1 / 32

Standardizacija/Priporočila testiranja HbA1c ob bolniku (Standardisation/Recommendations of HbA1c point of care testing)

Standardizacija/Priporočila testiranja HbA1c ob bolniku (Standardisation/Recommendations of HbA1c point of care testing). . Milan Skitek S impozij DLM Ljubljana, 28. maj 2012. Glikirani hemoglobini (GHB) kot biooznačevalci.

amory
Télécharger la présentation

Standardizacija/Priporočila testiranja HbA1c ob bolniku (Standardisation/Recommendations of HbA1c point of care testing)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Standardizacija/Priporočila testiranja HbA1c ob bolniku (Standardisation/Recommendations of HbA1c point of care testing). Milan Skitek Simpozij DLM Ljubljana, 28. maj 2012

  2. Glikirani hemoglobini (GHB) kot biooznačevalci Glikirani hemoglobini (GHB) predstavljajo stabilne komponente hemoglobina, ki se tvorijo počasi in neencimatsko med hemoglobinom in glukozo. HbA1c je specifična oblika GHb, ki se tvori z vezavo glukoze z aldehidno skupino na eno ali obe končni NH2 skupini aminokisline valina ß polipeptidne verige hemoglobina. Glikirana HbA0in HbA1frakcija predstavlja z več izoformnimi oblikami (HbA1 a1, a2, b, c, d, e) približno 7 odstotkov (%) glede na celokupni hemoglobin, od tega je večina HbA1c. Možnost zanesljive določitve HbA1c predstavlja največji napredek pri oskrbi, nadzoru in zapletih ter diagnostiki sladkorne bolezni v zadnjih 30 letih.

  3. Metode določanja GHB V rabi več različnih metod in analitskih sistemov, ki temeljijo na ločitvi teh molekul na osnovi : naboja (elektroforeza/kapilarna in ionsko izmenjevalna kromatografija visoke ločljivosti-HPLC, HbA1c) strukturnih lastnosti (afinitetna kromatografija,celokupni glikirani hemoglobin-GHb) antigenskih lastnosti (imunološke metode z monoklonalnimi protitelesi s specifično vezavo na HbA1c). Rezultati so izraženi v % ali mmol/mol Hb.

  4. Klinična standardizacija GHB Velika variabilnost med številnimi metodami, ki so merile različne frakcije glikiranega hemoglobina (HbA1c, HbA1 in GHb) GHB/HbA1c lahko vodi do različnih rezultatov (tudi znotraj istih metod različnih analitskih sistemov). • Koncem osemdesetih in v začetku devetdesetih letih prejšnega stoletja standardizacija na podlagi klinične obdelave bolnikov in 2 študij (Diabetes Control and Complications Trials-DCCT in UK Prospective Diabetes Study-UKPDS) ter globalnega programa (National Glycohemoglobin Standardisation Program - NGSP), ki je zagotavljal sledljivost HbA1c z omenjenima študijama in mrežo certificiranih laboratorijev/proizvajalcev (medicinska sledljivost z interpretacijo laboratorijskih rezultatov, kriteriji ukrepanja, referentnimi vrednostmiin stalnimi pred-, analitičnimi in poanalitičnimi kazalci kakovosti oz. napakami).

  5. Klinična standardizacija GHB , nad. Poznana sta še dva lokalna programa s podobno zasnovo kot NGSP in sicer t.i. švedski in japonski model z manjšim obsegom in vplivom na mednarodnem trgu. 1993 DCCT poročilo: intenzivna terapija zniža retinopatije, albuminurije in neuropatije v povprečju za več kot 50%. Stopnja glikemične kontrole (merjene kot HbA1c) pri diabetesu tipa I je tesno povezana z rizikom razvoja in/ali napredovanja kroničnih diabetičnih komplikacij.

  6. Klinična standardizacija GHB , nad. DCCT je postavila temelje za določitev specifičnih ciljev zdravljenja diabetikov z uporabo HbA1c kot indeksa povprečne glikemije 1998 United Kingdom Prospective Diabetes Study (UKPDS) zagotovlja dokaze zmanjšanja rizika za diabetične komplikacije z intenzivno kontrolo krvnega sladkorja pri bolnikih z diabetesom tipa II. American Diabetes Association (ADA) izda 1994 priporočila in cilje dobre oskrbe diabetika (HbA1c <7%), ki temeljijo na DCCT “referenčni metodi” (kationska izmenjevalna kromatografija-HPLC).

