Deutsch Intern
Institute for Clinical Epidemiology and Biometry

NAPKON-TIP

National Pandemic Cohort Network - Therapeutic Intervention Platform

Medical recommendations are based on high-quality evidence, preferably generated by randomized controlled trials (RCTs). However, this usually requires conducting a new RCT for each new therapeutic approach, which is associated with long implementation times, high costs and a lack of flexibility. Adaptive platform studies offer a viable solution to these problems, especially in fast-moving areas such as during a pandemic.

Project goals:
In the context of the COVID 19 pandemic, the study landscape in Germany was critically scrutinized. Compared to countries such as France and the United Kingdom, Germany has conducted significantly fewer clinical trials and, in particular, adaptive platform studies on COVID-. This is due to the lack of central coordination of nationally relevant studies in the field of infectious diseases and the lack of a comprehensive infrastructure for adaptive platform studies. In order to be better prepared for future pandemics and medical challenges, there is a need for a network that bundles the capacities of university medicine and is able to conduct complex clinical studies independently. The aim of the project is therefore to establish a Therapeutic Intervention Platform (NAPKON-TIP) using existing NUM recruitment networks and infrastructures and to demonstrate its performance in a specific trial. If successful, NAPKON-TIP will become part of the NUM infrastructure, providing both the NUM and external parties with the necessary services to conduct adaptive platform studies.

Challenges:
In NAPKON-TIP, therapy studies are planned independently of the first application. The studies will evaluate drugs, devices/software (medical devices) and non-pharmacological interventions. Patients will be stratified according to individual markers or a combination of clinical profiles, biomarkers, imaging markers and psychometric data. Data from digital health applications will also be considered. Regular interim analyses and mathematical modeling are required to continuously adapt the clinical trials to the latest state of knowledge (principle of the adaptive study). This is done in structured working groups organized in clearly defined work packages. Within these working groups, master protocols and routines have to be developed, regularly communicated and, above all, harmonized between the working groups.

Implementation & project set-up:
Under the guidance of an interdisciplinary steering committee, NAPKON-TIP will first create the necessary organizational and structural prerequisites for conducting clinical trials in accordance with the German Drug Law (AMG) and the German Medicines Act (MPG), especially with regard to adaptive platform studies. The efficiency will be demonstrated by means of a concrete study case, the first use case. NAPKON-TIP consists of six work packages (WP), which are listed in the figure.

The adaptive structure is expected to have the following advantages over the classical study design:

  • accelerated evaluation and translation of basic research into clinical practice in terms of stratification markers, interventions and outcomes
  • direct benefit to participating patients, who immediately benefit from the planned treatments
  • rapid generalization of rapidly obtained safety and efficacy results to all patients enrolled in the trial

Methodologically sound and sufficiently large clinical trials are essential to generate clinical evidence and develop guidelines to improve patient outcomes. NAPKON-TIP provides the NUM with the opportunity to conduct practice-changing clinical trials on a national scale,  thus providing a crucial infrastructure to revitalize the clinical trial landscape in Germany.

Further information on the study can be found at: https://www.netzwerk-universitaetsmedizin.de/projekte/napkon-tip

The IKE-B is involved in WP 3 "Stratification" in cooperation with the University Hospital of Würzburg and as one of several executing study centers in WP 6 "Use Case". The use case "Randomised adaptive assessment of post-COVID syndrome treatments - Reducing Inflammatory Activity in Patients with post-COVID Syndrome (RAPID-REVIVE)" will deal with the treatment of patients with post-COVID.