Monday, January 25, 2010

India on Gifts to Docs: Just Say No

The following item came my way courtesy of the Healthy Skepticism list-serv and as the material itself is labeled for public release, I asume I have permission to post it here. It suggests yet a further way in which India may be ahead of the U.S. I have bolded what I take to be the key messages below.

The following editorial will appear in the Monthly Index of Medical Specialities, New Delhi, India in its January 31, 2010 issue. Released in advance for public information.

Indian Medical Council Defines Do's and Don'ts for Doctors

Extensive media coverage of the unethical, "you-scratch-my-back-I-scratch yours" nexus between most doctors and drug companies has spurred the Medical Council of India (MCI) to take action. In a notification issued last month, MCI has banned all relationships that can potentially harm the patients and bring medical practice to ridicule. The new rules cover both individual doctors and professional associations. Some examples:
Gifts: A medical practitioner shall not receive any gift from any pharmaceutical or allied health care industry. Since there is no mention of any monetary ceiling, even small value items are not permitted.
Travel: Any travel facility inside or outside the country for self and/or family members even for attending conferences, seminars, workshops, CME programme etc is not permitted. In the past drug manufacturers and doctors used to argue that such facilities were meant to advance the scientific knowledge and hence not improper. MCI has rejected this self-serving logic.
Hospitality: Any hospitality like hotel accommodation for self and family members under any pretext stands prohibited.
Cash or monetary grants: Receiving funds by doctors under any pretext has been banned. Funding for medical research, study etc. can only be received through approved institutions by modalities laid down by law / rules / guidelines adopted by such approved institutions. Such funding is to be publicly disclosed.
Medical research: Doctors are allowed to carry out research projects funded by pharmaceutical and allied healthcare industries under certain specific conditions such as after prior permission from the competent authorities including the Drugs Controller General, India (DCGI), relevant Hospital Ethics Committee, provision of proper facilities to human volunteers, public disclosure of the source and amount of funding at the beginning of the research itself. Above all the medical practitioner must have the freedom to publish the results of the research by inserting such a clause in the agreement or any other document before accepting such assignment.
Most drug companies routinely prohibit the publication of clinical trial results by individual investigators/hospitals under one pretext or the other. In such a scenario, there is an in-built risk of concealing unfavourable results of drug and medical devices trials to the detriment of patients.
Endorsement: of any commercial product by doctors was already banned in the year 2002. Two important additions have been made to his rule. Firstly, the professional associations of doctors are also barred from endorsements and secondly, any study conducted on the efficacy or otherwise of such products shall be presented to and/or through appropriate scientific bodies or published in appropriate scientific journals only. Thus doctors should not permit the use of results of such studies for any purpose by interested companies.
Violation of any of the MCI directives is considered "Misconduct" and therefore can invite penalties in the form of suspension or cancellation of registration to practice.
While the new rules deserve appreciation and applause, the real test will be the level and extent of implementation. Stronger and sharper teeth can be added to MCI regulations by amending relevant sections of the Income Tax Rules. All facilities with monetary value received by medical professionals from healthcare industry should be deemed to be perquisites in the hands of recipients and hence taxable. Similarly all expenses incurred by drug, medical devices and other healthcare companies in violation of MCI rules should be disallowed by amending income tax rules.
Dr. Chandra M. Gulhati,
Editor, Monthly Index of Medical Specialities, New Delhi, India.
Chandra Gulhati

Friday, January 15, 2010

DOJ: Johnson and Johnson Paid Big Kickbacks to Push Risperdal in Nursing Homes

For background, start with Ed Silverman's post on Pharmalot:
Then go to the DOJ press release (1 page):
Then finally if you want all the details go to the actual complaint (34 pages):

Based on whistleblower disclosures, the Feds are charging Johnson & Johnson with paying tens of millions of dollars in illegal kickbacks to Omnicare, a pharmacy management company that deals with nursing homes, to promote the use of Risperdal (which J&J is licensed to market). Omnicare has already settled charges against it for $98M. The basic drill was: Omnicare pharmacists reviewed charts of nursing home patients with dementia and then recommended to the physicians that they add Risperdal if the patient showed signs of agitation or inappropriate behavior due to dementia. The docs (who did not know that these pharmacists were basically being paid bribes to recommend Risperdal) agreed with the recommendations about 80 percent of the time.

