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#####	Solutions to Session 5 Problems
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##### Author: D. Gillen
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#####	Problem 1: Monitoring the sepsis trial
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#####	Definition of sponsor's stopping rule
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#####	Definition of sponsor's chosen stopping rule
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binomFixed <- seqDesign( prob.model = "proportions", arms = 2, null.hypothesis = .3, 
		alt.hypothesis = 0.25, ratio = c(1., 1.), nbr.analyses = 1, 
		test.type = "less", power = 0.80, alpha = 0.025 )
binomFixed.1700 <- update( binomFixed, sample.size=1700, power="calculate" )

bnd <- rbind(	c(1-.0001, NA ),
				rep(NA,2), rep(NA,2),
				rep(NA,2), rep(NA,2) )
bnd <- seqBoundary( bnd, scale="P" )				

sepsis.Sponsor <- update( binomFixed.1700, nbr.analyses=5, P=c(1,.75) )
sepsis.Sponsor <- update( sepsis.Sponsor, exact.constraint=bnd ) 
1-seqBoundary( sepsis.Sponsor, "P" )

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#####	MONITORING OF SIMULATED CLINICAL TRIAL DATA
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#####		Treatment arm:  25% mortality
#####		Comparison arm: 35% mortality
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##### First analysis after 200 subjects on each arm
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interim1 <- read.csv( "http://rctdesign.org/ShortCourses/uwAugust2013/interim1Data.csv", header=TRUE )
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##### Monitoring on sample mean scale with re-estimation of sample size
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interim1.dsn <- seqMonitor(sepsis.Sponsor, response=interim1$resp1, treatment=interim1$tx1)
plot(interim1.dsn)
interim1.dsn

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##### Alternative approach if sample size was not to be re-estimated
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interim1.maxN.dsn <- seqMonitor(sepsis.Sponsor, response=interim1$resp1, treatment=interim1$tx1, future.analyses=sampleSize(sepsis.Sponsor)[2:5])
plot(interim1.dsn,interim1.maxN.dsn,superpose.design=T, dsnLbls=c("Original Design","Maintain Power","Maintain Sample Size"))


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#####	Second analysis after an additional 175 subjects on each arm
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## 	Simulate  indicators of treatment (tx2) and response (resp2) 
##	for additional subjects
interim2 <- read.csv( "http://rctdesign.org/ShortCourses/uwAugust2013/interim2Data.csv", header=TRUE )


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#####	Monitoring on sample mean scale with re-estimation of sample size
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interim2.dsn <- seqMonitor(interim1.dsn, response=interim2$resp2, treatment=interim2$tx2)
plot(interim2.dsn)
interim2.dsn