Big Data and Pharmacovigilance, Part I

By Dov Fox

So much new data are created every day that 90 percent of all data worldwide has emerged in just the last two years. This information revolution has the potential, argues Bill of Health guest blogger Ryan Abbott, to transform how we develop new drugs, set clinical practices, and finance health care. His interesting new article paints an alluring “vision of a drug regulatory system powered by big data”:

“When the Food and Drug Administration (FDA) approved the cholesterol-lowering drug simvastatin in 1991, it was based on pre-marketing controlled clinical studies that included a total of 2,423 patients. In 2011 alone, just in the United States, almost a hundred million prescriptions were written for the drug. Imagine the impact of being able to analyze data from every one of those patients to evaluate whether simvastatin is safe and effective.”

The surveillance of pharmaceuticals after they’ve gone to market will matter more and more, Abbott argues, as personalized medicines become more difficult – and perhaps less necessary – to regulate before they’re released. He proposes a new plan for the post-market regulatory system that relies on the health information exchanges (HIE) created by the HITECH and Affordable Care Acts. These exchanges are slated to amass a vast repository of data on individual patients. Their large size and inclusive nature will enable more accurate analyses in observational research, Abbott suggests, and in ways that minimize the bias and selectivity problems associated with current data sets.

There are at least three obstacles to the integration of these exchanges in drug regulation. First, HIEs will be expensive. While the federal government provided considerable funding to get these exchanges off the ground, Abbott recognizes that in order to remain viable, they will probably have to sustain themselves financially. Second, their meaningful impact on post-marketing surveillance will require consistent reporting standards and information-sharing mechanisms. Third are important patient concerns about the privacy of their personal health information. States are experimenting with different patient participation models to address privacy concerns. For example, Abbott notes that in some states HIEs are free to exchange information without patient consent, while in others patients can opt-out of information exchange altogether. Either is permitted by HIPAA, so long as the information is de-identified so it can’t be used to identify individual patients.

Abbott argues that it’s worth tackling such concerns that the adoption of HIEs pose for citizens, policy makers, health care providers, and the health care industry, so we don’t squander the opportunity to use health information exchanges to their full benefit. Public support for data collection isn’t enough. That data must be translated into a format that regulators can use—something I’ll address tomorrow in my next post on the subject.

House Holds mHealth Hearings, FDA Promises Final Guidance Forthcoming

by Dan Vorhaus

[Cross-posted from Genomics Law Report]

Digital Hospital - 262 wideThree days of hearings by a House of Representatives committee concluded yesterday with a pledge from an FDA official to finalize long-awaited guidance on the regulation of mobile medical applications “in coming weeks“; at the latest by the end of the FDA’s fiscal year (i.e., September 30th).

The hearings, convened jointly by several subcommittees of the House Energy and Commerce Committee, were announced last week following a pointed letter to the FDA (pdf) from seven committee members on March 1st. In the letter, the Congressmen pressed the FDA for information on the agency’s mHealth regulatory timeline and the implications for innovation and industry of the proposed regulations.

A Preview of Guidance to Come. As covered previously here at the Genomics Law Report, in July 2011 the FDA released draft guidance (pdf) outlining its intent to regulate a limited subset of mobile medical applications based on their perceived risk to patients and consumers.

In testimony before Congress, which was supported by a formal written response to the House subcommittee’s inquiry (pdf) as well as a recent FDA blog post, the FDA provided substantial additional clarity regarding its regulatory intent and the timeline for finalized mHealth regulatory guidance. Here are the highlights:

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Rethinking Biotechnology and Software Patents: A Myriad of Jurisdictional Issues Related to Subject-Matter Eligibility

by Adriana Benedict

Today, Professor Glenn Cohen announced on this blog that he, in conjunction with two others, filed an amicus brief in AMP v. USPTO (Myriad), a case concerning Myriad’s patents on isolated DNA and cDNA. In a paper I have been writing on the natural phenomenon doctrine as applied to biotechnology patents, I arrived at this conclusion about the doctrine’s implications for Myriad:

