MEDSCAPE'S CME ETHICS, PART II

19 June 2008

MEDSCAPE’S CME ETHICS, PART II

A few days ago I discussed Medscape’s parasitic use of professional organizations to embellish its mediocre CME offerings – “highlights” of the closed 2007 ACNP annual meeting, for example. One of the responses to my post called attention to Dr. George D. Lundberg’s video editorial of 13 June 2008, denouncing attacks on commercially sponsored CME activities. Among other claims, Dr. Lundberg, a past editor-in-chief of JAMA, stated that Medscape “follow(s) rules that prevent bias and improper influence.” He went on to boast that Medscape is “the largest single source of CE for health professionals” and that “We are just going to keep doing what we are doing. It is good. We are clean. Our work is transparent…. We welcome analysis and criticism. We function in the best interests of patients …” These words were spoken before Daniel Carlat and I published our critiques of Medscape a few days later (see here and here and here).

There seems to be a right hand – left hand problem at Medscape. Though I take Dr. Lundberg at his word about his intentions, I invite him to defend the products that actually appear under his oversight as editor-in-chief. Let’s look at a case study of an “Expert Interview” published on-line June 9, 2008 under the tagline Medscape Perspectives on the American Psychiatric Association (APA) 161st Annual Meeting, May 3-8, 2008, Washington, DC. A boilerplate legal disclaimer noted, “This activity is not sanctioned by, nor a part of, the American Psychiatric Association. Conference news does not receive grant support and is produced independently.”

The “Expert Interview” for our case study is titled “Pharmacologic Options for Treatment-Resistant Depression…” The featured expert is Charles Nemeroff, chairman of Emory University’s department of psychiatry. Dr. Nemeroff is well known for ethical controversy. In 2003 the Nature Publishing Group revised their policies on disclosure of financial conflicts of interest in the wake of Dr. Nemeroff’s widely publicized nondisclosures. In 2006 Dr. Nemeroff resigned as editor of the journal Neuropsychopharmacology after he failed to disclose conflicts pertinent to a review article he co-authored and placed in his own journal. As is always true of case studies, the devil is in the details if we wish to understand just how sly and subtle was the spinning. Here are some of the issues that arise from Dr. Nemeroff’s Expert Interview on Medscape.

1. Internal contradiction. The legal disclaimer noted above states that there was no grant support and that the conference news items were produced independently. However, Dr. Nemeroff’s featured item prominently acknowledges an unrestricted educational grant from Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc. These two companies jointly market aripiprazole, a member of a drug class highlighted by Dr. Nemeroff in his Expert Interview.

2. Infomercial format. The Expert Interview by Dr. Nemeroff resembles nothing so much as Lindsay Wagner promoting the Select Comfort Sleep Number Bed in television advertisements. Promotional statements are made without scientific backup.

3. Disease mongering. In this interview, Dr. Nemeroff backed away from his earlier strict definition of treatment-resistant depression (TRD), proclaiming that in his current view 40% to 50% of depressed patients have treatment resistance. This sleight of hand naturally expands the market for the agents he later promotes as augmenting agents.

4. The primary care “hook.” Dr. Nemeroff introduced a professional “hook” to primary care physicians, emphasizing the association of depression with cardiovascular disease. This strategy is a component of disease mongering. Dr. Nemeroff’s discussion of this association had approximately zero educational value. Why did Medscape not insist on more substantive content?

5. Inappropriate drug recommendation. In discussing the switch strategy from one antidepressant class to another for resistant depression, Dr. Nemeroff included a recommendation for nefazodone. That drug was withdrawn by Bristol-Myers Squibb Company several years ago because of hepatic toxicity. What kind of “expert” makes such a recommendation? And what kind of editorial oversight by Medscape waves through such an incompetent statement?

6. Uncritical reliance on uncontrolled studies. In discussing switch of antidepressant drugs, Dr. Nemeroff noted that in phase II of the STAR*D trial 25% of patients switched from citalopram to sertraline responded. Dr. Nemeroff’s discussion of that result was inadequate. He invoked a dubiously relevant effect of sertraline on the dopamine transporter (when you are stuck for an answer, invoke neurochemical mythology) but he ignored the default hypothesis that 25% would have been the placebo response rate had STAR*D been designed to include placebo control groups. This default hypothesis assumes that all SSRI drugs are basically similar in terms of efficacy. For an educational item in Medscape or anywhere else, this aspect of the Expert Interview falls short of expected standards.

7. Pushing dangerous drugs. Dr. Nemeroff has been a leader in promoting use of second generation antipsychotic (SGA) drugs as augmenting agents for resistant depression. I have commented previously on his promotion of risperidone for this purpose, here and here. Others have raised serious questions about his reports. Overall, Dr. Nemeroff promotes these drugs by exaggerating their efficacy and glossing over their toxicity in resistant depression.

8. False statements. In this Expert Interview, Dr. Nemeroff leads off his discussion of SGA drugs for TRD with an endorsement of risperidone. The 2 published references to risperidone in TRD have major scientific flaws. Indeed, the study by Rapaport et al (reference 12 in this interview)was retracted. Nevertheless, Dr. Nemeroff still claims this study supports his position on SGA use in TRD. Does Dr. Nemeroff not read the retractions of his own publications (by his own “research team”)? How naïve are Medscape’s editors to be ignorant of these retractions?

