The underlying policy is made explicit in the first paragraph of the Strategy’s Executive Summary (p4):
The policy of the United States Government is to seek regulatory approaches that protect health and the environment while reducing regulatory burdens and avoiding unjustifiably inhibiting innovation, stigmatizing new technologies, or creating trade barriers
Apart from clarifying the current roles of the FDA, EPA and USDA and setting out the path for future developments, both documents make it clear that they aim
to help the public understand how the safety of biotechnology products is evaluated and
to help businesses navigate the current regulatory structure.
This is the first time this particular technique has been used to produce a live, but I am not sure from an ethical standpoint the arguments are all that different. That said, for those deeply interested in the more philosophical question of harm to children and the propriety of best interests argument in light of Parfit’s Non-Identity Problem (my take here and here) it may matter whether mitochondrial replacement is done through Pronuclear Transfer or Maternal Spindle Transfer as argued quite well here.
The fact that the doctors are from New York, the Patients are from Jordan, and the procedure took place in Mexico is not insignificant. This is a form of medical tourism, a topic I wrote a book on, most similar to cases of fertility and stem cell therapy tourism I cover in the latter half of the book. Absent making domestic prohibitions extraterritorial, something that I argue is permitted by international law and justified in some instances, there is very little that a home country can do about this. The going abroad is likely in part at least a function of some U.S. laws on the subject Eli Adashi and I wrote about for JAMA prohibiting FDA from considering approval of the technology.
As I wrote on this blog in February in relation to the IOM report “whatever the US policy in a world where medical tourism is possible and other countries adopt their own systems, so long as not everyone adopts the approach of the US some of these problems will manifest no matter what. So this is about harm reduction not harm avoidance.” This was a bit quicker than even I thought, but is not surprising. More generally if your concern about MRT is harm to offspring and transmission to future generations, people born elsewhere through the technology will inevitably enter the United States and/or marry, and procreate with U.S. citizens who themselves become U.S. citizens. To sound a bit X-Files about it “THEY WILL BE AMONG US!” This is a great example of the limits of unilateral regulation in a world of globalized health care.
Interesting that it was a male birth. This may be coincidence or in keeping with the IOM recommendation that only male embryos be transferred (to get rid of germ line transmission). Eli Adashi and I raised some ethical questions in Nature about whether that was an ethically problematic form of sex selection or not but in the reporting I have seen so far it has not been clear that they used only male embryos on purpose.
I wish we could stop calling it in the media “Three Parent IVF” or “Three Parent Reproduction.” That assumes the answer to what I think of as a subtle and interesting set of questions — is the mitochondrial donor a “parent” and what sense of the word do we mean.
Nathan Nascimento thinks that right-to-try laws aimed at the terminally ill are sound public policy. He is wrong.
Mr. Nascimento’s commentary misrepresents the complexities of the drug development process and the issues surrounding granting access to experimental medicines before they have been fully tested.
The overarching issue, despite his rhetoric to the contrary, is that the safety and efficacy profile of a new medicine is not sufficiently understood until after the drug has completed at least a pivotal Phase 3 clinical trial.
The underlying principle of every clinical development program is to understand, via testing first for safety usually in a small number of patients afflicted with the target condition, and, subsequently, in increasing numbers of patients, the benefits as well as the risks of new medicines. Like it or not, this is a time-consuming, expensive, but appropriate and necessary process. […]
The United States is in the midst of what many are calling an opioid epidemic. According to the American Society of Addiction Medicine, more than 1.9 million people in the U.S. have a substance use disorders involving prescription pain medications, and another 580,000 have substance abuse issues with heroin. The human costs of these rates of addiction are staggering. Of the approximately 50,000 lethal drug overdoses that happen each year, almost 20,000 are the result of prescription opioids, and another 10,000 are the result of heroin. While prescription painkillers traditionally aren’t as dangerous as heroin, the connection between the two is well established. According to a 2013 survey, about 80% of heroin users started out abusing opioid painkillers.
