Filed under: Drugs & Devices, Monday Morning Recap
Well, once again it’s been two weeks since we last did a 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 there’s been a lot going on…
1. The September issue of The Milbank Quarterly contains an original empirical study by Genevieve Pham-Kanter analyzing the effects of the financial ties that members of the Food and Drug Administration’s advisory committees have with drug manufacturers. Among her very interesting findings is the fact that while a committee member with ties to one manufacturer was more likely to recommend approval of that manufacturer’s drug, committee members with ties to multiple manufacturers did not show an overall bias in favor of approval. Aaron Carroll wrote about the study at the New York Times, here, and David Schlaes wrote about it here. Per Schlaes: “The take-home lesson to me is that experts are actually experts. Those that are in demand by multiple companies for help in analyzing or developing their products are more likely to be the kind of experts the FDA is seeking and less likely to let their financial and other relationships with sponsors get in the way of their expertise.”
2. The contentious debate between the drug and device industry and the Department of Justice over where to draw the line between protected speech, on the one hand, and punishable fraud, on the other, continues. In an article at FiercePharmaMarketing this week, Tracy Staton calls attention to a brief the government filed at the end of August. Staton writes: “In essence, the brief asks the court to determine that ‘speech that serves as a conduit for violations of the law’ isn’t protected by the First Amendment. PhRMA, of course, is asking for the opposite. It wants the court to decide that the law only prohibits ‘at most, false speech,’ which would give reps the chance to talk about off-label use of meds, as long as they’re telling the truth.”
3. This week also brought news that a supervisory pharmacist at the New England Compounding Center was arraigned and pled not guilty to a single count of mail fraud. Denise Lavoie of the AP reports: “Chin, a supervisory pharmacist, is accused of participating in a scheme to fraudulently cause one lot to be labeled as injectable, meaning it was sterile and fit for human use. The drug was shipped to Michigan Pain Specialists in Brighton, Michigan, and injected into patients. As a result, 217 patients contracted fungal meningitis, and 15 died. Chin is the first person to be charged criminally in the case, but prosecutors have said the prosecution is part of a larger criminal investigation of Chin and others.“
4. At the New England Journal of Medicine, Rita Redberg argues that “[b]linded, randomized, controlled trials (RCTs), in which the proposed therapy is compared with a placebo or a ‘sham’ (nontherapeutic) intervention,”which are currently “rare for medical devices” need to become more common. Dr. Redberg recommends that “the risk associated with performing unnecessary procedures … be weighed against the risk of mistaking a placebo effect for therapeutic benefit and therefore subjecting thousands or millions of patients to a procedure that actually does them no good.”
5. Finally, at the New Yorker this week, Andrew Solomon discusses the “terrifying dilemma” confronting women with depression who must weigh a dizzying array of known and unknown risks when deciding whether to pursue treatment with antidepressant medication. Solomon writes:
The debate rages, and the choice is a difficult one: to be depressed during pregnancy, with troubling consequences, or to be on medication during pregnancy, with unclear ramifications. It is not helpful when the complexity of the decision is belittled. ‘Everyone’s happier with this idea that the medications are O.K.,’ [Roni Caryn] Rabin wrote, quoting an expert. Everyone is second most happy learning, as Rabin suggests, that the medications are poison but depression is fine—because clarity and simplicity make life easy. If the meds help more than they harm, you take them; if they harm more than they help, you don’t take them. The problem is that this is a highly nuanced question to which there is no consistent answer, and about which we know too little. That makes everyone excruciatingly uncomfortable.
In this article I wrote several years ago, I review some of the reasons for the dearth of information about the risk-benefit ratio of drugs when used during pregnancy and make recommendations for policy responses.
