IDeAl talk at FDA

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Coordinator Ralf-Dieter Hilgers and Nicole Heussen give a talk at the U.S. Food and Drug Administration on 2016 May 6 titled “Does Randomization protect against bias? What can be done to improve the level of clinical evidence of effectiveness?”. In their talk, they  share new findings on small population group methodology and connect them with the regulatory guidelines currently in effect. The talk will have a great impact on the awareness of IDeAl research at the regulators office in the U.S., and will therefore also impact the European small population groups.

IDeAl research spreads overseas

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IDeAl senior researcher Nicole Heussen and IDeAl coordinator Ralf-Dieter Hilgers disseminate IDeAl methodology to stakeholders from regulators to academia in the United States. During their three week stay in April 2016, they present their latest results at U.S. Food and Drug Administration (FDA) and give IDeAl input to FDAs guidelines. Furthermore, during their stay, they intensify the collaboration with EAB member W.F. Rosenberger. At George Mason University, Nicole Heussen gives a talk on the treatment of missing values in the randomization test. Ralf-Dieter Hilgers disseminates the latest results on the impact of bias on the test decision given different randomization procedures.

IDeAl researchers present latest results at DagStat

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Several researchers connected to the IDeAl group present their research at the Fourth Joint Statistical Meeting of the Deutsche Arbeitsgemeinschaft Statistik “Statistics under one Umbrella” that takes place at Georg-August University Göttingen this week (14th- 18th of March). Rosemary Bailey (EAB) talks about “Design of Dose-Escalation Trials”, presenting her “Research Spurred by a Trial That Went Wrong”.  Ralf-Dieter Hilgers (Coordinator) chairs a session on Design of Experiments. David Schindler presents the current research in WP2 in a session chaired by Rosemary Bailey. Other talks by IDeAl researchers cover topics ranging from the estimation problems in the Stepped Wedge Design (a cross-over design proposed for small population groups) to bias in survival analysis and to covariate adaptive randomization. In the course of the conference, the IDeAl researchers disseminate their research to stakeholders from industry and academics. They also seize the opportunity to engage in discussions with each other to further intensify their collaboration.

Tutorial on Adaptive Designs for Confirmatory Clinical Trials

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On behalf of the IDEAL consortium Franz König will give an invited tutorial on „Adaptive Designs for Confirmatory Clinical Trials” at the ENAR 2016 Spring Meeting in Austin, Texas, on March 8. The meeting is organized by  Eastern North American Region (ENAR) of the International Biometric Society (IBS). A recent review by Elsaeßer et al (2014) showed that about 59% of adaptive designs evaluated by the scientific advice working party of the European Medicines Agency related to trials in rare diseases and about 36% applied for orphan designation.

Since the first methodological papers on adaptive designs, some published more than 25 years ago (see Bauer et al 2016) , adaptive designs have gained increasing attention in drug development. Especially in pivotal phase III trials, their use is subject to enhanced scrutiny by regulators as the increased complexity of flexible study designs also increases the risk of operational and statistical biases and hidden fallacies. Broad enthusiasm about potential applications of such designs faced critical positions regarding their statistical efficiency. Despite, or possibly because of, this controversy, the methodology and its areas of applications grew steadily over the years, with significant contributions from statisticians working in academia, industry and agencies around the world. In the meantime, such types of adaptive designs have become the subject of three major regulatory guidance documents in the US and Europe and the field is still evolving. The main goal of this tutorial is to give an introduction to the key principles and statistical methodologies of adaptive designs for confirmatory clinical trials. Important applications of adaptive designs include sample size reassessment, treatment selection procedures, and population enrichment designs. The change of design parameters at an adaptive interim analysis may depend on any internal and external data available. Using adaptive multiple test procedures the type I error rate can be controlled even if the selection rule, the number of selected treatments or the final sample sizes are not prefixed. The tutorial shall provide an overview of methods from the published literature including the most recent developments. Special emphasis is put on sample size reassessment and multiple hypotheses testing with adaptive designs. Regulatory issues and case studies will be discussed.

Resources: https://www.enar.org/meetings/spring2016/index.cfm

References:

  • P. Bauer, F. Bretz, V. Dragalin, F. Koenig, and G. Wassmer
    Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls
    Statistics in Medicine 35, 325-347, (2016)
  • A. Elsaeßer, J. Regnstrom, T. Vetter, F. Koenig, R. Hemmings, M. Greco, M. Papaluca-Amati, and M. Posch
    Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency
    Trials 15, 383, (2014)

Rare Disease Taskforce meets in London

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Tomorrow, on March 3, 2016, in London, UK, a Workshop is held at EMA to discuss actions to reach agreement between the different stakeholders on appropriate small population studies. Under the roof of IRDiRC, a Task Force was founded to advance discussions on ways to optimise and improve commonly adopted approaches and to reach agreement between the different stakeholders on appropriate small population studies. The programme of the Task Force can be found here.

The IDeAl consortium will be strongly represented at the meeting with 10 (former) partners or members of advisory board:

Ralf-Dieter Hilgers (IDeAl; RWTH Aachen, Germany)
Paolo Baroldi (Vanda Pharmaceuticals, USA)
Frank Bretz (Novartis, Switzerland)
Carl-Fredrik Burman (Astra Zeneca; Chalmers University, Sweden)
Olivier Collignon (EMA, UK)
Mats Karlsson (Uppsala University, Sweden)
Franz König (Medical University Vienna, Austria)
Geert Molenberghs (KU Leuven, Belgium)
Gérard Nguyen (Rett Syndrome Europe, France)
Stephen Senn (Luxembourg Institute of Health, Luxembourg)

Together with the Scientific Secretariat, the Task Force is creating a draft document for debate on SPCT matters. In due time, this will be open for the community at large for comments and suggestions. This draft is available for comments and consultation on the Task Force’s Website.