National Quality Control Program Research Articles

Comparative analysis of image quality parameters and spatial resolution of three Small Animal PET scanner in Brazil

This study evaluated Image Quality (IQ) parameters and spatial resolution (SR) of Triumph® LabPET systems installed in three different Brazilian preclinical molecular imaging centers. A comprehensive evaluation of the PET scanner intrinsic parameters is important to optimize the acquired images, providing more reliable qualitative and quantitative analyses. Experiments were carried out at the centers: C1 - Molecular Imaging Laboratory of the CDTN/CNEN; C2 - Laboratory of Nuclear Medicine of HCFMUSP; C3 - Preclinical Research Center of the Brain Institute at PUC-RS. IQ phantom PET images were acquired as recommended in NEMA NU 4-2008 standard. Image reconstructions were performed in each system using the same reconstruction protocol. Data was processed using PMOD® software. The IQ parameters: (i) uniformity, (ii) spill-over ratio (SOR) and (iii) recovery coefficients (RC) were evaluated and compared. For Uniformity test, the percentage standard deviations of mean activity concentration were 7.8%; 7.3% and 6.4% for Centers 1, 2 and 3 respectively. Cold chambers RSO values in the systems 1, 2 and 3 were respectively 0.16, 0.19 and 0.21 for water; 0.26; 0.28 and 0.30 for air. The RC’s for rod diameters from 1 to 5 mm ranged from 0.08 to 0.91 for the three centers. Results revealed that the three PET systems have appropriate quality parameters for pre-clinical studies, presenting values compatible with international standards. This study was able to reveals the performance of preclinical PET system of different Brazilian imaging centers and may support the standardization of a National Quality Control Program for Small Animal PET scanners.

Proposal of Brazilian National Program for Quality Control in the small animal PET scanners

In Brazil, currently there are six preclinical molecular imaging centers and seven different small animal PET systems in use. However, there is still no national specific legislation for research laboratories focused on preclinical molecular images, unlike clinical nuclear medicine centers. A standardization of quality control protocols is needed to harmonize the use of small animal PET scanners in the research field. Thus, the aim of this work was to propose a National Program for Quality Control (NPQC) for the preclinical PET imaging systems in Brazil. This work was based on the quality control tests performed in Molecular Image Laboratory LIM/CDTN based on NEMA NU 4-2008 as described and presented in doctoral thesis of GONTIJO, 2019. The proposal of the NQCP was based on the CNEN NN 3.05 Publication (2013) and includes fundamental tests to be adopted, if possible, in laboratory practice to corroborate the experimental data. The Quality Control Program implemented in LIM/CDTN is an innovative and unprecedented proposal in the scope of preclinical molecular imaging services in Brazil. Therefore, the LIM/CDTN Program was carried out as a pilot to evidence the applicability and viability of the NQCP using small animal PET scanners. Summarizing, this work presents a viable set of Quality Control tests and their periodicities like a proposal for standardization to harmonize the use of this imaging technology in the field of research. Therefore, a National Quality Control Program (NQCP) applied to small animal PET scanners.

Determination of azoxystrobin, topramezone, acetamiprid, fluometuron and folpet in their commercially available pesticide formulations by liquid chromatography

A rapid, simple, precise and accurate high performance liquid chromatographic (HPLC) analytical method was developed and validated for the determination of the active substances (a.s.) azoxystrobin, topramezone, acetamiprid, fluometuron and folpet in their respective commercially available formulations. The method was used for the analysis of samples under the frame of the national quality control program of plant protection products in the Greek market. Chromatographic separation of the active substances from additives and co-formulants is achieved using isocratic elution with acetonitrile and 0.1% phosphoric acid solution (60:40 v/v) at a flow rate of 0.4 mL min−1 on a C18 monolithic column (Chromolith Performance-RP18e 100 × 4.6 mm) and UV detection at 230 nm. Validation parameters of the method fulfilled acceptability criteria. Recovery of all individual compounds was in the range 97.8–100.9%. Precision expressed as relative standard deviation was lower than the theoretical values of the modified Horwitz equation. Correlation coefficients of linearity of response were better than 0.999. The benefits of the proposed method are significant reduction in analysis time and total cost since all analytes were determined with the same extraction procedures and chromatographic system. Analysis of real samples for all active ingredients confirmed fitness for purpose of the suggested method.

