CLIA-Waived Tests Mean Nothing Can Go Wrong. . .Right?
CLIA-Waived Tests MeanNothing Can Go Wrong. . .Right?Norman Moore, PhDProprietary and confidential — do not distribute
Leading Causes of Deaths in the United States1. Cardiac eventsProprietary and confidential — do not distribute
Leading Causes of Deaths in the United States1. Cardiac events2. CancerProprietary and confidential — do not distribute
Leading Causes of Deaths in the United States1. Cardiac events2. Cancer3. Medical errorsProprietary and confidential — do not distribute
Medical Errors200,000 American deaths each year areassociated with preventable harm inhospitalsCost associated with errors exceeds 17billion annuallyUp to 70% of clinical decisions influencedby laboratory resultsDaniel M and Makary M. Medical error – the third leading cause of death in the US. BMJ 2j016. 353:i2139. Proprietary and confidential — do not distributeMay 15, 20185
Changes in Medical TestingProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 20186
Where Are Medical Tests Being Done?LaboratoryEmergency DepartmentDoctors’ OfficesAmbulancesUrgent Care CentersPharmaciesHomePublic Health VansNightclubs, concerts, . . .Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 20187
Who Is Doing tionists. .Proprietary and confidential — do not distribute8
Crisis In The LaboratoryLack of medical technologists is a national issue The US Department of Labor’s Bureau of Labor Statistics is estimatingdemand to increase for med techs by 22% from 2012 to 2022 Current programs expected to give half of what is needed Less than 5,000 people are graduating each year from accreditedprograms The number of accredited programs is declining About 50% of med techs are within 10 years of retirementCurrent medical technologists Senior people On the job trainingProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 20189
Why Aren’t People Staying In the Field?EducationMoneyProprietary and confidential — do not distribute Medical technologist requiresbaccalaureate and year of training inaccredited or approved laboratory training Medical technician requires associatedegree and a year of training Median salary is below registered nurses,physical therapists, and pharmacists.Enter title via "insert header and footer footer" May 15, 201810
Let’s Talk Clinical SamplingProprietary and confidential — do not distribute11 Enter title via "insert headerMayand15,footer footer"2018
Capillary Blood SamplingWhy?Who Less pain for thepatient Less invasive Easy and fast to collect Pediatric patients soless blood volumerestriction Obese Geriatric Anxious patients Severe burns Veins are hard to get –fragile or inaccessibleProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201812
What Can Affect Measuring Hemoglobin?Gender – Women are lower than men1Pregnancy – Hgb declines in first trimester and continues to fall in second before rebounding2Collection site – Ear stick can be higher than venous or fingerstick3Type of sample – Capillary blood has more Hgb than venous1Altitude – Hgb increase at high altitudes to make up for lower concentrations of oxygen2Smoking – Proportional change to how much the person smokes2Time of day – Hgb is usually highest in the morning2Body position – Hgb is increased when standing compared to sitting or laying down1Dehydration – Loss of plasma1CableRG, Steele WR, Melmed RS, et al. The difference between fingerstick and venous hemoglobin and hematocrit varies by sex and iron stores. NHLBI retrovirus epidemiologydonor study II (REDS II). Transfusion. 2012. 52: 1031-1040. doi: 10.1111/j.1537-2995.2011.03389.x2Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World HealthOrganization, 2011 (WHO/NMH/NHD/MNM/11.1). Available at: www.who.int/vmnis/indicators/haemoglobin.pdf. Accessed October 11, 2017.3Wood EM, Kim Dm, Miller JP. Accuracy of predonation Hct sampling affects donor safety, eligibility, and deferral rates. Transfusion. 2001. 41: 353-359.Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201813
. . .And Then There is Sample CollectionUse the appropriate finger Usually middle or ring finger. Ring finger has less painDon’t milk the finger as you get more interstitialfluid Appropriate size lancet Can massage up to first knuckleGet right sample Clean and disinfect site Wipe away alcohol so it doesn’t dilute blood Usually wipe away first drop (for Hgb, can be variable for first 3)Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201814
Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201815
Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201816
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Throat SwabsProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201818
Improper Throat Swabs with Strep AWhat happenswith cheek swab?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201819
Improper Throat Swabs with Strep AWhat happenswith saliva onthe swab?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201820
