New federal conflict rules released this week confirmed rumors that the National Institutes of Health had stepped back from stronger public transparency for biomedical researchers who accept industry support. The updates to the rule, last established in 1995, are still an important step forward, lowering the reportable dollar threshold that counts as a potential conflict from $10,000 to $5000 annually, and capturing more info on academic-industry ties both at the university and federal level.

Despite the disappointing retreat on requiring universities to publish investigators’ conflict info on a public website–(schools  must only be able to produce it upon request, much like FOIA)–the updated rule retained some major improvements and stated reasons that we supported in comments to the Institutes in 2009, including:

• The definition of a Significant Financial Interest, and therefore what is reported, be changed from its current level – payments above $10,000 – to $5,000, which would mean universities would have to report all such payments to the NIH. (The Association of American Medical Colleges, or AAMC, also backed this change.)
• Reports of Financial Conflicts of Interest (FCOI) to NIH should include more information, specifically the criteria and categories identified in the Physician Payments Sunshine Act.

The new rule will also broaden the types of payments an investigator must report to his or her institution, including sponsored travel, though an institution may not require a dollar amount—but at minimum a destination, sponsor and purpose of the trip. The NIH will also require grantee institutions to train investigators on conflicts of interest and the policies going forward.

As we noted last year, the AAMC and other university associations pushed back hard on many parts of the rule, even questioning in late comments the need for changing the conflict of interest rules:

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 … erode the trust between the regulators and those being regulated. (AAMC comments on proposed rule, the Federal Register, August 2010)

“Academic medicine revolted against it,” Public Citizen’s Sidney Wolfe told PostScript earlier this month. Wolfe said the public website component of the rule was an important “user-friendly place” for researchers and patients concerned about the potential bias of researchers who take money from drug companies to go.

Other watchdog groups said the rules stopped short of what was needed.

“The take-home message is that these are half steps,” Paul Thacker, a former aide to Sen. Grassley and now at the Project on Government Oversight, told the Washington Post. “[NIH] could have taken steps that ensured the trust of American taxpayers who are funding this research, but they chose not to take those steps.”

Thacker told the JAMA blog that keeping the website rule could have been as simple as ‘requiring institutions to add information about management plans and investigators’ conflicts to the NIH’s existing RePORTER database, in which institutions provide information about the use of grant funds.’

In our comments to the agency, we, along with Sens. Grassley and Kohl, stressed that the Physician Payments Sunshine Provisions would be an important tool for auditing disclosures made to NIH institutions. With the rollback on uniform public access to this information, Sunshine’s centralized, public-geared website becomes even more essential, and the agency should take care to preserve it, both in spirit and in letter.

–Kate Petersen, PostScript blogger

The FDA and generic drug makers have reached a deal that would raise nearly $300 million in annual fees to inspect foreign API makers and bring monitoring in line with domestic inspection rates. According to the New York Times, the agreement awaits some final specifics and is “almost certain to pass Congress” as part of the PDUFA 5 reauthorization, due up next year.

Under the outlines of the deal, as reported by the Times and Pittsburgh Tribune-Review, generic drug makers would pay $299 million annually so that the FDA can conduct inspections of foreign drug plants at the same rate – every two years—that it does domestic ones.

“If a program along the lines of what the parties are working on is enacted by Congress, it would represent a real breakthrough,” FDA Commissioner Margaret Hamburg told the Times. “FDA’s entire generic drug program would be placed on a much more stable footing.”

To those around the industry, the deal seems an important solution to a (sadly) familiar equation: that even as its demands of the FDA grow, Congress is unlikely to fund the agency sufficiently to meet its increasingly global inspection lode. In fact, lawmakers have been threatening to cut funding, and in the current political climate, the agency may find itself turning to industry for help maintaining current operations (as its user-fee program does now for approvals.)

Heather Bresch, President of generic drug maker Mylan, is credited with getting the deal this far, and has been an outspoken advocate in the industry for the fees and the parity they’re designed to bring. She told the Tribune-Review that “the rigor is just not there (at foreign manufacturing plants) as it is here in the United States.”

“As a mother of four children, I want to know the drugs I’m giving them are safe,” Bresch told the Times. “And as an American businesswoman, I want to keep jobs here, and that means making sure foreign drug plants have to meet the same standards as domestic ones.”

