Semaglutide single-dose pen-injector: Post hoc analysis of summative usability testing for weight management.
Ontology highlight
ABSTRACT:
SUBMITTER: Klonoff DC
PROVIDER: S-EPMC9292194 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: Not available
| S-EPMC9545130 | biostudies-literature
Project description:BackgroundThe statistical power or multiple Type II error rate in large-scale multiple testing problems as, for example, in gene expression microarray experiments, depends on typically unknown parameters and is therefore difficult to assess a priori. However, it has been suggested to estimate the multiple Type II error rate post hoc, based on the observed data.MethodsWe consider a class of post hoc estimators that are functions of the estimated proportion of true null hypotheses among all hypotheses. Numerous estimators for this proportion have been proposed and we investigate the statistical properties of the derived multiple Type II error rate estimators in an extensive simulation study.ResultsThe performance of the estimators in terms of the mean squared error depends sensitively on the distributional scenario. Estimators based on empirical distributions of the null hypotheses are superior in the presence of strongly correlated test statistics.AvailabilityR-code to compute all considered estimators based on P-values and supplementary material is available on the authors web page http://statistics.msi.meduniwien.ac.at/index.php?page=pageszfnr.
| S-EPMC3500624 | biostudies-literature
Project description:BackgroundInstrumented assessment of motor symptoms has emerged as a promising extension to the clinical assessment of several movement disorders. The use of mobile and inexpensive technologies such as some markerless motion capture technologies is especially promising for large-scale application but has not transitioned into clinical routine to date. A crucial step on this path is to implement standardized, clinically applicable tools that identify and control for quality concerns.ObjectiveThe main goal of this study comprises the development of a systematic quality control (QC) procedure for data collected with markerless motion capture technology and its experimental implementation to identify specific quality concerns and thereby rate the usability of recordings.MethodsWe developed a post hoc QC pipeline that was evaluated using a large set of short motor task recordings of healthy controls (2010 recordings from 162 subjects) and people with multiple sclerosis (2682 recordings from 187 subjects). For each of these recordings, 2 raters independently applied the pipeline. They provided overall usability decisions and identified technical and performance-related quality concerns, which yielded respective proportions of their occurrence as a main result.ResultsThe approach developed here has proven user-friendly and applicable on a large scale. Raters' decisions on recording usability were concordant in 71.5%-92.3% of cases, depending on the motor task. Furthermore, 39.6%-85.1% of recordings were concordantly rated as being of satisfactory quality whereas in 5.0%-26.3%, both raters agreed to discard the recording.ConclusionsWe present a QC pipeline that seems feasible and useful for instant quality screening in the clinical setting. Results confirm the need of QC despite using standard test setups, testing protocols, and operator training for the employed system and by extension, for other task-based motor assessment technologies. Results of the QC process can be used to clean existing data sets, optimize quality assurance measures, as well as foster the development of automated QC approaches and therefore improve the overall reliability of kinematic data sets.
| S-EPMC9015782 | biostudies-literature
Project description:ObjectiveIn SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA1c) and body weight (BW) reductions versus once-weekly dulaglutide in subjects with type 2 diabetes (T2D). This post hoc analysis investigated the impact of clinically relevant subject characteristics on treatment effects of semaglutide versus dulaglutide.DesignAnalyses by baseline age (<65, ≥65 years), sex (male, female), diabetes duration (≤5, >5-10, >10 years), HbA1c (≤7.5, >7.5-8.5, >8.5% (≤58, >58-69, >69 mmol/mol)) and body mass index (BMI) (<30, 30-<35, ≥35 kg/m2).Setting194 sites; 16 countries.ParticipantsSubjects with T2D (n=1199) exposed to treatment.InterventionsSemaglutide 0.5 mg versus dulaglutide 0.75 mg (low-dose comparison); semaglutide 1.0 mg versus dulaglutide 1.5 mg (high-dose comparison), all subcutaneously once weekly.Primary and secondary outcome measuresChange in HbA1c (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA1c targets (<7%, ≤6.5% (<53, ≤48 mmol/mol)) and weight-loss responses (≥5%, ≥10%) at week 40; and safety.ResultsHbA1c and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA1c targets and weight-loss responses were statistically significantly greater for the majority of comparisons of semaglutide versus dulaglutide within each subgroup category and, excepting glycaemic control within the low-dose comparison in HbA1c subgroups, this was irrespective of subgroup or dose comparison. Gastrointestinal adverse events, the most common with both treatments, were reported by more women than men and, with semaglutide, decreased with increasing BMI.ConclusionsConsistently greater improvements in HbA1c and BW with semaglutide versus dulaglutide, regardless of age, sex, diabetes duration, glycaemic control and BMI, support the efficacy of semaglutide across the continuum of care in a heterogeneous population with T2D.Trial registration numberNCT02648204.
