502 chapter 13 In cost-utility studies concerning the diagnosis of thyroid nodules, quality of life is oftentimes the least variable parameter: disease-related morbidity is relatively low and survival from differentiated thyroid cancer is very good as compared to other cancer types [28]. Therefore, according to the formula above, costs are often the main driver of the net benefit in these studies. Besides that, with the increasing incidence of differentiated thyroid cancer and the increased detection rate of thyroid nodules, critically evaluating the costs of the diagnostic workup of thyroid nodules is of vital importance [1-12]. In 2014, it was estimated that the annual health care expenses for differentiated thyroid carcinoma would increase from 1.6 billion US dollars in 2013 to more than 3.5 billion US dollars in 2023. In 2013, approximately 41% of this budget was spent on the diagnosis and treatment of newly diagnosed patients [734]. It is assumed that an important part of the incurring health care costs is generated by the overdiagnosis of benign and subclinical malignant disease [1]. Many thyroid-related cost-effectiveness studies therefore focus on improving the diagnostic workup while lowering its costs and maintaining HRQoL [29, 176, 178, 495, 579]. In the EfFECTS trial, we demonstrated that an [18F]FDG-PET/CT driven diagnostic workup may decrease the lifelong societal costs by almost €10,000 as compared to advising diagnostic surgery for all patients with a Bethesda III or IV thyroid nodule (€103,500 versus €113,400, respectively, p=0.14). The unfortunate statistical non-significance of this large cost difference was likely driven by the complex parameter uncertainty that was incorporated in our cost-effectiveness model [28]. Selective use of resources During the conduction of the EfFECTS trial, we encountered bidirectional crossover of patients between the surgical and active surveillance groups. This demonstrated the importance of patient counselling before conducting any additional diagnostics. In accordance with the Dutch guidelines and the principles of clinical utility, additional diagnostics should only be offered to patients in whom it may change the course of treatment and in whom it has the potential to change patient outcomes [30, 467]. This especially applies when aiming to rule out malignancy and prevent diagnostic surgery for benign nodules. When a patient has a strong desire to undergo diagnostic thyroid surgery due to mechanical or cosmetic complaints caused by the thyroid nodule, or when a persistent fear of malignancy is expected even when additional diagnostics would result negative, performing further rule-out testing should be withheld to prevent unbeneficial use of valuable resources. Conversely, additional diagnostics may be beneficial when a patient has a strong desire not to undergo surgery, because a reassuring negative test confirming a (likely) benign diagnosis would ensure that active surveillance is oncologically safe. When ancillary testing is performed with the aim to rule in malignancy (which does not apply to [18F]FDG-PET/CT but may apply to MD, in accordance with the results of this thesis), we should also
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