–Kate Petersen, PostScript blogger

Late getting to this, but wanted to comment on a good post by physician-blogger Howard Brody about Epocrates and how smartphone apps are replacing the drug rep office visit.

Brody points to a recent New York Times story about Epocrates, a company that markets a free smartphone app with drug information for physicians. According to the Times, pharma dollars account for 70 percent of Epocrates’ revenue. There are similar apps that are independent of industry ad money, but they cost something—UpToDate, which the Times highlights, costs between $395-$495 (which seems pretty reasonable in the context of physician earnings).

“Docs love Epocrates because its smartphone app is free,” Brody writes.

That’s probably true – see the Free Lunch Phenomenon. But despite (or alongside) the pharma ads, Epocrates also offers information on all the insurance company and public program formularies so a prescriber can actually check on the tier, coverage and cost to patients in the exam room if she wants to.  Whatever the reason, it seems physicians have been opting for Epocrates free model — which is free, of course, because pharmaceutical companies are underwriting the Rx info to get this 2.0 face time.

The Times dug up this assessment that the former chief of Epocrates, Kirk Loevner, made in an online interview: “It is a unique market, unlike any I have seen before…You have a drug industry that spends $14 billion a year to influence people who prescribe drugs. There are only 600,000 people who are allowed to prescribe drugs, so there is $14 billion spent against 600,000 people. If you have a channel to reach these physicians, it is a gold mine.”

A crushingly simple equation.

Brody writes:

The drug companies have recently been cutting back on their drug rep sales force, both to reduce costs as fewer brand name blockbusters remain on the market, but also because they see a greater marketing advantage in Internet and electronic approaches to practitioners–like Epocrates. Epocrates seems to be talking out of both sides of its mouth when it comes to who it works for–the docs or the drug industry. Which side is winning?

How long are we in medicine going to keep thinking we can get goodies for free and yet we won’t be biased and that the real goal is education, not marketing?

–Kate Petersen, PostScript blogger

‪Pressure’s building on the Office of Management and Budget to give a status update after Nature blog reported earlier this week that OMB may have tossed a rule proposed by NIH last year that would tighten conflict of interest reporting rules for biomedical researchers and institutions. Yesterday, Sen. Charles Grassley wrote to the Administration asking for documents related to the decision, and saying to rollback the rule “flies in the face” of its own transparency promise (hat tip Pharmalot).‬

‪In the spirit of disclosure, we supported the NIH rule in public comments with the Pew Prescription Project last year, and defended it here when university associations took aim at it late last summer. Despite progress among academic medical centers in tightening individual conflict policies, many AMCs still do not publicly disclose faculty ties to drug companies, and schools and investigators are left making the call if and what to report.

Meanwhile, media reports and industry-based disclosures like the Propublica ‘Dollars for Docs’ database show that millions of dollars are still moving from drug company to doctors’ hands. When those doctors are also doing tax-payer funded research that guides clinical practice and prescribing, we think the NIH–and the public–should know.‬

‪I talked to Dr. Sidney Wolfe of Public Citizen yesterday about the rule, the flap around conflict of interest at FDA, and just how hard it is to find an unconflicted expert around here.‬

‪‪PS: Many academic medical centers have strengthened or implemented better disclosure policies recently. And we have the Physician Payments Sunshine Act coming down the line. So why was this NIH rule needed? Where does its rollback leave us?‬‬

‪SW: Just think about the Dollars for Docs. Before a website like that (which only has data from the eight companies that currently disclose) you needed to go to each of the eight companies’ websites, instead of being able to get all of the information on a  specific doctor at one place. Instead of having to write to every academic medical center, [the NIH rule] would put it in a user-friendly place subject to analysis.  ‬

‪And academic medicine revolted against it. They don’t want this, they don’t want medical students to easily out find what’s going on. Because if you are a med student, you may have a different view of your instructor who’s positive toward a therapy if you find out he or she is getting a considerable amount of money from the company who makes it.‬

‪There’s little doubt as to why the academy pushed against this rule. They don’t want people to believe members of their faculty have a bias. Of course, many still have to disclose it, but now it requires leafing through papers, or waiting for a FOIA request.‬

‪PS: What happened? Is this about budget woes, or pressure from industry and the universities?‬