Despite continued efforts at nearly every level of government, the rates of opioid addiction and overdose have continued to climb. However, researchers have identified an unlikely ally that may have quietly been slowing the rise of opioid use in certain states: medical marijuana.
A study recently released by Columbia University’s Mailman School of Public Health suggests that medical marijuana availability is linked to decreases in opioid usage. The study looked at opioid prevalence in autopsy reports from fatal car accidents over 14 years, and found that states that passed medical marijuana laws in that period saw a relative decrease in opioid prevalence compared to states that didn’t. While this study is making a splash, it’s just the most recent piece in a long line of research into the connection between medical marijuana availability and opioid use. One study published in Health Affairs in July showed that states which implemented medical marijuana laws between 2010-2013 saw a significant decrease in Medicare Part D prescriptions filled for medications for which marijuana is a possible alternative therapy — including opioids. Another study from 2014 showed a 25% decrease in deaths from prescription pain medication overdoses in states that implemented medical marijuana laws. Continue reading →
This morning, the FDA finally reached a decision in the closely watched case of Sarepta Therapeutics and its drug for the treatment of Duchenne Muscular Dystrophy (DMD). The FDA granted accelerated approval to Sarepta’s drug, Exondys, on the condition that Sarepta complete a new trial demonstrating the drug’s clinical effectiveness. As regular FDA observers already know, Exondys’ path to approval has been highly contentious. The key clinical trial used to support approval contained just twelve patients and no placebo, and the FDA Advisory Committee voted against both full approval of the drug and accelerated approval. The FDA’s 126-page Summary Review, released today with their approval letter, reveals the intense disagreements within the agency over Exondys’ approval. FDA staff scientists charged with reviewing the drug recommended against approval but were overruled by Dr. Janet Woodcock, Director of the Center for Drug Evaluation and Research. FDA Commissioner Califf deferred to her decision.
Sarepta presented the FDA with a series of bad options. DMD is a rare, heartbreaking, and ultimately fatal genetic disease with no other real treatments, and it is clear why patients and their families would fight for access to anything that might work. At the same time, the FDA has rarely if ever approved a drug on less evidence than that provided by Sarepta, and approving the drug might send a dangerous signal to both the public and other companies investigating rare disease drugs. The FDA has now made its choice. Where do we go from here? In my view, there are at least three key issues to watch going forward. Continue reading →
For weeks now, the list price of Mylan’s EpiPen ($600 for a two-pack) has been exhaustively covered by journalists, debated by academics, and skewered by policymakers as an example of the pricing excesses of even generic pharmaceutical companies. Mylan’s latest response to the outrage? Announce that soon, it will be launching a generic EpiPen at a list price of $300 for a two-pack. I and others who study these issues full time cannot understand why Mylan thought this would work to quell the widespread indignation over its pricing practices.
The first red flag came when Mylan stated it would launch the product “in several weeks.” I often find myself defending the FDA against charges that it is too slow to approve new technologies, but let’s face it: it would be shocking news if they were able to approve a new version of anything in just a few weeks. Mylan has not had this in the works for months, so it seems that the new generic product is literally identical to the branded EpiPen – just with a different label. So, essentially, Mylan is preparing to cut the price of its product in half. (Even though that’s still higher than the price was just three years ago, before Mylan began its regular price hikes, and even though this should make us question their justifications for the $600 price.) Great, right? Not so fast.
