Friday, July 29, 2011

Epocrates: Having Your Cake and Eating It Too

Duff Wilson in the New York Times did a nice job of shining a spotlight on a phenomenon that has lurked for too long in the shadows:

Epocrates, an increasingly popular information service for physicians, has been scoring big with its free smartphone app that allows physicians to pull up drug prescribing infomation in the midst of a patient visit. Here's what one of my colleagues in family medicine says about this service:

"Dr. Robert M. Schiller, chairman of family medicine at Beth Israel Medical Center in New York, said he often uses Epocrates to look up drugs and advises medical students to use it, too.

“I have it on my iPhone,” he said. “It’s great for the convenience, being in a room with a patient and checking a medication. But the biggest problem is that it’s supported by the pharmaceutical industry.”

Drug companies, Dr. Schiller said, sponsor information that favors them. “To extent that this is a product that will influence physician prescribing behavior because it’s so efficient and useful, it really needs to have minimal bias,” he said. “And how do you assure that?”

Ah yes-- how do you assure that? Here's the dilemma-- as a seasoned physician educator notes, this type of service fills a real need, and yet there's the downside of commercial bias. So just how good a job is Epocrates doing in balancing those objectives?

Well, on the one hand, Epocrates acknowledges at least the marketing value of not being beholden to industry: “The credibility of our brand is dependent in large part on the medical community’s continued perception of us as independent from our health care industry clients, particularly pharmaceutical companies,” the company said in a securities filing this year.
... “Our first commitment is the value to the physician,”
Rosemary A. Crane, president and chief executive of Epocrates, said in an interview.

So that's what they say to the docs. What do they say to the drug firms that buy their ads?

"Epocrates says drug makers get $3 in increased sales from every dollar spent on DocAlerts. The claim comes from comparing prescription records of doctors who see DocAlerts with those who do not, company officials said. But they declined to share the research, saying it was paid for by drug companies and was confidential. ... Pfizer, the world’s largest drug maker, has certainly found the marketing channel to be an effective way to reach doctors. “The beauty of the work we do with Epocrates is that we literally put ourselves in the palm of their hand,” said Dr. Freda Lewis Hall, chief medical officer at Pfizer."

By the way, what was Epocrates' CEO Rosemary A. Crane's last job before she took over the firm? Oh yes--she worked for 26 years as a Pharma executive (Johnson & Johnson, Bristol-Myers Squibb).

Docs love Epocrates because its smartphone app is free. What else is available? "UpToDate, from Wolters Kluwer Health, has a Web-based disease reference guide that, it emphasizes, does not accept money from pharmaceutical companies. But UpToDate costs $395 to $495 a year, and its first iPhone app just became available on Monday."

There you have it. The drug companies have recently been cutting back on their drug rep sales force, both to reduce costs as fewer brand name blockbusters remain on the market, but also because they see a greater marketing advantage in Internet and electronic approaches to practitioners--like Epocrates. Epocrates seems to be talking out of both sides of its mouth when it comes to who it works for--the docs or the drug industry. Which side is winning? Well, who's paying the piper?

How long are we in medicine going to keep thinking we can get goodies for free and yet we won't be biased and that the real goal is education, not marketing? And just who's in the palm of whose hand?

Friday, July 22, 2011

SLAPP and Stem Cell Clinics

For this item I'm indebted to my distinguished bioethicist colleague Art Caplan:

In HOOKED I discussed how Pharma had occasionally made use of SLAPP, or "strategic lawsuit(s) against public participation." The basic idea behind SLAPP is that there are two parties to a dispute, one with a lot of power and money, the other with little of either. The weaker party has a legitimate gripe against the stronger. If it actually went to court, the weaker party would almost surely prevail. The stronger party then pre-emptively files, or threatens to file, a lawsuit against the other, knowing that while the suit is a sure loser in the long run the weaker party would be bankrupted by the legal fees required to defend itself. The stronger party then says it will make nice and drop the suit, so long as the weaker party agrees to be quiet and not get in the way of the stronger party's plans. Ideally the SLAPP has two outcomes. First, the party that is actually creating trouble for the stronger party's plans will go away. Second, other potential critics who might be waiting in the wings will be silenced out of fear of a similar action being taken against them.

