Monday, October 12, 2009

Nemeroff, Seroquel, and ACCME

Nemeroff, Seroquel, and ACCME

Roy Poses has discussed the atypical antipsychotic drug Seroquel (quetiapine) several times on this site, pointing out manipulation of clinical research results to enhance the appearance of efficacy, and suppression of studies with unfavorable results. I call this augmenting the marketed profile of the drug. Daniel Carlat has commented on published Seroquel data here and ClinPsych here.

AstraZeneca, the marketer of Seroquel, has also been busy with continuing medical education (CME) programs that augment Seroquel’s profile. Last December 8, one such program went on line, aired by the provider CME Outfitters. The program’s title was “Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough.” The corporate logo for CME Outfitters is Education with Integrity. I will allow readers to decide if the company is meeting its mission statement in this respect.

The key opinion leader engaged by CME Outfitters to discuss Seroquel and other atypical antipsychotic drugs was Charles Nemeroff of Emory University. He was joined by 2 KOLs-in-training, whom I will not name. The corporate sponsor that paid CME Outfitters and, indirectly, these presenters was AstraZeneca. I do not need to rehearse here the ethical issues that have surrounded Dr. Nemeroff for the past several years. Suffice it to say that, as a result of those issues, Dr. Nemeroff is no longer chair of the department of psychiatry at Emory University, he is no longer editor-in-chief of the ACNP journal Neuropsychopharmacology, he was removed from involvement with ongoing federally funded research grants at Emory University, and he was put on a short leash by the Emory administration.

On December 23, 2008 I filed a formal complaint about Dr. Nemeroff’s program with ACCME. My bill of particulars was lengthy, detailed, and backed up by extensive
materials. In due course, ACCME investigated the complaint and found that the program did violate ACCME standards. With respect to content, ACCME determined that Dr. Nemeroff’s program lacked sufficient information about possible adverse effects of treatment with atypical antipsychotic drugs; and failed to emphasize sufficiently the efficacy of alternative treatments. With respect to commercial bias, ACCME determined that bias existed as a result of the absence of contrasting therapy data, and through downplaying the drawbacks related to treatment with atypical antipsychotic drugs in depressed patients.

Following these findings by ACCME, the provider was notified of the violations in early September 2009, and the program was removed from the provider’s website. The sanitized statement of violations determined by ACCME does not capture the nuances of deceit, ineptitude, and deficient educational content in Dr. Nemeroff’s program. One remarkable example was Dr. Nemeroff’s citation of data, from one of his own publications, that were previously retracted. Did he think no one would notice?

A second example involved biased presentation of the sponsor’s data for Seroquel. Two doses of Seroquel (150 mg and 300 mg) were tested. Only the results for the 300 mg dose were statistically significant. Nevertheless, in the video presentation one of the junior presenters stated very clearly that there was “significant improvement in both response and remission with both doses” of Seroquel. That is a falsification of the scientific record. That falsification does not meet ACCME requirements for fair, balanced, truthful, and honest teaching. As moderator, Dr. Nemeroff was required to correct this false statement made by his junior assistant, but Dr. Nemeroff failed to do so.

The negative findings and sanction by ACCME against Dr. Nemeroff’s program are welcome, though I have to say it took ACCME an inordinately long time to complete their work. I also presented ACCME with several follow-on questions, which the Council is now considering. These are:

• Did ACCME notify the presenters that their program violated ACCME policies? If not, why not?

• Will CME credits be clawed back from physicians and other professionals who obtained credits through the noncompliant program? If not, why not? I believe this would be an effective form of negative feedback to the provider and the presenters.

• Does ACCME have a process to require the provider and presenters to ascertain whether any patients were injured as a result of the violations that created biased and deficient information in this program? If not, why not?

• Does ACCME require the provider to notify physicians and other professionals who completed the noncompliant program that the provider was sanctioned for violation of ACCME standards? If not, why not?

• Does ACCME require the provider to furnish corrective materials to such professionals in order to remedy the bias and incompetence to which they were subjected through violation of ACCME standards, and thereby to remove potential danger to future patients? If not, why not?

• Why did ACCME allow the noncompliant program to remain available long after the complaint was filed? I suggest that ACCME needs to place a hold on programs that are subject to active complaint. Had such a policy been in effect in December 2008, the violating program would not have been re-aired by the provider in early 2009, it would not have remained on-line for 9 months, and the damage to the continuing education community would have been contained.

