I think that any reimportation scheme has to be done on the basis (honest basis, not demagogic political windbaggery, which is where it usually ends up) of free trade- thus causing ME to "get to" YOU- because of the need to eliminate the egregious price discrimination that currently exists. The safety argument, as you state, is a legitimate reason to be cautious, not forbidding. Thus Canada is the perfect guinea pig- even citing NAFTA as the rationale. If a drug company sees that the Canadians are playing price control games with their product, they should be perfectly free to leave that market without having their patents violated, and the US should enforce the IP.


Eventually, the loss of market volume by the company, and the loss of treatment efficacy by the country, will cause the transaction prices to float to a more appropriate level. The ultimate price movements in smaller markets such as Canada will be less significant, as well as relatively slow, giving the lie to those politicians (leftist inheritance limo lib Mark Dayton, bawl your office) who claim that reimportation is a panacea for rising medical costs."


The situation in Canada is: would you rather make a little off your drug up there, or make nothing at all? Companies choose the former - there's no way out. Duane's right that in a more rational situation, the balance between the need for profit and the need for the drug would allow things to reach some sort of equilibrium, but I'm not sure that the warm, windless political conditions needed for that state are ever going to exist.


He goes on to say, in a discussion of what the future of drug pricing holds, that:


"I simply do not see a collapse in drug R&D and discovery. I see relatively significant changes in the business models, but they are already occurring regardless, as more and more of the sclerotic behemoths look to entrepreneurial startups and university spinoffs to feed their pipelines, and drug treatment follows network broadcasting into "narrow-casting". If market changes were established that reduced the ability to internationally price-discriminate, we should do three other things at the same time- a) make adjustments to patent laws (Forbes has made some good suggestions on this over the past couple of years); b) change the NDA process to reduce qualification costs and share risk more fairly (which means that ATLA attorneys have to be reined in a bit); and c) strengthen orphan drug incentives; perhaps even encourage more industry participation in NIH grants."


These are good points. I don't think, though, that there are enough startups and university ideas to keep everyone's pipeline alive - at least, not yet. The in-licensing game is very competitive, and has been for some years now. But he's right that changes in patent law and regulatory approval are basically going to have to take place eventually, and it's time that we starting thinking about what these should be. The idea of strengthening orphan drug-type incentives is floating around in several places, too. This week I'll be talking about a paper that's just appeared that argues for some changes like this in detail.


In coming years, we could be moving to different ways to reward drug discovery other than patent exclusivity and pricing power. It'll be a rough transition, too. The industry had better starting thinking about these issues seriously, or we're going to be dragged, biting and clawing, in directions not of our own choosing.

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February 15, 2004

Drug Prices and Costs - From the Mail

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Posted by Derek

Here are some of the responses to the recent posts on drug prices and research costs. First off, from Dave S.:


"I'm a skeptic on the idea that the proceeds from the temporary legal monopoly represented by a patent is, in fact, used by pharmaceutical companies to finance R&D. Yes, I know it stands to reason and it's the prevailing wisdom, but is it true? One way to investigate this would be to see how the companies themselves view R&D. This, in turn, may be determined by how real R&D expenditures vary with real revenue. If, as real revenue rises, R&D expenditures rise either proportionally or faster, it would be a reasonable conclusion that patents do support R&D. If, however, R&D expenditures grow more slowly than revenues or not at all, it would be equally reasonable to conclude that the prevailing wisdom is wrong and that patents do not in fact support R&D but just raise profits, which nice as it is for the companies involved is not the constitutional purpose of a patent."


Interesting point. I'll see if I can round up some figures, but I'm not sure how good they'll be. Like any other industry, pharma companies do all tricks with earnings statements that they possibly can, in order to tell Wall St. a coherent story. And there's also the tendency to think, as the money comes in, that "Hey, we don't need to increase research that much. Look how well we're doing with what we have!" Conversely, on the way back down, as revenues fall, R&D isn't always the first thing to get cut. By that time, it's clear that the only thing that will save the situation is for some new profitable breakthrough to emerge from the labs. But let's see what the numbers say.


