LATIN-AMERICAN BIOLOGICAL DOSIMETRY NETWORK (LBDNET) INTERCOMPARISON EXERCISE

Transcription

1 Latin-American Biological Dosimetry Network (LBDNET) Intercomparison Exercise Evaluation through triage and conventional scoring criteria. Development of a new approach for statistical data analysis Di Giorgio, M.; Vallerga, M.B.; Radl, A.; Taja, M.R.; Seoane, A.; Stuck Oliveira, M.; Valdivia, P.; García Lima, O.; Lamadrid, A.; González Mesa, J.; Romero Aguilera, I.; Mandina Cardoso, T.; Guerrero Carvajal, C.; Arceo Maldonado, C.; Espinoza, M.; Martínez López, W.; Di Tomasso, M.; Barquinero, F.; Roy, L.; Lloyd, D.; Lindholm, C. and Romm, H. Presentado en: 12 th International Congress of the International Radiation Protection Association. Buenos Aires, Argentina, octubre 2008 El presente trabajo se presentó con poster y oralmente durante el evento.

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3 LATIN-AMERICAN BIOLOGICAL DOSIMETRY NETWORK (LBDNET) INTERCOMPARISON EXERCISE Evaluation through triage and conventional scoring criteria Development of a new approach for statistical data analysis 1 M. Di Giorgio * ; 1 M.B. Vallerga; 1 A. Radl, 1 M.R. Taja; 1a A. Seoane; 2 M. Stuck Oliveira; 3 P. Valdivia; 4 O. García Lima; 4 A. Lamadrid; 4 J. González Mesa; 4 I. Romero Aguilera; 4 T. Mandina Cardoso; 5 C. Guerrero Carvajal; 5 C. Arceo Maldonado; 6 M. Espinoza; 7 W. Martínez López; 7 M. Di Tomasso; 8 F. Barquinero; 9 L. Roy; 10 D. Lloyd; 11 C. Lindholm; 12 H. Romm 1 Autoridad Regulatoria Nuclear (ARN), Av. Del Libertador 8250, C1429BNP, Buenos Aires, Argentina; 1a Centro de Investigaciones en Genética Básica y Aplicada(CIGEBA), Universidad Nacional de la Plata, 60 y 118 CC296, B1900AVW, La Plata, Argentina; 2 Instituto de Radioprotección y Dosimetría (IRD), Av. Salvador Allende s/n, Jacarepaguá, Rio de Janeiro, CEP , Brazil; 3 Comisión Chilena de Energía Nuclear (CCHEN), Amunátegui 95, Santiago Centro, Santiago, Chile; 4 Centro de Protección e Higiene de las Radiaciones (CPHR), Calle 20 No e/ 41 y 47 Miramar, 11300, La Havana. Cuba; 5 Instituto Nacional de Investigaciones Nucleares (ININ), Carretera México-Toluca s/n, C.P , La Marquesa, Ocoyoacac, México; 6 Instituto Peruano de Energía Nuclear (IPEN), Av. Canadá 1470, San Borja, Perú; 7 Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, Montevideo, Uruguay; 8 Universidad Autónoma de Barcelona - Facultad de Biociencias, Campus Universitario de Bellaterra, Barcelona, Spain; 9 Institut de Radioprotection et de Sureté Nucléaire (IRSN), Bâtiment UIS 31, avenue de la division Leclerc 92262, Fontenay-aux-roses Cedex, France; 10 Health Protection Agency (HPA), Chilton, Didcot, Oxon OX11 0RQ, United Kingdom; 11 Radiation and Nuclear Safety Authority (STUK), Laippatie 4 / P.O. BOX Helsinki, Finland; 12 Bundesamt für Strahlenschutz (BfS), Postfach D Salzgitter, Germany Abstract Biological Dosimetry is a necessary support for National Radiation Protection Programs and Emergency Response Schemes. A Latin-American Biological Dosimetry Network (LBDNET) has been constituted by the biological dosimetry laboratories from: Argentina, Brazil, Chile, Cuba, Mexico, Peru, and Uruguay (IAEA Regional Project RLA9/054, 2007). * mdigiorg@cae.arn.gov.ar 479