Caplan tells us how commercial stem cell clinics, many located outside of US jurisdiction and taking full advantage of lax oversight, are promising totally unproven cures. The International Society for Stem Cell Research, a group of scientists, has been worried about these practices and initially responded by posting on its website a list of the available body of evidence to show what is known about what stem cells have so far been proven to do (thus far, very little). But that part of their website came down when a group of clinic operators threatened them with an expensive lawsuit, far beyond the budget capabilities of the scientific nonprofit organization.

Just a small comment about what happens when commercial interests take over medical care...

Monday, July 18, 2011

Kid Gloves on Corporate Crime: A Different View

The following post takes off on Roy Poses' post on Health Care Renewal:
--which in turn is heavily based on a New York Times account by Gretchen Morgenson and Louise Story:

As I've demonstrated many times, Roy and I almost always have the same general take on an issue, albeit me more with a focus on Pharma and Roy on the corporatization of health care more generally. Here I find myself differing from Roy's analysis. So rather than simply appending a comment to his blogsite, I will take advantage of my own bully pulpit to make several points that seem to me pertinent.

First, the brief summary, though I recommend both of the above links to get the full picture. The U.S. Justice Dept. is said to be going soft on corporate wrongdoing, in terms of criminal prosecutions of corporate execs. They are increasingly using a tool called "deferred prosecution agreements," which advocates say gives them a bigger bang for the buck, getting companies to investigate themselves and to clean up their acts quicker than would be the case in a prolonged legal fight. Critics say that this is a form of mollycoddling white collar criminals and note that since the Great Recession, hardly any Wall Street execs have faced legal penalties.

Roy has for some time been harping on the need for CEOs to actually suffer consequences if the current wave of corporate wrongdoing is to stop. And he has a lot of ammunition in terms of the various corporate settlements we've reviewed here at nauseam, where a drug company can simply break the law so long as it has a blockbuster drug that brings in lots of cash--allowing it to set aside a big legal payout as simply a cost of doing business, after which it goes back on its merry, illegal way.

But I believe that Roy misses a deeper message in the NYT article. He says in his post that the new, softer policy was adopted by DOJ "for reasons that were not explained." But the real reasons seem to be staring us in the face in several places in the Times story. For instance:

Still, some lawyers applaud the closer relationship between the government and business. “Given the scanty resources that have been committed to corporate crime enforcement, I think the government’s leveraging of its prosecution power from corporations and their lawyers has been critically important,” said Daniel C. Richman, professor of law at Columbia and a former assistant United States attorney in New York.

But Professor Richman added that the government should have “a much more developed, funded and empowered S.E.C., Federal Reserve, E.P.A. and other agencies to do regulation, to do enforcement and feed cases where necessary to criminal prosecutors.”

Here, I think, is the answer. We've just had more then three decades of so-called leadership where Republicans and Democrats have vied with each other in their eagerness to "shrink big government." Just as we've seen here before that the FDA doesn't have enough inspectors to be sure that drug ingredients imported from China are safe, the Feds apparently lack the investigators to police corporate wrongdoing. The "deferred prosecution agreements" essentially outsource the Federal investigation--the company has to hire a big law firm to find out what it did wrong and then come up with a supposed promise-to-be-good-in-the-future plan. And as the critics note, the corporation is much more likely to resort of this strategy, and to be frank about what the problem is, when some underlings can he hung out to dry, and not when the criminality resides in the executive suite. But what can DOJ or SEC do when they simply have to few trained staff to run their own investigations, with real teeth?

