Comparison of FIT performance in screening programs. Carlo Senore

Transcription

1 Comparison of FIT performance in screening programs

2 Possible conflicts of interest None related to the presentation

3 Background Several FIT kits are now available Various FIT brands use a variety of sampling techniques and they report faecal Hb concentration in different units. It was proposed to standardize quantitative FIT results, to allow direct comparisons of tests performance using the same standardised cut-off. Fraser C et. Al. JNCI 2012 We need comparative data to orient the choice of the kit to be used in population based programmes, as well as to set criteria to inform tendering procedures. Comparative information are however limited.

4 Aims Systematic review of comparative studies of FIT performance, conducted in the context of population based CRC screening programs,

5 Research question Average risk subjects aged 50 to 74, screened within population based screening programs (including pilot studies) Comparative studies of FIT versus gfob other FIT same FIT, different positivity cut-off Experimental studies (RCT parallel arms; paired design) Outcomes: positivity rate (PR); positive predictive value (PPV) and detection rate (DR) of advanced adenomas and CRC.

6 Methods Literature search and selection of studies meeting the inclusion criteria Data extraction to calculate the indicators Within-test (OC Sensor) analysis of factors influencing test performance Comparison of tests performance using normalized cut-off - µg/g faeces (between tests analysis)

7 Literature search

8 Meta-regression OC Sensor Predictors Positivity rate % CRC Round 2 vs 1 Cut off >20 vs <=20 Country Italy, Spain vs Netherlands, France -1,76 (-2,64; -0,89) -2,66 (-3,52; -1,79) -0,71 (-1,72; 0,30) -2,20 (-2,52; -1,88) -0,27 (-0,60; 0,06) -1,19 (-1,58; -0,80) Detection rate Positive Predictive Value % Advanced adenoma -11,55 (-14,67; -8,42) -6,86 (-10,04; -3,69) -6,32 (-10,07; -2,58) CRC -1,57 (-2,57; -0,57) 3,70 (2,69; 4,72) -2,36 (-3,56; -1,17) Advanced adenoma -5,46 (-8,73; -2,19) 3,47 (0,15; 6,80) -8,80 (-12,72; -4,88) Round 2 vs 1-1,84 (-2,68; -0,99) -2,30 (-2,64; -1,95) -12,05 (-15,28; -8,81) -1,74 (-2,83; -0,66) -6,05 (-9,85; -2,24) Cut off >20 vs <=20-2,68 (-3,50; -1,85) -0,21 (-0,55; 0,13) -6,46 (-9,70; -3,23) 3,91 (2,82; 5,00) 4,48 (0,68; 8,29) Age > 69 Yes vs No 0,94 (-0,06; 1,94) 1,18 (0,75; 1,60) 5,93 (1,92; 9,94) 1,98 (0,63; 3,32) 6,32 (1,60; 11,04)

9 Predictors Positivity rate % CRC Round 2 vs 1 Cut off >20 vs <=20 PR Meta-regression OC Sensor <=3.5, >3.5<=5.6, >5.6 Detection rate Positive Predictive Value % -1,98 (-2,63; -1,34) 0,14 (-0,48; 0,76) 0,16 (-0,29; 0,61) Advanced adenoma -7,94 (-12,48; -3,41) -2,41 (-6,76; 1,93) 3,58 (0,41; 6,75) CRC -2,54 (-4,09; -0,99) 3,32 (1,84; 4,81) -1,16 (-2,25; -0,08) Advanced adenoma -9,28 (-14,57; -3,99) 4,43 (-0,64; 9,50) -2,67 (-6,38; 1,03) Adjusting for screening history and cut-off level, a higher proportion of men in the study cohort, or a higher background incidence rate, are associated with an increase in the CRC detection rate only

10 Comparing different tests Comparative studies of different FIT brands have been generally focused on the determination of the optimal cutoff value. Recent reports have however suggested that different quantitative FIT brands may perform differently even when using standardised cut-off values. Performance tends to become more similar when considering the same positivity rate (Chiang et al. 2014; Grobbee et al. 2016; Passamonti et al. 2017) Comparing tests performance at the same positivity rate provides crucial information to program planning: PR directly reflects the required colonoscopy capacity/workload Combining PR and PPV we can also derive an estimate of the expected DR for a similar number of endoscopies,

11 9,0 8,5 8,0 7,5 7,0 6,5 6,0 5,5 5,0 4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0 PR 9,0 8,5 8,0 7,5 7,0 6,5 6,0 5,5 5,0 4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0 MAG67 OC10 OC15 OC25 MAG103 MAG130 OC20 OC35 OC30 OC MAG67 PPV MAG103 MAG130 PPV 20,0 22,5 25,0 27,5 30,0 32,5 35,0 37,5 40,0 42,5 45,0 47,5 50,0 OC10 OC15 OC25 OC45 OC20 OC30 OC35 OC40 OC45 First screening CRC Advanced adenoma North

12 8,5 8 7,5 7 6,5 6 5,5 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 OC10 FOB17 FOB20 FOB25 PPV OC20 FOB30 FOB35 MAG80 FOB40 OC30 FOB50 MAG180 FOB60 MAG PR 8 OC10 7,5 OC45 OC68 OC60 Subsequent screening CRC North 7 6,5 6 5,5 5 4,5 4 3,5 3 2,5 2 1,5 1 FOB40 FOB50 FOB60 FOB17 MAG80 MAG180 MAG210 FOB20 OC20 OC30 FOB25 FOB30 FOB35 OC45 OC60 OC68 Advanced adenoma 0,5 0 PPV 20 22, , , , , ,5 50

