Wednesday, April 30, 2008

Is the HIMSS "Certified Professional in Healthcare Information and Management Systems" stamp substantive, or just alphabet soup?

This post might be subtitled "when spending millions on health IT, why spend thousands on true healthcare informatics education when you can get a 'Certified Professional' credential to hang on your office wall, cheap?"

Imagine your reaction to a web page for a major HC organization that said this:

Certification as an expert in medical devices available. No domain-specific, specialized educational requirements. Short multiple choice test where many wrong answers "forgotten" is only requirement. You will be identified as an elite member of the healthcare device team after receiving our certification. Send $xxx dollars to ...

Such a scam would likely invite a governmental investigation.

Electronic medical records and other clinical IT are, in fact, virtual clinical devices that happen to reside on computers.

Their impact on medical care and education can be profound, as pointed out in papers by Ross Koppel at Penn, Pamela Hartzband, M.D. and Jerome Groopman, M.D. at Harvard, and many others around the world such as at Bad Health Informatics Can Kill and my own growing aggregation of HIT stories at "Sociotechnologic Issues in Clinical Computing: Common Examples of Healthcare IT Difficulties."

Yet, the vendor-friendly organization HIMSS (The Healthcare Information and Management Systems Society) offers such a certification in health IT. HIMSS identifies itself as "the healthcare industry's membership organization exclusively focused on providing leadership for the optimal use of healthcare information technology and management systems for the betterment of healthcare."

Here are the details on their certification as a Certified Professional in Healthcare Information and Management Systems (CPHIMS):

The Healthcare Information and Management Systems Society (HIMSS) has launched a professional certification program for healthcare information and management systems professionals. An individual who meets eligibility criteria and successfully completes a qualifying examination is designated a Certified Professional in Healthcare Information and Management Systems (CPHIMS).

CPHIMS status provides both internal and external rewards. As a Certified Professional in Healthcare Information and Management Systems, you:

  • Distinguish yourself from your peers as certified in healthcare information and management systems;
  • Expand your career opportunities;
  • Signal that you have mastered proven, broad-based concepts through successful completion of the Certified Professional in Healthcare Information and Management Systems Examination;
  • Provide yourself with skills and tools to help you make a difference in your career, your organization, and your community;
  • Enjoy the pride of recognition of knowing that you are among the elite in a critical field of healthcare; and
  • Have a premier credential based on a sound assessment to distinguish yourself in an increasingly competitive marketplace.

Here are the eligibility standards:

  • Baccalaureate degree plus five (5) years of associated information and management systems experience*, three (3) of those years in healthcare.

  • Graduate degree plus three (3) years of associated information and management systems experience*, two (2) of those years in healthcare.

  • *Associated information and management systems experience includes experience in the following functional areas: administration/management, clinical information systems, e-health, information systems, or management engineering. [Is that vague and non-specific enough? - ed.]

And now, the certification instrument:

The CPHIMS credential is awarded to individuals who demonstrate eligibility for the Certification Program and who successfully complete a qualifying examination. The examination consists of 115 multiple-choice test items, presented during a 2-hour session. Scoring is based on 100 items pre-selected for desirable psychometric characteristics. The additional 15 test items are included as pretest items. Performance on pretest items does not affect a candidate’s score.

It is remarkable to me that there are no specific educational requirements relevant to HIT, such as a certificate in health informatics, informatics fellowship, or clinical medicine experience of any kind. In my humble opinion a 115-question multiple choice test does not qualify a person as an expert in anything. Further, it seems to me that any "15 test items" a test taker got wrong might simply be discarded, further diluting such a test's relevance at best, and a rather dubious manner of scoring an exam in healthcare at worst.

Also omitted is the calibre of one's "experience." What, exactly, did you do? Were you successful? Were you an asset? Or, did you set projects back? Did you contribute to failure?

I'd though the importance of formal education in healthcare had been resolved by the 1910-era Flexner Report. I guess I am mistaken.

The sequential FCC exams I took to achieve a ham radio license - a mere hobby - were far more exacting. And at the time there was an applied exam as well; I had to be able to receive Morse Code at twenty words per minute to achieve the "Extra class" license.

I won't even compare to medical board exams.

To this NIH postdoctoral fellowship-educated HIT professional, CPHIMS certification sounds more like a "credentials mill" operation than a legitimate eduational and certificational process.

An attempt to introduce such a certification process at any institution of higher education, such as the one in which I teach about clinical IT, would get laughed out of a Faculty Senate's Committee for Academic Affairs or similar curriculum-approval body. It might even harm the school's accreditation.

Could you imagine such a certification process for some other medical process or technology, e.g., fluoroscopy equipment or EKG machines?

Discouraging pursuit of formal informatics education increases HIT problems and delays, raises costs, and facilitate failures. Does the availability of "instant credentials" discourage acquiring a substantive health care informatics background, diluting the availability of true expertise in this difficult field?

Is such health IT certification somewhat of a fraud, a ploy to allow undereducated people an opportunity to add "alphabet soup" to their resume in order to secure positions in health IT, or is it legitimate certification?

I report, you decide.

-- SS

"Selective Reporting of Study 329"

A new study in a rather obscure journal has revealed more about the now infamous study 329. [Jureidini JN, McHenry LB, Mansfield PR. Clinical trials and drug promotion: selective reporting of study 329. Int J Risk Safety Med 2008; 20: 73-81. Link here.]

For the background, let me take the easy way out, and quote Ed Silverman from PharmaLot:

Back in 2001, an infamous study was published in the Journal of the American Academy of Child and Adolescent Psychiatry that declared Glaxo’s [GlaxoSmithKline, GSK] Paxil antidepressant - called Seroxat in the UK - [paroxetine] was “generally well tolerated and effective for major depression in adolescents.” Known as study 329, the findings were used to widely promote the drug, which became a huge seller.

Of course, the study was later held in disrepute after it was learned the results didn’t tell the whole story. In fact, 329 was one of three studies cited by former New York Attorney General Eliot Spitzer, who filed a suit charging Glaxo with “repeated and persistent fraud,” alleging the drugmaker had promoted positive findings, but hadn’t publicized unfavorable data (back story).

As it turns out, study 329, ... already had a sordid history that included ghostwriting charges (here’s some background)....
We did cover this issue in the past (here) on Health Care Renewal.

Furthermore, we can now turn to the Clinical Psychology and Psychiatry Blog for an analysis of what is new about the study by Jureidini et al. The main points were -

The study report (in the Journal of the American Academy of Child and Adolescent Psychiatry) featured results of manipulation of the measures used to assess efficacy to make the drug appear more efficacious:

  • Study 329 was designed to employ 8 measures of drug efficacy. It turned out that paroxetine was not statistically significantly superior to the comparator using any of these 8 measures.
  • After the study was underway, the authors added a bunch of new measures, including new instruments, and modifications of instruments used in the original 8 measures. Only when using some of these new measures did the drug exhibit any efficacy.

To summarize how the Clinical Psychology and Psychiatry blog put it:

Devising various cutoff scores on various measures on which victory could be declared, as well as examining individual items from various measures rather than entire rating scales, the authors were able to grasp and pull out a couple of small victories. In the published version of the paper, there is no hint that such data dredging occurred. Change the endpoints until you find one that works out, then declare victory.

Worse, the study report simply omitted mention of the data that serious adverse events were more common in patients treated with paroxetine than with placebo, making the drug appear safer than it really may be. Jureidini et al noted that the following phrase,

worsening depression, emotional lability, headache, and hostility were considered related or possibly related to treatment

was omitted from the published report. Furthermore, per Jureidine et al,

Suicidal thoughts and behavior were grouped under the euphemism of 'emotional lability'

Yet the final JAACAP paper only stated,

Only headache (1 patient) was considered by the treating investigator to be related to paroxetine treatment

Jureidini et al concluded,

The published conclusions of study 329 and information provided by GSK to health professionals understated adverse effect rates and emphasized post-hoc measures that were not consistent with the unpublished, protocol-defined primary and secondary outcomes.

