Late last summer, the Association of American Medical Colleges attempted at the eleventh hour to significantly weaken proposed rules to tighten up conflict of interest policies for NIH-funded biomedical research.

Now the rule, which would require institutions to collect and report more information about their investigators’ financial ties to drug and device companies, is facing threats from another corner, as OMB trawls the regulation fountain for small savings.

But looking to detooth or block conflict of interest regs isn’t the answer. We know from ProPublica‘s review of company payments and other recent reports that big dollars from pharmaceutical companies are still flowing into the hands of clinicians, who are often also publicly-funded researchers.  And we know from a series of Senate and media investigations that the current honor system of requiring researchers to report conflicts with the drug industry is broken in big ways.

The new rule would help fix that by creating common protocols and measurements, helping to ensure all NIH-funded institutions are reporting and managing COIs in the same basic way.

The AAMC and AAU’s earlier attempt to weaken the NIH proposal illustrates the difficulty an association that represents so many institutions can have setting a high bar, and there’s sometimes a tendency to recede to the lowest common denominator.

Indeed, many academic medical centers have been very proactive in taking steps to better manage the potential financial conflicts of their faculty. But the Senate’s investigation revealed many medical schools were guilty of lax oversight, and this would help them avoid similar problems in the future.

Recent sanctions of some high profile researchers at the center of the conflict of interest storm, including a prominent group of Harvard psychiatrists, remind us why NIH proposed the new rule in the first place, and of the potential costs of not changing them.

Harvard psychiatrist Joseph Biederman contributed to a 40-fold increase in pediatric bipolar diagnoses between 1994-2003, running NIH-funded research even as he was on the payroll of the companies whose drugs he was studying – netting $1.6 million from the drug industry from 2000-2007 alone. He urged one company to fund a Harvard research center “to move forward [its] commercial goals.”

The explosion of pediatric bipolar treatment is a part of a larger rise of mental health diagnosis and treatment. One in 10 Americans over age six now take an anti-depressant, and the newer class of atypical antipsychotics—about which relatively little is known—is now the top-selling drug class in America.

So how much has this high-stakes blurring of the line between research and marketing cost us?

In its assessment of the new rule, HHS estimates that it will take an institution one hour to review an investigator’s conflict, and two hours a year for an investigator to adhere to the reporting rules. It estimates only an incremental cost for institutions to post the information to a public website, since all of them already have such websites.

So how much is it worth to us to make sure that future leading-edge clinical science–which guides so much medical practice in this country–is done with transparency and objectivity? How much is it worth to improve a system that has clearly been ineffective in ensuring that taxpayer-funded pharmaceutical research is about good science, not good marketing opportunities?

The Administration would do well to calculate all this before watering down important reforms needed to ensure responsible use of taxpayer funds.

–Kate Petersen, PostScript blogger

Last week the Association of American Medical Colleges and three other university associations took aim at the NIH’s proposed rule to tighten disclosure and reporting requirements, departing from their initial support of tightened regs last summer.

Like the AAMC and Association of American Universities (AAU), who joined AAMC in its comments, we voiced our support for reform and suggested ways to strengthen reporting and transparency when the NIH solicited public comment last summer on ways to shore up rules aimed at promoting objectivity in research.

This May, the Institutes issued a proposed rule with many strong reforms (you can read about that here on PostScript.) The rule was amended and the comment period extended after it came to light that an National Institutes for Mental Health director Thomas Insel had recommended psychiatrist Charles Nemeroff for a job at University of Miami, despite Nemeroff’s failure to report large sums he received from GlaxoSmithKline while working on an NIH–backed grant on a GSK drug. That violated NIH rules and led to his resignation from Emory University, but Insel apparently assured Miami administrators that Nemeroff would be eligible for NIH funds at a different university. (Carlat Psychiatry Blog and Pharmalot have the backstory.)

In its newest comments, AAMC asks for reporting exclusions that would significantly weaken the proposal.  As currently written, NIH would exempt disclosures only for seminars at institutes of higher ed and government agencies. AAMC suggests exempting all speaking gigs, lectures and seminars at academic teaching hospitals, medical centers, research institutes affiliated with an institute of higher education, and other non-profits involved in research.

