The document provides guidelines for reporting animal research studies in a transparent manner. It outlines the ARRIVE guidelines, which include 10 essential items that should be reported in research papers involving animal subjects. The guidelines aim to improve reproducibility, transparency and quality of reporting. They include reporting the study's objectives and design, the animals used, experimental procedures, and the statistical analysis to allow rigorous assessment of the study. Adhering to these guidelines can help improve communication of research findings.

1. Professor David Baker
(david.baker@qmul.ac.uk)
ESNI Amsterdam 2019
Reading Papers
• Paper Construction
• Reporting & Understanding Basic Science & Clinical Papers
www.ms-res.org
• Understanding multiple sclerosis models

2. Reading Papers
CLINICAL TRIAL PAPERS
RESULTS: EFFICACY & SAFETY
LITTLE INTERPRETATION
SCIENCE PAPERS
RESULTS: RESULTS EVOLVE
(OVER) INTERPRETATION
MECHANISM OF ACTION
RESEARCH PAPERS
Often written by Professional Writers

3. Reading Papers
Questions to think about:
• RELEVANCE
• RELIABILITY
• Are the methods appropriate to the study aims?
• Is the Analysis appropriate?
• Are the Data & Pictures convincing?
• VALIDITY - How convincing are the authors arguments for their results in relations to others?
DON’T BELIEVE EVERYTHING YOU READ
READ READ, READ, READ

4. Reading Papers
KNOWLEDGE IS THE KEY TO GAINING KNOWLEDGE
Allows You to Understand the Paper
Allows You to Interpret the Results
Allows you to Understand the Discussion
Allows you to Place the Work in Context of its Relevance
Allows you to see the flaws that may affect interpretation
Allows you to Judge the Value of the Work
Allows you to Exploit the Information from the work
Allows you to learn from your and others mistakes
GIVES YOU THE CONFIDENCE IN ALL OF THE ABOVE
READ READ, READ, READ

5. Reading Papers
NON PEER-REVIEWED
Patents
Meeting Abstracts
Internet/Web pages There is a lot of Rubbish Out there!
Media Sensationalisation
PEER-REVIEWED
Reviews Lots of References,
Brings Threads together, Sorts conflict
Are citations broad or focused?
Dogma/Expertise/Conflicts of Interest?
Case Reports
Clinical Trials Quality Class of Evidence
Original Articles Quality & Supporting Evidence
PERCIEVED Serious Science/Pop Science
QUALITY OF JOURNAL
TYPE OF RESEARCH PAPER

6. Reading Papers
CONSORT GUIDELINES (Human Trials):
Consolidated Standards of Reporting Trials (www.consort-statement.org)
ARRIVE GUIDELINES (Animals Studies)
Animal Research: Reporting of In Vivo Experiments
(Kilkenny, C. et al (2009), PLoSOne, 4 (11))
•Checklists of Reporting Items
•Improve Transparency and Replication
•Ensure critical appraisal and interpretation
NEUROIMMUNOLOGICAL ARRIVE
Baker D, Amor S. Publication guidelines for refereeing and reporting on animal use
in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2012; 242:78.
Animal Studies
Sample Size Calculations: <5%
Randomization <20%
Blinding <30%
RESEARCH PAPER-STRUCTURE

7. Reading Papers
DEMOGRAPHICS: Comparing Like for Like (Sex, Age, History)
SAMPLE SIZE Power to Detect Change
Too Small- Miss Important Events
Too Large-Extra Cost/Risk to People in Study
BIAS REDUCTION:
•RANDOMIZATION: Methods to Achieve this. Was it achieved?
•BLINDING (Single Blind/Double Blind)
METHODS OF Is the correct analysis used?
ASSESSMENT
OUTCOMES: Are they fit for purpose?
Are the Outcomes Responsive?
Control Response (Placebo Effect)
COMPLIANCE Drugs don’t work if people do not take them
SIDE-EFFECTS Tolerability
*
*
*
IMPORTANT ASPECTS OF HUMAN STUDIES

