Wednesday, November 19, 2008

Was GSK Merely Incompetent About Medical Informatics, Or Is There a Management Directive To Avoid Specialists Who Might Find "Unacceptable" Problems?

At my post "GSK, Avandia and Medical Informatics: More on Why Pharma Fails" I outlined repeated rejection of Medical Informatics expertise by GSK, based on what I believed essentially to be the narrowminded and tunnel-visioned thinking of information technologists and others in pharma. I wrote:

It is my belief that a view [at GSK] of medical informatics professionals as "writers of algorithms to solve business problems" reflects a fundamentally narrow and mechanistic view of the field, or perhaps a mislabeling of the position as being one of Medical Informatics. The lack of a requirement for formal Medical Informatics education and training suggests the latter.

The U.S. Institute of Medicine (IOM) of the National Academy of Sciences seems to agree with that assessment, as I pointed out in another post entitled "IOM gets it regarding Medical Informatics." The IOM recommends:

...that CDER [FDA's Center for Drug Evaluation and Research] build internal epidemiologic and informatics capacity in order to improve the postmarket assessment of drugs. In recognition of the limitations in human resources in the current employment market to meet this role, a combination of advancing professional skills through continuing education and support for academic training programs is needed.

and that

Informatics experts should track progress on the national health-information infrastructure, look for opportunities to gather information about drug safety and efficacy after approval, coordinate partnerships with external groups to study the use of electronic health records for [drug] adverse event surveillance, participate in FDA’s already strong role in setting national standards and track the development of tools for data analysis in industry and academe, and encourage the incorporation of the tools into FDA practice where appropriate.

A story in today's Wall Street Journal raises additional questions about what appeared to simply be strategic missteps in talent management (recognition and acquisition of new and/or enhanced skills and emerging fields of value to an organization).

Perhaps these were not strategic missteps at all, but simply a manifestation of a calculated policy set at higher levels to avoid discovering - beyond a certain point and before a certain time - information that might adversely affect a new drug's FDA acceptance, marketing, and sales. This might be accomplished through what might be called "internal capabilities inhibition via talent mismanagement."

The WSJ story today reports on actual directed, purposeful attempts by GSK to suppress possible adverse effects information about Avandia, as well as silence a number of its clinician critics. Those critics had prescribed the drug in good faith to their patients and noted troubling responses in the form of heart failure and pulmonary hypertensive (high pressure in the arteries of the lungs) side effects.

Wall Street Journal
Nov. 19, 2008

Doctors Claim Glaxo Dismissed Worries on Avandia (subscription required)

Drug Maker Tried to Make Physician at Maryland Hospital Stop Talking About Concerns; Company Defends Its Effort


HAGERSTOWN, Md. -- Last year, after news broke that the diabetes drug Avandia was linked to a high risk of heart attacks, reports that the drug's maker had tried to stifle safety questions from a prominent Duke University researcher years earlier provoked a furor.

Now it turns out that the Duke researcher wasn't alone in suggesting a tie to heart problems. A doctor from a small Maryland hospital [Internist Mary Money of Hagerstown, Md.] linked Avandia to congestive heart failure in 2000, but the drug's maker, GlaxoSmithKline PLC, rejected her warning and tried to make her stop talking about it with other doctors and hospitals, according to documents and interviews.

... The Senate and House in 2007 began looking at whether Glaxo suppressed information and threatened the Duke researcher, charges that Glaxo has denied. Now the Senate probe, led by Chuck Grassley of Iowa, is investigating whether Glaxo's efforts to defend Avandia's safety led to intimidation against other doctors who were suggesting possible links to cardiac dangers. Mr. Grassley, the ranking Republican on the Finance Committee, has demanded documents from Glaxo and is expected to release a detailed report on Avandia soon, according to staffers.

Earlier in 2007, a study in the New England Journal of Medicine reported that Avandia could raise the risk of heart attack by 43%. The FDA called for a black-box warning on the drug's label about the risk of congestive heart failure and heart attack.

Dr. Money talked recently about a patient who came to her in 1999 with congestive heart failure. "That fall, I had a woman patient with massive fluid overload and such shortness of breath that she had to sit up at night," she said.

The patient had begun taking Avandia two weeks earlier, and an echocardiogram showed high pressure in the arteries of the lungs. Dr. Money said she took the patient off the drug, and within a few days the symptoms almost disappeared.

In the next few months, Dr. Money and the head of the hospital's diabetes center, Stephen Lippman, found other patients who had similar symtoms.

Dr. Money alerted SmithKline Beecham, the name of the drug maker before a 2001 merger. The company met with her and Dr. Lippman at Washington County Hospital in Hagerstown in April 2000.

The two doctors presented data on 85 of their patients who had used Avandia, according to documents from the meeting. More than half of the patients had significant edema, or swelling, and about half of that group also had high pulmonary pressure and shortness of breath. Three had been hospitalized for congestive heart failure.

