Bioreactance assessment of cardiac output lacks reliability for the follow-up of patients with pulmonary hypertension.

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).

Cost-effectiveness of the ONCORAL multidisciplinary programme for the management of outpatients taking oral anticancer agents at risk of drug-related event: protocol for a pragmatic randomised controlled study.

INTRODUCTION: The development of oral anticancer agents (OAA) has profoundly changed cancer care, leading patients to manage their chemotherapy treatment on an outpatient basis. The prevention of iatrogenic effects of OAA remains a major concern, especially since their side effects are not less serious than those of intravenous chemotherapy. The ONCORAL programme was set up to secure the management of OAA in cancer patients followed at the Lyon University Hospital. This multidisciplinary programme involves hospital pharmacists, nurses, oncologists, and haematologists, as well as community health professionals. Given the economic stakes that this programme entails for the health system, a medico-economic study was designed. METHODS AND ANALYSIS: This is a prospective controlled study, with individual open-label randomisation. A total of 216 outpatients treated with OAA and at risk of developing a drug-related iatrogenic event, will be randomised (2:1) to undergo follow-up in the ONCORAL programme or usual care. The primary outcome will be the estimation of the incremental cost-effectiveness ratio (difference in total costs per quality adjusted life years gained) at 12 months between the two groups. The secondary outcomes will be evaluation of OAA management consequences (relative-dose intensity, adherence, adverse drug events, drug-drug interactions, and proven medication errors), evaluation of overall survival and cancer-related quality of life, and patient-reported outcomes in relation to the treatment. A budget impact analysis will be implemented. Patient and health professional satisfaction regarding the ONCORAL programme will be measured. ETHICS AND DISSEMINATION: Approval to conduct this study was obtained from an Ethics Committee (Comité de Protection des Personnes Ile-de-France VI) in October 2019, and from the French data protection agency (Commission Nationale de l'Informatique et des Libertés), according to the French Law. Trial results will be disseminated at clinical conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT03660670.

Clinical impact and cost-saving analysis of a comprehensive pharmaceutical care intervention in older patients with cancer.

BACKGROUND: Hospital admission and discharge are at high risk of drug-related problems (DRPs) in older patients with cancer. This study aimed to assess the clinical and economic impact of a comprehensive pharmaceutical care intervention (RECAP) to optimize drug therapy in patients with cancer ≥75 years admitted to oncology or geriatric wards. METHOD: RECAP intervention was defined as follows: at admission and discharge, hospital pharmacists conducted comprehensive medication reconciliation and review, identified relevant DRPs and provided optimization recommendations to prescribers; at discharge, pharmacists also provided patient education and shared information with primary care providers. The impact of the intervention was assessed by the rate of implementation of recommendations by the prescribers and the evolution of polypharmacy rate; a peer review of the clinical significance of DRPs was performed by an expert panel of geriatric oncologists and pharmacists. A cost saving analysis compared cost avoided through resolution of DRPs to cost of pharmacist's time. RESULTS: From January 2019 and August 2020, 201 patients were included (median age 80 [75-97] years), 68.7% with solid tumors. DRPs requiring optimization were identified in 70.9% of patients at admission (mean 1.7 DRP/patient) and 47.7% at discharge (0.9 DRP/patient). Most pharmacist recommendations (70.8%) were followed by prescribers, allowing the correction of 1.2 DRP/patient at admission and 0.7 DRP/patient at discharge. Half of resolved DRPs were rated as clinically significant. However, polypharmacy rate was not reduced at discharge. Cost comparison showed $7.2 avoided for $1 invested, with an estimated total net benefit of $354,822 (mean $1766 per patient). CONCLUSIONS: The RECAP model significantly reduces DRPs in hospitalized older patients with cancer. The model was cost saving, confirming the value of implementing it in routine practice.

Hospital-based health technology assessment of innovative medical devices: insights from a nationwide survey in France.