What reasons (other than public relations) might Mylan have for introducing an authorized generic of this type and how might they attempt to use the two products to maintain their current level of revenues? By bringing the first generic EpiPen to market, Mylan has now planted its flag in the generics space. Although epinephrine (the drug inside the EpiPen) is now generic and cheap to produce and sell, companies do seem to find it difficult to replicate the device portion of the EpiPen, with Sanofi’s product recently removed from the market due to dosing issues and Teva’s application for a generic denied by the FDA with no public explanation just a few months ago. Mylan has now benchmarked a new price for those products if they return – they must price below $300 for a two-pack to compete effectively with Mylan. Continue reading →
Our guest this week is Ameet Sarpatwari, an Instructor in Medicine at Harvard Medical School and an Associate Epidemiologist at Brigham and Women’s Hospital based in the Program On Regulation, Therapeutics, And Law (PORTAL) within the Division of Pharmacoepidemiology and Pharmacoeconomics. Ameet’s research focuses on the effects of laws and regulations on therapeutic development, approval, use, and related public health outcomes. He is currently examining the public health implications of variation in state drug product selection laws, the risk of re-identification under HIPAA pathways for data sharing for post-approval drug research, and the comparative safety and effectiveness of biosimilars.In the lightning round, Nic addressed the Notice Act and ongoing controversy over hospitals’ use of “observation status” to dodge readmissions penalties and game reimbursements. We also mentioned the strange politics of bill naming. (One also wonders what exactly vulnerable patients are supposed to do once they receive notice that they could soon be hit by huge bills.)
Our conversation with Ameet focused on his many articles on counter-detailing, medical research ethics, the opioid crisis, and large firms’ misues of the FDA’s regulatory system. Links to all are available at his website.
The Week in Health Law Podcast from Frank Pasquale and Nicolas Terry is a commuting-length discussion about some of the more thorny issues in Health Law & Policy. Subscribe at iTunes, listen at Stitcher Radio, Tunein and Podbean, or search for The Week in Health Law in your favorite podcast app. Show notes and more are at TWIHL.com. If you have comments, an idea for a show or a topic to discuss you can find us on twitter @nicolasterry @FrankPasquale @WeekInHealthLaw
The FDA has issued a final guidance on low risk wellness devices, and it is refreshingly clear. Rather than applying regulatory discretion as we have seen in the medical app space, the agency has made a broader decision (all usual caveats about non-binding guidances aside) not to even examine large swathes of wellness products to determine whether they are Section 201(h) devices. As such, this guidance more closely resembles the 2013 guidance that declared Personal Sound Amplification Products (PSAPs) not to be medical devices (aka hearing aids).
The FDA approach to defining excluded products breaks no new ground. First, they must be intended for only general wellness use and, second, present a low risk. As to the former, FDA has evolved its approach to referencing specific diseases or conditions. Make no such reference and your product will sail through as a general wellness product. Thus, claims to promote relaxation, to boost self-esteem, to manage sleep patterns, etc., are clearly exempt. On the other hand, the agency will clearly regulate products that claim to treat or diagnose specific conditions. Continue reading →
Under the grant, BU Law will coordinate more than $350 million in new funds for R&D over the next five years, in partnership with BARDA, NIAID, the Wellcome Trust, the AMR Centre, MassBio, the California Life Sciences Institute and the Broad Institute at Harvard and MIT. Kevin Outterson is the PI and Executive Director of CARB-X.
While the bulk of the project funds pre-clinical R&D, we are also interested in the role of law, IP and other innovation incentives, using the unique dataset that CARB-X will generate.
July has been a busy month for those following the controversy around off-label promotion of drugs and devices. As many on this blog know, federal law requires that prior to marketing any drug or device, companies must prove to the FDA’s satisfaction that it is safe and effective for all intended uses. If the company reveals that it intends unapproved uses, sales of the drug or device are illegal. Nonetheless, physicians can prescribe “off-label,” and companies are free to sell for those known-but-not-intended purposes.
This carefully-wrought policy may seem convoluted, but it serves important epistemic and economic purposes, as I have argued elsewhere. This month, I have a new draft paper on SSRN, assessing recent assertions of a First Amendment right to promote for uses not approved by the FDA, and consider whether such a right would be equally applicable to drugs that have no FDA-approved label at all. I worry that the entire pre-market approval regime may be at stake. Feedback on that intentionally-provocative analysis is quite welcome.
