1 / 31

FMS and the development of biostatistics during 25 years

FMS and the development of biostatistics during 25 years (mostly from a pharma industry perspective) FMS jubilee conference at Utö, 25 October 2012 Bernhard Huitfeldt BH Statistical Consulting. Your future depends on your history. Janus: The Roman god of beginnings

swinfordg
Download Presentation

FMS and the development of biostatistics during 25 years

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. FMS and the development of biostatistics during 25 years (mostly from a pharma industry perspective) FMS jubilee conference at Utö, 25 October 2012 Bernhard Huitfeldt BH Statistical Consulting Bernhard Huitfeldt 24 Oct 2012

  2. Your future depends on your history Janus: The Roman god of beginnings and transitions and …… time and he looks to the future and the past. Bernhard Huitfeldt 24 Oct 2012

  3. Bernhard Huitfeldt 24 Oct 2012

  4. By-law aims for FMS • Contribute to improved use of statistical methods within medicine • Be a forum for discussions about statistical applications, primarily within drug industry • Promote exchange of professional skills between the members • Represent Swedish medical statistics in international relations such as EFPSI (from 2004) Bernhard Huitfeldt 24 Oct 2012

  5. The first FMS members elected on November 27, 1987 (n = 17) Tore Haglund Astra Alab Stephan Ogenstad Astra Alab Carl Johan Lamm Astra Draco Klas Svensson Astra Draco Mats Lörstad Astra Hässle Sören Romare Astra Hässle Christina Eskilsson Kabi Vitrum Olivier Guilbaud Kabi Vitrum Leif Trulsson Kabi Vitrum Örjan Nordle Leo Läkemedel Göran Nilsson Pharmacia Ingemar Selinus Pharmacia Alexandra Tsipogianni Sahlgrenska sjukhuset Sture Holm Göteborgs Universitet Ann-Sofie Matthiesen Stockholm Universitet Marie-Louise Nordström Uppsala Universitet Bernhard Huitfeldt 24 Oct 2012

  6. FMS presidents 1987 - 2012 1987-1989 Mats Lörstad Astra Hässle - Mölndal 1989-1991 Bernhard Huitfeldt Pharmacia - Uppsala 1991-1993 Stephan Ogenstad Astra Arcus - Södertälje 1993-1996 Hans Wedel Nordiska hälsovårdshögskolan 1996-1998 Eva Kelty CDC - Lund 1998-2000 Juni Palmgren MEB, Stockholms Universitet 2000-2002 Elisabeth Svensson Örebro Universitet 2002-2005 Ziad Taib AstraZeneca - Mölndal 2005-2007 Tom Britton Stockholms Universitet 2008-2009 Stig Johan Wiklund AstraZeneca - Södertälje 2010-2012 Anna Torrång AstraZeneca - Södertälje 2012- Anna Ekman Sahlgrenska sjukhuset - Göteborg Bernhard Huitfeldt 24 Oct 2012

  7. Membership Distribution 1996 • 1987 (n = 17) • 1996 (n =175) • 2012 (n > 200) Bernhard Huitfeldt 24 Oct 2012

  8. Main activities • Spring and autumn meetings with a scientific program (n = 50) • Workshops (n = 9) • Courses (n = 11) • Guidelines reviews - ICH, EMA, FDA (n ≥ 8) • Founding member of EFSPI (1989) Bernhard Huitfeldt 24 Oct 2012

  9. Workshops • Intention-to-treat, Adverse drug effects: Bob O’Neill, 1990 • Meta-analysis of clinical trials: John Lewis, Peter GØtzsche,1991 • Sampling designs for public health investigations: (Surveysektionen), 2003 • Adaptive design: Christopher Jennison, 2007 • Methods for consultations: 2008 • Statistical methods for cancer patient survival: 2009 • Statistical issues in medical statistics: (DSBS), 2010 • Model based drug development: (SSL), 2011 • Benefit-risk assessment methodology: (DSBS), 2012 Bernhard Huitfeldt 24 Oct 2012

