Online Health Law Graduate Certificate Programs

Center for Health & Pharmaceutical Law & Policy Introduces First Edition of Pharmaceutical and Medical Device Compliance Manual

The Seton Hall Law Center for Health & Pharmaceutical Law & Policy, American Health Lawyers Association (AHLA) and the Food and Drug Law Institute (FDLI) have released the first edition of the Pharmaceutical and Medical Device Compliance Manual. The Manual is a guide to deciphering the intricate web of federal and state laws and the practices of regulatory and enforcement authorities within the healthcare and life sciences arena, while also providing the practical skills needed to implement an effective compliance program.

Designed to aid health law attorneys, compliance professionals and others in the pharmaceutical and medical device field, the Manual explains the law in layman’s terms in addition to providing advice and guidelines on creating, managing, monitoring and auditing an effective compliance program, in essence, marrying legal expectations with the operational demands of business units.

The book was co-edited by Seton Hall Law Associate Dean Kathleen M. Boozang, J.D., LL.M., who founded the school’s Health Law program in 1990, ranked among the top 10 by U.S. News & World Report for the past 16 years; and by Simone Handler-Hutchinson, J.D. ’93, Executive Director of the Center for Health & Pharmaceutical Law & Policy.

Dean Boozang notes: “Over the last two decades the trend in government oversight has resulted in a regulatory environment of increased accountability among organizations across a number of sectors, with the health and life sciences industries being the subject of particular attention – a trend that shows no sign of waning. We produced this manual for compliance officers, health and life sciences lawyers and their clients to enable them to build a framework for creating and sustaining an effective compliance function.”

As co-editor, Ms. Handler-Hutchinson said, “Each chapter was written by a leading regulatory official, practicing attorney, or healthcare consultant who has either shaped the policies as an official and/or counsel in the nation’s regulatory agencies, served as counsel to or built compliance functions within life science corporations. They offer first hand, in-depth compliance insight and actionable advice.”

The Pharmaceutical and Medical Device Compliance Manual is available as a softbound book and a variety of eBook formats; it may be ordered by visiting http://law.shu.edu/compliancemanual.

The Seton Hall Law Center for Health & Pharmaceutical Law & Policy advances scholarship and recommendations for policy on the varied and complex issues that emerge within pharmaceutical and health law. Additionally, the Center is a leader in providing compliance training on the wide-ranging state, national and international mandates that apply to the safety, promotion and sale of drugs and devices. Seton Hall University School of Law, New Jersey’s only private law school and a leading law school in the New York metropolitan area, is dedicated to preparing students for the practice of law through excellence in scholarship and teaching with a strong focus on experiential learning. Founded in 1951, Seton Hall Law School is located in Newark and offers both day and evening degree programs. For more information visit law.shu.edu.

The American Health Lawyers Association (AHLA) is the nation’s largest nonpartisan educational organization devoted to legal issues in the healthcare field. The Association’s 11,000 members practice in a variety of settings in the healthcare community. For information about our resources, publications, and educational offerings, visit www.healthlawyers.org.

Research Fellow & Lecturer in Law Kate Greenwood in a Featured Op-ed in Pharmalot on the U.S. Supreme Court and Liability for Defects in Generic Drugs

Research Fellow & Lecturer in Law Kate Greenwood published a Featured Op-ed in Pharmalot on the U.S. Supreme Court and the prospect of liability for personal injury from defects in generic drugs. In “Betting on Liability for Generic Defects,” Ms. Greenwood writes:

As reported on Pharmalot, the US Supreme Court has agreed to review the First Circuit Court of Appeals’ decision in Mutual Pharmaceutical Company v. Bartlett that federal law did not preempt a New Hampshire jury’s determination that the generic drug sulindac had a “design defect” and so should have been recalled (back story with briefs).

It is highly likely that the Supreme Court will reverse the First Circuit’s decision, and, in so doing, confirm that manufacturers cannot be held liable for failing to re-design or recall unsafe generic drugs, just as they cannot be held liable for failing to update the labeling of such drugs. The ball will then be in Congress’ court to fill the resulting postmarketing safety gap.

As the First Circuit explained in the Bartlett decision, New Hampshire law provides that a drug has a design defect “‘if the magnitude of the danger outweighs the utility of the product.’” At trial, plaintiff Karen Bartlett’s expert testified that sulindac met this standard and the jury agreed, finding Mutual Pharmaceutical liable for selling a product with a defective design and awarding Bartlett over $21 million for the horrific SJS/TEN-related injuries she suffered after taking sulindac.

Read more in the feature Op-ed, “Betting on Liability for Generic Defects.”

 

United States v. Caronia: Some Preliminary Thoughts on the Second Circuit’s Decision Invalidating the Ban on Off-Label Promotion

Earlier this week, the Second Circuit Court of Appeals at last issued its decision in United States v. Caronia and it is momentous (and predicted to be heading to the Supreme Court).  A two-judge majority of the Circuit Court held that Alfred Caronia, a pharmaceutical sales representative, “was convicted for his speech – for promoting [the central nervous system depressant Xyrem] for an off-label use – in violation of his right of free speech under the First Amendment.”

