HHS OIG Notifies Drug Manufacturers of New Enforcement Initiative for Price Reporting Requirements

On September 28, the Office of the Inspector General (”OIG”) released a Special Advisory Bulletin regarding a new enforcement initiative regarding the timely submission of certain pharmaceutical data.  Manufacturers will face civil money penalties (CMP) for failing to comply with reporting requirements.

The Center for Medicare & Medicaid Services (”CMS”) relies on the timely reporting of average manufacturer prices (”AMPs”) and average sales prices (”ASPs”) for the implementation of four different programs: the Medicaid Drug Rebate Program, the 340B Drug Pricing Program (340B Program), the Federal Upper Limit (FUL) Program, and the Medicare Part B outpatient prescription drug benefit.

Under the Medicaid Drug Rebate Program, CMS uses AMPs to calculate the rebates owed to state Medicaid programs.  The 340B Program, which requires manufacturers to sell their prescription drugs to certain safety net health care providers at or below specified prices, also uses AMPs to establish price ceilings.  Medicaid’s FUL Program uses AMPs to act as a prudent buyer of multiple-source drugs.  Finally, the Medicare Part B outpatient drug benefit relies on ASPs to establish Part-B covered drug and biologic payment amounts.

Timely and accurate price reporting is important to the effective and efficient administration of the Medicaid Drug Rebate Program, the 340B Program, the FUL Program, and the Medicare Part B drug benefit.   Manufactures are required to report and certify timely and accurate drug pricing information, including AMPs on a monthly and quarterly basis and ASPs on a quarterly basis.

However, multiple reviews of historical reporting by OIG have demonstrated that voluntary compliance has not been fully effective.  For instance:

• The February 2008 report, “Average Sales Prices: Manufacturer Reporting and CMS Oversight,” found that, “between 41 and 52 percent of manufacturers provided ASPs after the statutorily defined due date.”
• The OIG report, “Drug Manufacturers’ Noncompliance With Average Manufacturer Price Reporting Requirements,” released the same day as the Special Advisory Bulletin, determined that during 2008:
  • 53 percent of the 592 manufacturers that were required to submit quarterly AMP reports failed to provide pricing data by the statutorily defined due date.
  • 78 percent of the 579 manufacturers that were required to submit monthly AMP reports failed to provide pricing data by the statutorily defined due date.

Moving forward, OIG will work with CMS to “identify and penalize noncompliant manufacturers through the CMP process.”  Upon a report from CMS that a manufacturer has not submitted a timely report of product pricing information, OIG will exert its authority to impose CMPs of $10,000 per day upon the manufacturer in an effort to improve compliance.

A Well Placed Question by Professor Mirkay: “Should Medical-Related Charities Increase Disclosure of Their Donors?”

We’ve written a great deal here at HRW about the need for transparency in industry/profession interactions and the elimination of conflicts of interest–the Center for Health & Pharmaceutical Law & Policy here at Seton Hall Law has, in fact, over the course of the last two years, issued two White Papers on the subject–with another on the way. In the last, “Conflicts of Interest in Clinical Trial Recruitment & Enrollment: A Call for Increased Oversight,” the Center proposed legal and policy changes to address conflicts of interest in the relationships between industry and doctors that can create unwarranted risks to trial participants and to the scientific integrity of research. In the Paper prior,  ”Drug and Device Promotion: Charting a Course for Policy Reform,” The Center recommends: (1) making payments by drug and device companies to doctors transparent, with public disclosure by industry and physicians of their financial relationships; (2) adopting federal legislation to ban gifts, meals and other benefits provided to doctors as part of the current marketing model; (3) setting new policies to give FDA the authority to require studies of safety and efficacy of drugs and devices used off-label; and (4) undertaking a fundamental change in funding for continuing medical education to end industry support.

But over at Nonprofit Law Prof Blog, Professor Nicholas A. Mirkay of Widener University School of Law, has a post–and an additional question–well worth considering:

“Should Medical-Related Charities Increase Disclosure of Their Donors?”