Effectiveness of the National Quality Control Program in Mycology of Argentina and performance evaluation of participating laboratories

The National Quality Control Program in Mycology (PNCCM) of Argentina was established in 1996 to improve the quality of the mycological diagnosis, to help establish and to set up standardized procedures and continuous training of laboratory staff. The aim of this study was to assess the effectiveness of the PNCCM in the 1996–2018 period. Data from the National Mycology Laboratory Network (NMLN) and PNCCM database was used to estimate the increase in the number of controlled laboratories and jurisdictions, the percentage of participation, the improvement in the quality of results and the adherence to the program. Satisfaction surveys were performed to assess user satisfaction. The number of controlled laboratories increased from 29 to 146; participation increased from 49% to 93% and general adherence was 72% in the evaluated period (1996–2018). Improvement in the quality of the results was 15% for low complexity samples; 7% for intermediate complexity samples and 14% for the identification of high complexity strains. Up to 84% of the users consider the PNCCM to be “very good” and 16% “satisfactory”. These results show the importance of the PNCCM, which is widely accepted by mycological diagnostic laboratories from Argentina.

94P - Two years of BRCA1 and BRCA2 somatic external quality assessment with Gen&Tiss scheme in France

BackgroundTesting for germline BRCA1/2 mutations has an established predictive role in breast and ovarian cancer risk assessment and EQA on germline mutation testing have been performed for a long time. With the European extension of indication for the PARP inhibitors, the screening of tumors first is increasingly important. However, tumoral BRCA1/2 testing is a different analytical process on formalin-fixed, paraffin-embedded (FFPE) material and with some challenging variants as large rearrangements. Validation of the test method and participation in external quality assessment programs are therefore required. MethodsIn the French national quality control programs (Gen&tiss) of 2017 and 2018, laboratories received 5 samples from ovarian cancer patients and 1 educational artificial sample with mutations present at different variant allelic frequencies in BRCA1/2 and a large rearrangement in BRCA1. ResultsThe number of participants was 21 in 2017 and 26 in 2018. The number of labs with severe error was 3 in 2017 (14%) and 4 in 2018 (15%). For BRCA1, the average score remained stable between 2017 [9.6/10 (N=21)] and 2018 [9.6/10 (N=26)]. In both years, 2 laboratories made severe errors (false positive/false negative). In 2017 only 11 laboratories (N=20) identified the educational variant present at 7% VAF. For BRCA2 the score slightly decreased from 9.8/10 (N=22) to 9.4/10 (N=26) and the number of laboratories with severe errors increased from 1 to 3. Half of the laboratories (N=20) detected all three mutations present in the educational sample (VAF 10% to 30%) in the 2017 scheme. In 2018 a large deletion in BRCA1 present in the educational sample was only detected by 4 out of 20 laboratories. Three out of 26 laboratories detected the additional RAD51C variant and none the RAD51D variant. The main methods applied in France focus on BRCA1 and BRCA2 genes and amplification-based enrichment. ConclusionsThe genotype results were very similar between 2017 and 2018: acceptable but there are still more than 14% with severe errors. The limit of detection is a critical point. Few labs are ready to extend testing beyond BRCA1/2 genes. The question of large rearrangements is not yet solved for tumoral screening. EQA on tumoral BRCA1/2 testing is therefore essential to improve laboratory performance. Legal entity responsible for the studyGen&tiss - GFCO and AFAQAP. FundingAstraZeneca. DisclosureAll authors have declared no conflicts of interest.

Szkolenia w zakresie ochrony lotnictwa cywilnego

Polish accession to the EU and which consequently adapt Polish law to EU standards drew attention to the aviation community on the need for training and improvement of the quality of work people employed at the airport. Similarly, the subject was developed in the protection of civil aviation. Here, however, the direct stimulus for the formation of all kinds of regulations were the events in the USA 11.09.2001 r. It was then that apart from the obvious need to introduce more restrictive rules related to the security control of passengers and their luggage, it was also noted for staff training, their skills, threat detection and appropriate response to all types of custom passenger behavior. Then also placed special emphasis on quality control work, which is reflected in even the National Training Programme and the National Quality Control Programme, which are designed, on the one hand, professional prepare of the screeners for the implementation of the their statutory tasks, on the other hand, has created a tool to supervise the quality of the work done by this group of workers. Awareness of the human factor as an element that could significantly affect the level of airport security makes this factor is particularly treated in the protection of civil aviation. The consequences of human error, resulting from an act of conscious or unintentional, may in fact be catastrophic for the airport, the carrier and passengers.

