Missouri validation

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External Validation

Comparison of the model structure with other models

  • Comparison of the structures of published diabetes models with Shannon A (incl. purpose of a model)
Palmer et al., 2000
261114 structure Palmer.png

Reference: Palmer AJ, Sendi PP, Spinas GA. Applying some UK Prospective Diabetes Study results to Switzerland: the cost-effectiveness of intensive glycaemic control with metformin versus conventional control in overweight patients with type-2 diabetes. Schweiz Med Wochenschr. 2000 Jul 11;130(27-28):1034-40.

The models differ in the following points:

  • The model of Palmer et al. has a star structure, while MissouriA has a mesh strusture
  • Palmer et al. respect other forms of diabetes complications such as: stroke, amputation, renal failure and blindness.
  • Palmer et al. desccribe the diffferent states "MI", "heart failure" and "angina" but don't illustrate the relation of those states
  • In the model of Palmer et al., the patient starts every cycle with the same probebilities to develop an complication with no respect to his/ her course of disease
Palmer et al., 2000
261114 structure Palmer 2.png

Reference: Palmer AJ, Weiss C, Sendi PP, Neeser K, Brandt A, Singh G, Wenzel H, Spinas GA. The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective. Diabetologia. 2000 Jan;43(1):13-26.

Abbreviations used:

  • AMI = acute myocardial infarction
  • PTCA = percutaneous transluminal coronary angioplasty

The models differ in the following points:

  • Palmer et al. describe the following state, which MissouriA does not take into account:
    • PTCA
    • Thrombolysis
    • No reperfusion therapy
  • MissouriA respects "Angina", whereas Palmer et al. don't.
  • The model of Palmer et al. does not allow immediate death due to the first myocardial infarction
CDC Diabetes Cost-effectiveness Group, 2002
271114 structure CDC.png

Reference: CDC Diabetes Cost-effectiveness Group. Cost-effectiveness of intensive glycemic control, intensified hypertension control, and serum cholesterol level reduction for type 2 diabetes. JAMA. 2002 May 15;287(19):2542-51.

Abbreviations used:

  • CHD = coronary heart disease
  • CA/MI = cardiac arrest/ myocardial infarction

Comparison of CDC-model and MissouriA:

  • Both model take angina and MI into account
  • CDC-model additionaly defines a state "coronary heart diesease"
  • Missouri a enables the possibility differenciating between first and recurrent MI
  • In the CDC-model death at normal state is not possible
  • MissouriA differs between history of angina and history of MI
Hayashino et al., 2004
261114 structure Hayashino.png

Reference: Hayashino Y, Nagata-Kobayashi S, Morimoto T, Maeda K, Shimbo T, Fukui T. Cost-effectiveness of screening for coronary artery disease in asymptomatic patients with Type 2 diabetes and additional atherogenic risk factors. J Gen Intern Med. 2004 Dec;19(12):1181-91.

Abbreviations used:

  • CAD = Coronary artery disease
  • MI = myocardial infarction
  • LMT = left-main trunk disease
  • CABG = coronary artery bypass grafting
  • PTCA = percutaneous transluminal coronary angioplasty

Comparison of CDC-model and MissouriA:

  • Model by Hayashino et al. is much more complex (15 vs. 7 states, 35 vs 17 transitions)
  • Model by Hayashino et al. has redundant states (Nonfatal MI, History of MI, Death)
  • Model by Hayashino et al. does not describe "angina"
  • MissouriA doesn't describel 1-vessel disease, 2-vessel disease, 3-vessel disease or LMT, PTCA and CABG
Hoerger et al., 2004
011214 structure Hoerger.png

Reference: Hoerger TJ, Harris R, Hicks KA, Donahue K, Sorensen S, Engelgau M. Screening for type 2 diabetes mellitus: a cost-effectiveness analysis. Ann Intern Med. 2004 May 4;140(9):689-99.

Abbreviations used:

  • CHD = coronary heart disease
  • CA/MI = cardiac arrest/ myocardial infarction

Comparison of Hoerger-model and MissouriA:

Palmer et al., 2004
021214 structure Palmer.png

Reference: Palmer AJ, Roze S, Valentine WJ, Minshall ME, Foos V, Lurati FM, Lammert M, Spinas GA. The CORE Diabetes Model: Projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus (types 1 and 2) to support clinical and reimbursement decision-making. Curr Med Res Opin. 2004 Aug;20 Suppl 1:S5-26.

Abbreviations used:

  • MI = Myocardial infarction
  • CHF = Congestive Heart Failure

Comparison of Palmer(2004)-model and MissouriA:

  • The Palmer model is split up in three submodels
  • The model of Palmer et al. does not allow death due to angina
  • The submodel of Palmer et al. do not allow death without any previous heart disease
Zhou et al., 2005
021214 structure Zho.png

Reference: Zhou H, Isaman DJ, Messinger S, Brown MB, Klein R, Brandle M, Herman WH. A computer simulation model of diabetes progression, quality of life, and cost. Diabetes Care. 2005 Dec;28(12):2856-63.