The majority’s decision begins with a threshold question.  Was Caronia convicted for conspiracy to misbrand Xyrem because he engaged in off-label promotion qua off-label promotion, that is, for his speech?  Or, was his speech simply “evidence that the ‘off-label uses were intended ones[] for which Xyrem’s labeling failed to provide [the required] directions[,]” as the government argued on appeal?  The former would implicate the First Amendment, but the latter would not.  The Supreme Court has held that “[t]he First Amendment … does not prohibit the evidentiary use of speech to establish the elements of a crime or to prove motive or intent.”  As the Caronia dissent (colorfully) explained, “Abby and Martha [do not have] a First Amendent right to offer arsenic-laced wine to lonely old bachelors with the intent that they drink it. … And any statements Abby or Martha made suggesting their intent—even if all of the statements were truthful and not misleading—would not be barred from evidence by the First Amendment…”

The majority found that Caronia was convicted for his speech alone, pointing to the lower court’s instructions to the jury and to a number of statements that the government made at trial including “[Caronia] conspired through some act of misbranding, and that act of misbranding … was the promotion on October 26^th and November 2^nd[,] marketing [a] drug for unapproved uses.”  Caronia’s conviction must therefore be vacated, the majority concluded.  The Food Drug and Cosmetic Act does not “criminaliz[e] the simple promotion of a drug’s off-label use because such a construction would raise First Amendment concerns.”   The majority did not disagree with the general proposition that speech may be used as evidence of intent, and it expressly declined to decide the specific question whether the FDCA violates the First Amendment by “defin[ing] misbranding in terms of whether a drug’s labeling is adequate for its intended use, and permit[ting] the government to prove intended use by reference to promotional statements made by drug manufacturers or their representatives.”  Even if the Second Circuit’s decision stands, then, the government may be able to argue that Caronia is a case about an erroneous jury instruction with limited practical effect

The majority went on to hold that a ban on off-label promotion qua off-label promotion—like the Vermont law barring drug companies from using physician-specific prescribing data to craft physician-specific sales pitches at issue in the Supreme Court’s 2011 decision in Sorrell v. IMS Health (which I discussed on this blog here)—is unconstitutional regardless of whether strict or intermediate scrutiny applies.  The majority gave short shrift (no shrift, really) to the argument that the ban on off-label promotion is necessary to preserve the integrity of the FDA’s drug approval process, suggesting that the government could “minimize … manufacturer evasion of the approval process” by imposing “ceilings or caps on off-label prescriptions.”

The majority did not elaborate on how ceilings or caps on off-label prescriptions would work, on the grounds that the First Amendment puts the burden on the government to demonstrate that they would not.  Here, too, there may be an opening for the government, to make a stronger case to the Supreme Court than it did before the Second Circuit (in its briefs or at oral argument) that ceilings or caps would not be “administrable, feasible, or otherwise effective” and that the ban on off-label promotion therefore provides a direct, narrowly-tailored, and crucial incentive to clinical research into already-approved drugs.  As the dissent suggested, “[a] ceiling on off-label prescriptions would require collecting data from countless numbers of doctors and patients and, given the medical uncertainties involved, could needlessly (and simultaneously) result in the denial of some effective treatments and the overprescription of ineffective and even dangerous ones.”

 

Canaries in a Coal Mine: Patient Complaints (Finally) Lead to Withdrawal of Generic Wellbutrin XL

Recently, the Food and Drug Administration announced that the manufacturer Impax Laboratories has asked the agency to withdraw its approval of a generic version of the antidepressant Wellbutrin XL 300 mg that is manufactured by Impax and marketed by Teva Pharmaceuticals.  A bioequivalence study sponsored by the FDA compared the Impax/Teva 300 mg generic to Wellbutrin XL 300 mg and found that the generic tablets failed to release the medication’s active ingredient into the blood “at the same rate and to the same extent” as the name brand.  While the results of the study only recently became available, the FDA acknowledges that it has been aware of concerns about the Impax/Teva 300 mg generic for over five years.

The Impax/Teva 300 mg generic was approved in 2006 on the basis of a study establishing that Impax’s 150 mg generic was bioequivalent to Wellbutrin XL 150 mg.  The FDA did not require that a bioequivalence study of the 300 mg generic be done, because the 300 mg dose of the drug poses a risk of seizures.  Soon after the Impax/Teva 300 mg generic was approved, the FDA began to receive “reports describing either adverse events or lack of an effect.”  As ABC News reports here, Joe Graedon of the consumer advocacy group the People’s Pharmacy was hearing the same things, and, in 2007, he asked Consumer Lab –according to its website, “the leading provider of independent test results and information to help consumers and healthcare professionals identify the best quality health and nutrition products”–to compare the Impax/Teva generic to its name brand counterpart.

Consumer Lab published an analysis demonstrating that “[i]n the first two hours of a dissolution test, we found [the generic] released 34 percent of the drug, while Wellbutrin released 8 percent” and that “[a]t four hours, the [Impax/]Teva product released nearly half of its ingredients, while original Wellbutrin released 25 percent.”  Consumer Lab’s president explained to ABC that the patent on the extended release technology used in Wellbutrin XL was still in effect when the Impax/Teva generic was approved.  As a result, the generic contained the same medication as the original but used a different (or perhaps no) extended release technology.

