davis inpatient xpert - 13mayl2013long - california ... j.#lucian#(luke)#davis,#md,#mas#...
TRANSCRIPT
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J. Lucian (Luke) Davis, MD, MAS Division of Pulmonary & Cri>cal Care Medicine
San Francisco General Hospital May 30, 2013
Xpert MTB/RIF in the inpa3ent se5ng: A High Value Proposi3on
Breakout Session: U>liza>on of NAATs for TB Control A few ques3ons and a few poten3al answers
• What are NAATs and why aren’t we using them?
• What’s Xpert and how does it perform?
• Respiratory isola3on: is the juice worth the squeeze?
• Can Xpert have an impact in this se5ng?
– Performance at San Francisco General Hospital – Cost-‐benefit analysis
NAATs have been recommended for a long 3me
microfluidics.stanford.edu
Because of high accuracy and poten3al impact
Greco et al Thorax. 2006
Catanzaro et al JAMA 2000
NAATs uncommonly used in rou3ne prac3ce
High costs and anecdotal concerns about accuracy
Lab barriers
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Clinician barriers
With permission, www.cartoonstock.com
Diagnos3c accuracy of Xpert MTB/RIF NAAT
(n=8)
(n=10)
CDC: NAATs for all?
More evidence of clinical and public health impact needed
Inpa3ent evalua3on of possible infec3ous TB
• “All pa3ents with suspected or confirmed infec3ous TB disease should be placed under airborne precau3ons un3l they have been determined to be noninfec3ous”
Jensen PA et al MMWR Recomm Rep. 2005
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Impact of isola3on algorithm on hospitals
Hospital Years AFB+ Mtb Cx+ Pa>ents tested/year
Excess annual isola>on days
Vancouver General1 2003-‐07 2.2% 1.2% ~1000 ≥1960
Jackson Memorial, Miami2 1996-‐97 ~6.0% 9.6% ~1400 ≥2600
St. Luke’s, New York City2 1995-‐96 ~4.2% 6.7% ~700 ≥1300
Univ of Iowa, Iowa City3 1987-‐92 0.8% 1.1% ~800 ≥1580
1. Wilmer A et al Can J Infect Dis Med Micro 2011 2. Tokars JI et al Infect Control Hosp Epidemiol.2001 3. Scon B et al Arch Intern Med 1994
≥ 90% in respiratory isola>on do not have TB
NAAT as a replacement for sputum smear?
Inpa3ent study design Inpa3ent study measures and outcomes
Two poten3al ways to provide Xpert tes3ng
• Processed Assay (Pa3ent admined to await results)
Sputum
Sputum
• Direct Assay (Pa3ent waits for results in ED)
Inpa3ent enrollment flow diagram
155 excess sputum pellets available
30 not Xpert tested -‐28 QNS -‐2 other 1 Xpert invalid 2 Xpert errors 16 one smear result
106 sputa tested
7 AFB smear-‐posi3ve 99 AFB smear-‐nega3ve
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Characteris>c (N=103)*
N (%)
Median age, years (IQR) 52 (43-‐59)
Women 24 (23)
HIV+** 32 (31)
Homeless 15 (15)
Died 5 (5)
Median length of stay, days (IQR)*** 5 (4-‐10)
Induced sputum 29 (28)
Tracheal aspirate 6 (6)
Pa3ent characteris3cs
*3 pa3ents admined 2x **10 missing ***5 missing discharge date
Diagnos3c accuracy (N=106)
TP FP
FN TN
Mtb Cx posi>ve
Mtb Cx nega>ve
Smear Posi>ve
6 1
Smear Nega>ve
1 98
Mtb Cx posi>ve
Mtb Cx nega>ve
Xpert Posi>ve
6 0
Xpert Nega>ve
1 99
1 1 0 1 0 0
Sensi>vity 86% (42-‐100) Sensi>vity 86% (42-‐100)
Specificity 99% (95-‐100) Specificity 100% (96-‐100)
PPV 86% (42-‐100) PPV 100% (54-‐100)