The article by Jureidini et al adds to our understanding of the various devious ways commercial sponsors of clinical research and the supposedly independent academic investigators who collaborate with them may manipulate the design, implementation, analysis and reporting of clinical studies to make the sponsors' products look better.

As we have said again and again, patients and physicians require the best possible information about benefits and harms of treatments to make the best decisions about such treatments. When those with vested interests in supporting a particular treatment distort the information available to make such decisions, they risk harming patients. In addition, manipulation of clinical studies violates the trust of study participants who thought they were taking part to advance science or health care.

The ongoing revelations about study 329 unfortunately remind doctors and patients who skeptical they must be about how well drugs and devices really are supported by clinical research. Combined with numerous other reports of manipulation and suppression of research, they suggest that:
  • medicine, and particularly academic medicine ought to do a far better job of policing itself to ensure the integrity of clinical research
  • pharmaceutical, biotechnology and device companies lead by businesspeople and lacking strong corporate cultures and explicit codes of conduct supporting ethical conduct may not deserve our trust
  • government regulation of drug and device companies need to be far more stringent
  • consideration ought to be given to require that all clinical research be conducted at true arm's length from organizations and people with vested interests in promoting particular products or services assessed by such research
I must note that there is also a local angle to this. As Jureidini et al wrote, "in 1992 Martin Keller MD, Chairman of Psychiatry at Brown University, Rhode Island and colleagues successfully proposed to SKB [SmithKline Beecham, the predecessor of GSK] a multi-site study of a selective serotonin reuptake inhibitor and tricyclic antidepressant in adolescent major depression."

As PharmaLot reported, "The latest study prompted a complaint concerning possible scientific misconduct to be leveled against study 329’s lead author, Martin Keller, a psychiatry professor at Brown University, by David Egilman, a clinical associate professor in community health at Brown. We are awaiting a reply from Keller and Brown provost David Kertzer, who was sent the complaint by Egilman. UPDATE: A Brown spokesman declines to comment."

As I noted in my previous blog post, I am currently on the voluntary faculty of Alpert Medical School of Brown University. I am a former full-time faculty member, and an undergraduate and medical school alumnus of Brown. I am saddened to see the ongoing damage to the reputation of the institution from this case. I do believe that Dr Egilman's complaint warrants full, open, and transparent investigation.

Tuesday, April 29, 2008

The AAMC Report on Medical Schools' Industry Relationships: A Glass Half Empty

The Association of American Medical Colleges (AAMC) just unveiled a report on relationships among academic medical institutions and the pharmaceutical, biotechnology, and device industry. The report was notable in its toughness in certain areas, laxity in others, and for what it did not mention, and what kinds of conflicts of interest it actually encouraged.

Where it was tough:
  • It advocated banning "acceptance of any gifts from industry by physicians and other faculty, staff, students, and trainees...."
  • It considered "industry supplied food and meals" as "personal gifts" which should be therefore banned (but see below).
  • It advocated prohibiting "physicians, trainees, and students from directly accepting travel funds from industry." (But see below.)
  • It advocated prohibiting "physicians, trainees, and students from allowing their professional presentations of any kind, oral or written, to be ghostwritten by any part, industry or otherwise."

Where it was lax

  • It did not ban interactions among physicians, faculty, staff, students and trainees and pharmaceutical or device representatives (sales people), only restricting such interactions to "nonpatient care areas and nonpublic areas," "by appointment or invitation of the physicians." Furthermore, it suggested that "involvement of students and trainees in such individual meetings should occur only for educational purposes."
  • It allowed "industry representatives who wish to provide educational information on their products" to do so "by invitation in faculty-supervised structured group settings"
  • It allowed "access by device manufacturers' representatives" if they are "appropriately credentialed."
  • It allowed participation in industry funded continuing medical education (CME) programs as long as they are accredited by the Accreditation Council for Continuing Medical Education (ACCME)
  • It allowed industry-sponsored food and meals as long as they are part of ACCME accredited CME.
  • It advocated that "participation by ... faculty in industry-sponsored speakers' bureaus" should be "strongly discouraged," but not prohibited.
  • It allowed industry to reimburse travel "for legitimate reimbursement or contractual services."

What it encouraged:

  • It acknowledged "the value of permitting academic medical center faculty to interact appropriately with industry." It deemed appropriate "faculty participation on industry boards of directors and scientific advisory boards," and faculty "services provided through professional service agreements and consulting contracts," as long as they are "in full compliance with the policies of the medical center and applicable law," and compensated according to "fair market value." It did not require, or even suggest disclosure of such financial relationships.

What it did not mention:

  • Institutional conflicts of interest, in general.
  • Industry manipulation or suppression of clinical research, and how contracts between academic medical institutions and industry allow such manipulation.
  • Some specific kinds of financial relationships between faculty and industry, including faculty holding executive positions with or founding health care corporations, and faculty receiving royalty payments.

In my humble opinion, at best this report, which I suspect will be highly influential, is a glass half empty.

There is reason to ban gifts and food to trainees, and physicians. Such gifts imply the need for reciprocity, and hence may be influential beyond their monetary value. See our posts (here, here, and here) on how gifts are used for marketing purposes by pharmaceutical representatives.

Yet given the evidence (see posts above) that the goal of pharmaceutical (and biotechnology and device) representatives is to market product, not provide education, the report's allowance of "educational" activities by such representatives is at best disingenuous.

Furthermore, given the evidence that industry sponsored CME is likely to be biased in favor of the sponsoring companies' products and services (see posts here, and here, and numerous posts on the Carlat Psychiatry Blog and the Hooked: Ethics, Medicine and Pharma blog ), and the logic behind this assertion, the report's allowance of such "educational" activities is also at best disingenuous.

I believe that the report's failure to address the issue of manipulation and suppression of industry funded research is astonishing given how obvious such problems have become. (Try searching these topics on this blog, to begin with.)

Finally, the report's encouragement of certain often lucrative financial relationships (such as consulting, service on advisory committees, and service on boards of directors of health care corporations), while it ignored other lucrative relationships (service as a corporate executive, founding of health care corporations, and receipts of royalties) suggests cynicism and hypocrisy.

First, even though small gifts may have influence beyond their monetary value, very large payments are likely to be more influential. Even without empirical research, common sense suggests that a faculty member who receives tens of thousands of dollars for consulting or serving on an advisory committee or speakers' bureau is likely to look favorably on his or her corporate part-time employer, and its products or services. Furthermore, serving as an executive of a corporation, and particularly serving on the board of directors of a corporation should demand loyalty to the corporation, and such loyalty can be enforced in court. Surely such loyalty is likely to be much more powerful than warm feelings generated by the receipt of a free pizza.

If there is a reason to ban gifts of pens, coffee mugs, or pizza slices due to the concern that such gifts may influence trainees and physicians' behavior, there is more of a reason to ban service on speakers' bureaus and advisory committees, consulting contracts, and particularly service as company executives, and on boards of directors.

Otherwise, we may well see the spectacle of a the director of a health care corporation punishing a medical student for accepting a pen with that corporation's logo on it.

And a postscript - It appears that this report may be so ambivalent about conflicts of interest because several of its authors were affected by such conflicts. On the PharmaLot blog, Ed Silverman reported that three authors are on the boards of directors of large health care corporations, and three other authors had significant financial relationships with health care corporations. None of these relationships were disclosed in the report. The report did disclose that four other authors were not academics or medical college administrators, but CEOs of pharmaceutical or biotechnology corporations. Why the AAMC saw fit to ask such people, who are obviously likely to be more loyal to their corporations than to academic medicine, is a mystery yet to be solved.