EXTERNAL QUALITY CONTROL EVALUATION IN THE HEMATOLOGY, PARASITOLOGY AND URINALYSIS AREAS IN A HIGHER EDUCATION INSTITUTION BIOMEDICAL CLINIC IN THE BETWEEN OCTOBER 2012 TO SEPTEMBER 2012.

The External Quality Control (EQC) is an important tool to ensure the Clinic Laboratory (CL) services quality. This way, the objective of this study was to evaluate the EQC in the hematology, parasitology and urinalysis sectors of Biomedical Clinic, at a Higher Education Institution from October 2011 to September 2012, through a descriptive study with a performance data collection in the National Quality Control Program (NQCP) from the Brazilian Society of Clinical Analyses (BSCA). The urinalysis sector presented the best percentage of accuracy, a 94,5%, while the hematology one obtained 86.15 % and the parasitology sector presented 58.83 % of accuracy. However, in general terms, Clínica Biomédica obtained 82.83 % fitting on the level of “Excellence”, according to the standards set by NQCP, underscoring the reliability of its analyzes. The continuity of the EQC implementation must be preserved to ensure accurate diagnosis, minimizing negative impacts to the patient’s health.

Retrospective analysis of the results of acellular pertussis vaccine toxicity tests performed in Korea

Specific toxicity test is a major quality control test for acellular pertussis (aP) vaccines performed by manufacturers and regulatory authorities. The ‘mouse body weight gain test (MWGT)’, the ‘leukocytosis-promoting test (LPT)’ and the ‘histamine sensitization test (HIST)’ have been conducted to check the specific toxicity of all batches of aP vaccines used in Korea through the national quality control program, which requires a lot of animals, labor and time. In this study, test results obtained in the past 9 y from a total of 258 lots of aP vaccines were examined retrospectively to evaluate the three test methods. A pairwise comparison of the test results indicated a good correlation between LPT and HIST, whereas MWGT showed no correlation with either LPT or HIST. Moreover, the reversion to toxicity was higher than the residual toxicity in the majority of lots tested by HIST, which indicated that the histamine-sensitizing toxicity, although rated within a safe range, increased during the vaccine storage. Thus, the vaccine safety test results accumulated in the past might be useful for the improvement of test protocols.

Analytical quality of assays and comparison of procedures for the sweat test

Sweat test measuring the chloride ion (Cl(-)) concentration in sweat is a tool for the cystic fibrosis (CF) diagnosis. We evaluated analytical criteria of different available methods and compared them into five hospitals and throught a national quality control program. Sweat tests were performed by stimulation using pilocarpine iontophoresis, sweat collection and measurement of sweat Cl(-) (mmol/L) by titration (colorimetric or coulometric end-point) or by in situ direct potentiometry using a chloride-selective electrode. Indirect determination by sweat conductivity measurement was expressed in mmol/L sodium chloride (NaCl) equivalents (Eq). Linearity range was demonstrated for all measurement procedures in the range 10 to 120 mmol/L. Intra-laboratory coefficients of variation (CVs) were <5% for values between 10 and 100 mmol/L. Inter-laboratory CVs were <3% only for conductivity measurement whatever the range. The comparison of results obtained for a same sweat sample, simultaneously by coulometric and conductivity measurements, demonstrated a first degree linear distribution between 30 to 60 mmol/L Cl(-) allowing us to establish an analytical correspondence table for this range. Thus, calculated values for 30, 40 and 60 mmol/L Cl(-) were respectively 57, 66 and 84 mmol/L NaCl Eq. In conclusion, comparison of methods highlighted that the less the sweat test is automatically controlled, the more the operator influence on results quality is important. Our study supports that sweat test result <50 mmol/L NaCl Eq is unlikely with CF diagnosis in absence of clinical arguments.

A quality control programme for medical X-ray films in India

Medical X-ray films are continued to be the major image receptors in diagnostic radiology in India. About 9×10⁶ m² of medical X-ray films are used per annum for diagnostic imaging in India, and its magnitude may further increase as the number of diagnostic X-ray units is increasing rapidly. A national quality control programme was initiated for testing the medical X-ray films of various suppliers/manufacturers so that optimum quality film can only be used in diagnostic radiography examinations. X-ray laboratory of Radiological Physics and Advisory Division, Bhabha Atomic Research Centre was recognised as national film testing laboratory. A dedicated test phantom was fabricated as per the prescription of International Organization for Standardization (ISO 9236-I, 1996), simulating the attenuation and scatter properties of chest of an average patient for periodic X-ray sensitometric evaluations of the medical X-ray films. The basic fog, speed, latitude, maximum optical density, uniformity and artefacts of all the films tested so far were found well within the requirements specified in the national standards. The average gradient for a few blue and green sensitive films were found less than the specified value. Suppliers/manufacturers of such films were advised to improve the performance quality of their films.