8. Reading Papers
1. TITLE & ABSTRACT
2. BACKGROUND & OBJECTIVES
3. TRIAL DESIGN
4. PARTICIPANTS (Eligibility)
5. TREATMENT
6. OUTCOME MEASURES
7. SAMPLE SIZE CALCULATION
8. RANDOMIZATION METHOD
9. ALLOCATION OF RANDOMISATION
10. IMPELEMENTATION OF RANDOMISATION
11. BLINDING
12. STATISTICS
13. PARTICIPANT FLOW RESULTS
14. RESULTS-RECRUITMENT
15. RESULTS-BASELINE DEMOGRAPHICS
16. RESULTS-NUMBERS- HOWMANY PEOPLEIN EACH GROUP
17. RESULTS-OUTCOMES
18. RESULTS ADDITIONAL ANALYSIS
19. RESULTS-SIDE EFFECTS
20. DISCUSSION-LIMITATIONS
21. DISCUSSION- GENERALISABILITY (VALIDITY)
22. DISCUSSION- INTERPRETATION
23. REGISTRATION (www.clinicaltrials.gov)
24. SOURCE OFPROTOCOL
25. FUNDING
Checklists of Reporting
Items
Improve Transparency and
Replication
Ensure critical appraisal
and interpretation
http://www.consort-statement.org/
DESIGN OF TRIAL

9. Reading Papers DESIGN OF TRIAL
Assessment for Eligibility
Randomization
Allocated to Intervention
Received Intervention
Follow Up
Analysed
Did Not Receive
Lost to Follow Up
Not Analysed
Allocated to Intervention
Received Intervention
Follow Up
Analysed
Did Not Receive
Lost to Follow Up
Not Analysed
Excluded
TEST CONTROL

10. Reading Papers IMPORTANT ASPECTS OF HUMAN STUDIES
BIAS REDUCTION
RANDOMIZATION
Process by which people are allocated to an intervention
after assessment eligibility
• It eliminates selection bias
• It eliminates confounding issues by adjusting co-variants
(gets same demographics in test and control groups)
• Facilitates Blinding of investigators, participants, and assessors
BLINDING/MASKING
Individuals withheld the knowledge of the treatments
OPEN LABEL No Blinding
SINGLE BLIND pwMS unaware of their Treatment
DOUBLE BLIND Neuro & pwMS unaware of their treatment

11. Reading Papers DATA ANALYSIS
BIOLOGICALLY SIGNIFICANT
A difference between groups that has a real impact on biology
STATISICALY SIGNIFICANT
Mathematical Measure of a difference between groups. Does this occur at a
level greater than may be expected by chance.
PROBABILITY VALUES
Likelihood of obtaining a statistical result by chance, assuming there is no
Difference in the results (null hypothesis) being investigated
P=0.05 is 1 in twenty chance of event occurring
P=0.01 is 1 in one hundred chance of event occurring by chance
P=0.001 is 1 in one thousand chance of event occurring by change
Less Likely due
to chance

12. Reading Papers DATA ANALYSIS
A (50%)
B (25%)
(4%)
D
(21%)
C
PIE CHARTS
These show the proportions of response, seldom used in trials, but may
occur in Marketing material

13. Reading Papers DATA ANALYSIS
BAR CHARTS
These show the magnitude of the response/outcome
Treatment A Treatment B
Count
Bar Chart
0
Measurement (Units)Frequency(%)
Histogram
10 20 30 40 50

14. Reading Papers DATA ANALYSIS
LINE GRAPHS
These show the analysis over a period of time (serial analysis)

15. Reading Papers
Error Bars & Variability
No Difference DifferentHelp
Statistics Needed
Overlap of Error Bars
DATA ANALYSIS

16. Reading Papers
KAPLAN-MEIER SURVIVAL CURVE
The curve represents the proportion of the study population that are free of the event
(Progression, Time to relapse etc ) as successive times.
i.e Time to an event
Commonly used to represent overall efficacy.
The larger the difference in the curves the larger the difference
DATA ANALYSIS

17. Reading Papers DATA ANALYSIS
HAZARD RATIO
The Hazard Ratio is the Relative Risk of the Event (e.g. Disease progression)
happening in one arm of a trial compared to another arm over the time of the trial
Difference between groups that has a real impact on biology
Hazard Ratio = 1 means there is no difference
Hazard Ratio = 2 means there is twice/double the risk
Hazard Ratio = 0.5 means there is half the risk. Reduced risk by 50%
This methodology uses all available information, including people who didn’t
complete the study