The FDA was made aware of Consumer Lab’s results, but declined to act on them.  The agency believed that differences in rate of release were unlikely to be clinically significant because “[t]he antidepressant effect of this drug does not appear for several weeks after initiation of treatment, and the effect is, in large part, related to long-acting metabolites.”  The FDA concluded that “[t]he recurrent nature of [major depressive disorder] offers a scientifically reasonable explanation for the reports of lack of efficacy following a switch to a generic product.”

As the FDA explains in a Questions and Answers document posted to its website, despite its conclusion that the Impax/Teva generic was clinically equivalent to the name brand, in November 2007 the agency “asked Impax/Teva to conduct a study directly on its 300 mg extended-release product to compare its bioequivalence to Wellbutrin XL 300 mg … [in]patients who had reported lack of efficacy after switching from Wellbutrin XL 300 mg to [the Impax/Teva product].”  That study was terminated in late 2011 because “Impax/Teva was unable to recruit a significant number of affected patients to generate the necessary data.”  It was not until 2010 that the FDA decided to sponsor its own bioequivalence study.  That study, of 24 healthy adult volunteers, was not completed until August of this year, because the agency had to “get funding for the study, design[] the study, obtain[] approval from the Institutional Review Board for Protection of Human Subjects, recruit[] and enroll[] healthy volunteers, conduct[] the study, develop[] an analytical method of analyzing the data, and complete[] its analysis of the study data.”

As a result of its experience with the Impax/Teva 300 mg generic, the FDA reports that it “is revising its guidance to industry for how to conduct premarket bioequivalence studies in generic [Wellbutrin] products.”  It will no longer be possible for a company to extrapolate the results of bioequivalence studies done on 150 mg tablets to 300 mg tablets.

One wonders whether there might be other lessons to be learned from the Impax/Teva 300 mg generic experience.  For one, I wonder if the FDA could have–and, if so, if it should have–acted more quickly.  The agency does seem to have taken patients’ complaints about the Impax/Teva tablets seriously.  At the same time, it took six years to withdraw a generic drug that patients complained about immediately upon its approval.   Delays of this sort have the potential to undermine trust in generics generally.

Another potential lesson to be learned from the Impax/Teva 300 mg generic experience is specific to antidepressants.  As Michelle Hottinger and Bryan A. Liang note in their article Deficiencies of the FDA in Evaluating Generic Formulations: Addressing Narrow Therapeutic Index Drugs, which is forthcoming in the American Journal of Law and Medicine, much about antidepressants’ mechanism of action is still not understood, which “may leave some uncertainty as to [their] pharmacokinetics.”  Even where an antidepressant meets the FDA’s bioequivalence standards, Hottinger and Liang write, “therapeutic equivalence is not guaranteed.”  Given this, the FDA might be well-advised to pay heightened attention to adverse event reports about generic antidepressants.

Industry Funding of CME Down, According to ACCME

When we think about health care reform, we need to remember that we have been attempting reforms through many avenues of myriad parts of our health system.  The IRS revised Form 990 and schedule H in anticipation of the ACA; critics of conflicts of interest have been working on multiple fronts simultaneously.  One of the challenges about all of these changes is how we measure whether they have made any positive difference.

The Accreditation Council for Continuing Medical Education (ACCME), which is the accrediting entity for Continuing Medical Education (CME), just released its annual report, which was much less interesting than I had hoped, as it is mostly a financial statement for the year’s CME activities.  Nonetheless, it shows that industry grants to CME have declined from 50 to 30 percent of total CME income, which is attributed to the tremendous scrutiny CME has received over the years.  Importantly, industry has not lost interest in medical conferences, as ad revenue from exhibits rose 7.2 percent to $296 million.  You can read a summary of the report on Pharmalot or read the whole report.

While interesting, it’s hard to make out exactly what to conclude from this news about CME funding.  First, it could be a response to the economy, but that’s belied by the increase in exhibit funding.  And besides, pharma has historically been of the “you have to spend money to make money” mind.  So, perhaps industry is indeed responding to the criticism about funding CME.  Not mentioned is the possibility that CME sponsors have been turning away industry money, but that too is a possibility.

Some were concerned that if this happened, health professionals would be unable or unwilling to pay for their own CEUs.  The total income for 2011 CME appears to be in line with prior years (especially given a methodology change adopted in 2011).  While the number of physicians participating in CME was down slightly, that decline is consistent with a multi-year downward trend; the number of non-physician participants in CME is slightly up.  Finally, as noted by Pharmalot, “other income, which includes registration fees paid by participants, rose 4.4 percent [in 2011] to nearly $1.2 billion.”  While more than one year of experience will give a better picture, it seems fair to conclude so far that physicians are indeed willing to underwrite their own CME.