Abbreviations used:

  • CA/MI = cardiac arrest/ myocardial infarction
  • CVD = Cardiovascular disease

Comparison of Zhou-model and MissouriA:

  • The Zhou-model doesn't enable death without previous heart disease
  • The Zhou-model has no state "history of angina"
  • The Zhou model doesn't differ between the first and following MI/CA
Kang et al., 2009
021214 structure Kang.png

Reference: Kang HY, Ko SK, Liew D. Results of a Markov model analysis to assess the cost-effectiveness of statin therapy for the primary prevention of cardiovascular disease in Korea: the Korean Individual-Microsimulation Model for Cardiovascular Health Interventions. Clin Ther. 2009 Dec;31(12):2919-30; discussion 2916-8. doi: 10.1016/j.clinthera.2009.12.013.

Abbreviations used:

  • CVD = Cardiovascular disease

Comparison of Kang-model and MissouriA:

  • The Kang-model doesn't differ Angina and myocardial infarction
  • The Kang-model doesn't model the concrete CVD-events

Comparison of transition probabilities with other models

  • Literature comparison with methods and transition probabilities of other published models
p_NoToNo p_NonToAngina p_NonToFirstMi p_NonToDeath p_AnginaToDeath p_AnginaToHxAngina p_FirstMiToDeath p_FirstMiToHxMi p_HxAnginaToHxMi p_HxAnginaToDeath p_HxAnginaToHxAngina p_HxMiToHxRecMi p_HxMiToDeath p_HxMiToHxMi p_HxRecMiToDeath p_HxRecMiToHxRecMi p_DeathToDeath
# UKPDS33 UKPDS56 Bundesamt,2011; Roper et al., 2002; UKPDS33 Malmberg et al., 2000 # Miettinen et al., 1998 # p_HxAnginaToDeath; Malmberg et al., 2000 p_NonToDeath # ? p_NonToDeath; Lowel et al., 2000 # p_NonToDeath; Thune et al, 2011 # #
Palmer et al., 2000

Probabilities are based on

Palmer et al., 2000

The probabilities to develop AMI is described by: Anderson et al., 1991, Diabetes Control & Complications Trial Research Grouip, 1993. No other references for transition probabilities are listed in the publication.

CDC Diabetes Cost-effectiveness Group, 2002

Transition probabilities are based on data of following studies:

Hayashino et al., 2004

The only listed transition probability source is: Anderson et al., 1991.

Hoerger et al., 2004

Same transition probabilities as Missouri_validation#CDC_Diabetes_Cost-effectiveness_Group.2C_2002_2

Palmer et al., 2004

The submodels are based on various studies:

Zhou et al., 2005
p_NormalToAngina p_NormalToMI/CA p_AnginaToMi/CA p_AnginaToDeath p_MI/CAToHistoryMI/CA p_MI/CAToDeath p_HistoryMI/CAToMI/CA p_HistoryMI/CAToDeath
UKPDS33 UKPDS56 Malmberg et al., 2000 Malmberg et al., 2000 UKPDS33 UKPDS33 Ulvenstam et al., 1985 Löwel et al., 2000
Kang et al., 2009

Transition probabilities are based on the following studies:


  • Cross-testing of diabetes disease models

Model outcomes

  • Target: Compare the results of the MissouriA model to those of clinical long-term studies

Internal Validation



cohort characteristics

The model offers the following cohort characteristics input parameters:

  • initial age (in years)
  • gender
  • duration of diabetes (in years)
  • smoker/ nonsmoker
  • HbA1c level (in %)
  • systolic blood pressure (in mmHg)
  • total cholesterol (in mmol/l)
  • high density lipids (in mmol/l)

economic evidence


Complete transparency of the model structure and the model itself leads to an understanding of the developement processs --> "The documentation is the model!"


Correct reporting of model results is performed by showing output tables and diagrams.

Face Validity

Sensitivity Analysis

Four subgroups were generated (men smoking, women smoking, men non-smoking, women non-smoking). The distribution between these subgroups was defined by offical values from census bureau:

Absolute sizes of these subgroups (n = 10000):

  • male non-smoking: 3478
  • male smoking: 1420
  • female non-smoking: 4067
  • female smoking: 1035

Other parameters of these cohorts were set to the following standard values:

  • inital age = 40 years
  • duration of diabetes = 5 years
  • HbA1c [%] = 6.5
  • systolic blood pressure [mmHg] = 120
  • total cholesterol [mmol/l] = 5
  • high density lipids [mmol/l] = 1.3

For the sensitivity analysis these parameters as well as te above listed distributions were varied for +10% and -10% (+10% is equal to higher male percentage or higher smoking percentage)

Changes of total costs: Tornado costs missouri.JPG

Changes of life expectancy: Tornado lifeExpectancy missouri.JPG