Professor Mirkay points to a recent Chronicle of Philanthropy article which raises the issue as the National Alliance of Mental Illness (NAMI) has begun disclosing the names of corps and foundations who (does Citizens United make that “who” correct? Never mind appropriate.) donate more than $5,000. NAMI is said to have done so on the heels of an investigation by Senator Chuck Grassley into their financial relationship with the pharmaceutical industry. Mirkay writes:

NAMI’s actions have given Grassley further impetus to force 33 other nonprofit medical associations to follow NAMI’s lead.  In a related article, the Chronicle reports that Grassley’s inquiry into these other groups represents a “broader effort by the senator and others to expose and curtail corporate influence on the medical field.”  Grassley commented that “[t]hese organizations have a lot of influence over public policy, and people rely on their leadership.  There’s a strong case for disclosure and the accountability that results.”

Professor Mirkay also writes

In December 2009, Grassley sent a letter to 33 such nonprofit associations requesting information on the amount of funds received from pharmaceutical, medical-device and insurance companies from 2006 to 2009, the identity of the donors and how their money was spent by the medical group, and additional information on the outside income earned by the groups’ top executives and board members.

The (partial) results of those queries are not particularly heartening, but are certainly worth considering. Mirkay writes:

The Chronicle acquired more than half of the solicited groups’ responses to Grassley’s letter, finding that such groups receive aggregately more than $100 million annually from medical-related companies via “donations, advertising revenues, exhibit fees, corporate memberships, and support for continuing medical education.”  For some groups, this can represent as much as 78% of their revenue, while for others it only represents a small percentage of their total receipts.

Despite the longings of Elvis Costello, it’s hard to bite the hand that feeds you–and 78% of revenue pretty much constitutes (in)visible means of support. In pushing further with our (or more accurately, the Supreme Court’s) Citizens United “who” conceit, one might think 78% sufficient in some sense to constitute dependent status under the tax code–at least for purposes of context. Having said that, in addition to not biting, it’s not hard to imagine the dependent regularly fed doing that which it may to help assure the continued regularity of that feeding. Especially if the feedings are invisible.

It should also be noted that Mirkay rightly points out that “This effort is further evidence of Grassley’s commitment to increased transparency of tax-exempt nonprofits.” He’s right. And being that Senator Grassley follows HRW on Twitter, and as I have at times been critical of some of his positions in the past regarding other issues, it’s worth noting that the Senator should be roundly applauded for his efforts.

[And if you haven't been over to the Nonprofit Law Prof Blog, you should. It's in our blog roll for good reason-- their work is informative, brief and well written.]

We May Need More Than A Spoonful Of Sugar To Help Our Medicine Go Down

Today CNNMoney reports that drug recalls quadrupled from 426 in 2008 to a record 1,742 in 2009.  The recalls have been attributed to “manufacturing lapses” in raw material quality, labeling and packaging, and contamination.  Generic and over-the-counter drugs have been affected the most.  CNNMoney notes that the race to put generic products on the market and the pressure to cut costs have caused drug companies to

sometimes fail to spend enough time learning how best to make the drug….  And since generic and over the counter drugs aren’t as lucrative for drugmakers as prescription drugs, companies may not be investing enough resources to make high-quality, safe products.

One such cost-cutting measure involves outsourcing production to foreign manufacturing sites and this measure seems to have received the most attention.  (Check out fellow blogger Jae W. Joo’s post on outsourcing.)

Earlier this month, Senator Michael Bennet (D-Colorado) introduced the Drug and Safety Accountability Act of 2010 which seeks to ensure the safety and efficacy of drugs sold in America, regardless of their manufacturing location.  The bill would require, among other things, that:

• manufacturers have quality management plans which the FDA can inspect;
• manufacturers maintain supply chain documentation;
• the Secretary of Health and Human Services track facilities manufacturing drugs or active ingredients for the American market; and
• the FDA be given more power to ensure drug safety, including the authority to enact mandatory recalls for batches of drugs that pose risks and to assess civil penalties for violations of the Federal Food, Drug, and Cosmetic Act.

