French National Authority for Health assessment of metabolic surgery for type 2 diabetes remission-A meta-analysis in patients with class I to III obesity.

OBJECTIVE: Randomized controlled trials (RCTs) have demonstrated the superiority of metabolic surgery (MS) over medical therapy (MT) in patients with obesity and type 2 diabetes, leading, to a joint statement in 2016 proposing MS to patients with class I obesity and uncontrolled glycemia. Yet, these RCTs included few patients with class I obesity (body mass index 30-35 kg/m2) and even fewer patients with overweight. Our aim was to provide an updated systematic review (SR) with meta-analysis (MA) of RCTs reporting diabetes remission (DR) after MS in these patients. RESEARCH DESIGN AND METHODS: We included in the SR with MA only RCTs with at least 24-month follow-up found in Medline, Cochrane Library, Embase, and LiSSA between January 2008 and September 2022 comparing DR post-MT versus post-MS. We calculated relative risk (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel random-effects approach to examine differences in DR between patients allocated to MS versus MT. RESULTS: DR was significantly higher in MS versus MT after 36 months' follow-up in patients with obesity (RR = 6.65 [95 %CI 2.24;19.79]; I² = 27 %; 5 trials, 404 patients), but also specifically in patients with class I obesity (RR = 5.27 [1.31;21.23]; I² = 0 %; 4 trials, 80 patients). Furthermore, and in line with previous results, all additional MAs performed in patients with obesity in this work favor MS (specifically Roux-en-Y gastric bypass) over MT at 24, 36 (only) and 60 months of follow-up. CONCLUSIONS: Although the data available in patients with class I obesity and type 2 diabetes remains limited, MA shows higher rates of DR after MS compared with MT after 36 months' follow-up in these patients. Consequently, the French National Authority for Health French (HAS) recommends MS for these patients.

Assessment of non-inferiority with meta-analysis: example of hypofractionated radiation therapy in breast and prostate cancer.

The aim of this study was to propose a methodology for the assessment of non-inferiority with meta-analysis. Assessment of hypofractionated RT in prostate and breast cancers is used as an illustrative example. Non-inferiority assessment of an experimental treatment versus an active comparator should rely on two elements: (1) an estimation of experimental treatment's effect versus the active comparator based on a meta-analysis of randomized controlled trials and (2) the value of an objective non-inferiority margin. This margin can be defined using the reported effect of active comparator and the percentage of the active comparator's effect that is desired to be preserved. Non-inferiority can then be assessed by comparing the upper bound of the 95% confidence interval of experimental treatment's effect to the value of the objective non-inferiority margin. Application to hypofractionated RT in breast cancer showed that hypofractionated whole breast irradiation (HWBI) appeared to be non-inferior to conventionally fractionated RT for local recurrence. This was not the case for accelerated partial breast irradiation (APBI). Concerning overall survival, non-inferiority could not be claimed for either HWBI or APBI. For prostate cancer, the lack of demonstrated significant superiority of conventional RT versus no RT precluded any conclusion regarding non-inferiority of hypofractionated RT.

Cost-Effectiveness of Sensor-Augmented Pump Therapy with Low Glucose Suspend Versus Standard Insulin Pump Therapy in Two Different Patient Populations with Type 1 Diabetes in France.