OBJECTIVES: To better understand the process of hospital acquisition of innovative medical devices (MDs) and the hospital-based health technology assessment (HB-HTA) pathways in France, an in-depth study based on a quantitative approach is needed. The aim of the present study was to assess through a national survey how HB-HTA is currently implemented in French hospitals and to identify its level of formalization. METHODS: A quantitative online survey was conducted among hospitals performing HB-HTA in France, with a focus on the acquisition of innovative MDs for individual use. The survey, conducted between March and June 2022, was developed by a scientific board composed of members of the French-speaking Society for HB-HTA. RESULTS: Sixty-seven out of 131 surveyed hospitals with HB-HTA activities responded, including 29 university hospitals, 24 nonprofit private hospitals, and 14 local hospitals. Sixty-one respondents (91 percent) reported the existence of a process dedicated to evaluating innovative MDs; of these, 16 declared that their hospitals had a formalized unit with HB-HTA activity. These units were more frequently found in larger hospitals with more than 500 inpatient beds (n = 16, p = 0.0160) and in university hospitals (n = 12, p = 0.0158). No hospital reported any collaboration with HAS, the French national HTA agency. CONCLUSION: A diverse range of HB-HTA organizations with different structural levels exist in France for MD procurement linked to the category of hospitals. The study highlights the need for recognition of HB-HTA activity at the regulatory level in France and for direct collaboration between HTA activities performed at local and national levels.

Cost-effectiveness of a bone substitute delivering gentamicin in the treatment of chronic osteomyelitis of long bones: Protocol for the CONVICTION randomized multicenter study.

Introduction: Chronic osteomyelitis is a serious osteoarticular infection that most often occurs in the long bones, responsible for significant morbidity with the risk of fracture and amputation. Despite advances in both antibiotics and surgical treatment, the probability of recurrence of infection remains at around 20%. Cerament-G (BONESUPPORT AB, Sweden) is a synthetic bone substitute that fills the bone void left by surgery, prevents infection and promotes bone regeneration within this space. Cerament-G also provides the local delivery of high doses of gentamicin over several weeks. Two prospective observational studies described a number of infectious recurrences of 4 and 5% after the use of Cerament-G. Although available in France, Cerament-G is currently not reimbursed and its high cost constitutes a barrier to its use. We hypothesize that the use of Cerament-G will lead to fewer costs to the collectivity while improving patient utility and, as an innovative strategy, will be superior to standard of care on recurrence of infection. Methods and analysis: The Conviction Study is a prospective, multicenter, randomized, single blind study conducted in 14 French Reference Centers for Complex Osteoarticular infections. The main objective is to evaluate the cost-effectiveness of using Cerament-G in the treatment of chronic long bone osteomyelitis by comparing this innovative strategy to standard of care. A cost-utility analysis from the collective perspective will be conducted over a 24-month time horizon after the initial surgery. The outcome for the main medico-economic evaluation will be Quality Adjusted Life Years (QALYs). Discussion: The study is being conducted throughout the CRIOAc network in France, in referral centers for the management of complex infections which will facilitate patient recruitment. This study has several limitations: the investigators have to be trained to handle the device, and it was impossible to blind the surgeon. Conclusion: If the use of Cerament-G is demonstrated to be superior to leaving the dead space empty during surgery for patients with stage III chronic long bone osteomyelitis, its use will be recommended to improve the prognosis of such patients, and this device may eventually qualify for reimbursement through the French Health Insurance scheme. Ethics and dissemination: This protocol received authorization from the Ethics Committee CPP Sud Méditerranée V on April 27, 2021 (21.03.10.77652) and the French National Agency for Medicines and Health Products on May 6, 2021 (2020-A02299-30). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals.

Perspectives in prospective comparative economic evaluations: a systematic review.

