WHO-EMlLABI294/EL Distribution: Limited Report on the
REGIONAL INTERCOUNTRY WORKSHOP ON QUALITY ASSURANCE IN LABORATORY MEDICINE Teheran, Islamic Republic of Iran, 10-14 May 1997
World Health Organization Regional Office for the Eastern Mediterranean Alexandria, Egypt 1998
O World Health Organization 1998
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CONTENTS I . INTRODUCTION .................................................................................................................. 1
2 . COUNTRY REPORTS .......................................................................................................... 3 2.1 Afghanistan ....................... ..... .... ......................................................................... 3 2.2 Bahrain ............ ....... ...................................................................................... 4 2.3 Egypt ........................................................................................................................... 5 2.4 Islamic Republic of Iran.............................................................................................. 6 2.5 Morocco .................................................................................................................... I0 2.6 Oman ...................................... 14 2.7 Pakistan .................... ................................................................................................. 15 . ........................................................................................ 17 2.8 Sudan ....................... . 2.9 Syrian Arab Republic ................ . . . ......................................................................... 18 . . ~ a ....... 2.10 T u n ~ s............... ......................................................................................... 20 2.11 Republic of Yemen .............. . . . .......................................................................... 21 2.12 Discussions .................... ................................................................................ 21
. .
. . .
22 3 . PRESENTATIONS ............................................................................................................... 3.1 Economic aspects of quality assurance, and cost effectiveness ............................... 22 23 3.2 Quality management in medical laboratories ............................................................ 3.3 Standard operating procedures ................................................................................ 24 . . 3.4 Quality assurance in virology ............................................................................... 25 3.5 External quality assessment schemes........................................................................ 27 3.6 Statistical and nonstatistical internal quality control measures ................................ 28 29 3.7 Quality assurance in bacteriology ............................................................................. 30 3.8 Evaluation of results and data handling .................................................................... 3.9 Quality manual .......................................................................................................... 32 . ................................................. 33 3.10 Quality assurance in parasitology .................... 3.11 Self production of control materials .................................................................... 34 3.12 Self production of reagents ..................................................................................... 35 . ....................................................................... 36 3.13 Reference methods ...................... . 3.14 Quality assurance in pre-analytical phase ............................................................... 37 3.15 Quality assurance in the post-analytical phase ...................................................... 38 39 3.16 Quality assurance of measuring instruments and devices ................................... .. 3.17 Traceab~l~ty ............................................................................................................. 40 3.18 Interference and interfering factors ......................................................................... 41 3.19 Quality assurance in dry chemistry ......................................................................... 43 3.20 Quality assurance in blood glucose monitoring ......... . . . .................................... 45
4 . PLAN OF ACTION ............................ . . ......................................................................... 46
Annexes 1. AGENDA .................................................................................................................... 47
2. PROGRAMME ........................................................................................................... 48 3. LIST OF PARTICIPANTS .......................................................................................... 50
4. INTERCOUNTRY COOPERATION AS FORMULATED BY THE PARTICIPANTS Oh '1'Ht: WOKKSHOP .......................................................................................... 56 5. QA CHECKLIST ........................................................................................................ 57 6. PLAN OF ACTION OF THE REGIONAL MEETING OF DIRECTORS OF HEALTH LABORATORY SERVICES, DAMASCUS, SYRIAN ARAB REPUBLIC, 12-1 5 MAY 1996 ............................................................................ .58 7. PLAN OF ACTION OF THE INTERCOUNTRY WORKSHOP ON QUALITY ASSURANCE IN HEALTH LABORATORIES, NICOSIA, CYPRUS, 29 JUNE-3 JULY 1992 ....................................................................................... 61
1. INTRODUCTION The World Health Organization (WHO) Eastern Mediterranean Regional Office (EMRO) organized a Regional Intercountry Workshop on Quality Assurance in Laboratory Medicine which was held in Teheran, Islamic Republic of Iran, from I0 to 14 May 1997. The 11 c u u ~ ~ t ~ of i eLhc s Region. workshop was attended by 12 participants and 13 obscrvels fiu~ll The objectives of the workshop were to evaluate the implementation of the plan of action endorsed in Nicosia, Cyprus, in 1992, assess achievements and define further steps to upgrade/establish quality assurance programmes in Eastern Mediterranean Region (EMR) countries. Dr Bagher Larigani, Iranian Undersecretary for Curative and Pharmaceutical Affairs, addressed the participants on behalf of the Minister of Health and Medical Education. Dr Larigani stated that the clinical laboratory played a major role in the prevention, diagnosis and monitoring of disease in all disciplines of medicine. Although there might be random cases where patients were treated successfully even though they were given erroneous results, such errors could end in a fatal outcome. It was essential to combine the scientific knowledge and expertise of the clinician with sound data from the clinical laboratory. Obsen~ations originating in physical examinations alonc could be quitc subj~clivs,so ubjectivt: elements should always be included, provided that data made available from objective analysis were reliable. Reliability implied two main concepts, he said: accuracy and precision. In the Islamic Republic of Iran laboratories had been monitoring the quality of their measurements in an ad hoc manner over the past 20 years or more. However, with the re-establishment of the National Reference Laboratory the implementation of quality control at different levels of laboratory services had been achieved in a coordinated and systematic manner. The National Reference Laboratory was at the apex of the pyramid of bodies responsible for quality control of the laboratories within the country, the biochemistry department being a WIIO Collaborating Centre for Quality Control in EMR countries. The Reference Laboratory had established an internal quality control training programme for implementation of quality control in laboratories throughout the country with special emphasis on peripheral laboratories. Cxte111al quality assurance stalted about 10 yeals ago, and a1 Lhe moment about 1000 laboratories were controlled in different disciplines, including clinical chemistry, bacteriology and haematology. In order to achieve better feedback from these programmes, an evaluation scheme for the assessment of equipment and reagents before their distribution in the country had also been established. Dr Larigani stated that the programme was still at the preliminary stage and there were many points of weakness. However, it was hoped that with time and the continued activities of colleagues in the field of clinical laboratories the level of services offered by the laboratories would be improved and health care services maen more effective as a result.
WHO-EMILABI294IEIL Page 2
Dr J. Hashmi, WHO Representative to the Islamic Republic of Iran, read out a message from Dr Hussein A. Gezairy, WHO Regional Director for the Eastern Mediterranean. Dr Gezairy welcomed the participants and thanked the Government of the Islamic Republic of Iran for hosting the workshop. He pointed out that health laboratory services' mission was to provide high quality services in the right place and at the right time in respect of the needs of patients and the community in general. Flcalth laboratory services would be able to contribute to the improvement of the quality of health care only if quality assurance programmes, using documented traceable systems with specific goals, were established. Specifications for meeting quality assurance goals must be developed. These specifications should be determined by the expectations of users based on their needs. The users of laboratory services were many: they included patients, physicians, nurses, public health workers, administrators and external regulatory agencies. A proper system of communication bctwccn performers and users of health laboratory services should be established to assess whether satisfactory quality is being achieved. Dr Gezairy recalled that quality assurance was a part of total quality management and quality improvement. Quality improvement was a method used to anticipate and prevent problems before they occurred. Quality improvement required that everyone involved in the process understood the objectives and made a commitment to improvement. Quality was "conformance to requirements" and referred to how well a test is perfonned in the laboratory and its utility in patient care; and it should occur at the place where the work is done. In order to improve confidence and assure both laboratory staff and clinicians about reliability of results, it was necessary to adopt the broad concept of the total quality management. Total quality management and continuous quality improvement were the responsibility of every one of the health laboratory staff. Emphasis should be placed o : r the importance of the satisfaction of the users, taking into consideration utility and cost. Thc cost involved in setting up quality assurance should be looked at in the light of the costs of lack of quality. Personnel were the key to enhancing implementation of total quality management, s a ~ d Dr Gezairy. The process of recruitment of staff, training, development, motivation, involvement, responsibility and teamwork were important elements in quality assurance programmes. People should be considered to he a primary resource and continually developed through training and education. Investments in education and training of resource people should be made to support continuous improvement, including in-service training and continuing education, as well as a commitment to formal educational processes for clinical laboratory personnel at all levels. Training and education would support individuals and encoilrage t h e i ~cnntrihi~tinns . a tenni memhers and involvement by establishing participatory mechanisms for problem-solving. For teamwork to thrive, each individual's contribution to the group effort must be valued. A higher quality of service could be provided when the entire operation, including organization, management, processing, and reporting, was addressed in the quality system. Such a systemic approach aimed at continuously iderllifying and preventing possible sources of error that influence the outcome of the process. In this context, the Eastern Mediterranean
WHO-EM/LAB/294/E/L Page 3
Regional Office had prepared guidelines for implementation and monitoring of quality systems for medical laboratories. The Regional Director said that EMRO was continuing to back up national efforts to establish quality assurance programmes. Sixteen countries of the Region were making a remarkable effort to establish and upgrade quality assurance programmes. Mechanisms to audit and appraise the operation of laboratories had been established in 10 countries and were on the way in another four countries. Documentation of in-house measurement procedures (standard operating procedures) was followed in 14 countrics and would bc soon in four more. Fifteen countries reported that they had started in-service training on internal quality control practices. Seven countries had appointed professional quality assurance managers, and arrangements were being made in seven other countries. Task forces to resolve operat~onai and technical difficulties in laboratories participating in quality assurance programmes had been established in 10 countries. Thirteen countries had introduced the concept of quality assurance in the curricula of training programmes for laboratory personnel. Sixteen countries were reported to have reliable sources for supplies of good quality. Legislation andlor regulation related to quality were available in nine countries. The Reference Laboratory in Teheran, Islamic Republic of Iran, had been nominated as a Regional Training Centre for Quality Assurance in Health Laboratories. Despite these achievements there was still a long way to go for reaching the goals and satisfactory quality of health laboratory services. Finally, Dr Gezairy mentioned that he was looking forward to the outcome of the workshop, hoping that by the end of thc workshop thc participants will have gained additiv~ral experience and agreed on realistic approaches to overcome difficulties and obstacles facing implementation and upgrading quality assurance programmes in their countries. The participants then introduced themselves and elected Dr M. Abbassi as Chairman and Mrs 2. Khatami as Rapporteur. The agenda and the programme of work were adopted (see Annex 1 and Annex 2 respectively). A list of participants is in Annex 3.
2. 2.1
COUNTRY REPORTS Afghanistan
Initiatives to introduce quality control practice in laboratory medicine started in the 1970s with the assistance of WHO. With the invasion of Afghanistan by Russian troops that practice stopped. At the present time there is no regular laboratory service in most of the cities of Afghanistan except Jalalabad, where commercial kits are used. However, there is no internal quality control or external quality assessment, and there is no national legislation in this field.
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Page 4 2.2
Bahrain
The laboratory services are provided by a network of laboratories distributed all over the state and are run by different organizations. Under the Ministry of Health, these services are provided by the Directorate of Laboratory Services in three major areas: Salmaniya Medical Centre (SMC) laboratory, health centre laboratories and public health laboratories. The Ministry of Health laboratories carry out various types of tests. The Salrnaniya Medical Centre laboratory applies internal quality control and participates in external quality assessment schemes. Irztcr-rral qurili<v contrnl. SMC laboi-ato~yhas develvped all i~~tclllal quality control programme for primary hcalth centre laboratories in the fields of haematology and clinical chemistry.
Exterttal quality assessmetzt. The SMC participates in many international quality assessment schemes for different laboratory disciplines. Biochemistry section. The biochemistry section at SMC participates in the Murex Biotech Limited immunoassay quality assessment scheme; the cyclosporin quality contrnl programme, Beirut, Lebanon; the Middle Bast External Quality Assessment Scheme for clinical chemistry; and the Riyadh Al-Kharj programme. Microbiology section. The microbiology section participates in the WHO external quality assessment scheme in clinical microbiology. ffaen~aiology section. The haematology sections at Salmaniya Medlcal Centre and AlNaim Health Centre take part in the United Kingdom National External Quality Assessment Schcme In the ilelds of routlne haematology, retlculocyte count, haemoglobinopathy and cnzymopathy. They also participate in the WllO quality assessment scheme for coagulation studies.
Safety manlml. The Directorate of Laboratory Services has published a booklet on safety rules and precautions in medical laboratories. This booklet has been distrihnted tn all laboratories in Bahrain. Laboratory handhook. The Directorate has published and distributed a handbook on laboratory tests and blood collection procedures. iCfcu.,urcrrrunt p r u ~ r d u r m Dctailcd . dcscriptiun of dimrent test procedures followed by different laboratory sections is available. The procedures manuals are updated every year.
Stnff. A new post of manager of' quality contrnl systems in laboratory medicine has been proposed.
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Egypt
The Central Health Laboratory (CHL) in Egypt is responsible for all the activities of hospital laboratories belonging to the Ministry of Health and Population. One of these responsibilities is the application of internal quality control in these laboratories, which is checked periodically. These laboratories use control materials imported by different suppliers.
In 1990, a quality assurance programme arranged by the Regional Office of the Eastern Med~terranean(EMRO) of the World Health Organization began in the CHL after the visit of a team froln WHO/EMRO and t l ~ eTnslilute for Standardization and Documentat~on In Laboratory Medicine (INSTAND) in Germany for implementing a quality management system in Egyptian laboratories. An initial workshop was conducted after which specialists from the CHL were sent to LNS'I'AND to be tratned on different aspects of quality assurance. The first trial of extemal quality assurance involved four laboratories in Cairo. The encouraging results of that trial were followed by workshops for laboratory staff from the greater Cairo area and other governorates to train on how to implement internal quality control and on pre-analytical measure, and to encourage them to participate in the national extemal quality assessment (NEQA) programme. Most of the CHL specialists received further training either at INSTAND or in Hungary. National workshops were also conducted to implement quality assurance in all Laboratories belonging to the Ministry of Hcalth and Population. WIT0 supplied CHL with instruments needed to upgrade the level of work. The nurnbcr of laboratories participating in the quality assurance programme organized by the CHL is 35 laboratories in Cairo, Giza and other governorates in upper and lower Egypt. 'l'he CHL pertbrms surveys twice yearly in: clinical chemistry for glucose, uric acid. urea creatinine, cholesterol, triglycerides, protein, albumin, bilirubin, sodium, potassium, calcium, phosphorus, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatases. haematology for haemoglobin, red blood cells, white blood cells, platelets, mean corpuscular volume and blood film for differentiated cells and case diagnosis. coagulation for prothrombin time and activated partial thromboplastin time. uri~le fur evalualiun of the quality of urine strips in the Egyptian market
The CHL distributed material for the sixth and most recent survey in March 1997. After collecting the results, the CHL evaluates them and gives the participants a certificate for the analytes fulfilling the requirements.
