Validation of economic and health outcomes simulation model of type 2 diabetes mellitus (ECHO-T2DM)

Figures & data

Figure 1. ECHO-T2DM schematic. SBP, systolic blood pressure; BMI, body mass index; AE, adverse event; IHD, ischemic heart disease; UKPDS, UK prospective diabetes study; MI, myocardial infarction; CHF, congestive heart failure; BDR, background diabetic retinopathy; PDR, proliferative diabetic retinopathy; ME, macular edema; MA, microalbuminuria; GPR, gross proteinuria; ESRD, end-stage renal disease; PVD, peripheral vascular disease; LEA, lower extremity amputation.

Table 1. Validation simulation analyses.

Trial	Population	Duration (years)	Treatment groups	Sample size
UKPDS [17]	Interventional study of newly diagnosed T2DM, aged 25–65, no MI in previous year and no current AP or CHF in the UK.	12	Conventional/Intensive	3867
CARDS [20]	Interventional study of relatively healthy T2DM.	3.9	Placebo/Atorvastatin	2838
MICRO-HOPE [22]	Interventional study of T2DM with high risk of CVD.	4	Placebo/Ramipril	3657
WESDR [18]	Observational study of DM diagnosed at or after 30 years of age in an 11-county area in southern Wisconsin.	Up to 30	Older Onset Group, Older Onset With Insulin, Older Onset W/out Insulin, Mixed Newly Diagnosed	1370, 143, 296, 639
EASTMAN [12]	Seminal model of T2DM. Comparison of conventional with intensive care (goal of normoglycemia) for newly diagnosed T2DM.	Lifetime	Standard/Comprehensive	Model
Sasaki (OSAKA) [23]	Long-term follow-up mortality study in Osaka, Japan. Survival in age groups: 35–44, 45–54, 55–64, and 65+.	Up to 20	Observational	1939

T2DM, type 2 diabetes mellitus; MI, myocardial infarction; AP, angina pectoris; CHF, congestive heart failure; CVD, cardiovascular disease.

Figure 2. Conceptual summary of methods.

Figure 3. Predicted vs actual mean cumulative incidence (all outcomes, full validation data set).

Table 2. Actual and predicted study outcomes.