There have been several letters along the lines of this one, from Mark S.:


"What I find baffling is that no one is pointing out who the enemies really are. Americans are subsidizing the world. Subsidizing AIDS drugs in Africa may be defensible, but subsidizing cholesterol drugs in Europe isn't. I'd like to see some information about what would happen to American drug costs if Europe (and Canada) were just cut off. Obviously some money is getting into pharma coffers, the question is how much? What sort of profits are European Pharmas making in America vs Europe (i.e. are they extorting Americans, too)?"


Well, the larger European companies depend on revenue from American sales, too, I can assure you of that. As for cutting off the European market, it would be a difficult, although intruiging, thing to calculate. I don't know of any company that publicly breaks down cost-of-sales for the two markets, though (although I'm sure that these figures are worked out internally.) Marks' suggestion:


"While not a big fan of regulation, I think it would be fair to regulate drug prices in America this way: The cost to Americans is the lowest cost negotiated with any other country. It doesn't cap drug costs, it just evens them out. Drugs could cost anything, but everyone would be paying the same amount for the same product. Pharmas are free not to sell to any country if doing so would lower the US price. They are also free to negotiate different prices for different countries, the US would always match the lowest."


I think that this would fall victim to a sort of Gresham's Law - bad prices would drive out the good. Countries with national health plans already can use their muscle to negotiate prices that couldn't be sustained across the worldwide market - "You want to make a tiny amount of money here, or nothing at all?" As long as the US runs a different sort of market, things wouldn't mesh too well. Here's an approach to that problem, from reader Clark H:


"If the US, the last of the free markets, ever starts allowing reimports or does "National Bargaining", I would suggest that the Drug Companies start the bargaining BEFORE they have finished their R&D. When they still have leverage. The problem with any product with a large up-front cost and relatively small operating costs is that it is at a huge disadvantage bargaining with a small number of customers after all the costs are "sunk". The customer knows the hand of the supplier. The supplier can't walk away because any positive cash flow is a good thing at that point. The drug companies should get to phase 2, when they know roughly what to expect (after all they are designing the phase 3 endpoints), and then bargain. If the countries aren't willing to pay an adequate rate, they walk away having spent only the cost that would otherwise have been spent. Not a perfect solution, but. . ."


I think that there's something to this, although the Phase III failures would throw a wrench into the works. Of course, that's what they do now, actually. I wonder, though, if what would happen under this plan is that countries would just apply a standard calculation for what they thought the Phase III trials and regulatory approvals would cost, which would take things right back to the "already knowing the hand of the supplier" stage.


Well, the mail on this topic doesn't show much sign of letting up, so we'll keep it open and revisit it in a few days. Brainstorms appreciated.

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February 12, 2004

More on Prices, High and Otherwise

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Posted by Derek

The key questions raised in the e-mail I quoted in the last post are: is it fair to fund drug research through high prices on drugs? And especially, is it fair to do so by raising prices on individual drugs, rather than across the board?


My answer to the first question, as you'd guess, is "yeah boy!" I have some disagreements with the assumptions that Nick H. is making. For one thing, the money spent on research isn't necessarily an "investment cost" in the way that some might think of it. Now, overall, it's true that we expect a return on research money, so you could classify the whole think as an investment that way. But research (unlike, say, bonds) involves a lot of sunk costs. Once spent, they can't be recovered or converted back to cash. The investment equivalent is a stock that goes to zero. A drug company's "investment portfolio" consists of a bunch of Webvans and the occasional Microsoft.


But that analogy isn't quite right, either, because it gives too much credit to the individual drugs. Microsoft can, by its own actions, try to preserve its profits indefinitely (and boy, don't they ever.) But every drug is a wasting asset, essentially. The key difference is intellectual property. A drug's patent will always expire after a few years, although companies will try every contortion they can think of to delay the day. The longer the R&D&A (A for approval!) process takes, the shorter the lifetime left on the patent. It is very common, and has been for some years now, that a drug chews up more than half of its patent life before it ever makes it to market. So every drug is born onto the market from a deep pit of sunk costs, and has a relatively short time to make them up (and pay everyone's salaries, and fund the current research projects, some of which had better pay off to keep the whole thing going.)