On Wednesday, two medical device company executives, were convicted of promoting a product “to deliver steroid medications to patients’ sinuses, though it was only approved by the U.S. Food and Drug Administration for keeping sinuses open.” The prosecutors thought the case was particularly egregious, because the company had intended the broader use to deliver medicine all along, but sought to mislead the FDA, denying it the chance review the safety and efficacy of the real intended use. The jury instructions and verdict form are particularly interesting, to see how the government’s trial strategy avoids the holding of a Second Circuit case of Caronia, which overturned a conviction on First Amendment grounds. I’ll return with some analysis later. Continue reading →
The American Society for Law, Medicine & Ethics (ASLME) is pleased to announce the second annual bioIP Faculty Workshop on May 5, 2017 at Loyola University of Chicago School of Law in Chicago, IL.
The Workshop offers a unique opportunity for three scholars in their first decade of teaching to present their work in progress for in-depth critique and commentary by respected senior scholars in the field.
Topics for the workshop are at the intersection of biotechnology, life sciences, food and drug law, and intellectual property (hence, bioip), broadly defined. A Review Committee comprised of faculty from the Boston University School of Law, Georgia State University College of Law, and the Loyola University Chicago School of Law will select papers for the Workshop in a blind process. Papers should present an original thesis and contribute to scholarly literature. The Workshop will not review published work.
Scholars with less than ten years of teaching experience, including VAPS and Fellows, are eligible for participation in the Workshop. Those interested in participating should submit an abstract (up to 750 words) of the proposed paper (without identifying details) along with a c.v. to Ted Hutchinson, Executive Director of the ASMLE at firstname.lastname@example.org by Oct 14, 2016.
Selected abstracts will be announced later in Fall 2016 with the full draft papers due by April 1, 2017. The organizers will cover reasonable travel and lodging expenses for selected scholars.
Below are the papers identified from the month of June. The selections feature topics ranging from lessons from the history of randomized controlled trials, to the prevalence and predictors of generic drug skepticism among physicians, to the availability and dissemination of results from FDA-mandated post-approval studies of medical devices. A full posting of abstracts/summaries of these articles may be found on our website.
The Food and Drug Administration (FDA) has recently taken three steps toward providing consumers with more and better information about food products that the agency regulates. First, in response to several citizen petitions, the agency requested comments on the use of the term “natural” on food labeling. Second, the agency issued a statement in early May indicating that “in the near future” it planned to solicit comments reevaluating how nutrient content claims are regulated — including the term “healthy.” And third, the agency issued a final rule on an updated Nutrition Facts label, with which large companies must comply by July 2018.
With each of these actions the FDA is attempting to ensure that information provided to consumers by food manufacturers comports with the latest scientific understanding about food components. Indeed, the updated nutrition facts label will provide important information and potentially allow consumers to make more informed choices about what they eat. The agency, however, has set itself a far trickier task in defining words such as “natural” and “healthy.”
In the past, the FDA has repeatedly declined to define the term “natural.” The Nutrition Labeling and Education Act (NLEA) of 1990 required the FDA to standardize definitions for nutrient content claims, like “fat free” or “high in fiber,” and to limit the use of health claims, like “heart healthy” (21 U.S.C. §§ 343(r)(1)(A), (B)). The word “natural,” however, does not fit into either of these categories.
The Petrie-Flom Center is pleased to announce the availability of a new resource on its website: the legislative history of the Biologics Price Competition and Innovation Act (BPCIA). The BPCIA, passed as part of the Affordable Care Act (ACA), created a pathway for the approval of biosimilar products and awarded innovator biologic companies twelve years of exclusivity for their products. Modeled after the Hatch-Waxman Act of 1984, which established our system of generic small-molecule drug approvals while simultaneously creating a five-year period of exclusivity for new drugs, consideration of the BPCIA’s history is often lost in the discussion over the ACA’s history as a whole. This resource selects only those documents relating to the BPCIA and may thus prove particularly useful for scholars of FDA law.
