Clincal Trials: Introduction

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Dortmund 227, Sheffield 4 The Record of
Dortmund-Sheffield Exchanges Nick
Fieller Department of Probability Statistics,
University of Sheffield visiting Fachbereich
Statistik, Universität Dortmund 8th March 2004
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• Synopsis
• The Universities of Dortmund Sheffield have had
  a formal Academic Cooperation Agreement since
  1980 which is renowned throughout both countries
  and further afield.
• How did this develop?
• Who was involved?
• What are the benefits?

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• Outline
• Historical Development
• Personalities
• Statistical analysis
• Benefits
• Statistics in Sheffield

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• Historical Development
• The story starts in Karlsruhe, 1976
• ICME 1976
• International Congress on Mathematical Education
• chance? meeting between Peter Holmes, Vic
  Barnett Fred Eicker
• Vic Head of Department in Sheffield
• Peter Director of Statistical Education Centre
• Discovered common interest in Statistical
  Education, particularly at school level

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• I recall Vic reporting later in Sheffield that
  he had met a Professor from a German University
  which had a new Statistics Department
• This Department felt lonely since it was the
  only real statistics department in the country,
  so had suggested forming a link with Sheffield.

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• Various meetings and visits followed
• Particularly
• Vic Barnett and Clive Anderson
• Siegfried Heiler, Fred Eicker, Wolfgang Urfer
• A draft proposal was drawn up signed on 11
  November 1979
• A formal Programme of Academic Cooperation was
  signed in Dortmund on 8 August 1980

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• The first six students from Dortmund came to
  Sheffield in October 1980
• every year from then until 2002
• I ( family) spent three months in Dortmund in
  Spring, 1981
• Wolfgang Barbara Urfer came to Sheffield in
  Spring 1981 for a month
• kindly lending us their flat
• In 1982 the first Sheffield student came to
  Dortmund
• the second in 1994, the 3rd in 2000, 4th 2003!

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• Other Landmarks
• 1988 Start of ERASMUS scheme by EU
• University of Lisbon joins as a third partner to
  form network
• Provides generous funding for staff travel
• Annual Sheffield meeting for all network
  coordinators
• Bilateral visits
• 1991 the 100th student from Dortmund comes to
  Sheffield Mathias Rusert

Bob Loynes presents a beer tankard to Mathias
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• Other Landmarks
• 1987 Start of ERASMUS scheme by EU
• University of Lisbon joins as a third partner to
  form a network
• Provides generous funding for staff travel
• Annual Sheffield meeting for all network
  coordinators
• Bilateral visits
• 1991 the 100th student from Dortmund comes to
  Sheffield Mathias Rusert
• 1989 ? other partners join the network
• UPC Barcelona, Amsterdam, AUEB Athens, Perugia,
  Montpellier, Tampere,
• Many student exchanges in all directions
• (especially from Dortmund)
• 40 incoming students to Sheffield each year
  199095

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• 1994 Last meeting of Erasmus network
  coordinators in Sheffield

Luigi(Perugia)
Ali(Montpellier)
Wolfgang(Dortmund)
Kiki(Athens)
Lupe(Barcelona)
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• A Solar Eclipse marks the event

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• Since then Erasmus Network replaced by Socrates
  bilateral agreements
• Less money
• More bureaucracy
• But
• Sheffield students started to travel
• New degree scheme MMath(Eur) allows 30 of time
  studying language
• German/French/Italian/Spanish/Dutch/Catalan
• Took 7 years from 1st idea to 1st student abroad

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• France
• 14 Montpellier
• 5 Versailles
• 3 Caen
• 4 Le Mans
• Spain
• 2 Barcelona
• Italy
• 1 Perugia

• Germany/Austria
• 2 Dortmund
• 5 Augsburg
• 2 Dresden
• 1 Kaiserslautern
• 2 Graz
• Netherlands
• 1 Amsterdam

42 in Total

• enough of history

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• Personalities
• The first ambassadors in 1980
• Heiko Becher
• Sabine Brenneisen
• Soeren Kristiansen
• Petra Neumann
• Willi Sauerbrei
• Wolfgang Schumann

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Heiko
Sabine
Soeren
Petra
Willi
Wolfgang
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• Followed by
• 1981
• Gisella Kesting
• and in 1982
• Arno Schell
• Rainer Muche

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• And in 1983
• Marita Durek
• Reiner Latsch
• Uwe Müller
• Christoph Schröder
• Claudia Spix

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Via
Berthold Lausen 1984
Sabine Landau 1985
Johannes Faßbinder 1989
Dietrich Alte 1995
Vivian Lanius 1997
Achim Zeileis 1998
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• To the most recent (2002)

Wiebke Haupt
Henrike Feuersenger
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• Including several family pairs

Astrid (1999) Henrike (2003) Feuersenger
Note one of these was NOT a student in Sheffield
Klaus (1993) Joerg (1995) Langohr
Ulrike (1995) Siegfried Schach
Viviane (1987) Veit (1994) Grunert
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• Including several family pairs

Frühling 1981
Astrid (1999) Henrike (2003) Feuersenger
Klaus (1993) Joerg (1995) Langohr
Daniel Fieller
Ulrike (1995) Siegfried Schach
Viviane (1987) Veit (1994) Grunert
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• not forgetting
• Stephanie Scheid
• Klaus Nordhausen
• Frauke Jantzen
• who took my Medical Statistics course in
  Tampere, April 2000
• ( with apologies to the 200 not commemorated
  here)

