The Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) has released a brief, titled Ethics and Ebola: Public Health Planning and Response, following its consideration of specific ethical questions that emerged while the U.S. government was responding to the Ebola virus outbreak in western Africa. Ebola virus cases in the U.S. began to appear last fall, the but Guinea, Sierra Leone and Liberia experienced significant outbreaks during 2014, and the World Health Organization reports an ongoing struggle in these countries. The commission advanced several recommendations to improve international responses, as well as the U.S. domestic response and capabilities:
Strengthening the capacity of the World Health Organization to respond to global health emergencies through the provision of increased funding and collaboration with other international, national, and non-governmental public health organizations.
Identifying and empowering a single U.S. health official accountable for all federal domestic and international public health emergency response activities.
Strengthening the deployment capabilities of the U.S. Public Health Service, including by streamlining command structure for deployment and providing appropriate resources to train and maintain skills needed for emergency response.
The Commission also highlighted the need to embed ethical considerations into disease management and responses in a coordinated ethics framework:
In addition, the Bioethics Commission recommend[s] that ethical principles be integrated into timely and agile public health decision making processes employed in response to rapidly unfolding epidemics. It call[s] for qualified public health ethics expertise to be readily available to identify ethical considerations relevant to public health emergencies and responses in light of real-time available evidence. Specifically, it recommends that a single U.S. health official should be accountable for ethics integration.
While recognizing that public health measures can compromise individual liberty in emergency situations, the Commission addressed the need for possible quarantine:
On the contentious issue of quarantine and other policies related to movement restrictions, the Bioethics Commission recommend[s] that governments and public health organizations employ the least restrictive means necessary—based on the best available scientific evidence—when implementing restrictive public health measures.
The Commission recognized that clinical trials during a public health emergency can pose ethical choices regarding trial design, and particularly regarding the use of placebos, but did not rule out their use:
Clinical research during a serious communicable disease epidemic creates a stark ethical dilemma: On one hand, using placebo controls appears to deny some patients the possibility—however small and uncertain—of a benefit from experimental interventions; on the other hand, research that does not yield conclusive results about an intervention’s safety or effectiveness could exacerbate the tragedy of the epidemic by providing misleading and potentially harmful information. Navigating this tension requires careful analysis of the range of possible trial designs coupled with a commitment to core principles of research ethics.
In upcoming work, the Bioethics Commission will further consider “the importance of democratic deliberation and public education in bioethics.” While the role of the Bioethics Commission is deliberative and advisory, it has a broad and singular mandate to consider how the government ethically responds to the emergence of new life science technologies and ethically reacts to medical or health crises that necessitate competent and agile federal involvement.
The FDA is holding two upcoming public workshops in the next several months that consider several areas of genetic test regulation which may be the subject of upcoming FDA actions. The FDA derives authority for any proposed oversight of genetic testing from its general mandate to regulate medical devices; one category of device is the in vitro diagnostic (IVD), a term that generally captures tests and assays that are used in the diagnosis (or treatment) of disease, including genetic tests. The ongoing issue of whether laboratory-derived tests (LDT) should be directly regulated by the agency continues to be unresolved. Because LDTs constitute the majority of commercially available genetic tests in the U.S., the absence of regulation regarding the utility and/or validity of these tests means that most of the genetic tests in the U.S. are not subject to FDA oversight (however, general certification of laboratories does occur under the Clinical Laboratory Improvement Amendments (CLIA). The FDA published its Framework for Regulatory Oversight of Laboratory Developed Tests last fall, and generally proposed a risk-based classification and regulatory structure for LDTs. The agency’s rationale for increasing its involvement in this genetic testing sector was provided:
LDT’s are important to the continued development of personalized medicine, but it is important that in vitro diagnostics are accurate so that patients and health care providers do not seek unnecessary treatments, delay needed treatments, or become exposed to inappropriate therapies.The FDA has generally not enforced premarket review and other applicable FDA requirements because LDTs were relatively simple lab tests and generally available on a limited basis. But, due to advances in technology and business models, LDTs have evolved and proliferated significantly since the FDA first obtained comprehensive authority to regulate all in vitro diagnostics as devices in 1976.
The public workshop for discussion of the LDT framework will be held on January 8-9, 2015; public comments to the online document can still be filed until until February 2, 2015.
