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TRAINING SCHOOL IN EXPERIMENTAL DESIGN & STATISTICAL ANALYSIS OF BIOMEDICAL EXPERIMENTS

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TRAINING SCHOOL IN

EXPERIMENTAL DESIGN &

STATISTICAL ANALYSIS OF BIOMEDICAL

EXPERIMENTS

March 30 – 1 April

2015 University of Coimbra, Portugal

Supporters:

CPD accreditation:

FRAME delivers regular training schools in experimental

design and statistics to increase awareness among scientists

about the need to reduce animal numbers in experiments and

to refine procedures. Participants gain a better understanding

of how to properly design and effectively analyse their

experimental programmes so that they can go on to produce

higher quality science, which has made the most efficient use

of a minimum number of animals.

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Training School in experimental design & statistical analysis of biomedical experiments

U N I V E R S I T Y O F C O I M B R A , P O R T U G A L

INTRODUCTION

Russell and Burch (1959)1 identified that the way in which reduction in laboratory animal use can most effectively be achieved is by rigorous experimental design and appropriate statistical analysis of any results. An effective experimental design must incorporate the aims of the work to be carried out, the choice of experimental animals and techniques, the parameters to be measured and the methods to be used for analysis of the results. However, there is a general lack of knowledge on the part of biologists about these issues, and an urgent need for statistical experts to appreciate the issues and problems that biologists face. A Training School involving these individuals was an ideal opportunity to facilitate dialogue and enhance the application of experimental design and statistical analysis to animal experimentation to improve: a) animal welfare; b) the amount of information from a given number of animals involved; and c) the quality of biomedical research and testing.

The ninth Training School was co-organised with the Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Portugal and held at the University’s health science campus in March/April 2015.

OBJECTIVES

The key objectives of the Training School were:

 to provide researchers from across Europe with an understanding of basic design concepts that they do not seem to be gaining from other sources,

 to give them the ability to use more efficient designs for their experiments, and

 to stimulate engagement with the Three Rs and useful discussion between animal users in industry

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STRUCTURE

The programme (appendix 1) was taught by five expert tutors:

 Dr Michael Festing

 Dr Derek Fry

 Mrs Michelle Hudson-Shore [also acted as Training School Coordinator]

 Dr David Lovell

 Prof. Richard Preziosi

The format included lectures, group discussions, and individual exercises. The programme was structured to lead the participants from simple experimental design and statistical ideas, through more complex

methods and analysis to effective presentation of findings. Participants were also able to discuss their own research problems/experiences with the Training School tutors. This interactive approach strengthened and supplemented the information given in the more traditional lectures. The residential nature of the School also fostered networking and dissemination of information between participants.

PARTICIPANTS

On this occasion as the hosting country the majority of participants were from Portugal but the School also attracted participants from seven other countries (table 1) and a variety of research backgrounds. The majority of participants were postgraduates and postdoctoral researchers, but several other roles were also represented including senior members of staff, such as an assistant professor and lead statistician (table 2).

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Table 1: Origin of participants who attended the Training Table 2: Scientific roles represented

School, March/April 2015 among participants, March/April 2015

Country Number of Participants Scientific Position/Role

Portugal 14 PhD Student

UK 6 Animals in Science Inspector for ASPA

Denmark 6 Junior Researcher

Germany 3 Assistant Researcher

Belgium 2 Research Fellow

Norway 1 Lead Statistician, Science Directorate

Luxembourg 1 Senior Scientist

Switzerland 1 Post Doc Research

Total 34 Assistant Professor

No. of applications received 40 Research Technician Technical Coordinator Laboratory Technician Data Analyst

MSc Research Student Bachelor Student Investigator

Quality Innovation Facilitator Head of animal facilities in the Research Unit

OUTCOMES

Par ticipant Feedback

The Training School was very well received with participant’s providing very positive feedback. All of the 33 participants who provided feedback said that they would recommend the course to colleagues, that the instructors provided helpful assistance and 30 agreed that the course had exposed them to new knowledge and practices (see appendix 2 for a full summary of responses). Many participants made additional comments, such as:

Thank you for this very useful course. I had no experience with experimental animal design and statistical analysis in these designs since I have previously worked with

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Thank you very much for organizing the course. Lectures were captivating and helped to get a better understanding of experimental design and statistics. Tutors were very approachable and helpful too.

