Publications

1. Efficient adaptive designs for clinical trials of interventions for COVID-19, Statistics in Biopharmaceutical Research (2020)

Statistics in Biopharmaceutical Research: Vol 12, No 2

Nigel Stallard, Lisa Hampson, Norbert Benda, Werner Brannath, Thomas Burnett, Tim Friede, Peter K. Kimani, Franz Koenig, Johannes Krisam, Pavel Mozgunov, Martin Posch, James Wason, Gernot Wassmer, John Whitehead, S. Faye Williamson, Sarah Zohar & Thomas Jaki (2020) Efficient adaptive designs for clinical trials of interventions for COVID-19, Statistics in Biopharmaceutical Research, DOI: 10.1080/19466315.2020.1790415

ABSTRACT

The COVID-19 pandemic has led to an unprecedented response in terms of clinical research activity. An important part of this research has been focused on randomized controlled clinical trials to evaluate potential therapies for COVID-19. The results from this research need to be obtained as rapidly as possible. This presents a number of challenges associated with considerable uncertainty over the natural history of the disease and the number and characteristics of patients affected, and the emergence of new potential therapies. These challenges make adaptive designs for clinical trials a particularly attractive option. Such designs allow a trial to be modified on the basis of interim analysis data or stopped as soon as sufficiently strong evidence has been observed to answer the research question, without compromising the trial’s scientific validity or integrity. In this paper we describe some of the adaptive design approaches that are available and discuss particular issues and challenges associated with their use in the pandemic setting. Our discussion is illustrated by details of four ongoing COVID-19 trials that have used adaptive designs.

Key w0rds: Adaptive trial Group sequential design, Multi-arm multi-stage, Platform trial, SARS-CoV-2, Pandemic research

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2. Systematic review of available software for multi-arm multi-stage and platform clinical trial design, BioMed Central (2021)

Elias Laurin Meyer, Peter Mesenbrink, Tobias Mielke, Tom Parke, Daniel Evans and Franz König on behalf of EU-PEARL (EU Patient-cEntric clinicAl tRial pLatforms) Consortium (2021). Systematic review of available software for multi-arm multi-stage and platform clinical trial design, BioMed Central.  DOI: 10.1186/s13063-021-05130-x

ABSTRACT

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. In this publication, its authors argue that both an open-source modular software 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.

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3. Identifying challenges in neurofibromatosis: a modified Delphi procedure, European Journal of Human Genetics, 2021

 

Britt A. E. Dhaenens, Rosalie E. Ferner, Annette Bakker, Marco Nievo, D. Gareth Evans, Pierre Wolkenstein, Cornelia Potratz, Scott R. Plotkin, Guenter Heimann, Eric Legius &  Rianne Oostenbrink. Identifying challenges in neurofibromatosis: a modified Delphi procedure, European Journal of Human Genetics, April 2021. DOI:10.1038/s41431-021-00892-z

ABSTRACT

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are rare conditions with pronounced variability of clinical expression. We aimed to reach consensus on the most important manifestations meriting the development of drug trials. The five-staged modified Delphi procedure consisted of two questionnaires and a consensus meeting for 40 NF experts, a survey for 63 patient representatives, and a final workshop. In the questionnaires, manifestations were scored on multiple items on a 4-point Likert scale. The highest average scores for NF experts deciding the ‘need for new treatment’ were for malignant peripheral nerve sheath tumour (MPNST) (4,0) and high grade glioma (HGG) (3,9) for NF1; meningioma (3,9) for NF2 and pain (3,9) for SWN. The patient representatives assigned high scores to all manifestations, with plexiform neurofibroma being highest in NF1 (4,0), vestibular schwannoma in NF2 (4,0), and pain in SWN (3,9). Twelve experts participated in the consensus meeting and prioritised manifestations. MPNST was ranked the highest for NF1, followed by benign peripheral nerve sheath tumours. Tumour manifestations received highest ranking in NF2, and pain was the most prominent problem for SWN. Patient representative ratings for NF1 were similar to the experts’ opinions, except that they ranked HGG as the most important manifestation. For NF2 and SWN, the patient representatives agreed with the experts. We conclude that NF experts and patient representatives consent to prioritise development of drug trials for MPNST, benign peripheral nerve sheath tumours, cutaneous manifestations and HGG for NF1; tumours for NF2; and pain for SWN.

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