‪SW: Nothing has happened yet.  But from what [Nature reporter] Meredith Wadman reported, it certainly pushes away from what should have been now been finalized.‬

‪No one is disputing there is a big glitch in this process. I doubt whether out of a clear blue sky, [OMB's] Cass Sunstein says, ‬Oh, that is not a good idea‪. I assume he read the letters, and he may be just more ideologically attune to academic medicine and those trying to fend off what was originally proposed by the government 15 months ago.‬

‪PS: Conflict of interest rules at FDA are also in the news after Commissioner Hamburg said at a Public Citizen meeting this week said that limiting financial conflicts has made it hard to fill advisory boards. But Health News Review and Project on Government Oversight offer lists of independent experts, and say the rule is not to blame.  Is this a real problem? ‬

‪SW: There’s no doubt that it’s more difficult to find someone without a conflict, but it’s obviously very important to do so, because these decisions are best made by people who don’t have a conflict of interest. The advisory committee I serve on, the Drug Safety and Risk Management Advisory Committee, had some empty slots, but the slots have all been filled now.

I don’t think there have been any committees that have not met because of unfilled slots.  One could argue that having tougher conflict laws and missing two or three people on a committee actually makes the decision-making better. This decision-making is too important to be polluted with a conflict of interest. ‬

‪There are two questions, and it’s not clear which Commissioner Hamburg was referring to.‬

‪Question A: Does someone get put on a committee or not?‬

and Question B is: Even if they are on a committee, should this person be recused from a given meeting? Someone with a conflict can also be given a “waiver,” but this happens much less than it used to six, eight, 10 years ago. ‬

‪PS: NIH has rules around advisors’ conflicts, too. To be an NIH reviewer, one must receive less than $10,000 from an involved company per year, as I understand it. Do you know if NIH has similar vacancies, or problems finding unconflicted experts? ‬

‪SW: NIH reviewers pretty much have a final say, whereas we are just advisors to the FDA. I doubt seriously that NIH will tell you that they have a very difficult time finding enough reviewers. And if it’s a little more difficult, remember, the whole purpose is to be as unfettered as possible. So it’s worth the extra effort.‬

interviewed by Kate Petersen, PostScript blogger

When it comes to inspections, collaboration and info-sharing helped FDA and international regulators cover more ground globally, the agency said in a report on two pilot projects it conducted with its European and Australian counterparts.

The two pilots, one focused on clinical trial inspections and the other on API manufacturers, were designed to test feasibility—and work out some of the kinks—of a more cooperative inspection model that FDA has put at the center of its new comprehensive plan to catch up with demands of watch-dogging the global drug supply. They were conducted between December 2008 and March 2011.

FDA said it was able to cut down on redundant inspections by relying on shared reports, and could better flag factories or trial sites that should be checked sooner, versus ones that could wait. Such basic risk assessment in a resource-intensive operation like field inspection is sorely needed. FDA noted that it banned the import of a product based on a negative European inspection. Concrete actions like that are strong evidence that this cooperation really worked, and that’s a good thing.

While they cover some predictable ground, the reports offer a close look at the nuts and bolts of what info-sharing and joint inspections really require  – the fine balance of having enough teleconferences vs. too many, planning joint inspections far enough in advance so everyone you want to be there can be there, and the eternal question: Should we put this in an Excel sheet? But inspections are nothing if they aren’t about the details—and about getting them right.

All told, these pilot projects offer good evidence that the FDA’s move toward sharing its regulatory burden is both a workable and wise one.

But big roadblocks still exist. One of the challenges these agencies still face is how to best work with inspectors in countries with newer or less-developed regulatory cultures—countries such as India and China that are also the site of more and more ingredients manufacture and clinical trials. For instance, FDA’s Deborah Autor pointed out at the Pew Health Group’s After Heparin meeting that before inspecting factories in some countries like China, agencies are required to have a written invitation from the government to obtain a visa.

“All partners are supportive in principle of continuing the API inspection collaboration and extending the project to new partners,” the report says, but of course there are often miles to go between ‘in principle’ and ‘in practice.’

And these pilots move the US, Europe and Australia down the ‘in practice’ field.

You can download the reports at FDA’s site.

–Kate Petersen, PostScript blogger