  7. Analitična standardizacija GHB Metrološka standardizacija mednarodne federacije za klinično kemijo (IFCC)temelji na razvoju sledljivega, referentnega kalibratorja (očiščen hemolizat z izolirano frakcijo HbA1c in HbA0) in na razvoju definitivnih analitskih metod (specifično določanje N-končnih ostankov beta verige): HPLC/masne spektrometrije ali kapilarne elektroforeze(metrološka sledljivost višjega reda s sprejemljivim izkoristkom označene vrednosti za standard, certificiranim referentnim materialom, referentno metodo in akreditiranimi referentnimi laboratoriji).

  8. Usklajevanje/povezovanje standardizacij Primerjava rezultatov HbA1cmedicinske/NGSP in metrološke/IFCC sledljivosti dokazala značilno razliko s sistemskim odklonom (znižanjem) IFCC rezultatov za 1.5 do 2 % HbA1c skozi celotno območje koncentracij: NGSP-HbA1c(%)= 0.915 * IFCC-HbA1c(%) + 2.15% SKITEK, Milan, ŠTER, Mateja. Standardizacija določanja in harmonizacija rezultatov HbA1C = HbA1C standardization and harmonization. V: 2. Slovenski kongres klinične kemije z mednarodno udeležbo: TIVADAR, Andrijana (ur.). Zbornik razširjenih povzetkov, (Farmacevtski vestnik, letn. 55, posebna št.). Ljubljana: Slovensko farmacevtsko društvo, 2004, str. 327-328. [COBISS.SI-ID 1600881]

  9. Standardizacija izvidov/rezultatov HbA1c Priporočila IFCC/ IDF/ADA/EASD (Consensus Statement 2007): • HbA1c rezultat mednarodno standardiziran na IFCC referentni sistem • HbA1c rezultat izražen v IFCC/SI enotah (mmol/mol Hb) inNGSP enotah (%) • Če “študija ocene povprečne plazemske glukoze” izračunane iz HbA1c (ADAG ali e-AG) zadosti predhodnim specifičnim kriterijem, lahko na izvidu prikažemo tudi ADAG kot interpretacijo HbA1c(uspešno zaključeno 2008: e-AG mmol/L = 1.59 X %HbA1c_ 2.59).

  10. Standardizacija izvidov/rezultatov HbA1c, nad. Priporočila ADA/EASD/IFCC/ISPAD (Consensus Statement 2010): HbA1c rezultat naj bo izražen v IFCC/SI enotah (mmol/mol Hb) inNGSP enotah (%) Obe enote skupaj se uporabljata v člankih in raznih publikacijah Trenutno stanje: ZDA (tudi Slovenija) nadaljujejo z NGSP enotami HbA1c(%) in dodajajo ADAG, večina evropskih dežel po vmesnem obdobju 1 – 2 let (obe enote) prešla na IFCC/SI enote vključno s Kanado, Avstralijo, Novo Zelandijo, Avstralijo. Japonska ostaja pri svoji standardizaciji JDS in NGSP enotah (%).

  11. HbA1c in diabetes diagnoza International Expert Committee Report on the Role of HbA1c Assay in the Diagnosis of Diabetes (2009): • prednosti HbA1cv primerjavi z glukozo: standardiziran in sledljiv DCCT/UKPDS/IFCC, boljši indeks celokupne glikemije in rizika za dolgoročne komplikacije, nižja biološka variabilnost, boljša predanalitska stabilnost, vzorec kadarkoli brez “na tešče”, velika nihanja glukoze brez večjega vpliva, HbA1c že uporabljan za spremljanje, oskrbo in prilagajanje terapije • Slabosti HbA1c v primerjavi z glukozo: interference na variante Hb in stanja povečanega obrata eritrocitov, večji stroški in nedostopnost v določenih delih sveta.