Note, see somewhat more optimistic opinions about this report on the Carlat Psychiatry Blog and the Hooked: Ethics, Medicine and Pharma blog. Also, a New York Times editorial accused of the AAMC of "flinching" from banning service on speakers' bureaus, and industry supported CME, but did not mention the report's support of consulting, service on advisory committees and boards of directors, service as a corporate executive, etc. But I agree with its general conclusion, "Patients need to be assured that their doctors are prescribing what’s best for them, not what’s best for companies. "

ADDENDUM (30 April, 2008) - See also coverage in the Gooznews Blog, in which Merrill Goozner noted that the report "stopped short of calling for prohibiting faculty members from consulting or speaking on behalf of drug and device companies, or for eliminating industry’s role in financing continuing medical education (CME)." On the other hand, the Postscript blog by the Prescription Project noted the AAMC report without much comment.

ADDENDUM (30 April, 2008) - On theRetired Doc's Thoughts blog, Dr James Gaulte is also skeptical, "My non-insider take is that there will be a flurry of high profile (within the institutions at least) announcements of 'no more free lunches' and much self congratulation and talk of professionalism but somehow I doubt the faculty will give up the lucrative lecture gigs although a veneer of word smithed propriety and oversight will be grafted onto it."

Monday, April 28, 2008

BLOGSCAN - "Regulatory Capture," Heparin and the FDA

On the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody discusses the recent case of toxic heparin (see our most recent post here) in terms of "regulatory capture" of the US Food and Drug Administration (FDA). Regulatory capture occurs when a regulatory agency starts to view those whom it is supposed to regulate as clients (rather than viewing the general public as its client). More comments on this issue by Dr James Gaulte can be read on the Retired Doc's Thoughts blog.

BLOGSCAN - Disease Mongering and Indefinite Use of Smoking Cessation Pharmaceuticals

On the Bioethics Forum, Dr Adriane Fugh-Berman and Dr Douglas Melnick discuss what appears to be the latest example of disease-mongering. An article in the Annals of Internal Medicine, written by authors with ties to companies that make pharmaceuticals for smoking cessation, argued that tobacco addiction should be reclassified as a chronic disease, such that patients should be expected to be on smoking cessation products indefinitely. Such indefinite use, of course, is unsupported by clinical evidence, but would create a huge new market for these drugs.

Pharma Union cowed into submission?

In various posts including this one, I've commented on the environment of cutbacks, quality issues, and fear that seems to permeate pharma.

Now a labor union leader at Merck has responded to the Philadelphia Inquirer article "FDA report shows problems at Merck vaccine plant." He writes in a letter to the editor:

Concerns at Merck

The article "FDA: Problems at Merck's vaccine plant" (Inquirer, April 24) indicated the concerns raised after an inspection at our facility, Merck's West Point site. We, the United Steelworkers Union members, are dedicated to the creation of quality products through all phases of the manufacturing process. We are committed to following FDA guidelines, industry standards, and the FDA's Good Manufacturing Practices, all of which are the foundation for a successful pharmaceutical and vaccine production plant.

The company has implemented new ideas on how to function at our site. The expectation placed on our members is that they are required to do more with less. This business philosophy is not unique to large corporations but it is new to the pharmaceutical industry. Our members have worked diligently to ensure that the demands that have been placed on them have been met. They also want to ensure that their jobs are secure, but the article has raised concerns for them and their families about the future.

Phil Hughes
Vice president
United Steelworkers Local 10-0086
North Wales (PA)

This somewhat cryptic letter can be interpreted in a number of ways. A clear message is that the union members are being asked to "do more with less", implying overwork. This seems an explanatory theme in the FDA 483 Inspection Report referenced in the Inquirer article, a copy of which I have obtained. There are, in fact, phrases in paragraphs of that FDA inspection report that do not belong in the same paragraph, such as:

5. SOP 1330, Headquarters Review of Lot Numbers for Product Quality Complaints (PQCs), dated 14 May 2007, states that all deaths and life threatening adverse experiences [with vaccines] require lot checks with batch record review. This is not always performed.

Rejects from the first pass through the inspection equipment are sent through the inspection equipment a second time and only those that are rejected a second time are discarded. [Four examples involving vials of Varivax, Zostavax and ProQuad follow.]

What is most concerning about the union leader's letter to the editor, however, is this:

They [our union member Merck employees] also want to ensure that their jobs are secure, but the article has raised concerns for them and their families about the future.

I ask why an article such as the one published in the Inquirer would raise concerns for Merck unionized workers about their "future" (i.e., jobs).

Is the union concerned about retaliation in the form of layoffs for the substandard report? Since it's unlikely Merck vaccine sales will be affected by easily correctable FDA inspection problems, and since it's also unlikely Merck Vaccine Division will go out of business, being touted as it is by Merck management as a significant source of company income (e.g., via the new Herpes vaccine), the fear of layoff retaliation appears possible.

I can only say that if the unions are so concerned and so milquetoast in their approach to employee overwork via mild-mannered letters to the editor, imagine what the non-unionized employees must be feeling.

Finally, I once worked as Medical Programs Manager for the regional transit authority in Philadelphia. The leader of its biggest union, Transport Workers Union local 234, would likely have had quite a different response in the Inquirer to the problems caused by his employees being made to "do more with less" in a life-critical operation.

When I first met Mr. Lombardo it was at a medical department meeting where he was banging his fists on the table, shouting at the doctors for f***ing around with his employees via workers comp denials, drug tests, etc. At the time I thought this behavior frightening and unprofessional, but now I see its value.

I wish I'd had a union leader will testicles representing me in my past few positions.

-- SS

Sunday, April 27, 2008

On the Pitfalls of Going Electronic: Should Physicians Reject Hospital EMRs?

Yes, I believe they should, and with a spine, especially when they're lousy and their design and implementation have been led by people with superficial "certification" and/or no clinical credentials whatsoever. And sometimes no discernible IT credentials, either, unless you consider the "school of hard knocks" a credential.

(More on the credentials issue below. Also see my website "Common Examples of Healthcare IT Difficulties" for more on these issues.)

A viewpoint article was just published in the NEJM by Harvard physicians Pamela Hartzband, M.D. and Jerome Groopman, M.D. entitled "Off the Record — Avoiding the Pitfalls of Going Electronic" (NEJM 358:1656-1658, April 17, 2008).

The authors note:

... The ultimate goal of the electronic medical record — a technological solution being championed by the Bush administration, the presidential candidates, and New York Mayor Michael Bloomberg, as well as Google, Microsoft, and many insurance companies — is to make all patient information immediately accessible and easily transferable and to allow its essential elements to be held by both physician and patient. The history, physical exam findings, medications, laboratory
results, and all physicians' opinions will be collected in one place and available at a single keystroke. And there is no doubt that these records offer many benefits. We worry, however, that they are being touted as a panacea for nearly all the ills of modern medicine. Before blindly embracing electronic records, we should consider their current limitations and potential downsides.

As we have increasingly used electronic medical records in our hospital and received them from other institutions, we've noticed several serious problems with the way in which notes and letters are crafted. Many times, physicians have clearly cut and pasted large blocks of text, or even complete notes, from other physicians; we have seen portions of our own notes inserted verbatim into another doctor's note. This is, in essence, a form of clinical plagiarism with potentially deleterious consequences for the patient.

Residents, rushing to complete numerous tasks for large numbers of patients, have sometimes pasted in the medical history and the history of the present illness from someone else's note even before the patient arrives at the clinic. Efficient? Yes. Useful? No. This capacity to manipulate the electronic record makes it far too easy for trainees to avoid taking their own histories and coming to their own conclusions about what might be wrong. Senior physicians also cut and paste from their own notes, filling each note with the identical medical history, family history, social history, and review of systems. Though it may be appropriate to repeat certain information, often the primary motivation for such blanket copying is to pass scrutiny for billing. Unfortunately, these kinds of repetitive notes dull the reader, hiding the important new data.