| S-EPMC7670946 | biostudies-literature
Project description:BackgroundGLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk.MethodsSUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction P values. Risk of major adverse cardiovascular event was analyzed according to prior stroke.ResultsA total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46-1.00]; P=0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29-0.89]; P=0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37-0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47-1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (Pinteraction=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke (Pinteraction >0.05 for all).ConclusionsSemaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT01720446 and NCT02692716.
| S-EPMC9389936 | biostudies-literature
Project description:IntroductionOctreotide acetate subcutaneous injection is indicated to treat acromegaly and the symptoms of carcinoid tumors and vasoactive intestinal peptide tumors (VIPomas). This formative human factors study assessed the octreotide acetate pen injector and accompanying instructions for use (IFU) with self-trained participants.MethodsThe study enrolled patients with diagnoses of acromegaly, carcinoid tumors, or VIPomas and healthcare practitioners (HCPs) who treat patients with these diagnoses. The IFU provided a stepwise process with illustrations to train participants on using the pen injector. Participants familiarized themselves with the pen injector and the IFU before administering 2 unaided injections into skin-like pads; administering the full dose into the pad was considered a successful injection. The investigators evaluated each injection by performance measures-specific tasks necessary to safely and correctly administer the medication-and subjective measures, which included participant comments, feedback from questions, and suggestions for improvements.ResultsThe study enrolled 11 participants-8 patients and 3 HCPs. Participants had a success rate of 100% for both injections. Errors included 1 participant priming the pen with the incorrect dose and 2 participants not holding the injector button for 10 s after the injection. Neither error led to a failed injection. To improve the IFU, participants suggested changing the order of wording on the priming step, clarifying illustrations of the plunger, and stronger indications to hold the injector button.ConclusionThe octreotide pen injector and IFU were usable by self-trained participants. Participant errors and suggestions provided a foundation for recommendations to improve the IFU.
| S-EPMC8189973 | biostudies-literature
Project description:IntroductionThe standard of care for reversal of opioid-induced respiratory depression associated with opioid overdose is injectable naloxone. This study compared the usability of two naloxone delivery devices, a naloxone auto-injector (NAI) and a naloxone intranasal delivery system (NXN), in the administration of naloxone during a simulated opioid overdose emergency. NAI (EVZIO (®) ; kaleo, Inc., Richmond, VA, USA) is a Food and Drug Administration approved single-use pre-filled auto-injector containing 0.4 mg of naloxone.MethodsStudy participants were randomly assigned to administer naloxone using NAI and NXN, sequentially. The primary endpoint was successful administration of a simulated dose of naloxone into a mannequin during a simulated opioid emergency, both before and after receiving training. Secondary endpoints included using the NAI or NXN in accordance with the instructions-for-use and the comparative measurement of successful completion time of administration for both NAI and NXN.ResultsA total of 42 healthy participants aged 18-65 years were enrolled in the study. The proportion of participants able to successfully administer a simulated dose of naloxone was significantly greater for NAI compared to NXN both before (90.5% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 57.1%, respectively, P < 0.0001) participant training. The proportion of participants able to administer a simulated dose of naloxone in accordance with the instructions-for-use was also significantly greater for NAI compared to NXN before (85.7% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 0.0%, respectively, P < 0.0001) participant training. The average time to task completion for administration attempt before training was 0.9 ± 0.25 min for NAI versus 6.0 ± 4.76 min for NXN and after training was 0.5 ± 0.15 min for NAI versus 2.0 ± 2.15 min for NXN.ConclusionLaypersons experienced substantially greater success administering a simulated dose of naloxone, both before and after training, using NAI versus NXN during a simulated opioid overdose emergency. No participants correctly used NXN without training.
