Performance Standards for Allergen Skin Testing: An Approach to Proficiency Testing

Abstract

The importance ascribed to clinical laboratory tests with respect to having well-defined and validated methodology, test that fall within acceptable limits for accuracy, precision, and sensitivity, and ongoing documentation that operators performing test are proficient are subject of federal regulations derived from Clinical Laboratory Improvement Amendments (CLIA) of 1988. 3 The Health Care Financing Administration (HCFA) operates CLIA laboratory certification program in conjunction with Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). 3 CLIA defines laboratory testing as the examination of materials derived from human body for purpose of providing information for diagnosis, prevention, or treatment of any disease or impairment of, or assessment of health of human beings. 2 Under CLIA all entities providing laboratory testing are regulated and required by law to perform proficiency testing for specific tests. 2 Proficiency testing involves sending blind sample specimens with defined properties to each laboratory during year to evaluate whether laboratory's matches samples' defined properties. 2 Samples are required to be tested in same manner and by same individuals performing patient testing. 2 Results of proficiency test programs have been analyzed, 2 resulting in recognition that physician-operated testing laboratories experience a lower rate of successful test performance than traditional, previously regulated laboratories or physician-operated laboratories in which a laboratory professional provides supervision. The introduction of required proficiency testing has increased accuracy of test and quality of laboratory practice in physician-office laboratories, reflecting positive impact of CLIA over time. 2,15 FDA-licensed allergen vaccines approved for diagnostic use commonly are employed clinically to detect cutaneous immediate hypersensitivity to allergens of interest. Results of allergen skin tests impact clinical decisions. Positive test may indicate likelihood of life-threatening hypersensitivity to food, insect, or drug allergens or presence of environmental aeroallergens responsible for allergic disease. In each circumstance, there is an important impact on quality of life in terms of interventions designed to avoid exposure, pharmaco- and immunotherapeutic interventions indicated to reduce expected allergic response (if re-exposed), and psychosomatic sequelae and economic cost to patient associated with diagnosis. The adverse impact if test are falsely positive or negative should be considered, and attendent health and economic costs should be calculated. Similar considerations concerning adverse impact of inaccurate tests on quality of health care lead to passage of CLIA to increase patient and physician confidence in ability of tests to perform accurately according to objective standards, thus improving medical decisions and quality of care and decreasing economic burden of inaccurate test results. 2 Practice parameters for allergen skin testing 1 specify that the proficiency of skin tester should be validated by intrapatient and interpatient test results 1,11 and refer to proficiency tests and performance standards required by FDA for allergen standardization. 1 In latter context, investigators who submit allergen skin test data to FDA to define biologic potency of allergen vaccines for estimating US Standard of Potency 23 and to estimate cutaneous sensitivity of subjects 23 enrolled in clinical trials submitted to FDA in support of diagnostic or therapeutic efficacy of allergen vaccines are provided a skin test proficiency 22 The method is suitable for assessing proficiency of operator who is carrying out this technique and can be used to qualify personnel for submission of skin test data to CBER. 22 Before submitting allergen skin test data to FDA, Investigators should be familiar with Proficiency Method … and have submitted proficiency data qualifying their use of this method. 23 The allergen skin test Proficiency Method based on parallel line bioassay methodology described in 1982 24 has been subjected to international collaborative evaluation. 12,17,21 It has been used in support of skin test data submitted to FDA in support of licensure of standardized cat, housedust mite, and grass pollen extracts (see FDA-approved package inserts that reference use of FDA skin test methods). Test performance can be divided into two categories: analytical test performance and clinical test performance. 19 Analytical test performance refers to accuracy, precision, and sensitivity of a test to measure analyte of interest. 5 Clinical test performance is defined by clinical accuracy of test with respect to whether test accurately discriminates between disease and nondisease states. 25