The Fight Against Antimicrobial Resistance: Important recent publications

By Timo Minssen

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.

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Serious Risks from New Prescription Drugs

by Donald W. Light

Based on https://www.ethics.harvard.edu/lab/blog/436-new-prescription-drugs-a-major-health-risk

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.

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Antibiotics in animal feed and thin statutory interpretation: NRDC v. EPA

By Guest Contributor Diana R. H. Winters

Legal commentators have spent a lot of time this week sparring over statutory interpretation and the contrasting readings of the ACA by the Halbig and King courts.  The potential consequences of these cases demonstrate just how high the stakes of this enterprise can be.

With less fanfare, the Second Circuit decided a case yesterday that may too have large consequences for the health and welfare of the public.  In NRDC v. EPA, the court reversed a district court’s decision to require FDA to hold hearings on the withdrawal of approval for the use of two antibiotics—penicillin and tetracyclines—in animal feed.  This issue has enormous public health consequences, but the consequences of this case extend beyond antibiotic use, to agency practice in general.  The opinion sanctions egregious agency delay and a tremendous lacuna in decision making.

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Pharmaceutical Pricing– The Story That Just Keeps Going

By Bob Bohrer

Cross-post from Pharmaceutical Policy

After last week’s foray into patents and pharmaceutical policy, which is perhaps the most technical and specialized area of pharmaceutical policy, I will return to the never-ending story of pharmaceutical prices and the controversy over Sovaldi, Gilead’s break-through Hepatitis C drug. Sovaldi has a “sticker price” of $84,000 for a 12-week course of treatment, at the end of which 90% or more of patients would be expected to be cured. Since Sovaldi is a pill that is given once a day, the 12-weeks of treatment means that there are 84 daily doses. The math is easy, even if the price, unlike the pill, is hard to swallow–$1,000 per pill. The drug has been a huge financial success for Gilead, which reported $2.274 billion in sales in just the first quarter of 2014.   However, the backlash has been equally huge. In a rare display of bipartisanship in Washington, Senator Ron Wyden (D.-Ore), the Chair of the Senate Finance Committee and Senator Chuck Grassley (R.-Iowa), the Ranking Member of the Finance Committee, sent a demand for information concerning the development costs of Sovaldi and Gilead’s pricing decision. However, even more than the investigation by two senior senators, the impetus for today’s post came from the blog RxObserver, which featured a post entitled Sovaldi: A Poster Child for Predatory Pricing [sic]. Before discussing the epithet “predatory pricing,” the perspective of RxObserver requires a bit of explanation. RxObserver is a site that primarily provides the views of pharmaceutical benefit managers (PBMs), or as the blog itself states its purpose: “the Clearinghouse of the Future for Pharmacy Benefits.” It is, in general, a very high-quality blog, with an editorial staff composed primarily of well-recognized academic and government experts in health care policy. I regularly read it and find it useful, although I was taken aback by that “predatory” epithet. Read More

When Should you Be Able to Subpoena Clinical Trial Data? “Clinical Trials and the Right to Remain Silent” in JAMA Internal Medicine

Should litigants in products liability or other litigation be able to subpoena data from clinical trials to help prove their case? Does it matter whether the clinical trial is ongoing, finished recruiting but still analyzing data, or published? Michelle Mello and I have an invited commentary on this issue in JAMA Internal Medicine “Clinical Trials and the Right to Remain Silent” with our analysis and recommendations. We are discussing a real case from Yale where a subpoena was sought for data from a placebo-controlled trial of pioglitazone conducted there, where the person seeking the data had sued the manufacturer and believed she had been injured by pioglitazone but was not a clinical trial participant. In the same issue of JAMA IM, Yale gives its own account about how it handled the case here.  Dr. Kernan (the investigator) and I also have a nice interview podcast on the issue

On Agency Accommodations and Least Restrictive Alternatives

By Nadia N. Sawicki

Did HHS shoot itself in the foot by providing an accommodation to religious non-profits?

In holding that the contraceptive mandate imposed by HHS on Hobby Lobby and Conestoga Wood was not the “least restrictive alternative” for providing no-cost contraceptive coverage to women, the Supreme Court pointed to the accommodation HHS recently provided to religiously-affiliated non-profit corporations. Under the accommodation, “eligible organizations” such as religiously-affiliated hospitals and universities can avoid funding insurance coverage for contraceptives if they certify that they have a religious objection to providing such coverage. In such cases, the eligible organization’s insurance issuer must exclude contraception from the organization’s group health insurance plan, and instead provide a separate issuer-funded contraceptive plan directly to employees. Given that such an accommodation is already in place for some employers, the Supreme Court noted, “HHS itself has demonstrated that it has at its disposal an approach that is less restrictive than requiring employers to fund contraceptive methods that violate their religious beliefs.”

