Proefschrift

PWB insurgically treated trauma patients with peri- and/or intra-articular fractures of the lower extremities is cost effective 107 concordance with the guidelines, all hours of unpaid work were valued as replaced by payed help.23 The costs of medication were based on the price per dosage. Prescription costs were added for all medications except for over-the-counter drugs. Costs were, where necessary, indexed for the year 2018 (in Euros). Due to the lack of information about the travel arrangements of the family members, the assumption was made that they only traveled by car. For the travel tariffs the distinction was made between hospital visits and non-hospital visits. Tariffs were provided by the Dutch guidelines.21,22 All costs were indexed for inflation to the year 2018 using the consumer price index.24 Discount rates did not apply due to the time horizon of 26 weeks. Economic analysis For the CEA, we calculated the incremental cost and effectiveness of the PWB compared to the RWB. Incremental costs are defined as the mean difference between both groups in total costs over 26 weeks post-surgery. Incremental effectiveness is the mean difference in the LEFS over 26 weeks post-surgery. The incremental cost-utility was calculated as the difference in total costs divided by the difference in QALYs. The Incremental Cost-Effectiveness Ratios (ICERs) were given as costs (€) per unit improvement on the LEFS and costs (€) per QALY. All analyses were performed according to the intention-to-treat principle. Clinical difference between the PWB group and the RWB group, were assessed using a linear mixed-effects regression model in IBM SPSS Statistics, Version 25.0, Armonk, New York. As costs data are generally skewed and not distributed normally, non-parametric bootstrap re-sampling techniques were performed in STATA 14, with 5,000 replications to estimate cost-effectiveness uncertainty intervals around the ICERs.25,26 Bootstrapping is a non-parametric way to repeatedly conduct an analysis by resampling, with replacement, from the observed data.27 Seemingly unrelated regression equations (SURE) were bootstrapped (5,000 times) to allow for correlated residuals of the cost and utility equations. The uncertainty interval is represented by the 2.5th and 97.5th percentiles. The results of ICER bootstraps are presented in costeffectiveness planes and cost-effectiveness acceptability curves (CEACs).28 Costeffectiveness planes show differences in effect on the horizontal axis and costs on the vertical axis. Bootstrapped cost-effectiveness pairs located in the northwest quadrant indicate the PWB to be inferior to conventional care (more costly and less effective); in the south-east quadrant to be dominant (more effective and less costly); and with respect to the north-east and south-west quadrant, the preference for an intervention depends on the threshold value, that is, what society is prepared to pay for an

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