They also suggest that travel funds be exempted from reporting requirements, as well as any funding for CME presentations that meet ACCME standards. However, in this compliance-savvy climate, most industry-backed CME presentations in which NIH investigators participate are ACCME accredited – and such accreditation does not eliminate inherent bias in such programs.

Unfortunately, those are pretty big slices of the pie. A lot of research-related dollars are flowing through third parties at this point—including the non-profits and other third parties that AAMC asks to be exempted. Most patient organizations and professional medical associations are non-profits, and the grants money they receive is often passed on to individuals for fellowships, participation in research symposia, or education. As you can see on Pfizer and Lilly’s websites, most grant recipients from the two drug companies listed here are non-profits, and many of those grants seem to be for these research-related purposes.  
Just because they are issued through a non-profit does not mean these funds cannot somehow influence how an investigator conducts his research.

The AAMC and its cosigners also suggest that NIH should rely first on investigators to decide what to report, based on their judgment of the relatedness of a financial interest to their research.

Well, this is how much of this started – Sen. Grassley and others found that investigators, who decide under current regs what they do and don’t report to their institution, weren’t reporting some pretty big industry payments related to their research. See Nemeroff, Schatzberg, Biederman, et al. In most cases, the medical schools that AAMC represents were the ones to get the bad press and in hot water for these omissions. The NIH proposed rule change would help protect these institutions by taking the evaluative reporting decision away from the investigator. With the Sunshine Act providing a national database of company payments to physicians and teaching hospitals, we don’t want institutions that are accountable to NIH to be caught out if they aren’t aware of a payment to an investigator that shows up in the Sunshine database.

The AAMC also proposes that if undisclosed conduct is discovered, an investigation could be waived.  But we support NIH’s proposed mandatory investigation if someone fails to report a Financial Conflict of Interest (FCOI). The new regs were proposed and will be implemented for good reason. There is no current mechanism for NIH or an institution to judge whether an investigator failed to report a FCOI “in bad faith” or whether the unreported interest affected research. Unless you investigate, there is almost no way to uncover intentional and problematic non-disclosures. We can’t count on whistleblowers to enforce this.

Worryingly, the groups frame their comments by calling into question the very need for the reforms.

There is a paucity of evidence that the disclosure and management of financial conflicts of interest affect objectivity and integrity. In the absence of such evidence, onerous regulations are not only unwarranted, but could create a glut of policies that increase activity without adding protections and at the same time erode the trust between the regulators and those being regulated.

We think this is a tough claim to make, since the rule was proposed and amended in large part because of Congressional investigations and media stories that revealed millions of dollars of undisclosed industry funds in the hands of publicly-funded researchers.

While there may be no study yet that links disclosure of FCOIs to research integrity, there is increasing evidence of bias in research and disclosure is one step we can take to try to reduce this bias.

–Kate Petersen and Ian Reynolds, PostScript

MedPac approves disclosure recs

Last week, the Medicare Payment Advisory Commission approved recommendations that would require pharmaceutical and medical device companies to disclose payments to clinicians, academic medical centers, continuing medical education programs, and other health care entities in a public database.

We discussed the recommendations and their potential influence on the next Congress last week here.

Medical school mashup

Conflicts of interest in academic-industry relations were the hot topic at the annual meeting of Association of American Medical Colleges last week, said Stanford School of Medicine Dean Phillip Pizzo in his Dean’s newsletter last week.

Speaking of academic-industry relations, Emory University has announced that it has formed an ethics panel to look into its management of researcher conflicts of interest. The move comes after a Senate Finance Committee investigation into the extra-curricular and undisclosed industry payments of Dr. Charles Nemeroff led to his stepping down as chair of Emory’s psychiatry department last month.

Check out RxP director Rob Restuccia’s op-ed on why greater transparency like the kind the Finance Committee is seeking is essential for good medicine, and find out more about the new Emory ethics panel here.