According to Mayo v. Prometheus, the preemption rationale for the natural phenomenon doctrine suggests that any patent on a diagnostic biotechnology product or process should be limited to the inventive use of that product or process as defined by its associated process or product, respectively.  As applied to Myriad, this qualified interpretation of the natural phenomenon doctrine would suggest that ideally these patents ought to be limited to Myriad’s one remaining valid method claim, namely claim 20 of the ‘282 patent, “a method for screening potential cancer therapeutics.”  The unavoidable and unsettling problem with such a conclusion, of course, is that at this stage in litigation, it is not possible for the Court to limit Myriad’s gene patents in this way.  This procedural limitation sheds some light on the elephant in the natural phenomenon doctrine: If the doctrine was meant to exclude certain categories of discoveries from patentability before Congress had the opportunity to refine more specific patent validity rules, then perhaps it should be limited to carrying out that function at the outset of a patent prosecution.  The natural phenomenon doctrine serves the important purpose of ensuring that patents do not contravene their Constitutional objective by too broadly preempting the use of “basic tools of science.”  It does so by balancing the scope of preemption against the scope of invention, and ensuring that the scope of preemption does not exceed that which is justified by the inventor’s handiwork in applying natural phenomena.  At the patent prosecution stage, the natural phenomenon doctrine is a useful “catch-all” analytical tool that allows flexibility in promoting the spirit of patent law when the letter of patent law has not kept pace with the progress of science. But at the litigation stage, its Achilles heel is that it may prove too much: In the absence of a procedural option to limit a patent at this stage, the natural phenomenon doctrine is forced to err on either the side of all or nothing.  While the doctrine may be useful at the patent prosecution stage, it was not (as other statutory patentability requirements were) appropriately designed to assess the validity of patents once they’ve been issued in a way that is compatible with today’s patent litigation procedures.  As a doctrine of limitation, it must in this context either fall, and prove nothing at the expense of unwarranted preemption, or rise, and prove too much at the expense of patent holders who have been reasonably relying on guidance from the USPTO regarding gene patents for many years.  

I am unable to find any commentary exactly on this point, but some issues concerning the jurisdictional authority of §101 have been raised in response to both Mayo and CLS Bank v. Alice.  While these cases concern biotechnology processes and software, respectively, they are extremely relevant to Myriad if we consider isolated genes / cDNA to be the equivalent of biological software. Indeed, Professor Ronald Mann observed that “Though most of the attention to …[Mayo]  has focused on its immediate implications for medical providers, the broader effect of the case probably will be on the software industry.”

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Impact of the Sequester on Health Care: By the Numbers

By: Katie Booth 

The looming sequester will have a significant impact on health care, including cuts to Medicare, FDA, CDC, NIH, and Affordable Care Act programs. Budget cuts could slow down the drug approval process, impede the tracking of infectious diseases, and lead to layoffs for hundreds of thousands of workers in the health care sector. Read on for sequestration by the numbers…

Medicare:

  • Medicare cut by 2% ($11 billion) (not set to begin until April 1st, 2013, unlike other sequestration cuts, which are set to begin on March 1, 2013)
  • Physicians’ payments cut by 2%
  • Hospital Medicare reimbursement cut by $5.8 billion
  • Hospitals could end up with especially large cuts under the sequester because other parts of healthcare system run on longer term contracts
  • Loss of almost 500,000 health care sector jobs in the first year of the sequester according to an American Medical Association and American Hospital Association study, including job losses for 40,000 practitioners such as physicians and dentists

FDA:

  • FDA cut by 8% ($318 million)
  • FDA public funding cut by $206 million
  • FDA industry user fees cut by $112 million (for an interesting discussion of user fee cuts and the sequester, see Patrick O’Leary’s Bill of Health blog post)
  • Cuts by department (assuming 8% across-the-board cuts): $71 million to Foods, $39 million to Human Drugs, $17 million to Biologics, $11.3 million to Animal Drugs, and $26.5 million to Devices
  • Longer drug approval process is likely
  • Layoffs and furloughs likely
  • 2,100 fewer food safety inspections

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No Access to Medicines without Access to Research

by Adriana Benedict

In December, I wrote a blog post noting that access to biomedical research is critical not only for informed patient care, but also for the sustainable development of pharmaceutical R&D responsive to local needs, especially in developing countries.  In recent years, open access issues have taken on an increasingly important role in global health discussions.  In 2009, the Institute for Information Law and Policy, the Justice Action Center and Health Information for All 2015 made the case for a rights-based approach to the issue in a report called Access to Health Information under International Human Rights Law.  In 2011, a medical student in the Right to Research Coalition explained 6 Reasons Open Access Matters to the Medical Community.  And the 2012 WHO CEWG Report recommending a binding treaty on Research and Development to Meet the Needs of Developing Countries includes as one of its proposals “open approaches to research and development and innovation which include precompetitive research and development platforms, open source and open access schemes.”

