Filed under: Drugs & Devices, Litigation and Liability, Recommended Reading
Cross-Posted at Bill of Health
As I have blogged about before, last year, in Kaiser v. Pfizer, the First Circuit joined the handful of courts to have approved a causal chain of injury running from a pharmaceutical company’s fraudulent promotion, through the prescribing decisions of thousands of individual physicians, to the prescriptions for which a third-party payer paid. To establish but-for causation in the case, Kaiser submitted an expert report and testimony from Dr. Meredith Rosenthal, a health economist at the Harvard School of Public Health. Dr. Rosenthal conducted a regression analysis to determine the portion of physicians’ prescribing of the drug Neurontin that was caused by the defendant’s fraudulent promotion, arriving at percentages ranged from 99.4% of prescriptions for bipolar disorder to 27.9% of prescriptions for migraine.
Pfizer argued that Dr. Rosenthal’s regression analysis should not have been admitted (and at least suggested that such an analysis should never be admitted in a third-party payer case) because regression analysis could not “take into account the patient-specific, idiosyncratic decisions of individual prescribing physicians.” Dr. Rosenthal’s report, the company argued, “merely demonstrated ‘correlation’ and not ‘causation.’” The First Circuit disagreed, upholding the lower court’s determination that the challenged evidence was admissible under Federal Rule of Evidence 702, because “regression analysis is a well-recognized and scientifically valid approach to understanding statistical data” and because it “fit” the facts of the case.
Eric Alexander, a partner at Reed Smith, made a similar argument to Pfizer’s when he critiqued a decision issued in July in a third-party payer case in the Eastern District of Pennsylvania. Writing at the Drug and Device Law blog, Alexander criticized the court for failing to address “the fundamental—to us—issue of whether an economist [Dr. Rosenthal was the plaintiff’s expert in that case, too] can ever determine why prescriptions were written.” Alexander points out that “[t]o get to millions of dollars of revenue from prescriptions, many physicians have to prescribe the drug to many patients[,]” and those physicians can “pretty much do what they want[.]” Economists, Alexander argues, should not be allowed to by-pass this complexity and simply “assume” causation.
I would argue that, as idiosyncratic as physician decision-making may be, it is not uniquely so. As the First Circuit noted in Kaiser v. Pfizer, “courts have long permitted parties to use statistical data to establish causal relationships” in antitrust, employment discrimination, and other types of cases. In their article The Use and Misuse of Econometric Evidence in Employment Discrimination Cases, which is forthcoming in the Washington and Lee Law Review, Joni Hersch and Blair Druhan explain that plaintiffs have used regression analyses in employment discrimination cases for more than thirty-five years, to establish a prima facie case of disparate treatment or disparate impact. Plaintiffs in these cases use such analyses to “show that, all other qualifications equal, being a member of a protected class decreased the plaintiff’s expected wage or likelihood of receiving a promotion or being hired.” In class action cases, plaintiffs can also use regression analyses “to establish commonality between the members of the class as required by statute.”
In their article, Hersch and Druhan evaluate the three most common challenges to regression analyses—that they “suffer from omitted variables, a small sample size, and a lack of statistical significance”—and explain that there are “very few circumstances” under which these challenges are meritorious. The authors go on to describe the results of a regression analysis they performed to try to understand the consequences of courts’ considering econometric critiques in a sample of employment discrimination cases. Their analysis revealed that “if [an] opinion mentions any of the econometric critiques … then the plaintiff is 28.3 percentage points less likely to have a favorable result.” This is concerning in light of the examples Hersch and Druhan present of courts that are not “aware of the tricks that expert witnesses argue when attempting to impugn the reliability of valid statistical evidence presented by plaintiffs.” Hersch and Druhan recommend that “court[s] exercise [their] gatekeeping function by either acting under Daubert or establishing a peer-review system to guarantee that only valid challenges to regression results enter the courtroom.”
