Laboratories And EQA for effective Tuberculosis Control Programe Gokarna Raj Ghimire Senior Medical Technologist National Tuberculosis Center

Introduction The global burden of TB is high Untreated smear positive cases are highly infectious Nepal has steady case finding rate (75%) Treatment success rate (90 %) Slide positivity rate still on average 10 % DO NOT miss diagnosis DO CORRECT TREATMENT FULL DOSE FULL PERIOD OF TIMR

Laboratories and lab networks are a fundamental component of NTP. It provides testing for diagnosis, treatment monitoring, evaluating the success of treatment and surviellance. Laboratory should do: New Initiatives Strengthen the lab capacity including HR Implement rapid and new diagnostic tests Implement quality system and safety system

Strength of lab network reflects the success of NTP Good quality microscopic centers (ZN technique) Fluorescence Microscopy (Auramine techniques) Culture and DST (Solid and Liquid) Molecular techniques, (Gene Xpert, LPA) Trained staff Good Quality management System

Microscopy Microscopy remains mainstay of rapid, cheap, easy method of TB case detection ZN smear is still the most common test. Low sensitivity, so look for advanced method FM has high sensitivity Concentrated technique with FM has more higher sensitivity Monocular microscope-binocular-fluoresence microscope

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Culture and DST Confirmed diagnostic test Need high quality lab infrastructure, equipments and HR Useful diagnostic tools for EP cases, childhood TB cases, HIV-TB cases, MDR-TB Cases, XDR-TB cases FLD/SLD DST Facilities are available at NRL/NTC and GENETUP Purposed places: BPKIHS Dharan, RTC Pokhara, Mid west Surkhet EQA Overview

Mycobacterial Colonies on Egg based Culture Medium (LJ medium) 8

Nucleic Acid Amplification tests Gene Xpert : Fully Automated, Cartridge based, Real Time, Nucleic Acid Amplification Test (NAAT) LPA: Manual PCR, Detection by Hybridization strip,

Specimen Transportation 10

EXTERNAL QUALITY ASSESSMENT (EQA) IN NEPAL FOR SPUTUM MICROSCOPY EQA Overview

External Quality Assessment (EQA) A system for objectively checking the laboratory’s performance using an external agency or higher authority Ensures customers (physicians, patients and health authorities) that the laboratory can produce reliable results An indispensable part of a laboratory quality management system EQA Overview

EXTERNAL QUALITY ASSESSMENT The Quality System Quality System Essentials (QSE) Set of coordinated activities that function as building blocks for quality management EXTERNAL QUALITY ASSESSMENT EXPLAIN that the laboratory operation consists of a complex system, with a whole set of events to begin with the ordering of a test, to the reporting of results back to the provider. And it is very important that all parts of this cycle or all aspects of the system work correctly. Any error in any part of the cycle can produce a poor laboratory result. To be sure that all parts of this laboratory system are working properly, a quality system approach to the laboratory setting is to be applied. In other words, all aspects of the laboratory operation need to be addressed to assure quality; this constitutes a quality system. Guidelines of the Clinical and Laboratory Standards Institute (CLSI) describe a quality management system model that consists of 12 essentials. Quality system essentials are set of coordinated activities that function as building blocks for quality management. According to CLSI quality management system model, external quality assessment forms a part of the Assessment quality system essential and is an indispensable part of a laboratory quality management system. EQA Overview

Requirements Regarding EQA The laboratory should participate in inter-laboratory comparisons such as those organized by EQA schemes ( Total 554 Microscopy centers are exists in Governmental organization and NGO/INGO/Private institution) The lab management shall monitor the results of EQA and participate in the implementation of corrective actions EXPLAIN that international standards stress the importance of laboratories’ participation in EQA schemes. International Organization for Standardization has developed the standard named ISO 15189:2007 – Medical laboratories: particular requirements for quality and competence. This is a guideline for implementing quality systems in medical (clinical) laboratories. An independent external quality assessment of laboratory performance by a recognized scheme is the requirement of this standard. NTP should establish a functioning mechanism to monitor the results of external quality assessment, to review and investigate discordant findings as to root causes and to provide with corrective and preventive actions, when necessary, based on results of investigations. All findings and recommendations for actions should be appropriately documented. EQA Overview