Most important to remember, however, is that the funding issue was merely a surrogate for the question of whether CME is biased either substantively or in subject matter coverage.  I don’t think we really knew the answer yesterday, any more than the ACCME report enlightens us about what the answer is today.  An annual report about CME in which I and others would really be interested would look at whether the subject matter of conferences has changed — are things being covered that weren’t before.  Is comparative cost-effectiveness being addressed in presentations that address alternative treatments?  Are real responses to racial health disparities being discussed?  Is education being delivered to audiences comprised of interdisciplinary healthcare teams rather than the homogenous audiences found at many academy and similar meetings?  Is CME delivery itself being studied to determine what learning methodologies are most effective?  In short, if we can conclude that industry is listening to its critics by redirecting its funding, can we also infer that changes are occurring in response to other critiques of CME, such as those posed by the IOM report entitled “Redesigning Continuing Education in the Health Professions” and Seton Hall Law’s Whitepaper entitled “Drug and Device Promotion: Charting a Course for Reform?”

Presumably, it is a good thing to have less industry funding of CME — although we only see the change in the United States, not elsewhere . But it doesn’t get to the heart of the matter, which is the need for significant reform of CME generally.  That’s the report I want to read.

Graduate Certificate Program in Pharmaceutical & Medical Device Law & Compliance to Start Again, October 7, 2012

Seton Hall Law School’s Center for Health & Pharmaceutical Law & Policy starts classes again on October 7th for the Graduate Certificate in Pharmaceutical & Medical Device Law & Compliance. The priority application date is September 24, 2012.

The Graduate Certificate in Pharmaceutical & Medical Device Law & Compliance is a non-degree program designed for individuals who seek in-depth knowledge about legal, regulatory, and ethical issues related to the pharmaceutical and medical device industries. Taught exclusively online, it offers students nationwide a targeted immersion in key substantive issues along with the practical skills necessary to research and communicate effectively about the law.

The intensive program is geared to busy professionals who want to cover a significant amount of material in a relatively short period of time. The program is open to students who have earned a baccalaureate degree from an accredited college or university. It is specifically designed to meet the needs of mid- to senior-level professionals in the health care industry, but highly motivated students from other backgrounds are also welcome to apply. It is not necessary to have prior academic or work experience in health care in order to do well in the program.

Additional information and registration is available here.

Why study pharmaceutical and medical device law at Seton Hall School of Law?

Seton Hall Law School has specialized in health law for more than a decade, and its health law program is consistently ranked among the top ten in the nation by U.S. News & World Report.  The Law School’s health law faculty specialize in a wide range of health law topics, including healthcare organizations, nonprofit governance, healthcare financing, healthcare fraud and abuse, food and drug law, research with human subjects, genetics and the law, public health law, and bioethics.  In addition to training future lawyers, Seton Hall Law offers a Master’s of Science in Jurisprudence degree for individuals working in the health care industry, as well as an innovative compliance certification program for pharmaceutical and medical device professionals.  Seton Hall Law is also a center for scholarship and public policy development related to health care, particularly through its Center for Health & Pharmaceutical Law & Policy, whose mission is to foster informed dialogue among policymakers, consumer advocates, the medical profession, and industry.

Of Drug and Device and a Lack of Personal Jurisdiction

As much as I write about medical malpractice, it seems only fair that I devote a post and direct our fair readers to the other side of the bar: The Drug and Device blog put out by a number of Dechert, LLP attorneys involved in pharmaceutical and medical device product liability litigation– from the defense side– And  Writing in Their Individual Capacities (yes, I read the disclaimer– which is itself a piece of art).

I don’t know that our non-law-based readers would find the site of much interest, but for those of you who do have a legal background– it’s really quite good– and rather funny (though it doesn’t hurt if you have a taste for the acerbic). And I’m not just saying this because today’s post I so enjoyed turned out to have a hat tip to former classmate and worthy opponent Lincoln Wilson at the bottom of it. The blog is good. And if you’re a lawyer– or a law professor– today’s post should be disquieting for you.

The post, entitled “Another Homework Failure By Plaintiffs,” is about a suit against Endo Pharmaceuticals  re: Darvocet and how the plaintiffs cause of action burst into flames when it saw the light of a federal judge– for lack of personal jurisdiction. The article points out (pointedly) that the court notes that although the burden of showing jurisdiction is “relatively slight,” plaintiff’s offered no facts. None. Plaintiffs asserted that Endo, which purchased three entities (which still now exist) that had formerly produced the drug in question, “may have assumed responsibility for the acts…” and claimed the court needed to find personal jurisdiction based on the facts. The court:

But what “facts”? The portion of the complaint relied upon by the plaintiffs merely implies that the Endo Defendants “may have” somehow assumed the liabilities of their subsidiaries; the only factual assertion [plaintiff's allegation] contains is that the plaintiffs do not have the information they need to establish personal jurisdiction.  Thus, even if the plaintiffs were permitted to stand on their pleadings, they would fall woefully short of the necessary prima facie showing.

I think that’s going to leave a mark.

I said above that if you were a law professor or a lawyer you would find the Drug and Device post disquieting. But maybe I was hasty with regard to other lawyers. Although there is great value in a learned bar, the value of an unprepared opponent is, I suppose, inestimable. At least in the short run.