  12. HbA1c in diabetes diagnoza, kriteriji HbA1c >= 6.5% (48 mmol/mol; IFCC HbA1c (mmol/mol) = 10.93 x DCCT/NGSP unit (%) – 23.50 ) ALI FPG >= 7.0 mmol/L ALI 2 urni 75 g OGTT: glukoza >= 11.0 mmol/L ALI Naključna glukoza >= 11.0 mmol/L pri bolniku s klasičnimi simptomi hiperglikemije HbA1ctestiranje samo z verificirano klinično laboratorijsko opremo, POCT instrumenti še niso dovolj ponovljivi in pravilni v diagnostične namene. SKITEK, Milan. Screening for gestational diabetes mellitus. Clin Chem Lab Med, 2005, vol. 43, no. 6, str. 664-666. [COBISS.SI-ID 1746801],

  13. Izboljšave določanja HbA1c Evolucija NGSP certifikacijskih kriterijev za proizvajalce: 1996: Evaluacijski protokoli EP9 (odklon) in EP5 (ponovljivost <=5%); HbA1cobmočje 4-14% 1999: Sprememba iz EP9 na Bland/Altman oceno primerljivosti (95% meja zaupanja znotraj ± 1% HbA1c) 2002: Zvišanje kriterijev za ponovljivost iz <=5% na <=4%) 2007: Zvišanje kriterijev za oceno primerljivosti iz ± 1% na ± 0.85% HbA1c (oženje območja na 4-12%) 2010: Zvišanje kriterijev za oceno primerljivosti iz ± 0.85% na ± 0.75% HbA1c (oženje območja na 4-10%).

  14. Izboljšave določanja HbA1c, nad. Evolucija kriterijev sprejemljivosti (odklon od referenčnih vrednosti) College of American Pathologists (CAP) zunanjih presoj (PT) za laboratorije*: 2007: Začetek PT z dovoljeno mejo odstopanja ± 15% HbA1c 2008: Dovoljena meja odstopanja se zniža na ± 12% HbA1c 2009: Dovoljena meja odstopanja se zniža na ± 10% HbA1c 2010: Dovoljena meja odstopanja se zniža na ± 8% HbA1c 2011-2012: Dovoljena meja odstopanja se zniža na ± 6% HbA1c. *Klinično značilna razlika v območju 6-9% HbA1c je ± 10%.

  15. Izboljšave določanja HbA1c, nad. Zmanjševanje interferenc: Zavedanje dejstva interferenc pri določanju HbA1c (globalno HbS najpogostejša varianta, sledijo HbE, HbC in HbD) Evaluacija interferenc za vsako analitsko metodo Priporočeno uporabljati analitske metode dokazano brez interferenc (več kot 20% laboratorijev uporablja metode z različnimi interferencami).

  16. The National Academy Of Clinical Biochemistry Presents LABORATORY MEDICINE PRACTICE GUIDELINES EVIDENCE BASED PRACTICE FOR POINT OF CARE TESTING 2006

  17. Does the provision of the HbA1c result at the point of care lead to an improved patient (clinical) outcome, when compared with central laboratory testing? (Literature Search 42) Guideline 68: We conclude that there is good evidence to support the use of POCT for HbA1c in both the primary and secondary care setting. The benefit comes from the diabetes specialist having the result at the time of the patient consultation. This recommendation assumes that the POCT is implemented under proper conditions e.g. trained and certificated operators, quality control and quality assurance and with an analytical system comparable with that used in the central laboratory. The evidence base would benefit from studies conducted over a longer period of time. Strength/consensus of recommendation: A Level of evidence: I and II (two randomized controlled trials and two controlled trials ).

  18. Does the provision of the HbA1c result at the point of care lead to an economic benefit, when compared with central laboratory testing? (Literature Search 42) Guideline 69: We conclude that there is some evidence to show that POCT testing for HbA1c will lead to an economic benefit. However the data are limited and more detailed studies are required which should focus on the wider benefit of POCT i.e. beyond the immediate costs of providing the test and the change in clinic attendance. The evidence would benefit from studies conducted (and impacts judged) over a longer period of time. Strength/consensus of recommendation: B Level of evidence: II (randomised controlled trial and control trial, but small numbers). Laurence CO et al. BMC Health Services Research 2010, 10:165; “The incremental cost-effectivenes ratio for POCT was found to be unfavourable for INR but somewhat favourable for ACR, while substantial uncertainty still surrounds POCT for HbA1c and lipids as the non-standard intermediate outcome indicator”.