Trial	End-point	Years	Treatment group	Actual study cumulative incidence	Predicted cumulative incidence	Difference
UKPDS	Stroke	12	Conventional	0.061	0.101	−0.040
			Intensive	0.061	0.093	−0.032
	MI	12	Conventional	0.190	0.225	−0.035
			Intensive	0.160	0.212	−0.052
	AP	12	Conventional	0.067	0.093	−0.026
			Intensive	0.068	0.088	−0.020
	CHF	12	Conventional	0.033	0.081	−0.048
			Intensive	0.030	0.077	−0.047
	Microalbuminuria	12	Conventional	0.340	0.223	0.117
			Intensive	0.230	0.208	0.022
	Proteinuria	12	Conventional	0.103	0.083	0.020
			Intensive	0.068	0.066	0.002
	ESRD	12	Conventional	0.008	0.002	0.006
			Intensive	0.006	0.002	0.004
	Retinopathy	12	Conventional	0.490	0.369	0.121
			Intensive	0.390	0.270	0.120
	Survival	12	Conventional	0.850	0.828	0.022
			Intensive	0.850	0.839	0.011
	Blindness in one eye	12	Conventional	0.035	0.003	0.032
			Intensive	0.029	0.002	0.027
CARDS	Primary end-point (fatal and non-fatal stroke, MI, and AP + cardiac arrest)	4	Placebo	0.090	0.125	−0.035
			Atorvastatin	0.058	0.097	−0.039
	Stroke	4	Placebo	0.028	0.031	−0.003
			Atorvastatin	0.015	0.028	−0.013
	Death from any cause	4	Placebo	0.058	0.076	−0.018
			Atorvastatin	0.043	0.069	−0.026
MICRO-HOPE	MI	4	Placebo	0.129	0.172	−0.043
			Ramipril	0.102	0.166	−0.064
	Stroke	4	Placebo	0.061	0.055	0.006
			Ramipril	0.042	0.051	−0.009
	Mortality	4	Placebo	0.140	0.182	−0.042
			Ramipril	0.108	0.177	−0.069
	CHF	4	Placebo	0.045	0.026	0.019
			Ramipril	0.045	0.025	0.020
WESDR	Mortality	4	Older Onset Group	0.240	0.203	0.037
	Mortality	10	Older Onset Group	0.550	0.571	−0.021
	New incidence of BDR	4	Older Onset With Insulin	0.474	0.636	−0.162
		4	Older Onset Without Insulin	0.344	0.344	0.000
	New incidence of PDR	4	Older Onset With Insulin	0.074	0.031	0.043
			Older Onset Without Insulin	0.023	0.012	0.011
	BDR	10	Mixed Newly Diagnosed	0.600	0.717	−0.117
	BDR	20	Mixed Newly Diagnosed	0.720	0.797	−0.077
	BDR	30	Mixed Newly Diagnosed	0.740	0.808	−0.068
	PDR	4	Mixed Newly Diagnosed	0.020	0.008	0.012
	PDR	16	Mixed Newly Diagnosed	0.050	0.097	−0.047
	PDR	30	Mixed Newly Diagnosed	0.175	0.120	0.055
EASTMAN	BDR	Lifetime	Standard Care	0.790	0.892	−0.102
			Comprehensive Care	0.270	0.255	0.015
	ME	Lifetime	Standard Care	0.520	0.645	−0.125
			Comprehensive Care	0.150	0.165	−0.015
	PDR	Lifetime	Standard Care	0.190	0.070	0.120
			Comprehensive Care	0.010	0.008	0.002
	Blindness	Lifetime	Standard Care	0.190	0.056	0.134
			Comprehensive Care	0.050	0.007	0.043
	MA	Lifetime	Standard Care	0.530	0.557	−0.027
			Comprehensive Care	0.320	0.312	0.008
	GPR	Lifetime	Standard Care	0.400	0.229	0.171
			Comprehensive Care	0.050	0.014	0.036
	ESRD	Lifetime	Standard Care	0.170	0.076	0.094
			Comprehensive Care	0.020	0.005	0.015
	Neuropathy	Lifetime	Standard Care	0.310	0.461	−0.151
			Comprehensive Care	0.100	0.291	−0.191
	LEA	Lifetime	Standard Care	0.150	0.214	−0.064
			Comprehensive Care	0.050	0.140	−0.090
Sasaki (OSAKA)	Survival (ages 35–44)	4	Observational	0.970	0.988	−0.018
		10	Observational	0.900	0.957	−0.057
		14	Observational	0.800	0.910	−0.110
		20	Observational	0.700	0.734	−0.034
	Survival (ages 45–54)	4	Observational	0.950	0.976	−0.026
		10	Observational	0.810	0.909	−0.099
		14	Observational	0.690	0.809	−0.119
		20	Observational	0.580	0.500	0.080
	Survival (ages 55–64)	4	Observational	0.850	0.949	−0.099
		10	Observational	0.640	0.801	−0.161
		14	Observational	0.520	0.609	−0.089
		20	Observational	0.370	0.220	0.150
	Survival (ages 65+)	4	Observational	0.720	0.871	−0.151
		10	Observational	0.330	0.512	−0.182
		14	Observational	0.180	0.236	−0.056
		20	Observational	0.080	0.027	0.053

MI, myocardial infarction; AP, angina pectoris; CHF, congestive heart failure; ESRD, end-stage renal disease; BDR, background diabetic retinopathy; PDR, proliferative diabetic retinopathy; ME, macular edema; MA, microalbuminuria; GPR, gross proteinuria; LEA, lower extremity amputation.

Figure 4. Predicted vs actual cumulative incidence (macrovascular end-points, full validation data set).

Figure 5. Predicted vs actual cumulative incidence (survival end-points, full validation data set).

Figure 6. Predicted vs actual cumulative incidence (microvascular end-points, full validation data set).

Figure 7. Predicted vs actual cumulative incidence (all outcomes, dependent external validation data set).

Figure 8. Predicted vs actual cumulative incidence (all outcomes, independent external validation data set).

Figure 9. Predicted vs actual cumulative incidence (all outcomes, cross-validity endpoints).

Figure 10. Predicted vs actual differences in cumulative incidence (all outcomes, comparative studies).