4 The biological dosimetry laboratory of Argentina organized an international biological dosimetry intercomparison for the analysis of some relevant parameters involved in dose assessment, to reinforce the response capability in accidental situations requiring the activation of mutual assistance mechanisms and thus, constituting the bases of the LBDNET organization. General Objectives To evaluate the inter-laboratory reproducibility. To identify potential difficulties and to promote the necessary modifications for the collaborative task. Specific Objectives To initiate, with this exercise, periodic intercomparisons among LBDNET participants. To develop technical competence of associated laboratories inside the country. INTERCOMPARISON PROGRAM Participant laboratories from the LBDNET, Spain (UAB), France (IRSN), United Kingdom (HPA), Finland (STUK) and Germany (BfS). ACTIVITIES: Are at present in progress and should be concluded in June Human blood samples were irradiated in vitro with a 60 Co source (Regional Reference Center for dosimetry of the Atomic Energy Commission), two points of doses and a control. Cultures and slide preparations were performed according to standard methods. 2. Samples were distributed to the laboratories. 3. Analyzing the samples: In progress in each participant laboratory. The following data are required: -Number of dicentrics observed in 50 cells/30 dicentrics (triage scoring criteria), 100 cells (as an intermediate step) and 500 cells/100 dicentrics (conventional scoring criteria). In the case of two scorers: cells each; reporting raw data, frequency and standard deviation associated to the observations. -Dose estimates with 95% confidence limits, reporting the calibration curve applied (coefficients and its standard deviations). -Distribution of aberrations in the analyzed cells, relative variance, Papworth u test index. 4. Statistical analysis: The presence of individual laboratories or values that appear to be inconsistent with all other laboratories may change the estimates and thus, decisions have to be taken. To discard or correct inconsistent values, two approaches will be used (ISO /5): -Numerical outlier tests (Cochran and Grubbs tests): To discard data that give rise to a test statistic that exceeds the critical value of the test at the 1% significance level. -Robust methods for data analysis: To yield robust values of the average and standard deviation of the data. 480

5 5. Estimating the mean value and the standard deviation inter-laboratory: To estimate the parameters once outliers are discarded or corrected. 6. Determining laboratory s performance: To calculate parameter from the laboratory results, the reference value and the estimated standard deviation. To determine u-score parameter, which evaluation includes both participant measurements and reference value uncertainties. 7. Reporting results: To allow to implement corrective actions to reinforce service capabilities of the laboratories. PRELIMINARY CONCLUSIONS: Proficiency tests are essential tools for the quality assurance of the laboratories as they constitute an objective evaluation of its performance, from both human and technical point of view. Actions for a steady quality assurance and quality control, such as this Intercomparison exercise, will be the technical support of the LBDNET. Additionally, it will contribute in the accrediting process (ISO 19238:2004 and ISO/IEC 17025:2005 requirements). Keywords: Biological Dosimetry; Intercomparison Exercise; Triage; Statistical Data Analysis 481

6 The participation of Latin- American biological dosimetry laboratories in: Goiania (Brazil) and El Salvador accidents, and more recently, Cochabamba (Bolivia) and Concepcion (Chile) accidents, and Venezuela incidents show that the laboratories have reached a common background level in the organization and in the response in cases of overexposures to IR that have allowed to formalize a LBDNET for cooperation purposes. Two important tasks of the present intercomparison exercise are: 1. Evaluation through triage and conventional scoring criteria: The required data focus on cytogenetic triage (to evaluate approximately and rapidly the radiation doses received by individuals in order to support the clinical categorization of casualties) and conventional dosimetry. The assessment (correlation) of these results would allow to establish the applicability of triage criteria in emergency situations. 2. Development of a new approach for statistical data analysis: A software and Excel tools for data analysis were developed and validated by the organizer and were agreed to by the participant parties (during a meeting held in La Havana - Cuba, November 2007 in the frame of the IAEA Regional Project RLA9/054). It was also decided: a) to use robust methods (Algorithm A). This algorithm yields robust values of the average and standard deviation of the data to which is applied. When robust methods are used, the outlier tests and consistency checks described in ISO or-5 should be applied to the data, and the causes of any outlier should be investigated; 2) to apply z- scores and u- scores for determining the laboratory s performance; u-scores includes uncertainties of the participant measurements and the uncertainty of the reference value. Laboratories performing well in classical proficiency testing will not necessarily exhibit the same level of performance when their analytical uncertainties are considered in the evaluation. 482

