Original Title: Efectividad, seguridad y coste-efectividad del sistema flash de monitorización de glucosa en líquido intersticial (FreeStyle Libre®) para la diabetes mellitus tipo 1 y 2

Authors' objectives: The objective of this report is to identify, evaluate and synthesize the available scientific knowledge on the effectiveness, safety, cost-effectiveness and budget impact Flash glucose monitoring system in interstitial fluid (FreeStyle Libre®) versus traditional self-monitoring, in patients with DM1 and DM2.

Authors' results and conclusions: RESULTS: EFFECTIVENESS AND SAFETY: [Type-1 Diabetes Mellitus] In a recent randomized controlled study on the flash glucose monitoring system in people with DM1, no significant differences were obtained in the number of patients who suffered severe adverse events (AEs): 5 (4.2%) in the intervention group (IG) and 4 (3.3%) in the control group (CG) (relative risk (RR) = 1.27, 95% confidence interval (CI): 0.33, 4.86). The total number of events was 5 in each group and none were considered related to the device. The number of patients who suffered AEs was 62 (52%) in IG and 60 (50%) in the CG; the difference was not significant (RR = 1.04, 95% CI: 0.81, 1.34). In the IG, these AEs were attributed to the flash system in 10 patients (8.4% of total). In the reduction of severe hypoglycemia events (requiring attention from another person), at 6 months, 2 patients in IG (1.7%) and 3 in the CG (2.5%) had hypoglycemic events, with no significant differences. No significant differences between IG and CG were observed in reducing levels of HbA1c (mean difference (m.d.) = 0.00%; 95% CI -0.11 to 0.12). At the biochemical hypoglycemia threshold (<70 mg/dL), the IG showed a statistically significant difference versus the CG in reducing the number of hours per day below 70 mg/dL (mean difference (m.d.) = -1.24, 95% CI: -1.71, -0.77), representing a decrease of 38%. In other measures related to biochemical hypoglycemia, results at 6 months were also significantly favorable to IG. Regarding health-related quality of life, significant differences in favor of IG were obtained in two subscales of the Diabetes Treatment Satisfaction Questionnaire (DTSQ): "total satisfaction" (m.d. = 6.1, 95% CI: 4.45, 7.75) and "perceived frequency of hyperglycemia" (m.d. = -1.0, 95% CI -1.43, -0.57), representing effect sizes of 0.94 and 0.59, respectively. ECONOMIC EVALUATION: The electronic search did not find published economic evaluations. Abbott Diabetes Care provided to the Health Technology Assessment Unit of Canary Islands (SESCS), during the process of preparing the report, an economic evaluation and a budget impact analysis for this technology in the NHS. Both studies were conducted by Pharmacoeconomics & Outcomes Research Iberia S.L. (PORIB) for Abbott Diabetes Care. In addition, Abbott provided restricted access to both the economic evaluation model implemented with specific software and online access, and to the implementation of the budget impact model in an Excel file. Subsequently, and beyond the time set for the allegations phase, Abbott provided a new report with clarifications and modifications in light of the limitations previously identified during SESCS's critical assessment of the initial material delivered by Abbott Diabetes Care. This new report was prepared by the Health Technologies Assessment Unit (UETeS) of Francisco de Vitoria University. The economic evaluation conducted a cost-effectiveness analysis of the FreeStyle Libre® against SMBG, both with insulin, for glucose monitoring in type-1 and type-2 DM patients with multiple daily injections (MDI) versus SMBG, currently considered the standard strategy. The model design is based on the CORE Diabetes Model (CDM), adapted to the Spanish context as a model for type-1 and type-2 DM progression. The analysis was performed from the perspective of the NHS. For this reason, only direct health costs are included in the analysis. The time horizon comprised 40 and 50 years for type-1 and type-2 DM, respectively, considering annual cycles. The results of the economic evaluation, considering the threshold of €30,000 per QALY, indicate that the FreeStyle Libre® is a cost-effective intervention in the control of glucose and prevention of hypoglycemia events, for both type-1 and type-2 DM patients treated with MDI. The results of the economic evaluation study provided by Abbott present areas of uncertainty and limitations associated with the use of certain relevant inputs of the model, and the absence of a sensitivity analysis. Although the documentation provided in the claims process addresses some of these issues and provides a new sensitivity analysis, the study continues to present uncertainties and limitations, and the sensitivity analysis is not implemented correctly in all its aspects and is not complete or informative. This implies that the results should be interpreted with caution when issuing recommendations on the use of the FreeStyle Libre® system in patients with DM. Despite some limitations, the budget impact of using the FreeStyle Libre® system in patients with DM is sufficiently reported. CONCLUSIONS: EFFECTIVENESS AND SAFETY: - There is limited scientific evidence on the safety and effectiveness of FreeStyle Libre® System, based exclusively on two industry-funded RCTs (One recently published with patients with DM1 and the other with patients with DM2, not published at the time of issuing this evaluation report on health technologies). - There is low quality evidence about the safety of FreeStyle Libre® System, compared to traditional monitoring. However, there has been no serious adverse events that may be attributed to the device and the previous research on systems of continuous glucose monitoring shows that it is safe devices generally only produce AEs mild in the insertion of the sensor. In any case, the recommendation of its use would have to be accompanied by a detailed explanation to the patient with DM over its potential adverse effects and risk/benefits, in a framework of shared decision making. - The existing evidence on the effectiveness of the device to decrease the rate of severe hypoglycemia in patients with DM1 is of poor quality. However, there is evidence of moderate quality that the device is more effective than traditional monitoring to reduce events and time elapsed in biochemical hypoglycemia (defined according to different thresholds), both during the day and at night, in patients with DM1 With controlled HbA1c levels (<7.5%). - There is moderate quality evidence that such improvements happen without a worsening of HbA1c levels. - There is low quality evidence that the use of device increases levels of patient satisfaction with treatment. ECONOMIC EVALUATION: - The electronic search has not found published economic evaluations. - The results of the economic evaluation study provided by Abbott present areas of uncertainty and limitations associated with the use of certain relevant inputs of the model, and the absence of a sensitivity analysis. Although the documentation provided in the claims process outweighs some of them while providing a de novo sensitivity analysis, the study continues to present uncertainties and limitations, while the sensitivity analysis is not implemented correctly in all its meanings, and is not complete enough and informant. This implies that the results should be interpreted with caution to issue some recommendations on the use of the FreeStyle Libre® System in patients with DM. For its part, despite some limitations, the budgetary impact of using the FreeStyle Libre® System in patients with DM is sufficiently reported.

