Transition of care from adolescence to early adulthood in severe asthmatic patients treated with omalizumab in real life.

Half of severely asthmatic adolescents treated with omalizumab transitioning to adulthood discontinue the treatment, suggesting insufficient asthma control. However, most of the other half have low rates of HCRU markers, their asthma being under control. https://bit.ly/49ixpxt.

Real-life omalizumab exposure and discontinuation in a large nationwide population-based study of paediatric and adult asthma patients.

BACKGROUND: This real-life study aimed to assess omalizumab treatment patterns in adult and paediatric asthma patients, and to describe asthma control and healthcare resource use (HCRU) at omalizumab initiation and discontinuation. METHODS: The French healthcare database system (Système National des Données de Santé (SNDS)) was used to identify asthma patients aged ≥6 years who initiated omalizumab for at least 16 weeks from 2009 to 2019. We examined omalizumab treatment patterns using dispensation records. RESULTS: We identified 16 750 adults and 2453 children initiating omalizumab. Median treatment persistence before discontinuation (TSTOP) was 51.2 (95% CI 49.3-53.4) months in adults and 53.7 (95% CI 50.6-56.4) months in children. At 2 years of omalizumab exposure, rate of hospitalisation for asthma decreased by 75% and use of oral corticosteroids (OCS) by 30%, in adults and children. Among adults who discontinued omalizumab while asthma was controlled, 70%, 39% and 24% remained controlled and did not resume omalizumab at 1, 2 and 3 years after discontinuation, respectively. These proportions were higher in children (76%, 44% and 33%, respectively). Over 2 years of follow-up after discontinuation, HCRU remained stable in adults and children, notably rate of hospitalisations for asthma (none before TSTOP, 1.3% and 0.6% at 2 years) and use of OCS (in adults and children, respectively: 20.0% and 20.2% before TSTOP, 33.3% and 24.6% at 2 years). CONCLUSION: This is the first large-scale study describing omalizumab real-life exposure patterns in adult and paediatric asthma patients in France with >10 years of follow-up. We showed the long-term maintenance of low HCRU in adults and children who discontinued omalizumab while asthma was controlled, notably for OCS use and hospitalisations for asthma.

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France.

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.

Use of available clinical evidence to extrapolate drug effects from adults to children.

The extrapolation of the benefit risk ratio from adults to children is performed during drug development and often implicitly used by many paediatricians when prescribing off-label drugs in children. This is due to the specific constraints of paediatric clinical research leading to a lack of safety and efficacy data in children. Extrapolation frameworks for drug development have been proposed by several regulatory agencies. Using a meta-epidemiological approach, we explored the similarities and differences of the benefit, the benefit risk ratio and the perceived placebo effect between adults and children from meta-analyses including randomized double-blinded placebo-controlled trials evaluating a drug intervention in an indication in adults and children with separate data for both populations. We also explored the use of the effect model using adult data to predict the treatment effect in children and to calibrate future paediatric clinical trials. Our research highlights the importance of using all available evidence and quantitative methods before extrapolating the benefit risk ratio from adults to children and carrying out new studies in the context of the existing evidence. More generally, this should be applied to any research to avoid a waste of time and resources invested.

[Justification of off-label antibiotics uses in hospitalized children]. / Justification de la prescription hors-AMM d'antibiotiques chez l'enfant hospitalisé.

Unlicensed and off-label (UL/OL) drugs are commonly used in pediatrics wards, especially the antibiotics. It remains unclear if this strategy is justified by randomized controlled trials of good quality? OBJECTIVE: The aim of this study was to compare the level of evidence of UL/OL antibiotics prescription in hospitalized children. The initial hypothesis was that the UL/OL antibiotics prescriptions had a lower level of evidence than licensed antibiotics. METHOD: This observational study assessed the antibiotics prescription in the children mother and women hospital of Lyon. Each antibiotic medicine courses was classified depending on: (i) they were licensed, UL or OL, (ii) their level of evidence for efficiency (sufficient evidence, insufficient evidence, no evidence) and (iii) the existence or not of randomized controlled trials (RCT) or not. The antibiotics medicine courses in atypical cases were excluded (rare disease, lack of diagnosis, comorbidities modifying antibiotic use). Data were collected with computerized patient file data. The data were compared using Fisher exact test and χ2. RESULTS: One hundred and eight medicine courses were identified, corresponding to 72 mono, bi or tri-antibiotic therapies administered to 62 patients; 34% were OL and 66% were licensed. No prescriptions were UL. Thirty-two prescriptions were excluded from the evidence assessment. No proof of efficiency was found for any of the 76 analyzed medicine courses. RCTs were found for 36 of the analyzed medicine courses (47%); licensed medicine courses were significantly more justified by RCTs than UL/OL medicine courses (63% vs. 16%, P<0.001). DISCUSSION: This study has shown the absence of RCTs of good quality to justify the prescriptions of antibiotics in pediatrics, regardless their license status. Nevertheless, the licensed prescriptions have shown more data of efficiency than OL prescriptions. Still, even when data were found, no antibiotics prescriptions reach the threshold of good quality studies. New clinical trials should respond to the patient needs.

Is the perceived placebo effect comparable between adults and children? A meta-regression analysis.

