Appendix(This material will be made available online at the time of publication)

Table A Full listing of studies used in the meta-regression and meta-analysis including utility values (standard error), study and patient characteristics and methods of elicitation

Study / # of patients / Mean age / Prop. Male / Mean utility / SE / Type
Ose et al. 2009 / 1291 / 70.3 / 0.46 / 0.67 / 0.006 / EQ-5D
Morgan et al. 2006 / 360 / 64.9 / 0.58 / 0.74 / 0.015 / EQ-5D
Sakamaki et al. 2006 / 220 / 63.3 / 0.50 / 0.86 / 0.015 / EQ-5D
Sakthong et al. 2008 / 303 / 61.1 / 0.29 / 0.76 / 0.020 / EQ-5D
Hart et al. 2003 / 274 / 38.2 / 0.54 / 0.88 / 0.010 / EQ-5D
Sullivan et al. 2008 / 547 / 64.0 / 0.47 / 0.76 / 0.012 / EQ-5D
McEwen et al. 2009 / 749 / 68.9 / 0.54 / 0.73 / 0.007 / EQ-5D
McEwen et al. 2009 / 320 / 70.0 / 0.54 / 0.73 / 0.011 / EQ-5D
McEwen et al. 2009 / 429 / 68.1 / 0.54 / 0.74 / 0.010 / EQ-5D
McEwen et al. 2009 / 7143 / 60.0 / 0.45 / 0.81 / 0.002 / EQ-5D
Marrett et al. 2009 / 1984 / 58.1 / 0.57 / 0.78 / 0.004 / EQ-5D
Redekop et al. 2002 / 1348 / 64.9 / 0.50 / 0.74 / 0.007 / EQ-5D
Boye et al. 2006 / 228 / 59.4 / 0.58 / 0.82 / 0.015 / EQ-5D
Boye et al. 2006 / 227 / 54.8 / 0.56 / 0.84 / 0.015 / EQ-5D
Boye et al. 2007 / 294 / 67.5 / 0.50 / 0.70 / 0.017 / EQ-5D
Currie et al. 2006 / 419 / 53.5 / 0.51 / 0.68 / 0.016 / EQ-5D
Currie et al. 2006 / 768 / 66.5 / 0.59 / 0.66 / 0.011 / EQ-5D
Clarke et al. 2009 / 7348 / 66.0 / 0.62 / 0.81 / 0.003 / EQ-5D
UKPDS62 / 3192 / 63.3 / 0.56 / 0.77 / 0.005 / EQ-5D
Lundkvist et al. 2005 / 114 / 64.2 / 0.56 / 0.70 / 0.025 / EQ-5D
Lundkvist et al. 2005 / 193 / 65.4 / 0.62 / 0.77 / 0.017 / EQ-5D
Farmer et al. 2009 / 152 / 66.3 / 0.56 / 0.80 / 0.012 / EQ-5D
Farmer et al. 2009 / 150 / 65.2 / 0.59 / 0.78 / 0.011 / EQ-5D
Farmer et al. 2009 / 151 / 65.5 / 0.58 / 0.81 / 0.012 / EQ-5D
Matza et al. 2007 / 129 / 55.9 / 0.64 / 0.76 / 0.026 / EQ-5D
Lloyd et al. 2008 / 49 / 52.6 / 0.56 / 0.83 / 0.029 / EQ-5D
Lloyd et al. 2008 / 978 / 67.0 / 0.71 / 0.85 / 0.005 / EQ-5D
Arne et al. 2009 / 2149 / 67.5 / 0.47 / 0.72 / 0.005 / EQ-5D
Bagust & Beale 2005 / 4641 / 67.0 / 0.48 / 0.69 / 0.004 / EQ-5D