Click here for more details about the bill and here for Sen. Bennet’s own promotion of it.  Sen. Bennet has lamented how:

[f]or too long, the FDA has lacked the proper authority to adequately safeguard our drug supply.  Americans need to be able to trust that the drugs in their medicine cabinets are safe, no matter where they’re made.

A father of three, Sen. Bennet has said that the recent McNeil recall of over-the-counter children’s medicine spurred him into action.

Pharmaceutical Research and Manufacturers of America (PhRMA) Senior Vice President Ken Johnson has issued a statement in response to the bill, saying that:

[t]he lifeline of America’s biopharmaceutical research companies is the safety and integrity of the products they develop.  Brand-name pharmaceutical companies make tremendous investments in quality control systems and take extensive measures to help protect patient safety and to help prevent adulterated ingredients from entering into America’s prescription drug supply.

In addition, drug manufacturing for the U.S. market — regardless of where it occurs — is regulated under Good Manufacturing Practices (GMP) by the Food and Drug Administration (FDA).  These GMP requirements help to assure the safety, quality and purity of drug ingredients that are used in the U.S. prescription drug supply.

The U.S. regulatory system for prescription drugs is the toughest and safest in the world….

Okay.  But other people here don’t think so.  (Click here to read a good opinion by Dr. Lynn Parry, Chair of the Colorado Prescription Project, on why this bill should pass.)

According to a recent Pew Prescription Project poll, less than 10% of Americans feel confident about medications manufactured in India and China.  89% of Americans support Congressional action to introduce new drug safety measures.  How many of those people realize that approximately 80% of the materials used to make or package drugs sold in America comes from foreign sources?  I didn’t, but then, is such high a percentage really that surprising?

Reading through the CNNMoney report, I was reminded a little of a scene from a seventh season episode of Friends:

Phoebe: It’s amazing! My headache is completely gone! What are those pills called?
Monica: Hexadrin.
Phoebe: Oh, I love you, Hexadrin!  Oh look!  It comes with a story!
Monica: No, Phoebe, those are, like, the side effects and stuff.
Phoebe: Say what?
Monica: You know, the possible side effects.
Phoebe: Oh my God!  Dizziness, nervousness, drowsiness, facial swelling, nausea, headache…  Headache! Vomiting, stomach bleeding, liver damage!  Now, okay, I don’t recall any of this coming up when you gave me these little death capsules! Oh, I’m sorry, extra-strength death capsules!

Admittedly, the scene concerns how potential side effects can be worse than the problem being treated (and that’s a whole other blog post).  Yet it’s also a reminder of how we can forget about the other potential hazards of these potent drugs, delivered in easy-to-swallow capsules/tablets/liquids, if there are quality control or other manufacturing issues.  It’s as easy to forget as it is to pop them, well, like candy.

Limit Physicians’ Off Label Prescribing Practices?

Off label prescribing has become fairly common practice for many medical professionals.  Once a drug has been approved by the Food and Drug Administration (FDA) for a specific purpose, physicians are given the freedom to prescribe the approved drug “off label” for other beneficial uses of the drug.  There is a great interest for physicians to retain this autonomy of  prescribing drugs off label as the practice expands treatment options.  Both the American Medical Association and the FDA have recognized that physicians are in the best position to determine the method of treatment for their patients.

However, the practice of off label prescribing has not been without controversy.  Many politicians and regulators view off label prescribing as a way to avoid clinical testing and FDA approval process.  In addition, studies have shown that many physicians prescribe off label with little or no scientific rationale.  According to the Daily News Central, an example can be found in a particular study: “in all, the study estimated that 1 in 7 prescriptions were written [by doctors] without good medical evidence that they would work.”

A LA Times article has recently highlighted the problems of off label prescriptions.  In the article, it has come to light that the off label use of statins, one of the world’s most prescribed medication, may not have the efficacy that many doctors had previously thought.  The LA Times reports,

Statins were initially approved by the Food and Drug Administration for the prevention of repeat heart attacks and strokes in patients with high cholesterol who had already had a heart attack. And used for that purpose — called “secondary prevention” — the drugs are powerful and effective medications, driving down patients’ risk of another heart attack or stroke by lowering their levels of LDL (or “bad”) cholesterol.

