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Analyzing the AgeRelated Macular Degeneration DatasetThe following command can be used to evaluate whether the change in visual acuity after 24 weeks is a good surrogate for the change in visual acuity after 52 weeks, as evaluated based on a reduced weighted mixedeffects approach in the informationtheoretic framework: > ARMD_Mixed_Fit_IT < MixedContContIT(Dataset = ARMD, Surr = Diff24, True = Diff52, Treat = Treat, Trial.ID = Center, Pat.ID = Id, Model = "Reduced", Weighted = TRUE) Applying the summaryO function to the fitted object ARMD_Mixed_Fit_IT provides the following output: > summary(ARMD_Mixed_Fit_IT) # Generated output: Function call: MixedContContIT(Dataset = ARMD, Surr = Diff24, True = Diff52, Treat = Treat, Trial.ID = Center, Pat.ID = Id, Model = "Reduced", Weighted = TRUE) # Data summary and descriptives Total number of trials: 36 Total number of patients: 181 M(SD) patients per trial: 5.0278 (2.9129) [min: 2; max: 18] Total number of patients in experimental treatment group: 84 Total number of patients in control treatment group: 97 TABLE 13.2 Surrogate package. Overview of the functions that can be used to evaluate surrogacy in the informationtheoretic framework when both S and T are normally distributed endpoints. Note. The indicator (. . .) refers to a number of required function arguments; for details see Section 13.2.2.
Mean surrogate and true endpoint values in each treatment group: Control.Treatment Experimental.treatment Surrogate 6.0309 7.8095 True endpoint 11.7423 14.6548 Var surrogate and true endpoint values in each treatment group: Control.Treatment Experimental.treatment Surrogate 188.9261 132.6380 True endpoint 264.7975 231.7709 Correlations between the true and surrogate endpoints in the control (r_T0S0) and the experimental treatment groups (r_T1S1): Estimate Standard Error CI lower limit CI upper limit r_T0S0 0.7693 0.0478 0.7022 0.8228 r_T1S1 0.7118 0.0525 0.6315 0.7770 # Informationtheoretic surrogacy estimates summary Triallevel surrogacy (R2_ht): R2ht CI lower limit CI upper limit 0.6864 0.4750 0.8388 Individuallevel surrogacy (R2_hind): R2h.ind CI lower limit CI upper limit 0.5339 0.4315 0.6292 The first part of the output shows descriptives like the number of trials (here: centers) in the data, the means (variances) of S and T in the different treatment groups, and so on. The last part of the output provides the estimates of trial and individuallevel surrogacy. As can be seen, i?h_{t} = 0.6864 with 95% confidence interval [0.4750; 0.8388], and .Rh_{indiv} = 0.5339 with 95% confidence interval [0.4315; 0.6292] (the same results as in Section 10.2.1). These results thus indicate (i) that the uncertainty about the treatment effect on T that is reduced when the treatment effect on S becomes known (triallevel surrogacy) is moderate, and (ii) that the uncertainty about T that is reduced when S becomes known (individuallevel surrogacy) is moderate as well. The results can be further explored by applying the plot() function and by directly accessing the components in the fitted ARMD_Mixed_Fit_IT object in the same way as was illustrated in Section 13.2.1. 
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