W110-CMILAB/294/EIL Page 6 INSTAND continues to support the CHL by supply~ngthe quahty control materials distributed in surveys. Besides that, the quality assurance surveys are evaluated for fulfilment of the German standards and certificates are issued from INSTAND to our participants in clinical chemistry, haematology, and coagulation. Meanwhile, the CHL participates in INSTAND'S surveys of clinical chemistry, haematology, coagulation, virology, tuberculosis and microbiology; all laboratories were found to fulfil the German standards and certificates were given to the different laboratories of the CHL.
The quality assurance programmes in health laboratories have been established in the Islamic Rcpublic of Iran for 10 ycars. Thc programme which started only in cli~licalchemistry has been expanded to bacteriology, haematology, parasitology and serology. To date, there are no programmes for immunochemistry (hormones and drugs), virology, mycology and cytopathology. The programmes established have been very diverse in nature and can be classified as follows: training on internal quality control establishment of external quality assessment programmes control of reagents, kits, and equipment preparntinn of qtandard snlutlons for substrate measurement for improved comparability between laboratory results. A ) Trainirzg on inter-rzal qualify corttrvl
Clinical chemistry 1. National reference laboratories. There have been more than 20 courses covering about 350 laboratories in both Teheran and the 26 provinces over a period of about 10 years. Training of trainers in quality control courses has included participants from Isfahan, Kermanshah, Sistan ve Baluchistan, Khorasan, Chahar Mahall ve Bakhtiari and three main university hospitals, which have coverage over all the laboratories in Teheran (private and public). Two courses were run for participants from the blood transfusion services and social insurance offices, covering about 10 participants. These trainers were given certificates for carrying out similar training under the protocol for improving quality of health scheme that was presented in the original course. Isfahan rcfcrcncc iahoratories. These laboratories carried out one training course in clinical chemistry for about 100 laboratories. Kcrmanshah reference laboratories. Kermanshah carr~ed out two training courses, covering 50 laboratories with the aim of validation of instruments and follow up of all the units checking the quality of tests, basic equipment, etc. Once the quality of these is
2.
3.
WHO-EMIL.ABI294IEIL Page 7
verified, the second stage of the quality control programme, which entails training on using controls for precision and accuracy, drawing up quality control charts will start.
4.
'Teheran University has had one training course in internal quality control for about 20 participants. Iran University has had one training course in internal quality control for about 20 participants. Khorasan reference laboratories have had a training course in internal quality control for about 20 participants.
5.
6.
Documents, reports and booklets for cartying out the courses are prepared either by the National Reference Laboratory or by the local organizers and distributed to all participants or other people as requ~red. The aitn is to carry out training progratrimes in three phases: Phase I: Phasc 11: Validation of basic equipment and verification; Establishment of' internal quality control with drawing up control charts for precision as a priority and accuracy as a second requisite;
Phase 111: Coordination of errors obset-ved with the quality required by physicians according to the objectives, i.e. screening. routine ciia;,nosis, treatment, hllow up, prognosis, or research: Phase IV: Inclusion of all laboratories in external quality assessment schemes (EQAS)
Bacteriology Two courses for general training of laboratory staff, have been carried out, each of which included 20 participants from Teheran and seven provinces. Another two courses have been carried out for training of trainers with 16 participants in each.
tiaernatology One course for training of trainers has bcen held with patticipants from six main units represented by two persons from each unit (blood transhsion serviccs, Khorasan central laboratory and three universities). The text covered the main topics in internal quality control. It should he added that another course was also held in Tsfahan for about 100 laboratories. 'Training has not been established for other disciplines yet.
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Page 8 B) External quality assessment schemes
Clinical chemistry
I.
National Reference Laboratory. Fifteen trials have been sent until now over the past decade. The laboratories covered have now been expanded to those in Teheran and nine provinces (about 1000 laboratories). It is hoped to expand the scheme to about 3000 laboratories (the total number of functioning laboratories throughout the Islamic Republic of Iran). At present, parameters include all substrates, electrolytes and f v c enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], creatinine kinase [CK], lactate dehydrogenase [LDH], and alkaline phosphatase [ALK ph]. About per yea1 al~e held acco~cling to availability of control materials. All results are twu t~ials processed as per the procedurcs employed in external quality assessment of the WHO Collaborating Centre for EQAS in Clinical Chemistry. Isfahan Reference Laboratory. Fifteen trials of external quality assessment covering 100 laboratories have been held for substrates only.
2.
Bacteriology I. National Reference Laboratory. This laboratory started an external quality assessment programme three years ago. Five trials have been performed up to now. At present, 800 laboratories arc covered, including those in Teheran and 11 provinces. In each trial two diverse bacterial species are sent and the identification (genus, species and subtype) are required accordingly. One of each species sent is reqi ired to have sensitivity testing. The baclrr-ia are i n a pule f v r ~ r Lake11 ~ frorr~sarnples sent by WHO to the Islamic Republic of [ran as part of the WHO external quality assessment scheme. lsfahan Kcference Laboratory. One trial has been held for 100 laboratories, including mixcd cultures containing two species of bacteria for identification and sensitivity testing.
2.
Haematology
I.
National Reference Laboratory. Six trials have been performed in the past four years. At present, about 800 laboratories are covered, including those in Teheran and eight provinces. Samples contain haemoglobincyanide (HiCN), hacmoglobin lysatc, reticulocyte, one blood smear for identification and one unstained blood smear for controlling the quality of staining. Isfahan Reference Laboratory. Two trials, one including an unstained smear for differential count which was also infected with malaria parasite, covering 100 laborator~es.Another trial collected for complete blood count (CBC) and platelet count from 40 laboratories.
2.
WHO-EM/LAB/294/E/L Page 9 Serology 1.
National Reference Laboratory. One trial sent to about 400 laboratories for Wright agglutination test using different methods. Isfahan Reference Laboratory. Two trials for Wright agglutination test to about 100 laboratories. One trial for Wright, 2ME (mercaptoethanol), Coombs Wright and antistreptolysin 0 (ASO) for 100 laboratories. 3. Control of kits, reagents and equipment
2.
111 cli~litial che~uistry,all reagents and equipment, whether produced locally or imported, should be subjected to control and validation before distribution by the national reference laboratories. As an example, during the past year about 150 kits were sent for evaluation, as well as two automatic analysers (Alcyon and Pronto) and other instruments including ELISA readers, refractometers, photometers, conductometers, pH meters and flamephotometers.
In bacteriology, control has been achieved for cell counters, microscopes, sediment pipettes, slides and cover glasses, reagents for blood grouping and coagulation tests (prothrombin time [PT] and partial thromboplastin time [PTT]) In serology, coritrol of Wright, Widal, antistreptolysin 0 (ASO), and pregnancy tests and other solutions has been done. 4. Future goals
1.
Expansion of training programmes mentioned in part A) to cover all the laboratories; Establishment of training courses in serology, immunology, parasitology, virology, cytopathology and pathology; Preparation of quality manuals for all of a11 laboratory disciplines; Establishment of external quality assessment ~ c h e m e s programmes in therapeutic drug monitoring (TDM), hormones, virology and cytopathology; Preparation of a unifom~checltlist for auditioning purposcs for thc health laboratories throughout the Islamic Republic of Iran; Expansion of external quality assessment schemes to all the laboratories;
2.
3. 4.
5.
6.
It is hopcd with the aid of international bodies (WHO, German Institute of Documentation and Standardization [INSTAND], International Federation of Clinical Chemistry [IFCC], etc.) to expand the above goals to all the countries of the Kegion.
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Morocco
After the incorporation of the National Institute of Hygiene (NTH) into the Directorate of Epidemiology and Disease Control, the laboratories of hygiene and epidemiology (LHE) and the laboratories supporting priority health programmes as well as the clinical biology laboratories (CBL) fell under the heading of the bureau of laboratories at the above-mentinned institute. The national laboratory network comprises 68 clinical biology laboratories, 33 peripheral laboratories, 174 laboratory units for tuberculosis, 155 laboratory units for schistnsomiasis and malaria, 14 laboratory units for leprosy, 30 laboratories for waterbomc diseases and food quality control. To assess the state of the network, a questionnaire was sent out and its results are being analysed. Field site visits were also conducted between September 1996 and April 1397. Thc following information was collected: r
The dispersion of sites resulted in duplication of equipment which could have been used by other laboratories within the network; There is a disparity between the two kinds of laboratories with a difference in technicians' workload. The CBL technicians have a high workload, but some of the LHE technicians have a minimal workload.
*
Equipment. While the LHE has plenty of new and underused equipment, the CBL has little cquipment, most of which is more than 10 years old. Equipn~entmaintenance. There is no equipment maintenance facility in the CBL and LME. The biomedical engineers working at the Directorate )f Equipment and Maintenance are not trained to maintain laboratory equipment. Rengents and expendable iterrts. The disparity is the same as for equipment Budget. l'he LHE are financed through generous sanitary programmes, while the CBL has a token budget. Training. Continuous training and refresher courses remain insufficient for both the CBL and the LEIE technicians.
Taking in consideration these facts, and the available site resources (human resources, or specific site capacities), and being aware of the sustnincd dccreasc of laboratory budget as well as financial resources, the NIH aims to optimize and rationalize the available resources. To achieve the laboratory network restructuring project, they have proposcd and discusscd the following reforul and reslruzturing models according to the size of each province (small, medium, or large). lnral dispnritinn
WHO-EM/LAB/294/B/I, Page 11 At the provincial level
This takes the form of the integration of activities for small provinces, the grouping of structures for medium-sized provinces, and the establishment of a resource pool for large provinces. In all cases, one person will be assigned responsibility for the laboratory network and will report directly to the provincial delegate. At the central level
The need for laboratory services from the users' perspective Directorate of Epidemiology and Disease Control (DELM), Directorate of Population (DP), and Directorate of flospitals (Dfl) arc rcvicw~ng what thcy nccd from thc lahoratory services. The PIltI is coordinating the crcatiun of the new laboratories needed by the different directorates according to the already existing structures. It is also coordinating w ~ t hall directorates involved in the management of laboratories in order to find the best and rnost economical way to run laboratories. The dcsired goal is to give the responsibility for equipment and reagent purchase as well as quality control and maintenance to the NIH. The latter should also have a decisive role in human resources management. T h e peripheral laboratories The p r r ~ p h ~ r lahnratnr~c< al :ire helng re-evaluated hefore d e c ~ d ~ n on g further expans~on ' I he budget for the new equ~pment IS already allocated. Curretit progress of the laboratory network reform The reform project financed by the WlIO in the bienniunl 199611997 has accomplished the following: constitution of a database of all the network laboratories including human resources, equipment and activities; audits in 30 provinces; authorization to audit the central directoratcs, recently received. The audits will be conducted during May 1997; and site visits to evaluate peripheral laboratories. These are being conducted and will be completed in Junc 1997. An agreement has been reached with the Ministry of Pubic Health for postgraduate PI-ofcssio~~al training to train bion~cdicalengineers on laho~atoiyequi11111e11t. A project to support training for technicians has becn submitted in collaboration with the International Association of Biological 'Itchnicians for French cooperation funds. A consensus seminar, gathering the prov~ncialrepresentatlves and the ccntral ci~rectorsand presided over by the Minister of Public Ilcalth is planned for Scpter~iber1997. It will allow the NIfl to take stock for the new functioning of the laboraton1 nctwork. and propose rcforn~s
WIIO-CM/LAB/294/E/L
Page 12 It is important to note that the restructuring project as described has been well received
by the provincial delegates. The DELM, which is the most important user of the laboratory services, is strongly in favour of this r e f o m project. The directorate is already establishing links between the LHE and the CBL, especially since NIH is now part of the Directorate of Epidemiology and Disease Control. Quality assurance programme The national programme of quality assurance started in 1991 with a ministerial circular letter that was sent to all laboratory users. The 1991-93 period was devoted to training o t ~ trainers. The application of the internal and external quality assessment schemes started in 1993. Training of trainers The chiefs of the departments (bacteriology, biochemistry, parasitology, haematology, immunology) in the National Institute of Hygiene (NIH) have been trained in specialized French laboratories on quality assurance. Five national seminars have heen conducted in biochemistry, microbiology, parasitology, haematology and immunoserology. Twenty-five medical biologists have been trained. WHO and the French cooperation ensured the financial support. Internal quality control French cooperation supported the cost of internal quality control sera in biochemistry for three years (1991-93) and the acquisition of the equipment for local preparation of internal quality control sera (lyophilizer, refrigerated centrihge, automated distributor). The department of microbiology took over the control of the preparation of the corresponding standards (references isolates). Quality control manuals The NIH has supported the preparation of quality control manuals in each discipline and the validation of a guide to good laboratory practices prepared by a national commission. External quality assessment External quality asscssmcnt su~vcyswelt: curlducted in 1993, 1994, and 1995. l'hey concerned four clinical biology disciplines. At present, the only epidemiological surveillance laboratory activity supporting external quality assessment is diagnosis of tuberculosis and malaria. Table 1 shows the enrolled and part~cipatinglaboratories in the clinical biology external quality assessment programme and the ratio of good laboratory rcsults in the disciplines tested.
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Table 1. Evolution of the national external quality assessment programme: percentage of participation and good responses (shown in brackets) ~~ ~ ~~~
.
