Precision Medicine Conference featured in November issue of AHLA Connections

The following article appeared in the November issue of AHLA Connections. 

Legal Challenges in Precision Medicine
April 2017 Conference

Jointly Sponsored by the American Health Lawyers Association and Law-Medicine Center at Case Western Reserve University

Introduction
by Maxwell J. Mehlman
 
In 2015, President Obama announced the federal Precision Medicine Initiative® (PMI) to more closely tailor medical decisions, practices, and products to individual patients’ genetic makeup and other patient-specific factors. In 2016, the National Institutes of Health (NIH) launched the All of Us Research Program to create a large, national biospecimen and genomic and medical database as part of the PMI efforts.

Although precision medicine offers the promise of better treatment and prevention, it also raises a number of challenging legal issues. In April 2017, the American Health Lawyers Association (AHLA) and the Law-Medicine Center at Case Western Reserve University (CWRU) School of Law jointly sponsored a conference to explore these legal issues.

Speakers discussed the policy overview, liability concerns raised by translating research findings into clinical care, the impact on health disparities and discrimination, health insurance and payment issues, and privacy and control of biospecimens and personalized genomic data.

Speaking were Carolyn Hutter, Ph.D., Program Director at the Division of Genomic Medicine, National Human Genome Research Institute at NIH; Mark Rothstein, J.D., Herbert F. Boehl Chair of Law and Medicine and Director of the Institute for Bioethics, Health Policy and Law, University of Louisville School of Medicine; Ellen Wright Clayton, M.D., J.D., Craig-Weaver Professor of Pediatrics and Professor of Law, Vanderbilt University; Maxwell Mehlman, J.D., Professor of Law and Bioethics, Director, The Law-Medicine Center, Case Western Reserve University; Shawneequa Callier, J.D., Professorial Lecturer in Law, George Washington University; Ruqaiijah Yearby, J.D., Associate Dean of Institutional Diversity and Inclusiveness, Professor of Law, Oliver C. Schroeder Jr. Distinguished Research Scholar, Case Western Reserve University School of Law; Peter Pavarini, J.D., Co-Leader, Healthcare Practice Group, Squire Patton Boggs (US) LLP and Past President, AHLA; and Kristen Rosati, J.D., Partner, Coppersmith Brockelman PLC and Past President, AHLA.

The following is an account of the discussion prepared by Kinal M. Patel, J.D., Associate, Squire Patton Boggs (US) LLP.

Summary of Proceedings by Kinal M. Patel

The Legal Challenges in Precision Medicine Conference, co-sponsored by AHLA and the Law-Medicine Center of CWRU School of Law, touched on a number of salient themes behind the growth and maturation of precision medicine, from the clinical application of increased data and improved interpretive modeling to the concomitant ethical, legal, and payment issues.

What Is Precision Medicine?

Precision medicine is often considered an emerging field, but it is not novel. Incorporating contemporary research from genomics and personalized medicine, precision medicine is an analytical approach to disease treatment and prevention blending lifestyle and environmental factors with genetic and molecular variability. From a clinical perspective, this concept asks health care professionals to consider the genetic and molecular bases of an individual in conjunction with environmental and lifestyle factors. This is a radical departure from the historical practice of disease prevention and treatment, which in general classified diseases based on the physical symptoms of the presenting patient. A primary factor driving the advance of precision medicine in research and clinical spaces is advances in technology, with corresponding lower costs.

What Are the Informational Drivers?

Data and information infrastructure are driving precision medicine

Speaker Carolyn Hutter’s presentation focused on the clinical and scientific innovations advancing precision medicine and the private-public partnerships building an open library of clinical, genomic, and environmental data. Hutter spoke about the development and importance of “knowledge databases” and “knowledge networks” for the advancement of precision medicine research efforts. An approach publicly advanced by the National Academies of Science, knowledge databases and networks aggregate vast amounts of patient data and experience to feed various medical and scientific research fields. There a number of global efforts to build knowledge bases using biospecimen and information-banking efforts—for example, the UK BioBank, the Million Veterans Program, and the All of Us Research Program, formerly known as the PMI Cohort Program.

The challenges to aggregated and organized data from accessibility and ownership

Hutter acknowledged that knowledge databases and networks present certain challenges. There is a tension between making the information widely available to commercial, academic, and citizen scientists, whilst encouraging and incentivizing the broader effort of knowledge building. There is also tension between the ownership of information in a knowledge database and the innovations derived from the same information. With greater quantities of useable information about participants and a greater depth of analyses to interpret that information, increased ethical concerns and corresponding obligations are bound to follow.