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• The Sheffield 4 in the other direction

Peter Cooper (1982)
Polly Hardy (1994)
Christine Romslo (2000)
Rhiannon Maudsley (2003)
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Peter Cooper (1982)
Polly Hardy (1994)
Now lecturing in Medical Statistics in London
(LSHTM)
Christine Romslo (2000)
Rhiannon Maudsley (2003)
Now working at Girling in Köln
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Peter Cooper (1982)
Polly Hardy (1994)
(50 English)
(English)
Christine Romslo (2000)
Rhiannon Maudsley (2003)
(Norwegian)
(Welsh)
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• To be followed by next year

Gemma Stephenson Oliver John
Both English 133 increase in total!
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• Statistical Analysis Future Trends

15
trend
10
Zero in 2003
Dortmund
??? 2004/5/6
5
1985
1990
1995
1980
2000
Sheffield
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• Statistical Analysis Future Trends

15
trend
10
Zero in 2003
Dortmund
??? 2004/5/6
5
1985
1990
1995
1980
2000
The Kramer-Huff Upper Bound may not apply in
this case
?
2
Sheffield
1
2000
2004
2003
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• Two useful statistical guides

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• The new
• edition

very
?
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• Objectives
• Original Agreement called for
• Student Exchange
• Take courses, transfer credits
• Staff Exchange
• Visits for 1-6 months
• Material Exchange
• Research reports, papers,
• Seminars/Colloquia
• Workshops, conferences
• Statistical Education
• Especially school level

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• Student exchange
• Yes (and improving)
• Staff Exchange
• Most Sheffield staff visited Dortmund in 1980
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• Many Dortmund staff visited Sheffield
• Only 1 extended visit (me in 1981)
• Very few visits in last 10 years
• Material Exchange
• Sheffield research reports sent to Dortmund
• None received from Dortmund for ? years

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• Seminars/Colloquia
• First Anglo-German Statistical Conference in
  Dortmund, 1982
• Second one in ??
• Statistical Education
• Any joint activity??

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• Objectives
• Original Agreement called for
• Student Exchange
• Staff Exchange
• Material Exchange
• Seminars/Colloquia
• Statistical Education

?
?
?
?
?
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• Benefits
• Clear benefits to participating students
• Many participants now in major positions
• Clear personal development
• (especially noticed in returning Sheffield
  students in last 6 years)
• Maybe partly self-selection but not entirely

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• Clear benefit to Sheffield
• Its a pleasure to have some of the best
  students from the best Universities across
  Europe
• Good for ordinary Sheffield students
• If they wont go to Europe then Ill bring
  Europe to them
• Provides a significant source of PhD ( MSc)
  students
• Viviane Grunert
• 6 other PhDs 8 MSc

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• Our Dortmund visitors particularly show our
  students different attitudes to study and
  different ways of approaching work
• Especially good in collaborative data analysis
  projects
• We particularly appreciate the courtesy when
  Dortmund students switch to English when talking
  to each other.

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• Statistics in Sheffield
• Bayesian Statistics
• Major Bayesian Statistics group in UK
• Tony OHagan 50 of Department
• Health Economics
• National Institute for Clinical Excellence (NICE)
• Risk Assessment in Industry and Government
• Environmental Statistics
• Clive Anderson et al
• Archaeostatistics
• Caitlin Buck, Paul Blackwell ( me)

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• My interests Currently 6 PhD students
• Facial identification
• Multivariate shape analysis
• Use of statistics in forensic evidence
• Funded by US Government (FBI)
• Archaeostatistics
• Tree-ring sequences, Robust Time Series analysis
• Bioinformatics
• Microarrays, tumour images, high content cell
  biology
• Funded by AstraZeneca Pharmaceuticals
• Design of Clinical Trials
• Covariate adaptive methods

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Bioinformatics
Data from microarrays gives gene expression
levels for 13,000 genes. Very high dimensional
data sets, very noisy data, subject to
contamination
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Bioinformatics (ctd.)
E14M34 50mg dose
NMR Images of tumour before after treatment
use statistical characterization of images as
measure of response to treatment. Very high
dimensional data sets, very noisy data, subject
to contamination .
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Norak Transfluor HTS samples of images
High Content Cell Biology
non-hit
false positives
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Archaeostatistics
PhD student Julie Hopkins measuring mummy pots in
British Museum, April 1997. What was their
provenance?
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Saqqara, Egypt
At top of 10m shaft leading to labyrinth
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Sample size calculations are important.
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Inside labyrinth note broken pots
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Intact pots in situ in labyrinth gallery Now
need a random sample of size 20Complex
sampling problems, messy data, ..
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Tree-Ring Dating

• This photo has 2 full rings, the left-most ring
  having a false band.
• This phenomena can also occur in ways much more
  difficult to detect.

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Artificial Example
Artificial Example
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Facial Identification (See GfKl 2004)
Traditional anthropometric landmarks
coordinates captured manually with public
domain software
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Four subjects from the 2002 pilot study Different
sections of the face are censored so only use
landmarks common to a pair of faces
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Indication of variability between different faces
Plots of range of ?3 s.d.s in mean position of 6
landmarks
Indication of variability between different
measures of same face
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Cluster analysis of Procrustes coordinates of
mean shapes of 48 images from 2 sections of
catalogue matches identified
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• http//www.shef.ac.uk/nickfieller