• Will ACCME issue a public listing of sanctions it has enforced against providers and presenters? If not, why not? State medical boards do exactly that in relation to physicians and other professionals who violate standards of practice.

• Finally, I reminded ACCME that its primary constituents are patients, physicians and other professionals, not commercial or academic CME providers. It seems to me that ACCME was altogether too laissez-faire and dilatory in the way it handled this matter. At the time of my initial complaint last December, I requested expedited review precisely because additional airings of this violating program were scheduled.

The good news is that ACCME seems to have got the message that things need to change. As one of their officers wrote to me recently, “We sincerely appreciate the time and effort you have put into participating in our complaints and inquiries process. You have raised important issues that the ACCME will review and address.” I await their next communications on the remaining questions.

As for Dr. Nemeroff, he is yesterday’s news. The adverse findings by ACCME about his program serve as a reminder to corporate sponsors and CME companies that Dr. Nemeroff is so compromised by now that he has lost effectiveness as a front man for Pharma. Indeed, he is so toxic that he now glows in the dark.

5 comments:

Anonymous said...

You have certainly raised serious issues and gotten a lot of people at ACCME thinking. As a small CME provider I would like to add some comments.

1- You gave the program a real once over and came up with a very detailed critique. I don't know what CME Outfitters did to review the program. But what do you think an analysis like this costs? Are physicians willing to pay for the added price tag now needed for CME? Alternately, some bias may be in the eye of the beholder (not here, of course). Perhaps audience feedback, like yours, is merely part of the process.
2- Your suggestion that the program be pulled immediately pending review seems appropriate given the findings in this case. But we have twice been the object of complaints and, in both cases, they were lodged by corporate representatives who were unhappy about content that was favorable to their competitors. In both cases their complaints were groundless beyond the boundary of their own discontent and were found to be so after independent review. I've been told that this happens a lot. So pulling a program just because someone complains can be unfair.

Bernard Carroll said...

Thanks for your thoughts, anonymous.

You say, I don't know what CME Outfitters did to review the program. But what do you think an analysis like this costs? I am sure it costs a lot less than having to do all the repair work would cost after violations are determined. The real answer is for the CME provider to do up front due diligence. That means have the content reviewed by genuinely independent professionals. Do not rely on the KOL presenting faculty to verify lack of bias – they have their own competing interests. It also means avoid doing dumb things like feature the corporate sponsor’s drug via non-peer reviewed meeting abstracts, some of which are not archival and all of which are of low educational value.

As to your second point, that is truly ironic. But when the complaint comes from a knowledgeable physician consumer of CME, then the case for putting a hold on the program is hard to deny. In the present instance, ACCME appeared incapable of shifting gears despite the gravity of the complaint. As things stand now, MECCs and CME providers know they can run with biased programs for many months before having to respond to a notice of noncompliance. So they are free to game the system, and by the time they receive a notice of noncompliance they are ready with a new program, and the scenario can repeat itself.

Bernard Carroll.

Anonymous said...

Nemeroff close relationships with CME Outfitters represent a substantial portion of the total revenue for this provider. Just look at all the programs where he appears as the KOL for CME Outfitters. Look also at the other KOLs appearing most often with Nemeroff, then combine all the programs this represent in terms of volume for CME Outfitters.

Then, "Follow the money."

FWIW, the partners are on a first name basis with Nemeroff. CMEO's medical writers are keenly aware of this factoid.

Nancy Frugé said...

The continuing education course described in this post was not only offered to physicians. The course was offered to nurses, pharmacists, social workers, psychologists, certified case managers, and physician assistants as well. My hope is that the professional accreditation bodies involved will notify their respective professionals who completed the course that the course content was biased.

Nancy Frugé said...

Recent news reports indicate that ACCME is taking the lead in addressing conflict of interest problems in medical education.

I would like to see ACCME and the American Nurses Credentialing Center (ANCC) present a united front on this issue.

In October 2008 Bernard Carroll called to my attention the CME Outfitters program. In November 2008 I filed a formal complaint with ANCC's Commission on Accreditation regarding the content of CME Outfitters' program materials. In December 2008 I filed a formal complaint with ACCME.

According to ANCC's commercial support standards for developing content and format without commercial bias, “The content or format of a continuing nursing education activity or its related materials must promote improvements or quality in health care and not a specific proprietary business interest of an entity with a commercial interest....Presentations must give a balanced view of therapeutic options....” See

http://tinyurl.com/ybn6hr7

ANCC's Commission on Accreditation reviewed the program. Nonetheless, the program remained online until ACCME tardily intervened in September 2009.