Precision Medicine’s Value for Whom?

The future of precision medicine is embedded in ethical and utilitarian concerns of costs and fairness

Precision medicine, and the concomitant advances in the clinical and technological sciences, blends ethical and utilitarian concerns of cost and fairness. According
to speaker Mark Rothstein, a key challenge for precision medicine as it matures in the near and future term is addressing the efficient allocation of resources
to vulnerable populations and avoiding resource waste.[1] While researchers likely have the capabilities to develop and pioneer game-changing advances, it is not guaranteed that the majority of the population can financially access such advances. Future health care advances are likely limited by the capital costs to produce such advances combined with
 the ability to recover those costs—whether from private pay, commercial insurance, or government payers.

The systems to collect, aggregate, and store data that do not filter for necessary and sufficient information result in enormous data sets that are costly to maintain and utilize

Rothstein proposed that the mass aggregation of the data supporting precision medicine efforts may have a similar limiting feature. The more data that individuals are willing to provide, the deeper the data sets available to researchers. However, some of the data sets collected by smart wearables and social media may or may not provide value to today’s or tomorrow’s researchers (for example, the number of flights of stairs climbed or check-ins at restaurants or shopping centers). Without demeaning smart wearable and social media trends, Rothstein questions whether the vast data sets monitoring human activity will provide tangible advances that benefit individuals and the community. Not all data in itself is useful, and volume does not automatically reverse uselessness. There is a point that the cost of aggregation and storing useless data no longer supports the opportunity cost for individual commercial enterprises as well as social value.

The mass aggregation of data in furtherance of precision medicine’s community value may conflict with normative privacy values

Rothstein also commented on the consumer privacy concerns intertwined with precision medicine. Even aside from the potential ownership of future innovations derived
from an individual’s data, precision medicine and the larger culture of information sharing and data mining are challenging individual norms for privacy. As technology improves social connectivity, Rothstein argued that privacy norms are shifting among generations.

What Are Precision Medicine’s Legal and Ethical Issues?

The policy tension between research efforts and the rights of individuals

Speaker Kristen Rosati discussed the policy tension between the public good of advancing research through the collection and analysis of biospecimens and genomic data, and the private rights of individuals related to their biospecimens and genomic data. In particular, there is an increasing push for individuals to have the right to control the use of biospecimens and genomic data for research (even if the biospecimens and genomic data are de-identified), to improve transparency about intended uses, to encourage more communication of research results, and in some instances to share in the profits or benefit produced as a result of research efforts.

Rosati instead proposed a regulatory path that effectively balances the public good and private rights. First, she proposed a prohibition against re-identification of de-identified biospecimens and data (with exception for research on re-identification), to take pressure away from the push for individual control of de-identified data, which will be expensive and unworkable, and will introduce substantial bias into some type of research. Second, Rosati suggested that policymakers take another look at whether federal law should preempt contrary state laws on biospecimen and data ownership, which may pose a challenge to research in the future.

Rosati discussed compliance issues in the use of biospecimens and genomic data, including recent changes to the federal “Common Rule” that governs federally funded biomedical and behavioral research involving human subjects in the United States, the Health Insurance Portability and Accountability Act, state health information confidentiality laws, and state genetic information protection laws. Rosati also discussed recommended contractual control and protection of biospecimens and genomic data.

The duty to warn and its application in the clinical practice of precision medicine

Speaker Ellen Wright Clayton presented on the topic of legal standards of care within precision medicine. Her presentation queried whether past jurisprudence, some of which is poorly reasoned, on the duty to warn would extend to the clinical practice of precision medicine. Clayton questioned whether clinical laboratories are under a modern duty to retest genetic specimens and reinterpret test results, given advances in the testing and interpretative sciences that will be incorporated into existing laboratory tests and protocols. To Clayton, this duty could create a perpetual burden to reanalyze specimens. She urged caution in voluntarily assuming new obligations.

The challenge of outfitting practice guidelines on the clinical practice of precision medicine

Speaker Maxwell Mehlman discussed the legal role practice guidelines may serve in precision medicine. He queried whether the patient-centered focus of precision medicine is fundamentally at odds with existing models of clinical and medical practice guidelines. In cases of malpractice, medical standards of care typically serve an important benchmark to determine reasonable professional activity. However, precision medicine’s consideration of individual genetic and environmental factors may support a factfinder determining that a plaintiff patient’s case is indeed different from and not representative of or reflected in practice guideline recommendations. If precision medicine is not suitable for reduction to recommended standards, then perhaps the weight on practitioners to possess and maintain a deep knowledge of broad clinical and research innovations will be heavier.

