302 chapter 4 Societal costs (in €) were assessed during one year calculated from the date of the [18F]FDG-PET/CT scan and included all direct medical costs for thyroid-related and other health care consumption, patient costs (i.e., informal care, travel expenses to any health care-related appointments) and productivity losses. For the thyroid-related health care consumption, the real volumes of health care consumption were extracted from individual patient files. The extracted data included all thyroid surgeries and associated hospital admission days, additional diagnostics, surgeries, and hospital admission days following surgical complications, all outpatient clinic visits and diagnostics related to the diagnosis and treatment of the index nodule, additional diagnostics and consultations with other physicians related to [18F]FDG-PET/CT incidental findings, and use of thyroid-related medication. Data concerning other, non-thyroid-related health care consumption and productivity losses were patient-reported at 0 (baseline), 3, 6 and 12 months, using the iMTA Medical Consumption Questionnaire (iMCQ), the iMTA Productivity Costs Questionnaire (iPCQ) questionnaire, respectively [472, 473]. To estimate health care consumption and productivity for the periods that were not covered by a cost questionnaire (by design of the trial and by the respective 3-month and 4-week recall periods of the iMCQ and iPCQ questionnaires), missing data were interpolated from the closest available questionnaires from the same patient. Health care was valued using reference prices and the 2019 reimbursement rates of the Dutch System of Diagnosis-Treatment Combinations, where appropriate and available [476, 477]. The estimated cost of one partial-body [18F]FDG-PET/CT scan was €754 [476, 477]. Costs for any complications of the diagnostic surgeries or completion thyroidectomies (i.e., admission days for prolonged hospitalization or re-admission, diagnostics and/or additional surgeries) were estimated using the Dutch reimbursement rates. Costs of productivity losses were assessed using the friction cost method and reference prices for productivity [477]. Travel expenses were estimated at €0.19 per kilometer [477]. We estimated all costs from a Dutch societal perspective in Euros. All prices were indexed to 1 December 2019 using the Dutch consumer price index [478]. All [18F]FDG-PET/CT-related costs, including procedure costs, costs for additional healthcare consumption for incidental [18F] FDG-PET/CT findings, travel expenses and other reported patient costs, were only taken into account for patients in the [18F]FDG-PET/CT-driven group. The total societal costs were estimated as the sum of medical costs for all thyroid nodule-related and all other health care consumption, patient costs (i.e., travel expenses and informal care), and costs from productivity losses. The differences in societal costs between the [18F]FDG-PET/CT-driven and diagnostic surgery group over the first year were calculated using independent two-sample t-tests with unequal variances. A generalized linear model (GLM) was used to adjust for the stratifying factors and malignancy rate; the adjusted p-value, corrected mean difference and 95% confidence interval are presented. As the postoperative treatment of the individual patients was based on the local histopathological diagnosis and likely influenced the costs, this diagnosis was included in the GLM.
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