A comparison between landmarking and joint modeling for producing predictions using longitudinal outcomes Dimitris Rizopoulos, Magdalena Murawska , Eleni-Rosalina Andrinopoulou, Emmanuel Lesaffre and Johanna J.M. Takkenberg Department of Biostatistics, Erasmus Medical Center [email protected]BAYES 2013, May 21-23, 2013
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A comparison between landmarking and joint …...A comparison between landmarking and joint modeling for producing predictions using longitudinal outcomes Dimitris Rizopoulos, Magdalena
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A comparison between landmarking and joint modeling forproducing predictions using longitudinal outcomes
Dimitris Rizopoulos, Magdalena Murawska, Eleni-Rosalina Andrinopoulou,Emmanuel Lesaffre and Johanna J.M. Takkenberg
Department of Biostatistics, Erasmus Medical Center
• Differences between prediction from joint models I-IV and landmark approachobserved
• Different joint models compared using DIC criterion → best Model I (td-value)
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Discrimination
• Focus on time interval when the occurence of event is of interest (t, t +∆t]
• Based on the model we would like to dicriminate between patients who are going toexprience the event in that interval from patients who will not
• For the first group physiscian can take action to improve survival during (t, t +∆t]
• For c in [0, 1] we define Sk(u | t) ≤ c as success and Sk(u | t) > c as failure
• Then sensitivity is defined as:
PrSk(u | t) ≤ c | T ∗k ∈ (t, t +∆t]
• And specificity as:PrSk(u | t) > c | T ∗
k > t +∆t
Erasmus MC, Rotterdam – May 21-23, 2013 17/25
Discrimination
• For random pair of subjects i, j that have measurments up to t discriminationcapability of joint model can be assesed by area under ROC curve (AUC) obtained byvarying c:
AUC(t,∆t) = Pr[Si(u | t) < Sj(u | t) | T ∗i ∈ (t, t +∆t] ∪ T ∗
j > t +∆t]
• Model will assign higher probability of surviving longer that t +∆t for subject j whodid not experience event
• To summarize model discrimination power weigthed average of AUCs used:
C∆tdyn =
∞∫0
AUC(t,∆tPrE(t)dt/ ∞∫
0
PrE(t)dt (dynamic concordance index)
E(t) = [T ∗i ∈ (t, t +∆t] ∪ T ∗
j > t +∆t]PrE(t)-probability that pair i, j comparable at t
Erasmus MC, Rotterdam – May 21-23, 2013 18/25
Discrimination
• C∆tdyn depends on ∆t
• In practice:
C∆t
dyn =
15∑q=1
ωqˆAUC(tq,∆t)× PrE(tq)
15∑q=1
ωqPrE(tq)
ωq-weights for 15 Gauss-Kronrod quadrature points on (0, tmax)
PrE(t) = S(tq)− S(tq +∆t)S(tq +∆t)
S(· )-Kaplan-Meier estimator of marginal survival function S(· )
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Discrimination
• AUC is estimated as:
ˆAUC(tq,∆t) =
n∑i=i
n∑j=1,j =i
ISi(t +∆t | t) < Sj(t +∆t | t) × IΩij(t)
In∑i=i
n∑j=1,j =i
Ωij(t)
• Comparable pairs are those that satisfy:
Ωij(t) = [Ti ∈ (t, t +∆t] ∩ δi = 1] ∩ Tj > t +∆t or
Ωij(t) = [Ti ∈ (t, t +∆t] ∩ δi = 1] ∩ [Tj = t +∆t ∩ δj = 0]
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Calibration
• Expected Prediction Error (Henderson et al 2002):
• PE(u | t) measures predictive accuracy only at u using longitudinal information upto time t
• To summarize predictive accuracy for interval [t, u] and take into account censoring
weighted average of PE(s | t), t < s < u considered, similar to C∆t
dyn
• Integrated Prediction Error (Schemper and Henderson 2000):
IPE(u | t) =
∑i:u≤Ti≤t
δiSC(t)/SC(Ti) ˆPE(u | t)∑i:u≤Ti≤t
δiSC(t)/SC(Ti)
SC(· )- Kaplan-Meier estimator of censoring distribution
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PE(9|7) IPE(9|7) AUC(9|7) C∆t=2
dyn
M1: value 0.201 0.118 0.787 0.854
M2: value+slope 0.197 0.114 0.793 0.855
M3: area 0.191 0.112 0.758 0.809
M4: shared RE 0.191 0.108 0.807 0.840
CoxLM 0.229 0.130 0.702 0.811
Erasmus MC, Rotterdam – May 21-23, 2013 23/25
Simulation Study
• Data simulated data using joint models with different association structure I-IV
• Baseline hazard simulated using Weibull distribution
• Censoring kept at 40-50%
• In each scenario 10 pts excluded randomly from each simulated data set
• For remaining patients joint models I-IV fitted
• For excluded patients predictions from joint models I-IV and landmarking comparedat 10 time equidistant points to predictions from gold standard model (model withtrue parametrization and true values of parameters)