UMDNJ Monitor Alleged "No Research Compliance Capability"

We have done a long series of posts about the troubles at the University of Medicine and Dentistry of New Jersey (UMDNJ), the largest US health care university. The university now is operating under a federal deferred prosecution agreement under the supervision of a federal monitor (see most recent posts here, here, here, here and here.)

We had previously discussed allegations that UMDNJ had offered no-bid contracts, at times requiring no work, to the politically connected; had paid for lobbyists and made political contributions, even though UMDNJ is a state institution; and seemed to be run by political bosses rather than health care professionals. (See posts here, and here, with links to previous posts.) A recent development (see post here with links to previous posts) was that UMDNJ apparently gave paid part-time faculty positions to some community cardiologists in exchange for their referrals to the University's cardiac surgery program, but not in exchange for any major academic responsibilities. Another was some amazingly wasteful decisions by UMDNJ managers leading to spending millions of dollars for real-estate that now stands vacant (see post here). Another was the indictment of a powerful NJ politician for getting a no-work job in the system, and the indictment of the former dean of the university's osteopathic medicine school for giving him the job (see post here). Most recently, we found out that UMDNJ had named one of its teaching hospitals for a pharmaceutical company in 2001 (see post here), that the federal monitor accused the dean of one of the UMDNJ campuses of fixing students' grades (see post here), and that the monitor found even more bizarre financial practices at the university (see post here).

All things must pass, so UMDNJ no longer has a federal monitor. Apparently, the publicly released version of the monitor's final report noted a number of positive changes at the university. However, a Newark Star-Ledger story revealed that even this report described contained yet another heretofore unknown problem.

Hundreds of millions in federal grants could be at risk because of lax research oversight at the state's medical university, according to a previously undisclosed portion of the federal monitor's report.

The new material, whose conclusions University of Medicine and Dentistry of New Jersey officials vigorously disputed, found the school had 'no research compliance capability' -- jeopardizing future funding, as well as the health of patients in clinical studies.

At issue is the university's problem-plagued Office of Ethics and Compliance, and UMDNJ's ability to audit research spending and report violations of clinical studies' guidelines to the federal government. The confidential portion of the report found the ethics office, whose director recently resigned and is missing other key personnel, had failed in performing critical oversight of federal research grants.

'UMDNJ admittedly has no research compliance capability at all and none is anticipated,' the monitor stated in the report.

University officials vehemently challenged the assertions.

'We have a significant amount of research compliance. We have over 20 years of history of research compliance at this university,' said Denise V. Rodgers, executive vice president of academic and clinical affairs. 'Do you think people ... would risk their reputation coming to an institution if there was no research compliance? Not a chance.'

U.S. Attorney Christopher Christie, who was briefed on the compliance findings, called it a 'serious matter' that seemed to have started long before UMDNJ came under the scrutiny of his office in 2005.

'It's always a problem when you don't have sufficient internal controls on any program. It is even a greater problem for an institution like this,' he said, citing UMDNJ's well-documented troubles with patronage, no-bid contracts and violations of Medicare and Medicaid laws.

In the public version of his final report, the monitor found UMDNJ had significantly improved since the string of scandals that nearly shut down the $1.6 billion university. However, he singled out UMDNJ's ethics and compliance office for criticism. The university's chief ethics officer, Michael R. Clarke, resigned last month after less than 18 months on the job, saying he wanted to return to the private sector. The university is now searching for a successor.

Stern's rebuke of the compliance office was far more harsh in the full report not released to the public. It alerted UMDNJ to failures that investigators only recently began looking into before the deferred prosecution agreement that led to the monitorship termination in December.

All of the monitor's reports released to the public have been edited to omit details of any ongoing investigations, and the final report cited 42 open investigative files based on 'allegations of legal and ethical breaches or conflicts of interest.'

Rodgers attributed the monitor's findings to a 'misunderstanding' over the fact that the university has not yet hired a research compliance officer. She said research at UMDNJ comes under multiple layers of oversight, including an Institutional Review Board; a Human Subjects Protection office; an office of research, as well as an institutional compliance officer and other academic officials.

'This university has over ($115 million) in grants from NIH,' she said. 'You can believe that if they had big concerns that we had no research compliance we would have not been able to get that money?'

I would note parenthetically that the rebuttals by UMDNJ officials seem to be based on logical fallacies, and therefore do not seem very convincing.