INTRODUCTION: Depending on countries and health systems, medico-economic assessment guidelines recommend to adopt one or several perspectives. We conducted a systematic literature review in order to assess the fit between the country guidelines and the perspectives announced in the published studies. AREAS COVERED: Searches were carried out within the Medline electronic database for records published between 1 January 2000 and 31 August 2020. Only studies from countries in which guidelines recommending a perspective to adopt were available online were selected. EXPERT OPINION: A total of 398 studies were included. Among those studies, 212 (54.9%) adopted as a main perspective a public payer perspective, 141 (36.5%) a societal perspective, 25 (6.5%) a hospital perspective, and 8 (2.1%) a patient perspective. Recommendations in terms of perspective were followed by 267 (67.1%) studies, mainly from Canada, the UK, and the Netherlands. Two thirds of the perspectives chosen in studies were in line with the recommendations. While the choice of a perspective does not question the quality of the studies published, it raises the question of the relevance of the perspectives that must be adapted to the question asked, the pathology studied, and the feasibility of the studies.

Efficacy and safety of Aflibercept for the treatment of inflammatory choroidal neovascularization: The ALINEA study.

PURPOSE: To evaluate mean change in best-corrected visual acuity (BCVA) at 52 weeks in patients with inflammatory choroidal neovascularization (CNV) treated with aflibercept. METHODS: We conducted a prospective non-comparative open-label trial. Following one mandatory intravitreal injection of aflibercept, patients were treated under a pro re nata (PRN) dosing regimen with monthly visits. RESULTS: A total of 19 patients were included, but one presented exclusion criteria; 16 patients were followed for the whole 52-week study, and data for the primary endpoint analysis were available for 14. At baseline, mean BCVA and mean central retinal thickness (CRT) were 64.53 (±19.64) letters and 351.79 (±97.77) µm, respectively. At 52 weeks, the mean change in BCVA was +9.50 (±12.90) letters [95%CI = +2.05-+16.95]. One patient had lost more than 15-letters at 24 weeks, and another one at 52 weeks. CRT change was -62.77 (±100.73) µm at 24 weeks and -66.53 (±97.47) µm at 52 weeks. There was a mean number of 3.56 (±3.29) intravitreal injections at 52 weeks (min = 1; max = 12). No serious ocular adverse events related to the treatment were reported. CONCLUSIONS: Our study shows that aflibercept is clinically effective, both anatomically and functionally in the treatment of inflammatory CNV. Following the first injection, the PRN strategy appears sufficient for treating most choroidal neovessels.

Microperimetry to predict disease progression in eyes at high risk of age-related macular degeneration disease: The PREVISION study.

PURPOSE: The aim of the present study was to determine whether microperimetric parameters could predict the progression of an eye at high risk of age-related macular degeneration (AMD) at 24 months. METHODS: We conducted a multicentric prospective non-comparative open-label study including patients with one eye in stage 4 of the Age-Related Eye Disease Study Group (AREDS) classification, and the other eye in AREDS stage 3 (study eye). A microperimetry examination (MAIA™, CenterVue, Padova, Italy) was performed at baseline and every 6 months during the 2-year follow-up. At the end of the follow-up, each study eye was classified as 'progressive' (i.e. AREDS stage 4) or 'non-progressive' (i.e. AREDS stage 3). RESULTS: A total of 147 patients were analysed, of which 30.6% progressed from AREDS stage 3 to stage 4. The microperimetry criterion 'mean retinal sensitivity' was significantly different at baseline between non-progressive and progressive eyes (p = 0.022), with lower values for the latter. With a threshold for mean retinal sensitivity set at 24.7 dB, diagnostic sensitivity was 80% [95%CI (65.4-90.4)], specificity was 30.4% [95%CI (21.7-40.3)], positive predictive value was 33.6% [95%CI (24.8-43.4)], and negative predictive value was 77.5% [95%CI (61.5-89.2)]. In the multivariate analysis including microperimetric parameters and other routine ophthalmologic examinations, mean retinal sensitivity was the only predictive parameter statistically associated with progression (p = 0.0004). CONCLUSIONS: Our findings are encouraging as regards the use of microperimetry, and mean retinal sensitivity value in particular, to predict the 2-year risk of progression to AREDS stage 4 eye.

Assessment of Patient Reported Outcomes (PROs) in Outpatients Taking Oral Anticancer Drugs Included in the Real-Life Oncoral Program.

