Can you prove the accuracy of your assay?
‘Data accuracy’ has been ranked as the most important attribute by the sequencing community (see figure below). However, the challenges facing laboratories in achieving this goal are highlighted in a recent worldwide EGFR Proficiency Testing Scheme and can be read in my previous post here. Only 70% of the laboratories passed the EQA in line with the findings of other previous EQA schemes (KRAS & BRAF)3.
Accuracy ranked highest in importance for users of next-generation sequencing systems. NOTE: Based on a survey of 108 end users. SOURCE: Frost & Sullivan
Perhaps reference materials provide the answer and there are many different available: Synthetic reference standards for example provide a renewable source (such as oligonucleotides/plasmids), however they tend to amplify more easily than equivalent template from cellular sources creating false-confidence in molecular assay workflows. Alternatively, patient-derived materials provide the ‘Gold Standard’ but come with a high degree of variability and are limited in supply which prohibits their daily use.
Therefore, laboratories face the challenge of sourcing reference materials that truly reflect patient samples with a defined copy number, precise allele burden and mimics genome complexity and tumour cell genetics, but are also renewable, consistent and reproducible.
Laboratory Developed Tests (LDTs) – What is their importance?
The vital information gained from clinical laboratory tests is now influencing approximately 70% of health care decisions with 6.8 billion clinical laboratory tests being performed in the United States annually alone1.
Due to the large influencing power on the ‘health care decision making’, the FDA on October 3, 2014, formally issued guidance: the “Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)” presents the details of a risk-based framework for regulating LDTs in three distinct categories due to four key reasons.
- UnitedHealth Center for Health Reform and Modernization, “Personalized Medicine: Trends and prospects for the new science of genetic testing and molecular diagnostics,” Working Paper 7, March 2012, http://www.unitedhealthgroup.com/~/media/uhg/pdf/2012/unh-working-paper-7.ashx.
- Patton, S; Normanno, N; Blackhall, F; Murray, S; Kerr, K’ Dietel, M; Filipits, M; Benlloch, S; Popat, S; Stahel, R and Thunnissen, E. Assessing standardization of molecular testing for non-small-cell lung cancer: results of a worldwide external quality assessment (EQA) scheme for EGFR mutation testing. British Journal of Cancer (2014) 111, 413–420 | doi: 10.1038/bjc.2014.353
- Deans ZC, Bilbe N, O’Sullivan B, Lazarou LP, de Castro DG, Parry S, Dodson A, Taniere P, Clark C, Butler R (2013) Improvement in the quality of molecular analysis of EGFR in non-small-cell lung cancer detected by three rounds of external quality assessment. J Clin Pathol 66: 319–325.