~
year
Enrolment/ Parasitology Haematology Microbiology Biochemistry Immunoparticipation YO % YO %( serology %
Only 35 of the 38 participating Iahoratories responded in parasitology
' Figures in brackets represenl the percentage range of good results in haematology (total respondeditotal oxpocted) ' Percentage of good results on direct examination and on isolation and identification of hactcria (ligurc in brackets represents the number of lahoratories responding in microbiology) Pclccntagc of good ~csults o n amrtil,iolic scnsilivily rtudy (figulr; ill hrackcls rcprcscnls lhc number of laboratories responding in microbiology) Percentage of good results in biochemistry (total respondeditotal expected). In 1993 the 23 responding laboratories responded for all the paranleters tested 'Percentage of good results in immunology (total respondeditotal expected)
Table 2. Participation ratio Enrolled laboratories Laboratories Biologists Technicians 41 22 156
Participating laboratories 31
h Ratio O 75Yo
18 131
81% 84%
Methodology and results A questionnaire was circulated by the CBL in May 1995. Twenty-two biologists and 156 technicians were enrolled from 41 clinical biology laboratories. Table 2 shows the participating ratio of the 178 biologists and technicians. The questionnaire showed that among the 18 participant biologists, 89% practise internal quality control (IQC). The IQC concerned haematology (22%); bacteriology (1 1%); and biochemistry (6776). When IQC is not practised, the rcasons arc lack of personnel and lack of reagents in similar proportions of 50%.
W HO-EM/LAB/294/E/L
Page 14 agreed w ~ t h the pract~ce of an external qual~ty assessment programme All the b~olog~sts but mentioned the need for more informative and annotated results as a form of continuous training. They also stressed the need for regular and more frequent controls. Twenty-five per cent of the laboratories fulfilled all the conditions required for quality control. while 75% did not. The results of the questionnaire sent to the technicians showed that only 29% have had training on quality control; 20% participated in seminars in quality control; 41% reported that they are well trained by biologists (70% of technicians are working with biologists); and 34% practice internal quality control. The technicians also reported a lack of information: (60%), lack uC rcagcr~lb(26%). and I d ~ k of cquip~ucnt(14%). 011ly 20% i~~dicaccd ll~alchcy wcre aware of the EQA programme, and 83% of the technicians showed interest in knowing more about the external quality assessment programme. About 89% of the laboratories directed by biologists have IQC in place, while only 34% of the laboratories directed by technicians have IQC in place. The reasons given by biologists for not practising IQC were lack of reagents (50%) and lack of personnel (50%). Technicians' reasons are lack of information (60%), lack of reagents (26%) and lack of equipment (14%). 2.6
Oman
The quality assurance programme was established a long time ago and recently has been expanded to include all regional laboratories within the Ministry of Health as part of the improvement of health services in Oman. There is no legislation on laboratory quality assurance as yet. However, the laboratories in Ornan do participate ill a r~urr~ber or quality assessment programmes in both international as well as local schemes. International external quality assessnzent schemes
These are multidisciplinary schemes. Participation in these schemes, however, is limited to large tertiary referral institutions such as the Central Health Laboratories, the Royal Hospital and the Sultan Qaboos University Hospital. These schemes are from various organizations such as the Middle Eastern External Quality Assessment Scheme (MEEQAS), the World Health Organization, the National External Quality Assessment Schemes, the Australian Quality Control Programme and the Murex (Wellcome) Diagnostic Quality Assessment Programme. National externul quality assessment schemes
A special unit responsible for quality control has been set up within the Department of Laboratories under the Directorate General of Health Affairs of the Ministry of Health. This unit acts as a focal point in coordinating and supervising quality assurance programmes in secondary and primary level laboratories in Oman.
WHO-CM/LAB/294/E/L Page 15 The unit is responsible for the preparation and d~spatch ofthe quality control material to all government laboratories and also follows up the performance of each individual laboratory. Those laboratories which report two successive unsatisfactory results, are subjected to an expert appraisal. This scheme has recently been expanded to include various disciplines. The two main tertiary institutions which are responsible for this scheme are the Central Health Laboratories, which are responsible for the supply of microbiological and serological quality control material; and the Royal Hospital, which is responsible for the supply of specilnsns for haematological and biochemical quality control. Factors coritr-ibuting to success
The success in implementation of the quality assurance programme in Oman has been mainly due to the following factors: The establishment of a quality assurance unit within the Central Health Laboratories whose sole purpose is to implement the quality assurance programme on a national level; On-the-job training and workshops which are regularly conducted in different fields: and Standard operating procedures are being implemcntcd. Factorr contribrrting to constraints
Inability to transport materials in a prompt mannr .to thc part~cipatinglaboratories; lnsuff~ciency of the existing human iesourccs. 2.7 Pakistan National lnstitule of Health
The National Institute of Health (NIH) was established and commissioned in 1967. The NlH has since been involved in the provision of facilities for laboratories, research and production of vaccines. During the years, NIII has rendered training facilities to local and foreign medical professionals, being one of the leading research centres in virology in thc Castcln Mediterranean Region. The main functions of NlH are. production of vaccine and sera public health actlvlties diagnostic and environmental health activities monitoring of nutritional status
WHO-EM/LAB/294/E/L Page 16 analyt~cal appellate funct~ons under the drug act of I W b quality control and assurance research and training activities collaboration with international agencies housing of preventive programmes on EPI, AIDS and IDD. The NIH has different technical divisions, which keep up with ongoing research and provide services which usually are not offered in the other institutes of the country. The main technical divisions are: biological production division public hcalth division nutrition division drug control and traditional medicine division clinical research division quality control for biologicals college of medical laboratory technology. The NIH also implements different projects, for example on AIDS and immunization, with the collaboration of international agencies. At present, a guinea-worm eradication programme and iodine deficiency diseases control programme have been implemented. Collaboration with national and international agencies
Several national and international agencies collaborate in the development of the institute and in eradication, control, and diagnosis of the diseases. The Wol.ld Heallh Organization, UNICEF, the World Food Programme, the United Nations Development Programme (UNDP), the Food and Agriculture Organization of the United Nations (FAO), the Japanese International Commission for Aid (JICA) and the Board of Science and Technology for International Development (BOSTID), USA, have supported NIH programmes on research, development, and training. The Canadian International Development Agency (CIDA) has helped in the establishment of poliomyelitis and IIDC rabies vaccine production laboratories. USAID has helped in the establishment of a tetanus toxoid production laboratory. The NIH is the only vaccine producer in the country. The quality control system is well established for the vaccines and sera which are produced in NIH, but the quality assurance system is not well developed. It is now in the initial phase. EPI is a government-controlled programme and is the largest importer of vaccines. In the private sector, multinational companies arc allowed to import any biulugical or pharmaceutical product in the country. The importer is bound to obeying the drug laws of Pakistan of 1976. Local producers are also bound to follow these laws.
WHO-EMLAB/294/E/L Page 17 Quality control system. A well established quality control laboratory with full facilities is available in the NIH premises and extensive fa'cilities also exist to test products on animals. NIH products are tested routinely in the laboratory. National Control AgencyWA) and quality assurance. The Directorate General of Health acts as NCA for biologicals. The samples from NCA are sent to the quality control laboratory, NIH, for testing. A quality assurance manager has been appointed recently for the quality assurance of NIH biological products. The NCA system of biologicals is not well estahlished hut there is an ongoing effort to improve it and makp it more efficient As NIH has not established a national quality assurance programme for laboratory medicine, no report covering this field was presented during this workshop. 2.8
Sudan
There are well established laboratories for control of food, water, toxic materials and drug quality. The food and drinks section assesses whether food and drinks satisfy the requirements and specifications and are free from contaminants to ensure their suitability for human consumption; it issues certificates to this effect. The water and sewage section analyses the drinking-water and assesses its chemical constitution and suitability for human and animal consumption and analyses sewage water and industrial waste material. The contaminants and toxic material sectinn carries out analysis for food and water contaminants and the environmental pollution caused by poisonous materials, as well as analysis of cases of poisoning from hospitals. The drug quality control laboratory tests random drug samples to establish their conformity with the required specifications. With respect to quality control in clinical laboratories, at present there is a unit under construction in the National Health Laboratory In Khartoum for quality control. Its purpose is to undertake quality control for all clinical investigations in the national laboratories, other hospital laboratories and private laboratories, as well as to control and assess all reagents, chemicals and kits brought in by commercial companies. At present, the departments in the National Health Laboratory depend mostly on external quality assessment, the use of serum pools and commercial control sera with each run nf iinknnwns (determination nf standard deviations for each component of a control specimen; day-to-day and batch-to-batch precision; and setting-up quality control charts). The laboratory hns a list with dctailcd instructions for specimen collection to mini~uize pre-analytical factors that cause misinterpretation of results.
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2.9
Syrian Arab Republic
Health laboratory services cover all of the Syrian Arab Republic. They are represented by the public and private sectors. The public sector consists of the Ministry of Health, the Ministry of Higher Education and the military medical services. The private sector consists of independent laboratories and private hospitals. The Central Health Services Laboratory Services (CHL) administration has the responsibility of supervising the public health laboratories, ihc hospital laboratories and the National Committee of Quality Assurance (NCQA). In 1992, the Minister of Health created the National Committee of Quality Assurance in Medical Laboratories based on legislation. The legal requirements cover all medical laboratories including private laboratories. Laboratories have to implement quality assurance and to participate in external quality assessment surveys. By law. laboratories which are not up to survey standard should be inspected and monitored. In case of continuation of bad performance, a laboratory may be restricted to a reduced analytical spectrum for a limited time, and as an ultimate measure, closing of the laboratory is possible. Internal quality control
Public sector 'l'he M~nlstry of Health in the Syrian Arab Republic has started internal quality control in major hospitals after nominating the quality control officers. The Central Health Laboratories (CHL) have developed and distributed, in Arabic, protocol sheets and control charts. A stable serum pool is prepared continuously by the quality assurance unit of the CHL. The protocol sheets are sent back to the quality assurance unit nt the cnd of cach month after the analyses of up to 24 analytes daily. Hospital laboratories report on their IQC results and send them back for statistical evaluation. Chemists, pharmacists and technicians work in the quality assurance unit located in the CF1L. A group from the quality assurance unit has prepared guidelines of internal quality control at bench level.
Private sector The CHL has no reliable data as yet regarding running quality control in private laboratories.
WHO-EMILAB/294/EIL Page 19 External quality assessment
The National Committee for Quality Assurance in Medical Laboratories renews its member after the visit of Professor W. Appel, of INSTAND, Germany, to the Syrian Arab Republic in October 1996. There are now three members from the Ministry of Health, two members from the Syrian Clinical Laboratory Association (private sector), two members from the Faculty of Pharmacy, four members from the Faculty of Medicine and two members from the Military Medical Services. The National Committee has performed 10 surveys since 1993 Human control material is used in some runs, pool sera nre stabilized by polyethylene glycol after withdrawal of a defined volume of serum the same volume of solution of stabilizer is added up to 10% (final concentration). In the other runs we are ready to use control sera from a commercial source. All the laboratories (private and public) in the Syrian Arab Republic are obliged by regulation to join the external quality assurance programme. The external quality assessment programme is partly financed by the contribution of private laboratories to the national committee of about US$ 50 per laboratory per year. Six training courses have been organized in major cities in the Syrian Arab Republic for staff of private and public sectors. The National Committee of Quality Assurance in coopcration with thc Syrian Clinical Laboratory Association (SCLA) has improved a previous version of a computer programme to organize the external quality assessment (EQA) scheme. On receipt of results of an EQA survey, results are statistically analysed using local computer software. The National Committee has adopted the consensus method. The reported results of each participant are printed in lists containing individual results, graphic presentation of all individual results in terms of means, range of results and ranking (score) Every laboratory is identified by a confidential number Plan of Action
To increase the biochemistry parameters in every run; To start with haematology parameters and microbiological investigations;
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Page 20 To develop a quality manual in Arabic; 7b start an external quality assurance programme in hormones and tumour markers;
To run training courses for postgraduates in the Ministry of Health, Ministry of Higher Education, and Military Medical Scrvice~
2.10 Tunisia Orgnniztrlion of health laboratory services
There are 40 1 laboratories distribured in three levels as follows: Central laboratories (68). These are university hospital laboratories, which usually specialize in one discipline. They perform analysis relating to their specialities, laboratory staff training activities and research. Intermediate laboratories (230). These comprise public clinical laboratories, of which there are 53, regional public health laboratories of which there are 25, and private clinical Iahnratnrics, which n~imhcr157.. These lahnratnries provide roiltine analysis Peripheral laboratories (1 03). The peripheral laboratories provide preliminary services relating to biological invcstigations of clinical scrviccs in thc district hospitals and primary health centres. Quallly assurance programnles of'rhr henlrh laboratory services
The quality assurance programmes are based on: continuous training of the laboratory staff by diffusion of education support, organization of workshops and other scientific events; the national external quality assessment assays laboratories covering all the disciplines of clinical hiology in accordance with a decree plihlished in May 1990; the revision of private clinical laboratory legislation; the in~plenientation of a national reagent vigilance system-all diagnostic reagents will soon be submitted for technical control before putting on the market; the listing of equipment selection criteria: technical performance and brand awareness, official appraisal results, after-sales services, operational costs, technical documentation provided with the equipment, the price of the equipment and spare parts, service contract clauses; and
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the appraisal visits of health laboratories Constraints of the quality assurance programmes
Most of the clinical laboratories meet the following difficulties when upgrading their services: shortage of qualified staff insufficiency of operating budget ineff~ciencyof equipment maintenance: poor follow up of servicing equipmcnt, and usually lack of spare parts in the market. 2.11 Republlc of Yemen
In spite of all measures taken since 1992 to promote quality control activities in the Republic of Yemen, regrethlly all efforts and plans to support the quality control as internal and external assessment and the international scheme have failed. This is due to several factors: a a
lack of knowledge of the importance of the quality control activities lack of fnnds for all laboratory activities bad administrative management of laboratory activities no legislative regulations on quality control as obligatory disciplines are issued in Ycmcn
These factors and others should be studied and monitored by the Ministry of Public Health with the support of WI-IO/EMRO, friendly countries andlor international associations interested in quality assurance.