The value of race as an identifier and future of racial bias in the clinical practice of precision medicine

Speaker Ruqaiijah Yearby spoke on the effect that racial bias has on the patient-practitioner relationship and medical decision making. Given that race is a social construct, Yearby questioned the clinical benefit of using race, which cannot be scientifically measured. Yearby further queried whether the practice of health care under precision medicine can evolve past the use of race. Yearby acknowledged comments by members of the audience that the ancestral and genetic information can be valuable to practitioners. However,
Yearby submitted that using race as a proxy for ancestral and genetic information is dangerous because it leads to misdiagnosis, like failing to find that a Caucasian is suffering from sickle cell disease since this is considered an African American disease. Also, using race presents a problem when trying to treat people who are of mixed race.

Precision medicine as a tool to reform health disparities and discrimination in clinical research

Speaker Shawneequa Callier also spoke on the legal issues related to health disparities and discrimination. In her presentation, Callier discussed the need for greater
diversity and inclusion in precision medicine research. She argued that advances in precision medicine, including genomics, can help to improve health disparities.

Such improvements need support from the research and clinical fields. Promoting diversity in drug studies provides additional information to avoid potential misdiagnoses of diverse subpopulations in a clinical setting. Full transparency of all information acquired from drug studies involving diverse constituent subjects, even if nominal, may help to avoid mischaracterizations of risk for those and representative subpopulations.

Similarly, research and clinical fields can improve health disparities by replacing the use of pan-ethnic categories (e.g., “Asian”) with more precise geographic
identifiers for subpopulations. In the case of a drug therapy treatment with a reported warning for a pan-ethnic category with a prevalence of a mutation, Callier pointed out that the cost of care for diverse subpopulations that fall into that category is higher and may not be justifiable from a third-party payer perspective.

Who Pays for Precision Medicine?

Cost recovery and reimbursement are a key financial limitation on public access to advances and innovations

Peter Pavarini argued that cost recovery and reimbursement is a key challenge for the future of precision medicine. Pavarini questioned whether precision medicine is
sensitive to the consumer cost consciousness. Building knowledge databases and knowledge networks to fuel advances in the research field and, accordingly, spawn clinical advances and innovations is financially costly. In large part, the growing availability of novel health care services and technologies outstrips the average patient access through third-party and private pay means. Under the current payer environment, it is highly questionable whether the majority of the population can financially access such advances.

The dissemination of advances and innovations is an uncertain limitation on precision medicine

A related issue to access is the challenge of disseminating such advances and innovations. Pavarini argued that that challenge can be reduced to cost. In a health carepayer system that is fractured between governmental, commercial, and employer payers, cost is the key hurdle to disseminating clinical and technological advances and innovations, whether game-changing or slightly improved. Pavarini proposes that the research and clinical fields within precision medicine should, in part, acknowledge and respond to the payer environment.

The fractured health care system in the United States handicaps the dissemination of advances and innovations

Pavarini additionally cautioned the fractured nature of the U.S. health care system is a handicap to the promotion of clinical and technological advances and innovations. From a patient population perspective, payers are not fully incentivized to cover high-cost early-stage preventative services and treatments that will alleviate health care expenses realized 10 or 20 years in the future. In contrast, a single-payer system supported or mandated by a central government is naturally incentivized to cover such services and treatments in order to achieve long-term cost savings.

Strategies to overcome uncertainty and promote the dissemination of advances and innovations

To promote dissemination, Pavarini argued that the federal government and/or payer groups should develop standards for determining when payment should be due on
new advances and innovations—a cost-benefit basis for clinical and technological advances and innovations. Advancing that discourse, members of the audience considered the self-insured employer and union plan market as a mechanism to promote standards for the diffusion of advances into clinical practice and consumer hands. That plan market holds potential to develop and normalize such standards. Putting aside the federal and state insurance programs and commercial insurance plans, future-oriented shifts in the benefit
design of several of the U.S.’s largest self-insured employer and union plans could have a significant effect towards developing standards to promote dissemination.

Members of the audience expressed promise that patients may lead the broader debate on the dissemination of advances and, correspondingly, strengthen the position for
health care professionals to advance the same agenda. While patient and physician advocates may promote actual advances and innovations, they will have less impact on the promotion of conceptual advances. Even so, a forward-looking set of payment standards may encourage the development of conceptual advances in the research fields, and thereby avoid potential opportunity losses.

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[1] Mark Rotherstein’sauthored a recent article based on his speaker discussion at the April 2017 Conference. See Mark A. Rothstein, Structural Challenges of Precision Medicine,
45 J.L. Med. & Ethics 274 (2017).