The HRI Working Group met again in December 2013 in Sydney to finalise the Paediatric Reference intervals and further review additional data on the Adult Reference Intervals including the potential impact on flagging rates as presented by Dr Ken Sikaris from Sonic Pathology, a major private pathology lab. HRIWG convened in February 2014 to finalise the program and speakers for the 3rd Stakeholder Harmonisation Workshop that was held in Sydney on 30 April and 1 May. 55 delegates representing all the major public and private pathology networks across Australia were presented. This meeting also coincided with a meeting attended by international harmonisation experts who kindly agreed to present at the workshop. Further analysis and group discussions achieved final consensus on the majority of adult and paediatric reference intervals under consideration A full listing of all the Workshop presentations and related outcomes is available on the AACB Website under the Professional Development, Scientific Regulatory Affairs Committee (SRAC) and Harmonisation tab. See also: Project Activity Plan – Appendix 1 Figures 1A and 1B summarise the above evidence based methodologies employed by the Adult and Paediatric HRI Committees. 5.3 Analysis of proposed reference intervals with checklist/ spreadsheet tools and validation of proposed reference intervals A spreadsheet tool (developed by Graham Jones) was disseminated to laboratories across Australia and New Zealand. Laboratories were asked to extract their own data from their laboratory information systems and use the spreadsheet to analyse. The spreadsheet had embedded formulas to enable Bhattacharya analysis of the extracted laboratory data and proved to be a valuable tool for validating the proposed HRI’s.13 The spreadsheet data was then compiled into a master document for further review by the HRIWG. 5.4 Flagging rates An additional tool was introduced at the May 2014 Workshop by Ken Sikaris when he presented an analysis of the impact of the proposed HRI’s on “flagging rates” for Sonic patients. In theory, a workable (95%) reference interval should only flag an abnormal result for 5% (2.5% low and 2.5% high) of the “normal” population. Figure 1A. based / consultation approach for Harmonised Adult Reference Intervals
12 Appendices Appendix 1. HARMONISATION ACTIVITY PLAN June 2013 - June 2014 Objective Activity Milestone to achieve objective Timeframe: expected dura- tion for each activity 1. Assisting laboratories adopt HRIs using a prepared checklist/ spread sheet The HRI checklist needs to be tested by laboratories using their own patient data and modifications made as necessary. To get uptake and adop- tion of this critical step small workshops will be run where representatives from laboratories can be shown how to analyse their own patient data and comparisons can be made between labs. We have budgeted for 3 such workshops to take place in Sydney and Melbourne. In addition we have also budgeted for travel by a relevant expert to individual laboratories All major laboratory networks will have used the checklist to process their patient data and produced Reference Intervals which can be compared to others including current Sonic RIs. Update as at June 2014 All major laboratory networks have reviewed the checklist and their associated data Dr Tina Yen has completed the analysis of the paediatric data submitted by 31 laboratories located across Australia and New Zealand July – December 2013 – completed Completed April 2014 Third Workshop completed May 2014 2. Resolving remaining analytical biases that prevent adoption of HRI Further survey work is be- ing conducted to deter- mine which analytes have analytical biases that might require analyser specific RIs. The results of this work need to be discussed at a face to face workshop similar to the one held by the AACB in 2012. The planned date for this workshop is in the 2nd half of 2013. (i). Completion of bias sur- veys and collation of data by April 2013. - done (ii). Review of results by HRI Working Party of SRAC. - done (iii). Presentation of data and decision on HRIs at workshop with representatives of all major labs/networks. – Presented at the 12 and 13 July Workshops in Sydney - 57 delegates (including clinicians) from major laboratory/ hospital networks across Australia and New Zealand attended. (i). July – September 2013 - done (ii) October 2013 - done (iii) December 2013 - done
Objective Activity Milestone to achieve objective Timeframe: expected du- ration for each activity 3. Collating and disseminating evidence to support adoption of HRI for each analyte Work is proceeding on collation of the evidence for HRIs into a standard template including: laboratory RIs survey data, manufacturers’ RIs, bias assessment results, literature, RI consensus data (e.g. ARQAG, SIQAG), RI formal studies (e.g. Aussie Normals), data mining data from Sonic Health. Once completed this data will need to be presented and reviewed at the HRI Workshop. (i). Completion of HRI template data for each analyte. – Completed, to be updated with December meeting outcomes (ii). Review and discussion at HRI workshop by representatives of all major labs/networks. – Actively discussed at the July HRI workshop – previously reported (i). July 2013 - done (ii). December 2013 - done 4. Review of existing RIs for paediatric patients and decisions on how to harmonise The Paediatric HRI Working Group needs to meet face to face on two occasions in order to discuss the various issues that exist in this area and to make decisions on HRIs for various analytes. (i). 1st meeting of the Paediatric HRI Working Group – proceeded successfully on July 11, 2013 (ii). 2nd meeting of the Paediatric HRI Working Group (iii). Agreement on Paediatric HRIs - data analysis complete (i). August 2013 - done (ii). November 2013- done (iii). May 2014 - done
Appendix 4. Example of method differences that prevent harmonisation (Koerbin, July 2013 Harmonisation Workshop)18 GGT Lipase LD Modular g-Glutamyl-3-Carboxy- Nitoanilide Spectro - Glutaric Acid Ester IFCC Recommended Method Integra g-Glutamyl-3-Carboxy- Nitoanilide Spectro - Glutaric Acid Ester IFCC Recommended Method Vitros g-Glutamyl-3-Carboxy- Nitoanilide Spectro-diacetylglycerol Pyruvate >0.7 mmolar (P-L) Au2700 Mod IFCC (Szasz) 1,2-Diglyceride subst./co- lipase Lactate to Pyruvate (NADH) Abbott g-Glutamyl-3-Carboxy- Nitoanilide Quinone dye Lactate to Pyruvate (NADH) DxC g-Glutamyl-3-Carboxy- Nitoanilide Spectro - Glutaric Acid Ester Lactate to Pyruvate (NADH) Advia g-Glutamyl-3-Carboxy- Nitoanilide Spectro - Glutaric Acid Ester Lactate to Pyruvate (NADH)