This is bad for at least three reasons:

Drugging demented patients so that they behave nicely and don't bother stretched-thin nursing home staff (so-called chemical restraints) is a bad mode of geriatric practice. Risperdal does nothing to reverse or ameliorate dementia.
Even if it was OK to drug demented old folks, there are much cheaper drugs that are equally good (or bad) for sedating them, and there's no advantage to being sedated by a top-price drug.
Risperdal has been linked to several severe side effects, most notably weight gain, which in many older patients is bad enough to trigger Type II diabetes.

None of this is all that new if you've been following the marketing methods of the big drug firms closely. What is particularly striking in this case, to me, is that the charge includes details about just how the kickbacks were paid. There are a number of problems with paying kickbacks, especially if the patients are covered by Medicaid, as often is true in nursing homes. So the payments have to be hidden in a variety of ways. One way J&J elected to hide kickback money was to pay it out in the form of "education" grants. For instance, while four-fifths of the docs meekly accepted the recommendations to start Risperdal, there were those nasty few who balked. So J&J paid out a grant to "educate" the Omnicare pharmacists on the proper techniques to overcome the objections of those rebellious physicians. (See complaint, pp. 22-24)
I mention this example because we are often told in academia that such-and-such a payment or gift from a drug company is ethically harmless because it's in the form of an "education" grant. So my question is--now that we have even clearer evidence that the industry is quite happy to use "education" as a cover for illegal kickback payments (assuming that the DOJ allegations turn out to be supported at the end of the day), how can we believe that other "educational" grants from industry are benign? Not to put too fine a point on it, can we trust anything at all that these people tell us?
Now, let's admit right off that the events in this charge supposedly occurred around 1999-2003, given how long it takes DOJ to do an investigation of this sort and get all their ducks in a row for a prosecution. Some will no doubt then insist that this is all old history. That bad behavior was then; nowadays of course the industry would never do such a thing. To which my answer is once again-- not to put too fine a point on it, can we trust anything at all that these people tell us?

Sunday, January 10, 2010

Biased Policies on Stroke: It's Only Partly Pharma's Fault

This (long) post is about how Pharma marketing can play a not-unimportant but still subsidiary role in pushing a misleading health message onto both the medical profession and the public. I focus here on an issue that I haven't discussed that much previously, stroke prevention and treatment.

Let me summarize what many of my evidence-based friends give as the recent history of stroke treatment in the US. It's a frankly biased account but at the end I'll provide some specific references that bolster the case. Then I want to assess the relative responsibilities of various parties for putting this message out there.

Several studies were done in the early 1990s on treatment of stroke with clot-buster drugs--a cheaper older drug, streptokinase, and an expensive new drug, tissue plasminogen activator (tPA). As about 3/4 of strokes are caused by clots and not by bleeding into brain tissue, it seemed reasonable to try this approach, especially as similar studies had proven these drugs helpful in many cases of heart attack, similarly caused by clots. (Aggressive neurologists were starting to mount the campaign that we should rename stroke as "brain attack" to emphasize both the similarities with heart attack, and the need for specialized units to treat stroke akin to coronary care units.)

Most of these studies were discouraging. The clot-buster drugs either provided no benefit or else caused too many new brain bleeds. However, in 1995, one major trial, the NINDS study (funded by NIH), came out showing a slight benefit for tPA. The benefit was that patients given tPA within 3 hours of onset of stroke symptoms ended up, at 3 months out, having fewer disabling neurologic symptoms than the placebo group. And the price paid for this benefit was an increased number of serious bleeds in those getting tPA.

Based on this one slightly positive study, a number of interesting things happened that we must, in the end, account for. One might have thought that because of the slim nature of the evidence for clot-busting, the main lesson from NINDS would have been the need to do more extensive studies and to replicate the findings if possible. But, over the next decade, this happened not at all. Very recently, a new study has been published which claims again to be slightly in favor of tPA therapy. But for most of the interval, investigators were content to simply rehash and slice-and-dice the NINDS data. It was almost as if, having finally found one study that seemed to support tPA, both the manufacturer and the neurologist community were afraid to do a new trial that might come out differently.

Next, a new set of policies were developed out of the NINDS results. Rallying around the motto, "time is brain," neurologists browbeat their colleagues to create emergency care systems to assure that any patient with a new onset of stroke could be delivered to a specialized stroke treatment center within the magic three-hour window, so as to allow the safe use of tPA. These policies downplayed another important limitation of NINDS--the fact that so many exclusion criteria were applied, to eliminate all those patients at higher risk of bleeding from the treatment, that in the end, a very small percentage of all stroke patients would be candidates for the treatment. Ideally, maybe 1 in 6 stroke patients might meet all the qualifying criteria; but in real-world settings, it is not unusual for only 1% of patients to qualify. A relative minority of physicians have questioned the cost-effectiveness of creating an entire stroke treatment system around such bizarre and unfavorable numbers.

