Value Health. 2004 Jul-Aug;7(4):442-54.
Patient preference and willingness-to-pay for Humalog Mix25 relative to Humulin 30/70: a multicountry application of a discrete choice experiment.
Aristides M, Weston AR, FitzGerald P, Le Reun C, Maniadakis N.
M-TAG Limited, London, England, UK
OBJECTIVES: To assess preference and willingness-to-pay (WTP) for the insulin mixture Humalog Mix25 relative to Humulin 30/70, from the patients' perspective, the relative importance of individual treatment attributes was also determined. Differences among five European countries were investigated. METHODS: Two hundred and ninety patients with type 2 diabetes were recruited from five European countries. Of these, 235 were suitable for inclusion in the analysis. Their mean age was 51.3 years and, on average, patients had had diabetes for 11 years. A discrete-choice conjoint analysis was conducted using face-to-face interviews. Treatment attributes, such as timing of injections around meals, 2-hour postprandial control, effect of prandial dosing, frequency of nocturnal hypoglycemia, and cost, and levels were derived after a systematic review of all published comparative clinical trial data. Meta-analyses were undertaken where appropriate. RESULTS: Ninety percent (95% CI 86-93%) of patients would choose Humalog Mix25 over Humulin 30/70, at the same cost. On average, European subjects were willing to pay 111 euros per month more for Humalog Mix25 (95% CI 86.71-156.91 euros). The primary driver was the reduced risk of nocturnal hypoglycemic events, contributing 49% of WTP. The convenience of dosing immediately before the meal contributed 37%. Preference results were similar in all five countries, although WTP and sensitivity to increasing cost both varied. CONCLUSIONS: Patients in all countries showed a preference and WTP for Humalog Mix25 over Humulin 30/70. The main drivers of patient WTP may be of interest to pharmaceutical prescribers, manufacturers, and reimbursement agencies.

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IEEE Trans Biomed Eng. 2005 Jan;52(1):3-12.
Insulin kinetics in type-I diabetes: continuous and bolus delivery of rapid acting insulin.
Wilinska ME, Chassin LJ, Schaller HC, Schaupp L, Pieber TR, Hovorka R.
Department of Paediatrics, University of Cambridge, Cambridge, CB2 2QQ, UK.
We investigated insulin lispro kinetics with bolus and continuous subcutaneous insulin infusion (CSII) modes of insulin delivery. Seven subjects with type-1 diabetes treated by CSII with insulin lispro have been studied during prandial and postprandial conditions over 12 hours. Eleven alternative models of insulin kinetics have been proposed implementing a number of putative characteristics. We assessed 1) the effect of insulin delivery mode, i.e., bolus or basal, on the insulin absorption rate, the effects of 2) insulin association state and 3) insulin dose on the rate of insulin absorption, 4) the remote insulin effect on its volume of distribution, 5) the effect of insulin dose on insulin disappearance, 6) the presence of insulin degradation at the injection site, and finally 7) the existence of two pathways, fast and slow, of insulin absorption. An iterative two-stage parameter estimation technique was used. Models were validated through assessing physiological feasibility of parameter estimates, posterior identifiability, and distribution of residuals. Based on the principle of parsimony, best model to fit our data combined the slow and fast absorption channels and included local insulin degradation. The model estimated that 67(53-82)% [mean (interquartile range)] of delivered insulin passed through the slow absorption channel [absorption rate 0.011(0.004-0.029) min(-1)] with the remaining 33% passed through the fast channel [absorption rate 0.021(0.011-0.040) min(-1)]. Local degradation rate was described as a saturable process with Michaelis-Menten characteristics [VMAX = 1.93(0.62 - 6.03) mU min(-1), KM = 62.6(62.6 - 62.6) mU]. Models representing the dependence of insulin absorption rate on insulin disappearance and the remote insulin effect on its volume of distribution could not be validated suggesting that these effects are not present or cannot be detected during physiological conditions.