This leads to an announcement I hope to be able to make soon about a new book that I have been working on for some time. It's about US policy, and not about pharmaceuticals, so I plan to take little space here to talk about it. But I have been spending time studying the origins and nature of a belief system that I think is most appropriately called economism. Economism is the belief in the all-powerful "free market," and the prescription that every problem in human life can be solved through the market, and that the only appropriate role of government in the market is to get out of the way and let it be "free." But economism is internally self-contradictory and so always ends up talking out of both sides of its mouth. In the case of "big government," economism desires half-powerful and half-powerless government. The powerless half is the part that could stand in the way of corporate profits--like too many DOJ or SEC investigators. But economism simultaneously desires all-powerful government when it comes to those aspects of government that can be tied to its own pursuit of wealth, and can secure monopoly privileges for those corporations now at the top of the heap. So, for example, making sure that Pharma continues to get huge tax breaks, and that the US government remains vigilant to protect its "intellectual property" so that no Indian generic firm can make AIDS drugs to sell in Africa at an affordable price, is a type of "big government" you never hear economism's boosters objecting to.

So, if I could wave my magic wand and make the corporations and the wealthy pay their fair share of taxes, and then we'd have enough government gumshoes to bring the corporate wrongdoers to justice, would I then be in favor of unleashing them mercilessly on the industry? Well, not exactly, which is my next-to-last point for this overly long post. I was quite persuaded when I wrote HOOKED by the Australian sociologist, John Braithewaite, who back in 1984 wrote an interesting and prescient book, Corporate Crime in the Pharmaceutical Industry. Braithewaite was an advocate of turning where possible to a cooperative rather than a big-stick approach to corporate wrongdoing, arguing that each corporation contains within it people who want to see the right thing done, that those folks are often better placed as insiders to see what is really going on, and that finding ways to form alliances with those people might actually pay off better in the long run in terms of responsible corporate behavior and safe and effective drugs. Braithewaite was a firm believer that sometimes you had to hit the proverbial mule over the head with the 2x4 to get its attention, and so he argued that focused prosecutions were a very good tool to use along the way. But he also argued that a policy simply of "throw the rascals in jail" was not the way to get what we want either. So I can see an argument for some balance here despite the fact that the situation as described by Morgenson and Story sounds way out of kilter on the mollycoddling side.

Final point: back to economism again. One of the main tools for economism's advocates in the last three decades or so has been the concept of "moral hazard." According to this so-called economic theory, you should never help the poor, because if you help them you reward their behavior, and that makes them just do whatever made them poor in the first place more often. But again economism talks out of both sides of its mouth, and here proves a point wittily made some time back by J.K. Galbraith: "The poor don't work hard enough because they're paid too much, and the rich don't work hard enough because they're not paid enough." (Quote courtesy Steve Keene, Debunking Economics, Zed Books, 2001.) In other words, so long as we are talking about the poor, then "moral hazard" is a universal law of human pychology, but economism changes its tune abruptly when we are talking about the rich. If the poor commit a crime, we lock them up for life under a 3-strikes law. But if the rich commit a crime, then we talk about deferred prosecution agreements.

Friday, July 15, 2011

Backpedalling in Maine

It's sad to read the latest news from Maine, thanks to our friends over at PostScript:

Here's what journalists call the "lede" from Kate Petersen's interview with Democratic state Rep. Sharon Treat: "The new Republican governor and majority in the Maine Legislature have together now repealed not only the state’s gift disclosure law, but nearly every progressive prescription drug policy we have, including our pharmacy benefit manager (PBM) law, and pricing transparency. This is not surprising as there are very close ties between the pharmaceutical industry and the Republican party in Maine. None of these laws were easy to pass in the legislature even when Democrats had the majority, because the drug industry is very powerful when it comes to influencing politicians."

Wednesday, July 13, 2011

The Sky Is Falling--What if New Drugs Actually Had to Add Value?

John C. Lechleiter, CEO of Eli Lilly, warns us in a Wall Street Journal op-ed (subscription required) of a truly terrible fate that might befall the U.S., if only American policymakers are so misguided as to follow the example now being set in Germany.

And just what are those terrible Germans doing? I hope you're sitting down when you hear this. They seem to have an effective system in place to require that new drugs do something of value before they'll pay for them.