Filed under: Drugs & Devices, Food and Drug Administration (FDA)
Last week, Seton Hall Law alum David Gibbons of Hyman, Phelps & McNamara published a blog post at the firm’s FDA Law Blog on a very interesting legal question, whether a court can order the FDA to order a drug manufacturer to recall a drug. In a suit brought by Hospira challenging the FDA’s approval of generic versions of one of Hospira’s drugs, a federal district court in Maryland recently reversed itself on this point. The court vacated its earlier–unprecedented–ruling that would have required the FDA to order the generic drug manufacturers to recall the generic versions of the drug at issue. As Gibbons explains:
Generally speaking, FDA cannot compel a mandatory recall, except in very limited circumstances as authorized by statute, none of which apply to drugs…
FDA states clearly and succinctly in its Brief: “FDA cannot order recalls.” The Agency goes on to argue that the recall ordered in the Hospira TRO could not even be requested by FDA because the basis for the recall was a patent dispute and not a matter of product safety or efficacy. FDA says: “consumers should believe that recalled products present a risk to health or are grossly deceptive. That is decidedly not the case here.” The Agency admitted that “[i]f a company chooses not to comply with an FDA request to recall, FDA has no mechanism to enforce its request because it does not have statutory authority to order drug recalls.”
Read the entire post here.
Filed under: Drugs & Devices, Monday Morning Recap
Well, another week has flown by and it’s once again time for the Monday Morning Recap, the post where we call out the recent drug and device law and policy developments that caught our eye and made us think. We are looking forward to a busy last week of summer on the blog, with posts from yours truly, from Seton Hall Law student Adam Mitchell, and from Tara Adams Ragone. We’ll take a break for Labor Day Weekend and then be back for the fall with lots of timely analysis and commentary from Seton Hall Law’s health law faculty.
1. This past week the ubiquitous ALS ice bucket challenge came to Seton Hall Law, with Professor Mark Alexander (video here) and Dean Patrick Hobbs (video here) taking part. For those interested in how the money raised will be spent, I recommend this post by Carey Goldberg at CommonHealth. Goldberg spoke with “Dr. Lucie Bruijn, chief scientist of the ALS Association that is reaping the ice-bucket windfall” who “describe[d] a field that is forging ahead in multiple directions.” To give just one example, the Association might direct some of the money towards a clinical trial of “a compound that has been approved for people who have changing emotions in ALS — laughing and crying that’s exaggerated” to see if it might also, as anecdotal evidence suggests, improve swallowing. On a sobering note, Dr. Bruijn notes that “trials can be anywhere up from $25 million plus, just for perspective. So these are not small investments.”
2. This interview, by Geoff Colvin at Fortune, of Kathy Giusti, a former pharmaceutical executive who founded the Multiple Myeloma Research Foundation (MMRF), touches on similar themes. There are currently six drugs approved to treat multiple myeloma, “and the MMRF played a role in advancing all of them, with more in the pipeline. Life expectancy for many patients has doubled.” Giusti credits her foundation’s success to her decision to focus on funding research (to the exclusion of advocacy or public policy or healthcare), and, in particular, to focus on fixing a cancer research system that Giusti describes as “broken.”
3. This week also brought news of a recent development in Depomed’s struggle to protect its drug Gralise, a once-a-day version of gabapentin, from generic challengers. As Arlene Weintraub reports at FiercePharma, “Judge Joel Pisano of the U.S. District Court in New Jersey ruled that Actavis’s filing for FDA approval of generic Gralise infringes all seven of Depomed’s patents on the product. With this ruling, Depomed’s market exclusivity will be protected until 2024.” Depomed continues to litigate on another front, however. As Weintraub explains: “Simultaneously, Depomed has been in a war with the FDA, which approved Gralise under its Orphan Drug program but did not grant the company the 7 years of market exclusivity that normally goes along with orphan designation. Depomed sued the FDA in September 2012 seeking that exclusivity and is still awaiting a decision from a federal district court judge, according to the company’s latest quarterly filing.“
4. Also at FiercePharma, and also by Arlene Weintraub, this article about the Drug Enforcement Administration’s re-classification of “combination drugs containing hydrocodone . . . as Schedule II products, imposing on them the same restrictions that apply to pure hydrocodone, as well as oxycodone and morphine.” As Weintraub explains: “Vicodin and similar products used to be grouped in the less restrictive Schedule III, but recent DEA research showed that the drugs can be as addictive as pure opioids and “may lead to severe psychological or physical dependence,” a statement from the agency says. “Adding nonnarcotic substances like acetaminophen to hydrocodone does not diminish its abuse potential.”
