In vitro diagnostic (IVD) devices, including genetic tests, provide information that is used to inform health care decision making. IVDs are devices that are used in laboratory analysis of human samples an d include commercial test products and instruments used in testing, among other things. IVDs may be used in a variety of settings, including a clinical laboratory, a physician's office, or in the home. IVDs have a number of uses, such as diagnosis, screening, staging, and disease management, including, for example, the selection and dosing of therapeutics. One estimate found that the results of clinical laboratory tests influence approximately 70% of health care decisions. Despite this broad effect on the delivery of health care, spending on IVDs represents a small portion of overall health care costs. The Centers for Disease Control and Prevention (CDC) estimated that, based on 2007 data, approximately 6.8 billion clinical laboratory tests are performed in the United States annually, but noted that "publicly available information about the economic status and quality of the laboratory medicine sector remains limited." IVDs may be used in the care of a patient in numerous ways (see text box) and at various points in the delivery of care. IVDs differ from other medical devices in that they do not act directly on a patient to produce a result as does, for example, an implantable stent that keeps an artery open to allow blood flow. Instead, the potential for risk of harm to the patient would be from the generation of inaccurate test results that could lead to the mismanagement of a patient's disease or condition (i.e., false negative test result) or to treatment for a disease or condition that is in fact absent (false positive test result). Given this potential risk, as well as the impact on the overall delivery of health care, the federal government has taken a role in the oversight of IVDs. Federal oversight of IVDs spans several federal agencies, including the Food and Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS). Oversight efforts focus on ensuring the safety and effectiveness of IVDs; the accuracy and reliability of IVDs; the quality of clinical laboratories that carry out IVD testing; the utility of the information in clinician and patient decision making; and the truthfulness of claims made about IVDs that are marketed directly to consumers. IVDs include genetic tests, a type of diagnostic test that analyzes various aspects of an individual's genetic material (DNA, RNA, chromosomes, and genes). Through basic research, scientists have "discovered hundreds of genes that harbor variations contributing to human illness." They have also found "genetic variability in patients' responses to dozens of treatments" and are using IVDs "to better predict patients' responses to targeted therapy." The use of an IVD companion diagnostic device to select the best therapy, at the right dose, at the correct time for a particular patient is often referred to as personalized medicine. Another term, pharmacogenomics, is sometimes used interchangeably with personalized medicine. Pharmacogenomics is the study of how individual genetic variation affects a person's response to drugs. Currently, more than 100 FDA-approved drugs contain pharmacogenomic information in their labeling. The regulation of genetic testing has raised several issues. Traditionally, most genetic tests have not been subject to premarket review by the FDA. It has been noted that, in the past, genetic tests were developed mostly by academic or research laboratories primarily for in-house use—tests referred to as laboratory-developed tests (LDTs)—to diagnose rare diseases and were highly dependent on expert interpretation. In recent years, LDTs have been developed to assess relatively common diseases and conditions, such as various cancers. The extent to which all LDTs should be regulated by the FDA has been a subject of debate. On July 31, 2014, the FDA officially notified the Senate Committee on Health, Education, Labor and Pensions and the House Committee on Energy and Commerce that it would be issuing draft guidance on LDT regulation; on October 3, 2014, the agency published a notice in the Federal Register announcing the availability of the guidance documents and requesting comments within 120 days to ensure their consideration in the development of final guidance. The agency announced in November 2016 that it would be delaying finalization of the draft guidance. In January 2017, FDA released a discussion paper on LDTs that included a possible approach to LDT oversight (for more detail, see " FDA's January 2017 Discussion Paper: A Possible Approach to LDT Oversight "). The appropriate degree and extent of federal regulation of direct-to-consumer (DTC) genetic testing has also been a subject of debate amongst relevant federal agencies as well as the affected entities (mostly for-profit companies, for example, 23andMe, Pathway Genomics, or Life Technologies). Genetic testing has become increasingly available for direct purchase by consumers, generally over the