Hersch and Druhan suggest that their article could be helpful to judges evaluating statistical evidence in employment discrimination cases; I think its usefulness extends further. As plaintiffs continue to turn to regression analyses to establish causation and injury in third-party payer cases brought against pharmaceutical companies, courts will continue to be challenged to evaluate the reliability of such analyses, and to evaluate the reliability of defendants’ challenges to them. Hersch and Druhan’s article can help. Causation is causation, and doctors are no more—in fact, one would hope they would be less—idiosyncratic than employers.
Filed under: Drugs & Devices, Monday Morning Recap
It’s Monday morning, time for our Monday Morning Recap, the post where we call out recent drug and device law and policy developments that caught our eye and made us think.
1. Seton Hall Law School’s Kathleen Boozang appeared on Bloomberg Radio this past week, discussing pending litigation brought by the Kentucky Attorney General against Purdue Pharma over its allegedly fraudulent marketing of Oxycontin in the state. Purdue has appealed an adverse state court procedural decision to the state’s Supreme Court; a decision is expected by early next year. If the case goes to trial, Bloomberg journalist David Armstrong writes, the company fears “a catastrophic $1 billion judgment against it, based on the state’s allegations as well as the potential for punitive damages and pre- and post-judgment interest.”
2. Also last week, at the New York Times Donald G. McNeil Jr. reported on a recently-released study “of more than 100,000 pregnant women in Argentina, Guatemala, India, Pakistan, Kenya and Zambia” that found that “[g]iving steroids to women who are about to give birth prematurely — a standard lifesaving medical practice in richer countries — may be useless or even dangerous in poor countries[.]“ Tragically, “the rate of stillbirths [in the study group given steroids] was about 10 percent higher, and so was the likelihood of [the baby dying in its] first month. And substantially more mothers who received steroids appeared to develop infections after giving birth.”
3. The week before last, Express Scripts, the largest pharmacy benefit management organization in the United States, released the second in its series of Exchange Pulse reports, and it is worth reviewing. Express Scripts found that the individuals it serves who purchased insurance on an Affordable Care Act exchange used 59% more high-cost specialty drugs than the individuals it serves who accessed insurance through an employer. This “is largely attributed to a higher prevalence of HIV and hepatitis C. … More than 56% of all specialty drug claims in health exchange plans are for HIV medications, nearly three times higher than health plans.“
4. On the subject of specialty drugs, in this article at JAMA, which came out last week in print but was published earlier this month online, Peter Bach recommends “indication-specific” pricing of cancer drugs. Per Bach, while our current system is not set up to track the indication for which a drug is used, and thus could not support indication-specific pricing, the system could be modified. Bach writes:
The primary reason to pursue this enhancement to the system is to make it possible to rationalize drug pricing. There would be some secondary benefits, consistent with important current trends in health care toward more electronic documentation and richer data on health care encounters. The cancer care system would become more transparent with regard to the utilization of cancer drugs by physicians, and the data would create an infrastructure for real-world outcomes analyses as relevant information about indication could be captured as part of the clinician’s workflow. Off-label prescribing could be identified, and outcomes data from those uses might be used to price those indications. Overall, the transparency of oncology care would be meaningfully enhanced, as the utilization of drugs and their indications would both be identified as a matter of routine care.
5. Finally, in the category of technical but important, the week before last Terry Mahn of Fish & Richardson wrote a piece at Pharmaceutical Compliance Monitor about the “legal conundrum whereby a skinny labeled generic goes to market with an FDA-approved drug label that, in fact, induces infringement of a brand patent listed in the Orange Book. And because courts are loathe to enjoin the sale of low cost generic drugs once on the market, brand drugs protected by use patents are in a potentially precarious position.“
Filed under: Drugs & Devices, Monday Morning Recap
It’s Monday morning, time for our Monday Morning Recap, the post where we call out recent drug and device law and policy developments that caught our eye and made us think…
1. Making the news this week was a release by WikiLeaks of “a second updated version of the Trans-Pacific Partnership (TPP) Intellectual Property Rights Chapter[,]” which will have significant implications for access to medicines. Public Citizen has released a detailed analysis of the pharmaceutical issues that remain under negotiation, here. Public Citizen notes that the negotiating countries are still wide apart on some issues and are, for example, “debating a range of possible monopoly periods for biotech drugs, ranging from zero years to twelve.”
