SOLO subproject 3: Pooled analysis of plutonium worker cohorts

Work package 3.1. Feasibility study: harmonising dosimetry data

Objectives:

To develop the methodology and approaches to be used for dose reconstruction for the proposed pooled epidemiological analysis of the Mayak and Sellafield Worker cohorts. Specifically, this research is directed toward a harmonisation of the overall approach to the internal dosimetry of plutonium and concentrates on: increased accuracy, a reduction of systematic bias; a reduction and quantification of uncertainties, in relation to the production of dose estimates for the proposed epidemiological analysis. This Work Package will result in a common internal dosimetry protocol that will be used as the basis of dose reconstruction for the Mayak and Sellafield cohorts under WP3.3.

Task 3.1.1 Analysis of the utility of existing bioassay data for reconstructing plutonium doses for Mayak workers (SUBI, HPA, UNIMAN)

The following sub-tasks will be conducted:

- analysis of the current SUBI database to identify workers with results obtained using the early, less reliable, methods and also more recent state-of-the-art techniques of radiochemical analysis;

- analysis of results on the DTPA enhanced rate of plutonium excretion in urine; refinement and verification of plutonium excretion enhancement factors;

- quality assessment of the effect on dose estimates of using plutonium bioassay monitoring data obtained using different (early and current) techniques of radiochemical measurement.

- assessment of the efficiency (scope and costs) of additional monitoring for the Mayak workers;

drawing up a list of the Mayak workers requiring additional measurements for improvement of dose estimates.

- identification of an optimal procedure for bioassay monitoring and applied measuring instrumentation; evaluation of the costs for additional measurements.

Task 3.1.2 External dosimetry review (UNIMAN, SUBI)

The compatibility of the external dosimetry systems used for the Mayak and Sellafield cohorts will be reviewed. In order to conduct this external dosimetry review, in the most scientific and cost-effective way, a recognized external dose expert who already has knowledge of historic Mayak dosimetry systems, through USDOE funded research, will be used on a sub-contract basis.

Task 3.1.3 Approaches to the calculation of doses to systemic organs (liver and skeleton) (HPA, SUBI, UNIMAN)

The following sub-tasks will be conducted:

Task 3.1.4 Approaches to the calculation of lung doses (HPA, SUBI, UNIMAN)

Knowledge and data held by the United States Transuranium and Uranium Registries (USTUR) on organ and tissue content of plutonium have been identified as being of direct relevance to the work on improved plutonium dosimetry methodology to produce best estimates of dose. Therefore, it is planned to make provision to include USTUR within the project through a sub-contract.

Task 3.1.5 Application of uncertainties (HPA, UNIMAN, SUBI)

Task 3.1.6 Harmonization of approaches to dose reconstruction (HPA, UNIMAN, SUBI)

- drawing a list of parameters for harmonization;

- inter-laboratory comparison of dose estimates;

- comparative analysis of dose estimates for two facilities, identification of the priority parameters for harmonization of dosimetry systems.

Work package 3.2. Feasibility study: harmonising health data

Objectives:

To conduct a feasibility study on the harmonisation of health data, specifically non-cancer and cancer mortality and cancer incidence data, for the Mayak and Sellafield plutonium workers.

To develop an outline and agreed final Research Study Protocol for a pooled analysis of plutonium worker cohorts.

To obtain appropriate consents and permissions and sufficient harmonisation of data to undertake a pooled analysis of plutonium worker cohorts.

Task 3.2.1 Written description of procedures for acquiring ICD coded non-cancer and cancer mortality and cancer incidence data (SUBI, UNIMAN, HPA)

A comprehensive written description of the procedures used for acquiring ICD coded non-cancer and cancer mortality and cancer incidence data for Mayak and Sellafield workers, will be produced. (Mayak workers deaths and cancer registrations 1948-2008, Sellafield workers deaths 1946-2008, cancer registrations 1971-2008). This will include, a complete history of change in procedures over time, together with full descriptions of the non-cancer and cancer mortality and cancer incidence data received, e.g. data items provided, data form (hard copy / electronic), data coding procedures, etc.

