Original Title: Seguridad, efectividad clínica y coste-efectividad de la estéreo-electroencefalografía en la cirugía de la epilepsia

Authors' objectives: The main objective of the present health technology assessment report were to evaluate the safety, clinical effectiveness and cost-effectiveness of EEEG for the location of the epileptogenic zone in people with refractory epilepsy programming for epilepsy surgery.

Authors' results and conclusions: RESULTS: CLINICAL EFFECTIVENESS AND SAFETY: The literature searches identified 1,061 potentially relevant citations, of which 161 reports were selected for full-text eligibility screening. Thirty-three cohort studies published in 39 reports were subsequently deemed suitable for inclusion according to predetermined selection criteria. The outcomes considered by the working group of this report as critical for decision-making were mortality, free-seizure status after surgery (Engel I), and permanent complications. The quality of the overall evidence was considered low. The 33 included studies enrolled a total of 2,959 participants who underwent an EEEG study. A total of 18,200 electrodes were implanted with a mean number of electrodes per patient of 11.3 (range 2-144). The mean time of implantation of the electrodes was 198 minutes (range: 45-480) and the mean recording time was 10.76 days (range: 2-30). Results showed that in 92% of patients who underwent EEEG, the epileptic focus was found (95% CI: 0.96-1.00). Of the 1,868 patients who underwent EEEG, 669 were free of seizures after surgery (pooled prevalence: 34%; 95% CI: 0.27 to 0.42) with expected heterogeneity by intervention groups (surgical resection, radiofrequency thermocoagulation, or both). If only patients who finally went for surgery are considered, 47% of patients remained free of seizures (95% CI: 0.37-0.58), again with heterogeneity by intervention groups. A good response after surgery (Engel I and II) was obtained in 45% of patients who underwent EEEG (95% CI: 0.38-0.53) and 66% when taking into account only patients who underwent surgery (95% CI: 0.55-0.75). A total of six deaths occurred among the 2,959 participants who were studied by EEEG, with no statistical heterogeneity between studies (I² = 0%; p <0.996). A pooled prevalence of 1.3% (95% CI: 0.9-1.7%) for all complications related to insertion and monitoring EEEG, and the subsequent intervention was obtained. Bleeding complications were those reported most frequently (pooled prevalence: 2%; 95% CI: 0.01-0.02; I² = 3.70%, p = 0.411). Among them, intracerebral bleeding was the most common type (pooled prevalence: 1%; 95% CI: 0.00-0.01; I² = 0.00%, p = 0.659). Infections were the second most frequent complications (pooled prevalence: 1%; 95% CI: 0.00-0.01; I² = 25.09%, p = 0.21). Among them, superficial infections and brain abscesses were the most common. In total, 20 patients had permanent neurological deficits (pooled prevalence: 1%; 95% CI: 0.00-0.03; I² = 59.90%, p = 0.008) and 17 patients had transient neurological complications (weakness or sensory changes) (pooled prevalence: 1%; 95% CI: 0.00-0.02; I² = 49.30%, p = 0.023). COST-EFFECTIVENESS: No cost-effectiveness analysis of EEEG versus no intervention from economic models was identified in the review of economic evaluations. Results of the economic evaluation in Spain showed that EEEG is a more effective alternative compared to non-intervention for localizing the epileptogenic zone in patients with refractory epilepsy considered for surgery but also more expensive. Health gains in terms of QALY favor the EEEG and appear sufficient to offset the increased cost. The obtained incremental cost-effectiveness ratio (ICER) is €12,100/QALY. The results of deterministic sensitivity analysis and scenarios show enough strength to provide high reliability to the deterministic result. Figures are significantly below the willingness to pay of €20,000-25,000/QALY in Spain. Meanwhile, the probabilistic sensitivity analysis shows a central value of €12,754/QALY, very close to the base case of the deterministic analysis and still below the willingness to pay of €20,000-25,000/QALY in Spain. The lower limit shows EEEG as a dominant alternative; however, the upper limit of the 95% confidence interval shows an ICER of €95,913/QALY. This is the only argument that can generate some uncertainty according to other results on the cost-effectiveness of EEEG versus non-intervention. CONCLUSIONS: The available evidence on clinical effectiveness and safety of EEEG for the location of the seizure focus in people with refractory epilepsy candidates to surgery derivates from observational studies with no control group. Pooled results of existing studies show that those participants with refractory epilepsy that went for surgery occording to EEEG results showed a high rate of epileptic focus localization. One third is free of seizures after surgery and approximately a half reduced seizures by more than 90%, becoming sporadic. Rate of total complications associated with the insertion and monitoring EEEG, and the subsequent intervention is low (pooled prevalence: 1.3%). The analysis of the available evidence, consisting of studies with very heterogeneous samples of participants, does not allow to identify which subgroups of patients would benefit most from the EEEG. No economic evaluations with cost-efectiveness analisys on the use of EEEG against no intervention to identify the epileptogenic zone in patients considered for surgery were found in the electronic databases consulted. The absence of these studies demonstrates the need to assess the EEEG for localizing the epileptogenic zone in refractory epilepsy patients scheduled for surgery. The EEEG is generally a cost-effective alternative for the location of the epileptogenic zone in patients with refractory epilepsy scheduled for surgery in Spain from the NHS perspective. This conclusion is robust enough according to sensitivity analyzes. This information should help decision making of clinicians and health managers.