Having said that, if you have a few minutes, check out the Drug and Device blog article– and the slip opinion of the case they’ve conveniently provided. It’s worth it. From a stand point of pedagogy, it may not be as useful as the numerous Texas appeals filed late resulting in execution, but it could certainly function as a cautionary tale.

Risperdal: Low Hanging Fruit for States with Medicaid Deficits?

Think of it as a clarion call, a shot across the bow, or even the smell of carrion wafting towards the nostrils of bean counters and state administrators everywhere–but any way you look at it, be sure that the Risperdal verdict of $1.2 billion dollars against Johnson & Johnson and its subsidiary, Janssen Pharmaceuticals, Inc., has states across America checking the terms of their own False Claims Act and counting how many prescriptions of the drug were filled through Medicaid.

It is no secret that states face shortfalls; it is no secret that Arkansas was awarded $1.2 billion, $5,000 per prescription plus a relatively minor amount for deceptive practices.  Think back to the tobacco litigation of the 90s for an apt analogy–states across the country plugged their deficits with tobacco money to the tune of billions. Make no mistake, the Risperdal verdict is a game changer–from the perspective of the litigation itself, the Risperdal litigation to come, and what that litigation signals– especially from  a Pharma and Healthcare legal compliance perspective going forward: because you can rest assure that after states have finished counting Risperdal prescriptions filled through Medicaid and prepped the requisite paperwork,  they will then commence their search for “the next Risperdal.”

In case you missed it, here’s a snippet from Zack Buck’s superb article on the verdict and the “rigid and severe” penalties associated with the False Claims Act.  Reading the rest of it is time well spent (link below).

News of the $1.2 billion verdict against Johnson & Johnson and its subsidiary Janssen Pharmaceuticals Inc. for their roles in marketing Risperdal during the middle of last decade sent reverberations through the industry earlier this week.  The award resolved Arkansas’ claims that the companies fraudulently marketed the “second generation” antipsychotic, misleading doctors and deceiving the state’s Medicaid program into paying for 239,000 prescriptions of the drug.  Specifically, the state claimed the companies minimized Risperdal’s dangerous side effects by not disclosing the risks on its label, marketed the drug for unapproved uses, and characterized it as more effective than competitors’ drugs.

After the jury found that the companies had misled doctors about the risks associated with Risperdal, Judge Tim Fox awarded $11 million for the violation of the state deceptive trade practices act. Further, Judge Fox turned to the Arkansas’ False Claims Act (FCA) – which carries a minimum $5,000 civil penalty for each violation of the Act (the federal FCA requires a minimum civil penalty of $5,500) – and applied Arkansas’ statutory penalty to the 239,000 prescriptions of Risperdal paid for by Arkansas Medicaid between 2002 and 2006, totaling $1.195 billion in damages.  According to Janssen, the state paid only $8.1 million for Risperdal during the 3½ year time period, which amounts to less than 1% of the damages amount.  The companies plan to appeal.

http://www.healthreformwatch.com/2012/04/15/rigid-severe-penalties-of-fcas-on-full-display/

Must-Read Articles on Drug Shortages

In February, Health Affairs featured Duff Wilson’s article on “Deepening Drug Shortages.”  As Wilson notes, “the number of reported drug shortages in the United States nearly tripled between 2005 and 2010, increasing from 61 to178 and emerging as a systemic problem in the US health care system.”  Sharona Hoffman has recently written on the topic:

How could such shortages plague premier hospitals in the twenty-first century in the wealthiest country in the world? How could even patients with comprehensive health insurance and abundant financial resources be denied adequate care because the medications they require are simply not available in the marketplace?

The Article posits that public health policies and standards must serve multiple roles. They should deter both carelessness that leads to product contamination and strategic decisions to discontinue or suspend manufacturing when such decisions will cause shortages. At the same time, governmental rules should encourage production of vulnerable drugs. Accordingly, the Article proposes a blend of legislative, regulatory, and private-sector interventions that should realign manufacturers’ incentives and significantly diminish the drug shortage phenomenon.

Hoffman’s article is well worth reading in full, and I hope it guides policymakers.  As I noted last year, a plutonomy will not reliably generate even the products that its most powerful consumers may occasionally need.

Recommended Reading: Recent Scholarship on Drug and Device Regulation

In Patients Over Politics: Addressing Legislative Failure in the Regulation of Medical Products (forthcoming in the 2011 volume of the Wisconsin Law Review and available on SSRN), Efthimios Parasidis proposes a significant expansion of drug and device companies’ responsibility to engage in “active post-market analysis” of drugs and devices, to be coupled with a new rule that only companies that conducted such analysis would benefit from preemption of state tort claims.  Professor Parasidis’ article includes a nuanced and revealing analysis of the historical and other reasons for the Food and Drug Administration’s heavy focus on pre-market review of drugs at the expense of post-market surveillance, as well as useful updates on both the caselaw regarding the preemption of claims involving branded drugs, generic drugs, devices, and vaccines and the ongoing efforts to use health information technology to glean information about the safety and efficacy of marketed products.  Most notable, though, is the article’s thorough explication of Professor Parasidis’ interesting proposal that “preemption laws, which often are enacted pursuant to industry lobbying efforts [be linked to] protocols that further the public health.”