18. Reading Papers DATA ANALYSIS
ABSOLUTE RISK REDUCTION (ARR)
The Difference between the number of events (e.g. pwMS who progressed)
in the test verses the control group.
e.g. Placebo progressed = 15% Test Drug = 10% progressed
ARR of the Test drug = 15%-10% = 5%
RELATIVE RISK REDUCTION (RRR). The RRR looks at the same difference
Between groups given different treatments but expresses the change in risk
As a proportion, rather than an absolute difference
e.g. RRR of Progression by Test drug = 15-10/divided by progression of control
15-10/15 = 5/15 = 33%
INTENTION TO TREAT (ITT) ANALYSIS
ITT analysis of the results of a trial is based on the initial treatment assignment and not on the treatment eventually
received. ITT analysis is intended to avoid various misleading artefacts that can arise such as loss of subjects, that
may break random assignment to the groups.
Medical investigators often have difficulties in accepting ITT analysis because of clinical trial issues like missing
data

19. Reading Papers DATA ANALYSIS
CONFIDENCE INTERVAL (CI)
The CI Percentage indicates the certainty that a result will fall into a
range of results noted by lower and upper limits
HR 0.55 (95% CI 0.40-0.77) The risk of converting to clinically definite
MS is reduced by 45% with estimates ranging from 60% reduction to 23%
reduction and 95% certainty that the result would lie between 23% and 60% risk
Reduction
The narrower the range the more precise the result.
The CI are used as an indication how a study would be reflected in the
general population

20. Reading Papers DATA ANALYSIS
NUMBER NEEDED TO TREAT (NNT)
The NNT is a statistic that tells one the actual number of pwMS that would need to be treated with a given
therapy for a one patient to get a particular endpoint benefit. Determines whether Large number or small
number of pwMS benefit.
The Lower the NTT the more effective the treatment.
ODDS RATIO.
A measure of treatment effectiveness. The OR is the odds of an event happening in the treatment group
expressed as a proportion of the odds of the event happening in the control group.
OR close to 1 the smaller the difference in the treatment effect
If greater (or lesser) than 1, then the treatment is greater (or less) than the control treatment.

21. Reading Papers
FOREST PLOT
Following meta-analysis of a number of different trials some showing
benefit some not showing for treatment or for analysis of subgroups within
a trial that may respond differently. A Forest plot is a way to compare
different groups of data.
Size of square is proportional to
the importance of that data set
and the horizontal lines are the
confidence intervals
DATA ANALYSIS

22. Reading Papers DATA ANALYSIS
Regression to the mean is the phenomenon that if a variable is extreme on
its first measurement, it will tend to be closer to the average on its second
measurement—and if it is extreme on its second measurement, it will tend to
have been closer to the average on its first.
In trials people are more likely to volunteer for trials if they are not doing
as well and natural history of disease will mean the flair resolves and they get
better

23. Reading Papers
SCATTER GRAPH (Relationships)
Individual data points are plotted showing two variables (e.g. height verses
weight) to show relationships
Random Positive relationship Negative relationship
Unrelated
Unrelated
Subset
DATA ANALYSIS

24. Reading Papers DATA ANALYSIS
REGRESSION (Relationships)
Spearman's rank correlation coefficient is a non-parametric measure of stastical dependence
between two variables. It assesses how well the relationship between two variables can be
described.
R= +1 perfect Correlation or R = −1 perfect inverse correlation.
R-squared is a statistical measure of how close the data are to the fitted linear regression line. It
is the percentage of the response variable variation that is explained by a linear model. Or: R-
squared = Explained variation / Total variation (It is between 0 and 100% or 0 to 1:)
90% explained40% explained

25. Reading Papers DATA ANALYSIS
BOX & WHISKER PLOT
Rather than show all the distribution of individual data. The data is presented as a box with
the whisker indicating deviation.