Task 3.2.2 Outline Research Study Protocol for a pooled analysis of Mayak and Sellafield plutonium worker cohorts (HPA, UNIMAN, SUBI)

An Outline RSP for a pooled analysis of the Mayak and Sellafield plutonium cohorts will be produced. The Outline RSP will include a Statistical Analysis Plan (SAP), a Data Management Plan (DMP), a review of availability of non-radiation health data, and a mechanism for dissemination of results. The DMP will describe how available ICD coding revisions for non-cancer and cancer mortality and cancer incidence data will be catalogued by calendar period (task 3.2.4) and the subsequent ICD coding to achieve consistent ICD coding revision and level of coding across Mayak and Sellafield non-cancer and cancer mortality and cancer incidence data (task 3.2.5).

Task 3.2.3 Final Research Study Protocol for a pooled analysis of Mayak and Sellafield plutonium worker cohorts (HPA, UNIMAN, SUBI)

A Final RSP for a pooled analysis of Mayak and Sellafield plutonium worker cohorts will be agreed by Month 36. The Final RSP will be submitted to a REC and the national tracing organisation, the NHS-IC, to obtain full permissions for the study. The Final RSP will include, a SAP, DMP, a review of availability of non-radiation health data, and mechanisms for dissemination of results. To ensure continued support and permissions for the study, study progress will be reported routinely to the REC through their reporting mechanism.

Task 3.2.4 Catalogue of available ICD coding revisions, by calendar period, for non-cancer and cancer mortality and cancer incidence data (SUBI, HPA)

For both death certificates and cancer registrations, we will identify and catalogue all available ICD coding revisions, by calendar period, from 1946 to 2008. The catalogue will also include the level of ICD codings available. That is, formortality: underlying cause only, underlying plus associated causes, and for morbidity: cancer site ICD code only, cancer site plus ICD morphology code. The use and availability of the ICD sub digit and the morphology code 5th digit behaviour code will also be established. This complete catalogue of available ICD coding revisions and level of coding, will identify all ICD coding inconsistencies between Mayak and Sellafield non-cancer and cancer mortality and cancer incidence data.

Task 3.2.5 ICD coding to consistent ICD revision and level of coding (SUBI, HPA)

Having identified all death certificate and cancer registration data with inconsistent ICD coding revision and/or level of coding, a coding exercise to attain full compatibility of ICD coding will follow. Firstly, where differences in ICD coding revision and/or level of coding exist, agreement for re-coding will be reached between SUBI and HPA. SUBI and HPA will then re-code their worker death certificate and cancer registration data accordingly in order to achieve full compatibility of ICD coding revision and level of coding. Note: Leukaemia and lung cancer mortality, cancer incidence data and circulatory disease mortality, will have priority for re-coding to compatible ICD coding revision and level of coding.

Task 3.2.6 Establish what needs to be done, e.g. cross-checks, to ascertain compatibility of ICD coded non-cancer and cancer mortality and cancer incidence data (SUBI, HPA, UNIMAN)

In addition to ensuring that the use and level of ICD codings is compatible, cross-checks will be identified to ascertain the consistency of coding to ICD. That is, to establish how any one death certificate or cancer registration has been coded. This will identify issues such as different interpretations of ICD coding rules, use of in-house rules for the selection of a particular body system, e.g. diseases of the respiratory system compared with certain infectious and parasitic diseases, introduction and use of additional internal ICD codes, handling of external causes of morbidity and mortality coding.

Task 3.2.7 Obtain all necessary consents and permissions for the Mayak and Sellafield study to be undertaken on a legal, consented and ethical basis (SUBI, UNIMAN, HPA)

The agreed Final RSP will be submitted to appropriate REC(s) for permissions for the study to proceed. To ensure this work is undertaken on a legal, ethical and consented basis, appropriate consents and permissions will need to be obtained.