2.12 Discussions The participants discussed in detail different issues of quality assurance. The following are highlights of the discussions: a
wnrking ernup s h n ~ ~he l d t.stahlisht?d to write the stnrcture of the meeting's plan of action. A mall
Quality assurance should bc carricd out rcgardlcss of facilities available. In case of inability to cany out some parts of the previous plans of action, for example preparation of standard operating procedures (SOPS) and quality manuals, consultants can be requested for assistance
WHO-EM/LAB/294/E/L Page 22 'Ihe main problems must be Identitled which have to bc overcoine in order to implement ql~alityassurance. Ilocurnentation of national plans for establishing quality control according to status quo of each specific country is important. There should be more training for nationals, as well as more exchange of information both between cou:~triesof the Region and with experts and consultants. Working groups should be established on an intracountry basis, to cany out tasks at national level and also to assist nelghbouriny countries. Practical workshops should be organized especially for people who are directly ~ e s ~ ~ o n sat ~ the b l ebcnch level. 0
Quality assurance should be considered in the WtrO!govemn~ent collaborating programme. Equipment purchasing policies should be established. Service engineers must be trained for maintenance and repair of the equipment. Training should he carried out at all levels and in all disciplines of quality assurance. This should be carried out through national training courses and also through joint programmes with WHO. Fellowships should be made possible. [t should be made surc that within national quality control programmes, the plans are job-oriented. Keference ranges should be estal;!ished and specific budget allocated to quality assurance programmes.
3. 1.1
PRESENTATIONS
Ecnnnmir aspects nf q i ~ a l i t y aqsuranre. and cost effectiveness Dr If! Apprl
Mcnsurcs of quality assurance (QA) arc intcgratcd in the t:rld of labolator-y irietlicine. These measures are mandatory in Germany and are supervised hy quality officers of the German Weights and Measures Office. There are no national or international standards asking for or even considering financial aspects of Q A for the medical laboratory bkonomic aspects of Q A are important bath in deve!oped and developing countries. Diffcrenccs may bc seen mainly in enlphasis: in Germany, for example, the high costs of personnel, including social security contributions, predominate; in othcr countries financial aspects of instrumentation, reagents and controls may play the primary role. An estimation of bcnefits of measures of QA seems to he extraordinary difficult. Rezarding the different disciples of lrthoratory mcdicitie the typcs and cxtents of internal and external QP schemes differ widely and the benefit. of better performance of laboratory tests and findings is not restricted to the laboratory but even mnrr to the piltient cnnrerried. It is obvio11.r.that "good" laboi-ato~y results will reduce the
WHO-EM/LAB/294/E/L Page 23 overall costs of patlent care. 'l'hese costs may be estimated to some extent for hospital inpatients, but this may be almost impossible in general health care. The cost-benefits of more reliable laboratory results induced by QA may be estimated only in general terms at present. Restricting to the medical laboratory some aspects may be demonstrated. Procedures for documenting the total analytical process in general and measures of QA in specific are usually based on "time-measurement" methods. Efforts and results are reported in the USA by the Coliege of American Pathologists (CAP, 1970), in Austria by Fischen et al. (1982) or Gibitz (1986) and in Germany by Osburg (1970 ff.), Haeckel (1986, 1990), Wust (1980, 1990) or Weinstock (1988, 1992). One of the major problems is seen in the difficulty of registration of "number of items" as a basis for "time necessary" and "costs required". There have been many studies on costs it1 mcdical laboratories looking specifically at personnel costs; the nral1t.r will not be discussed here (Von Boroviczeny, Wust, Appel). about the costs of In 1986 Walker published in Pathologist (a CAP journal) an art~cle QA in clinical chemistry for his laboratory. The costs of control materials, multiple tests, standards and calibrators in 1983 and in 1984 amounted to 43% of the overall costs of tests, in 1986 to about 39% and in the following years were estimated at less than 30%, due to reduction of the frequency of calibrations, use of control materials for double tests, and of broadening the acceptable range in internal quality control. In 1987. Von Boroviczeny published the results of an INSTAND inquiry answered by 20 large hospital laboratories. The quotient of the total (necessarily performed) laboratory findings and the number of primary analytical tests including QA tests varied from 1.22% to 2.49%, i.e. about 12%-50% of all tests performed for controls in clinical chemistry, haematology, immunology, microbiology units. and e~uergency Nowadays, statistical analyses performed on computers and more reliable data are available. The German Institute for Standardization, DIN, has developed drafts for German standards (DIN 13064, I'art 1 , 1991: Guidelines for recording of work in ntedical lahoruiories). In 1997 Y. Schmitt and '[h. Schultz published New .sofiware for co11tro1.sof cost.s in medical laboruiories in ho,spiial.s and ofices ~f'generalpractitioners. During this presentation different economic aspects wcrc discussed, based on registration of tinte and expense necessary for performing a single test of any anaiyte in terms of' cost.7 of' mciterial and overall costs of stafr regarding the daily workload in a central lahoratory o f a 1000-brd ho.~pital. 3.2 Quality management in medical laboratories Dr I ? Wnllheim In the past, quality assurance initiatives in medical laboratories were primarily focused on the analytical quality of the measurement results. Analytical quality is still essential but other qualities of the cbnical laboratory scr-vice may be also very important for the satisfaction of the patients and their physicians. Adequate turn-around time, minimal blood sample volumes, legible and informative reports or assurance of sample identity may be
WHO-EMILABI294IEIL Page 24
mentioned as part of good laboratory service. Economic and ethical aspects have to be considered also. The scope of quality management in the medical laboratory exceeds therefore that of technical standards like the International Standards Organization Guide 25. Actually, req~~irements that are specific for medical lahnratnries are wnrked out on at international level by the International Standards Organization (IS0 TCR12). The qun!ity system (QS) of the medical laboratory rcquires at least the definition u i goals and objectives regarding analytical processes and other parts of the laboratory service. The laboratory director has to build up a quality system for the analytical processes comprising internal quality control (QC) and external quality assessment (EQA). Further objectives are adequate instrument maintenance and improvement of laboratory service including consulting and education. 'The policies, organization, resources and procedures are documented in a quality handbook that is available to all employees. It is essential that the laboratory can be legally identitied. The description of its organization must include all parts of the institution including those at remote locations. Additionally, the responsibilities of the staR have to he defined and a quality manager has to be appointed. Further elements of the QS are: control of documents procedures for the referral of tests to other laboratories procedures for the selection and use of external suppli2s and services standard operating procedures for sampling and mcasurcment control of non-standard testing corrective and preventive action.
e
The use and the storage time of the different records (request sheets, patient reports, itistrun~ent printouts, quality improvement records, QC and EQA records, instrument maintenance records) have to be defined. Performance of the QS has to be supervised by regular internal audits that can he performed by the quality manager. The effectiveness of the quality plan is reviewed and, if necessary, corrective actions are performed. (management review). Quality mnnagcmcnt has successfully hccn implenlentcd in busillcbb a11t1~ ~ ~ a r t u f a ~ t u r i n g ; it should be realized as soon as possible in medical laboratories to improve their service capabilities. It may be crucial for the survival of independent laboratories.
3.3 Standard operating procedures Dr F: Wollheim Standard operating procedures (SOPS) are part of the documentation ~lecessaryfor quality managelnent. The SOP gives clear instructions on ho~.v to perform an analytical
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Page 25 procedure. Add~t~onally ~t should contaln all background ~nformat~on necessary for verification, interpretation and consulting that is part of good clinical laboratory service. The format of SOP documents is strictly standardized. Examples for the layout and the basic content are given by the NCCLS Standard GP2-A2. Ideally, the technician who performs that test compiles the SOP in cooperation with the quality manager. The document has to be approved by the head of' the institution. It is reviewed at regular intervals or for specific reasons. Storage time of documents has to be regulated. Each SOP must contain the following: cl~nical indications for perfon~iing the test specimen requirements, collection procedures, storage time, disposal of specimens principles of cxanlination procedure preparation of reagents, callbrators, qual~ty control materials, how to pertorm the test instrument maintenance protocols reporting and clinical interpretation other pertinent data. The preparation of SOPS is very labour-intensive. If kits or whole diagnostic systems are used for testing, information regarding the performance of the test could be taken from the description if the package insert is provided. Background information has to be taken from sources like textbooks and scientific publications. Much effort could be saved if these information sources were available in computer-readable form. 3.4 Quality assul-ance in virology
Dr K. Janitschke
Qual~tyassurance (QA) is essential for laboratory d~agnos~s, especially of significant viral diseases like HIV, hepatitis, and rubclla. QA in the serodiagnosis of infections is well established whereas the direct detection of virus particles is still in the early stages. The external QA scheme (EQAS) in virology has been established in Germany since 1988. INSTAND organizes the EQAS together with the two scientific societies for virology. Professor Zeichhardt (Berlin) is the head of these schemes. There are two running per year with 14 programmes: FIN-1, HIV-2, rubella, hepatitis A, hepatitis B (2 programmes), hepatitis C, hepatitis D, mumps, cytomegalovirus, varicella zoster, Epstein-Barr virus, tickborne encephalitis virus and measles. Mole than 500 labolatu~iestake part in Lhr EQAS. BeLween 1988 and 1994 more than 73 000 samples were analysed. The results are shown in the following table:
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Page 26
Virus FIIV-l HIV-2 Hepatitis A Hepatitis B Hepatitis C Rubella
EQAS success rate in serodiagnosis Actual prohlems Close to 100% Close to 100% Close to 100% Close to 100% 295% (haemagglutination inhibition) 65%-88% (haemolysis in gel) Close to loo?.<(ELISA)
low positive samples in radioimmunoassays variations of iull lower rates in genotype sensitivity of IgM tests
Mumps Cytclmegalovirus Varicella zoster Epstein-Barr
>9O% (general) 58%)-80% (itnmunofluorescence)
Subjective reading of immunofluorescence Mumps-IgG specificity
In general, virus diagnostics in Gernlany in experienced laboratories achieve a high standard as far as test management In the laboratones and reliability of commercial tests are concerned. When severe problems become evident, participants are informed. Additionally, manufacturers of the tests and the state institute responsible for the registration of diagnostics (Paul Ehrlich Institute) are informed in order to resolve the difficulties. This interactive management, scientifically coordinated, has proved to he an effective way to secure and improve virus diagnostics. In the past years, several participants from European countries have joined the German EQAS. Laboratories from any country are invited to participate in the scheme. The protocols are also available in English. INSTAND and the Institute also organize a worldwide EQAS for clinical and experimental virology under the sponsorship of the World Health Organization in Geneva. This EQAS lias been established for the Easlrr-11 Mcdilarranean Region, Africa, soutll-east Asia, and south America. Activities have been started on behalf of the European Community the quality control programmes in Europe. to harn~onize It is planned to includc further serological methods in the programmes. the first EQAS in electron microscopy has been successfLlly organized for the direct detection of virus particles. New quality control programmes for the detection of viruses and virus constituents (i.e. gene technological techniques) are planned. New methods of sample preparation and the procedures for quality assessment have opened new horizons, in particular, the p o l y m ~ r a s ~ chain reaction (PCR) and the ligasc chain reaction (LCR). They will have an important impact on the future handling of internal quality control.
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Page 27 3.5 External quality assessment schemes Professor H. Reinauer
External quality assessment is a very important instrument for making an objective judgement about the quality of a laboratory's performance, especially for accreditation purposes. In 1991 a European Accreditation of Certification (EAC) was founded by 17 European organizations. Its activities are to draft guidelines according to the standards EN 4500143. In the same field three European scientific medical societies are involved: the European Confederstion of Laboratory Medicine (ECLM), the Forum of European Socictics for Clinical Chemistry (European task force of the F C C ) and the European Community Confederation of Clinical Chemistry (EC4). They work towards the harmonization of accrcditation schemes including CQA schemes. EQA schemes have an educational aspect (Table 3). Fundamental views are acceptable (Table 4). Among other items two main aspects have to be discussed and are implemented in an ongoing process: a) target value, and b) type and range of acceptability criteria. Harmonization tendencies resulted in the proposal of "General Recommendations for Organization of a . . Network of External Quality Assessment Schemes for all Disciplines" by External Quality Assurance in Laboratory Medicine (EQALM), a European organization founded in 1997 based on national scientific organizers.
-
Table 3. Educational aspects of EQA schemes Reports of EQA schemes should be compared with internal quality control Reports should be discussed with co-workerslstaff In case of poor performance there should be discussions with the analyst, consultation with the manufacturer, and change of the method/instrument Workshops on EQAs Conferences with the reference laboratories Conferences with the government and health care agencies Reports in symposiums and congresses
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Page 28 Table 4. Fundamental views of EQA schemes
Each EQA scheme can only be performed if appropriate guidelines are developed, and clear organizational regulations are established and transmitted to the participants IQC and EQA are parts of a total quality management system and are additive procedures EQA cannot substitute for IQA. Both are essential for the medical laboratory IQC is a necessary basis for quality control but not sufficient EQA is a blind control of analytical and in some ways laboratory performance; EQA informs about the comparability of values, the accuracy of laboratory analyses and the distribution of analytical reagents and instruments to the participants EQA is an adequate instrument for monitoring of the analytical tools on the market (vigilance); for helping those laboratories with poor analytical perfolmance; ar~dfbr basic requirements for remuneration 'The anonyrnlty of data must be assured
*
The whole EQA system must create confidentiality
3.6
Statistical and nonstatistical internal quality control measures
Dr W Appel
Internal quality control (IQC) is the set of procedures undertaken by the laboratory staff for continuous monitoring of operations and results in order to decide whether the results are reliable enough to bc rclcascd. IQC primarily monitors the batch-wise trueness of results on quality control materials and precision on replicate analysis of test materials. IQC may be regarded as a whole system. General IQC measures may be arranged in the following order depending on the capabilities and budget of the laboratory. 1. Duplicate tests. These demonstrate the quality of results, reagents, kits, analytical devices, measuring instruments and skills of the staff. Repetition of at least 5 to 10 times gives a sample set of results, which can be treated statistically (patient material); Check tests (delta check) performed by another person, at another laboratory site, with another instrument, reagent kit or method or during another working shift or day (patient material);
2.
