Faculdade de Medicina de São José do Rio Preto

Conduct a systematic review and meta-analysis comparing Technosphere Insulin and traditional ultra-rapid insulin in T1DM.

Researchers conducted a systematic search on databases to identify randomized controlled trials (RCTs) comparing two insulin regimens-TI and RAI -in patients with type 1 diabetes mellitus (T1DM). The outcomes of interest included changes in HbA1c levels, body weight, and rates of overall and severe hypoglycemia.

Four RCTs were included. There was no significant difference between groups on change in HbA1c (MD 0.04; 95 % CI -0.19-0.27; p = 0.74; I² = 0 %). In terms of body weight change, the TI group exhibited significantly less (MD -1.05; 95 % CI -1.63 to -0.46; p = 0.0005; I² = 0 %) compared to the RAI group. Adverse events such as overall hypoglycemia (RR -0.97; 95 % CI 0.94-1.01; p = 0.24; I² = 26 %) and severe hypoglycemia (RR 0.63; 95 % CI 0.46-0.87; p = 0.005; I² = 0 %), were significantly more frequent in the RAI group.

The use of Technosphere Insulin (TI) in T1DM patients did not show a difference in HbA1c, suggesting that TI may offer advantages in weight stability and a lower incidence of hypoglycemic events compared to rapid-acting insulin (RAI).

Low-middle-income countries (LMICs) have increased their participation in international oncology trials. However, considerable disparities in treatment standards across countries have raised ethical concerns regarding the use of control arms that may not align with the established standards of care in high-income countries. This trial aims to describe the control arms of randomised oncology trials recruiting in Brazil, an LMIC where the majority of patients receive care through the public health system, the Unified Health System (SUS), which provides limited access to cancer treatments.

This cross-sectional study included randomised clinical trials recruiting in Brazil on 4 December 2023 (ClinicalTrials.gov). Abstracted data included sample size, sponsor, tumour site, study phase and control arm. Two independent investigators classified control arms as superior, equal or inferior based on National Comprehensive Cancer Network (NCCN), Brazilian private insurance and SUS standards. Data were summarised in means, medians and proportions. Fisher’s exact test compared categories. A p<0.05 was considered statistically significant.

A total of 98 studies were included. The median intended sample size was 555 patients (54–6000). Most studies were phase 3 (84.7%) and pharma-sponsored (97%). Lung (29.6%) and breast (24.4%) were the most commonly studied tumour sites. Regarding treatment setting, 23 studies (23.5%) were (neo)adjuvant trials, 48 (49.0%) first-line and 27 (27.5%) second-line or later. Overall, 80 (81.7%), 82 (83.7%) and 58 studies (59.1%) employed control arms considered equivalent to the standards of NCCN, private insurance and SUS, respectively. 18 studies (18.3%) had a suboptimal control arm according to NCCN guidelines, while 16 studies (16.3%) according to Brazilian private insurance. No studies used control arms inferior to SUS standards. Of the 18 control arms inferior to NCCN, 3 were superior and 15 were equal to standard of care offered by SUS. No studies had their control arms superior to NCCN or private insurance; whereas, 40 (40.9%) were superior to SUS.

A significant number of studies employed control arms inferior to NCCN guidelines; however, these were considered superior or equal to the standards offered by SUS. Such discrepancies may hinder the appropriate interpretation of study findings.

CoronaVac, an inactivated COVID-19 vaccine, underwent evaluation for its efficacy and safety during the PROFISCOV study conducted in Brazil.

Between July 21, 2020, and July 29, 2021, 13,166 participants provided informed consent, with 12,688 randomized for the trial. Participants were allocated between vaccine and placebo arms (1:1) and monitored for symptomatic COVID-19 cases, severity of disease, and adverse reactions after two doses given 14 days apart.

The primary efficacy analysis revealed a vaccine efficacy of 50⸱4 % (95 % confidence interval [CI], 35·3 % to 62·0 %; p = 0·0049) in preventing symptomatic COVID-19, leading to the issuance of Emergency Use Authorization for CoronaVac in January 2021. Upon completion of follow-up, vaccine efficacy was 44⸱6 % [95 % CI, 34·9 % to 52·8 %; p = 0·0023] in preventing COVID-19 and 82⸱1 % (95 % CI, 64·9 % to 90·9 %; p < 0·0001) in preventing severe COVID-19. Safety data indicated that adverse reactions were more frequent in the vaccine arm, primarily mild to moderate, with pain at the injection site and headache being the most common.

CoronaVac demonstrated moderate efficacy in preventing symptomatic COVID-19 and high efficacy against severe disease. While reactions were slightly more common in the vaccine group, they were generally mild and manageable.

Fundação Butantan, Instituto Butantan, and São Paulo Research Foundation (FAPESP; Grants 2020/10127-1 and 2020/06409-1).