An indirect treatment comparison of semaglutide 2.0 mg versus dulaglutide 3.0 mg and 4.5 mg using multilevel network meta-regression

Aims Currently no head-to-head data are available comparing semaglutide 2.0 mg with dulaglutide 3.0 mg or 4.5 mg. We conducted an indirect treatment comparison (ITC) of their effects on glycated haemoglobin (HbA1c) and body weight in patients with type 2 diabetes (T2D). Materials and methods Multilevel network meta-regression (MLNMR) was conducted, based on a connected evidence network of published results from the AWARD-11 trial and individual patient data (IPD) from the SUSTAIN FORTE and SUSTAIN 7 trials. Results Semaglutide 2.0 mg significantly reduced HbA1c versus dulaglutide 3.0 mg and 4.5 mg, with estimated treatment differences (ETD) of –0.44%-points (95% credible interval [CrI]: –0.68, –0.19) and –0.28%-points (95% CrI: –0.52, –0.03), respectively. Semaglutide 2.0 mg also significantly reduced body weight versus dulaglutide 3.0 mg and 4.5 mg with ETDs of –3.29 kg (95% CrI: –4.62, −1.96) and –2.57 kg (95% CrI: –3.90, –1.24), respectively. Odds of achieving HbA1c <7.0% were significantly greater for semaglutide 2.0 versus dulaglutide 3.0 mg (odds ratio [OR]: 2.23 [95% CrI: 1.15, 3.90]), while this did not reach significance for semaglutide 2.0 mg versus dulaglutide 4.5 mg (OR: 1.58 [95% CrI: 0.82, 2.78]). Sensitivity analyses supported the main analysis findings. Conclusions This ITC demonstrated significantly greater reductions from baseline in HbA1c and body weight with semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg. The findings of this study provide important comparative effectiveness information until randomised head-to-head studies become available.

Haloaerosoltherapy: Mechanisms of Curative Effect and Place in the Respiratory Rehabilitation

Introduction. Management of patients with chronic pathology requires development of long-term programs with organic combinations of medicamental and non-medicamental influences. Haloaerosoltherapy is a group inhalation of rock salt aerosol with concentration of more than 2-3mg/m3 and certain dispersion (with presence of large-, medium- and small-grained aerosol) aboveground. Material and method. On the basis of literature data review and results of own researches a comprehensive description of haloaerosoltherapy, its mechanisms, available technologies, indications and effectiveness at pulmonary pathology was given. Results and discussion. Basis of haloaerosol curative influence is hyperosmolar stimulus that improves drainage function of bronchi and provides sanitizing effect, which causes further changes at local and systemic levels. This justifies haloaerosoltherapy usage as method of rehabilitation treatment. Comparison of haloaerosoltherapy and other methods of halotherapy (use of halite), in particular, "salt rooms (caves)" was made. It has been proven that "salt rooms" can be used only as spa procedure. Conclusions. Application of term "halotherapy" to all methods that use halite or underground treatment is incorrect. This determines necessity for stop using this term. It is necessary to differentiate clearly applied methods of treatment using terms that reflect the essence of therapeutic effect. Haloaerosoltherapy should be considered a method of respiratory rehabilitation with a proven mechanism of action and effectiveness. Haloaerosol is obtained using specific devices - halogenegenerators. The effectiveness of haloaerosoltherapy immediately after the course of treatment and in remote period is testified. Keywords: Respiratory rehabilitation, halotherapy, haloaerosoltherapy, speleotherapy,

A Network Meta-Analysis of Randomized Controlled Trials Directed at Treating Lateral Epicondylalgia