2. Ebola drug development continued to make the news this week. This article by Peter Loftus and Betsy McKay at the Wall Street Journal provides a very helpful overview. Loftus and McKay quote Food and Drug Administration Commissioner Margaret Hamburg who “said the agency has shifted more employees to help speed the development of drugs, vaccines and diagnostics. ‘We’ve been up in the middle of the night in order to make product available’ on an emergency basis to infected patients in the U.S., she said in an interview this week.
3. Turning now to diseases for which safe and effective vaccines have been developed and are widely available, this week Karen Kaplan at the LA Times analyzes new Centers for Disease Control data on vaccine coverage among children in kindergarten. Kaplan highlights the fact that, “[a]cross the country, the median rate of MMR vaccination for kindergartners in the 2013-2014 school year was 94.7% for the MMR vaccine[,]” with “seven states and the District of Columbia [reporting] rates below 90%. At those rates, some communities are in danger of losing herd immunity – having enough people vaccinated to protect the small number of those who can’t get shots for medical reasons.”
4. At Forbes John Osborne reported that “Chairman Fred Upton (R-Michigan) and some of his colleagues on the House Energy & Commerce Committee want to talk about the off label issue.” Osborne notes that Congress could “direct the FDA to establish a new pathway under which truthful information outside the scope of the approved label would be able to be discussed with physicians. … Congress also could simply declare that the FDA may not regulate the communication of truthful information, and that may (or may not) limit the Justice Department’s determination to apply the False Claims Act to cases where off label prescribing is prevalent.” Osborne writes that “Chairman Upton plans to introduce an omnibus reform bill in the new Congress. If the off label issue is addressed, it would represent a historic change in attitude and behavior within the United States government that would clearly have significant implications for the way in which the FDA regulates drug, biotechnology and device company communications.“
5. Finally, not this week but still worth noting, earlier this month the Office of Inspector General of the Department of Health and Human Services published a proposed rule which “would amend the safe harbors to the anti-kickback statute and the civil monetary penalty (CMP) rules under the authority of the Office of Inspector General (OIG).” The rule “would protect certain payment practices and business arrangements from criminal prosecution or civil sanctions under the anti-kickback statute[,]” “codify revisions to the definition of ‘remuneration,'” and “add a gainsharing CMP[.]“ This McDermott Will & Emery summary of the proposed rule provides helpful context. Comments on the rule are due December 2, 2014.
Filed under: Drugs & Devices, Monday Morning Recap
It’s October and it’s Monday, time for our Monday Morning Recap, the post where we call out recent drug and device law and policy developments that caught our eye and made us think. And once again, there’s been a lot going on…
1. If the questions I have been fielding from friends and family this week are any indication, the development of vaccines to prevent, and anti-viral medications to treat, Ebola virus disease is on a lot of people’s minds. In an article in The New Yorker in August, James Surowiecki gave helpful background on “Ebolanomics”, here; Lecia Bushak provided an update in last week’s Newsweek, here. Our own Carl Coleman wrote about the Food and Drug Administration’s decision to allow compassionate use of the experimental treatment ZMapp, here; in early September, the Department of Health and Human Services announced that it was partnering with ZMapp’s manufacturer to develop the drug, here. The FDA has also granted permission to Tekmira Pharmaceuticals to provide its experimental drug TKM-Ebola to patients on a compassionate use basis, here. And just today, the biopharmaceutical company Chimerix announced that the FDA has authorized compassionate use of its experimental treatment, brincidofovir, here. And this is not all, e.g., here. The pace of development in recent months is both dizzyingly fast and much too slow. As much or more focus and funding must go to stopping the current epidemic using proven public health techniques. As Atul Gawande wrote in The New Yorker last week, “The diagnosis of the first U.S. case is not the sign that we need to shut patients out. It’s the sign that we need to bring more help in. The Ebola epidemic is stoppable.“
2. Last week, the Open Payments website, which tracks payments drug and device companies make to doctors and teaching hospitals, finally went live. At Pro Publica, Charles Ornstein had this, highly critical, take: “If the federal government’s new Open Payments website were a consumer product, it would be returned to the manufacturer for a full refund. … As a health care journalist at ProPublica, I’m reasonably competent at analyzing data, plus I’m lucky to have another data reporter and a news application developer helping me. Still, it took us hours just to upload the data onto our servers so that we could dig into it.” Ornstein opines that “after the fumbled launch of Healthcare.gov, it might have been better if agency officials had pushed this off until it was in better shape.“