Background In previous studies, patient-reported outcomes (PROs) have been shown to improve survival in cancer patients. The aim of the present study was to assess symptoms potentially related to adverse events experienced by cancer outpatients treated by oral anticancer agents (OAAs) using PROs. Methods Between September 2018 and May 2019, outpatients starting OAAs were included in a 12-week follow-up to assess 15 symptoms listed in the National Cancer Institute PRO Common Terminology Criteria for Adverse Events, using a 5-point scale of severity or frequency. Patients were requested to alert a referral nurse or pharmacist when they self-assessed high-level (level 3 or 4) symptoms. Results 407 questionnaires were completed by 63 patients in which 2333 symptoms were reported. Almost three-quarters (74.6%) reported at least one high-level symptom. The symptoms that were most commonly experienced were fatigue (>9 in 10 patients; 13.2% of symptoms declared), various psychological disorders (>9 in 10 patients; 28.6% of symptoms declared) and general pain (>8 in 10 patients; 9.4% of symptoms declared). Conclusion PROs are appropriate to detect potential adverse events in cancer outpatients treated by OAAs. This study is the first step for integrating the patient's perspective in a digital e-health device in routine oncology care.

Early Predictive Factors of Visual Loss at 1 Year in Neovascular Age-Related Macular Degeneration under Anti-Vascular Endothelial Growth Factor.

PURPOSE: To evaluate early predictive factors of visual loss in patients treated with anti-vascular endothelial growth factor (VEGF) injections under an as-needed regimen for neovascular age-related macular degeneration (AMD). DESIGN: Post hoc analysis from the randomized controlled trial Groupe d'Evaluation Français Avastin versus Lucentis (GEFAL). PARTICIPANTS: A total of 393 patients with neovascular AMD. METHODS: The present analysis is based on 1-year data from patients included in the study. Patients were separately categorized according to the best-corrected visual acuity (BCVA) change at 3 months and 1 year into 3 trajectories: (1) patients with no vision loss ≥5 letters at 3 months and 1 year (absence of loss ≥5 letters); (2) patients with no vision loss ≥5 letters at 3 months but loss ≥5 letters at 1 year (secondary loss ≥5 letters); and (3) patients with vision loss ≥5 letters at 3 months and 1 year (initial loss ≥5 letters). MAIN OUTCOME MEASURES: The following factors were evaluated at baseline and 3 months: age, sex, BCVA, presence of fluid, central macular thickness, angiographic choroidal neovascularization (CNV) subtype, CNV area measured in disc area on fluorescein angiography, and number of intravitreal injections. RESULTS: An absence of loss ≥5 letters was found in 225 patients (57.3%), a secondary loss ≥5 letters after 3 months was found in 109 patients (27.7%), and an initial loss ≥5 letters was found in 59 patients (15%). Baseline characteristics were comparable among the 3 groups except for the total CNV area, which was larger in the initial and secondary loss groups (P = 0.0412). At 3 months, a significant association was found between presence of subretinal fluid (SRF) (P = 0.0318) and vision loss ≥5 letters, and an even stronger significant association between the presence of intraretinal fluid (IRF) (P = 0.0066) and vision loss ≥5 letters. CONCLUSIONS: In the present study, we found that a large CNV area at baseline was significantly associated with initial or secondary loss of visual acuity ≥5 letters despite anti-VEGF injection. The presence of fluid, both SRF and IRF, at 3 months was found in patients with poorer trajectories.

EFFICACY AND SAFETY OF AFLIBERCEPT FOR THE TREATMENT OF IDIOPATHIC CHOROIDAL NEOVASCULARIZATION IN YOUNG PATIENTS: The INTUITION Study.

