House Oversight Chair Darrell Issa has been looking into the FDA’s action at a closed Johnson & Johnson medicine plant in Puerto Rico. Three months after the Justice Department took ownership of three troubled J&J plants through a consent decree, Issa is concerned that regulators and the company aren’t working quickly enough to fix the deep quality problems there.

According to Bloomberg, Issa complained that regulators have not reviewed corrective action plans for the plant since the division was taken over in March, and have not visited the site since September.

Remember, that’s before a pretty bruising hearing in late September 2010 at which J&J had few answers about why it carried out a “phantom recall” to pull faulty Motrin from shelves, and the FDA said that it found quality problems in every one of J&J’s plants.

While it’s good that Issa’s subcommittee is keeping an eye on the FDA and the progress of the J&J case, the Energy and Commerce Committee has already identified some of the root problems and drawn up smart, comprehensive solutions—not just to the J&J case, but to the system failures behind some of the company’s problems.

The Drug Safety Enhancement Act (HR 1483), introduced in April, would answer some of Issa’s question by boosting mandatory inspections, and giving the FDA better enforcement tools in the form of recall and subpoena authority.

Issa is right to question the J&J aftermath and be dismayed at the larger problems in our drug safety system. He and his committee members should recognize the DSEA as an important step toward fixing those problems, and make sure this bill has the support it needs to move in Congress.

Read more on the bill at the blog, and a summary of HR 1483 here (pdf).

-Kate Petersen, PostScript blogger

This week, I talked by email with physician and researcher Dr. Joseph Ross about the importance of using unique identifiers in pharma disclosure data, and other ways to take the guess work out of the Physician Payments Sunshine database.

PS: Last week, a commentary in JAMA (Carpenter/Joffe) suggested that unique investigator identifiers should be used in the Physician Payments Sunshine database to make the data most usable, accurate, and suitable for cross-reference with other databases.

You’ve spent a lot of time with data collected under similar disclosure laws in Minnesota and Vermont. From your point of view as a researcher, what aspects of an identifier are important or helpful to looking at these data?

JR: From our experience examining the data in Minnesota and Vermont, I can only say that some unique identifier is necessary. Neither the Minnesota or Vermont data that we used included a unique identifier, just the name of a physician, clinician, or hospital/clinic that accepted the payment from the pharmaceutical company.

We found that trying to determine exactly who accepted which payment was virtually impossible, because one could not be sure whether a “Dan Smith” in Minneapolis was the same or a different “Dan Smith” in St. Paul, for example. Without a unique identifier, doing research to examine which physicians or clinicians are accepting payments can only be done in the aggregate, not at the individual level.

However, what is most interesting about Carpenter and Joffe’s proposal is not the unique identifier in itself, but the development of an identifier that could be used across databases, linking payment disclosure data, to grant applicants, to manuscript submissions and publications, to service on NIH or FDA committees. I could imagine this identifier being an expanded use of the NPI (national provider identifier), or another number, but it would certainly make identifying potential conflicts of interest far simpler.

PS: One of the reasons these authors suggest a unique identifier is to capture payments made to non-physician investigators. Did you deal with this issue in your work with the Minnesota and Vermont data?

JR: Yes, examining the data in Minnesota and Vermont, there were a substantial number of payments made to non-physicians, although these clinicians were not necessarily investigators. I agree that if the PPSA is broadened to include payments made to non-physicians, an alternative identifier to the NPI might be necessary. NPIs are required by all health care providers, including non-physicians who bill insurance companies or write prescriptions. But some non-physicians who receive payments from industry may not fall into this category.

However, to me, the real issue is a shortcoming of the PPSA, which requires companies to include physicians’ NPIs in their annual submissions, but prevents these numbers from being made publicly available.

PS: Why is that a problem?

JR: This is a problem because, as it stands, the payment disclosure data cannot be confidently attributed to an individual without using the NPI as a unique identifier. Our prior experience suggests that individual physicians will appear in the disclosure data multiple times, potentially with different spellings of their names, different practice addresses and so forth. It becomes a bit of guess work to determine if a payment to Daniel Smith from Lilly in September should be combined with the payment to Dan Smith from Lilly in April.

PS: In your 2007 JAMA article, you wrote about difficulty you had obtaining the Vermont/Minnesota data, and the poor quality of the information once you received it. Out of this experience, what should some of the priorities be in developing Sunshine systems and payment categories to produce a meaningful public disclosure scheme?