In Enforcing Integrity (forthcoming in the 2011 volume of the Indiana Law Journal and available on SSRN), Katrice Bridges Copeland makes a strong case for her conclusion that neither the exclusion of pharmaceutical manufacturers from Medicare and Medicaid — a punishment which the government is reluctant to impose because it would spell the end for the company — nor the use of corporate integrity agreements coupled with large fines — which manufacturers agree to in order to avoid exclusion — works to deter illegal marketing activities.  As Professor Copeland notes, numerous companies have learned that “the punishment for multiple offenses is simply another CIA and another fine.”  She recommends that the government consider a number of alternative penalties for repeat offenders, including (1) requiring that manufacturers fund clinical trials studying the off-label uses for which they promoted their products, (2) requiring that they license the product or products at issue to other manufacturers, (3) holding high-level individuals criminally liable under the responsible corporate officer doctrine, and (4) amending the Social Security Act to allow for the exclusion of particular drugs (as opposed to entire companies) from Medicare and Medicaid.

Finally, I recommend Seton Hall Law’s own Jordan Paradise’s fascinating article, Claiming Nanotechnology: Improving USPTO Efforts at Classification of Emerging Nano-Enabled Pharmaceutical Technologies (forthcoming in the 2011 volume of the Northwestern Journal of Technology and Intellectual Property and available on SSRN), in which she argues that the United States Patent and Trademark Office’s system for classifying patents on nanotechnology-related inventions, “[w]hile undoubtedly helpful for internal purposes,” cedes too much to the courts.  Reviewing the facts of the recent case Elan Pharma International v. Abraxis Bioscience, which involved a dispute over two patents describing nano or near-nano scale versions of the same existing cancer-fighting agent and was tried to a jury verdict, Professor Paradise points out several ways in which the patents’ claims potentially overlap.  She argues that the courts are “a clumsy forum” for sorting out the “complex patent law issues that arise based on scale, size, and interactions at the nanoscale that transcend previously envisioned physical and chemical boundaries[,]” and offers concrete recommendations for steps the USPTO can take to improve its classification efforts to reduce the number of patents with potentially overlapping claims thereby making court involvement less necessary.

Does the Ban on Off-Label Promotion Bar On-Label Promotion?: The Case of Call Plans

As predicted, in the wake of the Supreme Court’s decision in Sorrell v. IMS Health pharmaceutical companies have raised First Amendment challenges to the ban on off-label promotion on a number of fronts.  Most recently, Par Pharmaceutical sued to invalidate the ban to the extent that it “criminalize[s] Par’s truthful and non-misleading speech to healthcare professionals concerning the FDA-approved use of its FDA-approved prescription drug.”  How is it that the ban on off-label promotion could be interpreted to bar the on-label promotion in which Par wishes to engage?  At the heart of Par’s dispute with the government are the “call plans” that pharmaceutical companies develop using the prescriber-specific prescription data at issue in Sorrell.

Call plans set forth which physicians pharmaceutical sales representatives should visit and how often.  In an article in the current issue of Next Generation Pharmaceutical magazine, Matthew Linkewich and Jay Margolis of IMS Health explain that a “properly conceived and configured … call plan directs reps to those physicians whose practice characteristics, constellation of prescribing behaviors and attitudes are conducive to supporting the brand goals.”  Because call plans embody “brand goals,” the government has focused on them as evidencing companies’ intent to engage in off-label promotion.

For example, in a December 15, 2010 press release announcing a $214.5 million settlement with Elan Corporation, the Department of Justice highlighted the fact that Elan’s “off-label marketing efforts” for its anti-epilepsy drug Zonegran “targeted non-epilepsy prescribers.”   A January 28, 2011 press release announcing the formal sentencing of Novartis in a case involving off-label promotion of its anti-epilepsy drug, Trileptal, similarly noted that the company “decided to market and promote Trileptal as a treatment for [two off-label indications, bipolar disease and neuropathic disease] and directed its sales force to visit doctors who would not normally prescribe Trileptal due to the nature of their practice.” Novartis’ plea agreement explains that while epilepsy is treated by epileptologists and neurologists, the company’s call plan included psychiatrists and pain doctors.

The corporate integrity agreement that Novartis entered into as part of the settlement of the Trileptal-related claims against it provides for independent review of “the bases upon which [health care providers] and [health care institutions] belonging to specified medical specialties are included in, or excluded from, the Call Plans based on, among other factors, expected utilization of Government Reimbursed Products for FDA-approved uses or non-FDA-approved uses[.]“  The corporate integrity agreement requires a similar review of the company’s sampling strategy and goes so far as to bar the company from delivering samples to health care providers identified by the company as “belong[ing] to a specialty group that is unlikely to prescribe” the sampled product on-label.