Hammerschmidt et al. 2004 / 41 / 63.3 / 0.46 / 0.70 / 0.043 / EQ-5D
Hammerschmidt et al. 2004 / 41 / 66.8 / 0.59 / 0.53 / 0.036 / EQ-5D
Vexiau et al. 2008 / 400 / 62.1 / 0.54 / 0.79 / 0.012 / EQ-5D
Zhang et al. 2009 / 42 / 53.0 / 0.55 / 0.90 / 0.023 / EQ-5D
Brown et al. 2008 / 118 / 77.0 / 0.25 / 0.71 / 0.030 / TTO
Brown et al. 2008 / 214 / 73.0 / 0.51 / 0.79 / 0.019 / TTO
Shah et al. 2004 / 71 / 66.2 / 0.35 / 0.88 / 0.022 / TTO
Shah et al. 2004 / 43 / 67.3 / 0.65 / 0.90 / 0.021 / TTO
Shah et al. 2004 / 22 / 75.4 / 0.39 / 0.76 / 0.048 / TTO
Brown et al. 1999 / 95 / 63.0 / 0.39 / 0.77 / 0.020 / TTO
Sharma et al. 2003 / 221 / 63.5 / 0.52 / 0.79 / 0.015 / TTO
Brown et al. 2000 / 292 / 61.7 / 0.44 / 0.88 / 0.010 / TTO
Huang et al. 2006 / 555 / 74.0 / 0.63 / 0.76 / 0.010 / TTO
Huang et al. 2006 / 555 / 74.0 / 0.63 / 0.77 / 0.015 / TTO
Huang et al. 2006 / 555 / 74.0 / 0.63 / 0.64 / 0.015 / TTO
Huang et al. 2007 / 701 / 63.0 / 0.42 / 0.76 / 0.012 / TTO
Brown et al. 2002 / 72 / 62.2 / 0.44 / 0.86 / 0.020 / TTO
Sullivan et al. 2002 / 52 / 56.1 / 0.43 / 0.87 / 0.028 / SG
Glasziou et al. 2007 / 978 / 67.0 / 0.71 / 0.78 / 0.004 / SF-6D
Wee et al. 2006 / 91 / 53.8 / 0.73 / 0.76 / 0.013 / SF-6D
Wee et al. 2006 / 74 / 52.0 / 0.65 / 0.75 / 0.015 / SF-6D
Wee et al. 2006 / 144 / 48.9 / 0.30 / 0.71 / 0.012 / SF-6D
Wee et al. 2005 / 308 / 40.3 / 0.51 / 0.77 / 0.007 / SF-6D
Clarke et al. 2006 / 4051 / 61.6 / 0.65 / 0.76 / 0.002 / SF-6D
Barnett et al. 2007 / 365 / 68.2 / 0.99 / 0.61 / 0.006 / SF-6D
Maddigan et al. 2004 (a) / 372 / 62.3 / 0.42 / 0.78 / 0.009 / HUI3
Maddigan et al. 2004 (a) / 372 / 62.3 / 0.42 / 0.60 / 0.016 / HUI3
Maddigan et al. 2004 (b) / 172 / 63.0 / 0.49 / 0.69 / 0.020 / HUI3
Maddigan et al. 2004 (b) / 200 / 61.9 / 0.38 / 0.59 / 0.023 / HUI3
Additional studies included into meta-analysis
Bharmal et al. 2006 / 165 / 0.89 / 0.007 / SF-6D
Douzdjian et al. 1998 / 17 / 0.59 / 0.60 / 0.049 / SG
Barofsky et al. 2004 / 559 / 0.70 / 0.010 / HUI3
Barofsky et al. 2004 / 172 / 0.61 / 0.015 / HUI3
Chancellor et al. 2008 / 0.75 / 0.026 / TTO
Chancellor et al. 2008 / 0.75 / 0.020 / TTO
Maddigan et al. 2005 / 1193 / 0.88 / 0.005 / HUI3

