Reward Drug Companies for Restrained Use of New Antibiotics?

The following announcement comes by way of a website of the Robert Wood Johnson Foundation:
http://www.publichealthlawresearch.org/news/pharmaceutical-conservation-key-slowing-rise-antibiotic-resistant-infections

The news release refers to an article in the new issue of Health Affairs:
http://content.healthaffairs.org/cgi/content/abstract/29/9/1689

The article, by Aaron S. Kesselheim (medicine-Harvard) and Kevin Outterson (law-BU), proposes a novel way to pay drug companies for new antibiotics. They note that the present payment system encourages the misuse (wide overuse) of new antibiotics as a way to increase revenue before the drug goes off patent. The too-wide use of new antibiotics speeds the development of resistance to the antibiotic among bacteria, making the antibiotic ineffective more quickly. Restrained use of the new antibiotic would slow development of resistance but cost the company in terms of revenue.

Their proposed solution is to pay rewards to drug companies based on data that the drug continues to demonstrate a low level of resistance among targeted bacteria. This would (presumably) give drug companies a financial incentive to work in tandem with hospitals and physicians to use newer antibiotics in a targeted, restrained, scientifically thoughtful fashion.

Spinal Fusion Devices: What's the FDA Hiding?

Thanks to Marilyn Mann, I was directed to this article by John Fauber on MedPage Today Orthopedics:
http://www.medpagetoday.com/Surgery/Orthopedics/21908

(Regular readers will recall that we've seen Fauber's excellent investigative reporting previously with the Milwaukee Journal-Sentinel.)

The story is a complicated one and I refer interested readers to the full report. A couple of medical device companies have manufactured some stuff that makes the body grow new bone wherever it lands. The idea is to put it in a little cage sort of thing to contain it, slip the cage in between two vertebrae of a person who otherwise would undergo a spinal fusion to lock the two bones together (using a bone graft, with a bit of bone taken from the hip), and you have a fusion done without the need to harvest the bone from another site.

Two problems. First, the above story assumes there's some advantage to spinal fusion surgery in the first place. In the vast majority of cases this is highly questionable. However, since surgeons make a lot of money off fusions, and since patients with chronic back pain are among the most desperate and unhappy patients known to medicine, it seems spinal fusion will be among us for some time to come, evidence be damned.

Second problem--the magic stuff that makes new bone wherever it lands really indeed has a Midas touch. Numerous complications have been reported where new bone grows where you don't want it. This is especially bad in the neck where there can be swelling that compromises breathing.

This whole business made some folks wonder about the original FDA hearing at which this magic stuff was first approved. It turns out that most of the favorable data was generated by docs who had financial conflicts of interest with the manufacturer. The stuff was approved with a label that said don't use it on the neck, use it in the lower back only, but even at the time people warned that off-label use would be highly predictable and a huge problem. Guess what? Since 2002 off-label use has been a huge problem.

So these folks went to the FDA and asked for a simple piece of information--tell us the list of investigators, whose data were reviewed by your advisory board in 2002, that indicate which of them had financial conflicts of interest with the manufacturer.

Seems simple. But the FDA has said that this data cannot be released. More interesting, the FDA has provided, on three occasions, three totally different reasons why the information cannot be released. The company, of course, has it, but refuses to release it.

Now, a couple of observations. First: we come back regularly to the issue of how devices are different from drugs. This seems to be a case in point. Whether the stuff will leak out and cause bone to grow where you don't want bone might very well have something to do with the technical skill of the guy doing the surgery. One of the most conflicted surgeons in terms of total money brought home, is conflicted because he's credited with inventing the device. It would not be surprising to learn that the surgeon who invented a particular operation has better outcomes than your average surgeon off the street, even if for no other reason than he's had more time to do more surgeries. So you can't draw quite the same conclusions as you might if this were a drug being studied and not a device.

Second: This is related to the first. Given all that, you can see how a company might behave if research integrity and public trust were actually Job One in their value system. They would realize that having the bulk of their research carried out by folks with serious conflicts of interest was not a good thing. So as early in the game as possible, they'd ask some hard questions about the research strategy. They'd specifically look for ways to launch a clinical trial under conditions that as much as possible eliminated financial conflict of interest as a variable. They'd insist on several layers of disinterested third-party monitoring as a minimum condition. And so on.