  19. Does patient self testing for HbA1c lead to an improved patient (clinical) outcome, when compared with central laboratory testing? (Literature Search 42) Guideline 70: We cannot make a recommendation here because no studies have been reported. Strength/consensus of recommendation: I Level of evidence: III (no studies addressing the question)

  20. What is the optimal frequency of HbA1c testing? Does more frequent testing lead to better outcomes? (Literature Search 42) Guideline 71: There are no studies that have investigated the optimal frequency of POCT for HbA1c and therefore we can only recommend that the guidelines generated from studies using a laboratory service for the measurement of HbA1c are adopted in the POCT setting. There are no studies that have formally investigated the frequency of measurement of HbA1c – in any setting. We therefore recommend that HbA1c testing is performed between 2 and 4 times per year in line with the patient’s individual requirements. It is recommended that more frequent testing is required in those patients with extremely elevated HbA1c levels and less frequently in those with levels approaching the reference range. Strength/consensus of recommendation: I Level of evidence: III (opinion of respected authorities based on clinical experience)

  21. NHS; Purchasing and Supply Agency, Centre of Evidence-based Purchasing Buyer’s guide POCT devices for the measurement of HbA1c and low concentration albumin in urine. CEP 08057 June 2009

  22. Ali POCT instrumenti zagotavljajo zadostno zanesljivost (ponovljivost, pravilnost/specifičnost, sledljivost, robustnost itd.) v primerjavi z referentno in rutinsko tehnologijo. The analysers (5) included in this guide could be used in a diabetic clinic setting within secondary care and some are suitable for use within primary care if demand issufficient. Any grade ofappropriately trained staff could use these devices with one exception which requiredlaboratory trained staff. Axis Shield now market the NycoCard only for laboratory usesince the procedure includes pipetting which is a laboratory skill.

  23. Limited technical evaluation • Twenty one venous whole blood patient samples, preserved with EDTA, wereanalysed in duplicate for HbA1c on each of the five analysers • Analyses were performed according to the IFUs in a well lit laboratory. Quality control samples were measured on eachdevice at the beginning and end of each analytical session • The samples had been previously measured in a clinical laboratory on a Menarini 8160 HPLC analyser • Regression analysis was performed to compare each POCT method with thelaboratory method. Confidence intervals are an indication of imprecision. Averagebias of the results relative to the laboratory method was calculated only if the biaswas similar across the measured range of the results • The results are presentedtogether with the manufacturers’ claimed performance

  24. Results The in2it results gave the best agreement with laboratory results. Atconcentrations close to the recommended targets HbA1c of 6.5 - 7.5%, Afinion, DCAVantage and in2it analysers provided results within 0.5% HbA1c of the laboratoryresult. The DCA Vantage performed well up to 8.5% HbA1c but overestimated athigher concentrations. A1cNow + results had a negative bias whichexceeded the 0.5% expected with the use of EDTA preserved samples. Accuracydata for most analysers agreed moderately well with manufacturers’ quotedperformance, the largest differences being shown by the A1cNow+ and the DCAVantage. The Afinion samples showed the lowest imprecision as indicated by theconfidence intervals. The cutoff tableshows % HbA1c underestimation by A1cNow+ andoverestimation by NycoCard. All the analysers have NGSP certification for 2008 and therefore have acceptableperformance. The analysers demonstrating the best analytical performance in thisstudy were the in2it, Afinion and DCA Vantage (Overall rating: Good for a quantitative system).