JR: Well, we’re still more than two years away from seeing how the PPSA plays out in practice. The legislation was fairly specific in terms of what information is to be collected.

Of all the categories pre-specified, the “nature” of the payment is most subject to interpretation.

My hope is that they interpret it as specifically as possible, so that, for instance, its disclosed when a payment is for a) speaking at a ACCME accredited educational event, b) speaking at a non-ACCME accredited educational event, c) attending a ACCME accredited educational event, or d) attending a non-ACCME accredited educational event. If the “nature” of a payment is disclosed vaguely, all four of those activities could be listed under the umbrella of “education.”

Otherwise, I agree with the Carpenter/Joffe commentary: Something needs to be done to ensure that a unique identifier is required for disclosure by companies and made available to the public. Without this, these payments may be misattributed, particularly within larger markets, limiting the effectiveness of this law within those communities.

Joseph S. Ross, MD, MHS, is an Assistant Professor in the Section of General Internal Medicine at the Yale University School of Medicine in New Haven, CT. He holds a medical degree from the Albert Einstein College of Medicine, Bronx, NY, and completed his post-graduate training in primary care internal medicine at Montefiore Medical Center in Bronx. As a fellow in the Robert Wood Johnson Clinical Scholars program at Yale University, Dr. Ross earned a Master’s degree in health sciences research. Using health services research methods, Dr. Ross’s research focuses on examining factors which affect the use or delivery of recommended ambulatory care services for older adults and other vulnerable populations, evaluating the impact of state and federal policies on the delivery of appropriate and higher quality care, and issues related to conflicts of interest, medical professionalism, and drug safety.

Interviewed by Kate Petersen, PostScript blogger

This Pharma With a Chance of Meatballs site is making the rounds, and it’s a great illustration of the issues on the Massachusetts gift ban we touched on yesterday.

(The site’s author clearly has a knack for story-booking policy issues. We can’t help wondering what an animated version of academic detailing or the Physician Payments Sunshine Act would look like…)

–Kate Petersen, PostScript blogger

When it comes to pharma meals, MA medical centers have already spoken

In its aggressive push to repeal the state’s gifts and meal ban, the Massachusetts restaurant industry (and pharma, the presumptive cooks in the kitchen behind this lobbying blitz) are hoping legislators will think the issue of doctors and drug companies is still, well, on the table. Since Bay State restaurant numbers don’t seem to have suffered from the law, these groups are betting that lawmakers will be willing to open the old and fundamental question: Should prescribers who are responsible for their patients’ best interests be letting pharma pay their way for meals, liquor and other perks?

But the question’s closed: Academic medical centers in Massachusetts have spoken loudly, and they’ve said that physicians and drug companies should work together at the lab bench, not the dinner table (or the bar). They’ve done this by developing and strengthening policies around industry marketing over the last four years, many of which set the bar nationally for rethinking conflicts of interest in the clinical setting, while protecting innovation.

UMass, Boston Medical Center, Tufts and Harvard Medical School have all demonstrated national leadership and done big work in setting ground rules to keep pharma’s marketing dollars out of doctors’ training, practice, and professional development. The American Medical Student Association scorecard, which evaluated conflict policies at all U.S. medical schools, recognized this leadership with top grades.   Specifically, all of these institutions received perfect “3s” on gifts and meals, meaning that “all gifts and on-site meals funded by industry are prohibited, regardless of nature or value.”

So, if Massachusetts’ flagship medical centers have done this, why all this hubbub over at the State House?

In 2008, lawmakers heard the message from these clinical centers about keeping medicine separate from marketing, and they realized that what’s good for patients and providers at UMass or Harvard is good for patients and providers outside the academic medical centers—on the Cape, or in Waltham, or Deerfield. Tchotchke-free waiting rooms and unbiased clinical care should be the norm everywhere in the state, and that could only be addressed by a state law. And so they passed a law limiting the kinds of gifts and meals drug and device companies could give docs—including the ‘educational’ wine-and-dines at some of the state’s priciest restaurants.

This wasn’t radical: This was the next step on ground cleared by AMCs and the industry itself (whose own code of conduct Massachusetts used as a template for its law).

The drive to preserve this law will be decided in the next few weeks.  The House voted to repeal the gift ban, but the Senate Ways and Means budget, released yesterday, does not include mention of repeal. Senate President Therese Murray championed passage originally as part of the effort to eliminate unnecessary health care spending, including that driven by drug company marketing.  And as for that claim that these meals are necessary educational opportunities for docs: What caliber of education do we really believe happens in the function rooms of Boston’s finest restaurants over a $40 cut of Kobe sirloin and a few bottles of a nice reserve cab?  (Dr. Carlat talks menus here.) Remember, the law doesn’t prevent companies from catering a legitimate program in the hospital, but that wouldn’t include liquor and elaborate meals.