So far as I can tell, none of those steps were taken; the company simply figured it could go about its usual business, using its own hired guns, and then push around the FDA approval process to get what it wanted (in this case, an approval that opened the doors wide to off label use and hence increased sales, and that asked no embarrassing questions about who needs spinal fusions anyway). The company was correct in its assessment of what it took to get what it wanted.

What Drug Companies Promote PSA Testing?

I've been very concerned for many years about the overuse of PSA screening for men, so I'm surprised that I was not aware of this op-ed in the New York Times back on March 10:
http://www.nytimes.com/2010/03/10/opinion/10Ablin.html?scp=2&sq=ablin+great+prostate+mistake&st=nyt

Richard Ablin, research professor of immunology and pathology at the University of Arizona, hammered away at what he calls the "great prostate mistake," routine screening for prostate cancer that costs $3B annually in the US and that ends up leaving 47 men "who can no longer function sexually or stay out of the bathroom for long" for each 1 man who might (under the most optimistic study yet published) have been saved from death by having had the test. (Another equally good study says that no men are saved from dying as a result of being tested.)

You might wonder what gives Prof. Ablin a right to sound off about the PSA test. Simple--he is credited as the discoverer of PSA back in 1970.

Ablin notes that despite recent major studies showing the lack of benefit from PSA screening, medical sopcieties and patient advocacy groups have been slow to change their advice on having the test. "So why is it still used? Because drug companies continue peddling the tests.... I never dreamed that my discovery of four decades ago would lead to such a profit-driven public health disaster."

So now it appears that I am doubly uninformed--I not only missed Ablin's op-ed, I also did not happen to notice that drug companies are pushing PSA testing. I don't know whether drug companies actually sell PSA test kits to labs or (more likely in my view) drug companies know that they'll sell a lot of prostate cancer drugs so long as men are stampeded into having themselves screened. (As I posted about earlier in describing how drug companies who want to sell osteoporosis drugs find it to their benefit to push bone mineral density tests: http://brodyhooked.blogspot.com/2009/12/npr-how-osteopenia-became-treatable.html.) Perhaps some of the kind people who put comments on this blog know the answers and can advise us.

A Wry Commentary on Medical Organizations' Corporate Links

I received an e-mail from Dr. Matthew R. Anderson, of the Department of Family and Social Medicine at Montefiore in New York, and editor of the journal Social Medicine. He wanted to call my attention to some recent articles in his journal that readers of this blog might find of interest.

First, the journal published a set of 3 papers commenting on the long history of medical society journals accepting cigarette ads:
http://www.socialmedicine.info/index.php/socialmedicine/article/view/459/902
http://www.socialmedicine.info/index.php/socialmedicine/article/view/460/910
http://www.socialmedicine.info/index.php/socialmedicine/article/view/461/911

As a cute illustration of this issue, the journal's website contains a 1947 ad that features, shilling for Camels, none other than the father of cellular pathology himself, Rudolf Virchow:
www.socialmedicine.info

If all this seems a bit far afield for us, Dr. Anderson's own editorial brings it back home. He addresses three more recent examples of corporate engagement by medical organizations, that he compares to the old practice of rationalizing taking tobacco company money by printing their journal ads. The examples are, first, the American Academy of Pediatrics and its links to manufacturers of baby formula; second, the American Academy of Family Physicians and its recent tie to Coca-Cola; and third, the AMA's role in selling its physician database to permit drug companies to keep detailed profiles of physician prescribing:
http://www.socialmedicine.info/index.php/socialmedicine/article/view/448/880

Some pertinent comments from Dr. Anderson's editorial: "We presume that these actions do not reflect the values of [the three medical organizations'] membership. It is legitimate to ask, therefore, if we have really progressed from the time when cigarettes were advertised in medical journals under the slogan 'more doctors smoke Camels.' ...Pulling our lens back, we see that these associations have become the captives of corporations which serve their profession. Rather than working for their patients or their members, they are promoting the ends of corporations."