The FDA is also considering how it might interface with the field of next generation sequencing (NGS), a term applied to high-throughput methods for generating multiple DNA sequences in parallel; such methods can produce whole-genome or exome-only DNA sequences efficiently and quickly. Typically, the sequencing operation does not start with a particular clinical goal in mind or a particular gene or mutation of interest; the approach is clinically neutral and aims to produce genome-wide DNA sequences. NGS sequencing therefore creates high-volume data that requires serious computational analysis in order to create meaningful, useful results for clinical application. NGS can generate data that reveals rare and previously unknown genetic variants. Because of the broad-brush nature of whole-genome sequencing, it has the potential to reveal incidental (undirected) findings; the ethical management of such information by medical personnel has been the subject of bioethical and academic debate. The FDA has issued a discussion paper which highlights specific concerns and possible standardization for NGS technologies:
NGS tests are unique among existing IVDs in the amount of data that can be generated, the lack of an a priori definition of what will be detected, and the number of clinical interpretations that can be made from a single patient sample. In order to continue to support the development of useful medical information, FDA believes the most efficient possible approaches to regulating NGS tests should be considered. Among the possibilities, a standards-based approach to analytical performance of NGS tests and the use of centralized curated databases containing up-to-date evidence to support clinical performance are under discussion.
The public workshop on NGS regulation will be held on February 20, 2015; the agency will receive comments until March 20, 2015.
The Presidential Commission for the Study of Bioethical Issues (PCSBI) has issued a report on one of the intersections between genetic testing and privacy. The PCSBI was established by President Obama; to date, their only other report focused on the regulatory landscape for synthetic biology (more here). Now, the Commission has published Privacy and Progress in Whole Genome Sequencing, which examines how the increasing availability of whole genome sequencing (WGS, where the full DNA sequence of a genome is obtained) in both clinical and research settings has to be matched with an attention to how such data is used in a manner that protects the privacy of the patient and/or research subject. The report illustrates the legal complexity of privacy in American law generally – a very mixed portfolio of (sectoral) protections. The legal concerns with the widespread introduction of genetic information into science and medicine are several and concern whether an individual has control of when genetic testing occurs, when genetic information can be disclosed, and how genetic information can be used. With respect to genetic information, much of the legal attention has focused on the issue of genetic discrimination, which concerns use, and has not focused on genetic privacy. Most simply, privacy is concerned with disclosure, while discrimination is concerned with misuse. Can the privacy of “genetic information” be protected with existing law? Is a genomic DNA sequence a category of "personally identifiable information" (PII), meriting special protection from unauthorized disclosure? In general, medical information generated during patient care is protected by the Health Insurance Portability and Accountability Act (HIPAA), which makes a provider accountable for maintaining both patient confidentiality and privacy of medical records. But, as the commission notes, it is not clear whether genetic or genomic information is always included in the protected health information that HIPAA addresses. Since 2008, the U.S. has the Genetic Information Nondiscrimination Act (GINA), which protect individuals from discrimination based on the use of their genetic information in employment and health insurance. Notably, it does not extend to the provision of life, long-term care or disability insurance.
The PCSBI report particularly focuses on how genetic information derived in the research setting will be protected from unauthorized disclosure, a project that not only requires the cooperation of researchers and health institutions, but auxiliary participants, such as database managers. Very generally, the U.S. does have norms for the protection of human subjects generally, most notably the Common Rule, which establishes standards to protect human research subjects and is applicable to all federally-funded research. While a patient can rely on HIPAA for some medical privacy, the research subject needs to be protected against the unauthorized disclosure of personally identifiable genetic information outside the medical care setting. One of its most significant recommendations is that no WGS be conducted without the consent of the individual. While that may sound straightforward and sensible, this point is relevant to the uses of surreptitious genetic testing that occur in criminal law, for example, but could be performed in other contexts (e.g., this issue addressed with the pending California bill on genetic privacy, SB 1267, which would “prohibit any person, as defined, from obtaining, analyzing, or disclosing genetic information without the written authorization of the individual to whom the information pertains”). The report notes a very uneven set of protections against unauthorized genetic testing and disclosure across the states. In total, the report calls attention to the wide array of entities that are involved in the processing of genetic information – not only scientific and medical, but third party data handlers – and calls for standardization of informed consent procedures to protect individual choice regarding genetic testing and its disclosure. It asks funders of such research to monitor privacy protections as a part of their review. While the report did focus on the ethical introduction of WGS into wider use, its recommendations are relevant to all types of genetic information and might serve to incorporate privacy safeguards as a routine dimension of genetically-based medical care and research.
A federal district court has rejected a legal claim by individuals in Guatamala who asserted their right to compensation for the unethical medical experimentation that was carried out by U.S. researchers in the 1940’s (Garcia v. Sebelius, Dist. D.C., 2012). The researchers from the U.S. Public Health Service exposed the plaintiffs to sexually transmitted diseases (syphilis, gonorrhea) to create research subjects. No informed consent or bioethical standards were used to conduct these studies; the participants were institutionalized (prisons, hospitals, etc.) and had little control over the conditions of their confinement. The legal claim was filed under the Alien Tort Statute, which provides a mechanism for aliens to file legal claims for violations of international law or treaties in U.S. courts. The statute has been used extensively to assert human rights claims in a variety of international settings; nonetheless, the scope of the statute is still hotly contested (see upcoming Kiobel v. Royal Dutch Petroleum, to be heard in the Fall 2012 term). The specific legal issue in the Guatamala case was whether the government, would face liability under the Federal Tort Claims Act (FTCA), which does expose government employees to liability when their acts are which ordinarily concedes a waiver of sovereign immunity by virtue of the existence of the statute for caused by the negligent or wrongful act or omission of any employee of the Government while acting within the scope of his office or employment, nonetheless would escape lliability due to an exception for activities conducted in a foreign country. Although the plaintiffs asked the court to carve out an exception to that clause in this case, the court rejected that argument: “Here, the plaintiffs' Alien Tort Statute claims all arise out of injuries suffered in Guatemala, and the claims are thus barred by the FTCA's foreign country exception.” The court further noted, that despite its inability to grant relief, the U.S. government has conceded the severe injustices of this case and has declared its intention to provide redress. Indeed, the State Department issued an official apology in 2010: “We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices.” The Presidential Commission on Bioethical Issues also issued a report (discussed here). No official compensation scheme has been announced by the U.S. government.
