This is the third in a series of articles that describe how different types of laboratory tests are developed, validated, and made available for use by patients and their health care providers. This section deals with the types of tests that are designed and developed to be used only in an individual lab and not sold to other facilities.
While most common laboratory tests are commercial tests, manufactured and marketed to several labs, some new tests are developed, evaluated, and validated within one particular laboratory. These tests, called "laboratory-developed tests" or "LDTs" are used solely within that laboratory and are not distributed or sold to any other labs or health care facilities. Often, a lab will choose to develop and use an LDT because a commercial test is not currently available.
There can be several reasons why a commercial test has not been developed for a particular analyte or disease of interest. For example, many LDTs are genetic tests that are developed for rare diseases. These are diseases that only a small subset of the population has, reducing the incentive for a manufacturer to develop a commercial version because the market for such a product would be small and not offer much, if any, return on investment. Or, an existing test may not apply to a particular subpopulation from which the lab has patients, so modification of the test is required. (Any FDA-approved commercial test that is modified in any way by a lab is considered to be a laboratory-developed test and is subject to the regulations applied to all lab-developed tests.)
Examples of some laboratory-developed tests include microscopic examinations (such as Pap smears and manual cell counts), erythrocyte sedimentation rates (ESR or sed rates), microbiology cultures and susceptibility tests, examination of tissue sections (including staining protocols), and blood cross-matching procedures. However, some of these tests may also be developed as commercial tests. For example, some susceptibility tests are produced and sold as kits; these would fall under the category of commercial tests and be subject to the regulations governing that category.
Because the laboratory-developed tests are not marketed to others, they do not require approval for marketing from the U.S. Food and Drug Administration (FDA) as do commercially developed and marketed tests. However, these types of tests must go through rigorous validation procedures and must meet several criteria before results can be used for decisions regarding patient care. Several governmental and non-governmental entities regulate and guide the development and validation of this group of tests:
- The federal government, through the Centers for Medicare and Medicaid Services (CMS) and the Clinical Laboratory Improvement Amendments (CLIA) highly regulates development, evaluation, and use of lab-developed assays. CLIA states that laboratories must demonstrate how well an LDT test performs using certain performance standards. Examples of such criteria include:
- Accuracy—the ability of a test to most closely measure the "true" value of a substance
- Precision—the reproducibility of a test result
- Test sensitivity—the ability of a test to detect a substance especially at relatively low levels
- Test specificity—the test's ability to correctly detect or measure only the substance of interest and exclude other substances
For a more in-depth discussion of these key concepts, see the section "Indicators of Reliability" in the article How Reliable is Laboratory Testing?
- Some state governments have requirements for validation of lab-developed tests that are equal to or more stringent than those outlined in CLIA. If CMS declares that the state standards are comparable to or more stringent than CLIA regulations, then the state is considered to be CLIA-exempt and the state requirements for evaluating a test or test system must be met. Currently, only New York and Washington are CLIA-exempt states.
- Several professional laboratory organizations such as the College of American Pathologists (CAP) and the Joint Commission offer laboratory accreditation programs. Participating laboratories must meet certain standards and criteria set by the accrediting agency. These standards often meet or exceed those set by CLIA, including standards regarding evaluation of lab-developed tests. Accreditation is an on-going process and labs must submit to regular inspections and evaluations of their policies, procedures, and documentation. Organizations such as Clinical and Laboratory Standards Institute (CLSI) seek to improve laboratory services by establishing, publishing, and promoting testing standards, including those to do with validation of LDTs.
In general, because they have not been evaluated by the FDA, LDTs must undergo a more lengthy and rigorous validation process by the individual laboratory wishing to implement the new method. The in-house procedure may involve numerous experiments, such as comparing the results from the new test method to those generated by a well-established test method.