Hunting caps

Based on the GlaxoSmithKline’s recent comment that it will be capping industry payments at $150,000 per doctor per year in line with the industry’s current standards, Ed Silverman at Pharmalot went on an epistolary hunt to see exactly what those industry norms were. Many of the responses he received from companies suggested they were looking at current practices, and referenced compliance with the revised PhRMA code which, incidentally, is silent on caps on payments to doctors.

Papers weigh in on pre-emption

And thought it seems forever ago, it was just last week: Before there was Election Hubbub, there were opening arguments in the Supreme Court’s hearing of Wyeth v. Levine, the preemption case that will determine whether consumers can file suits over FDA-approved drugs in state courts. Here are opposing editorials from the Boston Globe and Wall Street Journal – we’re sure they won’t be the last – and the Kaiser Daily Health Policy Report provides a good soup-to-nuts.

Subcommittee refutes FDA safety finding

In a follow-up to a story we touched on last month, Integrity in Science Watch reported that the FDA subcommittee assigned to look at the FDA’s prior ruling on bisphenol-A “blasted the agency for declaring the plasticizer safe, saying the agency used unacceptable criteria for selecting studies to inform its deliberations.” Some groups had been concerned with a possible conflict of the subcommittee chair, who received a large undisclosed gift for his University of Michigan research lab from a Michigan-based plastic maker.

Despite the subcommittee report, the FDA issued a statement saying it stands behind its position that BPA is still safe for water bottles everywhere.

This week, House Energy and Commerce Committee Chair John Dingell (D-Mich) and Oversight and Investigations Subcommittee Chair Bart Stupak (D-Mich.) sent a letter to the FDA asking about just how and why the agency chose non-profit EthicAd to partner on the creation of the “Be Smart About Prescription Drugs” website, launched last month to help consumers navigate drug ads.

In September, we had some questions of our own about EthicAd’s mysterious funding sources and close ties to Shaw Science Partners, a pharmaceutical marketing company with a long list of Big Pharma clients.  We broke news of Shaw Science Partners and EthicAd’s office- and phone-sharing arrangement here on Postscript, and look forward to hearing of the agency’s reply. 

And the latest joint probe of the Senate Finance Committee and the Special Committee on Aging, Senators Charles Grassley (R-IA) and Herb Kohl (D-WI) are looking into industry payments received by Columbia University cardiologist and stent entrepreneur Martin Leon and other Columbia researchers at the Cardiovascular Research Foundation.  The probe seems to center around the CRF’s industry–sponsored device conference, Transcatheter Cardiovascular Therapeutics, and Leon’s ties to the sponsoring companies.

Here’s more at Bloomberg.

But it’s only the latest investigation, and if history’s any guide, won’t be the last. With the troubling discovery of piles of undisclosed industry payments an Emory University psychiatrist took from a company whose drug he was testing on the government’s dime, and new revelations about the wag-the-dog marketing tactics used to push Neurontin, editors of the New York Times and Atlanta Journal-Constitution write this week that all this coziness between drug companies and doctors “underscores the need for Congress to pass a bipartisan bill, sponsored by Senators Chuck Grassley and Herb Kohl, that would require drug companies and other medical manufacturers to publicly disclose payments to physicians that exceed $500 a year.” (10/11, New York Times).

The Journal-Constitution went further in its recommendation, saying passage of the disclosure bill – also known as the Physician Payments Sunshine Act – is a “bare minimum,” and that the “culture that has infected drug company sponsorship of academic medicine needs a thorough cleansing,” including a “temporary reduction in the amount of money going into research and continuing physician education.”(10/12, Atlanta Journal-Constitution)

And another editorial in the Arizona Republic this week takes a puzzling non-stand on the PPSA: First they were against, then they were for it? In the end, we’re not really sure. Just like the writers don’t seem very sure whether or not doctors are influenced by pharmaceutical marketing. The verdict?  “Probably not.” Sure, we’d heard the West is a place of fewer words, but this is taking it too far.