PURPOSE: To evaluate the mean change in visual acuity at 52 weeks in patients with idiopathic choroidal neovascularization treated with aflibercept. METHODS: We conducted a prospective noncomparative open-label Phase-II trial. The dosage regimen evaluated in this study was structured into two periods: (1) from inclusion to 20 weeks: a treat-and-extend period composed of three mandatory intravitreal injections, and complementary intravitreal injections performed if needed; (2) from 21 weeks to 52 weeks: a pro re nata period composed of intravitreal injections performed only if needed. RESULTS: A total of 19 patients were included, and 16 completed the 52-week study. At baseline, the mean best corrected visual acuity was 66.56 (±20.72) letters (≈20/50 Snellen equivalent), and the mean central retinal thickness was 376.74 µm (±93.77). At 52 weeks, the mean change in the best-corrected visual acuity was +19.50 (±19.36) letters [95% confidence interval = +9.18 to +29.82]. None of the patients included lost ≥15 letters at 24 weeks or 52 weeks. The mean change in central retinal thickness was -96.78 µm (±104.29) at 24 weeks and -86.22 µm (±112.27) at 52 weeks. The mean number of intravitreal injections was 5.4 (±3.0) at 52-weeks. No ocular serious adverse events related to the treatment were reported. CONCLUSION: The present analysis shows clinically significant functional and anatomical treatment effect of aflibercept in case of idiopathic choroidal neovascularization. The treat-and-extend regimen proposed after the first injection seems adequate to treat most neovessels.

Cost of off-label antibiotic therapy for bone and joint infections: a 6-year prospective monocentric observational cohort study in a referral centre for management of complex osteo-articular infections.

Introduction: Costs related to bone and joint infection (BJI) management are increasing worldwide, particularly due to the growing use of off-label antibiotics that are expensive treatments (ETs), in conjunction with increasing incidence of multi-drug-resistant pathogens. The aim of this study was to evaluate the whole costs related to these treatments during the patient route, including those attributed to the rehabilitation centre (RC) stay in one regional referral centre in France. The total annual cost of ETs for managing complex BJIs in France was then estimated. Material and methods: A prospective monocentric observational study was conducted from 2014 to 2019 in a referral centre for BJI management (CRIOAc - Centre de Référence des Infections OstéoArticulaires complexes). Costs related to expensive treatments ("old" ETs, i.e. ceftaroline, ertapenem, daptomycin, colistin, tigecycline, and linezolid and "new" ETs, defined as those used since 2017, including ceftobiprole, ceftazidime-avibactam, ceftolozane-tazobactam, tedizolid, and dalbavancin) were prospectively recorded. In all cases, the use of these ETs was validated during multidisciplinary meetings. Results: Of the 3219 patients treated, 1682 (52.3 %) received at least one ET, and 21.5 % of patients who received ET were managed in RCs. The overall cost of ETs remained high but stable (EUR 1 033 610 in 2014; EUR 1 129 862 in 2019), despite the increase of patients treated by ETs (from 182 in 2014 to 512 in 2019) and in the cumulative days of treatment (9739 to 16 191 d). Daptomycin was the most prescribed molecule (46.2 % of patients in 2014 and 56.8 % in 2019, with 53.8 % overall), but its cost has decreased since this molecule was genericized in 2018; the same trend was observed for linezolid. Thus, costs for old ETs decreased overall, from EUR 1 033 610 in 2014 to EUR 604 997 in 2019, but global costs remained stable due to new ET utilization accounting for 46.5 % of overall costs in 2019. Tedizolid, used as suppressive antimicrobial therapy, represented 77.5 % of total new ET costs. In our centre, dalbavancin was never used. The cost paid by RCs for ETs and the duration of ET remained stable overall between 2016 and 2019. Conclusions: A high consumption of off-label ET is required to treat patients with BJIs in a CRIOAc, and the consequence is a high cost of antimicrobial therapy for these patients, estimated to be almost EUR 10 million in France annually. Costs associated with ET utilization remained stable over the years. On the one hand, the introduction of the generic drugs of daptomycin and linezolid has significantly decreased the share of old ETs, but, on the other hand, the need for new ETs to treat infections associated with more resistant pathogens has not led to decrease in the overall costs. A drastic price reduction of generic drugs is essential to limit the costs associated with more complex BJIs.

