Documents for Download

In this section, you can download the files that have been produced as official output in the project.

Articles in peer-reviewed journals



Input to Regulatory Documents


  • Jonker AH, Mills A, Lau LPL, Ando Y, Baroldi P, Bretz F, Burman CF, Collignon O, Hamdani M, Hemmings RJ, Hilgers RD, Irony I, Karlsson M, Kirschner J, Krischer JP, Larsson K, Leeson-Beevers K, Molenberghs G, O’Connor D, Posch M, Roes KC, Schaefer F, Scott J, Senn SJ, Stallard N, Thompson A, Torres F, Zohar S, Aymé S, Day S Eds.: Small Population Clinical Trials: Challenges in the Field of Rare Diseases. July 2016.

Dissertations & Theses

Short Courses / Workshop organization

  • Introduction to N of 1 Trials . S. Senn. Invited Course. 24-02-2017, University of Sheffield, UK.
  • PSI Course: The Design and Analysis of N of 1 Trials . S. Senn. 05-06 July 2016. Hayes, UK.
  • Statistical Issues in Drug Development. S. Senn. 10-11 May 2016. Luxembourg.
  • Workshop on analysing and planning n-of-1 trials. S. Senn. 2016 May 5. Biogen.
  • The Challenge of “Small Data”. Rare Diseases and Ways to Study Them.  S. Senn. 2016 May 5. Biogen.
  • Group Sequential and Adaptive Study Design. F. König. 29 June 2016. Summerschool  organized by Universität Salzburg, International Biometric Society (German Region and Region Austria-Swiss), Austrian Statisical Society, Austria.
  • Population Optimum Design of Experiments (PODE). A. Hooker. 20 June 2016. at Uppsala University, Sweden.
  • Longitudinal and incomplete data. G. Molenberghs. 16-18. March 2016. at University Vienna, Austia.
  • Tutorial on Adaptive Designs for Confirmatory Clinical Trials. F. König. 8 March 2016. ENAR 2016 Spring Meeting. Austin, Texas, USA.
  • Joint Workshop on Small Population Clinical Trials Challenges in the Field of Rare Diseases organized by IRDiRC-EMA Small Population Clinical Trials Task Force. F König. 03. March 2016.
  • Pseudo-likelihood and Split-sample Methods in Small and Very Large Studies G. Molenberghs.  13. January 2016. at London School of Hygiene and Tropical Medicine, London, UK.
  • Frontiers of Confirmatory Inference in Small Populations. F König. 02. September 2015. 9th International Conference on Multiple Comparison Procedures in Hyderabad, India.
  • ISCB Workshop in Stratification and randomization in clinical trials. R.-D. Hilgers, D. Uschner and D. Schindler in collaboration with Armin Koch. 23 August 2015. Utrecht, Netherlands.
  • Regulartory Panel Discussion. F. König. 27 June 2015.ISBS-DIA Joint Symposium on Biopharmaceutical Statistics. Beijing, China.
  • Trends in adaptive design and statistical approaches to small population group trials in EU. F. König. 23 March 2015. PMDA – Pharmaceuticals and Medical Devices Agency. Tokyo.
  • ISCB Short Course in “Novel approaches to multiple test problems, with applications to adaptive designs and dose finding”. F. König. 27-28 November 2014. Budapest, Hungary.
  • Summer school “Adaptive Designs and Multiple Testing in Clinical Trials”. F. König, and M. Posch. Universtat Politécnica de Catalunya. 8-10 July, 2014. Bacelona, Spain.
  • Surrogate marker evaluation in clinical trials. W. van der Elst. Symposium on Small Populations. July 2014. Vienna. Austria
  • Randomisation and Stratification in clinical trials. L. Aguirre Dávila, E. Budde, S. Ernst, T. Framke, A. Gonnermann, R.-D. Hilgers, A. Koch, M. Kottas, D. Schindler, L. Spineli, D. Uschner, K. Weber. Symposium on Small Populations. 2014 July 3. Vienna. Austria
  • Adaptive Clinical Trial Designs. F. König, M. Posch, G. Wassmer. Symposium on Small Populations. 2014 July 3. Vienna. Austria
  • Supporting the pathways to trials for rare diseases: Clinical trial design and other considerations. Part 1: Clinical trial designs for small population group trials. R.-D. Hilgers. ECRD Invited Workshop. 2014 May 9. Berlin, Germany.