Calculating Uncertainty of Measurement for Serology Assays by Use of Precision and Bias

In many countries, regulatory authorities that use International Organization for Standardization Standards to assess laboratory competence require an estimate of the uncertainty of measurement (MU) of assay test results. This estimate can be determined by identifying all sources of variation, calculating the extent of variation, and using established methods to combine the uncertainty. Alternatively, laboratory staff may use existing data generated from evaluations, proficiency testing, or external run controls to determine MU. A quality-control (QC) sample with low reactivity was tested by laboratories participating in a national QC program. The results of testing the QC sample were entered into a shared database by use of an Internet-based program, EDCNet. Using a statistical approach that accounts for imprecision and bias of test results, we estimated the MU of the laboratories. A total of 2167 test results of a single QC sample reported by 18 laboratories were analyzed, and the MU of 1 laboratory was estimated by the statistical model described. Using peer-group run control data, MU of serologic testing can be estimated by taking into account both imprecision and bias.

Japanese standard reference material for JDS Lot 2 haemoglobin A1c. I: comparison of Japan Diabetes Society-assigned values to those obtained by the Japanese and USA domestic standardization programmes and by the International Federation of Clinical Chemistry reference laboratories

The Committee on Standardization of Laboratory Testing Related to Diabetes Mellitus of the Japan Diabetes Society (JDS) previously recommended use of the primary calibrator (JDS Lot 1) prepared by the former Committee for Standardization of Glycohemoglobin for standardizing the measurement of haemoglobin A1c (HbA1c). Owing to the depletion of vials of Lot 1 in March 2001, the present committee certified a new reference material, Lot 2, now distributed by the Health Care Technology Foundation (HECTEF). The standardization programme for HbA1c measurement in Japan is currently based on Lot 2, which has values assigned from within Lot 1; the Lot 1 values were consensus values based on assays by laboratories in the Japanese national quality control programme. In this study, for the purpose of international comparison and standardization, Lot 2 was assayed by the JDS reference laboratories, the National Glycoprotein Standardization Program (NGSP) in the USA, and by reference laboratories approved by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The HbA1c values of JDS Lot 2 were transferred from those assigned to Lot 1 using KO500, a high-resolution HPLC method, at three laboratories approved by the JDS committee. Subsequently, vials of JDS Lot 2 were shipped to and assayed by the NGSP in the USA and 10 IFCC reference laboratories. The JDS-assigned HbA1c values (from Lot 1) are 4.04 for Level 1, 5.38 for Level 2, 7.32 for Level 3, 9.88 for Level 4, and 12.63 for Level 5, all expressed as a percentage of total haemoglobin. The values obtained by NGSP and the IFCC laboratories gave the following formulas: NGSP value(%)=JDS value(%)+0.3%; IFCC value(%)=1.068xJDS value(%)-1.741%. Although the values obtained by the IFCC laboratories are significantly lower than the values assigned to Lot 2 by the JDS, the relationship is linear. In addition, standardization of HbA1c based on JDS Lot 2 is currently at a satisfactory level in Japan. As a result, the reassignment of values for Lot 2 to agree with the IFCC values should be relatively easy and will be done after all relevant parties agree to the change.

L’assurance de qualité en coprologie fonctionnelle

Quality control in medical laboratories was defined in guidelines for good execution of laboratory analyses issued by the French health authorities in 1994. Application of these guidelines is difficult in coprology because the sample is a complex heterogeneous matrix which varies with disease, surgery, food intake, and treatment. In addition, commercial quality control kits are not available for stool biochemical analyses and a national quality control program has not been established. We thus developed our own fecal quality control technique using pooling lyophylized stool samples. Manual or partially automated methods are used in coprology, leading to a long pre-analysis phase which is not always taken into account in quality control. This implies the need for complementary tools to insure the quality of coprology analyses. For example, semi-quantitative microscopic lipid analysis can be used as an internal standard for a given specimen. Quality assurance also involves a post-analytical phase where results obtained for a given specimen are compared with other available data and interpreted in light of the patient's clinical and therapeutic status. This quality assurance strategy enables accurate reliable results useful for long-term patient management.