According to Mr. Lechleiter, you can kiss drug innovation goodbye if this thing were to happen in the US. The scenario that he depicts is a bit hard to follow but let me see if I can hit the high points. First, he makes a claim that most regular readers of this blog will find hard to swallow--"Contrary to myth, so-called blockbuster medicines are not the result of slick marketing campaigns but of demonstrated success in the actual practice of medicine." For a different perspective see: But for now, let that pass. The next step in the reasoning is that a drug may be a really fine drug but you cannot tell that when the drug is first introduced; it is only with extended clinical experience that you can see how really fine it is. Now, this reasoning runs contrary to what John Ioannidis has cogently argued: (showing mathematical reasons why the early reports of a drug's efficacy almost always overestimate its benefits compared to later data). So now we come to Mr. Lechleiter's grand conclusion, which is that if we did what the Germans are doing, then promising and powerful new drugs will get nixed right out of the starting gate and will never show us their real potential.

So the reasoning about the future public being robbed of valuable drug advances turns out to rest on some pretty shaky premises. Plus Mr. Lechleither--as typically occurs with those who try to market drugs-- seems to focus solely on efficacy and to dismiss concerns about safety. I'm grateful to my colleague Don Light, author of The Risks of Prescription Drugs that's mentioned in one of the above posts, for recently calling my attention to some published work by Mary Olson on the relationship between quicker FDA approval and greater risk of later adverse reactions (which I may detail in a later post). Olson has actually calculated an increase in the hospitalization and death rates due to adverse drug reactions for each so many months that the FDA approval time is shortened.

In sum--Mr. Lechleiter is upset that a careful pre-marketing vetting of new drugs will stifle valuable innovation. This fear seems to ignore two things. First, if we demand that drugs prove their mettle first, and then agree to pay for them, it is unlikely that we'll keep very many useful new drugs off the market, but we can save a ton of money on not-very-useful drugs. Second, if we took longer before we allowed new drugs to be marketed, evidence available today suggests that the safety factor would be enhanced. It is quite possible (see Don Light's book) that more lives are lost today in the US due to adverse reactions to prescription drugs than are saved by truly lifesaving new drugs (which are reliably estimated to be a tiny fraction of all new drug approvals).

Now we come to what may seem a gratuitous ad hominem attack--but I am sorry, if somebody treats me as if he thinks I am a complete idiot, then I am likely to get my back up. Mr. Lechleiter spends most of his article decrying the terrible model provided by Germany and hoping that the US will never follow that lead. (Don't worry, Pharma is spending every lobbying buck they can lay their hands on to make dead sure of that.) Then at the end he has the nerve to say: "We share Berlin's goals of generating value and limiting unnecessary costs in health care. We see ways of harnessing and improving health-outcomes research."

Come again? You have just trashed Germany's system precisely because they do certain things, and apparently very effectively--and then you have the gall to tell us you share the same goals? And this is supposed to make the pharmaceutical industry trustworthy brokers in our eyes?

Lechleiter JC. An ObamaCare drug preview in Germany. Wall Street Journal, July8, 2011, A13.

Tuesday, July 12, 2011

The Drug Pipeline--Not So Dry?

Keeping up with today's theme, which is what's happening over in the pharmaceutical industry these days, an encouraging article comes from Jonathan Rockoff and Ron Winslow in the Wall Street Journal (subscription required). The article raises an interesting possibility--that despite all that I don't know about the science of drug discovery, I may actually have been right in HOOKED when I charged the industry with pursuing a dysfunctional model of R&D.

First the good news--20 medicines deemed truly innovative (though not necessarily shown yet to be better than existing medicines) have been approved by the FDA so far this year, compared to only 21 all last year. A Credit Suisse analyst predicts that in the next 3 years, more than 20 innovative drugs that will be good enough to earn blockbuster sums ($1B annually or more) are likely to see approval. Two recent breakthrough drugs for advanced melanoma, two new drugs for hepatitis C, and the first new drug for lupus in half a century are given as examples of recent advances.

Why? Rockoff and Winslow say that Pharma has wised up and realized you cannot make useful new drugs by a science assembly-line approach--the model I derided in HOOKED. You actually have to understand the mechanism of the disease. Hence a new era of partnering with university scientists and small biotech startups. (It also works financially because the big brand-name company can let the small firm assume all the risk, and then come in later and scoop up the drug if it seems promising. For one of the new melanoma drugs, ipilimumab, Bristol-Myers paid a biotech firm, Medarex, about $250M when doing the same drug discovery process totally in-house could have cost it $1B.)