The officials first seemed to deliberately interpret the monitor's report in a very concrete way, that it alleged the university literally had not compliance efforts whatsoever. Then, they tried to rebut this straw-man argument by saying that yes, UMDNJ actually has an IRB, a human subjects protection office, etc. In fact, the report did not deny the existence of a compliance structure, it just somewhat sarcastically denied the structure was functional.

The officials then asserted that if the University had no functional non-compliance mechanism, someone ought to have already figured this out, and punished the university for it. This appears to be a version of a logical fallacy called an appeal to consequences of a belief (if X were true, there would be bad consequences. There have not been bad consequences, so X must not be true.) Why the particular problem mentioned in the report, a non-functional research compliance system, should have been more obvious than all the other problems at UMDNJ is not clear.

It's amazing how often the issues discussed on Health Care Renewal inspire health care organizational leaders to creatively use logical fallacies to defend their organizations and prior actions.

Unfortunately, this latest report reinforces the notion that the UMDNJ administration was a poster-child for poor management of an academic health care institution at multiple levels and in multiple spheres. Let's hope that things really are getting better there.

BLOGSCAN - Deftly Dissecting Dubious Defenses of Research Suppression

On the Clinical Psychology and Psychiatry blog, this post notes how a recent article about the effect of suppressing clinical research on SSRI (selective serotonin reuptake inhibitor) anti-depressants brought out some curious defenses of not publishing research results. The anonymous Clin Psych blogger deftly dissects these dubious defenses of research suppression.

Merck and Vytorin ... Who, Exactly, is Confused?

Treating the number rather than treating the patient is usually bad medicine.

In today's Philadelphia Inquirer and probably a number of other papers, a full page ad appeared with the following in a huge, Victory-in-Europe-WW2-is-Over!! font:

Are you taking Zetia (ezetimibe) or Vytorin
(ezetimibe/simvastatin)?

Then the following statement is made in a large bold font, smaller than the headline's but still very large (ellipsis in the original, but bolded emphasis mine):

If so, you may be worried about recent news stories questioning the benefit of these medicines ... on the basis of a single study that has generated a lot of confusion.

The font size goes down another notch with this:

In fact, ZETIA and VYTORIN have been proven to lower LDL (bad) cholesterol along with diet in multiple clinical studies involving thousands of patients. Both the American College of Cardiology and the American Heart Association agree that lowering bad cholesterol is important.

The font then goes up a notch in size once again:

All of us at Merck and Schering-Plough proudly stand behind the established efficacy and safety profiles of ZETIA and VYTORIN.

If you have high cholesterol, follow your doctor's recommendations on eating right, staying active, and taking your prescribed medicines.

The ad is signed by Richard Murray, MD, VP, External Medical and Scientific Affairs at Merck, and Robert J. Spiegel, MD, FACP, Chief Medical Officer, Schering-Plough Corp.

I cannot help but be touched by this ad. It is factually accurate, gives good medical advice about following your doctor's recommendations and taking your meds, and appeals to the authority of the very prestigious ACC and AHA.

Here's the catch. In the "Important Information" column below the above material, along with contraindications and possible side effects, the statement is made that (bold in original):

"Zetia has not been shown to prevent heart disease or heart attacks."

In which case, I'm not sure who, exactly, is "confused" by the "single study."

The ad calls for treating the number, perhaps in the hope that it is treating the patient. However, hope and wishful thinking are not the tools of science. Roy Poses provides more detail on this issue here:

As summarized by theHeart.org, they showed no statistically significant improvement in the thickness of arterial walls for patients who received ezetimibe, and no statistically significant decrease in the rates of revascularization, stroke, myocardial infarction (heart attack), or cardiovascular death in the group of patients given the drug. (The study was not big enough to have much statistical power to detect such an improvement, but the rates of all these outcomes except stroke were actually greater in the ezetimibe group.) Up until the the release of these results, no study had shown that ezetimibe produces any clinical benefit, e.g., prevents heart attacks or strokes, prolongs life, etc. And the long-delayed results of the ENHANCE trial again showed no such benefit.

I understand the rationale behind the new ad -- an attempt to keep sales of Zetia and Vytorin up to prevent yet another drug from failing in the setting of a thin pipeline of drugs ready for launch and looming patent expirations. I do not envy the difficult position these executives, trying to keep their businesses healthy, are in. However, I consider the ad to be bad spin, the kind in which politicians engage, not biomedical scentists and organizations. The real issues are:

Why should consumers and insurers spend extra on a drug like Zetia, which also can cause additional side effects, if it is shown to lower cholesterol but not shown to prevent heart disease or heart attacks, one of the major (if not the predominant) reason people take cholesterol-lowering drugs? Why "treat the number?"