Writing in a personal and independent way forces us to think and formulate our ideas. Notes that are meant to be focused and selective have become voluminous and templated, distracting from the key cognitive work of providing care. Such charts may satisfy the demands of third-party payers, but they are the product of a word processor, not of physicians' thoughtful review and analysis. They may be "efficient" for the purpose of documentation but not for creative clinical thinking.

In effect, the doctors have keenly observed that not only do EMR's impair documentation and thinking by seasoned professionals, especially those pressed for time, but the use of these technologies impairs the training of the next generation of physicians. I benefited much through learning how to properly document medical observations, findings, differential diagnoses, treatment plans, and other high level cognitive processes. IT designed by non clinicians with the maintenance of payor profit as a principal motivator may be, in effect, causing a further dilution in the quality of medical training. Social informatics predicts such unexpected adverse outcomes of any new information and communications technology (ICT).

However, the current environment of irrational exuberance over Health IT, as well as the potential for capital transfer from the healthcare to the IT and payer sectors and the motivators and conflicts this generates among hospital management, consultants, regulators and others, has had a marked blinding effect.

The NEJM authors also note:

Similarly, electronic medical records can reproduce all of a patient's laboratory results, often dropping them in automatically. There is no selectivity, because it takes human effort to wade through all the data and isolate the information that is pertinent to the patient's current problems. Although the intent may be to ensure thoroughness, in the new electronic sea of results, it becomes difficult to find those that are truly relevant.

A colleague at a major cancer center that recently switched to electronic medical records said that chart review during rounds has become nearly worthless. He bemoaned the vain search through meaningless repetition in multiple notes for the single line that represented a new development. "It's like `Where's Waldo?'" he said bitterly. Ironically, he has started to handwrite a list of new developments on index cards so that he can refer to them at the bedside.

...The worst kind of electronic medical record requires filling in boxes with little room for free text. Although completing such templates may help physicians survive a report-card review, it directs them to ask restrictive questions rather than engaging in a narrative-based, open-ended dialogue. Such dialogue can be key to making the correct diagnosis and to understanding which treatment best fits a patient's beliefs and needs.

... These problems, we believe, will only worsen, for even as we are pressed to see more patients per hour and to work with greater "efficiency," we must respond to demands for detailed documentation to justify our billing and protect ourselves from lawsuits. Though the electronic medical record serves these exigencies, it simultaneously risks compromising care by fostering a generic approach to diagnosis and treatment.

I agree with these assessments, especially for hospital based enterprise EMR's forced on doctors by management.

Physician leadership of HIT projects would be of great benefit. However, here's what typical healthcare organizational leaders have to say about physician leadership of HIT initiatives, in this case Denis Baker, the CIO of Sarasota Memorial Hospital, a major medical center on the Gulf Coast of Florida in an interview here:

I think that physicians bring a certain aspect to the job, but I don’t think they necessarily know how a hospital works. I think they know how their practice works and how they interact with the hospital, but I don’t think they absolutely know what nursing does, or any of the ancillary departments, and what they do.

Worse, as far as I can tell, the CIO making that statement appears to lack formal education in medicine, information systems, information technology and biomedical information science i.e., informatics. (I was unable to find any such credentials but will correct this if mistaken.)

Stereotypes of physicians do not come any more patronizing than that.

Oh, wait ... yes they do.

His statement is little different than a decade ago when I wrote this essay about stereotypes and observed others in influential positions holding marginalizing views of physicians - and indeed of professional education of any kind:
Several healthcare MIS Recruitment firms have published interesting views on healthcare MIS leadership, views that most clinicians will not identify with. " I don't think a degree gets you anything ," says healthcare recruiter Lion Goodman, president of the Goodman Group in San Rafael, California about CIO's and other healthcare MIS staffers.

Healthcare MIS recruiter Betsy Hersher of
Hersher Associates , Northbrook, Illinois, agreed, stating " There's nothing like the school of Hard Knocks ." (Who's Growing CIO's, Healthcare Informatics, Nov. 1998, p. 88).

In seeking out CIO talent, recruiter Lion Goodman " doesn't think clinical experience yields [hospital] IT people who have broad enough perspective . Physicians in particular make poor choices for CIOs. They don't think of the business issues at hand because they're consumed with patient care issues ," according to Goodman.

It appears there's been little change in ten years.

Oh, wait ... yes there has been "change."

"Specialists" and "managers" in HIT projects now undergo certification by vendor-centric groups such as the Health Information Management Systems Society HIMSS.

Here's a description of the value of certication as a HIMSS Certified Professional in Healthcare Information and Management Systems (CPHIMS):

CPHIMS status provides both internal and external rewards. As a Certified Professional in Healthcare Information and Management Systems, you:

  • Distinguish yourself from your peers as certified in healthcare information and management systems;
  • Expand your career opportunities;
  • Signal that you have mastered proven, broad-based concepts through successful completion of the Certified Professional in Healthcare Information and Management Systems Examination;
  • Provide yourself with skills and tools to help you make a difference in your career, your organization, and your community;
  • Enjoy the pride of recognition of knowing that you are among the elite in a critical field of healthcare; and
  • Have a premier credential based on a sound assessment to distinguish yourself in an increasingly competitive marketplace.

Wow! "You are among the elite" after taking this exam!

Here are the eligibility standards:

Baccalaureate degree plus five (5) years of associated information and management systems experience*, three (3) of those years in healthcare.

Graduate degree plus three (3) years of associated information and management systems experience*, two (2) of those years in healthcare.

*Associated information and management systems experience includes experience in the following functional areas: administration/management, clinical information systems, e-health, information systems, or management engineering.

And now, the certification instrument:

The CPHIMS credential is awarded to individuals who demonstrate eligibility for the Certification Program and who successfully complete a qualifying examination. The examination consists of 115 multiple-choice test items, presented during a 2-hour session. Scoring is based on 100 items pre-selected for desirable psychometric characteristics. The additional 15 test items are included as pretest items. Performance on pretest items does not affect a candidate’s score.

That is the certification that will be used to hire more "experts" in HIT.

This is pathetic. My exams to become a licensed ham radio operator were more challenging. I consider such a credential unmeritorious at best, fraudulent at worst. (I haven't even inquired as to costs.)

However, medical credentialing exams are just a bit more thorough.

By several orders of magnitude, that is.

In conclusion, medicine is in very sad shape when in an era of out of control technology costs ($100 million for an EMR?), unclear benefit and irrational exuberance over HIT it's demanded of physicians that they use tools designed by business IT personnel, processes and methodologies best known for failure, produced by an industry rife with conflicts, whose leaders often lack substantive credentials, patronize those who do, produce ill-conceived and/or shoddy products whose use is mandated by non-clinician hospital managers and that as the NEJM writers note, impair medical practice and education.

-- SS

Thursday, April 24, 2008

The wages of treating employees in biomedicine as expendible assets: FDA report shows problems at Merck vaccine plant

In "P for Poor Management" and "Tax Break Used by Drug Makers Failed to Add Jobs" I postulated that many of pharma's difficulties stem from understaffing, poor morale and overwork caused by the abandonment of the idea of employees as valuable partners - as opposed to "expendible assets."

I further postulated that many of Merck's problems were not due to deliberation but to demoralization of the workforce via the continuing spectre of layoffs. Layoffs artificially jack up the stock price in the short term but have long term detrimental effects.

Others apparently agree with this assessment.

In "FDA report shows problems at Merck vaccine plant", it appears Merck's vaccine manufacturing processes are suffering from significant problems. A company that has been manufacturing vaccines for decades, and with a relatively new state-of-the art facility, is now found to be experiencing problems more characteristic of an upstart:

FDA report shows problems at Merck vaccine plant

By Karl Stark, Inquirer Staff Writer

April 24, 2008

Federal inspectors documented unwanted "fibers" on the stoppers of vaccine vials at Merck & Co. Inc.'s vast vaccine plant in Montgomery County. They also found instances of contaminated children's vaccines and complaints that were not always investigated at the West Point plant.