Economic Study of 2-Stage Exchange in Patients With Knee or Hip Prosthetic Joint Infection Managed in a Referral Center in France: Time to Use Innovative(s) Intervention(s) at the Time of Reimplantation to Reduce the Risk of Superinfection.

Objective: Chronic prosthetic joint infections (PJI) are serious complications in arthroplasty leading to prosthesis exchange and potential significant costs for health systems, especially if a subsequent new infection occurs. This study assessed the cost of chronic PJI managed with 2-stage exchange at the Lyon University Hospital, CRIOAc Lyon reference center, France. A threshold analysis was then undertaken to determine the reimbursement tariff of a hypothetical preventive device usable at the time of reimplantation, which possibly enables health insurance to save money according to the risk reduction of subsequent new infection. This analysis was also performed for a potential innovative device already available on the market, a dual antibiotic loaded bone cement used to fix cemented prosthesis that releases high concentrations of gentamicin and vancomycin locally (G+V cement). Method: Patients >18 years, admitted for a hip or knee chronic PJI managed with 2-stage exchange, between January 1, 2013, and December 31, 2015, were retrospectively identified. Following, resource consumption in relation to inpatient hospital stay, hospitalization at home, rehabilitation care, outpatient antibiotic treatments, imaging, laboratory analysis, and consultations were identified and collected from patient records and taken into account in the evaluation. Costs were assessed from the French health insurance perspective over the 2 years following prosthesis reimplantation. Results: The study included 116 patients (median age 67 y; 47% hip prosthesis). Mean cost of chronic PJI was estimated over the 2 years following prosthesis reimplantation at €21,324 for all patients, and at €51,697 and €15,745 for patients with (n = 18) and without (n = 98) a subsequent new infection after reimplantation, respectively. According to the threshold analysis the reimbursement tariff (i) should not exceed €2,820 for a device which can reduce the risk of a new infection by 50% and (ii) was between €2,988 and €3,984 if the G + V cement can reduce the risk of a new infection by 80% (this reduction risk is speculative and has to be confirmed by clinical trials). Conclusion: This study revealed that chronic PJI requiring a 2-stage revision is costly, with significant costs in relation to the reimplantation procedure (about 15 k€). However, following reimplantation the rate of subsequent new infection remained high, and the cost of reimplantation following a new infection is considerable, reaching 50k€ per patient. These first cost estimates of managing chronic PJI with 2-stage exchange in France underline the economic interest of preventing new infections.

Immunomodulatory drugs in multiple myeloma: Impact of the SCARMET (Self CARe and MEdication Toxicity) educational intervention on outpatients' knowledge to manage adverse effects.

Long-term multiple myeloma therapy by immunomodulatory drugs (IMiDs) raises the question of management of adverse effects. The aim of this study is to assess the impact of an educational session for patients on the acquisition of knowledge to manage hematologic and thromboembolic adverse effects of IMiDs. In this prospective single-center study, patients attended an educational session with a hospital clinical pharmacist and a nurse. The primary endpoint was the patient's level of knowledge for the management of IMiDs adverse effects, assess with a dedicated questionnaire administered before the session then 1 and 6 months after. Assessment of knowledge was combined with self-assessment of certainty. The secondary endpoints were adherence and IMiD treatment satisfaction. 50 patients were included. Patient knowledge increased at 1 month (p<0.001) despite a loss of knowledge at 6 months (p<0.05). Six months after the educational intervention, the number of patients with skills considered satisfactory by the pharmacist and nurse increased (p<0.01). Most patients showed satisfactory adherence, with medication possession ratio ≥ 80%. The Self CARe and MEdication Toxicity (SCARMET) study highlighted the impact of multidisciplinary follow-up in multiple myeloma patients to improve knowledge of toxicity self-management.

Early patient access to health technologies: Is innovation needed for early management?