Consumers Union Poll: Public Cares about Pharma Influence

Pharmapologists have long complained that pharmascolds like me fantasize that the U.S. public might lose trust in physicians if they knew all about the shenanigans that go on with Pharma influence, when in actual fact they don't give a darn or else are thrilled that their docs are big industry fans. I've addressed the data on this in a previous post:
http://brodyhooked.blogspot.com/2010/04/what-do-patients-think-of-docs.html

Now Consumer Reports weighs in with a new poll conducted back in May and just released:
http://blogs.consumerreports.org/health/2010/08/consumers-say-big-pharma-influence-on-docs-is-concerning-consumer-reports-survey.html

Basic findings:

• 69% of Americans think drug makers have too much influence on physicians' prescribing decisions
• Half say docs are too eager to whip out the drug prescription pad when a non-drug treatment option works just as well or better
• 47% say gifts from the drug industry influence physicians to prescribe certain drugs
• 41% worry that docs tend to prescribe newer and more expensive drugs
• 51% grumble that docs don't consider a patient's ability to pay when prescribing

Policing Unsafe Drugs--A Toothless System

Two brief news items about how hard it is to get the drug industry to behave, and keep unsafe substances off our shelves.

First, among many useful and informative recent items on our fellow blog, Health Care Renewal, is a post:
http://hcrenewal.blogspot.com/2010/08/proprietary-information-confidentiality.html
--which in turn is based on a Wall Street Journal article by Alicia Mundy (see post for link). At issue is the 2007-8 deaths of 81 patients due to contaminated heparin imported from China, and sold in the US by Baxter and Scientific Protein Laboratories LLC. Previous accounts have suggested that we don't know where the contaminants in the heparin came from and who is responsible because the Chinese government investigation sort of petered out, and the FDA lacked the wherewithal to go in themselves and get to the bottom of it. In sum, we treated the deaths of 81 people as if it was a sort of natural disaster, with no one to blame. But Mundy's story tells a rather different tale-- that a Federal judge has ruled in favor of a motion by Baxter and SPL to declare various company documents proprietary and hence protected from publication. Other parties to the suit (admittedly who have their own financial dogs in the fight) objected to this motion on the grounds that the documents, if revealed, would be of great public health importance in identifying the likely sources of the contamination.

So what we seem to have is a Federal court that is willing to help private companies keep documents secret, that could actually have answered at least some of the outstanding questions about a drug safety problem that caused 81 deaths. Suddenly the disaster is not seeming so natural any more.

Next, we can turn to an article in the New York Times by Gardiner Harris (see comment below):
http://www.nytimes.com/2010/08/20/health/policy/20fda.html?scp=2&sq=gardiner%20harris%20glaxo%20memo%20avandia&st=cse
This article shows that one ancient element of FDA lore has not changed over many decades. The FDA ordered GlaxoSmithKline to send out a "dear doctor" letter in July, summarizing the conclusions of an expert panel on the risks of the diabetes drug Avandia (see my previous post about the panel, http://brodyhooked.blogspot.com/2010/07/follow-up-on-fda-avandia-hearings.html). Now, critics are charging that the letter is misleading and amounts to a whitewash of Avandia.

In HOOKED, I described an interesting incident in FDA history about the antibiotic chloramphenicol. It was found to cause a rare but deadly adverse reaction, but neither could the FDA withdraw it from the market because it was the only available treatment for a couple of rare but deadly infections. The end result was a peculiar dance, in which at every point the FDA was outmaneuvered by the manufacturer, Parke, Davis. The FDA would order Parke-Davis to write a "dear doctor" letter telling physicians about the risks of side effects with chloramphenicol, and not to use it for colds and sore throats but to keep it in reserve for really serious infections. Parke, Davis kept sending out letters which said that chloramphenicol had been found to be safe by the FDA--after all, they had not taken it off the market--and so doctors should keep using it with confidence.

Bottom line--if you want the letter to say what you want it to, write it yourself. The fact that the FDA keeps going hat in hand to beg the drug company to say what needs to be said is just one more sign of the system's inability to protect the public health.

My promised comment: I used to regard Gardiner Harris as one of the heroes of investigative journalism for his role in regularly exposing Pharma misdeeds. Now I need sadly to take anything he writes with a grain of salt, after his role earlier this year in trashing the Dartmouth Atlas research group without any discoverable basis in fact.