So as the debate heats up again, let’s remember that we’ve already had this one—and physician leaders have said clearly that gifts, food and booze don’t have a place in the medicine being practiced our prestigious academic institutions.  We hope these leaders will take the opportunity to remind the public in the coming weeks why they took a stand for reforming the relationships between the industry and physicians, and why their new institutional policies and the Massachusetts gifts and disclosure law are important to upholding the state’s reputation for clinical excellence and medical education.

–Kate Petersen, PostScript blogger

There’s been much said already about ProPublica’s latest installment of its “Dollars for Doctors” series, which looks at the industry money in medical specialty societies, using the Heart Rhythm Society and its annual meeting earlier this month as a case study.

Here are some good links to refresh:

-CardioBrief
-The Hooked blog
-PharmaExec blog
-Minnesota Post

Some of the punch of the report comes from the sheer volume of outlay: Medtronic spending $1.6 million on promotion at last year’s HRS annual meeting even as it paid out millions more in settlements on anti-kickback allegations, or the fact that two thirds of the society’s directors are also paid speakers or consultants for the leading defibrillator companies in the industry. (See this post for more on the industry’s recent trouble with the law around illegal marketing.)

Some of it comes from the now much-circulated and unfortunate analogy picked by American College of Cardiology’s CEO Jack Lewin, who compared his professions’ immunity to industry marketing to his choice to drink Coca-Cola – a brand not exactly known for its quiet marketing tactics.  In light of the wealth of data on the influence of advertising (it’s an industry for a reason) and small gifts, not to mention the millions of dollars drug and device companies have spent in recent years to settle illegal marketing cases and buy prescriber info to better target sales pitches, Lewin’s was a sort a head-shakingly tone-deaf defense of a question—that drug companies influence physicians—settled long ago.

Otherwise, would a company spend $45-70K (at just one meeting) to get its name on the hotel key of a cardiologist?

As Cardiobrief put it: “Neither Coke nor Medtronic are idiots and they certainly don’t waste their money.”

Dr. Howard Brody over at Hooked blog says to medical professionals: Go take a look at the exhibitor website before you go to the next meeting, and “see how [you yourselves are] being marketed to the drug and device companies as advertising fodder, whose behavior your society more or less promises to deliver over to the industry.”

I want to just underscore a couple of points:

This is not a new problem, or one without proposed solutions. In 2009, nine former leaders of major medical specialty societies got together and established a set of recommendations reduce and eliminate conflicts of interest from medical societies, which “represent expertise and authority to those inside and outside of medicine.”  Published in JAMA, it reads as a compact of sorts–one designed to preserve valuable science-based relationships with industry while protecting clinical care and professional medical conduct from the undue influence of marketing. The leaders address industry involvement in operating costs, treatment guidelines, society leadership, medical education, sponsorship, and meetings.

Here’s some of what they say on meetings:

“To distance Professional Medical Associations (PMAs) from industry marketing activities, and in light of the data on the power of gifts to influence treatment choices, conference meetings should not serve as a setting for industry to distribute branded items to members. No company logos should appear on tote bags, lanyards, pens, notebooks, and publications distributed to members at conferences.”

They point out that PhRMA and AdvaMed put these rules in their voluntary codes but made no mention of enforcement.

The authors also say that PMAs should aim to move toward a zero-dollar reliance on industry for general operating costs. (The HRS gets about 50 percent of its annual income from device companies, according to data on its website).

Additionally, the leaders stressed that presidents, officer and board members should be conflict-free during their term of service (ProPublica found that 12 of the Hearth Rhythm Society’s 18 directors are currently paid by or otherwise financially tied to the top three device companies in the defibrillator industry.)

“To allow commercial funding to dictate a PMA’s activities is, in effect, to put the organization up for sale,” the JAMA authors wrote.

Second, HRS is being held up as an example because it made this payment data available on its website, and it should get credit for this policy. While there’s some debate about whether disclosure deters untoward industry/medicine coziness, the value of knowing the extent of these relationships to patients, payers and the public is unquestionable, and offers a reminder about the importance of the coming Sunshine.

