390 chapter 7 in case of an incomplete or missing HRQoL assessment, patients were reminded up to four times by email or phone call, starting approximately two weeks and ending two months after the mailing date. Three questionnaires were used: the Thyroid Patient-Reported Outcome (ThyPRO), the EQ-5D-5L, and the RAND 36-item Health Survey v2.0 (RAND-36) questionnaire [471, 595-597]. The EQ-5D-5L is a generic health status measure that applies five levels of severity to address five dimensions of someone’s current well-being: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Utilities (index scores) were calculated from the EQ-5D-5L domain scores using the Dutch tariff, and are scaled from 0 (as bad as death) to 1 (full health) [471, 474]. The mean one-year QALYs were estimated as the area under the utility curve. The generic RAND-36 addresses eight health status dimensions on the domains of physical and mental health: physical functioning, social functioning, role limitations due to physical health problems, role limitations due to personal or emotional problems, mental health (i.e., emotional well-being), bodily pain, vitality, and general health perceptions. It also includes a single item that indicates the perceived change in health. The RAND-36 has a four-week recall period. For each dimension, item scores are subsequently added up and transformed to a 100-point scale. A higher score represents better health. Aggregate physical and mental component scores (PCS and MCS, respectively) are calculated from the corresponding domain scores [595, 596]. The 98-item ThyPRO is a validated, thyroid-specific HRQoL questionnaire. It uses a five-point scale to address 14 domains over a four-week recall period: four thyroid disease-related symptom domains (symptoms of neck-related goitre, hyper- and hypothyroidism, and eye symptoms), five domains of physical and mental functioning and well-being, and five domains examining the impact of the thyroid disorder on essential HRQoL aspects. Within each domain, the five-point-scale item scores are averaged and linearly transformed to a 0-100 scale, with higher scores indicating worse health states [597]. A composite score is additionally calculated, summarizing 22 items [598]. We used the predefined minimally important change (MIC) values to assess observed HRQoL differences within and between groups [599]. The MIC represents “the smallest difference in a score from a HRQoL questionnaire that is perceived by patients as important, either beneficial or harmful”, and that is therefore likely meaningful to patients and physicians [600]. cTT, completing total thyroidectomy. Excl., excluding. fT4, free thyroxine, reference range approximately 10-25 pmol/L (sex and age dependent). HRQoL, Health-related quality of life. Incl., including. IQR, interquartile range. SD, standard deviation. RAI, radioiodine therapy. TSH, thyroid stimulating hormone, reference range 0.4-4.0 mU/L. US, ultrasound. *: Three, one and two patients completed the 3-, 6- and 12-month HRQoL assessment, respectively, but not the baseline HRQoL assessment. a: Pearson’s chi square test. b: one-way ANOVA. c: KruskalWallis test. d: Mann-Whitney U test.
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