| S-EPMC4470965 | biostudies-literature
Project description:Cardiovascular risk reduction with liraglutide and semaglutide in patients with type 2 diabetes was demonstrated in the LEADER (ClinicalTrials.gov: NCT01179048) and SUSTAIN 6 (ClinicalTrials.gov: NCT01720446) cardiovascular outcome trials. This post hoc analysis assessed the impact of diabetes duration (<5, 5 to <15, 15 to <25 and ≥25 years at baseline) on cardiorenal efficacy of these human glucagon-like peptide-1 analogues using a Cox proportional hazards model. Proportions of patients in the LEADER trial across diabetes duration strata were 15% (<5 years, n = 1377), 50% (5 to <15 years, n = 4692), 27% (15 to <25 years, n = 2504) and 8% (≥25 years, n = 748); corresponding proportions in the SUSTAIN-6 trial were 13% (<5 years, n = 422), 48% (5 to <15 years, n = 1582), 30% (15 to <25 years, n = 977) and 10% (≥25 years, n = 316). Overall, longer diabetes duration was associated with higher age; higher prevalence of females; history of ischaemic stroke, peripheral arterial disease and insulin use; and inferior renal function. There was an increased frequency of major adverse cardiovascular events (MACE), expanded MACE and nephropathy events with increasing diabetes duration. Liraglutide and semaglutide consistently reduced the risk of cardiorenal outcomes across categories of diabetes duration (P-interaction was not significant for all endpoints analysed).
| S-EPMC6619033 | biostudies-literature
Project description:PURPOSE:Computerized adaptive testing (CAT) has been adopted in licensing examinations because it improves the efficiency and accuracy of the tests, as shown in many studies. This simulation study investigated CAT scoring and item selection methods for the Korean Medical Licensing Examination (KMLE). METHODS:This study used a post-hoc (real data) simulation design. The item bank used in this study included all items from the January 2017 KMLE. All CAT algorithms for this study were implemented using the 'catR' package in the R program. RESULTS:In terms of accuracy, the Rasch and 2-parametric logistic (PL) models performed better than the 3PL model. The 'modal a posteriori' and 'expected a posterior' methods provided more accurate estimates than maximum likelihood estimation or weighted likelihood estimation. Furthermore, maximum posterior weighted information and minimum expected posterior variance performed better than other item selection methods. In terms of efficiency, the Rasch model is recommended to reduce test length. CONCLUSION:Before implementing live CAT, a simulation study should be performed under varied test conditions. Based on a simulation study, and based on the results, specific scoring and item selection methods should be predetermined.
| S-EPMC6062673 | biostudies-literature
Project description:OBJECTIVE:To assess usability, bioavailability, and safety of subcutaneous self-administration of 0.3 mL of methotrexate 50 mg/mL solution via a prefilled autoinjector pen (methotrexate pen) in patients with rheumatoid arthritis. METHODS:The study enrolled methotrexate-naïve and methotrexate-experienced patients aged ?16?years. Visit 1 (Day 1) included methotrexate pen usage training with documentation, patient self-injection, and a patient-training questionnaire completed by the healthcare professional. Visit 2 (Days 8-10) included evaluation of patient self-injection through four scenarios: holding needle in place for 5?s, confirming methotrexate delivery, skin pinch, and pen disposal. At Visit 2, patient opinion and training retention (since Visit 1) were also assessed. Pharmacokinetic parameters were assessed in 25 patients, who were stratified by body weight and randomized to receive injections in the abdomen or the upper thigh. RESULTS:At Visit 1, 12 of 106 patients had questions about the pen, and 4 required self-injection assistance. At Visit 2, the mean performance rating for all scenarios was ?9.8 (scale: 1 (very difficult)-10 (very easy)). Successful completion rates were 96.2%-100%; 91.3%-100% of patients required no assistance. Impressions of the pen were favorable; 98.1% of patients passed the written examination. All methotrexate pens effectively delivered 0.3?mL methotrexate and were intact after use. Body weight >100?kg significantly decreased total and peak methotrexate exposure when administered abdominally. No adverse effects resulted in drug discontinuation. CONCLUSION:The methotrexate pen was used with a high degree of effectiveness, satisfaction, and safety, indicating that this delivery system may be a viable option for patients requiring subcutaneous methotrexate.
| S-EPMC4712753 | biostudies-literature