In response to the increasing demand for open access to biomedical research, PLOS Medicine partnered with WHO to issue a call for papers “intended to culminate in an open-access collection of original research and commentary articles to coincide with the launch … [of] World Health Report 2012: No Health without Research.”  However, the 2012 World Health Report was unexpectedly called off to be replaced by a 2013 report on “contributions to research to universal health coverage,” a far less politically polarizing topic.  In its editorial response to the cancellation of the 2012 Report, PLOS Medicine noted that “The reasons for these delays and for the changes in scope of WHO’s flagship publication, are unclear,” not in the least because “Previous World Health Reports … have represented bold political statements.”

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A Myriad of Options in the Spirit of the Law

by Adriana Lee Benedict

In a couple days, petitioners in AMP v. USPTO will be filing their brief on the merits following the Supreme Court’s grant of certiorari in late November.  For many, the Supreme Court’s ruling in this case will provide a long-awaited answer to the question of whether or not isolated DNA is patentable subject matter under §101.  In August, the Federal Circuit ruled on the case for a second time following a remand from the Supreme Court, in which the Federal Circuit was asked to reconsider its ruling in light of the Supreme Court’s recent ruling in Mayo v. PrometheusThe majority, written by Judge Lourie, found that Mayo did “not control the question of patent-eligibility of such claims. They are claims to compositions of matter” and that while “Plaintiffs and certain amici state, that the composition claims are mere reflections of a law of nature.  Respectfully, they are not, any more than any product of man reflects and is consistent with a law of nature.”  Judge Bryson’s dissent, on the other hand, explained that, “In cases such as this one, in which the applicant claims a composition of matter that is nearly identical to a product of nature, it is appropriate to ask whether the applicant has done ‘enough’ to distinguish his alleged invention from the similar product of nature,” concluding that Myriad had not made a “substantial ‘inventive’ contribution” or claimed anything more than a combination of “well-understood, routine, conventional” elements.”

It seems likely that the Supreme Court will agree with Judge Lourie that the gene patents in question in Myriad, whether or not they are products of nature, are not laws of nature, as some of the patents in question in Mayo were.  Yet I would be surprised if they took this to mean that Mayo therefore does not control the question of patent-eligibility in Myriad.  In Mayo, Justice Breyer’s majority opinion was incredibly clear that the metabolic correlation at issue was not patentable under §101 because it tied up a law of nature and therefore preempted its use for further research.  Isn’t that exactly what Myriad is about?  Certainly all parties would agree that Myriad’s patents, whether natural products (physical phenomena) or not, serve to preempt breast cancer research on the BRCA1 and BRCA2 genes.

When the Supreme Court articulated the §101 exception for laws of nature, physical phenomena and abstract ideas in Gottschalk v. Benson, it explained that these kinds of claims were not patentable because they consist of the “basic tools of scientific and technological work.”  It is difficult to dispute that Myriad’s isolated genes are basic scientific tools. But according to Myriad, under this rule, their patents would only be invalid if they claimed real human DNA, and that it is not dispositive that their isolated DNA is nearly identical to real human DNA, because it is not naturally occurring.

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Twitter Round-Up (1/13-1/19)

