Princess Health and British Government Concludes GSK Suppressed Paxil (Seroxat) Data. Princessiccia

Princess Health and British Government Concludes GSK Suppressed Paxil (Seroxat) Data. Princessiccia

clinical trials GlaxoSmithKline Paxil pharmaceuticals SSRIs suppression of medical research

Gusty 13:30 Add Comment

Last year, we summarized the results of a BBC investigation broadcast on the television program Panorama that charged that GlaxoSmithKline "distorted trial results of an anti-depressant, [Seroxat in the UK, Paxil in the US, chemical name paroxetine] covering up a link with suicidal teenagers." (See also the links in that post to extensive discussion on the Clinical Psychology and Psychiatry Blog.)

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has just completed an investigation, and it is fitting to quote the BBC story about its results.

It comes after the drugs regulator announced GlaxoSmithKline would not face criminal proceedings over claims it withheld information on Seroxat.

But they warned GSK should have been quicker to raise the alarm on the risk of suicidal behaviour associated with the antidepressant in the under-18s.

GSK has rejected claims it improperly withheld drug-trial information.

The Medicines and Healthcare products Regulatory Agency (MHRA) received data from clinical trials in May 2003 showing that patients under 18 had a higher risk of suicidal behaviour if they were treated with Seroxat than if they received a placebo.

Data also showed that Seroxat was not effective for treating depression in children and adolescents.

But Professor Kent Woods, MHRA chief executive said they were disappointed GSK had not given them information earlier and that drugs firms had an "ethical responsibility".

"I remain concerned that GSK could and should have reported this information earlier than they did.

"All companies have a responsibility to patients, and should report any adverse data signals to us as soon as they discover them.

The government decided not to pursue criminal charges, mainly because of "important weaknesses in drug safety legislation in force at the time."

Also,

Health minister Dawn Primarolo said the government would take immediate steps to secure a strengthening of the law in the UK and Europe.

She also said they wanted to make it clear to all pharmaceutical companies that, "notwithstanding the limitations that may exist in the law, they should disclose any information they have that would have a bearing on the protection of health".

The Guardian reported the forceful opinions of the [UK] Mental Health Foundation chief executive, Andrew McCulloch,

It is totally unacceptable to hear that, when information can be made available at speed, young people may have taken their own lives due to a lack of transparency by a pharmaceutical company.

Woods further commented in another article in the Guardian,

I really feel there is an ethical obligation that pharmaceutical companies ought to recognise and it seems to have been lost. Twenty years ago I was a prescribing doctor and I took it for granted that if there was information relevant to the drug I was going to prescribe, then it would be available. We're talking about something which has direct relevance to health and safety.

The Guardian also noted that Woods "could not rule out the possibility that other companies were sitting on unpublished data that could cause them commercial damage."

So, in case there was any doubt, based on this UK government report, it seems very clear that GSK suppressed data about the adverse effects of Seroxat in an effort not preserve sales. This was a blatant effort to put company profits ahead of patient well-being and a slap at the integrity of the clinical science data base. This has hardly been the only case of suppression of clinical research data because it reflected poorly on some company's products or services.

And pharmaceutical executives wonder why no one trusts them anymore?

I doubt there is any way to secure the integrity clinical research short of banning all involvement by corporations with vested interests in having specific research studies come out in ways that favor their products or services.

See also the forceful comments by Dr Aubrey Blumsohn on the Scientific Misconduct Blog. He called it "a day of shame."

Princess Health and Fat Chance: Conflicts of Interest and Calorie Counting. Princessiccia

Princess Health and Fat Chance: Conflicts of Interest and Calorie Counting. Princessiccia

conflicts of interest GlaxoSmithKline medical organizations obesity Sanofi-Aventis

Gusty 11:08 Add Comment

Stephanie Saul in the New York Times, and Karl Stark in the Philadelphia Inquirer have covered the curious story of the downfall of the president-elect of the Obesity Society. Last month, Ms Saul set the stage,

New York City�s new rules for menu labels at chain restaurants have set off a food fight among the nation�s obesity experts.

Most support the theory of the city�s health commissioner that forcing chain restaurants to list the calories alongside menu items � flagging that a Double Whopper With Cheese has 990 calories, for example � will make patrons think twice about ordering one. The rules are set to take effect at the end of March.