HER-2 expression and cell proliferation: prognostic markers in patients with node-negative breast cancer.

We analyzed the clinical relevance of HER-2 expression, widely investigated in breast cancer but with contradictory results, in the largest case series of node-negative breast cancer patients investigated to date. The pure prognostic value of HER-2 expression was investigated in 529 patients treated with locoregional therapy alone until early relapse. Proliferative activity was evaluated as [3H]thymidine labeling index and HER-2 expression by immunohistochemistry. All biologic determinations were conducted within the context of an intra- and interlaboratory National Quality Control Program. HER-2 expression was not related to relapse-free survival in the overall series but was a significant discriminant of prognosis in the subgroup of patients with rapidly proliferating tumors. Six-year rate of relapse was 40% for patients with highly (> or =30%) positive tumors and 26% for those with weakly HER-2-expressing tumors (P =.039). HER-2 expression in association with proliferative activity identifies a subgroup of node-negative breast cancer patients with the worst prognosis, who are candidates for specific intensive adjuvant therapy.

French national quality control for pH and blood gases: ten years experience.

A national quality control program for blood gas analysers has been established in France since 1983. Buffer solutions are used at two levels of pH, Po2, Pco2 for testing 950 laboratories using 22 different models. These annual programs inform about the accuracy and the precision of the instruments. They also make the user conscientious to different procedures of quality control. Information is also obtained on the yearly turnover of the types of analysers.

Hospital admission rates for asthma and respiratory disease in the West Midlands: their relationship to air pollution levels.

A study was undertaken to determine the relationship between hospital admissions for asthma and all respiratory conditions in electoral wards in the West Midlands and ambient levels of smoke, sulphur dioxide, and nitrogen dioxide, and to establish whether the relationship is independent of social deprivation and ethnicity, and is different for young children and older individuals. Data on hospital admissions for acute respiratory conditions were obtained by electoral ward from the West Midlands Regional Health Authority Information Department Körner inpatient data including asthma (ICD 493) and all acute respiratory disease (466, 480-486, 490-496) for the period April 1988 to March 1990. The population for each electoral ward, percentage of ward population that was from non-white ethnic groups, and Townsend deprivation score were all calculated from 1991 census information. Data on smoke and sulphur dioxide (SO2) levels were obtained for 24 wards in Birmingham, Coventry, Wolverhampton, Dudley, Stafford, and Burton-on-Trent, and on nitrogen dioxide (NO2) levels from 39 wards in the same local authority areas. All were background urban sites and most participated in the Warren Spring national quality control programme for SO2 and smoke monitoring. Indirect age-sex standardised hospitalisation rates (SHR) for all respiratory conditions and asthma were calculated using the 1991 rates for the West Midlands RHA as the standard. Multivariate regression models were used to assess the relationship between individual pollutants and the SHR. The Townsend score and percentage of the population from non-white ethnic groups were included in all models to adjust for ethnicity and socioeconomic deprivation. The SHR for asthma varied almost fourfold across the region, and all respiratory SHR showed more than three fold variation. Bivariate regression revealed both Townsend score and percentage of non-white individuals to be associated with SHR for asthma and all respiratory conditions at all ages, but not for children under 5 years. NO2 was associated with hospital admission rates for all ages including children under 5. SO2 and smoke were not associated with hospital admissions. Multivariate analysis including Townsend score and percentage of non-white subjects in the model revealed that NO2 was associated with hospital admission rates for all respiratory conditions only for children under 5. The Townsend score was associated with SHR for all respiratory conditions, and both the Townsend score and percentage of non-white subjects were associated with SHR for asthma in children under 5 in two of three models. The association between SHR for asthma and percentage of non-white subjects was negative. Socioeconomic deprivation, as measured by the Townsend score, is a significant predictor of hospital admission rates for respiratory disease in older individuals, and both the percentage of non-white subjects and the Townsend score are significant predictors of hospital admission rates for asthma in children. After correction for socioeconomic deprivation and ethnicity, background urban NO2 levels in the ward of residence are significantly associated with standardised hospital admission rates for all respiratory disease in children under 5. This may represent a causal effect of NO2 on the respiratory health of children, or the effect of confounding factors not corrected by use of the Townsend score.

