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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.