9. Talking up the sponsor’s product. In reviewing the toxicity of SGA drugs for TRD, Dr. Nemeroff found something negative to say about the side effects of olanzapine, quetiapine, and risperidone. However, he made no mention of aripiprazole’s side effects, even though he emphasized its recent approval by the FDA for TRD. How convenient, as BMS-Otsuka sponsored his Medscape spot. Where were Medscape’s editors, described by George Lundberg as working to prevent bias and improper influence?

10. Glossing over weak efficacy. Though Dr. Nemeroff endorsed aripiprazole for TRD, he neglected to discuss the weak efficacy of this drug. The Number Needed to Treat for remission with aripiprazole in TRD is a disappointing 10. The studies cited by Dr. Nemeroff only compared aripiprazole against placebo. Dr. Nemeroff surely knows that just beating placebo does not qualify a drug as clinically useful. Dr. Nemeroff neglected to address the comparative efficacy of aripiprazole versus established treatments of TRD, such as lithium augmentation. The available evidence suggests that patients will do better on lithium and that aripiprazole would not be the first line choice, especially in primary care. Where were Medscape’s editors?

11. Reckless promotion of SGAs early in the course of TRD. Dr. Nemeroff emphatically stated he is not opposed to the early use of SGAs for TRD. Here especially he resembled Lindsay Wagner. A conscientious educator would weigh the risks and benefits of the early and broad use of SGA drugs in TRD. Dr. Nemeroff did no such thing. He simply opined. Why did Medscape’s editors allow him to get away with this reckless promotion? There does not appear to have been any effective editorial oversight of this publication.

12. For Dr. Nemeroff to promote early use of SGAs in TRD is reckless because of the serious toxicity associated with these drugs. Where is the discussion of akathisia (26% in the most recent study of aripiprazole in TRD)? Where is the discussion of emergent suicidality associated with akathisia in depression? Where is the discussion of tardive dyskinesia caused by aripiprazole (5% within 12 months in schizophrenia, and quite possibly higher in mood disordered patients)? Where is the discussion of neuroleptic malignant syndrome associated with SGAs like aripiprazole? Where is the discussion of weight gain with aripiprazole in TRD (significantly greater than with placebo)? Where is the overall analysis of risk versus benefit? Where were Medscape’s editors? Who at Medscape was looking out for “the best interests of patients”?

13. Incomplete disclosures. Dr. Nemeroff has a long history of recidivism concerning failure to disclose pertinent financial conflicts of interest. His record in this instance continues that sordid tradition. He failed to disclose that he is currently chairing a national series of CME meetings promoting aripiprazole for TRD, sponsored by, you guessed it, Bristol-Myers Squibb/Otsuka. Perhaps he thinks that because the money is laundered through a Medical Education Communications Company he doesn’t need to disclose it. Tell that to Joseph Biederman, who was called to task last week by Senator Grassley’s Senate Finance Committee for exactly that obfuscation. Dr. Nemeroff also failed to disclose his support from Janssen for studying risperidone in TRD. He failed to disclose his association with CeNeRx, that is developing MAO inhibitors, mentioned favorably in his interview. There is more, but these examples will suffice. Doesn’t Medscape know by now that Dr. Nemeroff cannot be relied on to report his conflicts appropriately? Does Medscape have knowledgeable professionals or ciphers in its editorial office?

So, this sleazy example illustrates many of the systemic problems that Medscape will need to correct if it hopes to remain credible. This documentation gives the lie to Dr. Lundberg’s claims that “We are clean. Our work is transparent.” One suggestion is for Medscape to abandon the degenerate form of scientific journalism exemplified by “Expert Interviews” and News items. In their present formats they cannot be truly educational and balanced items. They do not qualify for CME credit, as I verified with the company. They are simply vehicles for promoting sponsors’ products. And the Medscape staff seem to think their job is to ensure that the spin is firmly in place. Does George Lundberg really intend that?

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.

New Dispute Over Industry Involvement with a New Definition of Hypertension: "Monetarization of Medicine?"

Almost a year ago we discussed a dispute that had broken out within the American Society of Hypertension (ASH) about the role of industry in and conflicts of interesting affecting the society's work.

The New York Times has followed-up with another story, this one highlighting the society's role in a new and more expansive definition of hypertension. This definition included some people with "pre-hypertension," previously defined as a blood pressure between 120/80 and 139/89, within a newly defined "state 1 hypertension" group. This expanded definition appeared in an article whose lead author was the current President of ASH (Giles GD, Berk BC, Black HR, Cohn JN, Kostis JB, Izzo JL Jr, Weber MA. Expanding the definition and classification of hypertension. J Clin Hypertens 2005; 7: 505-512.) The Times noted that "of the seven doctors who wrote the proposed new definition, six have said they served as consultants and speakers for pharmaceutical companies that make blood pressure medications. The seventh is a consultant and stockholder in a company that markets a diagnostic method to measure damage to blood vessels."