There is a countertheory, however, set forth by Dr. David B. Allison, the incoming president of the Obesity Society, a leading organization of obesity doctors and scientists. An affidavit he recently submitted to the United States District Court for the Southern District of New York has ignited a controversy within his organization.

In the filing, Dr. Allison argues that the new rules could backfire � whether by adding to the forbidden-fruit allure of high-calorie foods or by sending patrons away hungry enough that they will later gorge themselves even more.

It might be only a scientific debate among nutrition experts, except for the fact that Dr. Allison was paid to write the document on behalf of the New York State Restaurant Association, which is suing to block the new rules.

Dr. Allison�s role in the debate has angered some members of the Obesity Society, setting off an e-mail fury since word of his court filing began to circulate. Some have pointed to Dr. Allison�s other industry ties, which have included advisory roles for Coca-Cola, Kraft Foods and Frito-Lay.

Many of the group�s 1,800 members are �completely mad that a president-elect of the Obesity Society, an organization that cares about obesity and cares about healthy eating, wants to hold back information from people that helps them make healthy choices,� said Dr. Barry M. Popkin, a member of the organization, who is director of the Interdisciplinary Obesity Center at the University of North Carolina, Chapel Hill.

Dr. Allison, a professor of biostatistics and nutrition at the University of Alabama, Birmingham, is scheduled to start a one-year term as president of the Obesity Society in October. He has defended his affidavit. In a telephone interview, he said he did not take a position for or against menu labeling in the document but merely presented the scientific evidence that the labeling might deter over-eating but might not and, in fact, might be harmful.

He also defended his work for the restaurant industry, but would not disclose how much he was paid for his efforts.

�I�m happy to be involved in the pursuit for truth,� Dr. Allison said. �Sometimes, when I�m involved in the pursuit for truth, I�m hired by the Federal Trade Commission. Sometimes I help them. Sometimes I help a group like the restaurant industry. I�m honored that people think my opinion is sufficiently valued and expert.�

The executive vice president for the restaurant association�s metropolitan New York chapters, E. Charles Hunt, said that Dr. Allison was retained by the association�s lawyers. �Obviously, a lot of it was in favor of our position,� Mr. Hunt said, �although he didn�t come right out and say that.�

So this sounds like yet another story about conflicts of interest, and their possible effects influencing the publicly expressed opinions of a prominent academic. As usual, the conflicted party angrily denied that his financial relationships could have affected his scientific judgment. As we have noted before, this is undoubtedly a sincere belief, but psychological evidence and common sense suggests that having financial ties to organization x may influence one to take positions in line with organization x's interests, even if these influences do not reach conscious thought.

The variant here seems to be that the academic had a financial relationship not with a drug, biotechnology or device company, the usual suspects, but with an association of restauranteurs.

But wait, Mr Stark added more in his story in the Philadelphia Inquirer,

The relationship between academic researchers and industry is a front-burner issue in many fields. Several congressional inquiries are looking at drug-firm support for the American College of Cardiology, the national cardiology group, and the American Heart Association.

Compared with those groups, the Obesity Society, based in Silver Spring, Md., would seem like a tiny outpost with its $2.1 million budget. But the group's 1,800 members include many influential researchers, physicians and dietitians.

The society relies heavily on industry money, raising about $1 million in the last year from various companies, said Morgan Downey, the group's executive vice president. The biggest corporate donors were drugmakers sanofi aventis, GlaxoSmithKline and Allergan as well as the health-care conglomerate Covidien, he said.

About $230,000 of the corporate money funded a conference in September for health advisers to presidential candidates, Downey said.

Fast forward to this week, when Ms Saul reported in the New York Times that Dr Allison is giving up his leadership position for the Obesity Society,

A dispute over food industry influence has resulted in the resignation of the incoming president of the Obesity Society.

Dr. David B. Allison, who was to take over the society, a national group of obesity doctors and researchers later this year, submitted his resignation from that position on Friday.

So what happened? Did the Obesity Society cast out a leader because he had conflicts of interest that interfered with his ability to advance science, education and clinical practice? Or did the Obesity Society cast out a leader because he was aligned with commercial interests opposed to the commercial interests that provide most of the society's support? That is, was he cast out not because he had conflicts of interest, but because he did not have the same conflicts of interest as the society?

