Point of Care Testing Everything old is new again

Transcription

1 Point of Care Testing Everything old is new again POCT - Outline The story so far Considering POC testing New problems with an old POCT History At first, all lab tests were at the point of care Tests moved into central labs in early 20th century Driven by large and fixed instrumentation Driven by need for centralized expertise Driven by economies of scale Tests began shifting back to POC in the 1980s Driven by small and portable instrumentation Driven by diffusion of expertise Driven by economies of speed 1

2 History History History: CLIA 88 and categories of test complexity Waived tests are simple laboratory examinations that are cleared by the [FDA] for home use; employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible; or pose no reasonable risk of harm to the patient if the test is performed incorrectly. To perform waived tests a laboratory must Enroll in the CLIA program and pay applicable certificate fees Follow manufacturers test instructions Be inspected if complaints or issues arise The original 8 waived tests Urine dipstick, fecal occult blood, ovulation tests for LH, urine pregnancy, ESR, hemoglobin by copper sulfate, blood glucose meter, microhematocrit 2

3 History: The POC test is not CLIA-defined POCT Waived tes ng Waived: Legal term defined by CLIA POCT: Descriptive term defined by convention Near-patient testing that may be of low, moderate, or high complexity Nevertheless, the availability of waived tests drives POC testing Number of FDA-cleared waived tests has increased from 8 to History: Nevertheless, CLIA 88 made all testing on Human samples subject to regulation POCT - Hospitals % Glucose INR BGA Chem UA Cardiac US Hospital Point-of-Care Survey Report, Enterprise Analysis Corporation 3

4 100 POCT -primary care clinics % Pregnancy UA Strep Occult bld Gluose Influenza INR HbA1c Howick J, et al. BMJ 2014;4:e History: POCT growth Increasing at a rate of 10-15% per year Central laboratory testing 6-7% annually Main practice settings Self-monitoring (largest commercial market), especially glucose Community (pharmacies, health fairs) Clinics Hospitals First US patent for glucose strips for home use in 1963 History: Lab test evolution Research Lab Not fit for Humans Reference Lab Low-volume Labor-intensive Batched, TAT days Hospital Lab High-volume Automated TAT < 4 hrs POCT Lab TAT < 30 min 4

5 Considering POCT: Does it add value? Considering POCT: Costs Cost per reportable Usually higher than central lab, up to 4X per test Cost inversely proportional to volume Billing Often inadequately / incompletely billed Poorly reimbursed, depending upon payer May not be separately billable (DRG) Still need credit for allocation GreendykeRM. Am J ClinPathol 1992 Jan;97(1): DeCresceRP, et al. Arch Pathol Lab Med 1995;119: KefferJH. Am J ClinPathol 1995;104(suppl): WinkelmanJW, et al. ClinChem1994;40: HowanitzPJ, Jones BA. Arch PatholLab Med 2014;128: Considering POCT: Hidden costs Poorer quality of information Accuracy may be suboptimal Laboratory practices may be suboptimal May have different reference ranges on different devices Increased complexity requiring supporting infrastructure Training effusion (user turnover) and diffusion (user numbers) Limited connectivity Documentation of test ordering; generation of bill Documentation of QC parameters and identify of testing personnel Posting of results to chart; up to 60% never make it 5

6 Considering POCT: Benefits Reduced TAT Trimming of pre-analytic and post-analytic Analytic time shorter in some instances Fewer steps Fewer opportunities for process error Smaller sample size Patient and clinician satisfaction Salem et al. JAMA 1991; 266: Considering POCT: Benefits of reduced TAT may be Better medical management Outcomes are improved Better resource management Use of available beds, diagnostics, etc. improved Better staff time management Patient disposition with fewer node points Be er pa ent / provider sa sfac on Higher quality + Lower costs = Higher value Crocker B, et al. ClinChemActa 2013;424:8-11. ShephardM. ClinBiochemRev 2006;27: Considering POCT: Unexpected benefits Study comparing nursing me spent in POC glucose tes ng versus central lab 284 seconds for POCT; 486 (tube) to 603 (hand-carried) seconds for lab In some cases several minutes of difference attributed to bandaging collection site in patients on anticoagulant tx(not needed for fingersticks) Moultrie CA, et al [Abstract]. ClinChem1997;43:S162. 6