Inspectors from the U.S. Food and Drug Administration spent 30 days at the plant between November and January and cited 49 areas of concern, including a failure to follow good manufacturing practices.

The findings are detailed in an unpublished 21-page FDA report obtained by The Inquirer under the federal Freedom of Information Act. Independent experts who reviewed the report say it documents serious concerns in one of the country's premier vaccine plants.

Of note:

[Independent experts] suggested the problems could be a symptom of Merck's cost cutting [i.e., layoffs - ed.] in the face of rapid growth of its vaccine business.

"I would fault the management for not providing enough resources to do the work that needs to be done," said Scott M. Wheelwright, a biotech manufacturing expert and chief executive officer of the biotech consulting firm Strategic Manufacturing Worldwide, of Saratoga, Calif.

... Wheelwright, a consultant with 25 years' experience in vaccine manufacturing, suspects that the workload could be overwhelming. "I would not judge the plant as being out of control," he wrote in an e-mail. "There are numerous issues where they failed to comply with their own documentation and SOP [standard operating procedure] requirements. This suggests insufficient staff.

There are other instances where the validation was insufficient. This also looks to me like overwork of the available crew. Sometimes in a plant where everyone feels overburdened . . . they give up trying to do everything and just try to keep their heads above water."

And then there's this:

That Merck would be having problems with FDA inspectors surprised several longtime company observers. Sammie Young, a retired FDA deputy director, inspected the West Point plant early in his career and for many years oversaw vaccine-plant inspections for the entire agency.

"There are a lot of violations there [in the report]," Young said, after reading the report. "I'm surprised."

He said vaccine-makers were supposed to investigate vaccine lots if their use was associated with a death or a life-threatening event.

Merck failed to investigate two such cases, the FDA report said. A patient treated with the pneumococcal vaccine Pneumovax developed a half-dollar-size abscess and needed intravenous antibiotics to contain the infection. A pregnant woman who took the HPV vaccine Gardasil lost her baby, the FDA report noted. The Gardasil packaging warns against its use for pregnant women.

"I am concerned about the adverse-event reporting system," Young said. "It looks like the people didn't know when they were supposed to report. I find that hard to believe."

Of course, Merck denies all of this:

John T. McCubbins, who heads Merck's Global Vaccine Manufacturing and WestPoint Operations, disputed that assessment. He maintained that the division's employment had kept pace with vaccine production. He stressed that no contamination was found in finished vaccines and that Merck was addressing all the problems.

As the Inquirer reporter notes:

Merck is a fabled name in vaccines. It was at Merck that microbiologist Maurice Hilleman developed many of the most common childhood vaccines, which are credited with saving millions of lives."

As I had noted in this post (or, more correctly, as one state government's bureau of unemployment had noted):

The stress of losing a job is like the stress of a death in the family or a divorce. It involves loss of wages and benefits, role as worker and provider, dignity and self esteem, loss of the "American Dream", loss of trust, loss of control over your life, loss of the pattern of daily life, and loss of the "work family."

... Many of these employees carry corporate wisdom with them that is lost ... Remaining employees become overworked, burned out, extremely unhappy and put in a position of fear and uncertainty.

I don't believe overwork, burnout, extreme unhappiness and fear and uncertaintly make for the best compliance with procedures in difficult manufacturing processes. (Nor in R&D for that matter, in areas such as discovering new drugs.)

For the premier "fabled name" in vaccines to be found with a failure to follow good manufacturing practices and other problems, I think it more likely the company is reaping that which it sowed, with the reaping being represented by a grim, hooded figure with a scimitar - in the form of mass layoffs that began in 2003, breaking with century old traditions in this once fabulous company.

I offer this advice to pharmas:

If you enjoy mass lawsuits, and wish to continue to do try to do business from an empty wagon, continue to treat your employees as expendible assets.

(Full disclosure: I am a laid-off employee myself. After lobbying for and partially ending rationing of advanced scientific literature searching tools available to only a minority of discovery scientists, and filling critical unmet needs for scientific information by increasing the supply of scientific articles supplied to the research labs tenfold compared to decade-long norms, I found myself laid off in Nov. 2003. I was replaced by personnel lacking clinical and biomedical informatics credentials, i.e., they possessed the inferior credentials that led to the information-scarcity problems in the first place. I'm not sure how that will help the company. Borrowing a line I saw on the HISTalk blog recently, this brings to mind the adage "No company ever shrank to greatness." )

-- SS

What Influenced Derision of Evidence-Based Medicine as "One-Size-Fits-All?"

There he goes again. An op-ed a little while back by Peter J Pitts in the Washington Times took another whack at evidence-based medicine (EBM).

He started by saying all the current US Presidential candidates want to control health care costs using EBM.

One plan they all favor is ramping up federal funding for so-called 'evidence-based' medicine.

Pitts gave his own definition of EBM.

The theory behind evidence-based medicine is simple: If the government were to run clinical trials testing the effectiveness of drugs and medical technologies, and then use the results to determine what to cover, taxpayers would avoid paying for treatments that aren't effective enough to justify their price tag.

Sounds great, right? Too bad that in practice, evidence-based programs are largely driven by the political imperative to cut costs — not the medical imperative to give patients the best care possible.

Furthermore, Pitts derided what he asserted was evidence-based medicine's "one-size-fits-all approach."

Evidence-based programs encourage this approach. The underlying assumption is that the same care can be applied to every patient suffering from the same disease.
He concluded thus,

The theory behind and the practice of evidence-based medicine just don't match up. And until politicians can show how they'll resolve that tension, they need to look elsewhere in their quest to find politically palpable solutions to the country's health-care woes.
It is just amazing how little Mr Pitts' concept of EBM resembles that promoted by most EBM proponents. Contrast his concept of EBM with this one, written by one of the founders of the movement, Dr David Sackett, and colleagues [Sackett DL, Rosenberg WM, Muir Gray JA, Haynes RB, Richardson WS. Evidence-based medicine; what it is and what it isn't. BMJ 1996; 312: 71-72. Link here. ]

Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research. By individual clinical expertise we mean the proficiency and judgment that individual clinicians acquire through clinical experience and clinical practice. Increased expertise is reflected in many ways, but especially in more effective and efficient diagnosis and in the more thoughtful identification and compassionate use of individual patients' predicaments, rights, and preferences in making clinical decisions about their care. By best available external clinical evidence we mean clinically relevant research, often from the basic sciences of medicine, but especially from patient centred clinical research into the accuracy and precision of diagnostic tests (including the clinical examination), the power of prognostic markers, and the efficacy and safety of therapeutic, rehabilitative, and preventive regimens.

And here is a direct refutation, written 12 years ago, for Pitts' "one-size-fits-all" criticism.

Evidence based medicine is not 'cookbook' medicine. Because it requires a bottom up approach that integrates the best external evidence with individual clinical expertise and patients' choice, it cannot result in slavish, cookbook approaches to individual patient care. External clinical evidence can inform, but can never replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision.

One can find other definitions of EBM, but nearly all emphasize that the approach is designed to appropriately apply results from the best clinical research, critically reviewed, to the individual patient, taking into account that patient's clinical characteristics and personal values.

It makes no sense to call EBM a "one-size-fits-all" approach.

So Pitts' op-ed was basically one long straw man argument. He made up his own version of EBM, and then proceeded to knock it down. Why did he make the effort to give EBM a bad name?

Readers of the Washington Times op-ed were deprived of some clues to the motivation for his approach. The op-ed identified Mr Pitts as "president of the Center for Medicine in the Public Interest and a former associate commissioner of the Food and Drug Administration."

The Washington Times did not note that the Center for Medicine in the Public Interest, CMPI, received considerable industry support, as the NY Times did when it published an op-ed by Pitts lambasting comparative effectiveness research (see that article here, and our relevant post here.)