Table B Summary of studies reporting utility values (standard error) and number of patients for studies with patients that have a history of complications

Author / Publication year / n / Mean utility score / SE / Utility measure
No Complications
2002 / UKPDS62 / 2636 / 0.785 / 0.005 / EQ-5D
2009 / Ose et al. / 40 / 0.790 / 0.036 / EQ-5D
2009 / Ose et al. / 66 / 0.826 / 0.027 / EQ-5D
2006 / Morgan et al. / 360 / 0.735 / 0.015 / EQ-5D
2006 / Sakamaki et al. / 106 / 0.884 / 0.013 / EQ-5D
2002 / Redekop et al. / 1136 / 0.810 / 0.007 / EQ-5D
2007 / Glasziou et al. / 210 / 0.780 / 0.009 / SF-6D
2002 / Brown et al. / 72 / 0.860 / 0.020 / TTO
Myocardial Infarction
2007 / Glasziou et al. / 183 / 0.764 / 0.010 / SF-6D
2005 / Wee et al. / 46 / 0.770 / 0.019 / SF-6D
2002 / UKPDS62 / 200 / 0.719 / 0.020 / EQ-5D
2005 / Maddigan et al. / 172 / 0.770 / 0.015 / HUI3
2006 / Morgan et al. / 37 / 0.676 / 0.042 / EQ-5D
Stroke
2007 / Glasziou et al. / 102 / 0.744 / 0.014 / SF-6D
2002 / UKPDS62 / 69 / 0.570 / 0.043 / EQ-5D
2007 / Huang et al. / 701 / 0.700 / 0.012 / TTO
2007 / Huang et al. / 701 / 0.310 / 0.012 / TTO
2006 / Morgan et al. / 99 / 0.429 / 0.033 / EQ-5D
2005 / Maddigan et al. / 34 / 0.790 / 0.030 / HUI3
ESRD
2007 / Huang et al. / 701 / 0.350 / 0.012 / TTO
2006 / Morgan et al. / 9 / 0.328 / 0.131 / EQ-5D
2006 / Sakamaki et al. / 12 / 0.810 / 0.046 / EQ-5D
1998 / Douzdjian et al. / 17 / 0.400 / 0.046 / SG
Blindness
2007 / Glasziou et al. / 74 / 0.769 / 0.015 / SF-6D
2002 / UKPDS62 / 101 / 0.674 / 0.032 / EQ-5D
2006 / Huang et al. / 555 / 0.390 / 0.015 / TTO
2007 / Huang et al. / 701 / 0.530 / 0.014 / TTO
2007 / Huang et al. / 701 / 0.380 / 0.013 / TTO
1999 / Brown et al. / 95 / 0.590 / 0.184 / TTO
2003 / Sharma et al. / 43 / 0.478 / 0.072 / TTO
2003 / Sharma et al. / 3 / 0.340 / 0.208 / EQ-5D
Ulcer
2006 / Morgan et al. / 239 / 0.512 / 0.021 / EQ-5D
2006 / Sakamaki et al. / 19 / 0.840 / 0.036 / EQ-5D
2002 / Sullivan et al. / 52 / 0.760 / 0.032 / SG
2002 / Sullivan et al. / 52 / 0.620 / 0.042 / SG
2005 / Gore et al. / 60 / 0.700 / 0.026 / EQ-5D
2005 / Gore et al. / 84 / 0.500 / 0.033 / EQ-5D
2005 / Gore et al. / 108 / 0.200 / 0.029 / EQ-5D
2007 / Huang et al. / 701 / 0.660 / 0.013 / TTO
Amputation
2007 / Glasziou et al. / 53 / 0.730 / 0.021 / SF-6D
2002 / UKPDS62 / 19 / 0.371 / 0.076 / EQ-5D
2006 / Huang et al. / 555 / 0.450 / 0.015 / TTO
2007 / Huang et al. / 701 / 0.550 / 0.014 / TTO
2002 / Sullivan et al. / 52 / 0.740 / 0.033 / SG
2002 / Sullivan et al. / 52 / 0.610 / 0.040 / SG
2006 / Morgan et al. / 4 / 0.341 / 0.121 / EQ-5D

Table CIncremental QALYs gained as a result of simulated intervention (increase in HbA1C levels over a lifetime), using all mean utility values, all maximum utility values and all minimum utility values for states determined in the meta analysis