Two recent publications indicate a sense of how far we have come in treating stroke as a result of all this activity. (Hat tip to Rick Bukata and Jerry Hoffman, for their invaluable Primary Care Medical Abstracts audio series, in identifying and commenting on these studies.) Kleinig et al. from Australia identified 259 consecutive patients admitted to a specialized stroke unit, and did an intensive analysis of them. They calculated that, of the 183 patients who ended up diagnosed with disabling or fatal stroke, 135 had a risk factor that was being suboptimally managed. Based on standard criteria, they concluded that 70 of these strokes were preventable, had relatively simple and cheap measures such as controlliong high blood pressure been employed. By contrast, they took the most favorable existing statistics for tPA treatment of stroke (such as calculating that 15% of patients rather than 1% would end up being tPA candidates), and concluded that if tPA performed as it did under the most favorable circumstances, at most, it could have prevented disability in 4 of the 183 strokes. Kleinig and colleagues put forth this difference (benefiting 4 vs 70 patients) as a hint that maybe we have got it all wrong, and that the primary focus of so-called "stroke units" ought to be on prevention using known and cheap interventions, and not rushing patients to the center to get tPA after the fact. At any rate, it seems to huge amount of resources invested in aggressive stroke treatment might have been better employed.

That in turn raises the question of how tPA actually performs, given that the advantage noted by Kleinig et al., 4 out of 183 patients with some improvement, represents the best-case scenario, and is far from the usual outcome in community practice today. That's the focus of the second article by Jerome R. Hoffman and David L. Schriger of UCLA. With considerable effort, they managed to get hold of the complete raw data from NINDS, and the article (which on line runs 43 pages) represents their attempt to display the outcome data from NINDS graphically in every possible way. Hoffman and Schriger invite the reader to look at the graphs and draw their own conclusions.

The conclusions that the two believe that a fair-minded reader will come to are, first, that all the supposed advantage of tPA was most likely due to the fact that fewer subjects in the tPA group had severe stokes, compared to the placebo group. They point out that if you compare how patients with severe, moderate, and mild strokes did on tPA vs. placebo, within each category the outcomes were nearly identical. But, because there were fewer severe and more moderate and mild strokes in the tPA group, the overall outcomes were better with tPA administration. So the apparent success of tPA in NINDS ultimately reflects a failure of adequate randomization rather than the drug effect.

The second conclusion that Hoffman and Schriger believe we'll arrive at from their graphs is to examine what happens when tPA (or placebo for that matter) is given during each possible time interval after the stroke. According to the "time is brain" theory, those lucky enough to get tPA only 70 minutes post-stroke (as early as anyone managed to give it) would have done better than those who only got it 3 hours later. But the raw data of NINDS reveals no difference at all based on time to medication. In short, "time is brain" received no empirical support from NINDS.

OK, so I'll conclude that these two recent papers, along with a lot of criticism of NINDS already published elsewhere, goes to raise considerable doubts as to the wisdom of focusing on post-stroke clot-busting drugs as a major tool in preventing the worst consequences of stroke--and that this focus may well have diverted us from things that really would work like better stroke prevention. Now, if you have read this blog regularly, you are waiting for me to claim that this must be the result of over-the-top marketing of tPA.

My conclusion is that drug marketing has played some role in all this, probably most specifically, the failure to do adequate replicatory trials after NINDS. But it would be unfair to industry to attribute all the blame in that direction. The other group that must bear responsibility is the neurology community, the folks that my primary care colleagues sometimes refer to as the "brain attack mafia," who have been beating the drums for stroke treatment centers, faster EMT transport of stroke patients, and the "time is brain" theory ever since the ink dried on the first NINDS publication. These folks, so far as I can tell, were to some extent motivated by jealousy of their friends the cardiologists--who get to make really big bucks by sticking thin tubes into people having heart attacks and doing nifty procedures and injecting nifty drugs. But much more, these neurologists have been discouraged by the helpless feeling of watching stroke patients either get better or not, without having a "magic bullet" intervention that you believe will really help. So that when something came along and there was the tiniest smidgeon of evidence that it might be the magic bullet, these folks all leapt onto that bandwagon. The hope of finally being able to help a group of patients that medicine had previously been unable to do much for seemed to be the big motive here.