NPV 99% (95-‐100) NPV 99% (95-‐100)
Processed Xpert
Direct Xpert
Stepwise processing 3mes from admission
Added Hours*
16 (7-‐36)
+1 (0-‐6)
+10 (9-‐11)
+14 (13-‐15)
+24 (13-‐25)
*Median (IQR)
Smear ordered
Sputum reaches lab
Sputum processed
1st smear result
Final smear diagnosis
Smear Total 64 (52-‐85)
33 (27-‐52)
5 (3-‐9)
Respiratory isola3on u3liza3on saved
versus AFB smear x 2
Hours per pa>ent (IQR)
Total days per year* (95% CI)
Processed Xpert 35 (33-‐37)
197 (168-‐226)
Direct Xpert 45 (39-‐47)
255 (226-‐285)
*Extrapolated from 1st 9 months of data
Decision Analysis
Smear Microscopy Strategy
Xpert Strategy
Let’s Compare • Cost ($) • Hospital Days • Isola>on Days
Probabilis3c inputs Variable Base Value Range Epidemiologic Parameters TB prevalence (%) 6.4 0.5-‐15 Propor3on admined 9a – 4p (%)† 24 10-‐50 No admi5ng indica3on except TB evalua3on (%) 13 0-‐25 Number of annual inpa3ent TB evalua3ons 234 50-‐1000 Diagnos>c Parameters Sensi3vity of Xpert (%)
Smear-‐posi3ve specimens 98 97-‐99 Smear-‐nega3ve specimens 68 59-‐75
Specificity of Xpert (%) Smear-‐posi3ve specimens 98 92-‐100 Smear-‐nega3ve specimens 98 97-‐99
Sensi3vity of smear microscopy (%) 78.5 65-‐92 Specificity of smear microscopy (%) 98 97-‐99
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Cost inputs Variable Base Value Range
Xpert cost per test $218 $10-‐$1,000
Device (annualized over 10 years) $59 -‐
Maintenance* $64 -‐
Cartridge $60 -‐
Labor $35
Cost per hour (salary and benefits) $60 -‐
Minutes per test 35 -‐
Smear cost per test $10 $1-‐100
Materials $2.50 -‐
Labor $7.50
Cost per hour (salary + benefits) $60 -‐
Minutes per test 7.5 -‐
Hospital bed cost per day $2,292 $500-‐$5,000
Marginal cost respiratory isola3on per day $1,527 $0-‐$2,000
Cost of four-‐drug an3-‐TB therapy per day $4.55 -‐
Results
Outcome Smear Xpert Difference 95% UR
Cost per pa>ent $17,783 $15,503 $2,278 $1582, $4570
Hospital LOS (days) 5.9 5.8 0.1 -‐0.2, 0.1
Isola>on LOS (days) 2.7 1.4 1.3 1.1, 1.3
Total annual hospital days 1,381 1,358 23 -‐23, 47
Total annual isola>on days 632 328 304 281, 304
Total annual cost $4,161,222 $3,627,702 $533,520 $0.37-‐$1.07m
One-‐way sensi3vity analyses N
umbe
r of T
B E
valu
atio
ns p
er Y
ear
Two-‐way sensi3vity analysis
Incremental Daily Cost of Respiratory Isolation ($)
Diagnostic Strategy
Xpert cost-saving
Smear cost-saving
Thanks to… • SFGH Pulmonary & Cri3cal Care
– Lelia Chaisson – Jihane Benhammou – Alex Millman – Adithya Canamanchi – Phil Hopewell – John Metcalfe – Cecily Miller
• Johns Hopkins School of Public Health – David Dowdy
• Support – Cepheid – CFAR-‐GIVI P30 AI027763 – American Lung Associa3on – SFGH Hearts Founda3on – NIH K23AI080147
• SFDPH TB Lab (101 Grove) – Anna Babst – Sally Liska – Mark Pandori
• SFGH Microbiology Lab – Barbara Haller – Marguerite Roemer – David Cantu
• SFGH Infec3on Control – Chip Chambers – Lisa Winston – Elaine Dekker – Michael Jula
Ques3ons?
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Smear Strategy
Individual means & Annual totals
Outcomes • Cost ($) • Hospital Days • Isola>on Days
Xpert Strategy
Individual means & Annual totals
Outcomes • Cost ($) • Hospital Days • Isola>on Days