The concept of estimands has recently been implemented in therapy studies. An estimand represents the underlying research question and is defined by the attributes population, treatments, variable for measuring the individual treatment effect, summary statistics and intercurrent events. In particular, the differentiated handling of intercurrent events, which are often equated with protocol violations, is the new element. An example of an intercurrent event would be an emergency treatment during the course of the study.

Furthermore, strategies for dealing with intercurrent events are prespecified, e.g. the strategy could be not to use the results after an emergency treatment (while-on-treatment strategy). Depending on the strategy and the assumptions for possible resulting missing values, a suitable theoretical estimator results. In the example, a possible estimator would be the mean treatment effect, whereby in the case of emergency treatment only the data collected beforehand are used.

In diagnostic studies, too, intercurrent events as well as missing values and appropriate statistical methods for dealing with them are important topics. However, the concept of estimands does not yet exist and there are still large gaps in methods for dealing with missing values. For this reason, the present project aims to transfer the concept of Estimands from therapy studies to diagnostic studies. For this purpose, the attributes of the estimands and strategies for dealing with intercurrent events will be adapted for diagnostic studies. Furthermore, statistical methods for dealing with missing values will be further developed on this basis in order to arrive at suitable estimators. This joint concept of estimand and methods for dealing with missing values will be evaluated in simulation studies and for example studies.

In addition, adaptive designs for diagnostic studies will be developed with regard to estimands and missing values. Adaptive designs allow for prespecified adjustments during the course of the study and can lead to more efficient studies, but they also have their limitations. Therefore, adaptive designs will be developed and evaluated that, for example, allow number-of-cases adjustments based on frequencies of intercurrent events or allow design changes that imply modifications of the estimand.

Due to the new European medical device regulation, the requirements for diagnostic studies will increase significantly. For this purpose, the research project will provide recommendations for action, which will be disseminated in the form of corresponding documents and within the framework of workshops and a symposium. In addition, the methods developed are to be implemented in freely accessible software, thus enabling easy application.

Duration: 2022 - 2025

• Dr. Mouna Akacha (Novartis Pharma AG Basel, Schweiz)
• PD Dr. Norbert Benda (BfArM, Deutschland)
• Prof. Dr. Patrick Bossuyt (Amsterdam UMC, Niederlande)
• Prof. Dr. Nandini Dendukuri (McGill University, Montreal)
• Prof. Dr. Marc Dewey (Charité Berlin, Deutschland)
• Prof. Dr. Carl Moons (UMC Utrecht, Niederlande)
• Prof. Dr. Hans Reitsma (UMC Utrecht, Niederlande)

Workshop 2022

The next workshop is scheduled to take place in Hamburg in spring 2024. If you are interested in participating in the workshop, you can be added to the email distribution list.
To do so, please write an e-mail to Prof. Dr. Antonia Zapf .