Improper Throat Swabs with Strep AWhat happenswith back ofthroat?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201821
Nasopharyngeal SwabsProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201822
What Happens With Improper NP SwabMust use NP rather thannasal swab!Small tip swab collects lesssample in a site with lessvirus.Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201823
Nasal SwabProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201824
Immunological TestsProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201825
Defining Immunological TestingAntigen: the part of a molecule that an antibody bindstoAntibody: a molecule the body makes to bind to anantigenProprietary and confidential — do not distribute
Multiple Types Of AntibodiesIgM is first antibody to respond characterizes a recent infectionIgG is second antibody to respond Used for primary and secondary infectionIgGIgMProprietary and confidential — do not distributePolyclonal vs.Monoclonal
Serological Response To InfectionAntibody concentrationIgMIgGTimeProprietary and confidential — do not distribute
Lateral Flow SchematicProprietary and confidential — do not distribute
Lateral Flow TypesDirect antigen Pregnancy, Strep A, and InfluenzaSerological HIVCompetitive (a negative line means a positive result) DOAProprietary and confidential — do not distribute
Direct Antigen DetectionVisualizing AntibodyAntigenCapture AntibodyNitrocelluloseProprietary and confidential — do not distribute
Serology DetectionLooking for a person’s antibody response to disease (the blueantibody)Visualizing AntibodyAnalyteAntigenNitrocelluloseProprietary and confidential — do not distribute
Issues With Antibody BasedReactionsHeterophile antibodies, such as HAMA (human anti-mouse antibodies) Can cause false results Some tests can incorporate a HAMA blockerRheumatoid factors Autoantibodies in clinical sample, usually IgM that can bind to IgGantibodiesHook effect Analyte is in high concentrations capture and detector antibodiesare saturated Creates False negativesAntigen break-down If antigen denatures, antibodies may not be able to sandwich thetargetProprietary and confidential — do not distribute
What are Common Mistakes For Running Lateral FlowStorage Is it stored refrigerated? If so, is it supposedto warm up first? Was it not stored refrigerated when it shouldRead time Are you using a timer? What is the problem when you read too early? What is the problem when you read too late?ContaminatingreagentsProprietary and confidential — do not distribute Where did you put the sample? Is it in contact with your hands or reagentbottles?Enter title via "insert header and footer footer" May 15, 201834
Issues with People Reading the TestLight lines can be missed by some peopleMultitasking can lead to not reading at theright timeNot having clinical samples or tests properlyidentifiedTranscription errorsProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201835
What is Wrong With This Picture?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201836
Molecular TestsProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201837
Molecular AmplificationDouble-stranded DNA95 DenaturationHeating separates strands72 ExtensionTaq Polymerase reads existingDNAstrand to create a new matchingone57 AnnealingPrimers Bind to targetsequencesTaq Polymerase Binds at Primer SitesProprietary and confidential — do not distribute38
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What is Wrong With This Picture?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201840
Molecular Testing Near PatientWhat can go wrong Technician touches swab head and thentouches other samplesrunning positive Sample can be laid down on bench so canand negativecontaminate other areascontrol swabs?What Can Go WrongDuring? Anything that interacts with enzymes Point mutationsWhat can go wrongAFTER running a Amplicon!molecular test?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201841
PregnancyProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201842
What Does the Pregnancy Test MeasurePregnancy tests havedifferent hCG cutoffs High sensitivity tests Low sensitivity testsWhy?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201843
What Can Cause False Positives?Menopausal womenPost partum womenPeople taking hCG supplementsFertility medications that contain synthetic hCGOvarian cancerProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201844
What Can Cause False Negative?Testing too earlyPotentially testing late pregnancies! Breakdown of hCG into α and β subunits Publications have shown this can happen in late pregnanciesProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201845
InfluenzaProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201846
Influenza A versus Influenza BInfluenza A More severe disease than B Can cause disease in a wide variety of animalsInfluenza B Causes a milder flu, usually in the springmonths
