Clincal Trials: Introduction

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Transcript 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, Universit ät Dortmund

8 th 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? 2

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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 4

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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 3 rd in 2000, 4 th 2003!

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Other Landmarks:

 1988: – Start of •

ERASMUS

University of Lisbon joins as scheme by EU a third partner to form network • Provides generous funding for staff travel – – Annual Sheffield meeting for all network coordinators Bilateral visits  1991: – the

100 th

student from Dortmund comes to Sheffield –– Mathias Rusert 10

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 1990 –95 11

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1994:

– Last meeting of Erasmus network coordinators in Sheffield 12 Ali ( Montpellier) Luigi ( Perugia) Kiki (Athens ) Wolfgang ( Dortmund) Lupe ( Barcelona)

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 A Solar Eclipse marks the event 13

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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 1 st idea to 1 st student abroad 14

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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

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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: –

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Berthold Lausen 1984 Sabine Landau 1985 Johannes Fa ßbinder 1989 Dietrich Alte 1995 Vivian Lanius 1997

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Achim Zeileis 1998

To the most recent (2002)

Wiebke Haupt

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Henrike Feuersenger

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Including several family pairs: –

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Astrid (1999) & Henrike (2003) Feuersenger

Note: one of these was

Viviane (1987) & Veit (1994) Grunert Ulrike (1995) & Siegfried

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Schach

Including several family pairs: –

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Astrid (1999) & Henrike (2003) Feuersenger

Daniel Fieller

Klaus (1993) & Joerg (1995) Langohr Viviane (1987) & Veit (1994) Grunert Ulrike (1995) & Siegfried

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Schach

& 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) 24

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The Sheffield 4 in the other direction: –

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Peter Cooper (1982) Polly Hardy (1994) Christine Romslo (2000)

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Rhiannon Maudsley (2003)

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Peter Cooper (1982) Polly Hardy (1994) Now lecturing in Medical Statistics in London (LSH&TM) Christine Romslo (2000) Now working at Girling in K öln

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Rhiannon Maudsley (2003)

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Peter Cooper (1982) (50% English) Polly Hardy (1994) (English) Christine Romslo (2000) (Norwegian)

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Rhiannon Maudsley (2003) (Welsh)

To be followed by next year : –

Gemma Stephenson & Oliver John

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Both English — 133% increase in total!

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 Statistical Analysis — Future Trends

15 10 Dortmund 5 1980 1985 1990 trend 1995 2000 Zero in 2003 ??? 2004/5/6

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Sheffield

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 Statistical Analysis — Future Trends

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trend 10 Dortmund 5 1980

2 Sheffield 1 2000 Zero in 2003 ??? 2004/5/6 1985 1990 1995 2000 The Kramer-Huff Upper Bound may not apply in this case 2003 2004

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Two useful statistical guides : –

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very edition

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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 – 83  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 34

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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 37

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Clear benefit to Sheffield

 It’s a pleasure to have some of the

best

students from the

best

across Europe Universities  Good for ‘ordinary’ Sheffield students •

If they won’t go to Europe then I’ll 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 39  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 O’Hagan + 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) 40

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My interests: – Currently 6 PhD students

41  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 (ct

d

.)

:

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 44 High Content Cell Biology

non-hit hit potent hit

false positives toxicity compound fluorescence over confluency imaging error

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Archaeostatistics:

45 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 20………… Complex 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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Facial Identification

(See GfKl 2004)

53 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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+ + * * * * * + * * * + + * * * * + + + + + * * * + * * * + + + + + + + + * * * + * * * * * + + * * 55 Indication of variability between different faces -0.4

-0.2

0.0

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0.0

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Plots of range of

3 s.d.s in mean position of 6 landmarks

0.6

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Indication of variability between different measures of same face -0.4

-0.2

0.0

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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

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