Background: Lateral epicondylosis is the most prevalent cause of lateral elbow pain, occurring in 4 per 1000 patients. The aim of most treatments is to reduce inflammation even with histological evidence demonstrating that lateral epicondylosis is a non-inflammatory condition. Objective: To determine the relative merits of the different regimens used to diminish lateral epicondylosis pain using a mixed treatment comparison/network meta-analysis (NMA). Methods: A thorough literature search was performed. The eligibility criteria for this mixed treatment comparison were: randomized controlled clinical trials; human subjects; working age population (16 to 70 years); the outcome measure was an objective pain assessment; measured at a 1- to 3-month follow-up. The NMA were performed using the GeMTC user interface for automated NMA utilizing a Bayesian Hierarchical Model of random effects. The evaluation of confidence in the findings from NMA was performed using a semi-automated platform called CINeMA (Confidence in Network Meta-Analysis). Results: The model suggests that articulation technique is the most effective measure for decreasing lateral epicondylalgia followed by topical nitrates, acupuncture, kinesiology taping and low-level laser therapy, respectively. Muscle energy technique, local corticosteroid injection, prolotherapy and counterforce bracing displayed a trend toward being less effective than placebo. Conclusions: The results suggest that the most effective modalities for improving lateral epicondylalgia are those that decrease muscle tone and those that improve circulation, while measures meant to decrease inflammation appear to be of no or limited benefit.

PP216 Indirect Treatment Comparison Assessment: An Improvement Intervention In The Scottish Medicines Consortium

IntroductionThe Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of the National Health Service Scotland based on pharmaceutical company submissions. As the appraisals are conducted close to the point of marketing authorization, there is often a lack of direct head-to-head data. In 2019, assessment of relevant comparative efficacy was informed via indirect treatment comparisons (ITC) in 55 percent (36/66) of submissions. While the ITCs are essential to the decision-making process, they are frequently incomplete.MethodsA focus group was conducted with the clinical assessment team (n = 11) to explore problems in the submission process and to identify areas for improvement. It was agreed that providing improved guidance to companies prior to submission may prevent future inconsistencies. A working group (n = 5) was tasked with identifying and implementing potential solutions. The group reviewed the focus group findings, relevant literature, and guidance from other organizations. Draft guidance was developed that was reviewed by two pharmaceutical industry representatives (SMC subcommittee members).ResultsFindings from the focus group highlighted issues broadly related to the incomplete presentation and reporting of ITCs. The improved guidance document outlined specific requirements in a checklist format for reporting and presenting the results of different ITC data. This guidance was published in February 2020. To evaluate the impact of the updated guidance and to identify any further changes required, a follow-up focus group and survey of industry representatives is planned for March 2021.ConclusionsThe aim of the ITC guidance is to provide pharmaceutical companies with direction to improve the quality and transparency of reporting, which will in turn improve the quality of HTAs and thus strengthen the recommendations provided by the SMC. The follow-up focus groups and survey will assess the impact of the guidance. It is acknowledged that the results of this process may be limited by the small sample size and short duration of the assessment.

Patient and proxies’ attitudes towards deferred consent in randomised trials of acute treatment for stroke: A qualitative survey

Introduction Deferral of consent for participation in a clinical study is a relatively novel procedure, in which informed consent is obtained after randomisation and study treatment. Deferred consent can be used in emergency situations, where small therapeutic time windows limit possibilities for patients to provide informed consent. We aimed to investigate patients’ or their proxies’ experiences and opinions regarding deferred consent in acute stroke randomised trials. Patients and methods For this qualitative study, Dutch Collaboration for New Treatments of Acute Stroke (CONTRAST) trial participants were selected. Study participants were either patients or their proxies who provided consent and were selected with theoretical sampling based on patient characteristics. Semi-structured interviews were conducted face-to-face or by telephone. Themes and subthemes were iteratively defined. Results Twenty of the 23 interviewed participants (16 patients and 7 proxies) considered deferred consent acceptable. The received study treatment and consent conversation were remembered by 18 participations, although the concept of randomisation and treatment comparison were generally not well understood. Sixteen participants felt capable of overseeing the decision to give deferred consent. Distress in the first days after stroke, lack of understanding and neurological deficits were reasons for feeling incapable of providing consent. Four participants would have preferred a different timing of the consent conversation, of whom two prior to treatment. Conclusion Our study found that deferred consent was considered acceptable by most study participants who provided consent for acute stroke randomised trials. Though they felt capable, the recall and comprehension of consent were overall limited.