5. Finally, at The Hill, Peter Schroeder reports that the Inspector General for Tax Administration has found a number of problems with the Internal Revenue Service’s implementation of the Affordable Care Act’s device tax. Among other things, “IRS agents were still having a hard time determining exactly which medical device manufacturers were subject to the tax” and “both the returns filed and revenue raised have come in well short of expectations.”
Filed under: Bioethics, Drugs & Devices, Food and Drug Administration (FDA)
The Ebola outbreak, which has claimed nearly 1,000 lives since its emergence in West Africa in December 2013, has brought renewed attention to policies surrounding the “compassionate use” of unapproved medications – i.e., the provision of unapproved medications to individuals outside the context of clinical trials. The issue rose to the forefront early last week when it was reported that two American aid workers in Liberia were treated with an “experimental drug that has never before been tested for safety in humans.” Both workers appeared to respond well to the drug, known as ZMapp. The drug was also provided to a Spanish priest, who died shortly thereafter; it was unclear whether he took the drug before he died. Following some controversy over the fact that the first three recipients of the drug were all foreign aid workers, on Tuesday it was reported that the drug’s manufacturer had sent its remaining stocks of the drug to Liberia for the treatment of two African doctors.
The FDA recognizes three broad categories of compassionate use, which are grouped under the general label of “expanded access.” These include expanded access for individual patients, including for emergency use; expanded access for intermediate-size patient populations; and expanded access for large patient populations under a treatment IND or treatment protocol. All of these categories are limited to patients who have serious or immediately life-threatening diseases or conditions for which no comparable or satisfactory alternative treatment exists. The FDA must determine that the potential benefits of the unapproved drug outweigh the potential risks, and that the risks “are not unreasonable in the context of the disease or condition to be treated.” In addition, the FDA must determine that allowing expanded access “will not interfere with the initiation, conduct or completion of clinical investigations that could support marketing approval of the expanded access use or otherwise compromise the potential development of the expanded access use.”
The FDA typically grants most requests for expanded access. When requests are denied, they most frequently involve emergency requests to use drugs that are not already undergoing clinical trials – precisely the situation facing ZMapp. On the one hand, it is understandable that the FDA would be cautious in allowing expanded access when no safety information exists and when there is no time to perform an exhaustive assessment. On the other hand, patients who are expected to die in a short time because they have no treatment alternatives may reasonably decide that they are willing to assume a high level of risk. Moreover, if clinical trials have not even been initiated, allowing expanded access cannot possibly interfere with the trials’ completion. While there is some possibility that systematically allowing expanded access in emergency situations would interfere with the initiation of trials, the manufacturer would have its own incentives to initiate trials once the expected demand for the drug is sufficiently high.
For now, all of these questions are moot, as existing supplies of ZMapp have reportedly been exhausted. When more supplies become available, further requests for expanded access are certain to arise. However, granting access to the drug through compassionate use programs is not a long-term solution. As an ethics panel convened by the World Health Organization concluded on Tuesday, the ideal way to introduce new Ebola medications is “in the best possible clinical trials under the circumstances in order to definitely prove their safety and efficacy or provide evidence to stop their utilization.”
Clinical trials of Ebola treatment will of course raise difficult questions in their own right. Unlike with expanded access, where everyone obtains the medication they have expressly requested, in a clinical trial some participants may be assigned to control groups that receive different medications or even placebos. Because no effective treatment for Ebola currently exists, placebo-controlled trials of new Ebola treatments would appear to be consistent with the ethical principles in the Declaration of Helsinki. Yet, particularly after American and Spanish foreign aid workers received the first doses of the experimental medications through compassionate use programs, asking African patients to enroll in placebo-controlled trials would surely be controversial. As the WHO panel delicately put it, the goal should be to devise “ethical ways to gather data while striving to provide optimal care under the prevailing circumstances.” The challenge will be to figure out effective strategies for carrying this out.