  10. Courses • Repeated measurements: Mike Kenward & E. Allen, 1990 • Crossover-trials: Mike Kenward, E. Allen 1991 • Ordered categorical data: John Whitehead, 1992 • Meta-analysis: Anne & John Whitehead, 1993 • Survival analysis: Per K Andersen, Niels Keiding, 1994 • Dose-response: Aage Völund, Juni Palmgren, Sture Holm, Philip Hougaard, 1995 • Repeated measurements: Juni Palmgren, Sture Holm, Dietrich v Rosen, 1996 • Bayesian methods: Don Berry, 1997 • Missing data: Rod Little, T Raghunatan, 1999 • Mixed models: Robert Prescott, Helen Brown 2004 • Non-linear mixed effects models: Ed Vonesh, 2009 Bernhard Huitfeldt 24 Oct 2012

  11. Themes at spring and autumn meetings • Bioequivalence, 1987 • Design of experiments, 1988 • Development of diagnostic methods, 1989 • Quality of life, 1991 • Survival analysis and chaos, 1992 • Epidemiology, 1993 • Health economy, 1994 • Authorization of statisticians, 1995 • Genetic statistics, 1998 • Bioinformatics, 1999 • The role of statistics and statisticians in drug development, 1999 • Design and analysis of equivalence and non-inferiority trials, 2000 Bernhard Huitfeldt 24 Oct 2012

  12. Themes at spring and autumn meetings (cont’d) • Competing risks and multivariate survival data, 2000 • Current biostatistics research in Sweden, 2002 • Risk evaluation of drugs and food, 2002 • Bayesian inference in biostatistics (David Spiegelhalter), 2003 • Statistical issues in drug development (Stephen Senn), DSBS, 2004 • Modern statistical methods in medical research (Sir David Cox), MEB, 2004 • Statisticians in the medical debate – shut up or speak up, 2005 • Current biostatistics research and education, 2005 Bernhard Huitfeldt 24 Oct 2012

  13. Themes at spring and autumn meetings (cont’d) • Statistical issues applicable in drug development (Peter Diggle), 2006 • Important statistical issues in the drug industry, 2006 • Epidemiology and genetics (SSL, FSB), 2007 • Animal and statistics, 2007 • Jubilee conference 20 yrs (Andy Grieve), 2008 • Healthy statistics – ethical issues on the border between statistics and medicine (SSFr), 2008 • Multivariate 2.0, 2009 • Multiplicity (Yudi Pawatan), 2010 • Statistical issues in medical statistics (DSBS), 2010 • Register based statistics, (Surveyföreningen), 2011 Bernhard Huitfeldt 24 Oct 2012

  14. Guideline reviews • 1995: ICH guideline E3, Structure and content of clinical study reports • 1999: ICH guideline E10, Choice of control group in clinical trials • 2002: EMA points to consider, Adjustment for baseline covariates • 2004: EMA points to consider, Choice of non-inferiority margin • 2004: ICH guideline E 14, QT/QTc interval prolongation • 2005: EMA guideline on data monitoring committees • 2010: FDA guideline on non-inferiority studies • 2010: FDA guideline on adaptive designs Bernhard Huitfeldt 24 Oct 2012

  15. FMS partners (2009 -) Bernhard Huitfeldt 24 Oct 2012

  16. Holders of scholarships (stipendiater) (15 000 kr) • Therese Andersson Caroline Dietrich Anna Genell • Sandra Eloranta Anna Johansson Sharon Kühlman Berenzon • Anna Ekman Anna Lindam Rebecca Rylance Halef Darabi • Anna Johansson Achilles Tsounamis Adnan Noor (15 000 kr) (25 000 kr) (25 000 kr) Bernhard Huitfeldt 24 Oct 2012