On to the second question. I think that Nick's main objection is that prices get raised on individual drugs, rather than across the board. His point can be illustrated by Abbott's price hike on Norvir, a drug that has (from their perspective) been underperforming. If Abbott needs more money, why should only the HIV patients pay up? (I know, they've assured Medicaid, etc., that the price hike doesn't apply to them - but some HIV patients or their health care providers are going to pay more, though. Otherwise, why raise the price? Unless it's just to make Norvir more expensive for the competition, which is one possibility that can't be shaken off.)


One answer - not the best one- would be to turn the question around: why should someone who takes one of Abbott's other drugs have to pay for the problems they've having with Norvir? This argument doesn't hold up too well, though - after all, we pass on the research costs of the whole drug portfolio to everyone. Why not pass on the sales shortfalls?


Well, in a larger sense, we do. But I'd say that companies - and not just drug companies - raise prices where they think that they can, when they think they can. A company may decide that it's feasible to raise prices in one market, and not another. To use Nick's supermarket analogy from the previous post, should we require all the products in a supermarket to have the same profit margin? I would actually expect a supermarket to raise its profits by increasing prices on the items it thought would be most likely to bring in the most increased revenue. (That probably wouldn't be the bread and flour, though.)


This is what the marketing types call "pricing power," and it varies a lot. A drug company has quite a bit of it, during that time its drug are patent protected. Countering that, of course, is the negotiating clout of Medicare, HMOs, and other bulk purchasers. That's the general tug-of-war of the market (making some allowances for Medicare.) Really countering a company's pricing power, outside the US, is the governmental price-setting ability of national health plans. That's where the market mechanism is breaking down, to my eyes. Many people see intellectual property laws as a thumb on the scale in favor of the drug companies. But at least patent protection goes away.


(There's a lot of interesting e-mail coming in on this subject, and I'll bring up some of the points people raise in another post. I should mention that Nick, the person who starting this topic off, has a blog of his own, too.)

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February 11, 2004

The Contact Sport of Cost Accounting

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Posted by Derek

I have just enough time to post an interesting e-mail, from Nick H. in the Netherlands, responding to the links I posted the other day about research costs.


"I agree that accountants calculate costs in the way described, but accountants do a lot of accounting in ways which aren't always quite fair to all stakeholders. I have to disagree that all research costs should necessarily be paid fully by the buyer(s) of a limited number of products. The money spent during research/on research could also be seen as an investment cost. It is quite normal to defray part of investments by increasing the price of product X, it is just as normal to defray part of those costs in other ways (e.g. lower dividends, accepting lower profits or by raising the costs of all products to a lower extent). Saying this is the only (fair/possible) way to do things just isn't cutting it.


. . .the real argument which we can find buried way back in the mists of time is why a limited number of customers should pay for all costs incurred for no other reason than to increase business returns as well as increasing those returns. If your supermarket puts up a new building you'd be well miffed if they raised the price of ONLY the bread and flour to defray the building costs. Especially if the raised it to the extent needed to pay back all of the building costs within 10 years. It would be seen as unfair and wrong by pretty much everyone anywhere that this supermarket would hold just this limited (local) part of the population at ransom by suddenly raising the price of an essential condiment by a large margin in order to pay for what ultimately is mainly to the benefit of the supermarket itself. I hope you agree that there is a grain of reason in the madness of suggesting that costs should be divided more evenly over the various stakeholders."


I don't agree with all his points, but I thought I'd put them out there to stimulate debate. I'll post my response to these tomorrow. The phrases "intellectual property" and "sunk costs" will appear prominently.


(I should mention that my post-a-day schedule will probably be hitting a few potholes over the next few weeks. I'll keep the content flowing (I like doing it!), but there will be weeks when only three or four new posts appear.)