Who can tell?

Once again, this case is an illustration of the pervasiveness of conflicts of interest affecting health care organizations. It also shows how the pervasiveness of such conflicts sometimes makes it impossible to discriminate debates about science and health policy from the claims of conflicting pitchmen.

Full disclosure of these conflicts beforehand would at least have given warning that the nature of the debate was ambiguous.

But to figure out the best answer in the current policy debate, that is, whether it really is a good idea to have legislation to put calorie counts on restaurant menus, would really require the input from people who are not paid by either restauranteurs, or those selling obesity treatments. Fat chance that will happen soon.

Princess Health and Money for Nothing: More Guilty Pleas at UMDNJ, but Anechoic Effect Continues. Princessiccia

Princess Health and Money for Nothing: More Guilty Pleas at UMDNJ, but Anechoic Effect Continues. Princessiccia

anechoic effect crime power elite UMDNJ

Gusty 07:57 Add Comment

We have done a long series of posts about the troubles at the University of Medicine and Dentistry of New Jersey (UMDNJ), the largest US health care university. The university was operating under a federal deferred prosecution agreement under the supervision of a federal monitor (see most recent posts here, here, here, here and here.) We had previously discussed allegations that UMDNJ had offered no-bid contracts, at times requiring no work, to the politically connected; had paid for lobbyists and made political contributions, even though UMDNJ is a state institution; and seemed to be run by political bosses rather than health care professionals. (See posts here, and here, with links to previous posts.) More recent were some reports of amazingly wasteful decisions by UMDNJ managers leading to spending millions of dollars for real-estate that now stands vacant (see post here). There was the indictment of a powerful NJ politician for getting a no-work job in the system, and the indictment of the former dean of the university's osteopathic medicine school for giving him the job (see post here). We found out that UMDNJ had named one of its teaching hospitals for a pharmaceutical company in 2001 (see post here), that the federal monitor accused the dean of one of the UMDNJ campuses of fixing students' grades (see post here), and that the monitor found even more bizarre financial practices at the university (see post here). Although the monitoring ended this year, his most recent report found previously undisclosed problems with the university's research compliance (see post here).

Over a year ago, it was reported (see post here with links to previous posts) that UMDNJ gave paid part-time faculty positions to some community cardiologists in exchange for their referrals to the University's cardiac surgery program, but not in exchange for any major academic responsibilities. Last week, the Newark Star-Ledger provided some f0llowup,

Two cardiologists yesterday admitted signing on to high-paying, no-show jobs at the state's medical university in return for funneling patients to the school's troubled heart surgery program.

As part of the kickback scheme, the two were hired as clinical assistant professors at the University of Medicine and Dentistry of New Jersey, despite having no research credentials. They gave no lectures, taught no classes and acknowledged that they essentially did nothing more than refer patients for cardiac procedures while receiving hundreds of thousands of dollars in salary over three years.

The doctors -- Bakul Desai, 52, of Livingston and Laxmipathi Garipalli, 59, of Colts Neck -- are cooperating with the U.S. Attorney's Office and the FBI in a two-year criminal investigation that so far has implicated more than a dozen other part-time cardiologists and several top UMDNJ administrators. The scheme was hatched as part of an increasingly desperate effort to beef up a failing cardiac surgery program then on state probation, according to court records and reports by a federal monitor.

No university officials or any other physicians have been charged, although UMDNJ's chairman of medicine was forced to step down after the initial revelations became public.

In proceedings yesterday before U.S. District Judge Stanley R. Chesler in Newark, the doctors pleaded guilty to embezzling approximately $840,000 in payments from the university. The physicians stood quietly, answering questions with simple 'Yes' or 'No' answers. Both face possible jail time and suspension or revocation of their medical licenses.

U.S. Attorney Christopher Christie said others will be held accountable.

'UMDNJ has a culpable role in all of this,' Christie said. 'Don't take from these two guilty pleas today (the idea) that the institution itself is off the hook, because I will say quite clearly it is not.'

A university spokeswoman said UMDNJ and its board have 'worked aggressively' to restructure and reform the community cardiology program since concerns were first raised in 2006, including a reduction in the number of community cardiologists and changes in salaries and reporting requirements.

Desai and Garipalli should have known from the start that they were taking money for doing nothing, Christie said.