Then physicians came to believe statins could also reduce the risk of a first heart attack in people who have high LDL cholesterol but are nonetheless healthy. This use of statins — called “primary prevention” — has driven the growth in the market for statins over the last decade.

Statins certainly decrease rates of heart attack in people who have clear signs of cardiovascular disease but it’s not so clear they work that way in people who are healthy. In spite of that uncertainty, statins’ use for primary prevention has sky rocketed.

One wonders how so many physicians came to believe that statins could also reduce the risk first time heart attacks.  Dr. John Abramson, from Harvard Medical School, attributes statins’ off label growth to a “conspiracy of false hope.”  He states, “[t]he public wants an easy way to prevent heart disease, doctors want to reduce their patients’ risk of heart disease and drug companies want to maximize the number of people taking their pills to boost their sales and profits.”

So, with all these interests pushing for statins’ off label use, it should not be a great surprise that extensive research has not been performed regarding statins’ primary preventive effects– and conflicting results have emerged.  The LA Times reports,

In the first of three studies published in the Archives last month, medical researchers found that, contrary to widely held belief, statins do not drive down death rates among those who take them to prevent a first heart attack. A second article cast significant doubt on the influential findings of a 2006 study, called JUPITER, that has driven the expansion of statins’ use by healthy people with elevated blood levels of C-reactive protein, a measure of inflammation. A third article suggested potential ethical, clinical and financial conflicts of interest at work in the execution of the JUPITER study and concluded the widely hailed trial was “flawed” and raises “troubling questions concerning the role of commercial sponsors.”

Potentially, new findings regarding the efficacy (or lack thereof) of statins can have seismic effects.  If it is found that statins’ primary preventative effects are overstated or  nonexistent, this would amount to what has been a tremendous amount of healthcare waste (time, money, and effort) due to the popularity of the drug.  According to IMS Health, U.S. patients filled 201.4 million prescriptions for statins last year alone.

While there is a strong interest for physicians to retain their autonomy when assessing the best treatment for the patient, due to the potential of healthcare waste, there may be an equal or if not stronger interest for some regulation regarding the practice of prescribing off label drugs. As to industry funding of research, there seems little incentive for a pharmaceutical company with a blockbuster off label hit to do anything which would upset the apple cart– or should I say money cart?

Recommended Reading: Recent Legal Scholarship on Issues in Global Public Health

Redressing the Unconscionable Health Gap: A Global Plan for Justice (published in the Harvard Law & Policy Review). In this article Lawrence Gostin brings a big picture issue — the vast global health gap between rich and poor — into perfect focus. Professor Gostin reminds us of an “uncomfortable truth” — “that closing the health gap is well within the means of the international community” — and he proposes a simple (in concept if not execution) plan to do just that.  No international treaty would be required; Professor Gostin’s Global Plan for Justice would take the form of a World Health Assembly resolution.  No new organization or governance structure would be required either; rather, the World Health Organization would “assume its place as the global health leader.”  States would be asked to contribute a small percentage — Professor Gostin suggests 0.25% — of their Gross National Income each year to a Global Health Fund.  The WHO would then allocate the Fund’s resources based on “the health needs of developing countries measured by poverty, morbidity, and premature mortality.”  Professor Gostin suggests that the mission of the Fund be threefold: “(1) ensure the fair allocation of essential vaccines and medicines, with particular attention to low- and middle-income countries in a public health emergency; (2) meet basic survival needs [e.g. food, water, sanitation, and vector controls] and create the conditions in which people can be healthy; and (3) help countries that will suffer most to adapt to the health impacts of climate change.”  Existing efforts, such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, demonstrate the power of voluntary collective action; unlike the proposed Global Health Fund, however, they are too narrowly-targeted and inconsistent to close the global health gap.  Professor Gostin’s article is short (it’s based on the text of a speech), straightforward, and provocative in the best sense of the word.  I highly recommend it.