BACKGROUND: Sensor-augmented pump therapy (SAP) provides a useful adjunct relative to continuous subcutaneous insulin infusion (CSII) alone. It can provide early warning of the onset of hyperglycemia and hypoglycemia and has the functionality to suspend insulin delivery if sensor glucose levels fall below a predefined threshold. The aim was to assess the cost-effectiveness of SAP with low glucose suspend (LGS) versus CSII alone in type 1 diabetes. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using the CORE Diabetes Model, using published clinical input data. The analysis was performed in two cohorts: one with uncontrolled glycated hemoglobin at baseline and one at elevated risk for hypoglycemic events. The analysis was conducted from a healthcare payer perspective over a lifetime time horizon; future costs and clinical outcomes were discounted at 4% per annum. RESULTS: In patients with uncontrolled glycated hemoglobin at baseline, SAP + LGS resulted in improved discounted quality-adjusted life expectancy (QALE) versus CSII (10.55 quality-adjusted life-years [QALYs] vs. 9.36 QALYs) but higher mean lifetime direct costs (€84,972 vs. €49,171) resulting in an incremental cost-effectiveness ratio (ICER) of €30,163 per QALY gained. In patients at elevated risk for hypoglycemia, the ICER was €22,005 per QALY gained for SAP + LGS versus CSII as lifetime costs were higher (€88,680 vs. €57,097), but QALE was also higher (18.46 QALYs vs. 18.30 QALYs). CONCLUSIONS: In France, projected improvements in outcomes with SAP + LGS versus CSII translated into an ICER generally considered as good value for money, particularly in patients who experience frequent and/or problematic hypoglycemic events.

Post-approval studies in France, challenges facing medical devices.

Medical devices are characterized notably by a wide heterogeneity (from tongue depressors to hip prostheses, and from non-implantable to invasive devices), a short life cycle with recurrent incremental innovations (from 18 months to 5 years), and an operator-dependent nature. The objective of the current round table was to develop proposals and recommendations concerning the prerequisites needed in order to meet the French health authorities expectations concerning requests for post-approval studies for medical devices, required in cases where short and long-term consequences are unknown. These studies, which are the responsibility of the manufacturer or the distributor of the medical device, are designed to confirm the role of the medical device in the therapeutic management strategy in a real-life setting. There are currently approximately 150 post-approval studies underway, mainly concerning class III devices, and the majority face difficulties implementing the study or meeting the study objectives. In light of this, the round table endeavored to clearly identify the conditions for implementation of post-approval studies specific to the characteristics of medical devices. Various areas of progress have been envisaged to improve the performance of these studies, and by consequence, the efficiency of reimbursement of medical devices by the national health insurance. These include providing manufacturers with the opportunity to better anticipate post-approval requirements, defining a study-specific primary objective, integrating a phase allowing dialogue between the manufacturer, the health authorities and the scientific committee, and increasing awareness and training of health professionals on the impact of post-approval clinical studies in terms of the reimbursement of medical devices by the national insurance.

Drug-eluting stents in patients at high risk of restenosis: assessment for France.

BACKGROUND: In unselected patients, the incidence of restenosis is lower after placement of drug-eluting stents (DES) than bare-metal stents (BMS) without difference in safety at a time horizon of 4 years. However, DES appears less effective in "off label" patients. OBJECTIVES: The aim of the study was to assess available evidence of DES efficacy and safety by patient category to establish when DES placement may be recommended for reimbursement by the French national health insurance. METHODS: Based on a systematic review by patient category (January 2002 to August 2009), two health technology assessment (HTA) reports and thirty-eight clinical studies not covered by the HTA reports (eleven meta-analysis including ours, eleven randomized trials and sixteen cohort studies) were selected. After assessment of the methodological quality, the studies mostly comparing DES with BMS were reviewed by a panel of health professionals who defined a priori the most relevant end points of safety and efficacy. RESULTS: Seven to fourteen patients treated with DES were needed to avoid one target lesion revascularization (TLR) in patients with lesions >15 mm long, vessel diameter <3 mm, or diabetes, and with some complex lesions (total coronary occlusion, BMS in-stent restenosis multivessel disease, unprotected left main stenosis). DES appeared as safe as other alternatives over a follow-up of up to 4 years when dual antiplatelet therapy was continued for at least 1 year, but statistical power remains limited to conclude for some clinical features. CONCLUSIONS: For reimbursement, DES use should be limited to certain categories of patients. Treatment of particular cases requires a multidisciplinary approach.