BACKGROUND: A potential larger perceived placebo effect in children compared with adults could influence the detection of the treatment effect and the extrapolation of the treatment benefit from adults to children. This study aims to explore this potential difference, using a meta-epidemiological approach. METHODS: A systematic review of the literature was done to identify trials included in meta-analyses evaluating a drug intervention with separate data for adults and children. The standardized mean change and the proportion of responders (binary outcomes) were used to calculate the perceived placebo effect. A meta-regression analysis was conducted to test for the difference between adults and children of the perceived placebo effect. RESULTS: For binary outcomes, the perceived placebo effect was significantly more favorable in children compared with adults (ß = 0.13; P = 0.001). Parallel group trials (ß = -1.83; P < 0.001), subjective outcomes (ß = -0.76; P < 0.001), and the disease type significantly influenced the perceived placebo effect. CONCLUSION: The perceived placebo effect is different between adults and children for binary outcomes. This difference seems to be influenced by the design, the disease, and outcomes. Calibration of new studies for children should consider cautiously the placebo effect in children.

Protocol of GLUcose COntrol Safety and Efficacy in type 2 DIabetes, a NETwork meta-analysis: GLUCOSE DINET protocol-Rational and design.

The aim of this study was to propose a ranking of the currently available antidiabetic drugs, regarding vascular clinical outcomes, in patients with type 2 diabetes, through a network meta-analysis approach. Randomized clinical trials, regardless of the blinding design, testing contemporary antidiabetic drugs, and considering clinically relevant outcomes in patients with type 2 diabetes mellitus will be included. The primary outcomes of this analysis will be overall mortality, cardiovascular mortality, and major cardiovascular events. Diabetic microangiopathy will be a secondary outcome. Adverse events, hypoglycemia, weight evolution, bariatric surgery, and discontinuation of the treatment will also be recorded. Each drug will be analyzed according to its therapeutic class: biguanide, alpha-glucosidase inhibitors, sulfonylureas, glitazones, glinides, insulin, DPP-4 inhibitors, GLP-1 analogs, and gliflozins. The treatment effect of each drug class will be compared using pairwise meta-analysis and a Bayesian random model network meta-analysis. Sensitivity analyses will be conducted according to the quality of the studies and the glycemic control. The report will follow the PRISMA checklist for network meta-analysis. Results of the search strategy and of the study selection will be presented in a PRISMA compliant flowchart. The treatment effects will be summarized with odds ratio (OR) estimates and their 95% credible intervals. A ranking of the drugs will be proposed. Our network meta-analysis should allow a clinically relevant ranking of the contemporary antidiabetic drugs.

Different treatment benefits were estimated by clinical trials performed in adults compared with those performed in children.

OBJECTIVE: Our main objective was to see whether the therapeutic benefit observed in placebo controlled randomized controlled trials (RCTs) is different between adults and children. STUDY DESIGN AND SETTING: We searched three electronic databases for meta-analyses that included double-blind, placebo-controlled RCTs with separate results for adults and children. The selected reviews were classified according to disease and drug used. The heterogeneity of treatment response between adults and children was measured using ratio of odds ratios (RORs). RESULTS: We selected 89 meta-analyses and calculated RORs for 124 drugs. Heterogeneity in the direction of the treatment effect was observed in one drug and heterogeneity in the quantity of the treatment effect for 13 drugs, indicating significantly different treatment effect in adults when compared with children. RORs were not significantly different from 1 for 110 drugs. For 36 of these drugs, the treatment effect was confirmed in both populations. CONCLUSION: We found different treatment benefits estimated by clinical trials performed in adults compared with those performed in children for 14 of 124 drugs. Data on dose adjustment and child age groups from RCTs were not adequately reported to investigate their influence on the treatment benefit dissimilarities.

Solid oral forms availability in children: a cost saving investigation.

AIM: To assess the suitability and potential cost savings, from both the hospital and community perspective, of prescribed oral liquid medicine substitution with acceptable solid forms for children over 2 years. METHOD: Oral liquid medicines dispensed from a paediatric hospital (UK) in 1 week were assessed by screening for existence of the solid form alternative and evaluating the acceptability of the available solid form, firstly related to the prescribed dose and secondly to acceptable size depending on the child's age. Costs were calculated based on providing treatment for 28 days or prescribed duration for short term treatments. RESULTS: Over 90% (440/476) of liquid formulations were available as a marketed solid form. Considering dosage acceptability (maximum of 10% deviation from prescribed dosage or 0% for narrow therapeutic range drugs, maximum tablet divisions into quarters) 80% of liquids could be substituted with a solid form. The main limitation for liquid substitution would be solid form size. However, two-thirds of prescribed liquids could have been substituted with a suitable solid form for dosage and size, with estimated savings being of £5K and £8K in 1 week, respectively based on hospital and community costs, corresponding to a projected annual saving of £238K and £410K (single institution). CONCLUSION: Whilst not all children over 2 years will be able to swallow tablets, drug cost savings if oral liquid formulations were substituted with suitable solid dosage forms would be considerable. Given the numerous advantages of solid forms compared with liquids, this study may provide a theoretical basis for investing in supporting children to swallow tablets/capsules.