7 L5 L1 L6 L13 L11 Latin American Biological Dosimetry Network Intercomparison Exercise Evaluation through triage and conventional scoring criteria Development of a new approach for statistical data analysis M. Di Giorgio, M. Vallerga, A. Radl, M. Taja; A. Seoane; M. Stuck Oliveira; P. Valdivia; O. García Lima, A. Lamadrid, J. González Mesa, I. Romero Aguilera, T. Mandina Cardoso; C. Guerrero Carvajal; C. Arceo Maldonado; M. Espinoza; W. Martínez López, M. Di Tomasso; H. Romm; F. Barquinero; C. Lindholm; L. Roy; I. Güçlü; D. Lloyd - Argentina-ARN, Argentina-UNLP, Brazil-IRD, Chile-CCHEN, Cuba-CPHR, Mexico-ININ, Peru-IPEN, Uruguay-IIBCE; Finland-STUK, France-IRSN, Germany-BfS, Spain-UAB, Turkey-CNRTC, United Kingdom-HPA INTRODUCTION Biological Dosimetry is a necessary support for National Radiation Protection Programs and Emergency Response Schemes. A Latin-American Biological Dosimetry Network (LBDNET) has been constituted by the laboratories from: Argentina, Brazil, Chile, Cuba, Mexico, Peru and Uruguay (IAEA - RLA9/054, 2007) The biological dosimetry laboratory of Argentina organized an international biological dosimetry intercomparison, involving 7 Latin American and 6 European countries, for the analysis of some relevant parameters related with dose assessment, to reinforce the response capability in accidental situations requiring the activation of mutual assistance mechanisms and thus, constituting the bases of the LBDNET organization. Objectives: To evaluate the inter-laboratory reproducibility and intra-laboratory repeatability. To assess the results derived from conventional and triage scoring criteria. To apply an statistical approach for data analysis and performance evaluation based on ISO 43-1:1997, :1998 and 13528:2002 standards. To identify difficulties and provide the necessary modifications for the collaborative task in order to improve the technical quality and competence of Latin American laboratories. RESULTS AND DISCUSSION DI: 0.75 Gy Reproducibility (Algorithm A) 500 cells MATERIALS AND METHODS INTERCOMPARISON PROGRAM Participant laboratories from the LBDNET, Finland, France, Germany, Spain, Turkey and United Kingdom. Human blood samples were irradiated in vitro with a 60 Co source (Regional Reference Center for dosimetry of the Atomic Energy Commission), two points of doses and a control. Cultures and slide preparations were performed according to standard methods. Samples were distributed to the laboratories. Data required: Number of dicentrics observed in 50 cells/30 dicentrics (triage scoring criteria), 100 cells and 500 cells/100 dicentrics (conventional scoring criteria). For intra-laboratory evaluation (2 scorers): cells each; reporting raw data, frequency and standard deviation associated to the observations. Dose estimates with 95% confidence limits, reporting the calibration curve applied (coefficients and its standard deviations). Distribution of aberrations in the analyzed cells, relative variance, Papworth u test index. Data analysis: Robust methods were applied to yield robust values of the average and standard deviation of the data. A consensus value for inter-laboratory frequency results (robust average of the results reported by the participants) and a reference value for dose results (physical dose) were determined. Performance statistics (Z-score and U-score) were applied to the data. DI: 0.75 Gy - Cytogenetic triage Dose [Gy] Estimated 0,75 Gy Physical Dose 1,40 1,20 0,80 0,60 0,40 0,20 L4 L2 L7 L12 L14 L3 L9 L10 L8 Dose values determined by the laboratories with their expanded uncertainties Precision x* ; x*+1.96s* and x*-1.96s* x* ± s* [Gy]=0.744±0.109 Trueness Physical dose [Gy]= 0.75±0.023 Accuracy purpose is met Robust