Original Title: Inyección percutánea de etanol en patología nodular tiroidea y adenopatías cervicales metastásicas

Authors' objectives: The main objective of this Health Technology Assessment (HTA) report is to assess the safety, clinical effectiveness, and cost-effectiveness, as well as the ethical, legal, organizational, social, patient, and environmental aspects of the use of PEI, compared to usual treatment or care (surgery) or other percutaneous thermal procedures (laser, radiofrequency or microwave ablation) for the treatment of thyroid nodular disease and metastatic cervical lymph nodes.

Authors' results and conclusions: Systematic review of effectiveness and safety The evaluation of the effectiveness and safety is based on data from three RCTs (N=157), published between 2013 and 2022, which analyzed the use of PEI versus RFA in patients with benign thyroid nodular pathology. The evidence is considered as being of a moderate quality. In general, the results of the studies indicate that PEI is similar in effectiveness and safety to RFA in the treatment of benign thyroid nodules (solid and predominantly cystic). No statistically significant differences were observed in therapeutic success (thyroid lesion volume reduction ≥50%) (RR=0.96; 95% CI: 0.88 to 1.04; p=0.33; I2=14%), thyroid lesion volume reduction (%) (MD=-1.18; 95%CI: -8.73 to 6.37; p=0.76; I2=62%), pressure symptoms (RR=0.23; 95%CI: -0.26 to 0.71; p=0.36; I2=47%), cosmetic discomfort (RR=0.12; 95% CI: -0.09 to 0.34; p=0.26; I2= 0%) and major complications (RR=2.76; 95% CI: 0.12 to 64.41; p=0.53). In the subgroup analysis, no statistically significant differences were observed in the percentage reduction in lesion volume between solid nodules and predominantly cystic nodules (χ 2=1.63; df=1; p=0.20; I2= 38.5%). No studies were identified that evaluated the effects of PEI in patients with malignant thyroid nodules or metastatic cervical lymph nodes who met the pre-established selection criteria. No studies comparing PEI with surgery or with any other percutaneous thermal procedure other than RFA were identified. Cost analysis The SR did not find any previous economic evaluation that met the established criteria. The results of the base case of the economic model designed in the present report determine that, from the perspective of the NHS, the cost per patient of PEI is €326.19 compared to €4,781.46 for RFA, which means an incremental difference of -€4,455.27. The cost of the intervention itself is has the greatest weight in the total cost in both alternatives (€297.78 and €4,711.54, respectively). Deterministic and probabilistic sensitivity analyzes confirm the robustness of the base case results. Regarding the gross budgetary impact of the use of PEI in patients with benign thyroid nodules that are purely or predominantly cystic, who need treatment and do not receive surgery as first-line treatment, this technology is estimated to have a cost of €207.61 million euros for the NHS if a time horizon of three years is considered. Organizational, ethical, social, legal and patient-related aspects The scoping review did not find any study related to PEI. According to the results obtained in the primary study conducted with expert professionals and patients on ethical, legal, organizational, social, patient, and environmental aspects, there was no agreement among the experts in relation to considering EPI as a suitable therapeutic option for people with thyroid nodular pathology and/or metastatic cervical adenopathies. On the contrary, they agreed that its effectiveness varies depending on the type of lesion which it is applied to. Treatment with PEI in the Spanish hospital context would be possible as it does not require additional equipment to the existing equipment; however, it would be necessary to have enough properly trained health staff and to have an official protocol with well-defined clinical algorithms. The patients who were consulted valued PEI as a satisfactory, minimally invasive, almost painless, comfortable, and fast-recovery outpatient procedure. The main disadvantages mentioned were the limited information on the possible side effects and long-term benefits of PEI and the slowness of the procedure compared to surgery. Conclusions • The available evidence on the clinical effectiveness and safety of the technology comes from three studies (N=157) evaluating the use of PEI versus RFA in patients with benign thyroid nodules (solid and predominantly cystic). • The available evidence on effectiveness and safety allows us to draw the following conclusions about the use of PEI versus RFA for the treatment of benign thyroid nodules: − No effect was observed either for or against the therapeutic success rate (≥ 50% reduction in the volume of the thyroid lesion) (RR=0.96; 95% CI: 0.88 to 1.04; p=0. 33; I2=14%), − No effect was observed either for or against in terms of reducing the volume of the thyroid lesion (MD=-1.18; 95% CI: -8.73 to 6.37; p=0.76; I2=62%). − No effect was observed either for or against pressure symptoms (RR=0.23; 95%CI: -0.26 to 0.71; p=0.36; I2=47%). − No effect was observed either for or against cosmetic discomfort (RR=0.12; 95% CI: -0.09 to 0.34; p=0.26; I2=0%). − No effect was observed either for or against in terms of major complications (RR=2.76; 95% CI: 0.12 to 64.41; p=0.53). • No studies were identified that evaluated the effects of PEI in patients with malignant thyroid nodules or metastatic cervical adenopathies that met the selection criteria established in the SR. • No studies were identified that compared PEI with surgery or with another percutaneous thermal procedure different from RFA that met the selection criteria established in the SR. • No previous economic evaluations were identified that evaluated the PEI and that met the selection criteria set out in the SR. • Assuming equal effectiveness among alternatives, the economic evaluation of the present report concludes that PEI is a less expensive technology than RFA for the treatment of benign, predominantly cystic thyroid nodules that require treatment and do not receive surgery as firstline treatment, from an NHS perspective. • The application of PEI for the treatment of purely benign or predominantly cystic thyroid nodules, which need treatment and do not receive surgery as first-line treatment has a gross budgetary impact of €207.61 million for the NHS for a 3-year horizon. • No studies were found that analyzed the ethical, legal, organizational, social, patient-related and environmental aspects related to the evaluated technology. • From the consultation carried out with patients and professionals on ethical, legal, organizational, social, patient, and environmental aspects, it is concluded that: − There is no agreement among professionals on whether PEI is an appropriate therapeutic option for people with thyroid nodular pathology and/or metastatic cervical adenopathies, although they recognize its better risk/benefit ratio compared to other more invasive procedures is an advantage. On the contrary, they agreed that, based on their experience, its effectiveness varies depending on the type of injury which it is applied to. − Half of the clinical professionals considered that the implementation of PEI treatment in the Spanish hospital context would be possible since no additional equipment is required to that already currently available. However, it would be necessary to have enough properly trained health staff (specialists in specific skills in this technology), and to have an official protocol with well-defined clinical algorithms. − The patients who were consulted valued PEI as a minimally invasive procedure, which was almost painless, comfortable and quick to perform and recover from.