More Tidbits from White Coat, Black Hat

I recently announced Carl Elliott's new book, White Coat, Black Hat:
http://brodyhooked.blogspot.com/2010/08/new-book-of-interest-from-carl-elliott.html

What follows here is a set of brief quotes gleaned from my now having read the complete volume, and then I will end with some summary comments.

• On ghostwriters who work for medical communications companies: Carl quotes a biology PhD who went to work for a medical communications company and quit after a year, on being asked when exactly he decided "there was something ethically dubious going on at the agency": "The first day I was there."
• Objecting to the idea that what's wrong with ghostwriting articles is that the putative author, who did hardly any work, gets credit for having written the paper, and quoting the same former ghostwriter: "The moral crime that I was being asked to commit was to do with truthfulness." That is, the problem is the "spin" that the article contained, not whose name is on the paper. Notice that this is a mirror image of the defense of the practice of ghostwriting offered by pharmapologists, who say that so long as the paper is accurate, who cares whose name is on it?
• Carl's interview with psychiatrist David Healy of the University of Cardiff, on the latter's extensive insider's view of the psychology of physician "KOLs" or opinion leaders shilling for industry: Healy argues that most of these so-called "leaders" are distinctly second-rate intellects. They and the industry need each other. These guys realize after getting to a certain point in their early careers "that they're not going to get the chair at Harvard or Yale, but [they] enjoy the lifestyle of being courted by industry, and having [their] articles written for [them], of having articles in JAMA or NEJM, which [they] wouldn't otherwise have". They realize that the only way they are going to advance in the field commensurate with their ambition is to jump in bed with industry. Industry in turn needs people with this psychological weakness in order to have a gang of bought physicians who will reliably do what the industry wants.
• How a person who had worked all his life in pharmaceutical marketing came to have his career-changing moment of epiphany: "I was in the exam room waiting for my doctor...[Seeing the room filled with industry knickknacks and brochures, he immediately thought:] I hope he's getting his information from the medical literature and not from people like me....That's when I realized that I was part of a big scam..."
• Quoting from the same former marketer, Joel Roselin: "When Joel worked in medical advertising, he used to schmooze with one of his bosses over coffee. The two of them got along well, and Joel felt comfortable joking around with him. One day Joel asked, 'If someone asked you to promote a product you thought was dangerous, would you do it?' His boss paused and thought about the question for a while. Eventually he came up with an answer: 'I'd like to think we wouldn't.'" (Talk about a clarion call for ethical behavior!)
• Carl, reflecting on his visit to Western IRB in Olympia, Washington, the most successful and prominent for-profit research ethics review board: Carl was invited by the founder of WIRB to visit, so that he'd see that his criticisms of for-profit IRBs were misplaced. Just before his arrival he was sent a detailed confidentiality agreement to sign, basically gagging him from telling anyone, ever, a single thing he saw during his visit. He arrived at WIRB and told the staff person who met him that he would not sign the form, nor any modification of it. This caused considerable consternation, but eventually the leadership decided that Carl could stay and visit, so long as he did not actually sit in on any ethics reviews of any actual research protocols. All through his visit, Carl heard a steady refrain: if only he could have actually seen the way WIRB reviews protocols, he would finally see why it had such a good reputation and why for-profit IRBs could function in a highly exemplary way. "As I drove away from the WIRB campus, it struck me that this obsession with secrecy was the hidden perversity of putting research oversight into the marketplace. Once such competitive pressures are instituted, there is no reason for any commercial IRB to share techniques to improve oversight. In fact, there is every reason not to share, because each commercial IRB has a competitive interest in the failure of other IRBs. ... Even if the members of any given commercial IRB sincerely want to protect the research subjects they oversee, they do not have any financial reason to want other IRBs to protect them, because every IRB that fails represents a potential business opportunity for the ones left standing." This contrasts markedly with university-based IRBs that routinely share their technques for improving their reviews of protocols--assuming that they ever develop any such techniques, which critics of IRBs commonly wonder about.

Summary comments: I have offered these tidbits from Carl's book because the majority of his content is already well known to regular followers of this blog. What, then, is the advantage of his book? One advantage is the nice way he was organized the material, running down the list of actors in the drama, and not sparing our own fellow bioethicists. The other, as illustrated here, is the great set of interviews that he has done and his lively presentation of what he learned.