What Makes You Ache When You Have InfluenzaInfluenza Is attacking epithelial cells in the nose, throat, and respiratorysystemBody’s reaction Releases histamine which widens the blood vessels near infection Allows immune responses like antibodies to get to the infectionbetter Histamines also end up in other body parts like muscles Cytokines are also released that help coordinate the body’s attackon virusThe problem Histamines and cytokines can affect pain receptorsProprietary and confidential — do not distribute48
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What Can Increase Cases of Seasonal Influenza?Vaccine Mismatch Vaccine is madeby predictingstrains for nextseason so maynot be accurateProprietary and confidential — do not distributeMultiple strainshitting at the sametime Can havemultiple strainsas well as overlapof influenza Aand BVirulence ofStrains Some strains cancause an extremeimmuneresponse
Hypothesis On Evolution of Feeling BadWhen You Are SickIf a person feels sick,they are going tostay in bedIf they stay in bed,they are less likely toexpose other peopleProprietary and confidential — do not distribute51
Should You Get the Fever Down?Why Do YouGet a Fever? Your immune system releases chemicals called pyrogens The hypothalamus portion of the brain get the pyrogensand raises the temperatureIncreasedtemperature Can kill some bacteria Can inhibit the replication of some virusesWhen youreduce the feverDo you reducethe fever?Proprietary and confidential — do not distribute Don’t reduce the amount of virus Research is suggesting that tens of thousands of morepeople can be then infected! If too high, yes! If not too high. . .52
Differences Between the SexesWomen tend to generate stronger immune responses thanmen Helps clear virus faster from the systemThe good Lower virus can shorten intensity and duration of illness Especially important if pregnantThe bad More likely to have hyperimmune response so could have highermorbidity/mortality in outbreak or pandemic Chronic infections (like HIV) have been linked to accelerating theaging processProprietaryandHodgsonconfidentialdo not distributeKlein, SL,A, —RobinsonDP. Mechanisms of sex disparities in influenza pathogenesis. Journal of Leukocyte biology. 2012.53Jul: 92(1) 67-73
Influenza Sample CollectionAppropriate specimensSamples should be collectedwithin first 24 to 48 hoursof symptoms since that iswhen viral titers are highestand antiviral therapy iseffectiveProprietary and confidential — do not distribute Nasal wash/aspirate,nasopharyngeal swab, or nasalswab Throat swabs have dramaticallyreduced sensitivity Reduction in sensitivity overdays – NOT related to howpeople feel
Sensitivity vs Specificity vsPPV vs NPVSensitivity:Probability test positive if patient positiveSpecificity:Probability test negative if patient negativePPV: Probability patient positive if test positiveNPV: Probability patient negative if test negativeProprietary and confidential — do not distribute
Flu is seasonal. Prevalence of the disease is different in June than inJanuary.This will impact the perceived performance of the testTest 1,000 personsTest Specificity 99.6% (4/1000)Prevalence 10%True positive:100Positive predictive value:Proprietary and confidential — do not distributewww.cdc.gov/hiv/rapid testingFalse positive:4100/104 96%
Test 1,000 personsTest Specificity 99.6% (4/1000) Prevalence 10%True positive: 100False positive: 4Positive predictive value: 100/104 96%Prevalence 0.4%True positive:4Positive predictive value:Proprietary and confidential — do not distributewww.cdc.gov/hiv/rapid testingFalse positive:4/8 50%4
RSVProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201858
How many people have hadRSV in their lives?CONFIDENTIAL. FOR INTERNAL USE ONLY. NOT FOR PRINT OR DISTRIBUTION.59
Almost ALLpeoplein this roomhad RSV by the age of 2!CONFIDENTIAL. FOR INTERNAL USE ONLY. NOT FOR PRINT OR DISTRIBUTION.60
RSV – Who Do You TestUnder5? Lateral flow andNAAT tests areavailableOver65? Don’t do lateralflowProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201861
Strep AProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201862
Strep A ReagentsProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201863
Strep A IssuesReagent 1 and 2 When mixed,make unstablenitrous acid The acid is meantto expose theantigenProprietary and confidential — do not distributeHow can 2bottles be anissue? What happens ifcaps getexchanged? What happens ifsetting up early?Enter title via "insert header and footer footer" May 15, 201864
HIVProprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201865
CDC/APHL HIV Diagnostic Algorithm1Initiate CareInitiate CareProprietary and confidential — do not distribute66
How do rapid tests fit into HIV algorithm?Use the algorithm when practical Most situations where HIV testing isdone does not have largeinstrumentationRapid tests If negative, no further testing If positive, start at beginning ofalgorithmProprietary and confidential — do not distribute