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3.
Replicate tests, within day or between day (patient material, aqueous solutions, control materials); Control charts (control materials, calibrators); Patient data comparison (patient material); Intralaboratory comparison and interlaboratory comparison (patient materials, control materials, calibrators, aqueous solutions); Plausibility control !pa!ient material, clinical data); Scientific judgement (inspection, communication, dialog with staff andlor clinician). IQC systems cover the following items:
4. 5.
6.
7. 8.
quality of control materials types and frequency of possible errors number and types of control materials number of replicates of control probability of error detection probability of false rejection consequences of reject signals trouble shooting systems prevention of errors. 3.7 Quality assurance in bacteriology Dr K. .lanitschke
Extcrnal quality assessment schemes (EQAS) in bacteriology have been well established in Germany for more than 20 years. INSTAND organizes the EQAS together with a scientific society (German Society for Hygiene and Microbiology). Professor Schaal (Bonn) is the head of these schemes. 'The EQAS are organized according to the regulations of the German Chamber of Physicians. These guidelines were published in 1992. They consist of two parts, one for the gencral microbiology (common for all fields), and thc othcr for bactcr~ology (and in tile f u c u ~ c for virology, parasitology, and mycology). The participation in the EQAS for bacteriology is mandatory for some geographic areas in Germany and will be extended to more. There are three categories of EQAS in bacteriology: one for laboratories, which covers the whole field of diagnostic bacteriology, a second for private physicians or those in small t' hospital laboratories who perform bacteriological examinations only for their own p ~ients (urologists, gynaecologists, etc.), and a third for laboratories which perform tuberculosis diagnosis.
WHO-EM/LAB/294/E/L Page 30 The samples for the EQAS are first tested by reference laboratories for bacterial identification and also by target value laboratories for susceptibility. If the results are accepted then the probes are delivered. These are lyophilized pure cultures of bacteria (categories 1 and 2) and for tuberculosis slides with samples or sputum. The probes must be examined for bacteria identification (genus, species and serovar) and must be tested against antibiotics. In the EQAS for laboratory categories 1 and 2, the scores obtained for identification and susceptibility testing are summed up separately and used for calculating the percentage of corrcct rcsults of cach participant. Thcy successfully passed EQAS when they achieved tlre following results: Category 1 : identification of at least 70% of the maximum score, suseept~bil~ty of at least 85% of the maximum. identification of at least 67% of the maximum score, susceptibility of at least 85% of the maximum.
Category 2:
About 300 laboratories in category 1 and 900 laboratories in category 2 participate in the EQAS. The percentages of correct results of laboratories in category 1 increased between 1986 and 1996 in identification from 60.7% to 98.5% and in susceptibility from 93.494 to 95.3%. In category 3 (tuberculosis diagnosis), depending on the samples, between 97% and 73% of the laboratories successfully passed the EQAS, and the first tuberculosis EQAS for gene technological techniques has shown promising results. There are some handicaps in the performance of the bacteriological EQAS. These are the strict coupling of identification and susceptibility testing, the use of agar diffusion test only, and the use of nonclinical, pure bacterial cultures. These problems must be solved in the near future. The EQAS for bacteriology has been run until now only in Germany. INSTAND is interested in helping other countries to establish such schemes. Therefore, they welcome any proposals for cooperation, such as training courses, consultancies, or participation in the German EQAS. Further programmes, except in virology and parasitology, cover the serology of bacterial (tetanus, helicobacter, salmonella, borrelia) and fungal infections, as well as their direct identification. Evaluation of results and data handling U r W. Appel 3.8
Evaluation of results and data handling is considered as part of the post-analytical phase besides the biological validation of results and d~cumentationand is reflected in the items "generation of report" and "transfer of report to the client". In medical laboratories we have to
WHO-EM/LAB/294/E/L Page 3 1 differentiate between "laboratory result", "laboratory finding" and "medical finding". The last will not be discussed. For clarification some definitions may be introduced. Quality evaluation: systematic examination of the extent to which an entity is capable of fulfilling specified requirements (IS0 TC 176lSCllWG2 N66, 1996); a result of a measurement in the medical laboratory is regarded as an "entity". Result o f a measurement: value attributed to a measurand, obtained by measurement (V~III. 1993, 3.3) W ~ C Ithe I tern1 "rcsult of a mcasurcment " is uscd, it should bc madc clcar whether it refers to the uncorrected result, the corrected result or a single observation or an average of the valltes obtained by several observations. A complete statement of the result of a measurement includes information about the uncertainty of measurement and about the values of relevant influence quantities (Dybkaer, 1997). Laboratovy finding: objective of a laboratory test. It is described by the result of a measurement and includes the evaluation of the individual steps of the whole investigation procedure like sampling, analytical preparation of samples, analysis, analytical judgement and medical judgement of the result (DIN 58937-6, 1994). Report o f measzrrement: document that presents the name of the measurand and result of measurement, together with an expression of the uncertainty of measurement, the values of the relevant influence quantities, information necessary for the identification of the sample, tlie leyueste~, the organization of the laboratory issuing the report, and sometimes interpretative remarks (ISOIIEC Guide 2, 1991). Kesuult must be fully identifiable. Results covering more than one side must be numbered to allow for full identification. The results must first be released in terms of analytical quality (quality control in order). The medical appraisal of the analytical results leads to the medical resultldiagnosis. Persons responsible for analytical and medical release of results must he named (Schellenberg, 1997, details in DIN-EN 45001, Section 5.4.3). The content of results must include all important data (in so far as no exclusion clause exists) such as the name of the laboratory and person in charge; address, telephone and fax number(s) of the laboratory; name and address of the client; surname, first name, date of birth and sex of the patient; place of sampling, time of sampling, sampling volume (where relevant); date of dispatch from the client, time of receipt in the laboratory; identification of type of sample; pretreatment of sample (if relevant); concentration unitslactivity concentration, in full, if nonslal~clalcli~ctl abb~cviatiuns alc used; analytical ~esultwith cxplanatiuns (fuut~lutcs) alld interpretation; time of release of result; and name of person(s) responsible for the result (Schellenberg, 1997).
The report may be issued as hard copy or by electronic data transfer (draft ISOIIEC Guide 25 1996). In case of data processing data entry to computer must be validated, for instance by computer entry performed by two operators working independently. Data must not be amended after submission. Receipt of unsatisfactory samples must be recorded. Data c presented. protection should be guaranteed. Additional requirements h a ~ heen
WHO-EMILABI294IEIL Page 32 3.9 Quality manual Dr E WoNheim
The quality manual is at the top of the so-called documentation pyramid. It contains the documentation of the quality system of the laboratory comprising the policy and objectives, the resources and the procedures employed within the qrlality system Tt is the primary reference for all members of the institution and is well suited to inform new employees. Additionally it is used to demonstrate the quality of the laboratory service to persons outside the laboratoly. Different examples of quality manuals have been published by professional groups. Bascd on a very good u~udelqualily manual produced by the Nederlandse Vereniging voor Klinische Chemie; INSTAND published in 1995 a quality manual tailored to the specific German environment (for example, legal quality control regulations). It contains an ~nterpretation of the EN 45001 standard (general criteria for the operation of testing laboratories) for the medical laboratory. The INSTAND quality manual has been accepted at a national level and has become part of the German accreditation scheme. In the meantime an IS0 standard concerning quality management in medical laboratories is emerging. There is nearly total agreement between the interpretations given in the quality handbook of INSTAND and the I S 0 standard in preparation. The following structure for a quality handbook is recommended: introduction quality policy statements dcscriptiori o r the laboratory (legal identity, resources, main duties personnel and organization) facilities, safety, protection of the environment equcpment and supplies examination procedures preanalytic phase (request protocols, sample collection and handling) analytical control verification of results report documentation deviations, cooperation with clinics annexes.
It should be emphasized that the quality manual is unique to each laboratory as laburalurirs always differ with respect to their organization, resources and procedures.
W110-CM/LAB/294/E/L Page 33 3.10 Quality assurance in parasitology
D r K. Janitschke One of the preconditions for EQAS is standardized techniques as well as control or calibration sera. Some scientific societies, such as the former Federal Health Ofice, Germany, and the Gelman Institute for Standards, have established guidelines for the diagnosis of parasit~cinfections. Very essential in these projects is that one guideline only be worked out for each parasitosis. Nonmandatory EQAS in parasitology started in Germany in 1985, organized by INSTAND in cooperation with the German Parasitology Society. Two reference and one target value Iaboratorics arc nominatcd to manage the EQAS. There are three progranunes ~ u r ~ r ~ i ~ l g twice per year with two samples as follows. Microscopic en-aminatlon ,for parasites. Stool concentrates, blood sl~dcsor other preparations must be examined for parasites, and parasites should be identified to genus or species level. Immunodiagnosis I (toxop1asn~osi.s).Sera from patients must be examined qualitat~vely or quantitatively by appropriate techniques for antibodies, and participants are requested to interpret the tesults and indicate whcther it is concerning old or fresh infections. 1mmunndirrgnoci.v I1 (anio~hiosis. malrrvin, .schirtosomia.sis, echinococcosis). Sera must be tested accordingly and the results should be evaluated regarding existing or nonexisting infections.
The results of microscopic EQAS between 1988 and 1992 show that there is a strong need to improve the quality of cxaminations. This is especially significant for the diagnosis of malaria. Concerning the programme Inlnlunodiagnosis I, one-quarter to one-third of the participants did not fulfil the requirement:, of the study. One reason is that quantitative results are mostly requested, and these need tnore precise performance than qualitative tests. It is believed that onc can overcome problems if one uses more automated techniques. In the programme Immunodingnosi.~II, most of the participants apply hacmagglutination tests. In this case there is a problem of a wide range of reported titres, but in most recent studies there has been an improvcmcnt of reading the haemagglutinations. More ELlSAs are used now and some laboratories also perform inimunofluorescence tests. The interpretations of the results in both immunodiagnostic programmes are generally sufficient. Much work must be donc in the near future to improve the EQAS results in parasitology. This is especially important fix cal-e of plpglant W ~ I I I C I Iand nconatcs concerning toxoplasmosis. This showed to be successf2ul in specialized laboratorics using polymerase chain reaction (PCR) for toxoplasma. The EQAS are necessary as a precondition for the accreditatton of laboratones, whrch IS planned.
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Page 34 INSTAND is interested in supporting, on request, centralized laboratories to establish or improve EQAS in different countries.