QALY control / QALY intervention / Incremental QALYs gained
Mean utilities / 9.73 / 10.04 / 0.31
Maximum utilities / 10.82 / 11.14 / 0.32
Minimum utilities / 8.62 / 8.92 / 0.30

Table D Meta-regression results without taking into account within-study correlation reporting standard errors and looking at the effect of factors influencing utility values of the general diabetic population

Variable / Coefficient / Std. Err. / p-value / 95% CI lower / 95% CI upper
Intercept / 0.7549 / 0.0117 / <0.0001 / 0.7295 / 0.7803
Study population
*(per 1000 increase) / 0.0057 / 0.0055 / 0.302 / -0.0053 / 0.0167
Mean Age
**(per 10 year increase) / -0.0552 / 0.0117 / <0.0001 / -0.0787 / -0.0317
Proportion males in study
***(per 10% increase) / 0.0097 / 0.0073 / 0.187 / -0.0049 / 0.0243
Method of elicitation
EQ-5D (reference)
TTO/ SG / 0.0722 / 0.0226 / 0.002 / 0.0270 / 0.1175
HUI II/III, SF-6D / -0.0785 / 0.0223 / 0.001 / -0.1232 / -0.0337

Between study variability tau2 estimate = 0.0036

*Age standardised by deducting the mean age across studies of 62.6

**Study population standardised by deducting the mean population across studies of 806.44

***Proportion of males standardised by deducting the mean percentage males of 52.7%.

Table E Reports the mean utility value, 95% confidence intervals, number of observations, the I2 and tau2 estimate for meta-analysis results by the individual methods of elicitation: EQ-5D, TTO/SG & SF-6D/HUI3

Elicitation Method / Utilityvalue / 95% Confidence Interval / n / I2 / Tau2
EQ-5D / 0.76 / 0.74-0.78 / 33 / 98.4% / 0.002
TTO/SG / 0.78 / 0.75-0.82 / 17 / 94.5 / 0.005
HUI3/SF-6D / 0.73 / 0.69-0.77 / 16 / 99.1% / 0.005

Listing of the search strategy for the different databases and the abstracts identified for further review

Medline Search Strategy = (4794)