'They continued to do nothing and they continued to get paid in what is a classic New Jersey no-show government job scam,' Christie said during a news conference afterward. 'Extraordinary fraud and waste and abuse and illegality that was occurring with public money at UMDNJ.'

So here is even more documentation about the muck in which UMDNJ is mired.

We will wait and see whether there are more criminal charges in this case. In cases of health care corruption, it often seems that any penalties incurred affect those lowest on the totem pole, in this case, the two unfortunate cardiologists. Those higher up all too often get to walk away. This suggests how health care has come to be run by a power elite that do not have to follow the rules to which mere mortals are subject. I hope Mr Christie is able to buck this trend.

In the UMDNJ case, it seems obvious that someone in the management of UMDNJ had to have been involved in this scheme. It is hard to see how it could have occurred otherwise. So we wait and see if any such people are identified, much less convicted.

Another striking feature of the UMDNJ case is its manifestation of the anechoic effect. I put in a fairly long summary above at the beginning of this post emphasizing the magnitude, importance, and complexity of this case. I did so because many people, including many health care professionals and health policy makers, may be totally unfamiliar with the UMDNJ case. It has only been discussed in the news media in New Jersey (and to some extent the neighboring states of New York and Pennsylvania) and in Health Care Renewal. It has not, repeat not ever been discussed in any medical, health care, health services research, or health policy journal. It has not, repeat not appeared in any prominent medical. (I repeated the relevant searches today, of Medline, Google Scholar, and of the American Medical News, JAMA, and MedPage.)

An entire health care university admitting guilt, being subject to a deferred prosecution agreement, operating under a federal monitor, while all sorts of mismanagement and unethical behavior were uncovered, and NO ONE thinks it is worthy of discussion in any medical, health care, health services research, or health policy journal or newsletter?

The anechoic effect lives. And as long as it lives so vigorously, we make no progress in attacking the pervasive mismanagement, conflicts of interest, and outright corruption afflicting the management of health care. If we cannot even talk about these problems, how are we going to solve them?

Talking about them, however, might disturb the power elite that personally profits so much from their domination of health care. Hence, most health care professionals who are lower in status realize that to even mention such topics in public is to imperil one's career.

But as long as we cannot discuss the recent unpleasantness, things will continue to get even more unpleasant.

Fight the anechoic effect. Take back the future.

Princess Health and A SLAPP Against Clinical Research?. Princessiccia

Princess Health and A SLAPP Against Clinical Research?. Princessiccia

free speech intimidation medical devices

Gusty 14:11 Add Comment

Posts on the Wall Street Journal Health Blog, the Clinical Psychology and Psychiatry Blog, and by Dr Aubrey Blumsohn on the Scientific Misconduct Blog all picked up on a brief story in the Harvard Crimson about a lawsuit apparently claiming that a clinical research article, and a randomized controlled trial no less, was defamatory. Here is the gist from that news article,

Harvard Medical School professor Douglas P. Kiel is facing a lawsuit because of an article he published in the July 2007 issue of the Journal of American Medicine (JAMA).

In the study, Kiel, a gerontologist, said that hip protectors are not effective in preventing injuries among elderly patients, a claim challenged by HipSaver, a popular hip protector manufacturer, in a suit filed in Norfolk Superior Court on Feb. 15.

HipSaver�s president, Edward L. Goodwin, said in an interview that it was scientifically inaccurate for the conclusions of Kiel�s study to be applied to hip protectors in general.

Robert L. Hernandez, who is representing HipSaver, described Kiel�s article as 'disparaging' and 'grandiose.'

Actually, as quoted by Dr Blumsohn, the JAMA article's conclusions were framed in the typically measured terms of clinical research reports.

In summary, this large multicenter clinical trial failed to demonstrate a protective effect of a hip protector on hip fracture incidence in nursing home residents despite high adherence, confirming the growing body of evidence that hip protectors are not effective in nursing home populations.

These results add to the increasing body of evidence that hip protectors, as currently designed, are not effective for preventing hip fracture among nursing home residents.

[See Kiel DP, Magaziner J, Zimmerman S et al. Efficacy of a hip protector to prevent hip fracture in nursing home residents: the HIP PRO randomized controlled trial. JAMA. 2007; 298: 413-422. Link here.]