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February 8, 2004

Darn Those R&D Costs, Anyway

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Posted by Derek

I wanted to pass along a couple of recent articles that address drug pricing and research costs. It's a subject that attracts nonsense like a cloud of gnats; every so often you have to shoo them off. Here's a fine post from Alex Tabarrok at Marginal Revolution:

In 2003, Joseph DiMasi, Ronald Hansen, and Henry Grabowski published an important paper in the highly-regarded Journal of Health Economics that estimated that the average cost of developing a new drug was around $805 million dollars. Hal Pawluk at Blog Critics repeats some nonsense from Public Citizen to claim that high research costs for pharmaceuticals are a myth and that this paper in particular is part of a conspiracy of pharmaceutical companies to raise prices. Frankly, the comments of the critics are laughable but not everyone sees the joke so I will explain. . .


And his explanation is a good one, right on target. I can speak from experience that this is exactly the way that costs are calculated in the industry, and quite rightly. Check it out and see what you think.

I can also strongly recommend this column from the Wall Street Journal's Holman Jenkins. It's a broadside against the dime-store populism that's turning up in Presdential campaign speeches. Here's a sample:

If this column sounds like one four years ago, that's because Democrats are running against their usual list of "enemy" industries. The party's standard trope is that you're being denied things you need and deserve because enemies are keeping them from you, cheap drugs being today's case in point.


Let's make sense of the industry once more for a Democratic presidential cadre now reaching a high pitch of populist dudgeon. There's a reason analysts, investors and pharmaceutical reps talk about a "pipeline." In one end goes a bunch of money, and out comes a dribble of products years later. The metaphor is also useful in understanding drug pricing. Whatever comes out the end, whether it's nose drops or a chemotherapy drug, is priced at whatever level will allow its maximum contribution to recouping all the money that went into the front end of the pipe.


Just so. It's one of those darn businesses, which, As Is Well Known, are invariably run as a conspiracy against the little guy. (The huge population that actually works for these operations are, by definition, not little guys, it seems. Not after they issue you your Monopoly-man top hat along with your employee ID card.)

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January 29, 2004

From Each According To Their Creativity, To Each According To Their Difficulty?

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Posted by Derek

Alex Tabarrok over at Marginal Revolution is proposing an interesting idea: He's suggesting that the lifetime of a patent be adjusted for the R&D costs that went into the ideas behind it. Things that took little effort would have a short term until expiration, while those who went through expensive slogs would have a better chance to recoup costs.


That's an idea that had never occurred to me, by which you can tell that I'm not an economist. And I can see the appeal - but I can also see the potential for abuse. For a while in graduate school, I shared an apartment with a fairly doctrinaire libertarian. We had quite a few discussions, as you can imagine, but I found that they often fell into the same low-energy state. He would point out the benefits of some scheme, and I would agree in the abstract. But I'd then imagine how it would have worked out in the northeast Arkansas county I'd grown up in. Theory and practice tended, in my view, to diverge.


As I think they would here, too. What I think this would do is create a powerful incentive to hocus one's R&D figures. In the drug industry, each extra year of patent protection can well be worth hundreds of millions of dollars in revenue, which is an incentive indeed (with hot fudge and extra sprinkles on it.) It's not like our drugs come cheaply to us now, but I can see that for an anticipated blockbuster, ways would be found to ensure that the patent racked up the longest possible life. You already see that happening at the back end of patent terms, as the constant battles with generic companies illustrate. Every possible reason is trotted out for why a given patent is invalid, and every possible means to preserve or extend the patent's term is invoked in response.


Frankly, we have enough trouble working out how much things cost in this industry already. I mean, we can see how much money we're spending, but assigning specific amounts to specific projects is harder than it looks. The number of people working on a project fluctuates constantly, for example, and many of them have other simultaneous responsibilities. Many supplies are bought in bulk and shared between projects, and all the analytical work is done on large capital-budget machines that are used constantly for everything. I've seen all sort of schemes to track costs by project, but all of them have a voodoo component.


Another problem is that the big money-making drug is only one part of a large patent, which would typically exemplify dozens or hundreds of separate compounds. Naturally enough, some of these took a lot more effort to discover, make, and test than others. If keeping track of costs per project is tough, costing things out by compound would be insane. Then there's the problem of multiple patents protecting the same drug. You'll see a composition of matter patent, a method-of-medical-treatment patent, several patents on specific formulations. . .when a generic company comes after you, these things are used as firewalls and are fought out as separate issues. And these would all have different R&D cost structures, although I've no idea how you'd figure some of them out, and thus presumably different patent lifetimes.