I also highly recommend Kevin Outterson’s The Legal Ecology of Resistance: The Role of Antibiotic Resistance in Pharmaceutical Innovation (published in the Cardozo Law Review) in which he uses proprietary sales and volume data for the important hospital antibiotic vancomycin to test a number of widely-propounded theories about the interplay between antibiotic resistance and intellectual property law.  The vancomycin case study fails to support the hypothesis that a patent holder is likely to zealously market an antibiotic with an eye to the drug’s dwindling patent term, without regard for the risk that increased uptake could accelerate the evolution of antibiotic-resistant bacteria.  It also fails to support the hypothesis that if patent terms for antibiotics were extended, patent holders would better manage the sales and use of their drugs to forestall the development of resistance.  By contrast, the story of vancomycin is consistent with the hypothesis that antibiotic resistance stimulates innovation — as bacteria evolve that are resistant to an existing antibiotic a market for a new antibiotic arises.  All of this suggests that “tinker[ing] with the patent system” is unnecessary and could even backfire.  Professor Outterson concludes that a more direct and potentially more effective approach to preserving the antibacterial effectiveness of our antibiotics would be to fix our broken health care reimbursement system, under which infection control is an unreimbursed cost and “hospitals and doctors have generally gained revenues from additional infections[.]“

Pharmaceutical Outsourcing: Trading Quality for Lower Costs?

With the waning economy, outsourcing has never been a more popular route for businesses to take.  Why pay more when you can get a similar product or service for less overseas?  Traditionally, outsourcing has been limited to low-end, back-office type of work. However, in the recent years, more companies have been outsourcing complex services such as medical diagnostics.

So it should be no surprise that India, a country with an abundance of cost effective labor, has emerged as a hot spot for pharmaceutical companies to outsource their drug manufacturing.  The NY Times reports,

India’s drug industry — on track to grow about 13 percent this year, to just over $24 billion — was once notorious for making cheap knockoffs of Western medicines and selling them in developing countries. But India, seasoned in the basics of medicine making, is now starting to take on a more mainstream role in the global drug industry, as a result of recent strengthening of patent law here and cost pressures on name-brand drug makers in the West.

Not limited to just manufacturing, India is projected to further expand into more sophisticated aspects of drug making such as pharmaceutical research and development. Due to its cheap labor, Indian drug companies are able to “discover new drugs at a tenth of the cost” incurred in the United States, according to Ajay G. Piramal, the chairman of Piramal Healthcare.

This pharmaceutical boom in India has been relatively recent.  Initially, pharmaceutical companies were hesitant to outsource their internal operations.  Sujay Shetty, an associate director with PricewaterhouseCooper in Mumbai, described pharma as  “an incredibly arrogant industry” and predicted that “everything in the value chain will move to different parts of the world that are cheaper.”

But, what risks are these pharmaceuticals companies taking?  Outsourcing, in general, can be riddled with quality problems and pharmaceutical outsourcing to India has been no exception.  According to the NY Times,

Recent growth, though, has been shadowed by quality problems. The F.D.A. cited Ranbaxy [India's largest pharmaceutical manufacturer] for manufacturing violations several times in recent years, and in February ordered a review of the company’s global manufacturing operations.

In May, Sanofi-Aventis recalled vaccines made by Shantha Biotechnics that were distributed to the World Health Organization after users complained about white sediment in the vials. In June, after floating matter was found in some plastic IV bags, Pfizer recalled injectible drugs made by Claris Lifesciences and sold in the United States.

Maybe pharmaceutical companies were justified in being cautious, even to the point of arrogance, in deciding whether to outsource in the past.  Drug manufacturing is a complex process that needs proper review practices to prevent errors.

Fortunately, the Food and Drug Administration (FDA) has taken note of India’s growing influence in the drug industry and has been cracking down to prevent substandard and contaminated drugs from entering the United States.  In the past two years, the FDA has opened two new offices in India, one in Delhi and the other in Mumbai.  And just last month, as reported by The Wall Street Journal, the FDA stated that “it will propose stronger regulation for pharmaceutical companies that outsource manufacturing, putting more responsibility on the companies to ensure the purity and safety of the products…”

Whether or not the FDA’s crackdown improves the quality of the outsourced drugs remains to be seen.  But, with lower costs and regulation avoidance said to be the primary motivation behind pharmaceutical outsourcing, it’s uncertain whether the quality problems mentioned by the NY Times will be the last.