Furthermore, as we have noted before when he publicly criticized Dr Steve Nissen during the Avandia affair (see post here), and when he warned against restricting people with conflicts of interest from FDA advisory panels (see post here), Mr Pitts holds down the day-job of Senior Vice President for Global Health Affairs at the big public relations firm Manning, Selvage and Lee. Manning, Selvege and Lee has many big pharmaceutical accounts, as listed on the site. As Senior Vice President for Global Health Affairs, Pitts is presumably responsible for all these accounts. Thus, his livelihood seems to depend largely on his ability to convey the pharmaceutical industry's point of view. The Washington Times left all that out.

Presumably, Mr Pitts' pharmaceutical industry public relations clients may be worried about evidence-based medicine because rigorous EBM informed consideration may show that some of their products are not as good as their marketing hypes them to be. Perhaps that is the reason Mr Pitts had such an odd view of what EBM is, and felt so negative about what EBM might be able to do for health care.

At least, if Mr Pitts could be bothered to disclose where CMPI gets its financial support, and what his day job is, readers could make their own judgments about where his interests lie.

It is disappointing that a newspaper as influential as the Washington Times would publish a health policy article without disclosing all the author's relevant financial interests, particularly one so relevant and direct. Fostering more stealth health policy advocacy in ever more influential venues will just make the already confusing clamor about health care and its reform even muddier.

ADDENDUM (28 April, 2008) - See also these comments by Dr Alan Schwartz on the Making Medical Decisions blog.

Another Former "Dr Drug Rep" Outs Himself

I found this a little belatedly, but then again, it is from a slightly obscure source (at least, if one lives on the East Coast of the US).

The Willamette Weekly ran a profile of Dr Erick Turner, the author of a systematic review that showed incorporating the results of unpublished trials of selective serotonin reuptake inhibitor (SSRI) anti-depressants into the review produces much less optimistic results about these drugs than simply attending to the published trials. [Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008; 358: 252-60. Link here.] What is notable in the Willamette Weekly article is the account of how Dr Turner was once also a "Dr Drug Rep." (see our post here, and the Carlat Psychiatry Blog, written by the original former "Dr Drug Rep," Dr Daniel Carlat, here.)

... for 18 months, Turner pimped for antidepressants. He wouldn’t put it that way, of course, as many doctors do the same thing. But starting in 2004, Turner, who is the medical director of the Mood Disorders Program at the Portland VA and has worked at the Food and Drug Administration and the National Institute of Mental Health, became a speaker for Eli Lilly, one of the world’s largest pharmaceutical companies.

It’s not unusual in pharmaceutical marketing for doctors to be hired as 'consultants'—or members of a company’s 'speakers' bureau' in industry parlance—and then hit the road doing 'doctor talks.' These are typically lunches or dinners where area M.D.s are invited by a company to eat and drink while listening to a respected physician describe the benefits of a particular drug.

Lilly approached Turner around the time the FDA was set to approve a new Lilly antidepressant named Cymbalta. He was an especially good catch for the company because, in addition to his academic appointment at OHSU, Turner had spent seven years as a researcher at the prestigious National Institute of Mental Health and another three years as a clinical trials reviewer at the FDA.

'They’re using your reputation and political capital, as it were, as sort of a frontman for the drug,' says Turner, 54.

After training in Indianapolis in the summer of 2004, Lilly sent Turner out into the field in the Northwest, receiving anywhere from $500 to $750 per talk. He says he did about 12 talks for Lilly over the next 18 months.

He says his motivation wasn’t so much the money—he netted less than $10,000—as it was his desire to keep up his reputation as an expert on clinical trials.

Dr Turner discussed the positive incentives to do drug company talks.

'In the beginning, I think I got narcissistic gratification,' he says. 'They fly you somewhere else in the country and pick you up in a limo, and you stay in a nice hotel you could never afford otherwise.'
But Dr Turner soon realized that his talks were really not under his own control.

Turner found he could say only what Lilly allowed him to say. He could use only Lilly’s overhead slides of results from clinical trials of the drug. He couldn’t offer his own expertise as a researcher and former FDA reviewer to his fellow doctors.

'I began to feel straitjacketed,' he says.

Those feelings inspired Dr Turner to rebel, and to gather the data that lead to his NEJM article.

These new antidepressants—which critics argued had turned America into a culture of the quick fix and that proponents praised as lifesavers—didn’t perform very well. Turner knew this. And he decided in 2004, at the very same time he was taking money from Lilly, that it was time to start telling the truth.

'I guess you could say I bit the hand that fed,' says Turner of his revelation.

Turner quit doing doctor talks for the pharmaceutical industry in 2005, convinced he needed to make his case more strongly by collecting reports of pre-approval clinical trials for antidepressants that had not been published.

Note that Dr Turner's account of his career as a pharmaceutical company paid lecturer parallels the account of Dr Daniel Carlat in his "Dr Drug Rep" article, even though the two worked for two different companies.

Both were seduced by their treatment as minor VIPs; initially thought they were selected because of their expertise; and eventually discovered that they were only supposed to deliver the content that the drug company marketers dictated, and specifically could only show the slides that the companies' marketers had prepared for their speakers.

These are only two case reports, they both strongly suggest that physicians who give "drug talks" may be helping companies market their products, rather than imparting their professional wisdom or scientific expertise. Such talks are sales talks, not medical education. Those physicians who give them, and those physicians who attend them, should not pretend otherwise.

Hat tip to Ed Silverman on the PharmaLot blog.

Wednesday, April 23, 2008

Report Faults West Virginia University Leaders for Retroactively Granting Degree to Pharma Executive

The Charleston (West Virginia) Gazette reported on an unusual entanglement between a medical school's parent university and a health care corporation.

The article summarized the findings of a West Virginia University committee that investigated irregularities in the awarding of an MBA degree to Ms Heather Bresch. Ms Bresch is the daughter of the governor of the state, and is also Executive Vice President and Chief Operating Officer of Mylan Laboratories, a large generic pharmaceutical manufacturer. Also,

Critics of the university have long pointed to Bresch's political connections: The chairman of Mylan is a major benefactor of her father and the university.

In summary,

West Virginia University administrators showed 'seriously flawed' judgment in awarding Gov. Joe Manchin's daughter a master's degree she didn't earn, rushing to protect her and themselves from media scrutiny, a panel investigating the dispute says.

Failures of process and leadership were 'unique to this particular, high-profile case' involving Mylan Inc. executive Heather Bresch

Apparently, Ms Bresch was awarded the MBA degree although she had not fulfilled the requirements for the degree, under circumstances that suggested external pressure.

The damning 95-page report released today is harshest on Provost Gerald Lang and business school dean Steve Sears, who the panel said had no academic foundation for retroactively granting Bresch the 1998 degree.

'Mistake was compounded by mistake. An unnecessary rush to judgment, spurred in some measure by an understandable desire to protect a valued alumna and to respond to media pressure, produced a flawed and erroneous result. It didn't have to happen this way,' the panel concludes.

[The report] does, however, indicate a failure of leadership at high levels within the administration and suggest there was pressure from Lang and 'representatives of the president's office' to accommodate Bresch.

Lang, as chief academic officer, bears the brunt of the criticism for running the one-hour, Oct. 15 meeting where the decision to grant the degree was made. Also attending were Sears, WVU chief of staff Craig Walker, general counsel Alex Macia, communications director Bill Case and three educators from the business school.

'The panel believes the prevailing sentiment at the meeting, evinced by the actions and comments of the provost and the representatives of the president's office, was that a way should be found to justify the granting of the degree, if at all possible,' the report says.

Ms Bresch's official biography on the Mylan Laboratories web-site claims she "earned an MBA .. from West Virginia University."

It is beginning to seem like if one can imagine a possible connection between a health care corporation and an academic health care institution, somewhere, somehow such a connection already does exist.