Filed under: Drugs & Devices, Monday Morning Recap
Here’s this week’s Monday Morning Recap, the post where we call out the drug and device law and policy developments that caught our eye and made us think over the previous week. You can see all of our previous Monday Morning Recap posts here.
1. This past week, Julie Steenhuysen at Reuters filed a report on “[t]he worst Ebola outbreak in history[.]” The outbreak “is heaping new pressure on U.S. regulators to speed the development of treatments for the deadly virus, which has killed more than 700 people since February. The U.S. Food and Drug Administration on Friday said in an emailed statement the agency ‘stands ready’ to work with companies and investigators working with patients ‘in dire need of treatment.’ . . . FDA’s statement follow calls by doctors fed up by the lack of progress on Ebola treatments, a market deemed too small to gain much attention by large pharmaceutical companies. Earlier this month, the agency put a hold on a Tekmira Pharmaceuticals Corp clinical trial of TKM-Ebola, one of the few Ebola treatments advanced enough to be tested in people. The hold prompted a North Carolina physician with family members in West Africa to say enough. ‘This should be the last Ebola epidemic without a cure,’ said Dr. Ahmed Tejan-Sie, an internist from Burlington.”
2. The FDA announced that it was “notifying Congress of its intention to publish a proposed risk-based oversight framework for laboratory developed tests (LDTs), which are designed, manufactured and used within a single laboratory.” Andrew Pollack at the New York Times explains: “Test systems or kits that are sold to hospitals, laboratories, doctor’s offices and the public have long been regulated as medical devices, giving the agency the opportunity to review them before they are marketed. But tests developed and performed by a single laboratory, with all samples being sent there, have typically not been. The F.D.A. had claimed the legal authority to regulate these so-called laboratory-developed tests, but said it was exercising ‘enforcement discretion’ not to do so. The agency said on Thursday that such discretion must end because circumstances had changed. Lab-developed tests once were fairly simple, often developed by a hospital for tests on its own patients. Now the tests can be complex and are being developed by companies and marketed widely.”
3. Also this past week, BioMarin Pharmaceutical announced that it had sold its rare pediatric disease priority review voucher to Regeneron Pharmaceuticals for $67.5 million. BioMarin was awarded the voucher in February “when it received approval of VIMIZIM®, a new biological product for patients with Mucopolysaccharidosis type IVA, also known as Morquio A syndrome.” Per Ron Winslow and Joseph Walker at the Wall Street Journal: “The voucher was the first to be issued under the pediatric incentive program, and also the first to change hands.” For additional background, see my post here.
4. At Pharmalot, Peter Loftus reported that a group of medical societies and pharmaceutical industry trade groups has written a letter to the Centers for Medicare & Medicaid Services (CMS) expressing concern that when the first Physician Payments Sunshine Act report is released later this month it will not provide the context needed to allow the public to understand the reasons for payments made by drug and device companies to physicians. CMS, Loftus writes, responded that it “does plan to make available the nature of payment for each payment or transfer of value made to a physician or teaching hospital and will also include context on the website.”
5. Finally, at CommonHealth blog Deborah Becker discusses a newly-released report from The New England Comparative Effectiveness Public Advisory Council that “contains some surprising findings about medication maintenance addiction treatment. It says that methadone, long used to treat heroin addiction, may be the most effective and cheapest treatment. The report . . . found that when comparing methadone with suboxone (Buprenorphine) or naltrexone (Vivitrol), more patients stayed in treatment longer if they were taking methadone. In follow-ups with patients three to 12 months after they first started taking medication, 63 percent of methadone patients were still in treatment, compared with 52 percent of those taking suboxone and 28 percent on naltrexone. Methadone also appears to be the cheapest maintenance medication, despite the requirement of having a health care facility daily distribute the drug to patients.”