13 9,0 8,5 8,0 7,5 7,0 6,5 6,0 5,5 5,0 4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0 9,0 8,5 8,0 7,5 7,0 6,5 6,0 5,5 5,0 4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 JACK20 PPV JACK20 FOB17 OC15 OC20 FOB17 OC15 OC20 OC25 OC25 PPV 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 5,5 6,0 6,5 7,0 7,5 8,0 PR 15,0 17,5 20,0 22,5 25,0 27,5 30,0 32,5 35,0 37,5 40,0 42,5 45,0 First screening CRC Advanced adenoma South

14 7 6,5 6 5,5 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 PR 7 6,5 6 5,5 5 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 PPV OC20 JACK28 JACK20 JACK40 FOB17 1 1,5 2 2,5 3 3,5 4 4,5 PPV JACK20 OC20 JACK28 JACK40 FOB , , , ,5 Subsequent screening CRC South Advanced adenoma

15 Multivariable analysis Only studies adopting a single sample protocol Only tests assessed in several studies : OC-Sensor, FOB-Gold, Magstream, HM Jack Normalized cut-off - μg Hb/g. faeces - to ensure comparability

16 Multivariable analysis Coefficient; P>t DR CANCER OC-Sensor 1.0 (ref) Fob Gold 0.02; 0.92 Magstream -1.76; 0.00 JACK 0.48; 0.36 DR ADVANCED ADENOMA OC-Sensor 1.0 (ref) Fob Gold -0.32; 0.81 Magstream -5.65; 0.00 JACK -0.29; 0.94 PPV CANCER OC-Sensor 1.0 (ref) Fob Gold -1.14; 0.03 Magstream -4.52; 0.00 JACK -2.49; 0.07 PPV ADVANCED ADENOMA OC-Sensor 1.0 (ref) Fob Gold -5.78; 0.01 Magstream ; 0.00 JACK -7.81; 0.17 Model adjusted for round, cut-off, age, country and positivity rate

17 Limitations Limited number of studies for some tests Innovation is changing the picture Classification of advanced adenomas as well as of screening history was not homogeneous across studies

18 Conclusions 1 - reporting Ideal study design should ensure to get information about comparative performance by gender, age and screening history Need to standardize definitions of - advanced adenomas - screening history using the number of tests instead of the number of rounds. Colonoscopy rates should be reported Modified from Moss S. et al. 2016

19 Conclusions 2 choosing the outcome Comparisons of PPV at pre-specified positivity rates. As long as colonoscopy capacity is often the main determinant of the sustainability of a population based screening program, information about PR and PPV are crucial when implementing a program, or when considering changing the test, to favor an efficient utilization of limited endoscopy resources. Our analysis confirms the findings from previous reports showing that test performances may still be different when using the same standardised cut-off

20 Conclusions - 3 Do we need to adopt a different approach to standardize the reporting of the results of measurements of fecal hemoglobin concentration? It has been recently suggested to use mass of hemoglobin per volume of feces and not mass of hemoglobin per mass of feces: micrograms hemoglobin per milliliter of feces (µg Hb/mL feces) (Fraser C et al. JNCI 2016)

21 ACKNOWLEDGEMENTS The project was conducted within the Italian group for CRC screening (GISCoR ww.giscor.it) Co-authors Deandrea Silvia 1, Rubeca Tiziana 2, Anghinoni Emanuela 3, Randi Giorgia 1, Rapi Stefano 4, Bencivenni Sofia 5, Corradini Rosssella 6, Passamonti Ubaldo 7, Sassatelli Romano 8, 1 European Commission, DG Joint Research Centre (JRC), Ispra (VA), Italy 2 Cancer Prevention and Research Institute (ISPO), Florence, Italy 3 ASL Mantova, Mantua, Italy 4 Careggi Hospital, Florence, Italy 5 ULSS 9 Scaligera, Bussolengo (VR), Italy 6 AUSL Modena, Modena, Italy 7 AUSL 2 Perugia, Perugia, Italy 8 IRCCS Arcispedale S. Maria Nuova, Reggio Emilia, Italy

22 THANK YOU FOR YOUR ATTENTION

23 Test name Producer Type of test Detection Method Study N OC Light Eiken Chemical qualitative immunocromatography 1 Hemeselect Smith Kline Diagnostics qualitative RPHA 2 Instant-view Alpha Scientifics Designs, Inc. qualitative immunocromatography 1 FlexSure OBT Beckman Coulter/Smith Kline Diagn. qualitative colorimetric reaction 1 InSure Quest Diagnostics (Enterix) qualitative immunocromatography 2 OC SensoMicro (OC-Hemodia) OC Sensor Diana Magstream 1000 Eiken Chemical quantitative latex immunoturbidimetry 7 Eiken Chemical quantitative latex immunoturbidimetry 1 Fujirebio quantitative magnetic particles 4 FOB Gold Sentinel Diagnostics quantitative latex immunoturbidimetry 4 HM-JACKarc Kyowa MedexCo Ltd quantitative latex immunoturbidimetry 1 Name of presenter