Pharma marketing can do a certain amount of damage to rational medical care on its own. It can do much more damage when it joins forces with physician over-exuberance, however benignly intended.

Kleinig TJ, Kimber TE, Thompson PD. Stroke prevention and stroke thrombolysis: quantifying the potential benefits of best practice therapies. Medical Journal of Australia 190:678-682, 2009.
Hoffman JR, Schriger DL. A graphic reanalysis of the NINDS trial. Annals of Emergency Medicine 54:329-336, 2009.

Thursday, January 7, 2010

Return of the Usual Suspects: Shadowy Interest Groups Lobby on Health Reform

Dan Eggen, in the Washington Post:

--wanted to know who pays for some of the lobbying activities around health reform legislation. In some cases it's clear who pays what piper; in other cases the organization is registered as a nonprofit and it's harder to track down where the money trial leads. In the process Eggen reintroduces us to some of our ol' friends from "astroturf" days, that we have encountered previously in this blog, or even when I was writing HOOKED. (For newcomers, "astroturf" relates to false grass roots, and describes an organization that is intended to look like a legitimate, grass-roots citizen advocacy group, when in fact it is almost completely bank-rolled and controlled by powerful corporate interests channeling their funds through their usual PR apparatus.)

The oldest of our old friends (in more ways than one) is the 60 Plus Association, a self-proclaimed conservative alternative to the AARP. When AARP was lobbying against some Pharma-friendly provisions in the 2003 Medicare Part D legislation, notably the provision that prevents the government from using its buying power to bargain down drug prices, it found itself opposed by the 60 Plus Association, which posed as a legitimate senior advocacy group. As I recounted in HOOKED, investigations showed that this outfit and others like it were in fact the creations of Pharma-funded PR firms, and had no office addresses and no membership lists. 60 Plus in 2007 reported no membership dues and less than $2M in revenue. This past year 60 Plus has spent $9M on TV spots that attack health reform as an evil plot against seniors. The "founder and president," James L. Martin, insisted to Eggen that 60 Plus had received no funding from drug companies, insurers, or the Republican Party, but refused to say where the money did come from.

Other old friends: Partnership to Improve Patient Care, headed by former Congressman Tony Coelho, "formed by the drug industry in November 2008 to lobby against binding government effectiveness studies"; and Center for Medicine in the Public Interest, a "think tank" led by Peter Pitts, who co-incidentally works as global healthcare chief at Porter Novelli, a PR firm who is employed by many big drug firms. Eggen reports that Pitts earned $250,000 in 2007 as head of CMPI, but did not report what his other job at Porter Novelli paid during the same period.

The blurred money trail provides some insights into how a drug firm, if it wished, could have it both ways. Through PhRMA, the firm could get brownie points by insisting that it is pro-health-reform and even is willing to give up some future profits in the name of being a good corporate citizen. Behind the scenes, via one of these PR or lobbying efforts, the firm could be working to assure that whatever bill is passed is one favorable to Big Pharma.

Wednesday, January 6, 2010

If You Can't Lick 'Em...

Timothy Carney in the Washington Examiner notes President Obama's apparent turnaround on lobbying by PhRMA:

Candidate Obama made practically a career of holding up Billy Tauzin, former Congressman and President of PhRMA, as the main poster child for what was wrong with the Washington special-interest system--how Tauzin helped write a bill for Medicare Part D especially favorable to the drug industry, then switched sides and started collecting a $2M annual paycheck from PhRMA.

Since Obama became president, guess which lobbyist has visited the White House frequently, asks Carney, noting that visitor logs just released show Tauzin dropping in on his buddy Barack (or somebody in the White House) at least 11 times in the first 6 months of the new administration.

We have not very closely followed the story of how the horsetrading has gone between the administration and PhRMA over the year 2009. At first it seemed as if the White House had won a significant victory by getting PhRMA to agree to forgo $80B in future profits in the name of health care cost control. It later started to appear more evident that PhRMA simply planned to drive prices high enough before reform takes effect to compensate for the later losses in higher initial prices, making their apparent sacrifice instead a wash. So just who many have snookered whom in the negotiations over PhRMA's support for reform has yet to be determined.

The fact remains however that PhRMA at least officially and up front has claimed that it is supporting the Obama health reform effort. So one naturally might ask--how often did lobbyists for other organizations that support reform visit the White House during those months? There may be nothing exceptional about Tauzin's schedule when one looks at the bigger picture.