7 Considering POCT: Designing studies for potential benefits Status quo Collection Result Action Disposition Health outcome Financial outcome Collection Result? Action? Disposition? Health outcome Financial outcome Collection Result Action? Disposition? Health outcome Financial outcome Collection Result Action Disposition? Health outcome Financial outcome TIME Considering POCT: Cath lab coags and crea nine Phased study Implementation of POCT Evaluation and alteration of processes Simply moving testing from the central laboratory to the clinical service did not improve patient waiting time Documented decreased TAT for results But no measurable change in percentage on-time starts Systematic process changes, including the use of POCT, did reduce wait time Nichols JH, et al. Clin Chem 2000;46: Considering POCT: An array of tests in the ED No change in length of stay with access to POCT for Na, K, Cl, glucose, BUN Na, K, Cl, glucose, BUN, Hb, ph, CO2, PaO2, Bicarb, O2 sat Parvin CA, et al. ClinChem1996;42: Kendall J, et al. BMJ 1998;316:

8 Considering POCT: A satellite lab in ED Significantly shortened LOS in ED UA, Qual HCG, glucose, cardiac markers Difference not significant for any individual test (P=0.06 for cardiac markers) Achieved statistical significance when combined (P=0.006) Lee-LewandrowskiE, et al. Arch Pathol Lab Med 2003;127: Considering POCT: In summary, is cost offset by benefit? Twenty years of investigation and hundreds of studies Conclusion: it depends Setting (ED, clinic, ICU) Analyte Algorithm (is there one, and is the test result a node?) Intervention (is it immediate, and does it limit a downstream costs?) Desired endpoints Good reviews of POCT economics: Nichols JH, et al. Clin ChemActa. 2007;379: Lee-LewandrowskiE, et al. ClinLab Med. 2009;29: St John A, Price CP. ClinBiochem Rev. 2013;34: Considering POCT: The effect of setting POCT introduced into outpa ent clinic CMP, lipid panel, HbA1c Cost of testing compared to reimbursement netted $6.62 per patient Substantial decrease in number of tests ordered, follow-up letters, follow-up phone calls, and patient re-visits, estimated to save $24.65 per patient Overall financial benefit $31.27 per patient Crocker JB, et al. Am J Clin Pathol. 2014;142:

9 Considering POCT: Does it improve health outcomes? Review found 84 studies that met criteria Randomized direct comparison POCT to central lab At least 1 surrogate outcome measured Study quality was generally considered low Concluded that further study needed 19 NeontalBili 4 Procalcitonin 6 PTH 25 Troponin 30 Blood gas analysis PecoraroV, et al. Clin ChemLab Med 2014;52(3): Considering POCT: What we have learned POCT can reduce time-to-decisions and time-to-disposition POCT can save money, if implementation and accounting done properly No study to date asks whether these benefits can be achieved without POCT, by comparing to Streamlined (LEANed) processes (with central lab testing intact) POCT in the central lab Considering POCT: Why is there is still insufficient evidence outcomes? Wrong implementation Shortened work hours Wrong problem Keystone 9

10 Considering POCT: medical error Error is affected by Latent, Ac ve, and Amplifying Condi ons Latent conditions for error Training (operator incompetence) Instruments (uncontrolled reagents / equipment) Procedures (procedure non-adherence) Regulations Amplifiers of error Rapid result availability Immediate therapeutic implications Reason JT. Managing the Risks of Organizational Accidents. Ashgate; LeapeLL. JAMA1994;272(23): Considering POCT: medical error The CMS CLIA waived/ppmp laboratory project 436 labs with certificates of waiver in 10 states Testing personnel 19% had no training and no competence assessment 32% could not locate test instructions Adherence to procedure 25% failed to follow manufacturer instructions Reagents and equipment 32% of tests performed without QC; 20% QC cards from patient cards 6% expired reagents or kits Hasan D et al. Available at: Considering POCT: Error and risk mitigation Training Training (ini al and ongoing) of operators reduces risk Most errors (just like central lab) are preanalytical Instruments Design features prohibiting testing unless QC performed and in-range Lock-out features, out-of-range features, etc. Nichols JH. Expert Rev MolDiag2003;3: TigheP. Br J Biomed Sci 1999;56:6-15. Nichols JH, Poe SS. Clin Lab ManagRev 1999;13: Hopkins S. AdvAdm Lab 2004;13: KostGJ. Arch PatholLab Med 2001;125:

11 Considering POCT: Error and risk mitigation Regulatory Cleared by the FDA for home use Vast majority of current waived tests are not Likelihood of erroneous results negligible 13% of INR incorrect (misclassified) 9% of blood glucose incorrect (over 20%) Not posing risk if performed incorrectly. Common POCT: glucose, INR, pregnancy, TnI Guidelines made more rigorous in 2008 Applications have slackened considerably Meier FA, Jones BA. Q-Probes study Jones BA, et al. Arch PatholLab Med 1993;117: Considering POCT: Proposal application form Problem to be solved Analyte(s) and suggested vendors Number of tests anticipated Intended use Responsible POC director for clinical area Primary administrative responsibility resides locally (laboratory provides inspection, consultation, and other assistance) Primary CLIA responsibility remains with lab (right to rescind privileges) Financial analysis and cost center It is advised that budgeting for POC testing fall under the care area or under a separate POCT cost center Literature review Algorithm Considering POCT: Some tools WebContent/pdf/point-of-care-testing.pdf 11

12 Sometimes POCT is a practical necessity Troponin Transcutaneous bilirubin HIV Troponin in acute coronary syndrome The problem Laboratory TAT of under 1 hour from collection required Under 30 minutes desired ACC / AHA guideline: Door-to-intervention under 90 minutes NACB guideline: If 30 minutes not consistently achieved, consider POCT Evidence As compared to central lab, POCT demonstrates reduced TAT, reduced ED LOS, and reduced me to interven on StorrowAB, et al.aacb Press 2006 Ng SM, et al. Am J Cardiol2001;88: Apple FS, et al. Clin Chem Acta 2006;370: Renaud B, et al. AcadEmergMed 2008;15: Ryan RJ, et al. Ann Emerg Med 2009;53: Troponin in acute coronary syndrome Whole blood ANALYZER Result-in-hand About 20 minutes Whole blood Transport Receipt Centrifuge ANALYZER Middleware Result in HIS Reject? Repeat? Usually under 60 min 12

13 Transcutaneous (TC) bilirubin The problem Most pathologic jaundice presents in days 2-5 Most neonates discharged before 24 hours To prevent kernicterus, a risk assessment tool that involves bilirubin measurement has been developed Venipuncture avoidance Central lab bili imperfect test verificiation challenging Clinical use Bilirubin (TC or serum) on every infant who is jaundiced in 1st 24 hours Bilirubin levels interpreted according to nomogram RubaltelliFF et al. Pediatrics 2004;107: KazsmierczakSC et al. Clin Chem2004; AAP clinical practice guideline. Pediatrics 2004 Bhutani VK et al. Pediatrics 1999;103:6-14 Rapid HIV The problem 2006: CDC recommends Universal opt-out screening during each pregnancy Women informed and testing performed unless they object With second test in 3rd trimester for women Known to be at risk for HIV, or In jurisdictions with elevated HIV incidence, or In hospitals with high HIV prevalence 2010: Texas health and safety code mandates If no results available from 3rd trimester, then physician shall Collect specimen from newborn within two hours of birth Results received within six hours after submission 13

14 Glucose meters Glucose meters Clinical uses ED: Altered mental status Ward: Sliding scale glucose control ICU: Tight glycemic control Clinical issues in critical care patients Tight glycemic control and whether it is good POCT glucose meters and how good are they Regulatory issues in critical care patients Off-label use Proper validation of laboratory-developed tests Tight Glycemic Control in Critically Ill Patients 14

15 Tight glycemic control made it into numerous published guidelines from Surviving Sepsis Campaign Institute for Healthcare Improvement Michigan Health and Safety Coalition American Assn of Clinical Endocrinologists American Diabetes Association Tight glycemic control: Applicability Tight glycemic control: Reproducibility 15

16 Tight glycemic control: Reproducibility Tight glycemic control: Reproducibility Tight glycemic control: Reproducibility 16

17 Tight glucose control: The morning after No significant difference in mortality Significant reduction in septicemia Subgroup analysis showed this benefit limited to surgical patients Hypoglycemia increased 5-fold in tight glucose control groups Overall, this meta-analysis does not support tight glucose control POCT Glucose meters: Are they accurate? User error: collection, calibration, QC Patient ID Environment: Temperature Humidity Altitude Inherent Inaccuracy ±10%, 20%? Glucose Meter Exogenous: Maltose Ascorbate Endogenous: Hematocrit Perfusion ph JadhavPP, JadhavMP. IntJ Case Rep Im 2013;4(9): POCT glucose meters: Effect of hematocrit (54 mg/dl) Analyzer 1 Analyzer 2 Analyzer 3 Analyzer 4 KaronBS, et al. Diabetes technology & therapeutics 2008;10(2). 17