By Casey Thomson
The flu, gun control, and legal action against the FDA – all amongst our Twitter feeds this past week. Read on for more:
  • Frank Pasquale (@FrankPasquale) retweeted a link to the FDA’s current legal trouble concerning their failure to disclose antibiotic resistance data. The Government Accountability Project (GAP) is accusing the FDA of violating the freedom of information law, failing to release data on antibiotic drug usage within the meat industry in order to, as they claim, protect industry secrets. This failure takes special significance when considering that, according to GAP, “80% of all antibiotics sold in the US are utilized by the meat industry.” (1/14)
  • Michelle Meyer (@MichelleNMeyer) retweeted an article in the Health Affairs Blog concerning how to improve the Learning Healthcare System (LHS), which adapts data into knowledge that directs evidence-based practice and health system change. Specifically, the U.S. Department of Veterans Affairs is developing two approaches, namely Point-of-Care Research (“a method of performing clinical trials within the daily practicalities of the [health-care system] (with the intent of advancing these systems to LHS)”), and the Collaborative Research to Enhance and Advance Transformation and Excellence (strengthening health services research, which analyzes the factors regarding the obtainment of care). (1/14)
  • Arthur Caplan (@ArthurCaplan) reported on the American College of Physicians’ new recommendation that all healthcare providers receive the influenza vaccine for this particularly harsh flu season, in addition to other listed immunizations. (1/15)
  • Frank Pasquale (@FrankPasquale) additionally added a post on the inequality of the 2012-2013 flu outbreak – namely, the disproportionate number of lower-income individuals who are contracting the illness. The article noted the results of a study which found that while the majority of efforts for vaccinations occur in more wealthy neighborhoods, covering poorer neighborhoods with vaccine care early benefits the wealthier neighborhoods more so than if such vaccinations were delayed. (1/16)
  • Arthur Caplan (@ArthurCaplan) also shared a link to an examination into New York’s newly passed major gun control law, which addressed gun control ownership of those with mental illness. Caplan dissolved claims that the new measures were “draconian,” noting that such practices of reporting individuals that may pose concern for the safety of others have already been in practice but that these new policies make the process of reporting a legal imperative, and simpler.
  • Daniel Goldberg (@prof_goldberg) shared an article on SAGE Journals about the experience of gender within the healthcare science environment, specifically looking at the subtle practices of masculinist actions taking place that may remain unnoticed or unchallenged. The report is based on the discussed experiences of healthcare scientists with men in healthcare science laboratories. (1/16)
  • Alex Smith (@AlexSmithMD) linked to an article on an intervention for “post-hospital syndrome”, commonly known as the Acute Care for Elders (ACE) Unit. The intervention, while evidence-based and already in place in many hospital locations, may be overlooked by practitioners or healthcare authors. This unit works to reduce the effects that often derive largely from the “allostatic and psychological stress” accumulated during a hospital stay. (1/18)
  • Frank Pasquale (@FrankPasquale) posted a report on bias in reporting on breast cancer clinical trials. The study found that “nearly one-third of reports on large, randomized studies over-emphasize some benefits of therapy,” in addition to providing “insufficient attention or discussion of treatment side effects.” Considering that such reports factor prominently in how doctors decide to pursue treatment and therapy for patients, this misreporting leaves many doctors unaware of the true consequences of tested treatments – and may cause them to decide plans for treatment that they would not otherwise pursue. (1/19)

Note: As mentioned in previous posts, retweeting should not be considered as an endorsement of or agreement with the content of the original tweet.

Twitter Round-Up (12/2-12/8)

By Casey Thomson
This week’s Twitter Round-Up features an “American Idol-style” selection of research grant winners, the problems facing children in Syria attempting to be vaccinated, and a review of where we stand with current patient health information privacy and security.
  • Michelle Meyer (@MichelleNMeyer) retweeted an article about a newly emerging landmark case in the United Kingdom. In the suit, a childless couple denied IVF funding due to the woman’s age is suing Health Secretary Jeremy Hunt (because he is “ultimately accountable for healthcare in England”) on the basis of age discrimination. Thought to be the first venture to sue the Health Secretary concerning decisions about this NHS fund rationing, this case also will be the first instance where age discrimination laws have been employed to try for fertility treatment. (12/3)
  • Alex Smith (@AlexSmithMD) shared an article about a problem patients must deal with when approaching post-hospitalization care: Medicare’s offer to pay for hospice care or for a Skilled Nursing Facility (S.N.F.), but only rarely at the same time. Not only does the choice create a financial predicament, but it also has extensive repercussions for the patient’s health. Calls for a combined benefit process between hospice/palliative care and S.N.F. have been made, including a proposed “concurrent care” demonstration project in the Affordable Care Act. (12/6)
  • Dan Vorhaus (@genomicslawyer) linked to a summary of the Ponemon Institute’s Third Annual Benchmark Study on Patient Privacy & Data Security, reporting on the challenges still being faced to safeguard protected health information (“PHI”). (12/6)
  • Michelle Meyer (@MichelleNMeyer) additionally retweeted a link explaining Brigham and Women’s Hospital’s attempt to deal with the rising difficulty of choosing which research grants to support: an “American Idol-style” public online voting. With almost 6,500 votes cast, the public engagement experiment picked a project hoping to research methods for integrating genomic sequencing into newborns’ routine medical care. When future grant holders are struggling to award between a set of equally deserving project proposals, this push for public involvement (after having confirmed scientific rigor) may have intriguing implications. (12/6)
  • Daniel Goldberg (@prof_goldberg) also linked to a study in Denmark testing the relationship between socio-economic status (SES) and blood pressure levels. Despite having a healthcare system that is free and equal-access regardless of factors like SES, the study found that SES had a “significant effect on BP [blood pressure] control” in this survey. (12/7)
  • Arthur Caplan (@ArthurCaplan) posted a report by UNICEF on the efforts by parents in the Syrian Arab Republic to get their children vaccinated. With many medical centers destroyed by the conflict, and with health practitioners having to operate and transport supplies in the dangerous environment, children have been unable to receive routine vaccinations for several months. This campaign aims to provide such vaccinations (specifically for measles and polio) to children, having advertised via churches, mosques, schools, television, and even by SMS to get greater coverage. (12/7)
  • Frank Pasquale (@FrankPasquale) included a book review of Pharmageddon by David Healy, a look at how pharmaceutical companies are excessively influencing the medical industry particularly with “diagnostic categories and clinical guidelines.” The result, according to Healy: a society where people “think about their bodies as a bundle of risks to be managed by drugs,” with a workforce that is “getting ‘sicker,'” and with “major pharmaceutical companies…banking on further overdiagnosis and overtreatment,” all “undermining universal health care.” (12/8)