26. Reading Papers
Grade 1 Asymptomatic (no) or mild symptoms; for this grade of AE, treatment is
not indicated.
Grade 2 Moderate; for this grade of AE minimal, local or non-invasive intervention
may be indicated, for example, this might involve treating the symptom
(e.g. nausea and vomiting caused by a treatment
managed/prevented by giving the patient drugs to stop sickness, rather
than stopping the drug).
Grade 3 Severe but not immediately life-threatening; for such AEs hospitalization
and investigation/ management are often indicated.
Grade 4 Usually life-threatening consequences; for these AEs urgent intervention is
indicated.
Grade 5 Death related to AE.
IMPORTANT ASPECTS OF HUMAN STUDIES

27. Reading Papers
• Improve Reporting of Research Using Animals.
• Guide Authors as to the Essential Information to Include in a Manuscript,
• Flexible Enough to Accommodate Reporting a Wide-Range of Research
Areas and Experimental Protocols.
• Promote Reproducible, Transparent, Accurate, Comprehensive,
Concise, Logically-Ordered & Well-Written Manuscripts.
• Improve the Communication of the Research Findings to the
Broader Scientific Community.
Animals in Research: Reporting In Vivo Experiments
Call for Transparency

28. Reading Papers Call for Transparency
1 1 O C T O B E R 2 0 1 2 | VO L 4 9 0 | N AT U R E | 1 8 7

29. Reading Papers Call for Transparency
bioRxiv preprint first posted online Jul. 15, 2019; doi: http://dx.doi.org/10.1101/703181.
The Ten Essentials
Plus the Recommended Set

30. Reading Papers Essential Ten
Percie de Sert et al. 2019

31. Reading Papers
TITLE
Provide as accurate and concise a description of the content of the article as possible.
ABSTRACT
Provide an accurate summary of the background, research objectives, including details of the species or
strain of animal used, key methods, principal findings and conclusions of the study.
IF YOU DON’T DO THIS….. NO ONE WITH READ YOUR PAPER!
ARRIVE Guidelines

32. Reading Papers ARRIVE Guidelines
INTRODUCTION
3. Background
(a). Include sufficient scientific background to understand the motivation and context for the study, and
explain the experimental approach and rationale.
(Include relevant references to previous work)
(b). Explain how and why the animal species and model being used can address the scientific objectives
and, where appropriate, the study’s relevance to human biology.
4. Objectives
Clearly describe the primary and any secondary objectives of the study, or specific hypotheses being tested.
“A clear statement of the objective of the study, or the main hypothesis being tested, was described
in the introduction by 95% of the 271 publications (Kilkenny et al. 2009)”

33. Reading Papers ARRIVE Guidelines
METHODS
5. Ethical statement
Indicate the nature of the ethical review permissions, relevant licenses and national or institutional
guidelines for the care and use of animals,
UK Protecting Research Animals through Law since 1876. Animals (Scientific Procedures) Act 1986.
European Union. Directive 2010/63/EU. (Enshrined the Concept of 3Rs and Ethical Review Process) .
Animals Welfare Act 1966 USA 2000 Law for the Humane Treatment and Management of Animals in Japan

34. Reading Papers ARRIVE Guidelines
METHODS
5. Ethical statement
Indicate the nature of the ethical review permissions, relevant licenses and national or institutional
guidelines for the care and use of animals,
UK Protecting Research Animals through Law since 1876. Animals (Scientific Procedures) Act 1986.
European Union. Directive 2010/63/EU. (Enshrined the Concept of 3Rs and Ethical Review Process) .
Animals Welfare Act 1966 USA 2000 Law for the Humane Treatment and Management of Animals in Japan

35. Reading Papers ARRIVE Guidelines
METHODS…continued
6. Study design
For each experiment, give brief details of the study design including:
a. The number of experimental and control groups.
b. Any steps taken to minimise the effects of subjective bias when allocating animals to treatment (e.g.
randomisation procedure) and when assessing results (e.g. if done, describe who was blinded and when).
c. The experimental unit (e.g. a single animal, group, or cage of animals).
EVIDENCE OF BLINDING
~ 14% Randomly Selected papers (Kilkenny et al.2009).
~ 29% Experimental Stroke papers
~ 16% Experimental MS papers (Vesterinen et al. 2010)
EVIDENCE OF RANDOMISATION
~ 12% Randomly Selected papers (Kilkenny et al.2009).
~ 36% Experimental Stroke papers
~ 9% Experimental MS papers (Vesterinen et al. 2010)
Blinding Experiments

36. Reading Papers ARRIVE Guidelines
Blinded Assessment of Outcome
0
10
20
30
40
50
No Yes
%ImprovementinNeurologicalScore
P<0.002
BLINDING
Random Allocation to Group
%ImprovementinNeurologicalScore
0
10
20
30
40
50
No Yes
P<0.002
RANDOMIZATION
METHODS…continued
6. Study design
Vesterinen et al. Mult scler; 2010, 16:1044 2010

37. Reading Papers ARRIVE Guidelines
METHODS…continued
7. Experimental procedures
For each experiment and each experimental group, including controls, provide precise details of all
procedures performed. For example:
a. How (e.g. drug formulation and dose, site and route of administration, anaesthesia and analgesia used
[including monitoring], surgical procedure, method of euthanasia). Provide details of any specialist
equipment used, including supplier(s).
b. When (e.g. time of day).
c. Where (e.g. home cage, laboratory, water maze).
d. Why (e.g. rationale for choice of specific anaesthetic, route of administration,
drug dose used).