18 POCT glucose meters: Effect of ascorbate (54 mg/dl) Analyzer 1 Analyzer 2 Analyzer 3 Analyzer 4 KaronBS, et al. Diabetes technology & therapeutics 2008;10(2). POCT glucose meters: Are they accurate? Overall correlation with plasma and central lab measurement poor Even un-hindered, sub-optimal performance at decision points Acceptable accuracy for analytic validation ±20% At 80 mg/dl, the true value may be mg/dl Hindered by Oxygen tension and ph Several medications Hematocrit Poor perfusion Tang Z et al. Diabetes TechnolTher2000;2: Tang Z et al. CritCare Med 2001;29: Tang Z et al. Arch PatholLab Med 2000;124: Tang Z et al. Am J ClinPathol2000;113: Chance J et al. Am J ClinPathol1999;111: Louie R et al. Arch PatholLab Med 2000;124: Rao L et al. ClinChimActa2005;356: Chen E et al. Diabetes TechnolTher2003;5: Khan A et al. Arch PatholLab Med 2006;130: POCT glucose meters in critically ill patients Kanji S, et al. Crit Care Med 2005; 33(12): Agreement with the central lab significantly better with arterial blood analysis During hypoglycemia agreement was only 55.6% for arterial blood by glucose meter, and 26.3% for capillary blood by glucose meter Inoue S, et al. Critical Care 2013, 17:R48 Reviewed 21 studies in which ABG analyzer / glucometer was compared to central lab methods in critically ill adult patients Accuracy of ABG analyzer using arterial blood higher than glucose meter using arterial blood Accuracy of ABG analyzers and glucose meters using arterial blood higher than that of glucose meters using capillary blood In the hypoglycemic range (< 81 mg/dl) error rate was higher In unstable hemodynamics error rate was higher 18

19 POCT glucose meters Validated in ambulatory diabetics for titration of subq insulin Central lab glucose POCT glucose 100 deaths associated with whole blood glucose monitoring in ICU patients reported to the FDA (1992 to 2009) 12,672 serious injuries ( ) 19

20 Jan 7, 2014: FDA releases draft document Blood Glucose Monitoring Test Systems for POC Use Work with manufacturers to determine whether their device is appropriate in critically ill patients Provide data that will allow FDA authorization for use in critically ill patients. At about the same time NY State Department of Health issued a letter to lab directors that many uses of glucose meters will be off-label Cannot use in health fairs Cannot use on critically ill patients Cannot use to diagnose or screen for diabetes Nov, 2014: CMS issues S&C CLIA Off-label use of waived blood glucose monitoring systems Directed accrediting agencies to enforce manufacturer s published limitations and intended use statements, effective immediately Described the need for each facility to define the term critically ill Reminded that the FDA has approved only one meter (Nova Biomedical s StatStrip) to perform testing on critically ill patients and then only on non-capillary specimens Mar, 2015: CMS temporary withdrawal of Re-issued in draft form in order to Obtain feedback and promote education Issuance of the original memo in Nov 2014 prompted considerable feedback from those comments, it is apparent that Waived BGMS are being used in a variety of off-label applications There is risk of patient harm when off-label use has occurred without the necessary performance specifications being in place There may be confusion as to what hospitals must do to meet CLIA requirements for off-label use; this is particularly concerning as S&C Memorandum contained no new CLIA policies --the underlying CLIA statute and regulations have not changed 20

21 POCT glucose: So what do we do? Define critically ill patient Follow manufacturers published limitations and intended use directives Decide whether method validation is worth the cost (recognizing that many POC glucose meters will fail the validation experiment) If it s not worth it: optimize processes for central lab testing If it s worth it: See below POCT glucose: Utilize existing glucose meters off-label The laboratory becomes subject to CLIA high complexity requirements Must obtain an appropriate high complexity certificate Must appropriately increase testing and supervisory personnel qualifications Must establish and verify testing instrument performance specifications Design, review, and approve plan for method validation Accuracy, precision, sensitivity, specificity, reportable range, reference intervals Design, review, and approve QA plan Personnel at testing site meet high complexity testing qualifications; competency assessed annually according to all 6 elements Perform semiannual instrument comparisons, semiannual AMR verification, lot-tolot reagent verification, quality control, proficiency testing 21