EQA Benefits Allows inter-lab comparison of performance Serves as an early warning system Identifies systematic problems Provides objective evidence of laboratory quality Serves as an indicator for focusing improvement efforts Identifies training needs Source of continuing education Source of material for practice EXPLAIN that participation in EQA schemes is of benefit both for public health programs and individual laboratories: 1. Laboratory oriented objectives of EQA include: Identification of possible insufficiencies in laboratory practices, and guidance of participants in corrective actions to be used for making these practices better; Identification of reliability characteristics of methods, materials and equipment in routine-use and suggestion of appropriate corrective actions; Evaluation and monitoring of training impact; assistance in preparation of future training; Opportunity for continuous self-education 2. Public health oriented objectives of EQA: Establishment of bases for results comparability during epidemiological surveillance and disease control; Collection of information on laboratory measurements (intra- and inter-laboratory) in order to alert professionals and/or governments on results, traceability and harmonisation problems, and establishment of appropriate acceptable limits for results in a given prospective; Collection of information on operating authorisations or laboratory accreditation. Further education Creation of a channel for communication EQA Overview

EQA for AFB Smear Microscopy Consensus document: External Quality Assessment for AFB Smear Microscopy (2002)

Current EQA Structure If some slides incorrect If 100% slides correct QCA at National Quality Control Centre (NTC) National Problem slides If some slides incorrect QCA at Regional Quality Control Centre If 100% slides correct Regional DTLO DTLO holds meeting to discuss results with PMCs DTLO District PMC PMC PMC PMC PMC Local = Slides = Feedback

Structure of Quality Control System National TB Centre Central level Regional level WDR RTC EDR GoN/BNMT CDR NTC FWDR GoN/FAITH MWDR GoN DPHO/DHO District level Periphery level Microscopy Centre

Flow of Quality Control System On Quarterly Basis 2. Send Collected Smear Slides With Form (QC 1) Selecting by using LQAS DTLO 1. Keep all Slides 3. Cross Check Assessment (QC 2) Report Feed-Back (QC 3) Microscopy Centre Regional Quality Control Centre RTLO 5. Supervision Refresher Training EQA Overview

EQA Methods for AFB Smear Microscopy External Quality Assessment (EQA) – a process to assess laboratory performance; allows to assess labs’ capabilities and performances by comparing their results with those obtained in other labs in the network On-site supervision Panel testing Blinded rechecking EXPLAIN that EQA for AFB smear microscopy consists of three methods that can and should be combined to evaluate laboratory performance. These methods include panel testing, blinded rechecking and on-site supervision. EQA Overview

Panel Testing Process NRL sends out sets of stained and/or unstained sputum smears for testing Laboratory technicians analyze smears and return results to NRL Results are evaluated, scores are sent to participants Appropriate corrective actions are undertaken (and documented), if needed EQA Overview

Blinded Rechecking Random sampling of routine slides from a peripheral laboratory for rechecking by a higher-level laboratory The widely used system for rechecking of “10% of negative and 100% of positive smear” is no more recommended The proposed blinded rechecking method is based on the Lot Quality Assurance System (LQAS) EXPLAIN that the old sampling system “10% of negative and 100% of positive” is not efficient, with over-sampling in some laboratories and under-sampling in others. Lot Quality Assurance System (LQAS) sampling allows the smallest possible but appropriate sample sizes. STATE that detailed instructions on Lot Quality Assurance System (LQAS) are available in the Blinded Rechecking Module of this Workshop-In-A-Box. EQA Overview

On-Site Supervision Periodic visits to the laboratory to assess laboratory practices to: Obtain a realistic picture of laboratory practices Provide assistance with problem areas, including training Laboratory vs. TB supervisors When planning site visits, to consider: Frequency Use of checklists Follow-up visits Monitoring corrective actions Training EXPLAIN another EQA method – on-site supervision: it looks at specific testing areas of the laboratory, especially those that have been identified by a bad result to a panel testing or blinded rechecking scheme. EQA Overview

