An Opportunity For A Pharmaceutical Policy Experiment?
The Toronto Globe and Mail ran a story ($$$ subscription required) a little while back about cancer patients treating themselves with DCA, the drug which, according to reports out of the University of Alberta shows promise as a cancer treatment, based on its effectiveness in lab rats. Orac, who blogs at Respectful Insolence, ran a post here cautioning against getting your hopes up too high, based in part on the fact that it's easy to cure cancer in rats. If cancer were just a disease of rats we'd have wiped it out by now. DCA hasn't been tested in human as a cancer treatment, indeed hasn't yet been put through clinical trials as a cancer treatment. Still, and not surprisingly, cancer patients for whom all other treatments have failed are eager to give DCA a shot.
The complicating factor about DCA is that it's been around for a long time, and is now off patent. That means that if it's discovered that a particular dose of the stuff is effective against cancer, anyone who wants to will be able to manufacture it. That in turn means that there will be a lot of competition in the market supplying it - all the generic drug firms will make their own version - but it also means that nobody would be able to recoup the costs of the research necessary to find out whether it really does work on humans. And as Orac reminds us, over the years there have been lots of breakthroughs in cancer treatment in the lab, most of which turned out not to be effective in people. But even if it does work miracles, somebody has to pay for the testing, and Big Pharma is taking a lot of flack for not being willing to fund clinical trials on a drug that there's not just no hope of making a massive profit on, but not even a hope of recovering research costs on.
I'm eventually going to get around to making a suggestion about the economic issues involved, but first let's look at some background, from the Globe.
The story in question is by Anne McIlroy, published on 1 June / 07, and headed:
OK, so big pharma won't fund research into it. But what about the generic manufacturers? One thing you don't often hear mentioned in the drug debate is that generics' markup of price over cost is often higher than the markup for brand-name drugs: possible since the generic manufacturers don't have to pay research costs. And they can be pretty profitable - that's why, back in 2005, Novartis was willing to pay over $8 billion to buy two European generic manufacturers.
So what about in this case? They don't seem to have been asked, nor to have volunteered, to date, but the Globe piece does include a bit of relevant evidence:
(Actually, that's too broad a statement. There are a few generic drug companies, in Canada and India in particular, which are doing their own original research, and more power to 'em.)
OK, that's the background. Now, what about the economics?
A lot of people argue that the patent system is not a good fit for the pharmaceutical sector. They see the monopoly power it gives patent holders as a major source of loss of economic welfare. There have been a number of alternatives suggested, but one of the most popular ones is the prize approach.
Basically, somebody (meaning the government) offers a monetary prize to, in this case, the first firm which can show that DCA is useful for treating cancer in humans, and finds a formulation in which it can be brought to market. Once the conditions of the prize have been met, the government owns the patent on the cancer treating version of DCA, and allows any generic firm which wants to to manufacture the stuff.
Surely DCA is a good case to use to test drive the prize idea. The drug has already shown promise in the lab, and because it's been around for a while it won't need to go through Phase I testing (that's the phase of drug testing where you give a bit of the stuff to a handful of humans, to see whether simply taking it kills them). So it can go directly to Phase II: the phase at which you try it on a small sample of cancer patients to see whether the promise it showed when it was given to rats seems still to be there when you give it to humans. If a drug fails Phase II trials, there's no point taking it forward to Phase III, where it's tested on large numbers of cancer patients.
Since we're designing a policy experiment here, let's simplify the structure a bit more. Let's ask some level of government (in practice wither the feds or the government of Alberta) to fork out a paltry few million dollars fund the Phase II trial, and only start the prize competition if DCA passes Phase II.
So if it gets to Phase III, the deal is that the government will hand over a large, precommitted pile of dollars to the first drug company which can bring DCA successfully through Phase III trials to marketability.
How large a pile of dollars? Well, it'll have to be large enough to cover the costs of the Phase III trial. And since the drug company won't make any profit off marketing the stuff, it'll have to pay them something like the rate of return they would have made had they been able to patent the drug. That rate of return will have to include a risk premium because I've said that the prize will be paid to a company which brings DCA successfully through Phase III trials - if it turns out that the Phase III trials show that it doesn't, in fact, work in humans, nobody wins and any entrants swallow the trial costs as a loss, just as they would if they were working on a patentable drug and that drug didn't pan out.
Still, critics of Big Pharma are always claiming that the industry exaggerates the costs of research, and that a big part of their reported costs are really marketing costs in disguise. In this case there won't be anything much in the way of marketing costs - the generic manufacturers will pump the stuff out, if it works, and the news coverage of successful Phase III trials will be all the advertising the generic version needs.
So how big will the prize have to be? That'll be an experiment in itself - the government can keep raising the amount of the prize until it's large enough to attract entrants.