  17. Situation 1987 • Relatively simple statistics in design and analysis used in clinical trials 1987. • Regulatory authorities started to become more demanding (FDA mostly). • Almost no statistics provided by professional statisticians existed in preclinical research. • Computer facilities rather primitive, start of advanced database technology (Oracle), SAS, BMDP, lack of harmonization on data standards. Bernhard Huitfeldt 24 Oct 2012

  18. Stages in drug development Phase 3b Phase 1 Phase 2a,b Phase 3a Phase 4 Bernhard Huitfeldt 24 Oct 2012

  19. Number of drugs needed in each phase to achieve one approval Success Rate to Approval Source: R&D General Metrics 2007, Pharmaceutical Benchmarking Forum, slide 248 Bernhard Huitfeldt 24 Oct 2012 19

  20. Processes in clinical trials Clinical Study Protocol incl. SAP and CRFs Clinical Study Report andPublication Reporting Database Analysis & Reporting Output database Database design Data capture Data management • Processes • Tools • Roles & Responsibilities • Patient data listings • Summary tables & graphs • Statistical analysis output Bernhard Huitfeldt 24 Oct 2012

  21. Roles and responsibilities • From p-value producer to strategic project partner • Expert adviser • Leadership roles and decision • maker • Study statistician • Project statistician • Global project statistician • Research statistician • Expert roles – therapeutic area, adverse effects, pharmacokinetics etc Bernhard Huitfeldt 24 Oct 2012

  22. Statistical methodology 1987 -2012 • Bioequivalence • Generalized Linear Models, Mixed models, Random effect models, Repeated measures etc. • Missing data • Meta-analysis • Non-inferiority • Bayesian statistics, decision analysis • Adaptive designs including group sequential trials • Modeling & simulation • Outcome studies, mega-studies • Observational studies, non-intervention studies Bernhard Huitfeldt 24 Oct 2012

  23. Computer technology and software 1987 - 2012 • Increase of speed and capacity of computers • Database technology, increased volumes of data, bioinformatics, computer intensive methods • General statistics software packages, new procedures in • SAS, SPSS, S-plus, R etc. • Special statistics software • East, nQuery + interim, ADAPT, BUGS etc. Bernhard Huitfeldt 24 Oct 2012

  24. Regulatory guidelines 1987 - 2012 • International Conference of Harmonization (ICH) • Safety, Quality, Efficacy (E9 and E10 etc.) • Food Drug Administration (FDA) • General methodology and disease specific guidelines • European Medicines Agency • Points to consider Bernhard Huitfeldt 24 Oct 2012

  25. ICH/E9 Bernhard Huitfeldt 24 Oct 2012

  26. Dagens Industri 14 september 2004 “När sedan FDA:s statistikexpert gick till angrepp blev det den sista spiken i kistan ……..” Bernhard Huitfeldt 24 Oct 2012

  27. Globalization • Global companies and global markets, multinational studies, bridging • Cooperation between authorities (FDA, EMA, Japan…) • Strong professional organizations (ISCB, DIA, EFSPI, ASA, PSI..) • International conferences • Biopharmaceutical statistical science becomes global with dedicated journals • - J. of Biopharmaceutical Statistics (US, 21st year) • - Pharmaceutical Statistics (PSI, 10th year) • - Statistics in Biopharmaceutical Research (ASA, 3rd year) Bernhard Huitfeldt 24 Oct 2012

  28. Public trust challenged • The JAMA story • Ethics code • Authorization of statisticians Bernhard Huitfeldt 24 Oct 2012

  29. Quotation from a related area • “The work during the past 30 years in has in the best case been sensationally worthless or in the worst case directly detrimental” • “… the more frequent use of these models implied that the became less interested in the reality and more fascinated ofmathematical relations” macroeconomy economists Bernhard Huitfeldt 24 Oct 2012

  30. The evolution of biostatistics? Bernhard Huitfeldt 24 Oct 2012

  31. Happy birthday! • We can be proud of what we have achieved so far • We have many challenges to tackle in the future Bernhard Huitfeldt 24 Oct 2012

More Related