EQA methods: Which one is better? Advantages and drawbacks for all types Influencing factors: NTP goals set up for laboratory services development TB prevalence in the country Centralization / decentralization of health services Resources available and projected Cost, time Logistical questions STATE that effective use of each of these methods will highly depend on the availability of resources, goals set up by the NTP, TB prevalence, centralization/decentralization of health services and the stage of laboratory quality assurance activities development in a country. EQA Overview

Panel Testing ADVANTAGES DISADVANTAGES: Low workload for a peripheral center Improves laboratory credibility Rapid response countrywide possible Use of stained and unstained smears can help to identify the source of a problem May lead to identification of faulty equipment Does not measure routine performance High workload for NRL May not be motivating to improve daily performance

Panel Testing: Indications for Use Minimal first step for EQA with limited resources Rapid assessment of gross deficiencies Evaluates proficiency of laboratory technicians prior to and following training A tool during problem-oriented supervision

Blinded Rechecking ADVANTAGES DISADVANTAGES: Low workload for a peripheral laboratory Motivates to improve daily performance Reflects reality of routine performance Higher workload for a higher level center Needs close adherence to elaborated procedures Can not be used with very low positivity rates Indications for use: The best method for evaluating lab performance Countrywide Ongoing and permanent

On-Site Supervision ADVANTAGES DISADVANTAGES: Direct personal contact Motivating to staff Observation of actual work Identifies causes of errors Permits verification of equipment quality and function Usually poor coverage Labor intensive Costly Needs very good supervisors STRESS that on-site supervision is ineffective unless done by a well experienced / educated personnel. EQA Overview

On-Site Supervision: Indications for Use Complementary to rechecking and panel testing for constructive feedback and problem solving Implementation and monitoring of quality improvement measures Data collection and flow of information among laboratory levels

EQA: Important Issue Blinded rechecking or panel testing should be complemented by very targeted problem-oriented supervision conducted by a trained staff EQA Overview

Situational Analysis Of EQA Nepal Medium Size Population; Vast different territory Low Burden of TB Several hundreds of geographically dispersed peripheral laboratories RQCC’s (Intermediate laboratories’) infrastructure is not well developed; many intermediate labs experience lack of staff NRL/NTC is not well equipped and sufficient staffed DISCUSS WITH A GROUP what could be an appropriate strategy for EQA activities development in Country A. Large numbers of decentralized peripheral laboratories and, in particular, poor developed infrastructure of intermediate laboratories make implementation of all EQA methods difficult: Panel testing will result in high workload for NRL (preparation and distribution of uniform panels, review of results and preparation of feedback reports); Blinded rechecking is impossible without properly established intermediate laboratory network: it will be difficult to assign the required number of controllers to ensure even distribution of rechecking workload and, consequently, appropriate quality of controllers’ work. On-site supervision: NRL staff will not be able to visit all peripheral laboratories alone. Extra thorough consideration and critical assessment of all strengths and weaknesses of the situation should be recommended; data on smear positivity rates should be collected as well. As it is too difficult to implement the blinded rechecking program, it can be recommended to start with the panel testing program and take every effort to promptly develop intermediate level laboratories for further gradual implementation of the blinded rechecking program. Information on AFB smear positivity rates will help determine the sampling approach for the blinded rechecking program. In areas with medium positivity rates (around 5%) the stratified sampling would be applicable. EQA Overview

Key Messages (I): EQA can be defined as a system for objectively checking the laboratory’s performance using an external agency or facility EQA for AFB smear microscopy allows participating laboratories to access their capabilities and performances by comparing their results with those in other laboratories in the network EQA for AFB sputum smear microscopy include three methods: Panel testing Blinded rechecking On-site supervision

Key Messages (II): Effective use of each of EQA methods will highly depend on resources, NTP goals, TB prevalence, health services’ structure and the stage of laboratory quality assurance activities development in the country Blinded rechecking or panel testing should be complemented by very targeted problem-oriented supervision conducted by a trained staff

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