December 30, 2012

Advocates Call on HHS to Include Genetic Testing in ACA Benefits

As the Affordable Care Act (ACA) begins to shape some parameters of the health care system in the U.S., there are many details to be worked out. A centerpiece of the law is that states can set up health care exchanges for the purpose of pooling uninsured residents so they can obtain health coverage in an economically efficient manner. The goal is to provide a system that will facilitate access to comprehensive medical coverage and prescription drug benefits. However, several obstacles to the concept of the state exchanges are evident: states may decide not to set up a health care exchange or, alternatively states that do set up an exchange can define the contours of the coverage provided. Under the ACA, the concept of essential health benefits (EHB) has been central: the ACA mandates a set of guaranteed services that an insured can expect from any insurance plan covered by the ACA, including those provided through a health care exchange ("such as hospitalization, prescription drugs, and maternity and newborn care.") One of the ten categories of EHB is "laboratory services." In November, HHS issued proposed rules for covered insurance plans and state health care exchanges, detailing the EHB that are required to comply with the ACA. In a letter to The Centers for Medicare & Medicaid Services (CMS) (the laboratory-regulating agency in HHS) the College of American Pathologists (CAP) has called on HHS to clarify the definition of laboratory services, noting that some states are differentiating genetic testing from other tests, which will narrow the diagnostic options for those covered. 

The CAP strongly supports the inclusion of genetic and genomic testing, when medically necessary for clinically relevant diagnostic purposes, pre-disposition studies, and treatment, as a laboratory service required under PPACA for all qualified health plans in federal or state health insurance exchanges…..We therefore urge the agency to clarify that genetic and genomic testing, as a subset of laboratory services that are mandated for coverage under the Affordable Care Act, be included as a covered service offered by any qualified health plan under a state or federally operated health exchange. 

As the health care exchanges begin to take shape in 2013, the particular issue of genetic testing in the ACA mandate highlights how genomic medicine is taking a distinct profile in the health care system, but such individuation could be used to segregate new technologies due to concerns about cost. It is essential that any disparate treatment of genetic services be flagged early as the ACA begins to define health care access in the U.S.

December 29, 2012

Virus Research Controls Debated; Emerging Infectious Diseases

The recent meeting of the National Science Advisory Board on Biosecurity this month was a public event to consider the status of gain-of function experiments with highly pathogenic avian influenza H5N1 (HPAI). Such experiments were the basis of two controversial papers published earlier this year that elevated concerns over whether scientific research carried the danger of producing dangerous viruses that posed threats to human health. The meeting considered biosafety issues as well as the new NIH research funding framework. The development of a more stringent review process for NIH funding of such research is underway; public comments on the proposed policy are invited until January 10, 2013. Reports from the meeting indicate an emerging consensus from the participants that the current voluntary moratorium on HPAI research should be ended. Separately, the comment period to respond to the CDC’s question of whether HPAI viruses should now be included in the most stringent class of biological agents, Tier 1, has been extended to January 13, 2013. 

A recent review paper by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and colleagues looks at 20 years of emerging infectious diseases (EID). The concept of EID was elevated into prominence with the publication of an Institute of Medicine report in 1991 that considered EID as threats to U.S. health. The 20 year period since encompasses the AIDS and SARS pandemics, although the AIDS crisis began in the 1980’s. Both are viral diseases, and the difficulty in designing effective treatment regimens underscores the fears associated with a possible emergence of pandemic influenza. The concept of EID as a critical focus of public health research and surveillance is well-established, and the SARS pandemic in 2003 illustrated not only the obvious scientific challenges, but how international cooperation (e.g., data-sharing) was essential to tracking outbreaks. Another recent paper in PLOS Medicine analyzes pandemic preparation with reference to lessons learned from SARS and other international public health crises, noting that although pandemics will appear in the developed countries because of global travel, etc., the likelihood of initial pathogen emergence in less-developed countries means that public health infrastructure remains a general gatekeeper to the world's overall health. The authors caution that disease-specific programs (e.g., AIDS-specific, vertical) can shift focus and resources from baseline public health maintenance in a manner that facilitates the development of pandemic outbreaks. In an effort to locate the “proximate driver implicated in each outbreak” the authors find that the most significant predicate is the “breakdown of public health measures includes inadequate sanitation and hygiene, e.g., the shortage of potable water, poor immunization coverage or the lack of infrastructure to purchase and deliver vaccine, and the deterioration of vector-borne and zoonotic disease control.” Thus, pandemic preparedness relies on a combination of high-tech and low-tech measures; determining the genome sequence of an emerging virus is routine today, but such a technical achievement does not supplant the need for investment in the low-tech infrastructure that helps to limit the spread of any emerging pathogen.