Of course, if these conclusions were libelous, than practically any scientific article could be considered libelous.

Equally obviously, HipSaver leadership have a perfect right to criticize the Kiel article. But to sue the authors because the company disagrees with their conclusions could have a chilling effect on science. This lawsuit seems to be a deliberate effort to intimidate clinical scientists who dared to collect and publish data which suggesting that commercial products may not be as wonderful as their marketers claim.

If clinical scientists start fearing to publish such conclusions, then we can throw the whole of science based medicine out. This, of course, would be a catastrophe.

Furthermore, this lawsuit can be construed as an attack on basic human rights in the US context. In this context, it appears to be a SLAPP, that is, Selective Litigation Against Public Participation. This term was coined to describe lawsuits designed to intimidate people from speaking out about issues of public interest (but in a way that might threaten vested interests.) For more information about SLAPPs, see the SLAPP Resource Center. Also see this article from the First Amendment Center.

Most US states, including Massachusetts, have laws that allow SLAPPs to be countered. For example, in Massachusetts, the law provides (see the SLAPP Resource Center), ]

Any written or oral statement made to, or in connection with, a governmental proceeding is protected under the statute. In addition, any statement that is reasonably likely to encourage review of an issue by the government or enlist public participation is protected under the statute. Other important provisions of the statute include: (1) a special motion to dismiss; (2) an expedited review of the special motion to dismiss; (3) the government may defend or support the defendant in the special motion to dismiss; (4) all discovery is stayed upon the filing of the special motion to dismiss; (5) the burden shifts to the plaintiff to prove the statements were not protected by the statute; and (6) costs and reasonable attorneys� fees shall be awarded to a victim prevailing on the motion to dismiss.

I don't think it is too much of a stretch to apply the SLAPP concept to a lawsuit aimed at the free discussion of the effectiveness of treatments in health care, given that the government indirectly or directly pays for many of these treatments, and that determining the effectiveness of treatments is clearly a public health policy issue.

I fervently hope HipSavers withdraws this ill-conceived lawsuit. If the company persists, I fervently hoped its attempted SLAPP gets slapped down.

Here is another sorry example of how health care, particularly clinical research, is under seige by those with vested interests and private agendas.

Princess Health and Stories About Device Manufacturers' Payments to Orthopedic Surgeons Resurface. Princessiccia

Princess Health and Stories About Device Manufacturers' Payments to Orthopedic Surgeons Resurface. Princessiccia

conflicts of interest medical devices orthopedic surgeons

Gusty 13:48 Add Comment

Late last year, we posted (here, here, and here) about the payments, often huge, that five manufacturers of prosthetic joints (Biomet, DePuy Orthopaedics (a unit of Johnson & Johnson), Stryker Orthopedics,a unit of Stryker Inc, Zimmer Holdings, and Smith & Nephew) revealed they made to orthopedic surgeons and various academic and other organizations. The lists are here: Biomet, DePuy, Smith & Nephew, Stryker, and Zimmer. We also noted that some of the leadership of the major orthopedic societies have received substantial amounts from these companies, as have the societies themselves.

Despite the obvious potential for these payments to influence practice, teaching, and research, the issue received almost no attention after the initial media reports. Last week, however, it created a few more ripples. As reported by Bloomberg News, via the Washington Post,

Four makers of artificial hips and knees paid doctors more than $800 million in royalties and fees in four years to influence their choice of implants, a U.S. investigator told Congress.

The unidentified companies control about three-quarters of the $9.4 billion worldwide market for hips and knees, said Gregory E. Demske, an assistant inspector general at the Health and Human Services Department, at a hearing yesterday of the Senate Special Committee on Aging.

'Illegitimate' payments, the extent of which is unknown, influence orthopedic surgeons' medical judgment and are so common that it will be difficult to eliminate the practice, Demske and other witnesses said. The fees have enriched doctors and distorted the market by bolstering sales of lower-quality devices, they said.

'Industry and physicians are equally culpable,' said Sen. Herb Kohl (D-Wis.), chairman of the panel. 'Some physicians make it known to the companies that they will be loyal to the highest bidder. Where does the patient's well-being fit into the equation?'

Even an executive at one of the device companies admitted problems with the payments.

It's clear the device companies went too far, said Chad Phipps, Zimmer's general counsel.

