Quality and uncertainty in screening assays from taking the sample - PowerPoint PPT Presentation

Quality and uncertainty in screening assays from taking the sample to issuing the result Prof Jim Bonham Laboratory lead PHE Screening

Outline Ensuring that the testing operates smoothly as a programme not just a test Sample quality Assay quality and population monitoring Sample transport Reporting results and confirmatory testing

The quality of the spot xLeu: The edge of a large spot vs the centre of a small spot, approx 35% difference at 400 µmol/L ie 10 µL 20 µL 50 µL 75 µL +/- 70 µmol/L K Hall : 2014, personnel Communication

Blood Spot Quality

Blood spot quality Baby X Card 1 Front Back • Date of Birth 17/10/15 • Date of Specimen 22/10/15 (Day 5) • Received in laboratory 23/10/2015 (Friday) and processed. • Results reviewed on 26/10/2015 (Monday). • Poor quality spot (probably spot 1). • Result: C8= 0.39 Near Miss: A False Negative MCAD Screening Test Due To A Poor Quality Blood Spot

Blood spot quality Baby X Card 2 Front Back • An urgent repeat sample was requested by phone. • Received and analysed 26/10/15. • Results: C8= 0.66 C10= 0.3 C8:C10 = 2.2 • Referral was made 18:49 26/10/15. Baby was seen on the 27/10/2015. • Near Miss: A False Negative MCAD Screening Test Due To A Poor Quality Blood Spot

Method performance EQA experience • Leu (n=273), mean 168 µmol/L UL(95%) 231, LL (95%) 104 • C5 (n=268), mean 2.0 µmol/L UL(95%) 2.7, LL (95%) 1.4 • Met (n=261), mean 21 µmol/L UL(95%) 28, LL (95%) 13 • C5DC (n=275), mean 2.1 µmol/L UL(95%) 3.7, LL (95%) 0.40 CDC QAP Q3 2014

What have we done – population monitoring? • Each lab submits data and receives monthly and quarterly report • Reports are summarised by analyte • Snapshot of how one lab compares to another • Box whisker plots - scaled to analytical cut-off value Gives 10 th , 50 th , 90 th and 99 th centiles for each lab relative to “all • labs” data • Results split by instrument for each lab • Useful for identifying any significant bias • Regular meetings to discuss performance

What do we find - assay quality Xle - Feb 2016 C5 - Feb 2016 500 1 450 0.9 400 0.8 350 0.7 µmol/L 300 0.6 µmol/L 250 0.5 200 0.4 150 0.3 100 0.2 50 0.1 0 0 B B C C G G L L L M N O O P P S S V V A a e e i h B B C L L L M N O O S V V i r i r a v e x x o o t i i l C G G P P S A O O e e a a a e e i m m r e f f e l i i a a o o h t i i m w r r H p p r r O O v e x x l d S S d d n o o L r e e a e a a l r t t f m m m e w f f H H H c c s s f e a a a d n r r p p i i b i s s p r r S S d d o o t t f L n n f m m i r f h a d d e l t t b H H c c s s f e a a a r 1 2 o i h h i i b i f s s p r r i g g i 1 2 s e s n n h a d d m m l t t b 1 o e 1 2 l r f e i h h d t o o d 1 2 o h h s r 1 2 g g i 1 2 e s l e s g l l u u 1 o 1 2 a a t h h d t o o d r e 1 1 s 1 2 e 1 e t t g l l u u m m a a t e 1 h h 1 1 r e 1 e 2 m m t t 1 h h 1 2 1 1 2 r 2 1 2 1 1 2 Met - Feb 2016 45 40 35 30 µmol/L 25 20 15 10 5 0 B B C C G G L L L M N O O P P S S V V A a e e i h i i a v e x x o o t i i l r r O O a a a r e e e l m m m e w f f r r H p p d d d n o o L S S r t t f e a i i b i H H s s p c c r r s s f a a n n f i h a d d m m e l t t b r f o i g g 1 2 1 2 e h h i 1 e s l s d o 1 2 o o d h h t r s 1 2 g l l u u a a t e 1 1 e 1 m m e t t r 1 h h 2 1 1 2 1 2 Near Miss: A False Negative MCAD Screening Test Due To A Poor Quality Blood Spot

What can we do? Conclusions • The ENBS programme is not unsafe Analytical cut-offs generally well removed from 90 th centiles • Methionine is the exception but 2 nd tier testing is part of screening protocol • There is potential for false positives and unnecessary referral of babies and possibly false negatives • Harmonisation of ENBS should improve to maintain common cut-off values – common internal standard study • Co-ordination of approach at kit lot change - IRTs

Transport 2013/14

Results reporting Are the diagnostic (confirmatory) tests agreed? � Diagnostic protocol Are the results timely with clear metrics? � Quality dashboard Are the qualitative reports eg organic acids clear and unambiguous when they arrive? � No agreed standards in terms of layout or content � No training � No EQA or IQC � No user surveys � A variety of practice Can we support patients more effectively during this time of uncertainty? � Provision of information – an App with high quality information that is readily accessed � Thought about the processes of information receipt