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  1. exp Diabetes mellitus/
  2. exp Diabetes complications/
  3. (diabet$ complications).tw.
  4. exp Insulin/
  5. exp Hemoglobins/
  6. exp Hypoglycemia/
  7. exp Hyperglycemia
  8. (Type 1 diabetes).tw.
  9. (Type 2 diabetes).tw.
  10. (Diabetes mellitus type 1).tw.
  11. (Diabetes mellitus type 2).tw.
  12. (non-insulin dependent diabetes).tw.
  13. NIDDM.tw.
  14. (insulin dependent diabetes mellitus).tw.
  15. IDDM.tw.
  16. (adult-onset diabetes).tw.
  17. (diabetic patients).tw.
  18. (adult diab$).tw.
  19. (diabetes related complications).tw.
  20. (blood glucose level).tw.
  21. (glucose control).tw.
  22. (haemoglobin a1c).tw.
  23. (haemoglobin a1c level).tw.
  24. Diabetes treatment.mp.
  25. exp Quality-Adjusted Life Years/
  26. cost utility analysis.tw.
  27. CUA.tw.
  28. EuroQol-5D.tw.
  29. EQ-5D.tw.
  30. EQ5D.tw.
  31. (health utility index mark).tw.
  32. HUI$.tw.
  33. QALY$.tw.
  34. (Quality adjusted life year).tw.
  35. (preference based quality of life).tw.
  36. (preference based measures).tw.
  37. Health states.tw.
  38. exp Quality of Life/
  39. (quality of life).mp
  40. QoL.tw.
  41. Survey research.tw.
  42. (health preference).tw.
  43. (preference elicit$).tw.
  44. SF-6D.tw.
  45. SF6D.tw.
  46. (standard gamble).tw.
  47. SG.tw.
  48. (time-trade off).tw.
  49. TTO.tw.
  50. Utility analysis.tw.
  51. (utility assessment).tw.
  52. (utility scores).tw.
  53. (health state valu$).tw.
  54. (economic evaluation).tw.
  55. (cost-effectiveness analysis).tw.
  56. 1-24 OR
  57. 25-55 OR
  58. 56 AND 57 (4794 studies)
  59. Myocardial infarction.mp
  60. (Heart attack).tw.
  61. (Heart failure).tw.
  62. Myocardial infarction.tw.
  63. Coronary thrombosis.tw.
  64. Congestive heart failure.tw.
  65. MI.tw.
  66. Angina.tw.
  67. Transient ischemic attack.tw.
  68. TIA.tw.
  69. Angina pectoris.tw.
  70. 59-69 OR
  71. 58 AND 70 (218 studies)
  72. Amputation.mp
  73. “Diabetic Neuropathies”.mp
  74. Exp Diabetic foot/
  75. Lower extremity amputation.tw.
  76. LEA.tw.
  77. Amputation.tw.
  78. Lower limb amputation.tw.
  79. (diab$ amputation).tw.
  80. (diab$ limb amputation).tw
  81. (diab$ foot amputation).tw
  82. (diab$ neuropathy).tw.
  83. Vascular disease amputation.tw.
  84. (“Diab$ foot” or “Diab$ foot ulcers” or “Diab$ ulcers” or “Diab$ leg ulcers”).tw.
  85. DFU.tw.
  86. Charcot foot
  87. (Diab$ neuropathic ulcers).tw.
  88. 72-87 OR
  89. 58 AND 88 (454 studies)
  90. Stroke.mp
  91. Ischemic stroke.tw.
  92. Cerebrovascular accident.tw.
  93. Anticoagulation.tw.
  94. Stroke risk.tw.
  95. Hemorrhagic stroke
  96. 90-95
  97. 58 AND 96 (135 studies)
  98. exp Kidney Failure, Chronic/
  99. kidney failure.mp
  100. acute kidney failure.tw.
  101. chronic kidney failure.tw.
  102. (“chronic kidney” or “chronic renal”).tw.
  103. (“endstage kidney” or “endstage renal”).tw.
  104. (end stage renal disease).tw.
  105. (ESRD or ESKD or ESRF or ESKF).tw.
  106. (“Renal insufficiency” or “chronic renal insufficiency” or “acute renal insufficiency”).tw.
  107. 98-106 OR
  108. 58 & 107 (427 studies)
  109. Diabetic retinopathy.mp
  110. exp Blindness/
  111. (“Visual acuity” or “visual acuity loss”).tw.
  112. (Blindness in one eye).tw.
  113. Macular degeneration.tw.
  114. (Age related macular degeneration).tw.
  115. ARMD.tw.
  116. 109-115 OR
  117. 58 & 116 (178 studies)

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Embase Search strategy = (4157)

  1. ‘Diabetes mellitus’/exp AND ([article]/lim OR [article in press]/lim) AND ([adult]/lim OR [aged]/lim) AND [humans]/lim AND [1966-2009]/py OR ('type 1 diabetes' OR 'type 2 diabetes' AND ([article]/lim OR [article in press]/lim) AND ([adult]/lim OR [aged]/lim) AND [humans]/lim AND [1966-2009]/py) OR ('diabetes complications'/exp OR 'diabetes related complications' OR 'diabetic patients' OR 'diabetic'/exp AND [1966-2009]/py)
  2. ('euroqol 5d' OR 'eq 5d' OR eq5d AND [1966-2009]/py OR ('health utility index mark 2' OR 'health utility index' OR 'health utility index mark 3' OR 'hui2' OR 'hui3' AND [1966-2009]/py) OR ('preference based quality of life' OR 'preference based measures' OR 'survey research' OR 'health preference' OR 'preference elicitation' AND [1966-2009]/py) OR ('health states' OR 'health status'/exp AND [1966-2009]/py) OR ('sf 6d' AND [1966-2009]/py) OR ('standard gamble' OR 'sg' AND [1966-2009]/py) OR ('time trade off' OR tto AND [1966-2009]/py) OR ('health state valuation' AND [1966-2009]/py))
  3. 1 AND 2