Role for Rapid HIV TestsIncrease receipt of test resultsIncrease identification of HIV-infected pregnantwomen so they can receive effective prophylaxisIncrease feasibility of testing in acute-caresettings with same-day resultsIncrease number of venues where testing can beoffered to high-risk personsProprietary and confidential — do not distribute
HIV Infection & Laboratory MarkersModified after Busch et al. Am J Med. 1997
So Why Do CLIA-Waived POCTests?Proprietary and confidential — do not distributeEnter title via "insert header and footer footer" May 15, 201870
Let’s Talk PandemicInfluenza. . .Proprietary and confidential — do not distribute71 Enter title via "insert headerMayand15,footer footer"2018
Advantages of Rapid Testing forInfectious DiseasesFaster directed therapy to reduce: antibiotic resistance hospital length-of-stayReduced length-ofstay in EmergencyDepartmentLess adverseconsequencesTeachable momentTimely application of appropriateinfection control procedures72
AMR: If We Don’t Take Action NowDeaths attributable to AMR every yearcompared to other major causes of deathDeaths attributableto AMR every yearby 205073
Global Antibiotic Resistance Crisis“There aren’t enough good rapid tests to confirm theprofessional judgment of the doctor,. this is not acceptable:we need to encourage more innovation and ensure thatuseful products are used. I call on the governments of therichest countries to mandate now that by 2020, allantibiotic prescriptions will need to be informed by a rapiddiagnostic test wherever one exists.12- Jim O’Neill 2016“12. O’Neill, J. Tackling drug -resistant infections globally: Final report and recommendations. The Review on antimicrobial resistance. May 2016.74
What’s driving the need for rapid accurate diagnostic tests?Transition to “patient-centered” value based health service delivery8 Get the diagnosis right the first time Diagnose in an actionable timeframe Early optimal treatment selection Avoid the waste of unnecessary investigations Avoid the waste of over treating Avoid the consequences of incorrect patient management Better health outcomes and reduced healthcare costsThe results of diagnostic tests are immensely influential,affecting around 60–70% of all clinical decisions,although they still amount for only 4–5 % of healthcare costs.88. Akhmetov, I. and Bubnov, R.V. Assessing the value of innovative molecular diagnostic tests in the concept of predictive, preventive, and personalized medicine. The EPMNAJournal (2015) 6:19.75
CLIA-Waived Tests Mean Nothing Can Go Wrong. . .Right? Norman Moore, PhD. . Who Is Doing Testing Medical technician Doctors. Nurses. Patients . . Get right sample Clean and disinfect site Wipe away alcohol so it doesn’t dilute blood Usually wipe away first drop (for Hgb, can be variable for first 3) .
2017 CLIA Waived Tests 2017 CLIA waived list QW modifier on Clinical Lab Fee Schedule Some CLIA waived tests do not require QW modifier CPT Short Description SI 81002 Urinalysis nonauto w/o scope Q4 81025 Urine pregnancy test Q4 82270 Occult blood feces A 82272 Occult bld feces 1‐3 tests Q4 82962 Glucose blood test Q4
CLIA requires that waived tests must be simple and have a low risk for an incorrect result. However, this does not mean waived tests are completely error-proof. . When a test is approved for both waived and non-waived testing, the manufacturer's instructions may include instructions that could be performed using more than one type
Vulnerable Idahoans can resume public interactions, but should practice physical distancing, minimizing exposure to social . Insurance Company WAIVED WAIVED NOT WAIVED SelectHealthBenefit Assurance Company WAIVED WAIVED WAIVED
"intended use" of the test system as approved by FDA and result in a test that is no longerwaived. For example, if a test specifies urine as the waived specimen type and you test a different body fluid, then you are no longer performing a waived test and your laboratory is subject to an inspection and additional CLIA requirements. You must
6.3 Waived & Non Waived POCT : If the point-of-care testing procedures are identified by CLIA as waived while others are moderately complex. A site performing only waived tests must have a ―Certificate of Waiver‖ license but will not be routinely inspected. They must however adher
Jul 11, 2011 · CLIA classifies tests according to complexity into waived and nonwaived categories. The non-waived category is further subdivided into tests of moderate and high complexity. This checklist covers only tests that are classified as waived or moderately complex (provider-performed microscopy [PPM] i
Dec 05, 2014 · TESTS GRANTED WAIVED STATUS UNDER CLIA. This list includes updates from Change Request FFS 10958 . CPT CODE(S) TEST NAME MANUFAC
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