'In hindsight it now appears that as the industry expanded to meet patient needs, the use of consultants may have been excessive at times,' Phipps told the committee.

In addition, a Minneapolis Star-Tribune story referred to

Wine-tasting outings to California's Napa Valley. Ski trips to Colorado. Tickets to sporting events. Gourmet meals at swanky restaurants. Forays to 'adult entertainment' clubs. Fat checks for what some see as questionable work.

And a Wall Street Journal story gave this example

In some cases, a company sales representative would spend one or two hours in an operating room watching a surgeon implant his company's device. The company would then pay the doctor for eight to 10 hours of 'training' services, according to findings that government investigators shared with the committee.

Maybe I shouldn't be amazed that this story has provoked so little response, much less outrage. Even though some academic orthopedists were getting literally millions of dollars a year (see this post), very few seem worried that such fabulous payments might have had some influence on their clinical decisions, on what they taught their students or colleagues, or on their research.

As noted before, some people are concerned by how physicians may be influenced by gifts of pens, coffee mugs, and pizza lunches. If we should be concerned about coffee mugs, how much more should we be concerned by multi-million dollar royalties or consulting payments?

But of course, it's easier to forbid coffee mugs and pizzas for medical students and house-staff than making the chair of orthopedics choose between his job and his multi-million dollar royalties.

Princess Health and The Spooky Stability of U.S. Health Care. Princessiccia

Princess Health and The Spooky Stability of U.S. Health Care. Princessiccia

Gusty 15:16 Add Comment

I only read last week a terrific commentary by Lawrence Brown in the New England Journal of Medicine�s January 24, 2008 issue on reform of the U.S. healthcare system and its chances. It�s titled The Amazing Noncollapsing U.S. Health Care System � Is Reform Finally at Hand?, and full text is available free to everyone.

Like Brown, I remember in 1993 when the punditry was pronouncing that health care reform was inevitable (it wasn't). I don�t remember (I was a kid) but have read health care panel discussions on policy from the 60�s amazingly reminiscent of today�s discussions about what an ever-increasing share of the GDP healthcare costs had become and how this was unsustainable. Brown�s article discusses the strong forces that make for stability in our very problematic healthcare system.

DemfromCT at DailyKos noticed the article promptly and commented.

Jeff Goldsmith at the Health Care Blog also comments, but I think takes the discussion in a completely wrong-headed direction by suggesting that this stability is benign. As Brown points out, it is far from that. This stability allows the continuance of the false complacency Americans so frequently have about �everybody getting healthcare� (despite poor kids and adults without asthma medication, cancer patients who can't get treated, lack of dental care and its toll in both physical and mental pain and infection, unavailability of rehab care and needed medical equipment, etc., etc.). It allows the continuance of an expensive idolatry of technology and of rampant, unnecessary, and harmful overtreatment [see Shannon Brownlee's excellent book on the topic of overtreatment]. It allows the continuance of a dangerous and patchy �non-system of care,� as Brown so rightly points out.

But as Brown also points out, the forces making for stability and non-collapse are powerful indeed. If you missed the article too, it�s well worth reading.

Princess Health and Pharma arguments and hogwash. Princessiccia

Princess Health and Pharma arguments and hogwash. Princessiccia

Gusty 14:35 Add Comment

The heparin manufacturing scandal sheds light on the typically rampant cynicism of U.S. Pharma arguments. When before the Medicare drug benefit there was a lot of pressure to allow importation of Canadian drugs, both sides were rather disingenuous in their arguments.

The pro-import side typically just presented it as an issue of competition and of not letting U.S. companies rip off U.S. citizens. What went unsaid is that what we were importing (and I thought it was in many ways an excellent idea) was not really Canadian drugs, but Canadian price controls. Since �price controls� is a four-letter word in the American lexicon, this was rarely stated.]

On their side and much more cynically, Pharma companies (with FDA complicity) stirred up fears about FDA approval and importation of allegedly dangerous �foreign drugs�. Unsaid was how many "American" drugs were really manufactured in whole or in part abroad (something I noticed at the time because I had run into shortages of prescribed asthma pharmaceuticals from time to time and had heard it was on account of problems at foreign factories).

The heparin scandal really points up big-time just how intellectually dishonest and cynical pro-Pharma arguments often are.