[2000] A Pragmatic Approach to Assay Selection: Comparison of In-House Validated Assays Versus CE-IVD Assays for the Analysis of High-Throughput Molecular Theranostic Assays

Cathal O'Brien, Elaine Logan, John Gibbons, Orla Sheils, Stephen E Langabeer, Stephen P Finn. St James's Hospital, Dublin, Ireland; Trinity College, Dublin, Ireland

Background: The recent growth and expansion of molecular pathology has encouraged a concomitant growth in the range and variety of ready-to-use CE-IVD marked assays. This increased availability of off-the shelf assays begs the question: Is it better to use in-house or CE-IVD marked assays for routine laboratory use? To find an answer to this question we designed and conducted a framework based evaluation of two comparable methods for the detection of KRAS gene mutations in colorectal carcinoma.
Design: A multifacted evaluation of two KRAS mutation detection methods – a CE-IVD marked assay and an in-house assay – was conducted to determine the optimum assay for our production environment. The analysis incorporated five sequential steps
1) An unbiased literature review based on a modified ACCE system was conducted and used to identify decision criteria for assay selection.
2) Method evaluations were carried out to ensure that the assays met the decision requirements of the laboratory.
3) Failure Mode and Effects Analysis (FMEA) was conducted for each assay.
4) A cost benefit analysis (CBA) was performed for both assays.
5) Assay suitability decision in consultation with laboratory director.
Results: In-house evlauation coupled with the decision criteria from the literature identified that both assays were sufficiently sensitive and had an adequate reporting range to satisfy drug adminsitration criteria. FMEA analysis showed that the in-house assay carried a greater risk of producing an incorrect result. For example, the in-house assay required approximately 435 liquid handling steps versus 58 manual liquid handling steps for the CE-IVD assay (based on a 6 sample batch size). A complete analysis of staff time and reagent costs was also undertaken which showed the reagent cost per result to be comparable between assays at the expected normal batch size. However, the in-house method required a greater staff cost.
Conclusions: By using a thorough, predifined assessment schema, we were able to conclude that the CE-IVD marked assay meets more of the requirements of our laboratory. Traditionally, method evaluations tend to focus on the analytical sensitivity of the assay or the clinical sensitivity and specificity. The above framework takes all of these factors into consideration but utilises FMEA and CBA to supplement the decision making process. This results in an assessment that accounts for all aspects of assay performance.
Category: Quality Assurance

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 281, Tuesday Morning


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