Currently, Par Pharmaceutical’s call plan for its appetite stimulant Megace, which is FDA-approved for the treatment of AIDS-related wasting, does not include oncology practices or long-term care facilities.  With the help of an outside consultant, Par determined that physicians in those settings “reasonably may encounter patients suffering from AIDS-related wasting, and thus may have occasion to prescribe [Megace] for its on-label use,” but all agree that they would be much more likely to prescribe the drug off-label to treat wasting in cancer and geriatric patients.  In the concluding paragraphs of Par’s complaint, it explains that the U.S. Attorney’s Office for the District of New Jersey, which is investigating the company’s marketing practices, has informed the company that before it promotes a drug for its on-label use to doctors who prescribe the drug off-label it must “confirm that there are presently a sufficient number of patients being treated for whom the drug could be prescribed on-label.”

As Par points out, the government has offered no guidance regarding the number of on-label patients that a doctor must treat before he or she can be included in a company’s call plan.  On the one hand, this is to be expected because the call plan is only one factor that the government considers in determining a company’s intent.  On the other hand, it leaves companies like Par without a clear course to follow and, after Sorrell, likely to sue.

FDA’s ‘Bad Ad’ Program is in Full Effect

Last spring, the Food and Drug Administration (FDA) launched the Truthful Prescription Drug Advertising and Promotion Program (known more accessibly as the “Bad Ad Program“). The goal of the program is to enlist the help of health care professionals, consumers, and industry representatives in noting FDA violations and reporting activities and messages that are false or misleading. Common drug marketing violations include omitting or downplaying risk, overstating effectiveness, promoting off-label uses and making misleading drug comparisons. The program is run by the FDA’s Division of Drug Marketing, Advertising, and Communications (DDMAC), which is responsible for “ensuring truthful advertising and promotion of prescription drugs.”

The FDA published a year-end report in May noting that the program has been successful in raising awareness. DDMAC received 328 reports of potentially untruthful or misleading promotions in one year, with the majority of those submitted by health care professionals (188 reports) and consumers (116 reports). The report notes that prior to the Bad Ad program, the FDA received an average of about 104 reports per year.

And the Bad Ad tips are still coming in. Just at the end of last month, DDMAC issued a reprimand letter to Pfizer’s Vice President of US Regulatory Affairs regarding misleading advertising of drugs on the company’s Lipitor website. A complaint to the Bad Ad program observed that the links from the Lipitor site led to pages for the drugs Caduet (for high cholesterol and blood pressure), Norvasc (for high blood pressure), and Chantix (for smoking cessation). But each of those pages failed to note any of the risk information associated with the drugs, which is a violation of the Federal Food, Drug, and Cosmetic Act.

The FDA states that “by omitting the most serious and frequently occurring risks associated with Caduet, Chantix, and Norvasc, the webpage misleadingly suggests that these drugs are safer than have been demonstrated.” The letter ends with a request that Pfizer immediately stop the dissemination of violative promotional materials for the drugs. The company was to have submitted a written response to the complaint by September 14^th that states how they will comply with the request.

While the Bad Ad program may be working to raise awareness among health professionals and consumers, one violation may not be enough to induce compliance from pharmaceutical companies. In fact, DDMAC already chided Pfizer in March of 2009 for omitting risk information for Caduet and Chantix. In that case, Pfizer sponsored links for the drugs on Internet search engines. The sites linked to did not mention any risk information and therefore, presumably,  can be said to have also represented the products in a manner which, as above, suggests that these drugs are safer than have been demonstrated.” The most recent letter states that “DDMAC is concerned that Pfizer is continuing to promote its products in a similarly violative manner.” A citizen’s task force is a good way for the FDA to multiply their eyes and ears to keep tabs on misleading and/or violative advertisement. We’ll see what further successes the next year-end report for the Bad Ad program can show. Or, perhaps, success might also be measured in the absence of violations.

New Profit Opportunities In American Health Care

I notice there is a lot of handwringing over the Affordable Care Act’s “government takeover” of the health care system. So let’s take a look at some exciting new markets that are still thriving.

1) At the beginning of the summer, I noted some problematic drug shortages (bottom half of post). The problem keeps getting worse. There is a steady stream of heartrending stories about care being compromised. Reform measures to assure an adequate supply are moving at a snail’s pace, thanks both to truculent manufacturers and the bipartisan drumbeat to “cut health care costs.” But at least some folks are thriving: as the NY Times notes, ‎”Unscrupulous wholesalers have made matters worse by scooping up scarce drugs and offering them to hospitals at markups that often reach 20 times the normal price or more.”

What a great business model! So glad the “free market” is working its magic on health delivery. While we’re at it, let’s allow ER docs to force patients to sign over half their bank accounts before treatment. That will certainly increase the supply of emergency rooms, even if the transition is a little bumpy for some people.