3.11 Self production of control materials Ilr M Appel "Control material" or "calibrator" means any substance, material or article intended by its manufacturer to establish and/or verify performance characteristics of an in vitro diagnostic medical device in conjunction with the use of that device (Proposal of the Commission of the European Community for a European Parliament and Council Directive on in vitro diagnostic medical devices, April 1995). In 1981 WHO published a document on practical guidelines for the preparation of quality control sera for use in clinical chemistry [Kenny and Eaton], followed by another short document on preparation of stabilized liquid quality control serum to be used in clinical chemistry in 1986 [Browning, Hill and Olazabel]. These papers may be considered as fundamental, but they are restricted to clinical chemistry and do not cover enzyme, urine or immunoprotein analysis or haematological, coagulation, ELISA or molecular biological diagnostic routine measurement procedures. The documents describe in details essential topics: collection of blood; choice of frozen. lyophilized or fluid material; adjustment of "low, medium and high" analyte preparations; preservatives and wetting agents; filtration and dispensing; sterilization, deep freezing, lyophilization and addition of chemicals (ethylene glycol, thiomcrsolate, borate, fluoride, azide or antibiotics); labelling; storage; reconstitution; and the main requirements for attributes of good quality. The concentrations of analytes in human and animal sera are given in tables; the problems of target values are touched only briefly. Obviously the problem of self-preparation of control material still exists, not only in Reg~on. Regional, national or even individual ways of countries of the Eastern Med~terranean solving the problems may be necessary, combined with distinct clarification of requirements concerning the fields of application: a) individual laboratories, using control materials for evaluation of measurement procedures or instruments and/or for internal quality control; b) peer groups of 5-20 laboratories producing control materials for their own use and in addition for (unofficial) locally organized surveys; c) universities, governments, ministries, natinnal centres or companies (commercially) producing control materials for distribution and/or organization or performance of (national) external quality assurance schemes (in 1993 Loria, Pizone and Perez-Dominuez published their experiences in an EQA trial conductcd by thc Mexican Ministry of Health with the use of reagents and control materials prepared by the same Ministry). The participating laboratories were classified into three groups: a, b and c accllrdirlg cu Il~cilrcsulls. Fur group 'a' laboratories the self production of control serum, plasma, blood, urine, smears, strains of bacteria and immunoproteins is feasible without great problem; these materials may be used mainly for internal quality control purposes, even statistically based. This is performed already (in varying degrees) in countries of the EMR Region. For group 'b' laboratories some difficulties arise concerning the origin of biological material, amounts necessary and in countries with hot and/or humid climates or with big
WHO-EM/LAB/294/E/L Page 35 distances between laboratories, the stability of analytes. Problems of stability should not be overestimated: electrolytes and many substrates are stable for years, and the main point of quality control measures-the reliability of results of the system due to instruments and staff-will be ensured. Even national EQA surveys in countries of the EMR Region have been performed with success. For group 'c' laboratories a simple way of troubleshooting does not seem realistic. In addition to the requirements mentioned the problem of target values. organizational and legal issues will occur. Cooperation with local manufacturers, joint ventures with international operating companies and realistic and detail consultancies with scientific national or international societies and nongovernmental organizations is regarded as a basic requirement. 3.12 Self production of reagents
Dr W Appel ~ty reagents w ~ t h good qual~ty and acceptable prlce The lack of continuous a v a ~ l a b ~ l of seems to be one of the limiting factors facing improvement of the quality of laboratory test results in many countries. In June 1993, WHOIEMRO organized an Intercountry Workshop on Laboratory Diagnostic Reagent Production in Tunis, Tunisia. The recommendations of the participants are still valid: "Countries of the Region are encouraged to commence and strengthen diagnostic reagent production to achieve regional or sub-regional self-reliance in basic laboratory reagents ... Countries of the Region are urged to set priorities for the requirements of diagnostic laboratory reagents ... Governments are requested to encourage national andlor regional production of diagnostic reagents ... It is advisable to develop local production in phases, starting with relatively si~riplearid the rriost co~rirnunreagents ... Fur imported reagents a group of countries in the Region agree on a common tender, including common quality standard.^ ,.. Firms manufacturing diagnostic reagents in industrialized countries should consider joint ventures in local production ... There should be independent control mechanisms for the evaluation of locally-produced and imported diagnostic reagents against defined quality standards ... " In September of the same year during the Intercountry Conference on Quality Assurance in Clinical Chemistry organized by Dr M. El-Nageh, Regional Adviser, Quality of Care and Health Care Technology, WHO-EMRO, in Amman, Jordan, Dr Gruber (Germany) gave a lecture on production and control of reagents, with special reference to conditions in countries of the Eastern Mediterranean Region. His presentation focused on the cost for investments, personnel, marketing, distribution, safety, taxes, and the necessity to install total quality management according to the I S 0 9000 series. Dr Wood, a consultant who participated in the aforementioned workshop, demonstrated a practical way of decision asking: 1) are the chemicals wanted by the laboratory available on the market for purchase? If yes, is buying profitable? and 2) is it possible to synthesize the substance in one's own laboratory? "Possible" here means the availability of adequate rooms, equipment, well trained and competent personnel (chemist, biochemist), the non-existence of patents for the substance or procedures (synthesis or isolation from biological source) and, last but not least, the presentation of an official licence for production. If the second question is
WHO-EM/LAB/294/E/L Page 36 answered by "no", other possibilities may be investigated: "custom synthesis" by a local industrial producer; obtaining the substance from a colleague on private basis; or buying "parts" of the substance system (combination of substances, reagent kit) and final combination in a simple way. 'rhese general considerations are applicable to all diagnostic reagents not only in clinical chemistry, but also in hacmatology, haemostaseology, bacteriology, imrnunoprotein chemistry, urinalysis, drug analysis and even F.T.ISA tests in virology and parasitology. Descriptions for preparation of buffers, aqueous solutions of rcagcnts, calibrators, conttols, dipsticks, staining solutions, culture media and for rapid diagnostic tests based on latex or gelatine particles are available. The German Standardization Institute (DIN) has developed standards in haemostaseology by Beeser (Germany), for example DIN 58903, November 1996, on the "Preparation of deficient plasma", and WHOIEMRO has published Publication series No. 5 Blood grouping reagents-preparation and application methods; and series 11 WHOIEMRO publication Production ofhasic diagnostic laboratory reagents. Countries in the Region have practical experiences with self-preparation of reagents even for more sophisticated systems in haemostaseology (Quick test reagent), urinalysis (dip sticks) or in clinical chemistry (buffers, calibrators, auxiliary solutions).
3.13 Reference methods Ilr H. Reinalrer Rei'erence methods or, in a more distinct wording, reference measurement procedures (RMP) are a powerful tool to establish reference measurem2nt procedure values. These values may be linked to materials designated for reference materials, either to be used as control materials or calibrators. RMP also are needed as link in the traceability chain connecting field methods, assigned values and field calibr.dtors. RMP are "thoroughly investigated and described measurement procedures having analytical performance characteristics, especially bias and precision of measurements, permitting its use for assessing the accuracy of other procedures and characteristics" [CENITC 140/W(;4; prEN 12286 (1097)l. Besides activities in CENITC 140, lSO1TC 212 has established a working group, WG2 "Referencc Systems", dealing with "content 2nd description of reference measurement procedures utilizing nominal and ordinal scales"; "contents and description of reference materials"; and "requirements for laboratories performing reference procedures". Rcfcrence measurements are essential in standardization. They are indispensable to governments drawing up rules, to standardizing bodies, to the functioning of the European Quality System, to good laboratory practice and to individual laboratories producing accredited reports of results of performing daily routine measurements, whether in govelnmental departments, industry, health services, or private laboratories.
WHO-EMILABI294IEIL Page 37 The principles should also be applicable to other fields of metrology such as laboratory investigation in veterinary medicine. agricultural sciences, and environmental sciences when performing measurements on biological samples. The different types of analytical samples may derive from primary sample, calibrator material, or contrni material including matrix material (without analyte) The essential requirements in the approval of reference methods (proposal) are: analytical principle well known for its specificity and accuracy definition of performance criteria for the procedure control detailed description of the procedure available carefully documented evaluation of accuracy and interferences by means of comparison with definitive method (if available); certified reference materials; interference studies carefully designed transferability study including at least three laboratories goals for acceptability as reference method (depending on medical needs). These requirements may be correlated to our suggestions on maximal allowable CVs (%) for precision and bias (%) for trueness. Chloride: 111.2; creatinine 213; thyroxine 314; alolosterone, cortisol, estradiol, progesterone and testosterone: 314. The main advantages of RMPs are: there is only one target value for an analyte specified the comparability of the results of an analysis will be enhanccd uniform reference ranges are possible methods with maximal reliability are followed obsolete methods may be eliminaled basics for epidemiological studies are provided reduction of costs and better handling of the patient is possible. As example RMPs, some values for theophylline are given. FPIA: 36.6 mmolll; HPLC: 36.4 mmolll; GC-IDIMS: 36.8 mmolll; and for lower concentrations: 7.817.417.99 mmolll rcspectively: all values are established at INSTAND and validated by EQA surveys.
3.14 Quality assurance in pre-analytical phase Dr F Wollheim There exist many potcntinl sourccs of gross crror during thc prc-analytical phase. Quality management of clinical laboratory services has therefore to include this phase. The main items of concern are: sample collection procedures, labelling procedures outsidelwithin the laboratory, test requisition, transport and storage of samples and, reception of samplcs. Most of the information necessary is compiled in a sample collection procedure manual that is also used in the clinics thenlselves. The contents are:
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instnlction to and preparation of the patient in view of the sample to be collected containers, nature and amount of sample, additives need for special timing or handling proper patient identification and sample labelling nced for clinical data considering the relevant influence quantities and effects of disease identity of the person collecting the sample disposal of collecting materials. Note: As multiple blood drawing leads to iatrogenic anacmia, samplc volume should 110 be oversized. With modern instruments the following volumes of blood sample are sufficien for b95 % of requests: clinical chemistry, using serum: 4-5 ml; clinical chemistry, usine plasma: 3-4 ml; haen~atology:2-3 ml; coagulation resting: 2-3 ml; immunoassays: I mli32 assays; blood gas analysis: 1 ml; blood sedimentation rate: 2-3 ml. For identification of samples the use of bar codes is strongly recommended. Tht containers should be labelled before bcing filled. Stability of the samples has to be described with respect to additives and environmenta conditions. The maximally tolerable storage time can be derived from stability data. Figure: shol~ld he given in the SnPs for the individ~~al measi~rahla quantities. The standard requisition should contain the following: identification of the patient: name, surname, date of birth, sex name and address of the physician or other perscn authorized to order tests or use medical information kind of sample (e.g. heparinized arterial blood) tests requested dateitime of sample collection clinical notes necessary for sample hanc!ling or interpretation of results additional notes as required (e.g., informed consent of the patient in case of I-II\ testing). Reception of samples: samples have to he recorded in the laboratory on reception; alec the time of reception is documcntcd. There exist written rejection critcria. In case of rejectior or sample abnormalities the physician ordering the test is notified within a short time. 3.15 Quality assurance in the post-analytical phase Dr f? Wolllleim
The information generated by the laboratory in the report is the "product" of thr laboratory in which the clinical physicians are primarily interested. Turn-around time ha5 become very important for the assessment of the cluality of the service. Quality managemen of the clinical laboratory service should considcr:
WHO-EM/LAB/294/E/L Page 39 content of the report communication procedures traceability definition of turn-around times confidentiality. The report should be legible. understandable and informative. It contains: patient full name, date of birth, sex and medical record number datehime of sampling dateftime of reporting source and type of the sample test results units of measurenlent (if applicable) reference values interpretation, if appropriate other comments (e.g. possible interference). Critical results have to be communicated immediately to the physician responsible. They have to be defined for each test including the qualitative tests. The regular turn-around time has to be defined for each test. In case of unusual delay, the physician should he informed if essential results will not transmitted timely. The transport of printed reports or the translnission of reports by fax or by the hospital information system has to be organized in a manner to assure confidentiality. Copies or files of the results have to be retained for a defined time. Not only the results itself but also the person responsible should be traceable.
3.16 Quality assurance of measuring instruments and devices Dr W AppeI
The forthcoming Directive of the Commission of the European Community on in vitro Uiagnost~cMed~calOev~cessays: "In vitro diagnostic medical device (IVD) means any medical device which is a reagent, reagent product, calibrator, control, kit, instrument, equipment or system used alone or in combination, intended by the manufacturer to be used in vitro for the examinations of samples derived from the human body, including blood and tissue donations". The European standard EN 1685, February 1997, describes "Requirements for marking of in vitro diagnostic instruments". The German standard DIN 58937, part 7, July 1994, provides a text on "General laboratory medicine; listing features of in-vitro diagnostic systems". These examples demonstrate the implementation of instruments and devices into standards and, for the directive, into legal demands. Naturally the quality of instruments and devices is p~ovedand guala~iteedby the ~~rar~ufaclurer. But the gap between manufacturer, importer, trader and user varies in a large degree and the responsibility of the producer usually ends when the instrument or device is brought into the market. The fulfilment of the requirements in the medlcal laboratory must be checked after putting into service, during the life of the device and in case of reselling. The tools for testing the quality are 1) rechecking and evaluation of the device, especially in case of high priced partially or fully mechanized
WHO-EMlLAB1294EL Page 40 instruments, according to prescriptions provided by the manufacturer in total or partially, and 2) controlling the results of measurement procedures with synthetic or biological material, even samples of human origin. processed by the instrument and devices in use hy means of statistically evaluated quality assessment measures. This may be done by measures of internal quality control or participation in external quality assessment surveys at national, regional or intcmationnl Icvcls. Thc mcasurcs may be restricted to thc spccial pcrformancc of tcsts t p i c a l for the instrument under consideration (including devices). The frequency of measures of maintenance varies according to use. Mechanized analytical systems, photometers, cell counters, blood gas analysers, all other analytical measuring instruments and water bathes should be checked at the beginning of a working shift, at least once per working day; microscopes, centrifuges, incubators at the beginning of daily work; refrigerators, freezers, pH meters once a week; (the temperatures of refrigerators and freezers in blood transfusion laboratory units havc to be controlled continuously); additional instruments like spectrophotometers, flame emission or atomic absorption photometers, analytical balances, water purifiers, and air conditioning systems should be checked routinely according to manufacturer's recommendation. All activities must be recorded in a log book containing date and time of faillre, cause (if possible), measures nf re-establishment or repair and the name of the person who performed the troubleshooting, especially in case of involvement of a third party. For measuring instrument calibration, limit of detection, analytical range, linearity, drifts, prccision and accuracy of control measurcmcnts havc to bc rc-cvaluatcd. Participation in EQA surveys on instruments, if possible, is recommended. General or special noninstrumental devices, mainly volumetric measuring devices like pipettes, burettes, volumetric flasks and measuring cylinders, have to be maintained and checked before the first use, if possible, by the laboratory staff themselves. This is highly recommended for volumetric pipettes used for calibrations, manual or motor driven, and mechanical dispensers and dilutors. Photometric andlor gravimetric methods not radiochemical methods are suggested. Estimation of precision and accuracy have to be based on aqueous solutions and serum or whole blood, respectively. Optical cuvettes should be checked regularly due to protein layerinduced turbidity; this is necessary for fully automated systems, where single damage andlor drifts can be detected. Temperature measuring devices must be checked before first use. 3.1 7 Traceability Dr W Appel
Traceability is defined according to the forthcoming directive of the European Community on in vitro diagnostic systems. The following test refers to the preliminary result of a task force on traceability of Working Group 4 of the European Comm~tteeon Standardization (CEN), technical committee (TC) 140. The main idea is that field (routine) method calibrators should have assigned values, which are traceable to the highest order reference materials and procedures. Traceability assures that the mean of results of measurements with the field procedure on a given series of samples is indistinguishable from the mean of results obtained if the reference procedure itself had been used to measure the same series of samples.