–Kate Petersen, PostScript blogger

Today a coalition of nine major consumer and physician groups representing millions of Americans asked Members of the House of Representatives to get behind a bill that would give the FDA broader powers and better resources to ensure the safety of the imported drug supply.

The Drug Safety Enhancement Act, HR 1483, was introduced by members of the House Energy and Commerce Committee last month and based on a similar draft circulated last year. The drug safety reforms it proposes have won wide consensus across party lines among the public, who have opened their browser windows (or newspapers) lately to near-weekly drug recalls and huge, systemic quality failures that have put the safety of drugs in every medicine cabinet on the line.

The Drug Safety Enhancement Act would give the FDA recall authority to pull drugs it believes to be risky from market, and the power to stop importation of drugs from plants that fail safety inspections or deny access to FDA inspectors. It would also up inspection resources for FDA to better align foreign and domestic oversight, and update the GMP standards industry is required to maintain to sell drugs in the U.S.

In seeking Congressional co-sponsors, Community Catalyst joined AFSCME, the Alliance for Retired Americans, Consumers Union, Families USA, Medicare Rights Center, National Physicians Alliance, Our Bodies, Ourselves, and U.S. PIRG.

The co-signers cite a 2010 poll of 820 likely U.S. voters that shows the public consensus on this issue, and the need to address it now: 81% of Republicans, 87% of Independents, and 97% of Democrats support increased FDA authority to issue recalls, destroy contaminated products upon import, and inspect foreign manufacturing facilities.

“It is essential that we protect families from contaminated and substandard prescription and over-the-counter medications,” the groups write. “We hope Congress will act this year to close the gaps in our current system for regulating the drug supply chain, gaps which make all consumers vulnerable.”

Read more on the bill here, a summary of HR 1483 here (pdf) and the letter here (also pdf).

–Kate Petersen, PostScript blogger

A year into implementation of their new Good Manufacturing Practice (GMP) guidelines, Chinese authorities have begun an investigation into safety problems of “essential medicines” after a test sample of children’s medication contained twice the allowable amount of mercury.

Today there are more than 4,700 drug manufacturers in China. Of these, nearly 3,000 produce “essential medicines” and will be subject to the investigation by the Chinese FDA (SFDA), which will also look at traditional Chinese remedies. Though the probe is targeted at drugs sold in China, it could turn up manufacturing problems for companies that also import medicines to the U.S. and other countries.

“The two-month examination will look closely at how drugs are produced and where their raw materials are sourced,” the China Daily reported. A report on the findings is expected in June.

Safety problems with Chinese-made drugs that have come into the U.S. have been in the headlines ever since contaminated batches of heparin led to illness and the death of more than 100 American patients in 2007-2008. Last month, a warning letter from the FDA called out an API supplier for falsifying inspection documents and destroying records.

But the new investigation suggests that there are huge domestic failures in China’s drug supply, too. According to the Daily, severe adverse event reports to Chinese were up 16 percent in 2010 from the year before. The new GMP quality measures are designed to bring Chinese manufacturers in line with international standards, and include stricter sterilization requirements, risk management procedures, sanctions and required reporting, audits and adverse event reporting, according to a Gold Sheet story.

But Chinese sites have a 5-year grace period to comply with the 2010 GMP updates, and how the SFDA will staff or enforce the tightened rules is unclear. Regulators in China and abroad must be vigilant in ensuring the process stays on track, and that already-established firewalls keep unsafe and substandard medicines out of both the domestic and international supply chain.

For more on imported drug manufacturing safety, follow SafeRxWatch on Twitter or visit the Pew Prescription Project.

–Kate Petersen, PostScript blogger

A new study in JAMA this week shows about 70 percent of newly-marketed drugs in the last decade came to market with comparative effectiveness data – research done against at least one existing similar therapy. (Authors Nikolas Goldberg et al. excluded orphan treatments for which there exist no alternatives.) Depending on whether that number’s good news or bad depends on whom you talk to. FDA Center for Drug Evaluation and Research’s Dr. Robert Temple told Reuters the number was “pretty impressive,” considering FDA doesn’t require head-to-head trials for approval as the European Medicines Agency does. But other physicians warned that having no data against anything but a placebo for a third of all new drugs in the US is not something to write home about.

The bigger question, the authors suggest, should be: Is this data actually being used by prescribers, and if not, how can the system change to make data beyond placebo controls useful in the exam room? Comparing drugs to existing therapies—sometimes called comparative effectiveness research–is an important tool to judge a drug’s safety or efficacy before large, randomized-control trials and longitudinal population studies are complete. “Making the data more accessible to clinicians and payers can help maximize their utility in prescribing and coverage decisions,” they write.