Note: As mentioned in previous posts, retweeting should not be considered as an endorsement of or agreement with the content of the original tweet.

mHealth on the Horizon: Federal Agencies Paint Regulatory Landscape with Broad Brushstrokes

by Dan Vorhaus and Phil Ross (cross-posted from Genomics Law Report)

For years, and with increasing frequency, health care and information technology companies have touted the potential of mobile medical and health applications and technologies to improve the quality and delivery of health care through the use of technology. While the future of mobile health (frequently referred to as “mHealth”) is undoubtedly filled with promise, the legal and regulatory landscape in which mHealth technologies reside is only now beginning to take shape.

As mHealth developers, funders and even users consider investing in the field, or including in particular mHealth technologies, they should keep in mind the emergent and fluid nature of the mHealth regulatory landscape. Here, we outline the likely key players and discuss several recent and projected initiatives with respect to the oversight of mHealth technologies:

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Twitter Round-Up (11/25-12/1)

By Casey Thomson

From policy adoption at the federal level to debate over the health concerns of political figures, this week’s round-up focuses largely on the news for bioethics and health law in the realm of politics.

  • Dan Vorhaus (@genomicslawyer) posted a feature on the history of gene patent litigation and implications for next-generation sequencing technologies. (11/26)  He also included a link summarizing key information on H.R.6118, newly passed in the House and Senate and now being presented to the President. Otherwise known as the Taking Essential Steps for Testing (TEST) Act 2012, the bill gives the Centers for Medicare and Medicaid Services (CMS) “greater flexibility in enforcing CLIA [Clinical Laboratory Improvement Amendments] proficiency testing violations” (as noted by Vorhaus). (11/26)
  • Daniel Goldberg (@prof_goldberg) included a post on the inequality in self-rated health as considered by gender. The study, done in Spain, found that females’ lower sense of self-rated health is a reflection of the higher burden of disease in women, and encouraged systems of health to reconsider the approach towards afflictions with lesser impact on mortality that are possibly receiving less attention than is deserved. (11/26)
  • Daniel Goldberg (@prof_goldberg) additionally included a report on the problems parents with disabilities are facing in terms of retaining (or even gaining) their right to be a parent. Such bias against parents, the article notes, may not recognize that ensuring essential support may be all that is needed to discourage problems or eradicate risks for the majority of cases. (11/26)
  • Frank Pasquale (@FrankPasquale) linked to a blog post on the recent protests by AIDS activists in the office of House Speaker John Boehner. The protesters, stripped naked in order to reveal the painted “AIDS Cuts Kill” written on their chests, were there to protest the possible cuts to HIV/AIDS program funding that may follow a fiscal cliff deal.  (11/28)
  • Arthur Caplan (@ArthurCaplan) featured his talk with Boston Public Radio on the fine line politicians must walk when balancing their struggle with a health crisis along with the responsibilities of being a public official. The recent health concerns facing Boston’s Mayor Thomas Menino served as inspiration for this discussion. (11/28)
  • Frank Pasquale (@FrankPasquale) added a news article detailing the recent speech made by principal deputy national coordinator David Muntz of HHS’ Office of the National Coordinator for Health Information Technology. Muntz, in addition to discussing the need to better incorporate technology for fostering stronger communication between patient and doctor, mentioned some striking statistics: “only 15% of patients have renewed a prescription online,” while “just 10% have a personal health record.” (11/29)
  • Arthur Caplan (@ArthurCaplan) posted a link to a new feature on concierge medicine, where appointments can be paid for solely through cash and not through insurance. While previously considered an option only for the rich, concierge medicine has possible implications for the greater body of patients: as the article noted, it may become a more viable option especially as threats of regulation and backlash in a doctor shortage encourage traditionally high-priced firms to backtrack. (11/29)
  • Arthur Caplan (@ArthurCaplan) also shared a video by Canadian comedian Rick Mercer on getting flu shots. (12/1)

Note: As mentioned in previous posts, retweeting should not be considered as an endorsement of or agreement with the content of the original tweet.