Interlaboratory quality assessment of lymphocyte phenotyping. Etalonorme 1990–1992 surveys

A 3-year interlaboratory proficiency testing for lymphocyte subset phenotyping was initiated as part of the Etalonorme national quality control program. Specimens consisted of fresh whole blood and of lyophilised mononuclear cells (Cytotrol Coulter). The number of participating laboratories was 62 in 1990, 99 in 1991 and 129 in 1992. Statistical analysis indicated that results of phenotyping, expressed as percentages of positive cells, are not related to reagents, instruments or differences in methodology (like, eg time and temperature of incubation). The highest dispersion was observed for total lymphocyte counts and was found to correlate with the type of calibration of the instrument. The coefficients of variation for different lymphocyte subsets were similar if phenotyping was performed on whole blood or lyophilised cells and varied inversely with the percentage of positive cells in each specimen. The consistency of the results indicated that they could serve as a basis for clinical decisions.

Quality Control of Receptor Analyses of Breast Cancer Tissue in Denmark

Quality control investigations of estrogen and progesterone receptor (ER and PgR respectively) analyses can be undertaken using two principally different methods. The first, and the most frequently employed, is by comparing the results of analyses of a lyophilized, standard cytosol. The second method is by comparing the frequency of receptor positivity as well as the distribution of the receptor concentrations determined on a large number of representative biopsies in different laboratories. This latter method can, however, only be used provided that the composition of the population of biopsies studied is similar in the laboratories undertaking such an investigation. Both approaches have been used by the three Danish laboratories participating in the Danish Breast Cancer Cooperative Group (DBCG) project. The international and national quality control programs that these three laboratories have participated in are reviewed in the present paper. From having a poor degree of inter-laboratory reproducibility in 1981, the inter-laboratory reproducibility has improved due to a collaborative standardization effort. Using the clinical data available through the DBCG program, we have been able to demonstrate that suboptimally performed receptor analyses can influence the conclusions of clinical studies regarding patient prognosis in relation to receptor status.

How Physicians Use Laboratory Tests

The aim of our study was to measure the ways in which a physician perceives and reacts to a laboratory result. After reviewing a series of brief clinical problems, physicians were asked to indicate the change in test results that would alter the diagnosis or treatment. Although there were wide differences in attitudes, the pattern of responses from 125 internists offered estimates of what is a clinically important change. In selected clinical settings, the change in successive measurements chosen with the greatest frequency as indicators of a clinically important change in level were glucose, 35 mg/dl; BUN, 6 mg/dl; serum sodium, 4 to 6 mEq/liter; serum potassium, 4 to 6 mEq/liter; uric acid, 8 mg/dl; creatinine, 0.4 mg/dl; serum calcium, 4 to 5 mg/dl; triglycerides, 20 mg/dl; hemoglobin, 1 g/dl; and serum osmolality, 11 mOsm/kg. The responses were compared with estimates of laboratory precision drawn from a national quality control program. The quality of laboratory testing was rated as satisfactory for clinical use in four of five clinical settings. The study points out the need to correlate the activities in the clinical laboratory with the application of test results in the care of patients.

The Practical Application of Reference Method Technology

The main value of reference technology will be in the selection of techniques for service use and in defining reference ranges for the concentration of substances in the body fluids of normal individuals. Initially it should find application in the present national and international quality control schemes to distinguish those techniques which, as currently operated, are sound, from those in which accuracy can be demonstrated to be faulty. Over the long-term it is to be expected that when new techniques for service use are submitted for publication, they should not be accepted unless the results which they have produced have been satisfactorily compared with results obtained by the appropriate reference technique. In the application of the reference technique for calcium to the Wellcome Group Quality Control Program it has been shown that two widely used routine methods for calcium in serum tend to give lower results than the reference value at high calcium concentrations, and higher results at low concentrations. Attention can now be focused on this effect with a view to its elimination either by suggesting the modification or abandonment of the techniques in question. Herein lies the key to further improvement in interlaboratory quality control which has recently tended to plateau. Reference technology is likely to be required for four main purposes: 1. The assay of commercial quality control material. 2. The assay, either in prospect or retrospect of material used in national quality control programs. 3. One off measurements required by individual laboratories for development work on instruments and methods. 4. For monitoring the effects of drugs or their metabolites, etc. Definitive methods will almost certainly always be difficult and will be required only rarely, but even reference methods will not be easy to set up and are likely to prove uneconomic to keep running for individual laboratories to be able to do their own assays as required. Therefore centers need to be designated to carry out certain assays on a national and international basis.