The Times also noted "the work of the group that developed it was financed by $75,000 in unrestricted drug industry grants from Merck, Novartis and Sankyo...." Furthermore, a society staffer "confirmed that the dinners [to discuss the new guidelines] were financed by $700,000 in grants, also unrestricted, from the same companies."

Internal critics within the society criticized the process. "This is about the monetarization of medicine," said former society President Dr Michael H Alderman, who had withdrawn from the group which proposed the new hypertension definitions. Furthemore, he noted, "all this has got the ring of seeming to be of great benefit to the pharmaceutical industry without clear evidence that it's going to be the same benefit to the public." Dr Curt D Furberg, from Wake Forest University, also withdrew from the group. He charged that "its work was not evidence-based, ... [and] 'the industry wants to sell drugs and to as many people as possible.'" Jane E Sealey, who had been President-Elect of the society, said, "the truth of the matter is that we have many members who are leaders in our society who are making well into the six figures from their pharmaceutical-company-supported activities." Dr Sealey immediately resigned her presidency at the society's annual meeting, according to theHeart.org.

ASH President Giles countered that "the organization had always maintained a firewall between its activities and industry funding. 'We don't take money that has strings attached to it.'" One of the authors of the new hypertension definition, Dr Joseph L Izzo of the University of Buffalo, said "there are those who accuse us of being nothing more than shills of industry: a lot of us take pretty great offense at that."

This seems to be another example of how disease definitions get expanded, often with some degree of participation by pharmaceutical companies who have interests in increasing the market for their products. Note also that the sorts of possible conflicts of interest described may have largely unconscious effects on those affected, as we have discussed. So the indignation of people who are not conscious "shills of industry" is real, but perhaps misplaced.

Furthermore, this is another case that suggests physicians and patients need to be increasingly skeptical about the apparently authoritative guidelines that now rain down on us.

Finally, the Times also reported that Dr Steven E Nissen, new president of the American College of Cardiology, "suggested that the medical profession had become addicted to industry money just as the nation was addicted to foreign oil." Maybe it's time to kick the habit.

Papers from the Disease-Mongering Conference Now Available

We were happy to announce a while back that the Inaugural Conference on Disease-Mongering would be held in Newcastle, New South Wales, Australia, from 11 to 13 April, 2006.

Now we are also pleased to announce that a list of papers from the conference is available today from PLoS Medicine on the web here, and the links to the papers should go live later today. The papers look interesting, and we hope to report back on them after we have had a chance to read them.

A Conference on Disease-Mongering

Blimey, more positive news...

If you can get to Australia in April, you can attend the Inaugural Conference on Disease-Mongering to be held in Newcastle, New South Wales, from 11 to 13 April, 2006.

The conference will bring together academics, researchers, health professionals, health managers, journalists, writers and consumers who share an interest and concern over the trend to corporate definitions of diseases with a primary interest in making profits rather than a concern for the public health.

The Conference will feature speakers who are internationally recognized in this field. We are also inviting free papers on any topic related to disease-mongering and medicalisation.

For those who want to submit papers (original research or commentaries), the abstract deadline is March 1.

I am glad these sorts of problems are now coming out into the open. We first have to recognize the problems before we can come up with solutions.

Thanks to PharmaGossip for the tip.

More Downsides of a "Pill for Every Ill"

Two recent stories from the NY Times also accent the possible unintended effects of pharmaceutical companies' efforts to market "a pill for every ill."
One story was about the rush to develop drugs to combat obesity. Of course, obesity has health risks. But critics of the drug industry fear that the real appeal of such drugs would be to the only slightly overweight. This could lead to a huge market for such drugs. According to the Times, 60% of the US population is overweight. Thus "everybody is just foaming at the mouth to make money from obesity drugs." The danger, of course, is that new drugs often have rare serious side effects that are not detected in controlled trials on even thousands of patients. New obesity drugs might be taken by millions of patients, thus any such rare adverse effects could still affect substantial absolute numbers.
The other NY Times article was about increasing apathy towards safe-sex measures to prevent the spread of HIV. Some think that this is partly due to "drug company [direct to consumer] advertisements that gloss over the disease's effects by portraying patients as the pictures of perfect health." For example, Michael Weinstein, President of the AIDS Healthcare Foundation, cited an ad for Reyataz in Out magazine featuring two robust men on a beach. The ad includes an audio microchip. Opening the page "sets off the trill of a ringing phone and a man's voice essentially saying he is having too much fun to worry about his chronic illness." The San Francisco health department also fears that drugs for erectile dysfunction (ED, as the drug-makers like to call it) are another culprit, since they can counter the impotence caused by "crystal meth." ED drugs are widely marketed by direct to consumer advertisements, as anyone who has turned on network television in the last year must realize. Weinstein has called on Bristol-Myers-Squibb to stop running its audio enhanced ad, while the department of health is seeking to limit availability of "ED" drugs.
All the more reason to support the UK House of Commons Reports' call for "an industry led by the values of scientists, not those of its marketing force." (Quoted in the Guardrian.)