This new resource comes at an opportune time, as the courts and Congress have both turned their focus to the provisions of the BPCIA. In 2015, the Federal Circuit issued a divided opinion interpreting the BPCIA’s instructions to biosimilar and innovator drug sponsors, and that opinion has now been appealed to the Supreme Court. Just last month, the Justices called for the views of the Solicitor General on this question, a step which may significantly increase the likelihood of an eventual cert grant. At the same time, several members of Congress have introduced a bill that would decrease the BPCIA’s grant of exclusivity from twelve years to seven years, bringing it more in line with the five-year period in the Hatch-Waxman Act or seven-year period in the Orphan Drug Act. The twelve-year period of exclusivity may have been the most contentious aspect of the BPCIA as passed, with even the FTC arguing strongly against such a lengthy period at the time.
Members of the public may also be interested in an article written by Professor Erika Lietzan and colleagues providing an excellent analysis of the BPCIA’s legislative history.
CRISPR-Cas9 has drawn applause for being one of the biggest technological advancements in recent history, but it also raises important ethical issues. This technology, an efficient genome editing tool, is now taking its next big step: CRISPR might be going in for human trials for its potential use in fighting cancer (namely, by altering T-cells to treat cancer cells as “foreign bodies”). Trials have been proposed to be conducted at three sites over a period of two years. The Recombinant DNA Advisory Committee (RAC) at the NIH gave its unanimous approval for these trials earlier this week. Now permissions from FDA and Institutional Review Boards remain before this becomes a reality.
Whether or not the studies will get that approval is uncertain. The RAC already expressed concerns about conflict of interest, and the ghosts of the trial involving Jesse Gelsinger 17 years ago at UPenn have resurfaced. There are also important questions about risks, uncertainty, and informed consent from the research participants.
The scientific community and regulators have been wary of the gravity of the implications of genome editing. When a Chinese study involving gene editing in human embryos was submitted for publication, there was a hue and cry over whether journals should accept it, given ethical concerns. Currently, there is a moratorium on altering DNA that will subsequently pass on to new generations. Even when the CRISPR technology was approved for editing human embryos in the UK, it was mandated that embryos be destroyed within fourteen days.
Earlier today, the NIH rejected a request filed by consumer groups including Knowledge Ecology International (KEI) to exercise the government’s march-in rights on an expensive prostate cancer drug, Xtandi. Xtandi costs upwards of $129,000 per year, and KEI had asked the government to exercise its rights under the Bayh-Dole Act, which specifies a range of conditions under which the government may require a patentholder to grant licenses on reasonable terms to others to practice the patent. Specifically, the government may require such a license where “action is necessary to alleviate health or safety needs which are not reasonably satisfied,” 35 U.S.C. § 203(a)(2), or where the benefits of the invention are not being made “available to the public on reasonable terms,” 35 U.S.C. § 201(f).
For some time now, there has been debate over the question of whether high prices for pharmaceuticals are a sufficient trigger to invoke the use of march-in rights under these clauses of the statute. I don’t take a position on that question here. Instead, I want to ask whose responsibility it is to decide that question. Congress has the legal right to do so, but it seems unwilling or unable to. The agencies in question have recently declined to, even assuming they have the power to interpret the statute in that way. And so we might look to the courts. But there’s a puzzle here: it’s not clear that anyone can ask a court to decide whether high prices meet the statutory requirements unless an agency actually decides that high prices meet the statutory requirements.
Earlier this week, a bipartisan group of Senators introduced the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, a bill designed to speed generic drug approvals (and thus lower drug costs) by removing a delaying tactic some branded drug companies use to impede the generic approval process. Essentially, branded drug companies sometimes refuse to sell samples of their drugs to generic companies who want to come to market, preventing them (for at least a time) from performing the necessary bioequivalence testing and extending their market dominance. Sometimes companies try to hide behind a regulatory program, Risk Evaluation or Mitigation Strategies (REMS), in claiming that they legally cannot provide such access. Other times, such as in Martin Shkreli’s case, no such excuse exists and the company simply refuses to provide access.
These delaying tactics have received substantial attention from both scholars (Jordan Paradise’s work can be found here) and lawmakers. This is Congress’ third attempt at addressing the situation, although as Ed Silverman helpfully notes at Pharmalot, the previous attempts would have only dealt with REMS delays, not Shkreli-like closed distribution systems. By contrast, the CREATES Act would require brand-name companies to provide access to samples of their drugs, whether subject to a REMS or not, on “commercially reasonable, market-based terms” or face potential civil action from the generic drug company in question. There’s already been a lot of commentary on the bill, including a particularly helpful blog post from Geoffrey Manne providing background on REMS abuses and on why antitrust law has not sufficed to solve the problem. Here, I want to add two points that I haven’t yet seen in the discussion: one about drug shortages and another about remedies.
This week we spoke with Rachel E. Sachs, who will join the faculty of the Washington University in St. Louis School of Law in Fall 2016. Rachel earned her J.D. in 2013 magna cum laude from Harvard Law School, where she was the Articles Chair of the Harvard Law Review and a student fellow with both the Petrie-Flom Center and the John M. Olin Center for Law, Economics, and Business. Rachel has also earned a Master of Public Health from the Harvard School of Public Health. We focused on Rachel’s work on drug pricing and innovation for global health. As part of a broader academic agenda for developing access to knowledge, Rachel’s work illuminates the many trade-offs involved in optimizing innovation law. She has also illuminated the importance of “innovation beyond IP,” and the importance of legal synergies in accelerating or impeding innovation.
Listen here! The Week in Health Law Podcast from Frank Pasquale and Nicolas Terry is a commuting-length discussion about some of the more thorny issues in Health Law & Policy. Subscribe at iTunes, listen at Stitcher Radio, Tunein and Podbean, or search for The Week in Health Law in your favorite podcast app. Show notes and more are at TWIHL.com. If you have comments, an idea for a show or a topic to discuss you can find us on twitter @nicolasterry @FrankPasquale @WeekInHealthLaw
Each month, members of the Program On Regulation, Therapeutics, And Law (PORTAL) review the peer-reviewed medical literature to identify interesting empirical studies, in-depth analyses, and thoughtful editorials on pharmaceutical law and policy.
Below are the papers identified from the month of May. The selections feature topics ranging from a review of progress in the fight against multidrug-resistant bacteria, to the role regulators can play in increasing the affordability of drugs, to an assessment of the strength of the surrogate-survival relationship for cancer drugs approved on the basis of surrogate endpoints. A full posting of abstracts/summaries of these articles may be found on our website.
I am going to discuss some highlights of their just released report, but this is far from exhaustive and you should read the whole report.
For the non-cognoscenti this is the most important revision to the rules for U.S. human subjects research since their inception. The report is largely unfavorable to several key proposed rule changes on my first read, but you should read it yourself to make up your own mind.
I’ll share some choice passages from the analysis
The results of our review (Table 2) find significant opposition to most major proposals, with mixed support for mandated use of a single IRB and extending the Common Rule and greater support for the concept of standard security safeguards. In addition, a number of responses suggested that the NPRM is overly complex, poorly written, and not supported by data; highlighted areas that could have a substantial impact on a final rule but were not included in the NPRM (e.g., proposed security safeguards, a consent template, a list of minimal risk studies and a decision tool); and suggested that some of the proposals would adversely affect human health with little perceived benefit.
The majority of responses, approximately 1,520, addressed one or more of the proposed changes detailed above involving non-identified biospecimens. Of these responses, 94 – 100% of patients and members of the research community, including researchers, universities, medical centers and industry, opposed the changes. Those commenting suggested that the proposed changes will significantly reduce the availability of biospecimens for research, will have a significant negative impact on medical advances, and will adversely affect human health. Per one patient, “I am asking for life saving policy not life ending policies.” From a biorepository, “Respecting autonomy at the expense of patient lives is a significant ethical concern.”
More surprising was their finding that “Among members of the general public, 55% opposed and 45% supported one or more of the major proposed changes related to biospecimens.” (They do a better breakdown of the various sub-constituencies in the report).