The reporters also state that the more cost-conscious, generic-friendly environment works against the so-called drug discovery model that made profits in the past few decades--just tweak an existing molecule and make a me-too drug like The New Purple Pill. So companies are actually today trying to find diseases that don't already have a good treatment, and look for one. They count on the fact that while insurers in the future may not pay for the next Purple Pill, they will probably pay for the only drug that treats a deadly disease, even if it's priced very high. (Bristol-Myers intends to sock it to patients or their insurers to the tune of $120,000 for a full course of ipilimumab, which they will make pronouncible with the brand name Yervoy. How much they intend to make is shown by the fact that they purchased full control of Medarex for $2.1B.)

The news in this article, if accurate, is hardly the end of all that has been wrong with the drug industry that promotes a lack of professionalism on the side of medicine, and that hurts the public health in the name of profits. But it may be a sign that at least one aspect of the industry is moving in a direction that may actually help future patients, and that may gradually return the industry to an ethic of promoting health more than relying on slick marketing.

Rockoff JD, Winslow R. Drug makers refill parched pipelines. Wall Street Journal, July 11, 2011, A1.

What's Pharma Up To? Profits vs. Safety

A couple of news items these past couple of days reveal what the drug industry is up to--and what it isn't. (A reminder for newcomers--this blog is not about industry-bashing, it's mostly about medical-profession-bashing, arguing that many of the ethical problems at the interface between medicine and the pharmaceutical industry could best be resolved by a higher level of professionalism, and less greed, on medicine's part. But every once in a while we need to take a look on the other side of the fence to see what's going on there.)

First we see from the LA Times--,0,1832507.story
--how the industry is busy pulling out all the lobbying stops to make sure that any budget deal that passes Congress will not put a crimp in their profits. Some folks in Congress who want results and not political posturing have noted that demanding what seem to be reasonable discounts for government health care programs, for escalating drug costs, could save $112B over the next decade. The industry wants to put a quick stop to any such talk. So far, it's working.

The next question is what the industry is doing with its profits. Apparently, not assuring drug safety, according to a report recently released by the Pew Health Group and kindly summarized by our friends at PostScript:
Basic bottom line is that a bunch of people died from contaminated Heparin a few years back, traced to shoddy ingredients from a Chinese factory. Since then everything has gotten worse--40 percent of all finished drug products, and 80 percent of the ingredients used to make drugs for the US market, now come from overseas, yet the industry's ability to trace the origins of those ingredients, and the FDA's ability to inspect the plants that make them, remain virtually nonexistent. You'd expect Congress to be indifferent when people in other countries die because of bad drugs, yet to sit up and take notice when some Americans die. Apparently that wake up call didn't happen. Certainly, left unregulated, the industry has no intention of changing present practices. As the Community Catalyst group that worked with Pew reported with a quote from a major brand name drug firm, it's all about how cheaply one can make the product.

Monday, July 11, 2011

Outsourcing Trials: An Ethics Vacuum?

A report from the 7th World Congress of Science Journalists, courtesy The Guardian in the UK--
--raises a specter that we've addressed previously, that by moving clinical trials to developing nations, the pharmaceutical industry is making use of a setting in which protection of human research subjects may not be as stringent.

The developing-world advantages for the contract research organizations (CROs) that run these trials for Pharma are first, lower costs, and second, readier availability of subjects who are not already taking a bunch of meds.

The article states, " 'Less stringent ethical review, anticipated under-reporting of side effects, and the lower risk of litigation make carrying out research in the developing world less demanding,' said Ames Dhai, director of the Steve Biko Centre for Bioethics at the University of Witwatersrand, South Africa.

"While many countries have set ethical standards for clinical trials, this is not a guarantee they will be respected by those who perform the trials. 'The problem is implementing these [ethical] guidelines and the imperialistic attitude of researchers and sponsors who come to the country and frequently disregard our process,' Dhai added."

The article goes on to mention both South Africa and India as two research settings in which subject abuse can readily occur.

PS: Before we go tsk-tsking about the low ethical standards in other countries, we also have to ask if US institutions are up to the task of protecting subjects-- for example,