No, I think that passage of such a law would turn out to be the Cost Accountant and Patent Lawyer Full Employment Act of 200x. As I said, I can see the theoretical appeal. But in practice, I think that this attempt to reward the costs of innovation would only create more expensive makework, none of which would have anything to do with research itself. We've got too steady a supply of such as it is.

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January 14, 2004

The Pricing Weapon

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Posted by Derek

I've been meaning to get around to the subject of Abbott's HIV protease inhibitor, Norvir (ritonavir.) Actually, the subject I've really need to get around to is its price, which in December went up by about a factor of four. That's a pretty steep move for something that's been on the market for seven years, isn't it?


Norvir is a protease inhibitor, one of many these days. It was a front-line therapy when it came out, but now it's settled into an unusual role as a supporting player. When added into other "cocktail" treatment regimens for HIV, Norvir seems to make everything more potent. There's no voodoo involved here, actually. Norvir turns out to be a good inhibitor of one of the liver enzymes (CYP3A) that is responsible for metabolizing many other medications.


That effect is enough to stop development of some drugs, to tell you the truth. No one is going to take something for a lesser illness that's a CYP3A inhibitor, because it'll make the blood levels of so many other drugs go haywire. But for HIV, especially when Norvir first came out, all sorts of side effects were tolerated. And over the years, the liver enzyme inhibition has turned from a bug into a feature. (It's still something to look out for, though, if a patient taking Norvir also takes things like sidenafil (Viagra) or a statin - see this PDF for details.)


But there's a side effect of the side effect. Norvir's taken at lower doses than other anti-HIV drugs, because it's only partially being given for its intrinsic protease inhibition. Back in 1996, as a stand-alone therapy, it was given at 1200 mg/day, which cost about $20. Today, as an adjunct to other therapies, it's given at about 100 mg/day, with a corresponding decrease in Abbott's financial expectations.


Thus the price hike, or so one has to figure. Abbott has said that the new price "better reflects the current market value of Norvir," and they point out that newer therapies run in the $20/day range, while Norvir, even at the new price, will be $8.57/day, at a 100 mg dose. Of course, that would make the original 1200 mg/day dose pricey indeed, but you don't see Abbott mentioning that. (Here's their letter to physicians (PDF) on the issue.)


Companies can charge what they want to for their products, or at least they should be able to. So Abbott is completely within its rights to raise their price to try to recoup some of what they originally thought Norvir might bring in, although you wonder if the bad press doesn't cancel that out a bit. But there's another explanation that looks even less appealing: Abbott has a more recent combination HIV therapy (Kaletra) that has Norvir as one of its components.


The new Norvir price now makes other combination therapies more expensive than Abbott's own Kaletra. So in their way, they may well be trying to compete on price here, but by raising the price of their competition rather than lowering their own. That's a rough way to do business, but given the state the drug industry's in, it wouldn't surprise me if that's exactly the plan. Profits are where you find them. I'm sure that Abbott's competitors have already made up their minds about what's going on.


So, is it right to do this sort of thing? This is where arguments about drug prices diverge from arguments about, say, the price of pearls, chocolate chip cookies, or ski equipment. There's an unavoidable moral aspect that comes into the discussion when you're talking about patients with a deadly disease. It wouldn't be nearly as big an issue if Pfizer, say, racked up the price of something that hypothetically made Viagra work better. But HIV's different.


On the purely pragmatic plane, I realize that I just said up there that I think that companies should be able to charge what they want to charge. I'll stick to that, but that doesn't mean that it's always a good idea for them to go ahead and do it. Abbott needs to realize that its actions look - no matter how strenuously they deny it - like an attempt to body-check its competition by making everything more expensive. And they need to realize that we pharmaceutical companies might not have the pricing power that we once did. If we keep doing this kind of thing, we're going to end up with no pricing power at all, and people will be clapping and cheering while we all tip over into the trash. Think about it, guys.