Internet. In this type of testing—direct-to-consumer genetic testing—the consumer sends in a tissue sample, often cells from the inside of the cheek, and the results are conveyed directly to the consumer by the company that developed the test. Almost a decade ago, in 2010, the Government Accountability Office (GAO) testified that in its investigation of DTC genetic tests—priced from $299 to $999—from four companies, it found the DTC genetic test results to be "misleading and of little or no practical use to consumers." However, in a reflection of evolution in both DTC genetic tests themselves and FDA oversight of these tests, in April 2017, FDA approved the first DTC genetic test that provides information about the risk of developing disease (predisposition). This test, 23andMe's Personal Genome Service Genetic Health Risk, provides consumers with information about their likelihood of manifesting 10 diseases or conditions (e.g., celiac disease, Parkinson's disease). Congress and the regulatory agencies have historically been interested in balancing the goals of allowing consumers to have access, as quickly as possible, to new and improved medical devices with preventing devices that are not safe and effective from entering or remaining on the market. In the case of IVDs, and specifically, LDTs, Congress has introduced bills that attempt to address both of these goals, that is, to support innovation and to increase or expand regulatory oversight. Approaches have included, among others, streamlining regulation by concentrating it in a single federal agency or requiring the FDA to assert its enforcement authority over LDTs. In addition to its role as regulator, the federal government has a role as a payor for IVDs, primarily through the Medicare program. Medicare covers outpatient clinical laboratory testing and generally reimburses for these tests based on the Clinical Laboratory Fee Schedule (CLFS). Medicare also covers clinical laboratory testing conducted during inpatient care either in a hospital or a skilled nursing facility (SNF). Although an in-depth discussion of this issue is outside the scope of this report, the federal role as payer intersects with its role as regulator. This is due to the fact that, as a payor, Medicare generally will only cover IVDs that have passed FDA premarket review—either approval or clearance—where such FDA review is required by applicable statute and regulation. However, in these cases, FDA approval or clearance is not sufficient in and of itself to result in a favorable coverage decision by CMS for any given IVD. This report provides an overview of federal regulation of IVDs by FDA, through the Federal Food, Drug, and Cosmetics Act (FFDCA) and the Public Health Service Act (PHSA), and by CMS, through the Clinical Laboratory Improvement Amendments (CLIA) of 1988. It then provides a discussion of the oversight of LDTs—including the history of the debate over regulating LDTs and a description of FDA's recently announced Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) —as well as an overview of the regulation of DTC genetic tests. Terms used throughout this report are defined in the text box. As with other medical devices, the application of FDA regulatory requirements to IVDs depends on the IVD's risk classification according to its intended use. Risk classification "is based on the risk the device poses to the patient or the user and the information available to address that risk. " The risk classification process is described in more detail in the "IVD Regulatory Requirements" section of this report. IVDs are defined in regulation as a specific subset of medical devices that include "reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions ... in order to cure, mitigate, treat, or prevent disease ... [s]uch products are intended for use in the collection, preparation, and examination of specimens taken from the human body." As indicated by this definition, an IVD may be either a complete test or a component of a test. In either case, the IVD comes under FDA's regulatory purview. Test components include both non-diagnostic ingredients, called general purpose reagents (GPRs), and the active ingredient in a diagnostic test, referred to as the analyte specific reagent (ASR). There are two routes to market for an IVD used in the clinical management of patients. In one route, the product is developed, produced, and sold by a manufacturer for distribution to multiple laboratories—referred to as a "commercial test kit." In the second route, the product is developed by and used in a single laboratory—referred to as a "laboratory developed test," or LDT. LDTs may use ASRs or GPRs that are either manufactured in-house by the laboratory or that are commercially developed and distributed. The FDA has been generally exercising enforcement discretion for LDTs in that the agency has generally not enforced applicable regulatory requirements. IVDs that are used in the clinical management of patients generally fall under the definition of medical device and therefore are subject to regulation by the FDA.