Cinahl Search Strategy = (368)

  1. (MH "Diabetes Mellitus+") or (MH "Diabetes Mellitus, Insulin-Dependent") or (MH "Diabetes Mellitus, Non-Insulin-Dependent")
  2. "diabetes complications"
  3. (MH "Diabetic Patients")
  4. (MH "Insulin+")
  5. (MH "Hemoglobins+")
  6. (MH "Hemoglobin A, Glycosylated")
  7. (MH "Hypoglycemia+")
  8. (MH "Hyperglycemia+")
  9. TX (type 1 diabetes) or TX (type 2 diabetes) or TX (diabetes mellitus type 1) or TX (diabetes mellitus type 2)
  10. TX (diabetic patients) or TX (adult diabetes) or TX (adult diabetics) or TX (diabetes related complications)
  11. TX (blood glucose level) or TX (glucose control)
  12. TX (haemoglobin a1c) or TX (haemoglobin a1c level) or TX (haemoglobin treatment)
  13. "diabetes treatment"
  14. (MH "Quality-Adjusted Life Years") or (MH "Quality of Life+")
  15. TX cost-utility analysis or TX CUA
  16. TX EuroQol-5D or TX EQ-5D or TX EQ5D
  17. TX (health utility index mark) or TX HUI$
  18. TX QALYS
  19. TX (preference based quality of life)
  20. TX (preference based measures)
  21. TX (health states) or TX QoL or TX (survey research)
  22. TX (health preference) or TX (preference elicitation)
  23. TX SF-6D
  24. TX (standard gamble) or TX SG
  25. TX (time-trade off) or TX TTO
  26. TX (utility analysis) or TX (utility scores) or TX (utility assessment)
  27. TX (health state valuation)
  28. TX (economic evaluation) or TX (cost-effectiveness analysis)
  29. S1 or S2 or S3 or S9 or S10 or S13
  30. S4 or S5 or S6 or S7 or S8 or S11 or S12
  31. S14 or S15 or S16 or S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28
  32. S29 and S30 and S31

Econlit Search Strategy = (9)

  1. (‘diabetes mellitus’ OR ‘diabetes complications’ OR ‘diabet$ complications’)
  2. Insulin.kw
  3. (hemoglobins OR ‘hemoglobin A, glycosylated’)
  4. Hemoglobins.kw
  5. (hypoglycaemia OR hyperglycemia).kw
  6. (‘type 1 diabetes’ OR ‘type 2 diabetes’ OR ‘diabetes mellitus type 1’ OR ‘diabetes mellitus type 2’ OR ‘diabetic patients’ OR ‘adult diabetes’ OR ‘diabetes related complications’)
  7. (‘blood glucose level’ OR ‘glucose control’)
  8. (‘haemoglobin a1c’ OR ‘haemoglobin a1c level’ OR ‘haemoglobin treatment’)
  9. (‘diabetes treatment’)
  10. Quality adjusted life years
  11. (‘cost-utility analysis’ OR CUA)
  12. (EuroQol-5D or EQ-5D or EQ5D)
  13. (‘health utility index mark’ OR ‘HUI$’)
  14. QALY$
  15. (‘preference based measures OR ‘preference elicitation’ OR ‘preference based quality of life’)
  16. (SF-6D OR ‘standard gamble’ OR SG OR ‘time-trade off’ OR TTO)
  17. (‘utility analysis’ OR ‘utility assessment’ OR ‘utility scores’ OR ‘health state valu$’ OR ‘economic evaluation’ OR ‘cost-effectiveness analysis’
  18. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9
  19. 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17
  20. 18 AND 19

Search terms for other databases

TUFTS CEA registry (89)

Diabetes (utility weights)

Health Technology Assessment (18), Cochrane systematic reviews (56)

Diabetes

Digital Theses (1)

Diabetes AND quality of life

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