By the way, I’m sure some will argue that, if only Medicare weren’t paying for many of these drugs, we’d be fine. (Or at least the “we” capable of paying for the drugs at a “market price,” whatever that is, would be fine.) Query: Would there have been adequate incentive to create the drugs if a major purchaser like Medicare hadn’t paid what it did while the drug was on patent? No, I didn’t think so. Income and wealth in our society is still equally distributed enough (and coordination problems severe enough) that the top 1% won’t sustain a thriving hospital and drug research system all by themselves, even if they are the critical factors in one’s policy calculus. As I noted earlier, it’s hard to imagine individuals, or even wealthy groups, stockpiling all drugs they might need, particularly the sterile injectables or biotech solutions that are critical to advanced medicine. Even the very wealthy must rely on a steady, more general demand for these products. They can’t just order them up for just-in-time delivery, like a Tiffany watch. Public subvention—ranging from research grants to Medicare and Medicaid funding for the products research generates—provides that demand.

2) Pauline Chen reports on an “insurance maze” for US doctors, based on a new Health Affairs study comparing their practices to those of their neighbors to the north:

Physicians in Canada, where health care is administered mainly by the government, did spend a good deal of time and money communicating with their payers. But American doctors in the study spent far more dealing with multiple health plans: more than $80,000 per year per physician, or roughly four times as much as their northern counterparts. And their offices spent as many as 21 hours per week with payers, nearly 10 times as much as the Canadian offices.

Clearly the US has a comparative advantage in generating insurance-based hassles. Maybe we can keep specializing there, and aim to spend five times as much as the Canadians by 2014. The more choice, the better, whatever the cost, right? Think of all the people employed by this gauntlet of private sector checks and balances:

A young patient complaining of extreme fatigue, for example, might benefit from a $40 blood test that could confirm infectious mononucleosis in 10 minutes. But a doctor cannot order the simple test without first checking with the insurance company to see if it is covered and if there are any constraints on where the patient’s blood can be drawn and the test run.

Tracking down answers often means phone calls with long periods on hold, digging up old patient information and even recruiting office workers to act as specimen couriers to other labs and hospitals in order to expedite results or save frail patients or harried family members the hassle of traveling to an “approved site” for a test or procedure. “If someone comes in with a sick infant who needs a test, we often eat the costs and draw the blood ourselves,” Dr. Star said. “We aren’t going to tell them to put that kid in a car seat, drive a mile to an approved lab, park, register, then wait in line.”

If you’re an insurer (or the insurance industry), you’ve “won” to the extent you’ve foisted these costs and inconveniences onto doctors and patients. You certainly don’t want to abide by new Medical Loss Ratio requirements that limit the extent to which you employ these strategies of cost-shifting, delay, and denial of needed care. The “free market” is your friend, as is anyone who insists that health care delivery can be guided by the same economic principles that govern every other commodity.

Generic Drugs, Cost-Effectiveness, and Confidence

Smarter prescribing and better medication management are linchpins of current efforts to care for those with chronic medical conditions in a more consistent, coordinated, and, it is hoped, affordable manner.  A study reported in last month’s Health Affairs found that using medication to control patients’ blood sugar levels and lower their blood pressure and cholesterol is not just cost-effective, it can actually save money by reducing “downstream complications and the use of health services that outweigh the cost of the medications themselves.”  Notably, these cost savings can only be achieved if the medications in question are generics.  The authors conclude that “in a health care system strapped for resources, physicians will increasingly use generics, and patients will have to expect that most of their medications will be generic.”

As the authors also note, resistance to generics, on the part of both patients and their doctors, is longstanding and persistent.  Some of this can be chalked up to the intense and wide-ranging marketing campaigns that innovator companies mount on behalf of branded drugs.  Branded medications used to treat chronic conditions are especially heavily marketed, including through the use of free samples.  Numerous studies (here’s a recent one out of Vermont) show that physicians with sample closets in their offices are less likely than those without sample closets to prescribe generics where appropriate.

Interestingly, the Centers for Medicare and Medicaid Services announced earlier this year that Medicaid Part D prescription drug plans “may incur expenses related to distribution of and reporting on generic drug samples, provided to members within a physician’s office setting, under the plan’s administrative cost structure if doing so is consistent with a cost effective drug utilization management program.”  CMS explained that generic samples have the potential to reduce the government’s overall costs and to promote compliance with drug therapies by reducing enrollees’ current and future cost sharing expenses.  (George Van Antwerp argues here that CMS overstates the benefits of generic samples, but only because generic fill rates are rising so fast without them.)

Marketing is not the whole story behind lingering resistance to generics, though.  As the New York Times recently reported, most generic drugs are manufactured in “a shadowy network of facilities in China and India that are rarely visited by government inspectors, who sometimes cannot even find the plants.”  While plants in the United States are inspected at least once every two years, the Food and Drug Administration has historically lacked the resources to provide the same level of oversight to foreign facilities.  An “epoch-making” agreement between the FDA and generic drug manufacturers will, assuming it is approved by Congress, change this.  The manufacturers have agreed to pay $299 million in annual fees to, among other things, fund inspections of foreign plants on the same schedule that applies to domestic plants.  As the Times notes: “[T]he generic drug industry is no longer a motley collection of struggling mom-and-pop companies.  Years of consolidation have created giants like Israel-based Teva Pharmaceuticals that understand that their businesses depend on winning the confidence of patients and regulators alike, and they can afford to pay the fees needed to achieve that confidence.”

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