I believe there is good evidence that many of the statin drugs do lower the risk for heart disease. If zetia does not, then why assume the expense and/or take the risk until meaningful clinical benefit to the patient, if any, becomes clear?

Other recent widely-publicized drug debacles have certainly given support to "erring on the side of caution."

That would seem to be the "un-confused" approach.

In fact, massive full page ads that cost a lot of money like this one may "treat the pharmaceutical company", but likely generate even more skepticism about the industry among the lay public and among critical-thinking clinicians.

I also add that the creation of a "new" drug (Vytorin) via the combination of two existing drugs (statin and ezetimibe) is likely a sign of a company trying to "do business from an empty wagon." It's regrettable when a company that had done as well as Merck in the past in creating truly "breakthrough" drugs has had to resort to such repackaging to stay financially viable.

I spent much effort at Merck to increase access to important informatics tools by drug discovery scientists to which access was rationed, an accomplishment I am proud of, but probably would not have had to perform if the industry understood the priorities for long term survival and research creativity better. This seems unlikely in a pharmaceutical industry dominated by non-scientist/clinician, quarterly profit-oriented, management fad-centric businesspeople at the helm.

Perhaps if as much resource and energy had been devoted by the pharma industry to R&D as to marketing (recent studies show a 2-to-1 overspend on the latter), and less had been spent on bureaucracy, the need for "repackaging" and "spin" by the industry would not exist - they'd be selling good drugs. And, I might still be employed in the industry, rather than part of the 4,400 laid off in 2003 when several other new drugs failed to make it into the sales wagon.

-- SS

Addendum: the above full-page ad has now appeared for the third straight day in the Phila. Inquirer. Perhaps there were better uses for the money spent, such as R&D, or the postmarketing drug surveillance that pharma often skimps or simply reneges on?

Most post-market studies funded by industry are intended specifically to expand the market for a drug, and such studies are usually not undertaken unless the calculated probabilities indicate that the study will yield a positive financial return [1]. In approving a new drug, FDA may demand that a company conduct additional safety trials after release to the public, but the agency can't enforce these post-approval studies, which are tedious and expensive, as FDA has “limited authority to require that sponsors conduct post-market safety studies [2]. More than half of those agreed to by manufacturers never occur, according to a Department of Health and Human Services report in the March 15, 2004 Federal Register [3].

1. Preventing Medication Errors: Quality Chasm Series. Committee on Identifying and Preventing Medication Errors, Board on Health Care Services (Aspden P, Wolcott J, Bootman JL, Cronenwett L, editors), Institute of Medicine, National Academies Press, 2007 (prepublication copy), p. 238 (quoting Tunis et al., 2003).

2. Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight Process. p. 11, United States Government Accountability Office, Washington, D.C., March 2006, http://www.gao.gov/new.items/d06402.pdf

3. Dangerous Practices: Critics see flaws in drug-safety monitoring. Science News, Week of Feb. 5, 2005; Vol. 167, No. 6 , p. 90, http://www.sciencenews.org/articles/20050205/bob10.asp

BLOGSCAN - The Sorts of People Who Get to Run Large Health Care Organizations

Back blogging on BrandweekNRX, Dr Peter Rost just posted about the sort of people who now run Schering-Plough, the company that, with Merck Inc, just got a lot of unfavorable publicity after it was involved in delaying the release of results from the ENHANCE trial of ezeimibe (see our last related post here.)

According to Rost, "Sean McNicholas is now Schering-Plough's Senior Vice President, responsible for ZETIA and VYTORIN, reporting directly to [Schering-Plough President] Carrie Cox, who dumped $28 million SGP stock last year." Previously, "Sean McNicholas was Vice President Marketing, Endocrine Care, Pharmacia, responsible for Genotropin marketing until the year 2001." But, "Pharmacia entered into a Deferred Prosecution Agreement with the Government for its illegal promotion of Genotropin for such 'off-label' uses as anti-aging, cosmetic use and athletic performance enhancement...."

Furthermore, "Carrie Cox was Vice President, Women's Health Care at Wyeth, responsible for marketing of Prempro and for Pondimin and Redux, two slimming products.... In September 1997, the FDA requested the withdrawal of Pondimin and Redux [parts of the fen-phen weight loss drug combinations] and Wyeth ended up paying well over $20 billion in class action settlements to women who alleged heart valve damage."

It makes one wonder about the sorts of people who get to run big health care organizations, especially in an environment where there seem to be no negative consequences when top leaders make poor decisions.