WHO-EMlLABI294ElL
Page 4 1 A fundamental assumption is "the numerical ratio between results by the field procedure
and by the reference procedure (the 'intermethod ratio') is represented by the calibrator, and that this ratio is identical and constant . .. for all actual samples which the field procedure is applied." This assumption is correct only when the reference material is commutable. Commutability of a reference material is ".. . the ability of a reference material to show intermethod changes comparable to those observed in human serum for the identical quantities [of analyte]". Thesis: Without commutable reference materials, specified panels of patient samples, with analyte values (quantities) measured with a reference method, may be employed as o assign values to field calibrators. "working caliblato~s"for field lrletllodb L Key process elements in patient panels calibration scheme (one manufacturer's expenence): Select patient specimens with analyte quantities spanning full reportable range for field method; Measure patient specimens, employing a statistically designed protocol over 4 to 6 days, with both reference method and field method. Findings: The patient panels approach to field method calibration for assigning valucs to
field calibrators is a reproducible process, with measurable uncertainty. value assignment uncertainty and reproducibility include: Key factors in conlrollir~g random sample-related errors associated with method specificity method precision numbers of samples employed adequate coverage of reportable range Conclusion: When field method calibrators are not commutable, traceability to higher order standards is derived from method-specific "system" assigned vall~es;quantities (of substance) measured by the reference method in field method calibrators have no practical application to the field method. 3.18 Interference and interfering factors Dr F V Appel
The reliability of the results of clinical chemical procedures has improved to a high degree in the past decade. The reason may be seen not only in the improvement of instruments and reagents, but also in the introduction of internal quality control and external quality assessment schemes. In consequence more and more analytical results are observed which may not reflect the true situation of the healthy or sick person. This is not a question of
WHO-EM/LAB/294/E/L Page 42 imprecision, but inaccuracy, and the scale of the deviations may result in implausibility. The reasons are multifunctional and unknown in many cases. The principal causes of implausible results, even in emergency tests, are the effects of drugs. "Interfering factors" or "influence elements" may create these effects. The scientific evaluation of this topic has led to more than 30 000 publications in the past 30 years. After a large amount of papers the first comprehensive review was introduced by Young in 1972. Thc f o m ~ a at l L h a L Lirr~t. was a simple hard copy of an EDP collection of data, which was rather impracticable. For the time being some of the most important books are cited. Siest and Galteau, 1988: Drug effect. on laboratory test results. analytical interferences andpharnlucological effects. Kallner and Tryding, 1989: IFCC guidelines to the evaluatiot~o f drug eflects in clinical chemistry DIN, German Institute for Standardization 1993: D M 58936, part 8, Qualiy assurance in laboratoly medicine; preanalysis; biological influencefactors; interference.factors. Tryding, Tufvesson and Sonntag, 1996: Drug effects in clinical chemistry: clinically important analytical interferences and biological effects of drugs on biochemical and huematological laboratory invesligations (the accompanying reference volume covers 6495 [!I references). The latest activities are the preparation of a Technicui manual on drug interference by El-Nageh, WHO-EMRO in 1997 and the publication of the results of two symposiums on Drug efSccts in clinical chemistry methods by Breuer, Sonntag and Scholcr in 1997. Biological efecrs (biological influence factors) are seen at the level of and act on the individlrum. They result in changes due to illness(es) with diagnostic relevance or to other diagnostic irrelevant biological phenomenon. The result of an analytical test reflects the s~tuation in vivo restricted by methodological inaccuracy Interfering factors act on the analytical measurement procedure (test). They lead to variations of the concentration(s) or activity(ies) of the analyte(s) in the matrix of the biological sample or in the composition of the analytical sample. Often they are identical with thc analyte to be estimated and by this fact disturb the chemical, physicochemical nr biological reaction. The resulting signal or analytical result(s) does(do) not reflect the real situation in the organism of the individuum. Drugs may act as biological influence factors or nnnlyticnl interference factors likewise.
Meanwhilc lists of drugs relevant to regional, individual or physician's use exist containing the figures on direction and/or magnitude of effects depending on the concentration of the drugs applied or measured. Likewise lists reflecting the influence of haemolysis, hyperlipaemia, hyperhilirubinaemia and turbidity on the results of measurcments procedures are published for interpretations of implausible laboratory results or findings. In addition the effects of anticoagulants specified are studied and published. Efforts in EDP facilities to provide the laboratory, the clinician or even the general practitioner with relevant data concerning drug interferences have not been fortha-oming. For pharmacological (biological) cffects one may ask the producerlimporter of the drug or of the in vitro diagnostic medical device (diagnostic test reagent or kit).
WHO-EMILABI294IEIL Page 43 3.19 Quality assurance in dry chemistry Dr W? Appel
I . Overview The term "dry chemistry" has tn he defined to elucidate its very distinct position insidc the family of diagnostic systems of clinical chemistry. Even the term "carrier bound reagents" has to be used in a rather strict sense. The most fitting term seems to be "solid phase chemistry tests", yet the term is not in use in Gcrmany due to the need fur elimination of single test kits with antibodies bound to the wall of a vessel or cuvette. In Europe solid phase chemistry tests with or without instruments are included in the Directive of the European Cor~rrr~urrity "Proposal for a European Parliament and Council Directive on in vitro diagnostic medical devices (IVDs)" published in the official journal of the European Community in April 1995. Some of the most characteristic and specific features of these devices are: suitability to react to urgent medical demands; immediate response to the patient's needs; easy handling; practicability for less trained personnel and, rather import for laboratories in developed countries, comfort. The directive covers blood glucose meters using test strips or bioelectrodes. These devices are used by patients, by medical doctors in their offices and by hospitals to a very high degree and are marketed by companies and distributors to lay people. The latest and most important developments for primary health care laboratories of morc or less industrialized countries and possibly all countries in the Region may be seen in devices, that can be described as dry chemistry tests "without measuring instruments". Solid phase tests are extensively used worldwide. In 1993 more than 24000 EktachemNitros-systems were installed; more than 1 100 000 slides were sold worldwide in into the bench level 1993 fur veterinary medicine even though an expert system 1s ~ntegrated systems Ektachem DT, DTE and DTSC. Similar figures are known for Reflotron systems. In the past decade more than 60 000 instruments have been sold or placed worldwide. The distribution is markedly differentiated: 25 000 in Europe, USA, 20 000 in USA, hut l l I0 in Indonesia, 700 in Mexico, 650 in Saudi Arabia, 550 in Korea and 350 in Egypt (these figures are for 1994, actual andlor complete data are not given by the manufacturer). The figures for Blood glucose meters are astonishingly high. In the past decade more than 1 500 000 devices have been sold worldwide by Boehringer Mannheim (Reflomat, Reflolux, Diatek, Accutrend) and about 360 000 in the USA in 1994~
In principle there exists no diffeevence in quality assurance between diagnostic tests quality control and based on wet ohemistry and dry chcmistry. This is true likewise fur ir~ternal external quality assurance. In Germany infernal qualiry control of dry chemistry systems is mandatory even for glucose meters used by anyone performing blood glucose determinations except patient sclf testing. For the general doctor's office less stringent demands are required.
Meanwhile external quality assurance in dry chemistry is realized worldwide. Surveys are performed in the USA (CAP), France (Vassault). northern European countries
WHO-EM/LAB/294/E/L Page 45
4. Urinalysis with dipsticks INSTAND has conducted more than 54 surveys in external quality assurance of urine dip sticks with and without reflectance photometers systems since 1980. 5. Dry chemical systems without mea.~uring device
CENITC 140/WG 8 will cover quality assurance with these devices for physician and patient (self) testing. Publications about experiences in quality assurance with these devices reportedly do not exist world wide at the time being. 3.20 Quality assurance in blood glucose monitoring Dr W Appel
Blood glucose measuring devices are devices taking instrumental readings. In the future, more attention should be focused on devices with normal estimation, especially with nominal scale characteristics: "yes or no". This is discussed for dipsticks, test strips, single test dry chemical devices and EI.TSA-hased single devices The intended use of both categories is unclear: home environment, self testing, bed-side testing, medical laboratory, hospitals, emergency units, public health care, police/army stations, insurance, supermarkets, etc. The test performance of glucose measuring devices of various producers/distributors were demonstrated, and results of internal quality control measures and external quality assurance surveys were shown and discussed. INSTAND is the only EQA organizer offering and performing EQA surveys. The one of national, European and international standardization organizations and their input in mandatory and health care is discussed intensively. Details are offered based on INSTAND'S broad and long experience.
WHO-EM/LAB/294/E/L Page 46
4.
PLAN OF ACTION
Thc participants formulated and endorsed the following plan of action and comrnittcd themselves to implementing it and following to up at the national level and regularly report, every six months, on the outcome to EMRO. Activity 1. Implementation of those items, which are not as yet implemented, of the plan of action prepared and endorsed at the Intercountry Workshop on Quality Assurance in Health Laboratories held in Nicosia, Cyprus, during the period 29 June to 3 July 1992 (Annex 7) Speed up implementation of items of the plan nf action formulated by the directors of health laboratory services in their meeting held in Damascus, Syrian Arab Republic, from 12 to 15 May 1996; with special cmphasis on itcms 4, 5, 8, 9, 10, 11, 12, and 14 (Anncx 6) Speed up implementation of quality assurance programmes in microbiology. Implementation in this area is lagging. 5. Establishment of a Regional intercountry collaboration with regard to establishing and upgrading national quality assurance programmes in laboratory medicine. Countries will seek advice and assistance from other countries of the Region having the expertise and experience. The mechanism of this collaboration was discussed during the workshop (Annex 4)
Target date Mid 1998
By end 1997
Starting 1997
Starting 1997, ongoing
6. Establish national andlor intercountry regulatory authority laboratories for evaluation licensing of laboratory reagents and other laboratory in vitro diagnostic mcdical dcviccs 7. Legislation should be considered as a valuable tool to introduce and enhance quality in medical laboratories. Legislation should focus on measures of internal quality control and shall support an ongoing process of improvement.
As soon as possible
As soon as possible
WHO EM/LAB/294/E/L Page 47 Annex 1
AGENDA I. Registration 2. Opening session 3. Introduction of speakers and participants 4. Mechanics of the workshop 5. Quality management in medical laboratories 6. Quality manual 7. Country reports 8. Standard operating procedures (SOPS) 9. Quality assurance in virology 10. External quality assessment schemes 11. Statistical and non-statistical internal quality control measures 12. Evaluation of results and data handling 13. Quality assurance in bacteriology 14. Interaction of laboratory staff with physicians 15. Economic aspects of quality assurance and cost-effectiveness 16. Quality assurance in parasitology 17. Self-production of control materials 18. Self-production of reagents 19. Reference methods 20. Quality assurance of measuring instruments and devices 2 1. Quality assurance in pre-analytical phase 22. Quality assurance in post-analytical phase 23. Traceability 24. Interference and interfering factors 25. Quality assurance in dry chemistry 26. Quality assurance in blood glucose monitoring 27. General discussions of problems encountered in establishing quality systems and quality assurance programmes in countries of the Region 28. Working groups: revision of plan of action 29. Presentation and discussion of group reports and revised regional plan of action 30. Finalization of the regional plan of action 3 1. Concluding remarks and closing session
WHO-EMILABI294IEIL
Page 48
Annex 2 PROGRAMME
Saturdc~y,10 May 1997 09:OO - 09.30 Opening Session Opening address by H.E. the Minister of Health Message from Dr Ilussein A . Cezaiiy, WHO Regional DiictiLur fur the Eastern Mediterranean lntroductlon of speakers and participants Mechanics of the workshop Quality management in medical laboratories, Dr F: Wollheim Quality manual, Dr E Wollheim Country reports
IU.UU - 10.30
10.30 - 11.15 11.15 - 12.00 12.00 - 12.45 14.45 .16.45
Sunday, 11 May 1997 08.00 - 08.45 09.30 - 10.15 10.15 - 30 10.30- 11.15
Standard operating procedures, Dr F: Wollheim lypes of control measures, U r K. Janitschke External quality assessment schemes, Dr H. Reinauer Statistical and non-statistical internal quality control measures, Dr K Janitschke Evaluation of results and data handling, Dr W Appel Quality assurance in bacteriology, Dr K. Janitschke Interaction of labo~atory staff wit11physicians, Dr H. Reinauer Economic aspects of quality assurance, and cost-effectiveness, Dr W APP~~ Quality assurance in parasitology and virology, Dr K. Janitschke
11.15 - 12.00 12.00 - 12.45 14.30 - 15.15 15.15 - 16.00
16.00 - 16.45
WHO-EM/LAB/294/E/L Page 49
Monday, 12 May 1997 08.00 - 08.45 08.45 - 09.30 09.30 - 10.15 10.30 11.15 -
Self production of control materials, Dr W Appel Self production of reagents, Dr K Appel Reference methods, Dr H. Reinauer Quality assurance and maintenance o f measuring instruments and dcviccs, Dr K Appel Quality assurance in the pre-analytical phase, Dr I? Wollheim Quality assurance in post-aniilytical phase, Dr R Wollheim Working groups: case study