Ok, so there are still some details which would need to be fleshed out. But there are lots of researchers out there who have done theoretical work on the prize notion, and there's probably a game theorist or two who might be able to make a contribution.
So there it stands. Proponents of the prize idea should sort out the details of a workable prize. They should then start lobbying governments, not just in Canada, to conduct the experiment. If it works out as some people think it might, you get a new cancer drug. If it bombs, you at least get one real world test of the whole prizes instead of patents idea. And whatever the outcome, the questions about DCA are answered.
What more could you ask for?
The complicating factor about DCA is that it's been around for a long time, and is now off patent. That means that if it's discovered that a particular dose of the stuff is effective against cancer, anyone who wants to will be able to manufacture it. That in turn means that there will be a lot of competition in the market supplying it - all the generic drug firms will make their own version - but it also means that nobody would be able to recoup the costs of the research necessary to find out whether it really does work on humans. And as Orac reminds us, over the years there have been lots of breakthroughs in cancer treatment in the lab, most of which turned out not to be effective in people. But even if it does work miracles, somebody has to pay for the testing, and Big Pharma is taking a lot of flack for not being willing to fund clinical trials on a drug that there's not just no hope of making a massive profit on, but not even a hope of recovering research costs on.
I'm eventually going to get around to making a suggestion about the economic issues involved, but first let's look at some background, from the Globe.
The story in question is by Anne McIlroy, published on 1 June / 07, and headed:
The battle over a cancer pillA few snips:
[cancer sufferers] started self-medicating this spring after University of Alberta researchers announced that DCA (dichloroacetate) dramatically shrank tumours in rats without damaging healthy cells. But the Edmonton team was having trouble finding money to see if DCA works in humans.Note the hundreds of millions of dollars bit. Let's be a bit more clear than the Globe - not only will they not make massive profits on it, under the current research incentive structure (and that's what I'll eventually come back to) they'll take a pretty hefty loss, guaranteed.
DCA already has been in use for a long time to treat rare metabolic disorders, so it can't be patented as a new drug. And without a patent even a wonder drug won't make huge profits – major pharmaceutical companies won't invest the hundreds of millions of dollars required to test it and bring it to market.
Dr. Evangelos Michelakis, the principal investigator, has urged patients to wait for valid results, warning that they could poison themselves by taking DCA ordered over the Internet. The University of Alberta so far has raised more than $200,000 toward a small, initial clinical trial.I read somewhere that the University of Alberta held a Use patent on DCA but let it lapse, figuring that the return they would make on it wasn't worth the fees they would have to pay to keep the patent up. Dr. Michelakis has filed a use patent on it at some point.
But from Liverpool to Louisiana, people with cancer say they can't afford to wait.
They are experimenting on themselves, ordering DCA, sharing their results on a website and putting together a database in an attempt to figure out if it is working.
Their do-it-yourself approach illustrates the Internet's growing power to help patients circumvent – and perhaps undermine – traditional medical research on drugs. The Edmonton scientists have warned that by taking it on their own, patients are jeopardizing the chances of a real clinical trial ever taking place: What if anecdotal reports spread that DCA doesn't work, or makes people sicker?
“It's destroying the efforts to do this right,” Dr. Michelakis recently told the science journal Nature.
He is so opposed to patients dosing themselves that he would not be interviewed for this story, because it includes interviews with people who are taking the drug.
.....................................................................................................
But the patent issues were a huge obstacle when it came to getting financial backing. Since the DCA molecule can't be patented, a researcher can claim intellectual ownership only on how a drug is administered to fight a particular disease. “Use” patents are generally considered weaker than standard patents, and are much less valuable to pharmaceutical companies.
When the researchers couldn't interest any drug companies, the University of Alberta started fundraising. Contributions, anywhere from $5 to $1,000, have been steadily flowing in.
Helping cancer patients treat themselves with DCA clearly wasn't what Dr. Michelakis had in mind when he filed the patent, or when he published his results in January in the medical journal Cancer Cell.Taking it in doses based on the details which Dr. Michelakis reported in the patent - patents give a certain amount of protection, but the flip side is that in order to get one you have to put a lot of information into the public domain.
But he may have underestimated the power of the Internet, and the appeal of the DCA story. In January, he gave interviews to reporters from all over the world, but now he doesn't want to talk to the press about DCA.
“Dr. Michelakis is a highly ethical man and feels a great deal of responsibility for his research and the health of patients,” University of Alberta spokeswoman Jo-anne Nugent said in an e-mail.
“We have found that every time we participate in such publicity, it plants a seed of hope and results in more patients taking DCA.”
