The inverse of the Fisher Information Matrix is a lower bound for the covariance matrix of any unbiased estimator of the parameter vector and, given this, it is important for the construction of optimal designs. For normally distributed observation vectors with known variance, the Fisher Information can be easily constructed. For nonlinear mixed effects models, the problem of the missing closedform solution of the likelihood function carries forward to the calculation of the Fisher Information matrix. The often used approximation of the Fisher Information by linearizing the model-function in the fixed effects is generally not reliable, as will be shown in this article.
Background
In recent years, the popularity of multi-arm multi-stage, seamless adaptive, and platform trials has increased. However, many design-related questions and questions regarding which operating characteristics should be evaluated to determine the potential performance of a specific trial design remain and are often further complicated by the complexity of such trial designs.
Methods
A systematic search was conducted to review existing software for the design of platform trials, whereby multi-arm multi-stage trials were also included. The results of this search are reported both on the literature level and the software level, highlighting the software judged to be particularly useful.
Results
In recent years, many highly specialized software packages targeting single design elements on platform studies have been released. Only a few of the developed software packages provide extensive design flexibility, at the cost of limited access due to being commercial or not being usable as out-of-the-box solutions.
Conclusions
We believe that both an open-source modular software similar to OCTOPUS and a collaborative effort will be necessary to create software that takes advantage of and investigates the impact of all the flexibility that platform trials potentially provide.
Background and Aims: Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. Methods: Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project.
Results:Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design
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