Conference Posters

  • Influence of clinical trial design to detect drug effect in systems with within subject variability. Karlsson, M. 2015 June 2. – 5. The Population Approach Group in Europe (PAGE) conference, Hersonissos, Crete, Greece.
  • Perl speaks NONMEM (PsN) and Xpose. Harling, K., Nordgren, R., Hooker, A.C., Karlsson, M. 2016 June 7. – 10. The Population Approach Group in Europe (PAGE) conference, Lisboa, Portugal.
  • Quantifying drug effects in phase 2a anti-diabetic studies : Power of four HbA1c models. Wellhagen, G.J., Karlsson, M.O., Kjellsson, M.C. 2015 June 2. – 5. The Population Approach Group in Europe (PAGE) conference, Hersonissos, Crete, Greece.
  • Parameter estimations for various distributed  data with observations below a lower limit of  quantification. T. Berger, R.-D. Hilgers, Conference Poster. ISCB 2016. 2016 August 21-25.
  • Determination of Appropriate Settings in the Assessment of Parameter Uncertainty Distributions using Sampling Importance Resampling (SIR)Conference Poster.
  • Marketing authorisation of orphan medicines in Europe 2000-2013: a 13-year experience. Conference Poster.
  • Fast Saddle-Point Algorithm for Generalized Dantzig Selector and FDR Control with the Ordered l1-Norm. S. Lee, D. Brzyski, M. Bogdan. Conference Poster.
  • Minimierungsmethode bei binärem  Outcome und kleiner Fallzahl. C. Fitzner,  L. A. Dávila, R.-D. Hilgers. Conference Poster. DAGStat 2016. March, 14-18. Göttingen, Germany.
  • Adaptive two-stage bioequivalence trials with early stopping and sample size re-estimation. F. König, M. Wolfsegger, T. Jaki, H. Schütz, G. Wassmer. Conference Poster. ISCB 2014. 2014 Aug, 24-27. Vienna, Austria.
  • Adaptive designs for confirmatory model based decisions using MCP-Mod. S. Krasnozhon, A. Graf, B. Bornkamp, F. Bretz, G. Wassmer, F. König. Conference Poster. ISCB 2014. 2014 Aug, 24-27. Vienna, Austria.
  • Comparison of different allocation procedures in clinical trials in small population groups with respect to accidental and selection bias. D. Schindler, D. Uschner, M. Tamm, N. Heussen, R.-D. Hilgers. Conference Poster. ISCB 2014. 2014 Aug, 24-27. Vienna, Austria.
  • Split-sample based and multiple imputation estimation & computation for data hierarchies (Meta-analysis, clinical trials, and beyond.). Mohlenberghs, G., Spring Meetings of the Eastern North American Region of the International Biometric Society, Miami, FL, USA. 2015 March 15.
  • Evidence, Eminence,and Extrapolation: Adapted Levels of Evidence for Small Populations. G. Hlavin. Conference Poster. ISCB 2014. 2014 Aug, 24-27. Vienna, Austria.
  • Accelerating Monte-Carlo power studies through parametric power estimation. Ueckert, S., Karlsson, M.O., Hooker, A.C., Population Approach Group in Europe (PAGE), Alicante, Spain. 10th June 2014.
  • Integrated Design and Analysis of small population group trials. R.-D. Hilgers. Conference Poster. ECRD 2014. 2014 May 8. Berlin, Germany.


Press Articles

Awards & Distinctions

    • Damian Brzyski earns distinguished paper award for his work on SLOPE. 17th March 2017.
    • Arthur Linder Award of the International Biometric Society is awarded to Gerald Hlavin. 7th August 2015, Vienna, Austria.
    • Nicole Heussen has been offered a professorship in biostatistics at Sigmund Freud University Vienna. February 2015, Vienna, Austria.

Commemorative Publications

Webinars & Videos

Related Research

The following papers are related to IDeAl, either because they complement the work of IDeAl in close coorporation with IDeAl researchers, or they cite research that was conducted in the context of the IDeAl project without directly being part of IDeAl.

Meta-research quoting IDeAl

  • Tudor Smith, Catrin, Williamson, Paula R., and Beresford, Michael W.: Methodology of clinical trials for rare diseases.Best Practice & Research Clinical Rheumatology, 2, 247-62, 2014. Gives a detailed overview about IDeAls aims and research topics, and states that the research conducted in this project contributes to improving the efficiency of rare disease trials.
  • O´Connor, Daniel J., and Hemming, Robert James: Coping with small populations of patients in clinical trials. Expert Opinion on Orphan Drugs, 2, 765-768, 2014. Quotes IDeAl as one of three research initiatives funded by the European Unions Seveth Framework Programme dedicated to the development of new methodology for small population group trials.