Real medical benefit assessed by indirect comparison.

Frequently, in data packages submitted for Marketing Approval to the CHMP, there is a lack of relevant head-to-head comparisons of medicinal products that could enable national authorities responsible for the approval of reimbursement to assess the Added Therapeutic Value (ASMR) of new clinical entities or line extensions of existing therapies.Indirect or mixed treatment comparisons (MTC) are methods stemming from the field of meta-analysis that have been designed to tackle this problem. Adjusted indirect comparisons, meta-regressions, mixed models, Bayesian network analyses pool results of randomised controlled trials (RCTs), enabling a quantitative synthesis.The REAL procedure, recently developed by the HAS (French National Authority for Health), is a mixture of an MTC and effect model based on expert opinions. It is intended to translate the efficacy observed in the trials into effectiveness expected in day-to-day clinical practice in France.

Birth simulator: reliability of transvaginal assessment of fetal head station as defined by the American College of Obstetricians and Gynecologists classification.

OBJECTIVE: This study was undertaken to investigate the reliability of transvaginal assessment of fetal head station by using a newly designed birth simulator. STUDY DESIGN: This prospective study involved 32 residents and 25 attending physicians. Each operator was given all 11 possible fetal stations in random order. A fetal head mannequin was placed in 1 of the 11 American College of Obstetricians and Gynecologists (ACOG) stations (-5 to +5) in a birth simulator equipped with real-time miniaturized sensor. The operator then determined head position clinically using the ACOG classification. Head position was described as: (1) "engaged" or "nonengaged" (engagement code); (2) "high," "mid," "low," or "outlet" (group code); and (3) according to the 11 ACOG ischial spine stations (numerical code). Errors were defined as differences between the stations given by the sensor and by the operator. We determined the error rates for the 3 codes. RESULTS: "Numerical" errors occurred in 50% to 88% of cases for residents and in 36% to 80% of cases for attending physicians, depending on the position. The mean "group" error was 30% (95% CI 25%-35%) for residents and 34% (95% CI 27%-41%) for attending physicians. In most cases (87.5% for residents and 66.8% for attending physicians) of misdiagnosis of "high" station, the "mid" station was retained. Residents and attending physicians made an average of 12% of "engagement" errors, equally distributed between false diagnosis of engagement and nonengagement. CONCLUSION: Our results show that transvaginal assessment of fetal head station is poorly reliable, meaning clinical training should be promoted. The choice not to perform vaginal delivery when the fetus is in the "mid" position strongly decreases the risk of applying instruments on an undiagnosed "high" station. Conversely, obstetricians who perform only "low" operative vaginal deliveries also deliver unrecognized "mid" station fetuses. Therefore, residency programs should offer training in "mid" pelvic operative vaginal deliveries. Birth simulators could be used in training programs.

The assessment of deep vein thromboses for therapeutic trials.

In the current paper, we provide recommendations for the assessment of deep vein thromboses for the purpose of therapeutic trials evaluating antithrombotic drugs in the prevention of deep venous thrombosis. We have reviewed recently published articles on diagnostic and therapeutic studies, and we have evaluated methods of assessments. Ascending venography has been considered as the reference test for the confirmation of DVT. A roentgenographic image is subsequently available for review and allows classification by blinded, objective observers. However, venography poses substantial clinical and methodological limitations, particularly in the setting of systematic screening for all patients enrolled in a randomized clinical trial. Compression ultrasonography may replace venography for systematic screening of DVT in clinical trials, provided that specific methodological details are specified in the protocol and are fulfilled to ensure high and comparable sensitivity and specificity from all participating centers. This non-invasive technique has virtually no contraindications, and therefore more patients can be enrolled and evaluated. Furthermore, the compression ultrasonograph can be videotaped for central reading. Compression ultrasonography has already been adopted as the principal method for evaluating DVT in several ongoing large scale prevention trials with the approval of major drug agencies.