3. At Sidley Austin’s Original Source blog, Jaime Jones and Brenna Jenny call attention to two recently-decided cases in which courts allowed the government, in one, and the relator, in the other, to establish liability using statistical inferences. Jones and Jenny write that, in U.S. ex rel. Martin v. Life Care Centers of America, “the court determined that the fraud-fighting goals of the FCA would be stymied if the court sided with the defendants and effectively required a ‘claim-by-claim review’ in every FCA suit.” These developments are no doubt being watched carefully by drug and device manufacturers, who frequently find themselves defending against FCA suits. In an article published earlier this year, I discuss (and endorse) a similar evolution towards the use of standard statistical methods to establish liability in economic injury cases brought by third-party payers against drug and device manufacturers.
4. At FiercePharma, Tracy Staton reports on a 60 Minutes segment on cancer drug pricing that aired on Sunday, October 5th. She concludes:
Over and over, experts have said that rising drug prices will eventually force a public debate. Perhaps “60 Minutes” will help touch that off. But one of the biggest obstacles to overhauling cancer costs will be Americans themselves. Everyone wants access to the latest treatments, no matter how expensive. No one wants to put a number on the value of longer life, no matter how brief.
So, while private insurers may be setting up their own barriers to expensive meds, allowing public programs to do the same is frightening. Letting payers restrict access behind closed doors is more comfortable than facing the issue in the open.
5. Finally, I enjoyed reading FierceBiotech’s brief profiles of their top fifteen women in biotech for 2014. Making the list is Amy Schulman, who joined Pfizer as General Counsel, but was running that company’s consumer healthcare business by the time she left. Schulman is now a Venture Partner at Polaris Partners where she currently serves as CEO of Polaris-funded start-up Arsia Therapeutics, which is “working on technology to make large-molecule biologics easier to administer.” On the question of gender equity, Schulman comments: “We have to make sure we’re really being vigilant and look at, ‘Are we really gender neutral? Are we really color blind?'” she said. “… I’m hardly alone in the recognition that those of us who are here should be spending our political capital to open the doors to the next generation of women, and many of us are deeply committed to that.“
Filed under: Drugs & Devices, Food and Drug Administration (FDA)
Cross-Posted at Bill of Health
Earlier this week, the Food and Drug Administration announced that it was reopening the comment periods for the two draft guidances on the use of social media to promote prescription drugs and medical devices that it released in June: Internet/Social Media Platforms with Character Space Limitations: Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices and Internet/Social Media Platforms: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices. Both guidances have drawn criticism from industry and observers, with the FDA being charged with, in the words of Pharmaguy at the Pharma Marketing Blog, “not being technically savvy enough to understand the nuances of social media and search engine advertising.”
In the draft guidance on social media platforms with character space limitations, such as Twitter and sponsored links on Google and Yahoo, the FDA states that “if a firm chooses to make a product benefit claim, the firm should also incorporate risk information within the same character-space-limited communication.” The draft guidance would allow companies to limit the risks that are presented within a character-and-space-limited communication to those that are the most serious, as long as the communication also includes a direct hyperlink to a destination (for example, a landing page) that is devoted exclusively to a complete discussion of the product’s risks. The FDA emphasizes in the draft guidance that “[i]f an accurate and balanced presentation of both risks and benefits is not possible within the constraints of the platform, then the firm should reconsider using that platform for the intended promotional message (other than for permitted reminder promotion).” In the first round of comments, PhRMA commented that the amount of information that companies are required to include in a single communication “would make the use of Twitter and comparable platforms impossible in all but the rarest cases.” With regard to sponsored links, PhRMA also noted that the guidance assumes that advertisers have more control than they in fact do over “the appearance – and order of appearance – of information on such platforms.”