Friday, April 18, 2008

The Conflicted Again Defend Conflicts of Interest

The Boston Herald just ran an op-ed arguing against proposed legislation to ban gifts by pharmaceutical representatives to physicians. It included arguments that pharma reps are educators, not salespeople:

Despite extensive training, physicians cannot know the details of all products, especially new ones. Therefore, company salespersons complement physicians’ information derived from many sources.

To see what pharmaceutical representatives do other than providing education, see this post and its links to earlier ones. For a more graphic, and we do mean graphic demonstration of what some pharma reps are about, see this post (but be careful with the links).

Finally, the op-ed warned,

It threatens to dismantle a system that has served us well, and is deeply disrespectful of physicians and companies alike.

Not to be too snide, but I wonder to whom the "us" above refers. As discussed in posts by Ed Silverman on PharmaLot, and on the WSJ Health Blog, the two authors of the op-ed, Dr Thomas Stossel and Dr Dennis Ausiello, have multiple financial ties to the pharmaceutical industry.

Aussiello serves on the board of directors of Pfizer Inc, and hence has a fiduciary duty to protect the financial interests of the company's stockholders. According to PharmaLot, he is also "is on the advisory boards of Promedior, Proventys and Pulmatrix."

As we wrote last year, in a commentary in the New England Journal in which Stossel attacked the rigorous conflicts of interest rules that were once again imposed on the US National Institutes of Health (NIH), Stossel disclosed "having received consulting fees from ZymeQuest, owning stock options in ZymeQuest and Biogen, and having pending and issued patents, owned by Brigham and Women's Hospital, some of which are licensed to ZymeQuest." [Stossel TP. Regulating academic-industrial research relationships - solving problems or stifling progress? N Engl J Med 2005; 353: 1060-1065.] But in another paean to a laissez-faire approach to conflicts of interest in Perspectives in Biology and Medicine, Stossel also disclosed that he "is a member of the Board of Directors of Zymequest Inc, and the Scientific Leadership Advisory Board of Merck & Co. The author is a founding scientist of Critical Biologics Corporation and a consultant to Boston Scientific, Inc., and Gerson-Lehrman, Inc." [Stossel TP. Regulation of financial conflicts of interest in medical practice and medical research. Perspect Biol Med 2007; 50: 54-71. ]

So, the current system seems to have served Stossel and Aussiello well, at least financially. Whether their argument against restrictions of physicians' conflicts of interests are motivated by their own financial interests, or their concern for the future of health care for all, I cannot tell.

I have yet to see a good argument for physicians', especially academic physicians' financial involvement with for-profit health care corporations made by someone who does not have any such relationships.

ADDENDUM (19 April, 2008) - See also the comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.

Another Example of Manipulation of Clinical Research (Vioxx Department)

We have posted frequently about manipulation of clinical research by those with vested interests in having the research turn out a certain way. (Try clicking on the label "manipulating clinical research" below.) A recent JAMA article, companion to the article on ghost writing and guest authorship which we have already discussed, provided another vivid example of the manipulation of clinical research. [Psaty BM, Kronmal RA. Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation. JAMA 2008; 299: 1813-1817. Link here.]

Basically, the article was a case-study of how mortality results of trials of rofecoxib (Vioxx, by Merck, now off the market) were reported. The article focused on two clinical trials, 078 and 091, and compared results reported in publications, reported to the FDA, from the commercial sponsor's own analysis, and from an independent analysis of the original data done by an author of the JAMA article.

Our major interest is the manipulation of research as reported in the clinical literature (because published results are what are most available to physicians, other health professionals, and patients to provide evidence used in clinical decision making). So we will focus on these results.

Here is how the published reports of these trials discussed mortality (quoting from the JAMA article), first for study 078:

'A total of 39 deaths occurred in patients who were taking study treatment or from fatal adverse events that started within 14 days of the last dose (24 or 3.3% for rofecoxib and 15 or 2.1% for placebo). . . . There were an additional 22 deaths in the off-drug period (17 in patients assigned to rofecoxib and five in patients assigned to placebo); 12 of these (11 in the rofecoxib group and one in the placebo group) occurred more than 48 weeks after treatment discontinuation.' The report also states: 'In addition to evaluating efficacy, the present study provided important placebo-controlled data on the safety of rofecoxib 25 mg over periods of up to 4 years in an elderly population. . . . Rofecoxib was generally well tolerated by the elderly patients in the study, consistent with results from prior clinical studies in osteoarthritis (Langman et al, 1999; Reicin et al, 2002) and AD (Reines et al, 2004). The overall incidence of adverse experiences, serious adverse experiences, and discontinuations due to adverse experiences were [sic] similar or only slightly increased for rofecoxib vs placebo.' The overall impression created by this report, for which 8 of 11 authors are employees of the sponsor, is that rofecoxib was 'generally well tolerated.'

And for trial 091:

'There were no drug-related deaths during the study. Non-drug related deaths occurred in 11 patients (9 in the rofecoxib group and 2 in the placebo group) while taking study treatment or within 14 days of the last dose.' Deaths that may have occurred more than 14 days after the last dose were not reported. Regarding safety, the authors conclude that 'Rofecoxib was generally well tolerated by the elderly patients in our study, which is consistent with results from previous clinical trials in patients with osteoarthritis.'

Note that the reports both mentioned that there were more deaths in the group of patients who took rofecoxib, but did not analyze these results for statistical significance, and found no importance in these results.

Here are the results of the sponsor's own intention to treat analysis, which was done in 2001, and not sent to the FDA until 2003.

Study Rofecoxib Mortality Placebo Mortality Hazard Ratio (95% CI)
091 13/346 3/346 4.43 (1.26-15.53)
078 21/723 9/732 2.55 (1.17-5.56)

Note that in both trials the death rates were statistically significantly higher for patients taking rofecoxib compared to placebo.

And the JAMA author's independent analysis of data combined from both trials showed a total mortality of 57/1069 for patients treated with rofecoxib, 29/1074 for those on placebo, and a hazard ratio of 2.13 (1.36-3.33).

Thus, it appears that the two published trial reports minimized the drug's apparent relationship to mortality by failing to do an intention-to-treat analysis, and in fact failing to do any analysis of the mortality data.

This is just the latest (but certainly one of the better publicized) examples of how commercial sponsors of clinical research may manipulate the design, implementation, analysis, and/or dissemination of results of studies to further their vested interests.

This is bad for patients because clinical decisions supposedly based on apparently the best data from clinical research may be distorted by such manipulation.

This manipulation also betrays the trust of research subjects who volunteered to participate thinking that the results of the research were meant to further science and patient care. Instead, the manipulation of clinical research means that its results may really mainly further the marketing of the sponsors' products or services.

As the JAMA authors concluded,

The findings from this case study suggest that additional protections for human research participants, including new approaches for the conduct, oversight, and reporting of industry-sponsored trials, are necessary. A clinical trials system in which sponsors fund the trials that are conducted by independent investigators would provide additional protections.

In my humble opinion, continuing revelations about suppression and manipulation of clinical research suggest that all such research ought to be done by truly independent investigators who have no financial or other entanglements with organizations with vested interests in the research turning out a certain way.

Wednesday, April 16, 2008

Ghosts Come Home to Roost

We posted quite a bit starting in 2005 about ghost-writing (see post here with links backward).

Back then it became evident that a particularly pernicious type of ghost-writing was much more prevalent than anyone seemed to realize.This sort of ghost-writing has several important elements.

  • Commissioned by Those With Vested Interests - The writing is commissioned by an organization with a vested, usually commercial interest, e.g., a pharmaceutical company.
  • Directed to Support Vested Interests - The ghost-writer, perhaps a free-lancing medical writer or employee of a medical communication company, writes an article meant to support that organization's interest, often by setting the stage for the organization's new products. For example, a pharmaceutical company about to market a new drug may commission articles that makes the condition for which the drug is used seem particularly common or important, or which emphasizes the negative aspects of current treatments.
  • Fronted by an "Expert" - Finally, an expert, often a well-known academic, agrees to become the article's ostensible first author.