One obvious problem with the Court’s assertion, noted in Justice Ginsburg’s dissent, is that the Court expressly declined to determine whether such an accommodation would in fact be permissible under RFRA. Given the challenges to the accommodation-by-certification requirement already brought by organizations like Little Sisters of the Poor, it is far from clear that the current composition of the Supreme Court would uphold this requirement if faced with a direct challenge.

A second, perhaps less obvious, concern about the Court’s proposal that the eligible employer accommodation be extended to for-profit corporations is that HHS may now regret providing it – and as a result, HHS may refrain from making similar accommodations in the future, which would be a significant loss to defenders of religious freedom.

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Sincerity and Religious Belief in Hobby Lobby

By Nadia N. Sawicki

Courts evaluating First Amendment and RFRA claims have long held that they are in no position to evaluate the validity, centrality, or reasonableness of a claimant’s sincere religious beliefs. And while there is room for courts to evaluate whether a claimant’s beliefs are indeed “sincere,” many courts shy away from doing so because of a perceived overlap between judgments about centrality and about sincerity.

In Hobby Lobby, the sincerity of the corporation’s beliefs was not in dispute. Hobby Lobby asserted (and HHS accepted the claim) that it had a sincere religious belief that life begins at conception, and that this belief prohibited it from facilitating access to contraceptives that operate after that point.

But recent news reports have shown that Hobby Lobby has, in fact, been involved in activities that seemingly run afoul of this belief – including investing in pharmaceutical companies that manufacture the contraceptives they raise objections to in their lawsuit, as well as drugs commonly used for abortion; investing in insurance companies that cover abortion and emergency contraceptives; and actually providing coverage for emergency contraception in their own health plan until 2012.

While these facts were not raised before the courts hearing Hobby Lobby’s RFRA claims, First Amendment precedent suggests that they would be relevant to a judgment about the sincerity of Hobby Lobby’s religious beliefs. Surely a company that believes life begins at conception would have more difficulty demonstrating the sincerity of its beliefs when some of its conduct supports activities that are in direct opposition to this stated belief. This is not to say that a court would ultimately conclude that Hobby Lobby’s religious beliefs were insincere – but rather, that a court could legitimately consider these facts without treading into the dangerous territory of judging the merits and centrality of Hobby Lobby’s beliefs to the exercise of its faith.

REGISTRATION OPEN: 9/18 conference on post-trial access

pills_genericvariety_slidePost-Trial Responsibilities: Ethics and Implementation

Thursday, September 18, 2014

Harvard Law School, Wasserstein Hall, Milstein East AB, 1585 Massachusetts Ave.

This event is free and open to the public, but due to limited seating registration is required. Please register online.

Law, policy, and guidance are vague, sometimes conflicting, and generally lacking in concrete solutions for questions regarding post-trial responsibilities. The issues are complex and demand thoughtful discourse to move the clinical trial enterprise towards meaningful solutions.  Areas that currently lack clarity include:

  • What types of interventions or resources should be included within post-trial responsibilities?
  • What is a reasonable duration for post-trial responsibilities to extend?
  • What is the mission and purpose of various stakeholders in the conduct of clinical research and how do these roles intersect with post-trial access responsibilities?

This conference will bring together diverse stakeholders to address and develop consensus around some of these questions.

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Profits or Drugs?

By Bob Bohrer

Cross-post from Pharmaceutical Policy

There were two stories in The New York Times that, although not directly related, are the basis for today’s post. The first, by Andrew Ross Sorkin, Do Drug Companies Make Drugs, or Money?,appeared in the Business Section on page B1 on June 3, 2014. The second, by Andrew Pollock, New System for Treating Cancer Seen as Hopeful, appeared on the same page of The New York Times on the same day. Sorkin’s provocatively titled article focused on Valeant Pharmaceutical International’s takeover bid for Allergan and on Valeant’s strategy, which Sorkin characterized as buying pharmaceutical companies with revenues produced by active and successful pharmaceutical research programs and then increasing profits by cutting back on R&D. Sorkin’s article, as the title indicated, posited a tension between focusing on rewarding investors with increased profits and investing in the development of new and innovative therapies. My purpose in highlighting Sorkin’s article alongside Pollock’s is not to take issue with Sorkin’s analysis of Valeant’s business strategy, but to respond to the article’s title question.  Read More

Journal of Law & Biosciences publishes HLS student work

JLB coverThe Journal of Law and the Biosciences, the new open-access journal launched this year by the Petrie-Flom Center and Harvard Law School in partnership with Duke University and Stanford University, has published several articles in recent weeks by Harvard Law School students:

Check out these articles, and learn more about the Journal of Law and the Biosciences!