tips presentation v3
TRANSCRIPT
Effect of TIPS Placement on the Survival of Hepatorenal Syndrome Patients: An Instrumental Variable Approach
April 7th 2016
Rowena Crow MD
TIPS - Transjugular Intrahepatic Portosystemic Shunt
AASLD practice guidelines for TIPS procedure:
Recommended treatment for complications of portal hypertension due to severe liver cirrhosis such as
• Variceal Bleeding
• Refractory ascites
• Hepatic Hydrothorax
• Hepatorenal Syndrome - investigatory use pending publishing of controlled trials
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But…Up to 75 % of patients with severe liver cirrhosis will develop progressive renal failure is known as
Hepatorenal Syndrome aka HRS
• due to decrease in renal perfusion
• severe complication of liver cirrhosis
• very high mortality
Is TIPS a option for treatment?
TIPS rarely done for patients who develop HRS
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Treatments options for HRS
• Liver transplant - best option, limited availability
• Medical treatment - supportive care, intravenous albumin and vasoconstrictors
• TIPS - minimally invasive procedure to place stent through liver to increase blood flow and correct portal hypertension limited research into effectiveness
Research Question
Does the TIPS procedure improve
in-patient survival in patients with
severe liver cirrhosis who have
developed HRS?
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HCUP State Inpatient Sample 2000-2012
Discharge data - ICD-9-CM diagnosis and procedure codes, patient demographics, mortality…
Data from 13 states
Extracted data – hospitalized patients with Dx of liver cirrhosis plus Dx of hepatorenal syndrome
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Exclusion criteria
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To identify when TIPS is performed as a treatment of HRS plus compatibility with current HRS research
Any patient with concommitent diagnosis of- acute liver failure- chronic kidney disease- infection - SBP, UTI, sepsis, septicemia, bacteremia, pneumonia,
cholangitis- variceal bleeding- Budd Chiari Syndrome (thrombosis)- hypovolemia - abdominal compartment syndrome
Analysis model
Mortalityi = f ( TIPS, Patient Demographicsit, Sx of Liver Cirrhosisit,
Co-morbiditiesit, Hospital Characteristicsi, Yeari, Statei )
There are omitted variables potentially correlated with survival
no clinical data, labs etcno differentiation between HRS type 1 and type 2
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Instrument Variable Approach
Use a measure that is
• related to probability of treatment - TIPS
• not related to outcome – mortality
TIPS requires specialized Interventional Radiology facilities
• not available at every hospital
IV candidate - differential distance
• The difference between distance from patient’s home to nearest hospital and distance from patients home to nearest TIPS hospital
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Differential Distance
Assumption 1: a patient whose nearest hospital provides TIPs, is more likely to be offered TIPS procedure - can test this
Assumption 2: the location of a patient’s home is not related to mortality - cannot test - face validity
Aim: chose a measure (IV) that is related to treatment variation in the observational data that is independent of the unobserved patient characteristics
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Instrument Variable with 2 Stage Residual Inclusion
first stage:
prob(TIPS=1) = Logit( Patientit , Sxit , Co-morbiditiesit ,
Hospital Characteristicsi , Yeari , Statei, Distanceit)
Residualit = TIPSit - prob(TIPS=1)
second stage:
prob(mortality=1) = Logit( TIPSit , Patientit , Sxit , Co-morbiditiesit ,
Hospital Characteristicsi , Yeari , Statei, Residualit)
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Instrumental variable methods give an estimate of the Local Average Treatment Effect
• The average effect of the TIPS treatment for the observations affected
by the instrument - aka the marginal population
• Who is the marginal population?
• Patients whose likelihood of getting TIPS is effected by the
distance to suitable TIPS facility
• Does not include patients who are ineligible for TIPS
• Does not include patients who are the ‘perfect candidate’ for TIPS13
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Characteristic All patients
(N=10,052)
TIPS (N=175) Standard Medical
therapy (N=9,877)
Difference
Between the
Means
TIPS (%) 1.7
Inpatient Mortality (%) 34.3 28.6 34.4 5.8
ER Admission (%) 77.3 50.3 77.7 27.4
Ascites (%) 64.8 83.4 64.4 19.0
Hepatic Encephalopathy (%) 39.9 29.7 40.1 10.4
Portal Hypertension (%) 21.0 42.9 20.5 22.4
Teaching Hosp (%) 23.0 51.4 22.5 28.9
Liver Transplant (%) 2.6 6.9 2.5 4.4
Table 1: Patients with HRS 2001 to 2012
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F-stat = 9.5test for ‘strength’ of IV
Partial R2 = 0.001
Testing Assumption1 - The ‘strength’ of the Instrument Variable
Local Average Treatment Effect
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Marginal Effect
on Probability of
Death
Logistic Model 2SRI
IV - log(differential distance)
F-test 9.65
TIPS -0.02 (0.037) -0.85 (0.30) **
Residual 0.89 (0.31) ***
* p<0.1; ** p<0.05; *** p<0.01 Standard errors in parenthesis
In the marginal population, patients who receive the TIPSprocedure have a reduction in probability of death of 85%
Sensitivity Analysis - comparison with alternative models
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Marginal Effect
on Probability
of Death
2SRI IV 2SRI IV
w/o State FE
2SRI IV
ER admissions
excluded
2SRI IV subsample
states with consistent
data 2000 - 2007
TIPS -0.85 (0.30) ** -1.11 (0.29) *** -0.96 (0.43) ** -0.96 (0.31) ***
Residual 0.89 (0.31) *** 1.15 (0.29) *** 1.04 (0.44) ** 1.01 (0.32) ***
F-test IV 9.51 9.56 7.02 9.81
* p<0.1; ** p<0.05; *** p<0.01 Standard errors in parenthesis
Caveats…
Instrument Variable
Assumption 1: Instrument “strength” - F-test of 9.51 slightly less than the literature standard of a value > 10A "weak" instruments,will be poor predictor of treatment
Assumption 2: the location of a patient’s home is not related to mortality location may be related to factors such as access to teaching hospital - effects mortality- teaching hospital variable included in the first stage
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Conclusions
• IV approach used to give consistent estimates of treatment effect, a
way to account for omitted variable bias
• Large and statistically significant survival benefit found for TIPS
procedure to treat in patients with HRS - in the marginal population
• Survival benefit larger than the estimate from logistic regression
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Questions?