It will be interesting to see whether and how the FDA responds to these comments, as well as to any additional comments filed during the period that comments are reopened, which ends on October 29th. If the agency holds the line (as I think it should) and continues to require that companies provide at least some balance between risks and benefits in all advertising and labeling, regardless of platform, companies will no doubt (continue) to look for alternatives. At several points in the draft guidance on social media platforms with character space limitations, the FDA notes that “reminder” promotion “that calls attention to the name of a drug or device but does not, among other things, include indications, dosage recommendations, or other representations or suggestions concerning safety of effectiveness,” are exempt from the federal Food, Drug and Cosmetic Act’s risk disclosure requirements. Advertiser Simon Bein writes:
Reminder ads in paid search see some of the highest click through rates of any type of search ad and aren’t bursting at the seams with safety warnings. But when it comes to Twitter, the reality is more sobering: a reminder ad-based Twitter profile is probably about as boring as could be.
Disease awareness advertisements or labeling “that discuss a particular disease or health condition, but do not mention any specific drug or device or make any representation or suggestion concerning a particular drug or device” are likewise exempt from the FDCA’s risk disclosure requirements. Bein writes:
If your consumers are high in the funnel—searching for disease state information—unbranded communications, which drive great engagement for many of our clients, will be key. They’re relevant to a consumer’s information-seeking activities and help develop ongoing dialogues with the consumers. And with Twitter, let’s be realistic: branded accounts numbered in the single digits. Unless the FDA has a change of heart, it’s sure to stay that way.
In a recent article in The Pink Sheet, Sarah Karlin makes a similar point, noting that “disease-awareness ads could be a powerful marketing tool in areas of confined space and regulatory uncertainty[.]” Disease awareness ads are not without their issues, though. Karlin reports that the FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee and its Drug Safety and Risk Management Advisory Committee, both of which recently voted in support of a narrower indication for testosterone-replacement therapy, were concerned by the FDA’s lack of regulation of disease-awareness advertisements for age-related “Low-T”. The committees were shown a television advertisement run by AbbVie, the manufacturer of AndroGel, that says:
Feeling like a shadow of your former self? Don’t have the hops for hoops with your buddies? Lost your appetite for romance? And your mood is on your way down. You might not just be getting older. You might have a treatable condition called low testosterone or Low-T. Millions of men 45 or older may have Low-T. So talk to you doctor about Low-T and step out of the shadows.
Karlin explains that the advertisement “points viewers to a website, www.IsItLowT.com, which like the TV ad doesn’t mention any product name but does contain a page on available treatment options such as gels, patches and injections.” AbbVie does disclose its involvement with www.IsItLowT.com, albeit in the far right hand corner of the site, in gray text against a slightly lighter gray background. Companies are not required to make such disclosures and, in fact, doing so creates some degree of legal risk for them. Per a decade-old draft guidance, there are circumstances under which “the mere appearance of the company’s name in conjunction with a disease reference could trigger the act’s advertising or labeling requirements[.]“
Karlin goes on to report that the advisory committee members, understandably, “wanted to know how a company could discuss symptoms in a disease-awareness ad and imply treatment was available for these symptoms, when testosterone-replacement products weren’t approved to treat these symptoms.” In response, an FDA official emphasized that the agency does not have jurisdiction over such advertisements, the Federal Trade Commission does.
Particularly in character-space-limited platforms like Twitter, disease awareness advertisements merit FDA scrutiny, to ensure that they do not trigger the FDCA’s requirements, and the FTC’s scrutiny as well, to ensure that, if the FDCA does not apply, the advertisements are truthful and not misleading.