Authors' recommendations: - Based on the evaluated evidence, a conditional recommendation is made in favor of the use of the FreeStyle Libre® System for patients with DM1 with controlled HbA1c levels (<7.5%), and with a good prior adhesion in the use of self-monitoring glucose in blood. - Is necessary to have more scientific evidence on the effectiveness and cost-effectiveness of the FreeStyle Libre® System before making any strong recommendation. - An economic evaluation that provides greater robustness due to the uncertainty of the parameters used through a broader and more comprenhensive sensitivity analysis is required before making any strong recommendation.

Authors' methods: EFFECTIVENESS AND SAFETY: Electronic databases Medline, PREMEDLINE, Embase, Cochrane Central and Systematic Reviews and Web of Science to June 2016 were consulted to carry out a systematic review (SR) of secondary primary studies (randomized controlled trials) and (RS with meta-analysis). Systematic reviews (SR) with meta-analysis (MA) were included evaluating the effectiveness and safety of flash glucose monitoring FreeStyle Libre® system for DM1 and DM2, randomized controlled trials (RCT) evaluating the effectiveness and safety of the flash system glucose monitoring interstitial fluid (FreeStyle Libre®) for DM1 and DM2 and clinical practice guidelines (CPG) and other reports of health technology assessment (HTA) were also considered. Studies with adults, adolescents and children diagnosed using the standard criteria with DM1 or DM2 were included in outpatient care, the intervention group used the flash glucose monitoring system in interstitial fluid (FreeStyle Libre®) and the control group perform SMBG capillary or other CGMS-TR. The risk of bias of the primary studies was assessed using the Cochrane Collaboration tool. Global quality of evidence was assessed with the GRADE system, with the aim of exploring the values and preferences of patients about the intervention and comparison, to help establish the grade of the possible recommendations, so information on the acceptability and patient preferences regarding technology evaluated in the included RCTs was sought. ECONOMIC EVALUATION: An RS of the economic evaluations of FreeStyle Libre® system was carried out against the AMGS system for the monitoring of glucose in patients with DM. The search strategies were the same applied for the review of effectiveness and safety. Comprehensive economic assessments were included, i.e., those in which both costs and results of at least two alternatives are compared. Both economic evaluations developed parallel to clinical trials and economic models were included. A critical assessment was carried out, according to the Economic Assessment Guide (EAG) and the Budget Impact Guideline (BIG), of an economic evaluation study as well as a budget impact study carried out by the promoter industry, an alternative for glucose monitoring, the FreeStyle Libre® system against the WMSG performed by the patient himself for people with DM1 and DM2. The critical appraisal addresses the fundamental issues for both economic evaluation and budget impact which allow to issue a recommendation on the reliability of both studies for decision making on the financing of the FreeStyle Libre® by the National Health System (SNS).

Project Status: Completed

Year Published: 2016

URL for published report: https://sescs.es/sistema-flash-de-monitorizacion-de-glucosa-en-liquido-intersticial-freestyle-libre-para-la-dm-tipo-1-y-2/

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