Work package 3.3. Calculation of dose estimates and consideration of uncertainties

Objectives:

To develop validated systems to produce the estimates of dose, and associated uncertainties, for Mayak and Sellafield workers according to the common internal dosimetry protocol developed under WP3.1. Produce the estimates of dose and associated uncertainty required for the proposed pooled epidemiological analysis of the Sellafield and Mayak worker cohorts and validate them.

Task 3.3.1 Development of Plutonium Dosimetry Code (HPA)

Task 3.3.2 Investigation of the use of autopsy data for correct estimation of doses from incorporated plutonium (SUBI, HPA)

Task 3.3.3 Validation of implementation of protocol (doses and uncertainties) (SUBI, UNIMAN, HPA)

Task 3.3.4 Dose reconstruction for cohorts (SUBI, HPA)

Task 3.3.5 Validation of results (SUBI, UNIMAN, HPA)

Perform random independent validation of dose estimates produced.

Work package 3.4. Preliminary pooled analysis

Objectives:

  1. To ensure all consents and      permissions are in place and build the analysis database
  2. To study the dose-response      relationship between external dose and plutonium red bone marrow doses and      leukaemia mortality and/or cancer incidence. To examine the internal      consistency of these results, assess the changes in risks from using other      dosimetry systems and compare with published results.
  3. To study the dose-response      relationship between external dose and plutonium lung doses and lung      cancer mortality and/or cancer incidence. To examine the internal      consistency of these results, assess the changes in risks from using other      dosimetry systems and compare with published results.
  4. To study the dose-response      relationship between external dose and plutonium soft tissue doses and all      circulatory diseases mortality. To assess the changes in risks from using      other dosimetry systems and compare with published results.

Task 3.4.1: The database for the joint analyses has to be built and populated with data. Stakeholders have to be informed that the study is now underway.

Task 3.4.2: External and plutonium red bone marrow dose-response relationships will be evaluated through Excess Relative Risk, Excess Absolute Risk and Dose Window modelling of leukaemia mortality and/or cancer incidence analyses. Effect modification by gender, attained age and age at first exposure will be studied. All leukaemia other than CLL, CLL and myeloid leukaemia will be the outcomes studied. Cancer incidence and mortality results from the joint analyses will be compared with the separate Mayak and Sellafield results, and all results will be compared with Mayak and Sellafield worker results in the scientific literature.

Task 3.4.3: External and plutonium lung dose-response relationships will be evaluated through Excess Relative and Excess Absolute Risk modelling of lung cancer mortality and/or cancer incidence analyses. Effect modification by gender, attained age and age at first exposure will be studied. All lung cancers and lung cancers by morphology codes, including adenocarcinomas, will be the outcomes studied. Cancer incidence and mortality results from the joint analyses will be compared with the separate Mayak and Sellafield worker results and all results will be compared with the Mayak and Sellafield worker results in the scientific literature.

Task 3.4.4: External and plutonium soft tissue dose-response relationships will be evaluated through Excess Relative and Excess Absolute Risk modelling of all circulatory diseases mortality. All circulatory diseases mortality results from the joint analyses will be compared with the separate Mayak and Sellafield worker results and all results will be compared with Mayak and Sellafield worker results in the scientific literature.

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SOLO Project Meetings 2010 - 2015

1. 26-29 April 2010: Oxford, UK - hosted by HPA CRCE

2. 12 November 2010: Chelyabinsk, RU - hosted by URCRM

3. 14-17 March 2011: Lyon, FR - hosted by IARC

4. 19-22 September 2011: Chelyabinsk, RU - hosted by SUBI

5. 26-29 March 2012: Rome, IT - hosted by ISS

6. 4-7 March 2013: Brussels, BE - hosted by EC DG R&I

7. 10-13 March 2014: Munich, DE - hosted by HMGU

8. 16-19 February 2015: Oxford, UK  -  hosted by PHE CRCE