The question of early patient access to innovative health technologies arises from the assumption that, once a certain level of effectiveness or efficiency is achieved, waiting for mainstream coverage would represent a loss of opportunity for patients or for the community. This was the premise on which the round table based its dialogue. Early access is understood as the funding of a technology that comes within this field and is CE-marked but has not yet attained "mainstream" coverage. There are several early access schemes in France ("forfait innovation", early coverage, exceptional coverage, RIHN). This round table was an opportunity to establish mapping, extended to devices not dedicated to early access but which could nevertheless provide some patients with access to non-mainstreamed technologies (Article 51, ETAPES experiments, DGOS call for projects, local schemes). It is an initial step that would need to be further developed and complemented by the dissemination of common communication materials available to all, including patients. The existing schemes are in fact still poorly known. Consideration would also have to be given to the advisability of developing these schemes in order to adapt them to the new European requirements. More generally, early access schemes must be integrated into an ecosystem that is conducive for their relevance: consideration of procedures associated with medical devices benefiting from early access; short time frames of examination; patient information. Finally, the round table proposes the creation of a new early access scheme, complementary to those that exist and that would be positioned, after CE marking, between the "forfait innovation" and mainstreaming: PRESTO (Prise En charge Sécurisée et Temporaire de technologies innOvantes) (secure and temporary coverage for innovative technologies).

Mechanical circulatory support with the Impella® LP5.0 pump and an intra-aortic balloon pump for cardiogenic shock in acute myocardial infarction: The IMPELLA-STIC randomized study.

BACKGROUND: Percutaneous assist devices may be used as a bridge to recovery in patients with acute myocardial infarction complicated by cardiogenic shock (CS-AMI). AIM: To test the hypothesis that the Impella® LP5.0 pump (Abiomed Europe GmbH, Aachen, Germany) provides haemodynamic benefits and improves left ventricular ejection fraction (LVEF) in patients with CS-AMI already managed with an intra-aortic balloon pump (IABP). METHODS: This was a prospective randomized study. The primary endpoint was change in cardiac power index (CPI) from baseline to 12hours after implantation, measured with a Swan-Ganz catheter. Secondary endpoints included LVEF at 30 days. RESULTS: Fifteen patients with CS-AMI were randomized; 12 were available for primary endpoint analysis (IABP group, n=6; Impella LP5.0+IABP group, n=6). Baseline characteristics were similar in both groups. Change in CPI after 12hours was not significantly different between the two groups (IABP group: ΔCPI=0.08±0.08W/m2; Impella LP5.0+IABP group: ΔCPI=-0.02±0.25W/m2; P=0.4). There was no significant change from baseline CPI in either group over 96hours, and no difference in CPI between groups at each timepoint. In the Impella LP5.0+IABP group, the part of the CPI provided by the native heart decreased from 0.37±0.10 to 0.10±0.20 (P=0.01). LVEF was similar at baseline (29.7%±8.4% and 29.3%±6.7%) and 1 month (40.6%±12.5% and 38.6%±14.4%) in the IABP and Impella LP5.0+IABP groups, respectively. Adverse events, especially major bleeding, were common, and occurred mainly in the Impella LP5.0+IABP group. CONCLUSIONS: In patients with CS-AMI stabilized by initial treatment with inotropes and an IABP, the Impella LP5.0 did not provide additional haemodynamic support or improvement in LVEF at 1 month; its use in this setting might be futile and possibly harmful.

Flow Diverters for Intracranial Aneurysms: The DIVERSION National Prospective Cohort Study.