The first two editorials were no doubt spurred by the controversy around Dr. Nemeroff’s busy speaking schedule. News came this week that he’s about to get a little less busy – the National Institutes of Health have hit pause on the 5-year, $9.3 depression grant that Nemeroff was heading up at Emory. The AJC says despite his freed up schedule, Nemeroff is still turning down interviews.

And over at A Healthy Blog, RxP’s Kathy Melley looks ahead at what we’ve all been waiting for. Our 401Ks back? Ok, the other thing we’ve been waiting for – the decision from the U.S. Court of Appeals on prescription data-mining bellwether case, Ayotte v. IMS Health.

“The court ruling could have the effect of ratcheting up or down state legislative activity on data mining,” Melley writes, but that “regardless of where the court comes down, there’s a good chance the U.S. Supreme Court may be the final arbiter on this issue.”

Medical students and local physicians will rally at the Harvard Medical School campus today, urging their adminstrators to create better conflict-of-interest policies around pharmaceutical marketing.  According to a press release from the American Medical Student Association, which is capping its National PharmFree Week at the Longwood medical campus in Boston, “Students are asking for involvement in the policy drafting process, increased transparency, mandatory lecturer disclosure and a reasonable timeline for drafting and implementation.”

Check out the AMSA scorecard rating medical school COI policies here.

When is writing a memo fun? When the sender is you, the recipient is you, and its purpose is to authorize payment - to you.  We’re pretty sure Dr. Charles Nemeroff enjoyed getting that memo (from himself) authorizing $3000 to be paid (to himself) for writing a medical journal supplement, as much as we would enjoy a similar return-address windfall.

But what about that journal supplement itself? These ‘special sections’ in medical journals – often sponsored and usually focused around a related topic, like a disease group or drug class – tend to be less editorially rigorous, amounting to nothing more than glossy chances for companies to buy extra ad space.  In this Journal of the American Medical Association study, blinded reviewers found that the quality of the medical articles – in study design, sample size, and analysis — was inferior in the supplements to those published in the parent journals. And other scholars and clinicians have wondered openly whether they are worth the paper they’re printed on – much less $3000.

Yet, that self-payment was just one of the more trifling findings of the Senate Finance Committee into the large undeclared industry payments to Dr. Charles Nemeroff, former head (and by former, we mean Friday) of the Emory University Department of Psychiatry and principal investigator on an NIH grant to study a GlaxoSmithKline drug there. And by industry payments, we mean GlaxoSmithKline.

While the Committee has been hot on the trail of 30 academic psychiatrists and their disclosure sheets that don’t match up to company records, the case around Dr. Nemeroff – depicted in this letter from Committee Chair Sen. Charles Grassley to Emory and obtained by Pharmalot — is singular in the repeating and bald-faced quality to Nemeroff’s bucking of the NIH rules, which require universities to ‘manage’ conflicts caused by investigators’ significant conflicts of interest (defined as $10,000 per year).

For instance, in August 2004, Nemeroff wrote to Emory’s conflict-of-interest committee to say he was in compliance with the $10,000 limit — and in that month alone Nemeroff took in excess of that yearly maximum in speaking gigs and “non-product” phone calls alone.

After Emory’s COI committee raised questions about his failure to follow approval protocol of his consulting agreements and discrepancies on his disclosure sheets, Nemeroff wrote another memo, this one not as fun, about his future compliance, which read: “I will follow the management plans for my conflicts of interest”… and “I shall limit my consulting to GSK to under $10,000/year and I have informed GSK of this policy.”

Grassley’s letter goes on:

Barely a week after this promise, on July 12, 2004, GSK paid Dr. Nemeroff $3,500 in fees and $505.40 in expenses for a talk he gave regarding Paxil at the Larkspur Restaurant and Grill in Las Vegas, Nevada. The following day, Dr. Nemeroff gave two more talks in exchange for $7,000 from GSK ($3,500 per talk).

Maybe the maxim, What happens in Vegas, stays in Vegas, just hasn’t made it to the Beltway yet.