Nurses, Prescriptions and Pharma Influence– Under the Radar?

Very interesting point made over at Gary Schwitzer’s Health News Review Blog regarding Industry funding of Continuing Medical Education (CME) for Nurse Practitioners (if you’ve never visited Mr. Schwitzer’s blog you should, he is informative, well written and generally brief).

Seton Hall Law’s Center for Health & Pharmaceutical Law & Policy issued a White Paper last year, “Drug and Device Promotion: Charting a Course for Policy Reform,” which called for a cessation of industry funding of CME. The Center noted:

Reforming Funding for Continuing Medical Education (CME). Most states require physicians to undertake continuing medical education to maintain their medical license. The drug and device industry currently funds over half of the accredited CME courses available to physicians. The Center recommends that industry funding for continuing medical education should be phased out, and replaced by an educational process driven by physicians.

And that

• Ninety-four percent of physicians have some kind of financial relationship with industry, as reported in a major recent national study.

• Commercial support for accredited CME, nearly all of it from drug and device manufacturers, grew from $302 million in 1998 to $1.2 billion in 2006.

But what about nurse practitioners? Schwitzer, who attended the recent Georgetown Conference, “Prescription for Conflict: Should Industry Fund Continuing Medical Education?” noted that:

There are more nurse practitioners (147,000) than there are family physicians (100,000) in the US.

These advance practice nurse professionals can write prescriptions, and it’s estimated that the average nurse practitioner writes more than 6,000 a year.

And about 70-80% of those nurses who regularly attended lunch or dinner “continuing education” events sponsored by drug companies said they were more likely to prescribe the drugs that were highlighted in the lunch.

The presenter was nurse-researcher Elissa Ladd, PhD, RN, Asst. Clinical Professor, Massachusetts General Hospital Institute of Health Professions, who says the possible pharma influence on nurse-prescribers has largely flown “under the radar.”

A little quick and basic math will give us some inkling of just how much flies under that radar. We’ll use the minimum figure in all estimates. So…

147,000 Nurse Practioners each writing 6,000 prescriptions per year = 882,000,000 prescriptions. Yes, that’s 882 million prescriptions per year– conservatively estimated.

“More likely to prescribe the drugs that were highlighted in the lunch” we can estimate at 51%. We wind up with a potentially influenced 449,820,000 prescriptions. Again, conservatively estimated.

So now the only question is just what percentage or how many Nurse Practitioners “regularly attended lunch or dinner ‘continuing education’ events sponsored by drug companies?”

With a total pool of over 882 million prescriptions per year available– at least 450 million of them potentially swayed over lunch–my guess is that Pharma’s answer would be “As many as possible.”

Caring for Dogland

I always applaud health scholarship that incisively examines inequalities of access in the United States. However, sometimes it’s important to contextualize that work by emphasizing the degree of global inequality that makes even the poor in the US relatively well off by world standards. The following passage from Korzeniewicz & Moran’s 2009 book, Unveiling Inequality gives some sense of the divergence:

The magnitude of global disparities can be illustrated by considering the life of dogs in the United States. According to a recent estimate . . . in 2007-2008 the average yearly expenses associated with owning a dog were $1425 . . . For sake of argument, let us pretend that these dogs in the US constitute their own nation, Dogland, with their average maintenance costs representing the average income of this nation of dogs.

By such a standard, their income would place Dogland squarely as a middle-income nation, above countries such as Paraguay and Egypt. In fact, the income of Dogland would place its canine inhabitants above more than 40 percent of the world population. . . . And if we were to focus exclusively on health care expenditures, the gap becomes monumental: the average yearly expenditures in Dogland would be higher than health care expenditures in countries that account for over 80% of the world population. (xv)

Certainly public policy should take into account the problem of relative deprivation, which can lead to a much worse subjective experience for those at the “bottom” of the SES distribution in a rich country than those in the middle in a poorer country. Nevertheless, the statistics above help us understand why drug companies, already frustrated by low ROI in R&D, might shift from researching cures for tropical diseases to focusing on pet anxiety medications.