Very good explanations of statistical and experimental design terms that improved the overall understanding of the whys and how’s of the design. I really liked the aspect of animal welfare; it is all too often neglected in the design of new experiments.

Knowledge Acquisition

To gain insight in to how successful training of this nature is the Training School tutors designed a set of questions which were given to the participants at the start and end of the school. The answers to these questions were collated and analysed to determine the participants existing knowledge of the subject and then to establish if and what they have learned as a consequence of the training. There was an increase in understanding of all the areas tested (figure 1) and the individual overall scores also increased after the training (figure 2).

Figure 1: Coimbra 2015: Pre-/post-test comparison Figure 2: Coimbra 2015: Pre-/post-test

of correct responses by area of understanding comparison of correct responses by total score

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Appendix 1 Training School Programme, Coimbra 2015

Session

Number Session Title and Content

Sunday Informal Discussion and Introductions: Hotel Bar

Monday Basic Principles

Registration – IBILI building main entrance

1 Introduction to course: The Three Rs, legal and ethical aspects.

Quiz 1.

2 Principles of experimental design. Need for better design. Types of experiment (pilot, exploratory, confirmatory), objectives, controls, experimental units, replication, randomization, blinding.

BREAK

3 Common failings: unclear objectives, bias, lack of power, failure to randomize/blind, pseudoreplication. Costs of poor design.

4 Group Exercise 1: Objectives, controls, experimental units.

LUNCH

5 Revision of basic statistical inference. Null and alternative hypotheses, SD vs. SE, outliers, type I &

type II errors, variables affecting significance, summary statistics.

6 Sources of variability in animal studies and how they may be controlled.

BREAK

7 & 8 Computer session: Simulating experiments and the importance of controlling variability.

Randomisation, sampling, Type 1 and Type 2 errors DINNER – Solar do Bacalhau

Tuesday Experimental Designs and Statistical Analysis

9 The analysis of variance, interactions, post-hoc tests, assumptions, data transformations.

10 Group Exercise 2: Finding design faults.

BREAK

11 Completely randomised, randomised block and latin square designs. Power calculations, resource

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13 Factorial “designs”.

14 Group Exercise 3: Choosing the right design & over-night exercise.

BREAK

15 Experiments to test relationship: correlation, regression.

16 Computer session: ANOVA, power analysis and software.

DINNER – A Capella

Wednesday Applied Experimental Design and Presentation for Publication 17 Discussion of overnight exercise: Planning an experimental programme.

18 Presentation of results: The ARRIVE guidelines, summary statistics, graphs, diagrams, tables.

BREAK

19 Quiz 2 and discussion 20 Parallel Sessions 1:

Group Exercise 4: Are ARRIVE guidelines met in these papers?

Discussion of participants problems LUNCH

21 Parallel Sessions 2:

Group Exercise 5: Designing an experiment.

Discussion of participants problems

22 Answers to Quiz 2 & take home messages.

CLOSE

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Appendix 2 Training School Feedback Summary, Coimbra 2015

The Design of the Course

The objectives of the course were clear to you

Agree 31

No opinion 0

Disagree 2

The course contents met with your expectations

Agree 28

No opinion 4

Disagree 1

The lecture sequence was well planned

Agree 27

No opinion 6

Disagree 0

The contents were illustrated with adequate examples

Too few 6

Enough 27

Too many 0*

*1 said enough but too many

sometimes The academic level was

appropriate

Too low 2

Correct 29

Too high 2 The course exposed you to new

knowledge and practices

Agree 30

No opinion 1

Disagree 2

You would recommend this course to your colleagues

Agree 33

No opinion 0

Disagree 0

The Conduct of the Course

The lectures were clear and easy to understand

Agree 30

No opinion 2

Disagree 1

The course material handed out was adequate

Agree 25

No opinion 6

Disagree 2

The computer lab sessions were clear and easy to understand

Agree 13

No opinion 14

Disagree 6

The instructors provided helpful assistance

Agree 31

No opinion 2

Disagree 0

Background Information How did you hear about the School?

Internal email 10

Colleague 20

FRAME website 2

Some ticked >1

Other, please specify

2: head of lab & lab animal science course (Univ. Bergen, Norway)

Flyer

0 Direct email

1 Facebook, Twitter

0 Future Training

References

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