Authors' recommendations: With the available evidence at the time of preparation of this report and using the more usual willingness to pay used to assess the results of such studies in Spain, it is suggested to consider EEEG for the location of the epileptic zone in patients with refractory epilepsy candidates for surgery in whom the epileptic zone could not be previously determined using non-invasive techniques. (Strength of recommendation: conditional)

Authors' methods: Systematic review of published literature with no time limits until April 2016. MEDLINE/PREMEDLINE, EMBASE, SCI, and CENTRAL were searched. A comprehensive search strategy that included controlled vocabulary and free text terms was used. In addition, a manual search was performed with the references of articles included. Original studies published in English or Spanish that assessed the EEEG to identify the most accuracy epileptogenic zone were selected. Randomized and non-randomized controlled trials and cohort studies on adults and/or children with medically intractable epilepsy were included in the review for safety and effectiveness. Considered outcome measures were: the location of the seizure focus, the final decision to perform surgery and/or the site of the surgery, the result of surgery, complications and any other self-reported outcome by patients such as the functional capacity and health-related quality of life. Methodological limitations of the included non-randomized studies were assessed according to the criteria of the Cochrane risk of bias assessment tool for non-randomized studies of interventions (ACROBAT-NRSI). Data are presented through narrative synthesis and tables. Pooled estimates of the location of the seizure focus, the result of surgery and complications were obtained using meta-analysis (software Stata/MP 14 for Windows). Due to the lack of control groups in the included studies it was not possible to calculate relative risk ratios so that grouped proportions were calculated. The methodology of the international working group Grading of Recommendations Assessment, Development and Evaluation (GRADE) was follow to assess the quality of evidence and to grade the strength of the recommendations. For cost-effectiveness evaluation, a review of economic evaluations of EEEG against non-intervention for patients with refractory epilepsy considered for surgery was firstly performed. The search strategies and databases were the same applied for the review of the effectiveness and safety. Full economic evaluations were selected, i.e. those in which both costs and results of at least two alternatives are compared. Both economic evaluations developed in parallel to clinical trials and economic models were included. It was decided to evaluate methodological quality of economic evaluations according to criteria of López-Bastida et al. A full economic evaluation contextualized for Spain in which health and costs results of EEEG for the location of the seizure focus (or seizure network) in patients with refractory epilepsy considered for surgery were compared with non-intervention. A cost-effectiveness analysis in which the outcome measure was life years gained and a cost-utility analysis in which the outcome measure was quality-adjusted life-year (QALY) were undertaken. A decision tree for the first year and a Markov model for the rest of the years was implemented. National Health System (NHS) perspective for a time horizon spanning the entire life of the patient through annual cycles was considered. A design very close to the study of Burch et al. was taken as progression model of epilepsy. Complementarily, both deterministic and probabilistic sensitivity analysis were performed to determine the robustness of the model as well as the uncertainty about the parameters and results.

Project Status: Completed

Year Published: 2016

URL for published report: https://sescs.es/seguridad-efectividad-y-coste-efectividad-de-la-estereo-electroencefalografia-en-la-cirugia-de-la-epilepsia/

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