A Hat Tip to Pharmalittle

Health Reform Watch wishes to congratulate the folks over at Pharmalittle for being named one of the Top 100 Pharma Blogs. They deserve it–and if you’ve never checked out their site– I highly encourage you to do so. Upon the dissolution of Ed Silverman’s Pharmalot, which was hosted here in Newark by the Star Ledger, a group of contributors and commenters banded together to pick up the mantle. For those of you who have a keen interest in Pharma (and who doesn’t?), you’ll find truly insightful and often witty commentary over at Pharmalittle. As an example, this post of theirs announcing their Top 100 status is classic:

HAT TIP TO OURSELVES….

Pharmalittle to be Honored at White House

OK, so we lied. It’s all part of the same strategy. As the impressive badge on the left (suitable for framing) shows, this blog has been named one of the top 100 pharma blogs. Did anyone know there were that many pharma blogs?

Anyway, a lot of people out there will wonder how we accomplished this. It’s simple. We followed basic marketing principles:

1. We promoted the blog for off-label uses. For example, it makes a great eye chart and may help slow the growth of cataracts.

2. We gave kickbacks to everyone on the internet. Really.

3. We buried studies 34, 57, and 105.

4. We changed the endpoints in study 35 and left out the last six months of data.

5. We delayed the appearance of generic Pharmalittle (liloxazorx) through a bunch of nuisance suits.

6. We intimidated people who read other blogs.

7. We hired Key Opinion Leaders like Anonymous to talk us up.

8. We funded studies showing all the dangers of other pharma blogs.

9. We convinced people that failure to read Pharmalittle will result in the end of innovation in the industry and the complete dissolution of life-saving medications.

10. We avoided being bought by Pfizer.

11. There is no evidence reading Pharmalittle leads to weight gain, morbid obesity, and diabetes. And anyone who thinks differently will never find Study 57 anyway.

12. We don’t believe in morbid obesity. If you’re going to be obese, at least be up-beat about it.

And stuff like that.

Read more from Pharmalittle here.

Unpublished 1997 Study Linked Drug to Weight Gain and Diabetes, Now Thousands Sue Claiming They Were Not Warned of Side Effects

The Washington Post reported today on the “silenced drug study” of AstraZeneca’s antipsychotic drug, Seroquel.   The study, known as Study 15, was conducted in 1997 and showed an increase in weight gain and diabetes among Seroquel users.  The results were never published and the information was not released to the public or physicians.  The study was, however, provided to the FDA but they did not have the authority to publish the results.  Seroquel was approved by the FDA in 1997 after they received the study’s findings.

AstraZeneca contends that they did disclose the drug’s health risks on the label, as required by the FDA.  Spokesperson Tony Jewell wrote in an email to The Washington Post that the results of Study 15 “did not identify any safety concerns.”  Study 15 compared Seroquel to another similar drug, Haldol.  Jewell also wrote that “A large proportion of patients dropped out in both groups, which the company felt made the results difficult to interpret.”

Over 9,000 lawsuits have been filed against the drug by patients who experienced weight gain, hyperglycemia and diabetes.  It is through these lawsuits that internal documents and details regarding the buried study have emerged.  Internal documents show that AstraZeneca was well aware of the results indicating significant weight gain and worked to spin the results favorably.  The company presented information that Seroquel caused patients to lose weight at two meetings in 1999. This data was based on a much smaller company-sponsored study even though AstraZeneca had concerns with the study and the doctor who conducted it.

The Washington Post says:

The saga of Study 15 has become a case study in how drug companies can control the publicly available research about their products, along with other practices that recently have prompted hand-wringing at universities and scientific journals, remonstrations by medical groups about conflicts of interest, and threats of exposure by trial lawyers and congressional watchdogs.