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January 7, 2004

Good Sense Wins a Round

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Posted by Derek

Regular readers will know that I often rant about pharmaceutical price controls. The issue of Canadian drug reimportation is what usually sets me off, but that's far from the only border where pharmaceuticals can be profitably arbitraged. Take the countries of the EU, for example. There's no central EU health plan (not yet, anyway - can you imagine what an empire-sized bureaucracy that would be?) Each country's national health plan negotiates its own price. And some of them are indeed lower than others (Spain, for example.)


So, what happens is just what you'd expect would happen. People try to buy in the cheap places and sell in the more expensive ones, which activity has probably been going on since the goods involved were spear points and mastadon tusks. The middlemen are happy; the drug companies aren't. The only way they've been able to do anything about it is to try to restrict the amount of wholesale stock that makes it to the lower-priced markets, which is the same thing that we now see happening here with the Canadian pharmacies.


Bayer got dragged into court a few years ago for doing just that, and they lost their case on antitrust grounds. Fines ensued, and Bayer appealed to a higher court, which ruled in their favor in 2000. But another appeal went through to the European Court of Justice, which has just ruled in Bayer's favor again, to the delight of the pharma industry. Bayer's comment was particularly pithy: they expressed relief that they "are under no obligation to supply the entire European market from the member state with the lowest state-regulated prices." Just so.

It's not not just the pharma industry that applauded this news - car prices are just as out of whack across Europe, for example, and the same sort of games are played. As you'd expect, I agree with the court's decision, too. I'd much rather live in a world without price controls at all, but if we're going to let governments restrict the price of goods, then I think we should give the producers the option to restrict their supply. Trying to have it otherwise is like legislating sunny weather and free ice cream, which would be vote-getters, too, come to think of it.

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July 22, 2002

More on Drug Prices

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Posted by Derek

I can strongly recommend this piece from Robert Bartley in the Wall Street Journal today. It's a clear-eyed look at the issues involved.

There are a couple of misconceptions in it, though. He mentions an "acquisition" of Imclone by Bristol-Meyers Squibb, but their deal was always about clinical candidates, not acquisition. BMS did make a large equity investment in Imclone (well, at the time it was large,) but not enough to have control of the company. That was left in the strong, capable hands of the Waksals.

Bartley also proposes that some drugs be allowed onto the market after Phase II trials are complete, but before the larger (and longer) Phase IIIs. It's easy to see why proposals like this come up, since that's one of the few places in the whole drug business where you can push costs down.

Bartley states that Phase I and II trials "establish safety and offer some evidence of efficacy" as opposed to Phase IIIs. Unfortunately, it's often the other way around. Getting through Phase I does indeed show that there aren't any immediate toxicological issues. And Phase II trials, if well-run, can be enough to establish efficacy. Phase IIIs, though, can be just as much about safety as they are about efficacy. As you expand the patient population and the length of the study, problems that never even broke the surface during the earlier trials can surface.

So, I'm afraid that putting drugs on the market after Phase II would require some sort of tort reform. The sorts of unpleasant surprises that show up in Phase III would be now be showing up in your patient population. And then the liability lawyers would swoop down with eager squawks, pick us clean, and leave our bones bleaching in the sun.

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July 19, 2002

The Dismal Science of Drug Prices

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Posted by Derek

I'm a little disconcerted by Instapundit's endorsement today of the Wellstone drug reimportation bill. My position on this is closer to Andrew Sullivan's (and the reader he quotes here.)

That is to say, I believe prescription drugs aren't correctly priced in Canada and overpriced here. They're underpriced in Canada (and Europe,) and overpriced here to help make up for it. We can argue about individual drugs, and we can argue about just how much one side of the issue balances the other. But I've seen at first hand the amount of money that gets poured into projects that don't lead to a marketed drug, and that money's got to come from somewhere.

That's every single project I've worked on in my 13 years in the industry so far. No, that's an underestimate. I don't think that any of the projects to develop a completely new molecule at any of the companies I've worked for in the last 13 years has made it to market yet. I'm racking my brain, but I can't think of a single one. There are a couple of close calls in there, and a couple that look like they're going to make it, but so far, nothing. That's an insane amount of cash that we're never going to see again, and it's obvious that you can't run forever like that. What's going to give?

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