values of the average and standard deviation of the data were applied Dose[Gy] Estimated Estimated Dose ,75 Gy Gy Physical Physical Dose Dose x* ± s* [Gy]=0.749±0.191 L7 L4 L10 L14 L13 L5 L1 L6 L9 L8 L11 L12 L2 L3 50 CELLS 6, ,00 L3,L7 unsatisfactory L4 questionable L3 L13 L5 L1 L6 L9 L8 L11 L12 L2 L10 L14 L4 L L5 L1 L6 L13 L12 L14 L3 L9 L10 L8 L4 L2 L7 L11 z = (x i x ref ) /S* Z 2 satisfactory 2 < Z < 3 questionable - warning signal Z 3 unsatisfactory - action signal L11: questionable Dose[Gy] Estimated Estimated Dose ,75 Gy Gy Physical Dose Dose x* ± s* [Gy]=0.700±0.210 L7 L2 L14 L6 L8 L4 L12 L5 L9 L10 L11 L13 L1 L3 100 CELLS z score L3 unsatisfactory L11, L13, L14 questionable L3 L11 L13 L1 L6 L8 L4 L12 L5 L9 L10 L7 L2 L14 L5 L1 L6 L13 L12 L14 L3 L9 L10 L8 L4 L2 L7 L11 U = x ref x i / (u 2 ref + u 2 i)1/2 : the uncertainty of the participant s measurements result is taken into account for the evaluation of performance U critical value: If u > , the values differ significantly DII: 2.50 Gy - Reproducibility (Algorithm A) 500 cells Dose [Gy] Estimated 2,5 Gy Physical Dose x* ± s* [Gy]=2.315± ,50 L7 L9 L8 L14 L13 L10 L2 L5 L11 L6 L12 L3 L4 L1 DII: 2.5 Gy - Cytogenetic triage 50 CELLS L6, L12, L3,L7 questionable L6 L12 L3 L4 L1 L10 L2 L5 L11 L14 L13 L8 L9 L7 Dose[Gy] Estimated 2,5 Gy Physical Dose 3,50 L9 L4 L13 L3 L5 L6 L14 L1 L10 L11 L7 L2 L8 L12 Dose values determined by the laboratories with their expanded uncertainties x* ; x*+1.96s* and x*-1.96s* x* ± s* [Gy]=2.515±0.204 Physical dose [Gy]= 2.5±0.075 Accuracy purpose is met Dose [Gy] Estimated 2,5 Gy Physical Dose x* ± s* [Gy]=2.486± ,50 L7 L3 L10 L4 L11 L1 L6 L5 L14 L2 L8 L13 L9 L CELLS satisfactory L12 L3 L10 L4 L11 L1 L6 L5 L14 L2 L8 L13 L9 L7 Youden Plot for doses (500 cells) Youden Plot for doses (50 cells) L9: questionable warning signal L12 L4 L13 L3 L5 L6 L14 L1 L10 L11 L7 L2 L8 L9 Repeatability (Algorithm S) 500 cells This algorithm is applied to intra-laboratory standard deviations. It yields a robust pooled value of the standard deviations to which is applied. w*= robust standard deviation of n=2 replicate measurements. Sr= robust repeatability standard deviation = w*/ (n) 1/2 (ISO clause 6.4.1) S R = reproducibility standard deviation (ISO clause ) 8 laboratories presented data for this study DI DII Parameter Frequency Dose Frequency Dose S r S R The reproducibility (inter-laboratory) standard deviation resulted 22% for DII and 11.6% for DI S R and S r for frequencies presented lower values than those for doses L12 L4 L13 L3 L5 L6 L14 L1 L10 L11 L7 L2 L8 L9 DII 2,5 2,0 1,5 1,0 0,5 0,0-3,0-2,0-1,0 0,0 1,0 2,0-0,5-1,0-1,5-2,0 DI CONCLUSIONS Youden Plot: errors seem to be random -3,0-2,0-1,0 0,0 1,0 2,0-0,5 Robust methods (Algorithms A and S) were applied to calculate repeatability and reproducibility standard deviations: S R resulted 22% for DII and 11.6 % for DI. S R resulted greater for dose respect to frequency, indicating a higher dispersion in dose assessment associated with the different criteria applied to convert frequency into dose and to the diversity of calibration curves applied. Intra-laboratory indicated lower dispersion. S r resulted lower for frequencies than for doses. An increased dispersion with dose was observed as expected due to the complexity. Triage criteria: The evaluation of 50 cells (DI) reveled the probability to obtain false negatives as the confidence interval (CI) reaches cero dose in 6 cases. When analyzing 100 cells the CI tended to detach from cero. Overall, the laboratory performance was satisfactory for mutual cooperation purposes. Round exercises are suggested to maintain and reinforce the response capacity of the laboratories. DII 2,5 2,0 1,5 1,0 0,5 0,0-1,0-1,5 DI