OK, so big pharma won't fund research into it. But what about the generic manufacturers? One thing you don't often hear mentioned in the drug debate is that generics' markup of price over cost is often higher than the markup for brand-name drugs: possible since the generic manufacturers don't have to pay research costs. And they can be pretty profitable - that's why, back in 2005, Novartis was willing to pay over $8 billion to buy two European generic manufacturers.
So what about in this case? They don't seem to have been asked, nor to have volunteered, to date, but the Globe piece does include a bit of relevant evidence:
If it seems hard to believe that a promising and inexpensive treatment for cancer would never get tested, listen to Judes Poirier, director for the Centre for Studies in Aging at McGill University.But if someone else wants to run the trials, they'll make the drugs. Generic manufacturers manufacture, they don't research.
“I have been there before,” he says. “This is a recurring story. It happens in many different fields.”
Researchers are increasingly going back to look at older drugs to see if they might be good at treating more than one disease, he says.
In 1996, Dr. Poirier found that a heart-disease drug called Probucol showed promise in keeping Alzheimer's disease at bay. It worked in lab animals, and a small human trial conducted in the late 1990s was also encouraging.
But there is no patent for Probucol – like DCA, it has been around too long. Dr. Poirier filed a use patent and naively hoped that Probucol would be tested soon in a large clinical trial because it already had been proved safe in heart patients.
He couldn't interest any pharmaceutical companies. They wanted him to change the drug's chemical formula just enough to get a new patent, but that would mean time-consuming tests to prove that the new version was safe.
He turned to a generic drug company, one that sells cheaper versions of name-brand drugs once their patents have expired.
Too risky, he was told. Their business approach didn't involve trying an old drug against a new disease.
(Actually, that's too broad a statement. There are a few generic drug companies, in Canada and India in particular, which are doing their own original research, and more power to 'em.)
OK, that's the background. Now, what about the economics?
A lot of people argue that the patent system is not a good fit for the pharmaceutical sector. They see the monopoly power it gives patent holders as a major source of loss of economic welfare. There have been a number of alternatives suggested, but one of the most popular ones is the prize approach.
Basically, somebody (meaning the government) offers a monetary prize to, in this case, the first firm which can show that DCA is useful for treating cancer in humans, and finds a formulation in which it can be brought to market. Once the conditions of the prize have been met, the government owns the patent on the cancer treating version of DCA, and allows any generic firm which wants to to manufacture the stuff.
Surely DCA is a good case to use to test drive the prize idea. The drug has already shown promise in the lab, and because it's been around for a while it won't need to go through Phase I testing (that's the phase of drug testing where you give a bit of the stuff to a handful of humans, to see whether simply taking it kills them). So it can go directly to Phase II: the phase at which you try it on a small sample of cancer patients to see whether the promise it showed when it was given to rats seems still to be there when you give it to humans. If a drug fails Phase II trials, there's no point taking it forward to Phase III, where it's tested on large numbers of cancer patients.
Since we're designing a policy experiment here, let's simplify the structure a bit more. Let's ask some level of government (in practice wither the feds or the government of Alberta) to fork out a paltry few million dollars fund the Phase II trial, and only start the prize competition if DCA passes Phase II.
So if it gets to Phase III, the deal is that the government will hand over a large, precommitted pile of dollars to the first drug company which can bring DCA successfully through Phase III trials to marketability.
How large a pile of dollars? Well, it'll have to be large enough to cover the costs of the Phase III trial. And since the drug company won't make any profit off marketing the stuff, it'll have to pay them something like the rate of return they would have made had they been able to patent the drug. That rate of return will have to include a risk premium because I've said that the prize will be paid to a company which brings DCA successfully through Phase III trials - if it turns out that the Phase III trials show that it doesn't, in fact, work in humans, nobody wins and any entrants swallow the trial costs as a loss, just as they would if they were working on a patentable drug and that drug didn't pan out.
Still, critics of Big Pharma are always claiming that the industry exaggerates the costs of research, and that a big part of their reported costs are really marketing costs in disguise. In this case there won't be anything much in the way of marketing costs - the generic manufacturers will pump the stuff out, if it works, and the news coverage of successful Phase III trials will be all the advertising the generic version needs.
So how big will the prize have to be? That'll be an experiment in itself - the government can keep raising the amount of the prize until it's large enough to attract entrants.
Ok, so there are still some details which would need to be fleshed out. But there are lots of researchers out there who have done theoretical work on the prize notion, and there's probably a game theorist or two who might be able to make a contribution.
So there it stands. Proponents of the prize idea should sort out the details of a workable prize. They should then start lobbying governments, not just in Canada, to conduct the experiment. If it works out as some people think it might, you get a new cancer drug. If it bombs, you at least get one real world test of the whole prizes instead of patents idea. And whatever the outcome, the questions about DCA are answered.
What more could you ask for?
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