But there is little evidence, they say, that the comparative info included in approval literature up until now is getting factored in when scrips get written. They suggest possible ways to disseminate data, including independent drug info providers like RxFacts.org, and the paper provides good policy food-for-thought as the U.S. develops its own comparative effectiveness system – the Patient-Centered Outcomes Research Institute (PCORI).

For such a system to work right, determining where the rubber meets the road – i.e. what it’s going to take, statistically and pragmatically for CER data to be applied in a clinical setting – should be at the center of CER planning and design, says Leonard Zwelling in a recent piece on the Health Affairs blog. Research that has no chance of changing clinical practice for the better ought not to be done. Using certain methods associated with RCTs, Zwelling writes, could make CER – well – more effective, and therefore worth our time and money. He looks at the 2009 U.S. Preventive Service Task Force recommendations on mammograms as a case study in ineffective CER. Because the study didn’t determine at the outset what level of statistical significance would be needed to change practices, the medical community and public didn’t know how to weigh the data and balked. (It’s more complicated, of course: how risk gets communicated plays a big role, as does the classic conflict of weighing the aggregate against anecdote.)

As PCORI gears up, Zwelling comes to a similar place as the JAMA authors: figure out how to get comparative efficacy findings into the clinical setting in a way that makes for better medicine. Zwelling says PCORI would have a better chance of doing CER right by infusing a little RCT thinking: “establishing parameters that measure significant improvements in outcomes, reductions in costs, or increases in value, and the degree to which a study must show this benefit to be considered positive and thus alter current behavior by caregivers, patients and payers.” Otherwise, he asks, “why spend the money to even start the research?”

–Kate Petersen, PostScript blogger

As you may have read by now, the Massachusetts House has voted to repeal a chunk of its first-in-nation gift and meal ban, spurred on by cries from the state restaurant lobby. The law, which bans drug companies from treating Bay State physicians to some gifts and restaurant meals, aims to check the potential for conflict of interest inherent whenever pharma picks up the tab.

No matter that state numbers show restaurant revenues are up nearly 10 percent over last year (see here), or that drug companies are moving their operations into town (see here and here and here). Or that despite the ban, new state payment data suggests drug companies didn’t seem to lose face time with Massachusetts docs – companies paid individual docs $16.4 million in the last half of 2009 alone.

“The only thing that’s being hurt is the ability of the drug industry to market their high-priced drugs by wining and dining doctors at our expense,’’ Health Care for All’s Brian Rosman told the Boston Globe.

But a concerted push by the Massachusetts restaurant industry seems to have swayed House lawmakers, who, by a wide margin, voted last week to repeal the part of the law that prevents drug, device and biotech companies from footing physicians’ bill at restaurants. (Companies are still permitted to bring docs lunch in their offices for “educational” presentations.)

An editorial in the Globe yesterday says the legislature shouldn’t chip away at the law. It’s not just that such meals are medically unnecessary. “But there’s also an unsavory conflict of interest in doctors being feted by drug companies and then turning around and prescribing the companies’ drugs to their patients. Are the prescriptions really necessary? Are the drugs really the most effective treatment?”

Many doctors insist their professional judgment cannot be bought with fancy meals. But if wining and dining didn’t work, the drug industry wouldn’t spend $6 billion a year on direct marketing to physicians. The Legislature should send the repeal amendment and similar attempts to weaken the gift ban back to the kitchen.

In characteristic color, Newburyport psychiatrist and blogger Daniel Carlat agrees.

Yes, commoners escape workplace demands by going home at 5 or by taking a stroll through a park during lunch. But doctors need raw oysters and wine after a hard day of work—plenty of it, free, and with fawning pharmaceutical reps complimenting them on their knowledge of vintages.

Hopefully the State Senate will realize that Massachusetts doctors have stronger ethical compasses than Massachusetts politicians, who since 2009 have been barred from receiving anything of value from lobbyists. Lawmakers are, indeed, vulnerable to inappropriate influence from meals and other gifts. But physicians would never prescribe more Abilify after enjoying a steak dinner funded by Bristol-Myers Squibb. After all, they’re doctors!

The Massachusetts Senate is due to vote on its budget later this month. For more on industry-physician interactions visit Community Catalyst’s resource page and the Physician Payments Sunshine guide.

–Kate Petersen, PostScript blogger