A Survey to Assess the Current Status of Structured Benefit-Risk Assessment in the Global Drug and Medical Device Industry.

BACKGROUND: This industry survey was conducted to gain insight into the ways structured Benefit-Risk assessment (sBRA) of medical products is approached across drug or medical device developing companies, including frameworks and methods that are currently used and areas where future work is being planned. METHODS: A survey containing 28 questions covering five key areas of sBRA was set-up and shared with representatives from the participating companies. Each company was asked to complete a single survey response including inputs across the company's multidisciplinary key representatives involved in benefit-risk assessment. RESULTS: Of the 26 participating companies, 21 (81%) are conducting sBRA. Considering these 21 qualitative frameworks were used by almost every company (19, 90%), while only 12 (57%) have used a quantitative method. Many companies have sBRA training (17, 81%), document templates (16,76%), Standard Operating Procedures (SOPs)/checklists (13, 62%), and /or best practice manuals/examples (12,57%) available. Considering all 26 companies Software tools (15, 58%) and BR planning documents (11,42%) were identified as areas into which many companies intend to put effort. CONCLUSIONS: The industry survey confirmed a wide usage of sBRA by many companies involved in research and development. Nevertheless, sBRA is evolving and several future opportunities like the implementation of visualization tools were identified by the representatives of the pharmaceutical companies. Finally, challenges like the cross-functional comprehension of the added value of sBRA are still seen.

Safety and reactogenicity of the BNT162b2 COVID-19 vaccine: Development, post-marketing surveillance, and real-world data.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to urgent actions by innovators, vaccine developers, regulators, and other stakeholders to ensure public access to protective vaccines while maintaining regulatory agency standards. Although development timelines for vaccines against SARS-CoV-2 were much quicker than standard vaccine development timelines, regulatory requirements for efficacy and safety evaluations, including the volume and quality of data collected, were upheld. Rolling review processes supported by sponsors and regulatory authorities enabled rapid assessment of clinical data as well as emergency use authorization. Post-authorization and pharmacovigilance activities enabled the quantity and breadth of post-marketing safety information to quickly exceed that generated from clinical trials. This paper reviews safety and reactogenicity data for the BNT162 vaccine candidates, including BNT162b2 (Comirnaty, Pfizer/BioNTech COVID-19 vaccine) and bivalent variant-adapted BNT162b2 vaccines, from preclinical studies, clinical trials, post-marketing surveillance, and real-world studies, including an unprecedentedly large body of independent evidence.

GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis.

AIM: To evaluate whether the presence of diabetes-specific autoantibodies may predict the development of autoimmune thyroiditis (AIT) in children with type 1 diabetes (T1D). METHODS: Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase IA2 antibodies (IA2A), and insulin autoantibodies (IAA) were determined at T1D onset in 341 children and adolescents. Thyroid antibodies (anti-TG, anti-TPO), thyroid stimulating hormone (TSH), T(3) and T(4) were measured in 335 patients at T1D onset and thereafter annually with a follow-up time of 1-15 yr. In case of thyroid antibody positivity and/or TSH elevation, thyroid gland sonography was performed. Treatment with l-thyroxine was started if persistent elevation of TSH and/or thyroid volume was present. RESULTS: The majority of patients (92.1%) had at least one T1D antibody (71.6% GADA, 73.0% IA2A, and 44.9% IAA). GADA positive patients were older than those without GADA (p < 0.001). Thyroid autoimmunity was found in 15 of 335 patients (4.5%) at T1D onset with female preponderance (p = 0.013). At the end of follow-up, 70 patients (20.9%) had developed thyroid autoantibodies [cumulative incidence (CI) 0.36 ± 0.06 at 10 yr of T1D]. In 30 patients (9.0%), AIT was diagnosed up to 9.4 yr after T1D onset (CI 0.24 ± 0.06 at 10 yr). AIT incidence was not influenced by IAA or IA2A positivity. In multivariate analysis, GADA positive patients were estimated to have a 3.5-fold increased risk of AIT (CI 0.31 ± 0.11 at 10 yr) compared to those without GADA (p = 0.024). CONCLUSION: Based on the present results, a special focus should be given to GADA positive patients concerning screening for AIT as they are at increased risk to develop autoimmune thyroiditis.