11.15 - 12.00 12.00 - 12.45 14.30 - 16.45
Tuesday, 13 May 1997 08.00 - 08.45 08.45 - 09.30 09.30 - 10.15 10.30 - 12.45 Interference and interfering factors, Dr W Appel Quality assurance in dry chemistry, Dr W Appel Total quality management in laboratory medicine, Dr M. El-Nageh Grrir~al discussiu~~s of prublcrr~s cncuuntered in establishing quality systems and quality assurance programmes in countries of the Region Working groups: revision of plan of action
14.30 - 16.45
Wednesduy, 14 May 1997 08.00 - 10.15 Presentation and discussion of group reports and revised Regional plan of action Finalization of the regional plan of action Concluding remarks and closing session
10.30 - 12.00 12.00 - 12.45
WHO-EM/LAB/294/E/L Page 50 Annex 3 LIST OF PARTICIPANTS
AFGHANISTAN nr Sayed Alef Shah Ghazanfar Health Laboratory Services WHO Main Office Jalnlabad
BAHRAIN
Mr Rashid A1 Suwaidi Technical Director of Laboratory Salmaniya Medical Centre Ministry of Health P.O. Box 12 Manama Tel. +973 279514 Fax. +973 279649
ECYP'T
Ms Tabarak M.E. Nasr Head, Biochemistry Department Central Public Health Laboratories Ministry of Health and Population 19 El Sheikh Rihan St. Cairo Tel. t 2 0 2 355 0096 Fax. +20 2 354 35 17
ISLAMIC REPUBLIC OF IRAN Dr Elaheh Keihani Pathologist Of f~ce of Affairs and Instruments of Medical Laboratories
Ministry of Health and Medical Education Teheran Tel. -t-982 1 640 0080 / 640 9 106
WHO-EM/LAB/294/E/L Page 5 1 Dr Mohsen Soroushnia Laboratory Department-Quality Control Centre Isfahan University of Medical Sciences Feiz St, Mola Hadi I-Iospital Isfahan Tel. +98 21 619074 / 61 1254
MOROCCO
Professor Rajae El Aouad Health Laboratory Services 'lene National Institute of Hyb' Ministry of I'ublic Health P.O. Box 769 27, Ave Ibn Batouta - Agdal Rabat Tel. 07 771930 1 0 7 772162 - or - 07 681655 (direct line)
OMAN Dr Suleiman Mohammed Al Busaidy Director, Department of Laboratories and Chief Virologist Directorate-General of Health Affairs Ministry of Health P.O. Box 393 Muscat 113 Tel. 705740
PAKISTAN Dr S. Ali Fouad Naqvi Officer in Charge Quality Control Laboratory National Institute of Health Islamabad Te1.240503
SUDAN Mr Hayder Mohamod Abdel Rahim Head of Laboratory Department of Chem~cal Pathology National IIealth Laboratory P.O. Box 287 Khartoum
WHO-EM/LAB/294/E/L
Page 52 SYRIAN ARAB REPUBLIC Dr Fouad Harb Director Health Laboratory Services Ministry of Health P.O. Box 419 Damascus Tel. +963 11 666 5 172 / 963 11 441 3445 Fax. 963.11.4442 153
TUNISIA
Mr M'hamed .4li Memmi Director, Health Laboratory Unit M ~ n ~ s tof r y Publ~c Health Tunis Tel./Fax. 216.1.786434
REPUBLIC OF YEMEN Dr Mohammed Salim Bin Break Director Diagnostics Department Health Laboratory Services Ministry of Public Health P.O. Box 8786 Sana'a Tel. 1-9671 23 1442 / +9671 252223
OBSERVERS ISLAMIC REPUBLIC O F IRAN Dr Rana Amini I-Iaematology Department Reference Laboratory of Iran Ro-Ali Hospital Teheran-No Ave Teheran Tcl. +98 21 379 8G70-1 Fax. +98 21.379 6373
WHO-EM/LAB/294/E/L Page 53
L)r Katayon Khodaverdi Haematology Department Reference Laboratory of Iran Bo-Ali Hospital Tehran-No Ave Teheran Tel. +98 21 379 8670-1 Fax. +98 21.379 6373 Dr Bita Entekhabi Serology Department Reference Laboratoiy of Iran
Bo-Ali Hospital Tehran-No Ave leheran Tel. +98 21 379 8670-1 Fax. +98 21.379 6373 Dr Mostafa Farizan Haematology Department Reference Laboratory of Lran Bo-Ali Hospital Tehran-No Ave
Teheran Tel. +98 21 379 8670-1 Fax. 198 21 379 6373 Dr Shahla Farsi Microbiology Department Reference Laboratory of Iran Bo-Ali Hospital Tehran-No Ave Teheran Tel. +98 21 379 8670-1 Fax. +98 21 379 6373 Mrs Zary Akhavan
Director, Medical Engineering Department Institute of Standards & Industrial Research of Iran (ISIRI) P.0. Box 31585-163
Karadj Tel. +98 261 226 03 118 Pax. +YX 261 223013
WHO-EM/LAB/294/E/L Page 54 Dr Lotfali Moravege Salehi Assistant Professor of Pathology and Chief of Shariati Hospital Laboratory Chief of Medical Laboratory Affairs of Iran Teheran Medical School Teheran Tel. +98 261 633078 Fax. +98 261 633039 Dr Issa Fahamad
Assistant Professor of Pathology Educational Director of Pathology Department Teheran University Medical School Teheran Dr Afsaneh Rajabiani Assistant Professor of Pathology, Teheran Medical School Educational Director of Pathology Dept. and Director of Quality Control Shariati Hospital Laboratory Teheran Mrs Hamideh Motahari Supervisor of Shariati Hospital Laboratory Teherau Tel. +98 261 633078 Fax. +98 261 633039 Mrs Manijeh Shadab Executiwe Director of Quality Control Shariati Hospital Laboratory Teheran Tel. +98 261 633078 Fax. +98 261 633039 Dr Psrvin Fallahi
Supervisor and Director of Quality Control in Biochemistry Section Shariati Hospital Laboratory Teheran Tel. +98 261 633078 Fax. +98 261 633039
WHO-EM/LAB/294/C/L Page 55 Mr Hojat Yasdanbod Supervisor and Director of Quality Control in Microbiology Section Shariati Hospital Laboratory Teheran Tel. +98 261 633078 Fax. +98 261 633039
WHO SECRETARIAT
Dr M.M. El-Nageh, Regional Adviser, Quality of Care and Health Care Technology, WHO/EMRO, P.O. Box 1517, Alcxandrin, EGYPT, Tel. +20 3 483 0090 Dr H. Reinauer, President, Institute for Standardization and Documentation in Medical Laboratories, Johannes-Wcyer-Str. I, D-40225 Dusseldorf, GERMANY, Tel. +49 21 1 330033, Fax. +49 211 313051 Dr W. Appel, Vice-President, Regional Office, Institute for Standardization and Documentation in Medical Laboratories, Seydlitzstrasse 25, D-76185Karlsruhe, GERMANY, Tel/Fax. 1-49 721 555006, E-mail-Appel.INSTAND.KA@,t.online.de Dr F. Fonseca-Wollheim, Director of Central Laboratories, Krankenhaus Zehlendorf, Gimpelsteig 3-5, D-14160 Berlin, GERMANY, Tel. +49 30 81021 51 8, F a x t 4 9 30 81021909 Dr K. Janitschke, Director, Robert Koch Institute, Clini~al Parasitology, Nordufer 20, D-13353 Bcrlin, GERMANY, Tel. +49 30 45472276 / 45472263, Fax.+49 30 4547261 3
Dr M. Abbassi, WHO Temporary Adviser, Director, Reference Laboratory of Iran, Bo-Ali Hospital, Tehran-No Ave, Teheran, ISLAMIC REPUBLIC OF IRAN, Tel. +98 21 379 86701. Fax.+98 21 379 6373 Ms Zahra Khatami, WHO Temporary Adviser, Officer-in-Charge, Quality Control and Biochemistry Department, Reference Laboratory of Iran, Bo-Ali Hospital, Tehran-No Ave, Teheran, ISLAMIC REPUBLIC OF IRAN, Tel. +98 21 379 8670-1, Fax. +98 21 379 6373 Ms Azarm Nami, WHO Temporary Adviser, Quality Control and Biochemistry Department, Refrrcncr 1 ahoratory of Iran, Rn-Ali I-lorpital, Tehran-No Ave, Tehernn, ISLAMIC REPUBLIC OF IRAN, Tel. +98 21 379 8670-1, Fax. +98 21 379 6373 Mrs G. Ismail. Secretary, Quality of Care and Health Carc Tcchnology Unit, WIIO/EMRO, Alexandria. EGYPT
WHO-EM/LAB/294lElL Page 56
Annex 4 INTERCOUNTRY COOPERATION AS FORMULATED BY THE PARTICIPANTS OF THE WORKSHOP 1
Tn rhnnce a fncal point for communication with other member countries; To exchange information regarding the following: legislation and organization of QA scheme the standard purchasirig policy of equipment, including technical spec~iicat~ons, maintenance, repair and spare parts, calibration, personnel training, documentation on sales in other countries, operating and maintenance manuals the evaluation protocols for equipment the standard purchasing policy of reagents, including practicability (time consumed per test, cost, safety, expiry date, verification of quality product by FDA, CE, etc.), and reliability the evaluation protocols for reagents
2.
0
the training protocol of quality assurance officers in internal quality control and external quality assessment the documents and manuals produced nationally on QA tht: algorithm (steps included) of canying out the tasks of IQC and EQA
The above information to be submitted to WHOIEMRO. from where it is circulated to other EMR countries.
WI 10-CM/LAB/294/E/L Page 57
Annex 5 QA CHECKLIST AFG BAA EGY Pilot study to implement QA system
IRA MOR OMA PAK yes yes yes no
SUD yes
SYR TUN YEM -
no
yes
yes
yes
yes
yes
EQA
no no no no no
yes yes yes yes no
yes no yes no yes
yes
yes yes
yes yes no notofficially no
no no yes no no
no yes no yes no
yes no yes yes yes
yes no yes no yes
no no yes yes
SOP 'l'raining in IQC QA officers National expert comniittce on QA Problem-solvingteam
yes yes yes
yes yes yes unofficially
yes
no no
yes yes
no yes
yes yes
+
no no
yes no
no no
yes yes
yes yes
no yes
QA concepts introduced in regular training programmes Reliable sources for supplies o f quality Strategies for selection o f
yes
no
yes
yes
no
yes
yes
yes
no
yes
no
no
no
yes
no
no
yes
yes
yes
no
yes
yes
no
appropriate instruments and maintenance
WHO-EMILABI294IEIL Page 58 Annex 6 PLAN OF ACTION OF THE REGIONAL MEETING OF DIRECTORS OF HEALTH LABORATORY SERVICES, DAMASCUS, SYRIAN ARAB REPUBLIC, 12-15 MAY 1996 The participants formulated and endorsed the following plan of action, and committed themselves to implement it and follow it up at the national level and regularly report on the outcome to EMRO. Activity 1. Implementation of those items of the plan of action, prepared and endorsed at the meeting of the national health laboratory directors held in Nicosia in 1994, that are not yet completed (Annex 4) 2. Recommendations to the ministry of health that the directors of the national health laboratory services be assigned a position similar to that of directors responsible for other national health programmes, and accountable to the top management in the Ministry of Health. All health laboratory services should be integrated under this management. A specific laboratory budget should be giver1 lo tile laboratory services 3. Organizing and conducting national management courses and workshops for health laboratory managers and supervisors.
Target date End 1997
1997
1996-1 997
4. Improve laboratory recording and reporting system using standardized format and computerization whenever possible. 5. Development of an instrument and reagent evaluation and purchase policy.
1996-1997
1996
6. A n intercountry information exchange, especially with regards to performance of instruments and quality of reagents will be established. A newsletter to be distributed from an assigned focal point. Electronic facilities should bc uscd wt~enever possible.
1996
7. Annual reporting to EMRO of achievements (the present status of 1996 achievements is given in Annex 5). Format for this purpose has to be worked out and distributed from EMRO.
WHO-EM/LAI3/294/E/L
Page 59 8. Development of a quality manual containing the following detailed parts at the level of each laboratory. Countries are recommended to consult available literature, e.g. EMRO publication No. 14 Quality systems for medical laboratories. Emphasis should be on training of trainers Administrative procedures manual Staff manual Operational procedures manual Equipment maintenance and usage manual Specimen collection manual Safety manual Labu~aru~y Iriurllbvok ~ U 11cal~l1 I p~acliliu~lers Consider consumer requirements through regular communication.
9. Quality assurance systems to cover laboratory services, including private sector, in all health laboratory disciplines. 10. Self-assessment, applying available check lists, e.g. from EMRO publication No. 14 Quality s.vstems.for medical laboratories. 11. Upgrading of microbiological laboratory investigations, particularly at intermediate level: a) Improving the identification of major pathogens enccuntered in through standa~dized n~cll~uds the cuunt~y/Region, b) Establishment of policy for standardized methodology in sensltlvlty to antlb~ot~cs (WHO publ~cat~ons are ava~lable). 12. Establish national reporting systems on bacterial resistance to antimicrobial agents. Ongoing
Ongoing
1996
13. To continue the efforts initiated during the period of 1988 plan of action with regard to the development of virology laboratories at the level of individual countries 14. Establish policies for licensing and evaluation of reagents for serological tests with emphasis on HIV and hepatitis.
Ongoing
WHO-EM/LAB/ZY4/E/L Page 60 RECOMMENDATIONS TO WHO
I.
The participants strongly recommend that the WHO Regional Office for the Eastern Mediterranean conduct regularly, once every two years, a Regional Meeting of Directors of Ilealth Laboratory Services. Iri~crcuunt~y t~ainingcourses and workshops on management of health laboratories
2.
should be conducted.
3.
WHO should contlnue to support countries' activities to establish and upgrade national quality assurance programmes covering all disciplines of health laboratories. To bring the matter of appointing a Director of the National Health Laboratory Services to a position similar to that of Directors responsible for other national health programmes to the attention of Ministers.
4.
WHO-Ehl/LAB/294/E/L Page 61
Annex 7 PLAN OF ACTION OF THE INTERCOUNTRY WORKSHOP ON QUALITY ASSURANCE IN HEALTH LABORATORIES, NICOSIA, CYPRUS, 29 JUNE-3 JULY 1992 The participants endorsed and committed themselves to the following: Activity It IS adv~sable that the professional groups establish mechanisms to a u d ~and t appralse the operation of the laborarorles. (It is understood assessment is one element of this process.) that external qllal~ty
Target Date Starting 1992
111-houscmeasurement procedures should be carefully documented (Standard Operating Procedures) In-serv~cc tralning for laboratory statT should be implemented to expedite implementation of internal quality control procedures, beginning with central laboratorylies followed by intermediate-level laboratories. This training should be offered and conducted in cascade courses Managers should appoint skilled professionals (assisted by a committee of experts) to be responsible for the national quality assurance programme in their health laboratories, paying special attention to Good Laboratory Practices
Continuous process, starting in 1992 Continuous process, starting in 1992
End of 1992
A task force should be established to investigate and resolve operational and technical difficulties in participating laboratories It may be advisable to establish a pilot project, limited to a small number ot'laboratories, to adjust plans to local conditions and needs. If needed, the capacity of the laboratory systems (facilities, equipment, personnel, etc.) should be assessed, simultaneously, to evaluate the country's ability to implement a national quality assurance system Quality assurance concepts should be ~ntroducedInto the curr~cula of training programmes for laboratory personnel Reliable sources should be established for supplies of good quality chemicals, reagents, consumables and rcfercnce materials. The financial implications of alternative strategies for the provision of these materials should be evaluated in the pilot project mentioned above
End of 1992 Not later than 1993
End of 1993 End of 1993
WHO-EMILABI294lEIL
Page 62 National strategies for the selection of appropriate instrumentation and maintenance thereof should be reviewed. National groups should be encouraged to outline general procedures and contract specifications to be used in the procurement of equipment and reagents End of 1993