The meeting was a waste of time, Dr. Money said. "They came to tell us how wrong we were, not to listen," she said.

Meanwhile, a company consultant who called into the meeting from the University of Pennsylvania dismissed the Hagerstown doctors' echocardiograms as too poor to show anything useful.

"They suggested we were country bumpkins, and practically said, 'Don't worry your pretty heads. We have smarter people than you looking at this, and there's no problem,'" recalled Dr. Lippman, a physician who also holds a doctorate in molecular biology.

A GlaxoSmithKline spokeswoman, Mary Ann Rhyne, said Dr. Money's theories were "unsubstantiated" and she was misinterpreting journal articles to support her case.

The next month, two SmithKline executives wrote to the hospital's chief of staff, calling on him to stop Dr. Money from talking about her concerns to other hospital doctors.

"[W]e respectfully ask that your hospital not involve itself in the dissemination of information which has not been substantially verified, and that you take immediate steps to stop the dissemination of this unsubstantiated information to your medical staff," said the letter, signed by two SmithKline executives, which was viewed by The Wall Street Journal.

In effect, GSK is saying that these clinicians had no "right" to report their "unsubstantiated" findings to anyone without the company's "approval." That is the height of corporate hubris, especially in a country where freedom of speech and freedom of opinion is constitutionally guaranteed.

Unless these clinicians were fabricating their findings with ill intent, they certainly had very right to report their findings to anyone they chose. It is up to those so informed to make up their own minds based on the evidence and on trust.

But I state the obvious.

The company acted in a manner that might be construed as interference with medical practice and communication, and it seems to me potential interference with employment, by going to these doctor's superior. One must ask, who, exactly, did the company believe was required to perform the "substantiation" of adverse events information before the private clinicians could speak to others?

GlaxoSmithKline's Ms. Rhyne said the letter was justified. "When GSK learns about statements by physicians that are inconsistent with the scientific data on its medicines, it has the responsibility to do what it can to correct these inaccuracies," she said.

Resonsibility to whom, exactly? Its shareholders seem high on that list. Where do patients fit in to the taxonomy of corporate responsibility ?

It would seem to me the company also has the responsibility to maximize its ability to identify adverse events as soon as possible and as scientifically as possible, and conduct its talent management activities in a manner to enhance that capability.

Glaxo upgraded the warnings on Avandia's label more than a dozen times between 1999 and the 2007 black box, the strongest level of warning. One change, in 2001, said the drug could lead to excessive edema, which in turn could lead to congestive heart failure.

Better late than never.

Or perhaps not so much. From Alison Bass's blog:

It was not until 2007, after The New England Journal of Medicine published a meta-analysis showing an increased risk of heart failure among patients taking Avandia, that the FDA put black box warnings on the drug. (It's worth noting that researchers would never have been able to do this meta-analysis if not for the New York State Attorney General's lawsuit against GlaxoSmithKline for deceiving physicians and consumers about another of its drugs, the antidepressant Paxil; as part of settling that lawsuit, Glaxo agreed to post the findings of all its clinical trials, including those about Avandia).

Of one thing I am certain: diabetics did not need the additional problems caused by this drug before the black box warnings, when other proven, effective and less expensive therapies were readily available.

Perhaps that warning might have appeared sooner if GSK officials had not taken the stance that the value of Medical Informatics professionals is simply "to write algorithms to solve business problems." I wonder if a strategy of managing the narrative through questionable practices such as bullying and intimidation, while rejecting new fields of scientific endeavor, might be two sides of the same coin. (My own experiences are admittedly anecdotal, but formally trained medical informatics professionals are rare in pharma, and even at Merck I was kept an arm's length from adverse events informatics activities despite pointing out my expertise, for reasons never explained satisfactorily.)

My jobseeking experiences with SKB/GSK on informatics date back to 1996 or so. Rejections were the rule, even in one case in 2000 when I came highly recommended by their own senior internal recruiter after demonstrating the information system I built at a major hospital to detect drug and device adverse events in the field of invasive cardiology, and in 2004 when I again came highly recommended by their own retained British recruiter at Armstrong Craven Ltd.

I therefore raise the question:

Could my experiences and that of other informaticists with special competencies in building clinical IT to enhance adverse events data management have been a manifestation of a larger, somewhat unpublicized strategy? That is, a strategy meant to inhibit or suppress the employment and empowerment of individuals with formal training and expertise in newer scientific domains that might prematurely "endanger" the lifecycle of blockbuster drugs?

Perhaps the talent management activities, minutes, and hiring/layoff practices of relevant GSK departments and divisions should be scrutinized, in addition to the current Congressional scrutiny of specific instances of corporate arrogance as in today's WSJ article.

-- SS


Roy M. Poses MD said...

See also comments by Alison Bass on the Alison Bass Blog here:

Roy M. Poses MD said...

In addition, see comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma Blog here:

How do you spell DelRio? said...

see also this search engine, which allows mining of the FDA's AERS database.

e.g., a search for AEs reported for avandia: