Check out the August 22nd edition of the Petrie-Flom Center’s biweekly e-newsletter for the latest on events, affiliate news and scholarship, and job and fellowship opportunities in health law policy and bioethics.
In Part II of this blog on legal issues relating to the revival of phage therapy I discussed the US Supreme Court’s decisions in Myriad and Prometheus, which might present major obstacles to the patentability of phage-related technology (a more detailed analysis of the Myriad and Prometheus decisions is available here).
Yet, all is not lost. As indicated in Part II, Myriad does not directly affect the patentability of synthetically modified biological compounds and Prometheus would still allow patents on inventive applications of natural processes and correlations that add new features to “natural laws”. Thus there still seems to be considerable leeway for patenting within the area of page therapy.
One example, mentioned in a recent Nature article, could be the skillful selection and precise combination of different phages in order to attack one specific type of bacteria. Such selections, however, would face a tough battle to overcome the “additional features that add significantly more” and “not identical” thresholds set by Prometheus and Myriad. Another example with even better prospects for patentability relates to genetically modified phages that are – due to human intervention – enabled to target only specific bacteria. This technology was recently presented by MIT researchers at the 2014 American Society for Microbiology Meeting. The researchers led by Timothy Lu had genetically engineered phages that use a DNA-editing system called CRISPR to target and kill only antibiotic-resistant bacteria while leaving other susceptible cells untouched. The significant engineering and alteration of natural products and processes involved in such inventions would most likely meet both the Myriad and Prometheus standards.
Yet, while the USPTO has recently issued new patent eligibility guidance and the CAFC has begun to directly apply Prometheus and Myriad to reject patent claims in biotech cases (e.g. In re Roslin), many questions remain unsolved. In particular, it is still not sufficiently clear exactly how much modification is required to render a molecule or method sufficiently distinct from naturally occurring product and processes. And even if the patent-eligibility threshold could be met in extraordinarily circumstances, the claimed invention would still have to fulfil other patentability requirements such as novelty, non-obviousness and the written description-requirements. The threshold for these requirements, however, have been heightened in recent years (see e.g. KSR v. Teleflex (2007) , Nautilus (2014) etc.). Considering that phage therapy is almost a century old with a substantial common general knowledge and a state of the art employing routine methods, these crucial requirements might still prevent the patentability of many useful applications.
Check out the August 8th edition of the Petrie-Flom Center’s biweekly e-newsletter for the latest on events, affiliate news and scholarship, and job and fellowship opportunities in health law policy and bioethics.
Three days ago I commented on a couple of legal issues raised in the recent Nature report “Phage therapy gets revitalized” by Sara Reardon. One challenge concerns the reluctance of pharma companies to broadly invest in the development of phage therapies. As pointed out in the report, this does of course very much (but not only) relate to the question of patentability. Various aspects might present obstacles to the patentability of technology relating to phage therapy. To not complicate the discussion and considering recent developments I decided to focus on some of aspects under US patent law.
Like in Europe, the first door to patentability that phage-related technology would need to pass concerns patent eligibility. In the last years the US Supreme Court has rendered an astonishing number of fundamental patent-decisions, including not less than four (!) landmark judgments on patent eligibility, i.e. Bilski v. Kappos (2010), Mayo v. Prometheus (2012) , AMP v. Myriad (2013) and Alice v. CLS (2014). Most relevant in this context are the decisions in Prometheus and Myriad.
Last week I blogged about recent publications concerning the global battle against anti-microbial resistance (AMR). I did not mention a recent paper published in the June 2014 issue of Nature, which describes how European and U.S. researchers and authorities are increasingly considering clinical research in unconventional areas to fight AMR. The news-report “Phage therapy gets revitalized” by Sara Reardon concentrates on the use of viruses (bacteriophages) to battle bacteria. The idea is not new, but apart from some applications in the former Soviet Union, it never was established as a major research area elsewhere. In particular the paper examines the European Phagoburn project, which is the first large, multi-centre clinical trial of phage therapy for human infections, funded by the European Commission. It involves a phase I-II trial of using viruses for the treatment of bacterial infection following burns. The European Union (EU) is contributing €3.8 million (US$5.2 million) to the Phagoburn study demonstrating that it is taking the approach seriously. Meanwhile, the US National Institute of Allergy and Infectious Diseases announced in March 2014 that it regards phage therapy as one of seven key areas in its strategy to fight antibiotic resistance.
So far Western practice has concentrated on treating complex or unidentified infections with broad-spectrum antibiotics. These antibiotics would typically eliminate multiple types of bacteria, including those who have beneficial effects to the human organism. Despite resulting in direct negative consequences for patients, e.g. gastrointestinal disorders, these “atomic bomb” approaches can result in biological niches where resistant “bad bugs” can prosper. This is the reason why scientists are turning towards more targeted approaches. This is where phage therapy comes into play. Like “guided missiles”, phage-therapy has the ability to kill just species of bacteria or strain. Quoting the US virologist Ryland Young and the head of the scientific council at the Eliava Institute in Tblisi (Georgia), Mzia Kutateladze, the Nature report explains how nature offers an almost unlimited source of different phages and that so far no identical phages have ever been found. For this reason it is fairly simple to identify a particular phage for a bacterial target. If the bacterium should become resistant against that particular phage, researchers would modify the viral cocktails that are used for treatment by adding or substituting phages. At the Eliava Institute such updates occur – according to the report – approximately every 8 months and the scientists would not be fully aware of the precise combination of phages in the cocktail.
In light of these advantages the recent interest of US and EU stakeholders in phage therapy comes as no surprise. However, the scientific and legal challenges confronting these projects are complex. After all we are talking about viruses here, which triggers alarm bells with regard to public perception, safety concerns, and the regulation of relevant research. It also appears questionable if – or under what circumstances – regulatory authorities would be willing to grant market approval for such a rapidly changing product like in the case of e.g. influenza vaccines. Another significant problem for the development of new phage therapies, also addressed in the paper, lies in the reluctance of pharmaceutical companies to invest into the field. The potential obstacles for more private involvement in phage therapy are many and range from considerable risks of failure, reputational damage, and unforeseeable side-effects to insufficient certainty with regard to intellectual property protection and guarantees of a profit.
One of my previous blogs discussed the growing threat of antimicrobial resistance (AMR). I concluded that antimicrobial resistance is a growing and complex threat involving multifaceted legal, socio-economic and scientific aspects. This requires sustained and coordinated action on both global and local levels.
A recent medical review on drug resistant tuberculosis supports these findings and provides further fodder to the debate. In their study, which was published in April 2014 in The Lancet – Respiratory Medicine, the authors analyzed the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medico-legal aspects of extensively drug-resistant tuberculosis and other resistant strains. In particular, the authors discussed the increasing threat of functionally untreatable tuberculosis, and the problems that it creates for public health and clinical practice. The paper concludes that the growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis—and increased funding to strengthen global control efforts, research, and advocacy—even more pressing.
This was also recognized in the recent WHO’s Global Surveillance Report on AMR, which was published this April. It is the first WHO report that studied the problem of AMR on a global level. Noting that resistance is occurring across many different infectious agents, the report concentrates on antibiotic resistance in seven different bacteria responsible for common, serious diseases such as bloodstream infections (sepsis), diarrhoea, pneumonia, urinary tract infections and gonorrhoea. The results demonstrate a wide-spread growth of resistance to antibiotics, especially “last resort” antibiotics. In particular the report reveals that this serious threat is no longer a mere forecast for the future. AMR is a contemporary problem in every region of the world and has the potential to affect anyone, of any age, in any country. Consequently the WHO report concludes that antibiotic resistance is now a major threat to public health that needs to be tackled on a global level.
by Donald W. Light
Few people know that new prescription drugs have a 1 in 5 chance of causing serious reactions after they have been approved. That is why expert physicians recommend not taking new drugs for at least five years unless patients have first tried better-established options and need to. Faster reviews advocated by the industry-funded public regulators increase the risk of serious harm to 1 in 3. Yet most drugs they approve are found to have few offsetting clinical advantages over existing ones.
Systematic reviews of hospital charts by expert teams have found that even properly prescribed drugs (aside from misprescribing, overdosing, or self-prescribing) cause about 1.9 million hospitalizations a year. Another 840,000 hospitalized patients given drugs have serious adverse reactions for a total of 2.74 million. Further, the expert teams attributed as many deaths to the drugs as people who die from stroke. A policy review done at the Edmond J. Safra Center for Ethics at Harvard University concluded that prescription drugs are tied with stroke as the 4th leading cause of death in the United States. The European Commission estimates that adverse reactions from prescription drugs cause 200,000 deaths; so together, about 328,000 patients in the US and Europe die from prescription drugs each year. The FDA does not acknowledge these facts and instead gathers a small fraction of the cases.
Perhaps this is “the price of progress”? For example, about 170 million Americans take prescription drugs, and many benefit from them. For some, drugs keep them alive. If we suppose they all benefit, then 2.7 million people have a severe reactions, it’s only about 1.5 percent – the price of progress?
However, independent reviews over the past 35 years have found that only 11-15 percent of newly approved drugs have significant clinical advantages over existing, better-known drugs. While these contribute to the large medicine chest of effective drugs developed over the decades, the 85-89 percent with little or no clinical advantage flood the market. Of the additional $70 billion spent on drugs since 2000 in the U.S. (and another $70 billion abroad), about four-fifths has been spent on purchasing these minor new variations rather than on the really innovative drugs.
In a recent decade, independent reviewers concluded that only 8 percent of 946 new products were clinically superior, down from 11-15 percent in previous decades. (See Figure) Only 2 were breakthroughs and another 13 represented a real therapeutic advance.
Why would Congress have limited Affordable Care Act subsidies to residents of only some states – those that establish their own insurance exchanges? The law authorizes credits for the purchase of insurance “through an Exchange established by the State under section 1311.” The D.C. Circuit found that this wording excludes federally established exchanges and that Congress might have intended this to induce states to establish their own exchanges rather than letting the federal government take over.
But the Court acknowledged that there is no evidence of such intent in the legislative history. And such a purpose would conflict with the ACA’s overall goal of extending health insurance access to all Americans.
With no legislative history as a guide, is there another plausible explanation of Congressional intent? Is the best answer to the D.C. Circuit’s opinion that the phrase was a drafting error, as the dissent seems to imply? Why else would it have found its way into the law?
Inartful though it may be, the wording can be seen to serve a different purpose that is consistent with the rest of the ACA. It can be understood not as a way to distinguish exchanges established by a state from those established by the federal government but to distinguish those established publicly from those created privately.
By Greg Curfman and Holly Fernandez Lynch
It was as if lightning had struck twice in the same place.
On Tuesday two pivotal federal circuit court opinions that could dramatically impact the future of Obamacare were unexpectedly issued within hours of each other. And what’s more, the two opinions reached opposite conclusions on the same question, setting the stage for further appeals and possible Supreme Court review, potentially bringing the Affordable Care Act (ACA) before the high court for the third time since its passage.
At issue in both circuit court cases was the legality of providing subsidies in the form of Internal Revenue Service tax credits for the purchase of health insurance on the federal exchange (Healthcare.gov).
In a decision that stunned Obamacare supporters–but elated opponents–a three-judge panel of the Federal Appeals Court for the DC Circuit ruled in Halbig v. Burwell that the purchase of health insurance on the federal exchange may not be subsidized by IRS tax exemptions. This judgment would leave millions of Americans with earnings between 133% and 400% of the federal poverty level without affordable health insurance, and it would also threaten the viability of the employer mandate.
In contrast, in a unanimous (3-0) opinion in a nearly identical case, King v. Burwell, the Federal Appeals Court for the Fourth Circuit in Richmond, VA, came to the opposite conclusion.
By Abbe Gluck
I had hope to take a day off blogging about Halbig and King (the ObamaCare Subsidies cases), but I cannot allow another new, and inaccurate, narrative about ObamaCare to take hold. Over at Volokh, Ilya Somin argues that the holding in Halbig is not absurd because Congress uses statutory schemes all the time that try to incentivize states to administer federal law (and penalize them if they don’t). It is true we see schemes like that all the time–Medicaid is a prime example–but the insurance exchange design at issue in these cases is NOT one of them. This federalism argument was made before the D.C. Circuit and even Judge Griffith didn’t buy it in his ruling for the challengers. I tried to dispel this myth back in March, when I wrote the following on Balkanization. As I said there, this isn’t Medicaid—it’s the Clean Air Act.
In response to the SCOTUS decision granting Wheaton College a preliminary injunction against having to comply with the terms of the HHS accommodation available to non-profit religious organizations who object to covering contraceptives for their employees (i.e., submitting a form to their insurance providers), the Obama Administration has announced that it will revise the terms of that accommodation. Instead of requiring objecting employers to provide the form and notice to insurers or third party administrators of self-insured health plans so that they can jump in to provide free coverage directly to employees, HHS will issue new regulations in short order, the details of which remain to be worked out, but will likely allow nonprofit institutions to write a letter stating their objections, rather than filling out the form (see the WSJ story here). This will leave the government to make sure employees are not left without contraceptives coverage.
I may be oversimplifying things, but I think this extended accommodation really isn’t such a big deal. It seems to just add the government in as a middleman between the objecting employer and the insurer or third party administrator that was responsible for providing coverage under the original accommodation. In other words, before, nonprofit religious employers with an objection had to fill out the form and give it directly to their insurers; after the modification, those employers could just let the government know, and presumably the government will notify their insurers. A bit more bureaucracy, but shouldn’t be too big of a problem – probably just a drop in the bucket of the massive ACA bureaucracy, and potentially unnoticeable by the women seeking free contraceptives. That is unless the employers claim that even this approach leaves them complicit in violation of their religious beliefs.
Since SCOTUS’s substantial burden test as applied in Hobby Lobby focused on the hefty fines for noncompliance, rather than the extent to which the employers’ religious beliefs were directly v. indirectly burdened, the complicity point is an important one to keep an eye on. Will religious employers be satisfied with simply adding another link to the causal chain? Perhaps (and I hope). Technically, all they would be asked to do is announce to the world that they have a religious objection. What the government does with that information is beyond their control. If this works out, the revised accommodation could also be extended to the closely held for-profit corporations with religious objections to contraceptives coverage that SCOTUS determined could not be forced to comply with the mandate, such that their employees too could retain access.
So let’s see what HHS can come up with. Haters gonna hate, as they say, so I’m sure there will be more litigation on this, but hopefully we’re nearing a solution – and I think a good compromise. The bigger issue will be dealing with all those other services that must be included as essential benefits or preventive services to which religious employers may object, and to which insurers are likely to object to providing free coverage. But let’s see if the ACA lives to die another day after Halbig and King.
This morning the D.C. Circuit ruled that the ACA “unambiguously restricts the section 36B subsidy to insurance purchased on Exchanges “established by the State.” (See opinion here.) In other words, the court ruled that the subsidies that make insurance on federally-operated exchanges affordable are illegal.
In the news and blog coverage this has already received, the possibility of this decision being reversed “en banc” has been mentioned. (See here, here, and here for news, here and here for blogs. For other blog reading on the opinion itself, see here and here.) Having written a bit elsewhere about the logistics of the DC Circuit (see here), I thought I would chime in with specifics about exactly how the decision whether to rehear the case en banc, and en banc rehearing, would work.
The North Carolina Law Review has just released its symposium issue on Health Care Decisions in the New Era of Health Care Reform, featuring several Bill of Health contributors and friends of the Petrie-Flom Center. Take a look at the description and contents below. [HT: Richard Saver, who served as faculty advisor for this issue, alongside Joan Krause.]
Optimal decision making in health care often proves challenging. Health care providers often confront multiple treatments for each condition with limited evidence as to which interventions work best; moreover, treatment decisions can implicate questions of ethics and personal values that may not be answerable by clinical expertise alone. Fragmented delivery systems lead to insufficient coordination among providers in managing patients’ overall care. Patients face significant informational disadvantage not only in dealing with clinical information, but also in making choices regarding health care insurance coverage. Payers must make reimbursement and coverage decisions with incomplete information about the value and cost effectiveness of many treatments. Governmental officials must make complex regulatory decisions in managing a health care system with seemingly endless demand, escalating costs, and limited resources.
According to some optimistic accounts, the new era of health care reform will radically improve health care decisions. The Patient Protection and Affordable Care Act includes many reform initiatives aimed at improving health care decision making. For example, the law encourages the formation of integrated delivery systems that share information and coordinate care, fosters the development of shared decision-making between providers and patients, develops a more comprehensive evidence base through comparative effectiveness research, and creates insurance exchanges where patients as consumers can choose between plans offering standardized benefits and compared in standardized formats. But there are also reasons for concern that, in the new era of health care reform, decision making will become all the more complex and daunting. This symposium will consider both the promise and limitations of recent reform efforts, highlighting the important issues that are likely to emerge as the health care system tries to improve decision making.
Contents: Continue reading
Several months ago, I promised to post my thoughts on the viability of the American Hospital Association’s threatened lawsuit against the Secretary of Health and Human Services challenging the growing backlog of coverage appeals. (See my post here). That issue has become timely, because the AHA and several providers filed suit in May in the District of Columbia, and a few days ago filed a motion for summary judgment. (See here). There has been some coverage of the suit. (See here and here.) In short, their argument is that the statute says that a hearing must be held in 90 days and Medicare officials admit that the plaintiffs will not get a hearing for years, so therefore the court should order “mandamus,” forcing compliance with the 90 day deadline.
When I was in practice before moving to academia, I represented the Secretary in cases like this, so keep in mind my view might be biased. But the government’s response to the complaint is due (by my calculation) Monday, July 28, so I wanted to offer my quick reactions about the case and what sort of response we might hear from the government. I’ve just read over the AHA’s motion for summary judgment and I think that in a case like this, with an admitted violation of a statutory requirement, you have to start with the presumption that things could go bad for the government. But with that said, I don’t think that the government’s case is as gloomy as it might at first appear, so this could be an interesting case to watch going forward.
Call for Papers
AALS Section on Law, Medicine & Health Care
Works-in-Progress for New Law School Teachers
AALS Annual Meeting, Washington, DC
Saturday, January 3, 2015
The AALS Section on Law, Medicine and Health Care is pleased to announce a Call for Papers for a special Works-in-Progress for New Law School Teachers Program. The Section will run the Program from 5:15 to 6:30 p.m. on Saturday, January 3, at the AALS 2015 Annual Meeting in Washington, DC.
This program will bring together junior and senior health law scholars for a lively discussion of the junior scholar’s’ works-in-progress. Junior health law scholars will submit papers that they expect to submit in the spring 2015 law review submission cycle. After they briefly present their papers in a concurrent roundtable setting, senior scholars will provide oral comments and critiques. This new program presents an opportunity for the audience to hear cutting edge health law scholarship by recent members of the academy.
We will limit our selection to two or three papers. Continue reading
by Guest Blogger Wylie Burke MD, PhD.
When the Human Genome Project began in 1990, the National Center for Human Genome Research – now the National Human Genome Research Institute (NHGRI) – created a research funding program for evaluation of the ethical, legal, and social implications (ELSI) of genomics. ELSI scholars study a wide range of issues, from the responsible conduct of genomic research, to implementation and outcomes of genetic testing programs, to intellectual property challenges. But how should this research be evaluated? In particular, what impact should we expect for this kind of research? These questions are particularly challenging for those of us who work in the multidisciplinary Centers of Excellence in ELSI Research (CEERs) funded by the NHGRI, because these centers have been given a programmatic charge to consider policy-relevant questions and help to inform the policy-making process. A group of ELSI researchers, representing seven CEERs, have been deliberating these questions and recently published a paper with recommendations.
We noted, first of all, that policy-making occurs in many venues. Although discussions often focus on governmental policies, policy-making in other venues often influences genomic translation, including actions as diverse as Institutional Review Board (IRB) decisions about consent and return of results; guidelines promulgated by professional organizations; funding decisions of health insurers; and investment decisions of venture capital. In addition, policy-making in one arena may influence the need for policies in another. For example, practice guidelines influence the use of genetic testing and may in turn influence how clinical data are accessed to evaluate test outcomes, or how IRBs decide what genetic results should be returned to research participants. Continue reading
Call for Submissions: Journal of Law and the Biosciences
The Journal of Law and the Biosciences (JLB) is actively soliciting original manuscripts, responses, essays, and book reviews devoted to the examination of issues related to the intersection of law and biosciences, including bioethics, neuroethics, genetics, reproductive technologies, stem cells, enhancement, patent law, and food and drug regulation. JLB welcomes submissions of varying length, with a theoretical, empirical, practical, or policy oriented focus.
JLB is the first fully open access peer-reviewed legal journal focused on the advances at the intersection of law and the biosciences. A co-venture between Duke University, Harvard Law School, and Stanford University, and published by Oxford University Press, this open access, online, and interdisciplinary academic journal publishes cutting-edge scholarship in this important new field. JLB is published as one volume with three issues per year with new articles posted online on an ongoing basis.
Update: The Moore Foundation has generously paid to make my article available as open access on their website here. Today I am speaking at Health Affairs’ “Using Big Data to Transform Health Care” in DC, that will also launch its new issue devoted to the topic. I have a co-authored paper in the volume entitled “The Legal And Ethical Concerns That Arise From Using Complex Predictive Analytics In Health Care” that has just been released. Ironically the article is behind a paywall (while data wants to be free, I guess big data is different!) Here is the abstract.
Predictive analytics, or the use of electronic algorithms to forecast future events in real time, makes it possible to harness the power of big data to improve the health of patients and lower the cost of health care. However, this opportunity raises policy, ethical, and legal challenges. In this article we analyze the major challenges to implementing predictive analytics in health care settings and make broad recommendations for overcoming challenges raised in the four phases of the life cycle of a predictive analytics model: acquiring data to build the model, building and validating it, testing it in real-world settings, and disseminating and using it more broadly. For instance, we recommend that model developers implement governance structures that include patients and other stakeholders starting in the earliest phases of development. In addition, developers should be allowed to use already collected patient data without explicit consent, provided that they comply with federal regulations regarding research on human subjects and the privacy of health information.
I will also have a related paper on mobile health coming out later this summer that I will blog about when it comes out…
By Gregory Curfman and Holly Fernandez Lynch
[A quick follow up to our recent NEJM Perspective on the case, with I. Glenn Cohen]
Immediately after Justice Samuel Alito’s announcement on June 30 of the majority opinion in Burwell v. Hobby Lobby, the Supreme Court took further actions on the contraceptive mandate, and both supporters and opponents of the opinion were furiously assessing the implications and impact of what has proved to be a wild week for women’s access to contraception.
A report from the IMS Institute last April found that 24 million more prescriptions for oral contraceptives without a copayment were written in 2013 (when the contraceptive mandate was in full effect) than in 2012 (when it was not). This translates into a savings of $483 million for women (on average $269 per person). The percentage of women with no out-of-pocket costs for contraceptives increased from 14% to 56%. What will be the impact of the Supreme Court’s decision in Hobby Lobby on these trends?
The Hobby Lobby opinion is quite clear that the contraceptive mandate, spawned by the Affordable Care Act, may not be enforced against closely held, for-profit companies with religious objections to paying for contraceptives coverage. In other words, such companies will not face the hefty fines for noncompliance that would otherwise be imposed by the Department of Health and Human Services.
The opinion does not, however, apply to religious-affiliated, nonprofit organizations, such as Catholic schools or religious charities. For such organizations that object to paying for contraceptives coverage, the applicable regulation provided an accommodation by which the entities themselves were off the hook, but instead their insurers (or in the case of self-insured organizations, a third party administrator) would be required to provide free contraceptives coverage without cost to either the employee or the employer. In order to be eligible for this accommodation, the nonprofit entity must complete a form designating its objection and provide a copy to its health insurance issuer or a third party administrator. A number of nonprofits filed lawsuits asking that they be exempt from even this requirement, on the grounds that they were still being required to violate their religious beliefs by deputizing someone else to provide the objectionable services. One such group, the Little Sisters of the Poor in Colorado, a group of nuns who perform charity work, was granted an injunction by the Supreme Court last January.
Last month Medicare’s policy on coverage for sex change therapy changed somewhat. (See Matt’s earlier post here.) Specifically, Medicare’s Departmental Appeals Board invalidated the long-standing National Coverage Determination that dubbed sex change therapy to be non-covered, per se.
Co-blogger Elizabeth Guo and I have done some further digging on this issue and put together two posts answering some questions left open by Medicare’s decision and the news coverage surrounding it. In this post we discuss next steps: what the change in coverage policy means for Medicare beneficiaries who want coverage for sex change therapy, and what, if any, additional developments are likely to follow. In a companion post, we will be discussing the somewhat unusual process that was used to make this policy change.