In 2007, we posted to summarize an article on ghost writing which appeared in respected, but not widely circulated journals. Moffatt and Elliott made two clear points:

  • Ghost writing is common.
  • Ghost writing is wrong.

They also suggested some important things that ought to be done.

  • Universities need to treat the practice of signing on to ghostwritten journal articles as a case of academic misconduct.
  • Lawyers should start naming ghostwriters and sham authors as defendants in litigation against the pharmaceutical industry.
  • There needs to be a standing committee, task force, or office with an established institutional home whose job is to gather information about potential cases of ghostwriting, to sanction authors who have been determined to participate in ghostwriting, and to disseminate information about ghostwritten papers to the public.
  • There needs to be an effective strategy for identifying and discouraging ghostwriting.

Of course, this issue got little attention, and none of the measures noted above were implemented. Until yesterday....

Yesterday, a major article appeared in JAMA which described a case-study of ghost authorship and ghost writing of publications related to the drug rofecoxib (Vioxx, Merck, now withdrawn from the market) that used internal company documents made public in the course of litigation about alleged injuries due to Vioxx. [Ross JS, Hill KP, Egilman DS, Krumholz HM. Ghost authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation. JAMA 2008; 299: 1800-1812. Link here.]

This article should be required reading not just for anyone interested in ghost writing, but for anyone concerned about what has gone wrong with health care. The main points of the paper were:

Merck used a systematic strategy to facilitate the publication of guest authored and ghost written medical literature. Articles related to rofecoxib were frequently authored by Merck employees but attributed first authorship to external, academically affiliated investigators who did not always disclose financial support from Merck, although financial support of the study was nearly always provided. Similarly, review articles related to rofecoxib were frequently prepared by unacknowledged authors employed by medical publishing companies and attributed authorship to investigators who often did not disclose financial support from Merck.

The authorship pattern observed within these documents suggests there was a widespread practice of inappropriately attributing authorship to academic authors and a failure to disclose relevant financial relationships.

Unlike the stories of ghost authorship we discussed in 2005, the JAMA article got a tremendous amount of press coverage. I should note that this included some rebuttals from Merck and some of those identified as "front" authors by the JAMA article. Here is a sampling, first of the authors:

The fact that the draft was written by a Merck employee for later discussion by all the authors does not in of itself constitute ghostwriting [Dr Louis Kirby, identified as an added academic author of one article, quoted by Stephanie Saul in the NY Times.]

But Steven H. Ferris, a neuropsychologist at New York University School of Medicine who is listed as the second author, said [the charges of ghost authorship were] ... not true. He said he was on a committee that reviewed the clinical records of 195 patients who received diagnoses of Alzheimer's during the study -- a task that took many hours, and for which he was paid.

'I was directly involved in a very substantive way,' he said this week. 'If an entity like JAMA is going to make an effort to expose a problem, they better get their facts straight. It is harmful if they don't.' [per the Washington Post.]
Having had a 20 plus year previous career in academic medicine, I can state with conviction that first, second, and third authors of major research papers published in important journals are expected to have been the people who conceived, designed, and implemented the study, analyzed its results, and were primarily responsible for the interpretation of thse results. Note that neither "author" above described his role in the trial in such terms.

Most of Merck's initial response seemed to come from its lawyers, for example,

A spokesman for Merck's legal team dismissed the JAMA authors as 'people in the pay of trial lawyers.' [per the Washington Post]

[James] Fitzpatrick, Merck's attorney, said: 'It is correct that Merck would sometimes use an outside company to compile the literature in a field and do the first draft, much the way a professor would use a research assistant to do the same thing.' [Per the Washington Post.]

Jim Fitzpatrick, a Merck outside lawyer, said the company agrees that authorship and financial relationships should be properly disclosed. The company adopted guidelines in 2003 to commit to further transparency in its publications, he added. Merck acknowledged that it sometimes worked with outside medical writers 'to facilitate the publication' of the studies, but said academic researchers 'were involved with the drafting and review of the papers that bear their name.'

Merck research chief Peter Kim said, 'We are disappointed that such false and misleading statements about Merck from trial lawyers have made their way into a medical journal.' [per the Wall Street Journal.]

A Merck legal spokesman said the company sometimes uses outside companies to draft articles that summarize research on its drugs. 'That's a common evolving practice in the industry,' said spokesman Kent Jarrell.

'We do not consider that ghostwriting,' added Jim Fitzpatrick, lead counsel in Merck's defense against numerous lawsuits over Vioxx. He said the company expects that the person recruited to sign the article 'would carefully review and make sure that the paper accurately reflected his or her scientific opinion.' [per the Boston Globe.]

Note that none of these responses provided anything concrete to refute the major points of the article, that Merck or MECCs in its pay found "front" authors for the clinical trial report articles who were not, in fact, the people who conceived, designed, and implemented the trial, and analyzed its results and crafted their interpretation. Doing minor edits of a draft someone else writes does not an author make.

The Ross et al article was accompanied by an editorial by the Editor in Chief and Executive Deputy Editor of JAMA [DeAngelis CD, Fontanorosa PB. Impugning the integrity of medical science: the adverse effect of industry influence. JAMA 2008; 299: 1833-1835. Link here.]

Its main conclusions were:

The profession of medicine, in every aspect—clinical, education, and research—has been inundated with profound influence from the pharmaceutical and medical device industries. This has occurred because physicians have allowed it to happen, and it is time to stop.

What are the lessons from the 2 articles in this issue of JAMA, from other publications that have examined related issues, and from extensive experience with how clinical research has been manipulated by for-profit companies? First, manipulation of studies and misrepresentation of study results could not occur without the cooperation (active and tacit) of clinical researchers, other authors, journal editors, peer reviewers, and the FDA. Second, public trust for clinical research is in great jeopardy especially when the extent of how widespread such practices have become is unknown. Although we truly believe that the vast majority of researchers and other authors are honest and have the highest scientific integrity, manipulation of studies and publications by the pharmaceutical and medical device industries is either increasing or there has been more exposure of these practices. Third, in addition to clinical research, clinical practice and medical education also are greatly influenced by for-profit companies. Drastic action is essential, and cooperation of everyone involved in medical research, medical editing, medical education, and clinical practice is required for meaningful change to occur.

Some of the press coverage included more vivid comments by DeAngelis.

I consider that being scammed. [Referring to ghost written article in JAMA, per article by Stephanie Saul in the New York Times.]

The manipulation is disgusting. I just didn't realize the extent. We're the ones who have allowed this to happen. Now we've got to make it stop. [per the AP.]

[Ghostwriting is] a terrible form of prostitution. We've given up the profession. We've got to get it back. [Per the Philadelphia Inquirer.]

DeAngelis and Fontanarosa had a list of 11 detailed action items, many of which were relevant to those suggested by Moffatt and Elliott above. However, item 11 was radical.

Individual physicians must be free of financial influences of pharmaceutical and medical device companies including serving on speaker's bureaus or accepting gifts.

Maybe this time someone will be listening.

We on Health Care Renewal have been talking for years now about how clinical research and medical education have been influenced and manipulated to promote vested interests. It now appears that a substantial portion of the clinical evidence base and a substantial amount of medical education have been so undermined.

Dr DeAngelis is right. We have given up medicine and now we have got to get it back. If we don't, we will be left with unimaginably expensive health care that does little good except to the pocket books of the well connected.

ADDENDUM (16 April, 2008) - On the PharmaLot blog, Ed Silverman noted that Dr Ferris (see above) seemed to have trouble recalling his actual role in the Vioxx trial. Also on that blog, Ed Silverman noted that Senator Grassley is looking into the role of one of the MECCs mentioned in the Ross et al article.