Background and Purpose- Flow diverters are used for endovascular therapy of intracranial aneurysms. We did a nationwide prospective study to investigate the safety and effectiveness of flow diversion at 12 months. Methods- DIVERSION was a national prospective cohort study including all flow diverters placement between October 2012 and February 2014 in France. The primary end point was the event-free survival rate at 12 months, defined as the occurrence of morbidity (intracranial hemorrhage, ischemic stroke, noncerebral hemorrhage, or neurological deficit due to mass effect), retreatment, or death within 12 months post-treatment. A quality control was carried out on 100% of the collected data and of at least 10% of the included patients in each center, chosen at random. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran scale by an independent imaging core laboratory at 12 months. Results- We enrolled 398 patients harboring 477 intracranial aneurysms. At least 1 morbidity-mortality event was noted in 95 of 408 interventions representing an event-free survival rate of 75.7% (95% CI, 71.1-79.7). The rate of permanent-related serious events and mortality was 5.9% and 1.2% at 12 months, respectively. Multivariate analysis showed that high baseline blood pressure (hazard ratio, 2.54; 95% CI, 1.35-4.79; P=0.039), diabetes mellitus (hazard ratio, 3.70; 95% CI, 1.60-8.6; P=0.0022), and larger aneurysms (hazard ratio, 1.07; 95% CI, 1.04-1.11; P<0.0001) were associated with the occurrence of a neurological deficit. The satisfactory occlusion rate at 12 months was 79.9%, and the absence of high baseline blood pressure (odds ratio, 2.01; 95% CI, 1.12-3.71; P=0.0193) and postprocedural satisfactory occlusion (odds ratio, 2.75; 95% CI, 1.49-5.09; P=0.0012) were associated with a 12-month satisfactory occlusion. Conclusions- A satisfactory occlusion was achieved in almost 80% of cases after flow diverter treatment with a permanent-related serious event and mortality rates of 5.9% and 1.2% at 12 months, respectively.

Using connected objects in clinical research.

Connected objects (CO), whether medical devices or not, are used in clinical research for data collection, a specific activity (communication, diagnosis, effector, etc.), or several functions combined. Their validation should be based on three approaches: technical and clinical reliability, data protection and cybersecurity. Consequently, the round table recommends that the typology of COs, their uses and limitations, be known and shared by all, particularly for implementing precise specifications. COs are used in clinical research during observational studies (assessment of the device itself or data collection), randomized studies, where only one group has a CO (assessment of its impact on patient follow-up or management), or randomized studies where both groups have a CO, which is then used as a tool to help with assessment. The benefits of using COs in clinical research includes: improved collection and quality of data, compliance of patients and pharmacovigilance, easier implementation of e-cohorts and a better representative balance of patients. The societal limits and risks identified relate to the sometimes intrusive nature of certain collected parameters and the possible misuse of data. The round table recommends the following on this last point: anticipation, by securing transmission methods, the qualification of data hosts, and assessment of the object's vulnerability. For this, a risk analysis appears necessary for each project. It is also necessary to accurately document the data flow, in order to inform both patients and healthcare professionals and to ensure adequate security. Anticipating regulatory changes and involving users starting from the study design stage are also recommended.

SMABcare study: subcutaneous monoclonal antibody in cancer care: cost-consequence analysis of subcutaneous rituximab in patients with follicular lymphoma.

Rituximab is used as a standard of care for follicular lymphoma and is usually administered intravenously. A novel subcutaneous formulation recently showed non-inferior efficacy with similar pharmacokinetic and safety profiles compared to intravenous rituximab in patients with follicular lymphoma. This new approach is promising in terms of comfort for patients and time-saving for hospital staff. To evaluate the real-life economic impact of subcutaneous rituximab as maintenance therapy in patients with follicular lymphoma in real life, we conducted a cost-consequence analysis from the hospital's point of view in three French teaching hospitals. Health-related quality of life (EQ-5D-3L) was investigated as well as patients' and nurses' perception. Compared to intravenous rituximab, subcutaneous administration showed an estimated cost-saving of €109.20 per patient per cycle (p < 0.001), 78.6% of which could be attributed to the rituximab cost. Health-related quality of life showed no significant difference between the two groups despite tendencies for greater pain in the subcutaneous group and greater anxiety in the intravenous group. Thus, subcutaneous rituximab had a favorable pharmacoeconomic profile, with clinical efficacy similar to that of intravenous rituximab. The subcutaneous form was preferred by almost all patients, but further consideration should be given to improve the patients' experience: a dedicated day unit with trained medical, nursing, and pharmaceutical staff could be helpful.