Authors' methods: Effectiveness and safety A systematic review (SR) of the scientific literature published up to July 2022 was conducted. Randomized clinical trials (RCTs) were selected. The main outcome measures were: percentage reduction in lesion volume and success of the intervention (≥50% lesion volume reduction). The risk of bias was assessed according to the RoB 2.0 tool of the Cochrane Collaboration. When possible, a quantitative synthesis of the results was performed through meta-analysis using the Review Manager program in its version 5.4. The evaluation of the quality of the evidence and the grading of the strength of the recommendations were carried out following the methodology of the international working group Grading of Recommendations Assessment, Development and Evaluation (GRADE). Economic analysis / Cost-effectiveness The SR of the present report included the search for studies of complete economic evaluations conducted in parallel to primary studies or consisting of economic models, which considered, as a measure of result, costs expressed in monetary units and benefits in terms of years of life adjusted for quality (QALY), monetary benefits, or any of the other measures selected in the safety and effectiveness review. Two reviewers (economists) selected the identified references. Assessment of methodological quality was based on the Drummond et al. criteria list. 2005 and the recommendation guide, developed by López-Bastida et al. 2010. Finally, data extraction and a narrative synthesis of the results were planned. A de novo economic evaluation was also carried out, for Spain, to evaluate the cost-minimization of the use of PEI, from the perspective of the National Health System (NHS), in the treatment of patients with predominantly cystic benign thyroid nodules that, requiring treatment, do not receive surgery as first-line treatment. A decision tree was built for a 6-month time horizon, where only the costs of this technology were compared with radiofrequency ablation (RFA), since the same clinical effectiveness is assumed between interventions. The costs included cover direct healthcare costs (intervention, operating physicians and patient observation period after treatment), expressed in 2022 euros and without the application of discount rates. A deterministic and probabilistic sensitivity analysis was conducted to quantify the uncertainty around the model results. In addition, the gross budgetary impact for the NHS was calculated of applying this treatment to patients with purely benign and predominantly cystic thyroid nodules who require treatment and who do not receive surgery as first-line treatment. This analysis was conducted for a 3-year time horizon and the sensitivity of the results to variations in the target population and the total cost per patient was evaluated. Organizational, ethical, social, legal and patient-related aspects A scoping review was developed to evaluate the ethical, patient and social, legal, organizational and environmental aspects related to the technology. Since no evidence was identified on these aspects in the literature review, a consultation took place with a group of experts made up of professionals with experience in thyroid nodular pathology, metastatic cervical adenopathies and/or treatment with PEI and patients with any of these diseases or treated with PEI. A questionnaire was prepared where the participants were asked to answer questions to identify organizational, ethical, social, legal, environmental, and patient-related aspects of PEI.

Project Status: Completed

Year Published: 2023

URL for published report: https://sescs.es/wp-content/uploads/2015/09/67_SESCS_IPE_DEF_NIPO.pdf?x68814

Requestor: Ministry of Health

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es