An obvious concern with unpublished or silenced studies is that they may lead physicians to make medical decisions without all the information that should be available to them.  As the Center for Health and Pharmaceutical Law & Policy recommends in its recently-released whitepaper:

All those engaged in medical research and publication, including medical professionals and institutions, medical journals, and industry, should undertake reforms to ensure the integrity of the medical literature.  Transparency in the relationship of industry and physicians would be critical tool in this effort.

The Life Cycle of Objectionable Drug Marketing Practices

[This is a guest post by Nathan Cortez, assistant professor of law at the Dedman School of Law at Southern Methodist University. Cortez has published in the peer-reviewed Food and Drug Law Journal and teaches international health, pharmaceutical and administrative law. I've learned a lot from his work, and I'm happy he's agreed to let me post this here.]

By Nathan Cortez

The pharmaceutical industry spends some serious coin on sales and marketing-anywhere between $30 billion and $57 billion per year. And this money funds much more than the ubiquitous ad campaigns to which we’ve grown accustomed (sing along if you know the “Viva Viagra” jingle). Over the years, sales and marketing departments have conjured up increasingly creative marketing practices of questionable legality. For example, drug companies have funded “research” and “educational” grants of questionable validity, sponsored continuing medical education (CME), paid ghost writers to generate favorable journal articles, provided free gifts, meals, and entertainment to prescribers, paid prescribers as speakers, consultants, or preceptors, and even hired former college cheerleaders to gain access to prescribers. Most of these practices have been condemned, and many have been prosecuted, resulting in billions in settlements for federal and state governments. The pharmaceutical industry can’t even give away free drugs without being punished.

Last Monday, the New York Times highlighted yet another objectionable drug marketing practice: targeting medical schools. As the article explains, drug companies have long had ties to medical schools and their students by funding endowed chairs, faculty prizes, research grants, capital improvements, and even volunteering employees to teach classes. Students get showered with enough free pizza and trinkets to think that they might already have prescribing privileges. More recently, the Times reports that the faculty at Harvard Medical School has come under fire for its ties to drug companies that hire faculty as speakers, consultants, or even board members. More than 200 Harvard Med students have objected, leading the school to convene a 19-member panel to reevaluate the school’s conflict-of-interest policies (meanwhile, the University of Minnesota Medical School is loosening them).

In the “Life Cycle of Objectionable Drug Marketing Practices,” we’re currently at the “media coverage and public outrage” phase. Gradually, most of the practices listed in the initial paragraph have either disappeared or have lost their allure. Media coverage and public outrage is quickly followed by government outrage (possibly even Congressional hearings) and promises of self-regulation by the drug companies to preempt more stringent regulation. Self-regulatory efforts like the PhRMA Code and the AMA Ethical Guidelines provide some bright-line standards for complying with ridiculously broad laws like the federal anti-kickback statute and its complicated safe harbors. If companies still don’t get the hint, the government simply tells drug companies what not to do.

And if none of these events ends the Life Cycle of the Objectionable Drug Marketing Practice, litigation usually does. Pretty much every major pharmaceutical company has settled a Corporate Integrity Agreement with the government for violating federal drug marketing laws-the latest being a staggering $1.4 billion settlement paid by Eli Lilly to settle claims that it illegally marketed its anti-psychotic drug Zyprexa. By settling, companies thus avoid the “death penalty”–being excluded from Medicare and Medicaid.

Although the drug companies never die, the practices usually do, precipitated by an avalanche of government investigations, whistleblower suits, shareholder suits, and even marginally-related product liability suits. Federal and state lawmakers also pile on. In the last few years, nine states have enacted (and dozens have considered) pharmaceutical marketing laws, requiring disclosures of marketing payments made by drug companies to potential prescribers, in addition to caps on payments, disclosure of sales representative activities, and other prohibitions. Indeed, the Senate Finance Committee is currently considering a federal bill that would explicity preempt state laws.

Thus, the Objectionable Drug Marketing Practice dies a violent death. It can rest in peace, but the sales and marketing departments can’t. Because they have to find new ways to drive market share.

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