  25. Razprava, zaključki, perspektive Samo nekaj RC študij in veliko tehničnih/evaluacijskih študij in primerjav HbA1c-POCT s centralnim laboratorijem oz. referenčno/rutinsko tehnologijo v zadnjih 20 letih. Nekaj ključnih ugotovitev: HbA1c se lahko dandanes določa s hitrimi, avtomatiziranimi in povezljivimi POCT instrumenti Ponovljivost meritev se izboljšuje in je pri nekaterih instrumentih že enakovredna referenčno/rutinski tehnologiji Problem ostaja odklon od pravih vrednosti in interference (HbS itd.) in s tem povezana referentna območja ter v nekaterih sredinah kompetentnost/usposobljenost kadrov Ekonomska podprtost HbA1c-POCT je še vprašljiva in zavisi od političnih odločitev, koliko je posamezna družba pripravljena investirati v dolgoročno spremljanje bolnikov.

  26. Razprava, zaključki, perspektive New POCT system “Banalyst M” using a microfluidic chip achieves simultaneous rapid diagnosis of HbAlc and Glu Banalyst® M, a new microblood analyzing system for POCT, comprises a μTAS (Micro Total Analysis System) chip (l30 mm, w62 mm, t12 mm) and a compact desktop measuring instrument, and measures and mixes samples in a chip with micro channels. Unlike the Banalyst reported at the same academic conference, Banalyst® M measures maximum 5 items by one chip. “Banalyst M HbA1c/Glu” recently developed measures hemoglobin A1c (HbA1c) and glucose (Glu) simultaneously from only a 10 μL whole blood sample. Using this chip, system was evaluated at Kyushu University Hospital. CLINICAL CHEMISTRY, Vol. 57, No. 10, Supplement, 2011

  27. Razprava, zaključki, perspektive, nad. Novel Cellular Hemoglobin A1c Control - A Commutable Control Across HPLC, Immunoassay and Boronate Affinity Methods Commercial A1c controls are noncellular which do not test the entire analytical system of the instrument, including the lysing step. Lysate based A1c controls are also reported to give erroneous results.2 Streck A1c-Cellular® is the only cellular control which has intact RBC. Therefore, Streck A1c control tests the entire assay procedure. Streck A1c control is also commutable across different A1c analyzers of all methodologies. The importance of commutable calibrators is emphasized in order to harmonize the clinical instruments.3 The aim of the present study is to compare the performance of Streck A1c controls with the other commercial controls and establish its commutability across different A1c methodologies. CLINICAL CHEMISTRY, Vol. 57, No. 10, Supplement, 2011

  28. Primer In preliminary recommendations published today (18 October 2011) by NICE, exenatide prolonged release suspension for injection (Bydureon, Eli Lilly) isrecommended in triple therapy regimens (in combination with metformin and a sulphonylurea, or metformin and a thiazolidinedione) as a treatment option for people with type 2 diabetes, when control of blood glucose remains or becomes inadequate (HbA1c of 7.5% or above, or other higher level agreed with the individual), and the person has: a body mass index (BMI) of 35 kg/m2 or higher in those of European family origin (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or a BMI below 35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities. Treatment with exenatide prolonged release suspension for injection in a triple therapy regimen should only be continued if a beneficial metabolic response has been shown (defined as a reduction of at least 1 percentage point in HbA1c and a weight loss of at least 3% of initial body weight at 6 months).

  29. Primer - vprašanje Kakšna mora biti analitična variabilnost (standardna deviacija) analitskega sistema, da bi zagotovil zaznavo znižanja koncentracije HbA1c (zaradi uporabe GLP-1 agonista exenatida) za najmanj 8.0 mmol/mol Hb (cca 1 %, NGSP) na nivoju 5.0% rizika (biološka variabilnost HbA1c znotraj osebka kot standardna deviacija je 0.1 mmol/mol)?

  30. Primer - izračun P(%) 10 5 2 1 0.2 0.1 z 1.65 1.96 2.33 2.58 3.09 3.29 (x1 - x2) – m 1-2 z = ------------------ s1,2 S = 3.43 mmol/mol SA = 3.4 mmol/mol (pri 62.8 mmol/mol oz. 8.5% HbA1c znaša 5.4 % kot KV%).

  31. Fast is fine (and image op.avt.), but accuracy (and patient benefit op.avt.) is everything. Wyatt Earp

  32. HVALA ZA POZORNOST!

More Related