Bioequivalence for highly variable drugs: regulatory agreements, disagreements, and harmonization
AbstractRegulatory authorities introduced procedures in the last decade for evaluating the bioequivalence (BE) for highly variable drugs. These approaches are similar in principle but differ in details. For example, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommend differing regulatory constants. The constant suggested by FDA results in discontinuity of the BE limits around the switching variation at 30% observed within-subject variation of the reference product. The regulatory constant of EMA does not have these problems. The Type I error reaches 6 –7% around the switching variation with the EMA constant but 16–17% with the FDA constant. Various procedures were recently suggested, especially for the EMA approach, to eliminate the inflation of the Type I error. Notably, the so-called Exact algorithms try to amalgamate the positive features of both EMA and FDA procedures without their negative sides. The computational procedure for the EMA approach is simple and has a straightforward interpretation. The procedure for the FDA approach is based on an approximation, has a bias at small degrees of freedom, and requires a suitable computer program. All regulatory agencies impose a second requirement constraining the point estimate of the ratio of geometric means. In addition, EMA and Health Canada impose an upper limit for applying the recommended procedures. These expectations have psychological motivation and political rationale ...
DiscussionThe interventions of education and medication alerts resulted in a significant increase in the percentage of patients receiving appropriate doses of dilTIAZem and a nonsignificant decrease in the incidence of hypotension. This process-oriented intervention resulted in an improvement in appropriate dilTIAZem doses at our site. Rate control was not statistically significantly different between the 2 groups. Long-term sustainability of this intervention requires further study.
ConclusionsVitamin D insufficiency was prevalent in both newly diagnosed axSpA patients and healthy controls. There was no association between vitamin D and pain and disease activity in the newly diagnosed axSpA patients. Monitoring vitamin D levels is important and early intervention for vitamin D insufficiency is needed, especially in female patients.
ConclusionVacuum assisted dressing is more effective than traditional wound dressing in wound healing of open fractures.
This study aims to reflect on the process of adoption of the preprints publication model, briefly delimiting its history and current use by the national and the international scientific community. Departing from the literature and a consultation of preprint repositories, this reflection intends to highlight the main challenges that preprint implementation will face in the Nursing area, along with its specificities. While considering its benefits for scientific dissemination, this study points out the difficulties that may arise from the implementation of mostly north-American science models in a peripheral country such as ...
RESUMO Objetivo Identificar na literatura a avalia ção da qualidade dos serviços de Atenção Primária à Saúde sob a ótica de cuidadores de crianças por meio da aplicação do PCATool, versão infantil. Método Revisão integrativa realizada nas bases de dados MEDLINE, CINAHL, LILACS, BDENF e Web of Science. Resultados Foram selecionados 17 artigos. Todos os estudos incluídos eram descritivos (100%) e possuíam nível de evidência IV (100%). O componente grau de afiliação (média=7,...
CONCLUSIONS: Neonatal screening with the red reflex is not sufficient to detect intraocular disease. A normal neonatal red reflex does no exclude intraocular disease. It has a specificity of nearly 90%, but its sensitivity is only 56%. Most retinal haemorrhages are undiagnosed as they cannot be detected with a red reflex. PMID: 31826811 [PubMed - as supplied by publisher]
Reaction to claims of study misconduct have dominated the press and social media since the report dropped earlier this week.Medscape Medical News
At least 1,300 people have died from the flu so far this season, according to a preliminary estimate released Friday by the US Centers for Disease Control and Prevention.
Researchers have developed a self-cleaning plastic wrap that repels bacteria -- and could be used to prevent the transfer of antibiotic resistant superbugs, and other forms of dangerous bacteria.
There is evidence that an ancient Chinese form of martial arts improves your mind and body, and may even contribute to a longer life.