Sideline Research

  • Carl-Frederik Burman is part of the organizing committee of the EFSPI workshop on Biomarkers and Subgroups on 24th June, 2016, Leiden.
  • Carl-Frederik Burman is invited speaker for a session on rare diseases at ISCB in Birmingham from 21th till 25th August, 2016, Birmingham.
  • S. Jobjörnsson published the R Package bdpopot:  Optimisation of Baysian Decision Problems (March 2016).
  • A.G. Dosne, Bergstrand M., and Karlsson M.O.: A strategy for residual error modeling incorporating scedasticity of variance and distribution shape. Journal of Pharmacokinetics and Pharmacodynamics. 43, 2, 137-151, 2016.
  • M. Bogdan and P. Szulc are working with D. Siegmund from Stanford University and R.W. Doerge from Purdue University on explaining/preventing false discoveries in gene mapping due to polygenic effects (April 2016).
  • J. Korell, S.W. Martin, M.O. Karlsson, and Ribbing, J.: A model-based longitudinal meta-analysis of FEV1 in randomized COPD trials. Clinical Pharamcology & Therapeutic. 99, 3, 315-324. 2016.
  • Y. Aoki, R. Nordgren, Hooker A.C.: Preconditioning of Nonlinear Mixed Effects Models for Stabilisation of Variance-Covariance Matrix Computations. AAPS Journal. 18, 2, 505-518. 2016.
  • Frommlet, F., Bogdan, M., and Ramsey D.: Phenotypes and Genotypes – search for influential genes. Springer. 2016.
  • Ralf-Dieter Hilgers, Nigel Stallard and Kit Roes submitted a poster to the ERCD 2016 in Edinburgh (January, 2016).
  • S. Choy, M.C. Kjellsson, M.O. Karlsson, de Winter W.: Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes. CPT Pharmacometrics Syst Pharmacol. 5, 1, 11-19. 2016.
  • Ralf-Dieter Hilgers coauthored an editorial “Hedgehog blockade for basal cell carcinoma: does it come at a (secondary neoplastic) price?“, which shows the connection of small population trials to big data published in JAMA Dermatology.
  • Holger Dette has worked with Kirsten Schroning, Wenge Kee Wong, Frank Bretz and Kathrin Kettelhake on: Optimal designs for active controlled dose finding trials with efficacy-toxicity outcomes (January, 2016)
  • Christina Fitzner started working on the topic “Evaluation of categorical data after covariate adaptive randomization for small samples” at Uniklinik Aachen (January, 2016).
  • Ralf-Dieter Hilgers, Nigel Stallard and Kit Roes are writing a position paper about “Directions for new developments on statistical design and analysis of small population group trials” to be submitted to Orphante (from December 2015 til March 2016).
  • Ralf-Dieter Hilgers, Franz König, Geert Molenberghs and Stephen Senn were invited to  write an expert opinion paper entitled “Design and analysis of clinical trials for small rare disease populations“ to be submitted to Expert Opinion for Orphan Drugs (from December 2015 til March 2016).
  • Ralf-Dieter Hilgers coauthored a paper “Making sense of big data in health research – Towards an EU action plan in systems medicine and citizen science“, which shows the connection of small population trials to big data. The paper was submitted to Genome in Medicine in 2016.
  • Tanja Berger started working on the topic “Estimation approaches for distribution paramters in the case of observations under multiple lower limits of quantification” for small samples supervised by Ralf-Dieter Hilgers and Nicole Heussen (October, 2015).
  • Carl-Frederik Burman is invited speaker for a session on statistical methodology for clinical research in rare diseases at ISCB in Utrecht from 23th till 27th August, 2015, Utrecht.
  • A Bayesian model for the selection of sample size in clinical trials. S. Jobjörnsson. Contributed Talk. 2014 June 5. Nordstat, Turkey.
  • Nicole Heussen, William F. Rosenberger and Ralf-Dieter Hilgers are investigating “Randomization tests with respect to missing values”. Since January 2016, their work is supported by Kai Fuge (June, 2016).
  • Bram Burger investigates “Randomization tests with longitudinal (generalized) linear mixed models for small samples” supervised by Geert Molenberghs, Wim van der Elst, Bill Rosenberger, Ralf-Dieter Hilgers and Nicole Heussen (June, 2015).
  • Ann Christina Foldenauer investigates the “Evaluation of Stepped Wedge Design under consideration of carry-over effects for small sample clinical trials” supervised by Ralf-Dieter Hilgers and Nicole Heussen (April, 2014).
  • In 2014, the Drug Information Associations work stream on Adaptive Programmes, led by Carl-Fredrik Burman, decides to launch a working group on Small Populations. This working group is led by Prof. Bob Beckman, Georgetown University. The Small Population working group is collaborating with IDeAl WP 4 and 9 on designs when biomarker-defined subpopulations are present. The working group also conducts research on other topics around trial design for small population groups, without a formal link to IDeAl.