December 21, 2012

FDA: No Environmental Impact of Genetically Engineered Salmon

The FDA has released a draft environmental assessment (EA) for the proposed introduction of genetically engineered salmon as a food product (AquaBounty Technologies AquAdvantage salmon). To produce the GE salmon, Atlantic salmon is engineered to contain the growth hormone gene from Pacific Chinook salmon, which causes the fish to grow in less time; the gene is placed under the control of a promoter from ocean pout, which causes elevated expression of the hormone. The fish are to be only sterile females (although not 100%; the FDA notes that "proposed conditions of use specify that a minimum of 95% of the AquAdvantage Salmon eggs sold for commercial production use would be triploid (sterile)"). The production plans submitted to the FDA include the preparation of the GE fish eggs in Canada, and the actual production of the fish in Panama. Thus, neither process will occur in the U.S. The introduction of the new gene to the salmon triggers an FDA review of the genetic addition as a new animal drug application (NADA) (Federal Food, Drug & Cosmetic Act, 21 USC § 321 et seq.). The NADA review, conducted by the Center for Veterinary Medicine, must consider both food safety and environmental consequences of the proposed product; the 2010 FDA assessment concluded that food from these salmon “is as safe as food from conventional salmon, and there is a reasonable certainty of no harm from consumption of food” from these fish. The new EA prepared by the FDA pursuant to National Environmental Policy Act (NEPA) procedures – and its finding of no significant impact (FONSI) – means that the FDA will not be preparing an environmental impact statement for the introduction of the fish.

Food safety advocates have criticized the FDA’s record of assessments to date, and have called on the legislators to ban the production of the fish. The Alaska Congressional delegation is already on the record opposing the introduction of the GE salmon (see here). In addition, current FDA policy will not require the GE salmon to be labeled. The retail sale of fish requires at least country of origin labeling; the sale of food products in fish markets or restaurants does not carry any such labeling. What remains unsettled (and may further antagonized with this recent report) is whether efforts by food safety advocates to transfer GE fish into the more “conventional” category of food additive review processes will succeed; whether labeling could be required (the experience with other GE foods to date would suggest not); and even whether the environmental assessment to date is adequate (critics say no: not all fish were tested in the native conditions of production; reproductively-capable fish are present and could escape). More broadly, can a veterinary-based product review supply adequate oversight for the introduction of a genetically engineered food into the market? Does the review process for GE salmon establish a paradigm for other GE animal or fish products? The most direct response might come from Congressional action which singles out the GE salmon for targeted legislative regulation or prohibition (see here). The Alaska delegation has already responded, with Sen. Mark Begich (D-AK) sharply critical of the EA report, and calling for the public to provide comments to the FDA.

December 9, 2012

Regulation of Highly Pathogenic Avian Influenza H5N1 Virus Research: NSABB, NIH, CDC

Earlier this year, the controversy over recent scientific experiments that produced potentially pandemic-level viruses (highly pathogenic avian influenza H5N1; HPAI) largely centered on the merits of publishing such research. The National Science Advisory Board for Biosecurity (NSABB) initially recommended against publication by scientific journals, but later relented and supported publication (one in full, one edited). The broader question of whether such experiments should be funded by the National Institutes of Health (NIH) at all – the HPAI H5N1 work in both laboratories received NIH support – was left unanswered. However, in March, the NIH published its policy for the oversight of life sciences dual research of concern (DURC) (research capable of benign and malicious uses, such as the recent HPAI H5N1 experiments). More recently, the NSABB has returned to the difficult questions regarding the funding of DURC. At last week's NSABB meeting, the NIH unveiled a potentially more exacting review process to determine whether or how the “gain-of-function” experiments that produced the HPAI H5N1 viruses should be funded. "Gain-of-function” refers to research that is undertaken to investigate the genetic structure of viruses, but, in the process, results in the production of an even more dangerous virus. Could such an outcome be avoided? To illustrate how NIH would assess that possibility, the proposed NIH framework asks that applicants declare that their work is unlikely to produce a “gain of function” virus, unless that could demonstrate that such a virus is likely to occur naturally. Can that be meaningfully answered? The wild card in the attempt to set up a risk-managed funding program is how scientists can imagine the biological sources of risk before actual research has identified or confirmed such details.

The proposed framework from NIH also links public funding with public disclosure: “As a general matter, HHS should only fund research that is reasonably anticipated at the proposal stage to generate information, products, and technologies that can be openly communicated.” This statement recalls the controversy earlier this year, where the risks from already completed research were to be managed by publication controls imposed after the fact. The NSABB will hold a public workshop on gain-of function experiments with HPAI H5N1 viruses on Dec.17-18, 2012 to discuss "the implications of such research for global public health, risks and concerns associated with this research; the risks of not pursing this type of research; fundamental principles regarding the conduct and oversight of such research; and conditions under which such research might be conducted." The lineage of these discussions post-9/11 goes back to the 2004 National Research Council report, Biotechnology Research in an Age of Terrorism (Fink Report), as well as the NSABB’s own 2007 framework, which amplified the Fink Report’s concerns and signaled the need for points of intervention at the funding or communication stages of the research trajectory. Thus, these questions are not new; they are just made more acute by recent events and HPAI H5N1 viruses have become the pathogens of concern. To illustrate that point, the Centers for Disease Control (CDC) has published an announcement in the Federal Register asking for comments on whether HPAI H5N1 influenza should be added to the CDC list of select agents (such classification would authorize closer monitoring of research projects). Further, HHS has carved out a class of select agents with the greatest risk of misuse (Tier 1) and asks whether the classification should obtain for this influenza strain, given its properties. Comments are due by December 17, 2012.