Tuesday, January 5, 2010

The Increasing Price of Medical Journal Editors?

You're seen in the press these last few days that health care costs moderated last year, apparently under the influence of the recession, though they still grew at a faster clip than the rest of the economy.

But one health care cost may be rising--the cost of keeping a friendly journal editor in your back pocket. In orthopedics and spinal conditions, it may have reached the price of $20 million over a 7-year period. At least so says investigative reporter John Fauber in his continuing excellent series of reports in the Milwaukee Journal-Sentinel:

Fauber introduces us to Dr. Thomas Zdeblick, an orthopedic surgeon on the faculty of the University of Wisconsin. He became editor-in-chief of the Journal of Spinal Disorders & Techniques in 2002. Since then he's been paid $20M in royalties by Medtronic, the huge medical device firm.

Fauber reports that while the journal contains an average of one article per issue on a Medtronic product, the vast majority being favorable, readers are not told that the editor receives any funds from Medtronic. Dr. Zdeblick was also a co-author of some of these articles, but in at least some cases, the financial relations between the authors and Medtronic were not listed, either.

Fauber mentions the reactions of several former journal editors who make clear that in a case like this, the usual way many suggest that we deal with conflict of interest--disclosure--is insufficient. When these vast sums are changing hands, they suggest, the individual ought not be editor of such a journal, period. From which point of view I find it very hard to dissent.

Sunday, January 3, 2010

The Times They Are A'Changin'? So Says Harvard Affiliate

From the New York Times, reports of tighter rules governing senior physicians who serve on corporate boards at some Harvard affiliated teaching hospitals:

Two things are perhaps of most interest about this report. First, one of the main justifications given for the restrictions on what the big boys can make from serving on corporate boards is fairness. The tendency at academic centers is increasingly to restrict the ability of lower level faculty to earn extra bucks by serving as paid speakers for drug companies. The argument--if we are going to restrict the earning potential of mid-level faculty, we should be fair and assure that the senior faculty cannot walk off with $200K a year.

Second, the article contains no quotations from anyone disagreeing with these new rules, despite what I assume to be the usual journalistic rules of trying to tell both sides of the story. From Dr. Eugene Braunwald, probably the world's most prominent cardiologist, comes the blunt statement, “what was O.K. three years ago is not O.K. now.” As far as this group of academic docs is concerned, a page has turned and there is no going back.

Saturday, January 2, 2010

Slicing Salami as Drug Marketing

The phenomenon of "salami slicing" or "least publishable unit" is generally associated with academics and not commerce. One approaches the publication of a study that has yielded a certain amount of data not with the ideal mindset, "How could these data be reported in a way that most advances scientific knowledge?" but rather with, "How many publications can I generate from this given quantity of data?" The goal is generally the padding of one's CV.

The same technique, however, can be an effective tool for marketing drugs. If you do one study of a drug, and it results in six publications in six journals read by six different audiences, then you have spread the marketing message about the drug that much wider.

Glen Spielmans, Tracey Biehn, and Dustin Sawrey of the Department of Psychology, Metropolitan State University, St. Paul, MN, note that few studies have attempted to dissect salami slicing as it might pertain to pharmaceutical marketing. Thir review (subscription required) undertakes to analyze the phenomenon with regard to one drug, the antidepressant duloxetine (Cymbalta).

Their first finding was that a great number of pooled data analyses had been published, but that the vast majority were in one way or another a repackaging of only 8 controlled trials. Two of these 8 trials provided data for 33 pooled data analyses, and 6 of the 8 provided data used later in at least 20 pooled analyses.

The next finding had to do with redundancy in reporting data from the pooled analyses. For example, review of pooled data showed that it did not make any difference in either safety or efficacy if duloxetine was prescribed for men vs. women, African-American vs. caucasian, or Hispanic vs. non-Hispanic patients. One might have thought that a single published article would be sufficient to say that. Instead, three separate publications made those three comparisons.

None of this is any great surprise to those of us who have been following the drug-marketing and publication issues, nor is it news to find that the reviewers and editorial boards of medical journals appear to be easy pushovers for this sort of commercial marketing campaign. The present article, however, provides a finer-grained analysis of just how this can be accomplished and the extent to which the problem exists.

Spielmans GI, Biehn TL, Sawrey DL. A case study of salami slicing: pooled analyses of duloxetine for depression. Psychotherapy and Psychosomatics 79:97-106, 2010; e-pub 12/24/09