A scholarly survey of the emerging field of synthetic biology has been published by a team of researchers from the UK and Japan, and published in the open-access journal, PLOS One. This is a timely overview of this field, international in scope. The authors detail the language problems that can attach to new fields, where different practitioners or commenters use disparate terms to describe this work. For example, synthetic biology is a field that combines engineering with biology, but in this respect, it overlaps with the established field of genetic engineering, which has been around now since the 1970’s. So what accounts for the difference? Some of it is in the ambition of the field, where declarations of the goal to create entirely new organisms are routine; in contrast, genetic engineering usually relies on genetic manipulation of existing organisms (microbes, plants) to add useful phenotypes. Synthetic biology is also associated with the imperative to unravel biological mechanisms with the goal of establishing a catalogue of modular “parts” that can be used to design new biological circuits and new organisms (see, e.g., the Biobricks initiative which does just that). For legal purposes, this article locates the field against the backdrop of relevant international instruments which have bearing on this field (the Convention on Biological Diversity, relating to equitable sharing of genetic resources) and the Cartagena Protocol on Biosafety (relating to guidelines for the use and transport of living modified organisms). With respect to the U.S., the most authoritative consideration of the legal issues raised by synthetic biology was undertaken by the Presidential Commission for the Study of Bioethical Issues (PCBSI), which published its 2010 study of synthetic biology and issued recommendations for continuing vigilance (noting serious issues of risk assessment and management that could attend the design and release of novel organisms), but no calls for either a moratorium or specific regulation at that time (in fact, noting categorizing its approach as “regulatory parsimony”). More generally, the PCBSI defined a framework for “five ethical principles relevant to considering the social implications of emerging technologies: (1) public beneficence, (2) responsible stewardship, (3) intellectual freedom and responsibility, (4) democratic deliberation, and (5) justice and fairness.” What’s also interesting is a follow-on effort started this year by the Woodrow Wilson International Center for Scholars to track how the recommendations of the PCBSI are implemented. For example, their Synthetic Biology Project scorecard documents no federal activity pursuant to various recommendations relating to risk assessment, where there was federal activity related to ethics and public education. In sum, this new scholarly work on synthetic biology is a necessary prerequisite to any serious international oversight of the field, in that such an effort must be rooted in empirical knowledge of the scope of the field and its practitioners.
The Presidential Commission for the Study of Bioethical Issues released its report, Moral Science, on the state of human subject research in federally-funded studies. The report was commissioned following the revelations that the U.S. Public Health Service had conducted unethical research studies in Guatemala in the 1940’s, in which individuals were deliberately infected with venereal disease in order to study prevention and treatment. Following that report, a formal apology from the U.S. government to Guatemala was issued by Secretaries Clinton and Sibelius (State and Health and Human Services). This new report from the Commission concluded favorably that many protections are in place for human subjects (chiefly underpinned by the Common Rule norms of informed consent, independent ethical review and the minimization of risks) but that some further measures could increase transparency and monitoring. Over 55,000 federally-funded studies were identified by the commission, including medical and social science research. Specifically, the report strongly urges the U.S. to follow the lead of other countries which have established formal compensation schemes for victims of unethical research conduct. In that vein, this move echoes an earlier report here on the North Carolina state compensation fund for victims of state-mandated sterilization procedures. There is precedent for this commission and its work: a long line of bioethics-related advisory commissions established by the executive or legislative branches for the last forty years. These groups can respond to presidential requests for timely expert advice on new developments in life sciences (e.g., Clinton and human cloning; Bush and embryonic stem cell research). An interesting note to this report is the commission's acknowledgement that some of its work duplicates earlier recommendations of other advisory panels regarding formal compensation for research-related injuries: it calls on the executive branch to "publicly release reasons for changing or maintaining the status quo." This might be a useful mechanism to insert in other studies where redundancy of effort is apparent (a special trap for advisory committees without formal power) and the requesting party (here, the Obama administration) should be held accountable for a formal response to the committee's work, rather than silence, which often translates to disregard.