38. Reading Papers ARRIVE Guidelines
__________________________________________________
Source Mice Source Innoculum No.EAE/Total
__________________________________________________
Company X Company X 1/20
Company X Baker Lab 9/10
Baker Lab Company X 4/10
Baker Lab Baker Lab 10/10
________________________________________________
6-8 week oude, vrouwelijke ABH muizen werden subcutaan in 2 plaatsen in de rug van de flank met 0.1ml een sonicated (10min in
Bransonic Ultrasonicator, Sigma Ltd, Poole, GB) emulsie van 1mg syngeneic ruggenmerg homogenate fosfaat beschermd zouthoudend
en de volledige hulp van Freund ingespoten die 60µg kobalt-gebestralen Mycobacterium tuberculose op dag 0 en 7.
6-8 week old, female ABH mice were injected subcutaneously in 2 sites in the dorsum of the flank with 0.1ml a sonicated (10min in
Bransonic Ultrasonicator, Sigma Ltd, Poole, UK) emulsion of 1mg syngeneic spinal cord homogenate phosphate buffered saline and
Freund’s complete adjuvant containing 60µg cobalt-irradiated Mycobacterium tuberculosis on day 0 and 7.
METHODS…continued
7. Experimental procedures….continued
Al-Izki S et al. Multiple Sclerosis and Related Disorders 2012;1: 29–38

39. Reading Papers ARRIVE Guidelines
METHODS…continued
8. Experimental animals
a. Provide details of the animals used, including species, strain, sex,
b. Provide further relevant information such as the source of animals,
International strain nomenclature,
Genetic modification status (e.g. knock-out or transgenic) & Genotype,
Health/immune status, Drug or Test naïve, Previous procedures, etc.
PROVIDE DETAILS OF DEMOGRAPHICS!
_____________________________________
Source No. EAE/Total
_____________________________________
In-house Bred ABH mice 10/10
Commercial Bred ABH mice 5/10
_____________________________________

40. Reading Papers ARRIVE Guidelines
METHODS…continued
9. Housing and husbandry (This part of the Ethical review process) & Environment Enrichment
a. Housing (e.g. type of facility,e.g. specific pathogen free [SPF]; type of cage or housing; bedding
material; number of cage companions.
b. Husbandry Conditions (e.g. breeding programme, light/dark cycle, temperature, quality of water, access
to food and water, environmental enrichment).
c. Welfare-Related Assessments and Interventions that were carried out prior to, during, or after the
experiment.

41. Reading Papers
METHODS…continued
10. Sample size
a. Specify the total number of animals used in each experiment and the number
of animals in each experimental group.
b. Explain how the number of animals was arrived at. Provide details of any sample size calculation used.
c. Indicate the number of independent replications of each experiment, if relevant.
POWER ANALYSIS!
https://www.nc3rs.org.uk/experimental-design-assistant-eda
Experimental Design Assistant
Vesterinen et al. Mult scler; 2010, 16:1044 2010

42. Reading Papers
METHODS…continued
11. Allocating Animals to Experimental Groups
a. Give full details of how animals were allocated to experimental groups, including randomisation or
matching if done.
b. Describe the order in which the animals in the different experimental groups were treated and assessed.
12. Experimental outcomes
Clearly define the primary and secondary experimental outcomes assessed
In Human Trials failure to change primary outcome measure is a FAILURE!

43. Reading Papers
Time Post- Induction (Days)
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
MeanDiseaseScoreSEM
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Drug Not-Interesting?
Vehicle
Limp
tail
Hind Limb
Paralysis
Partial
Paralysis
Impaired
Righting
Reflex
Drug
Treatment
METHODS…continued
11. Allocating Animals to Experimental Groups

44. Reading Papers
Time Post- Induction (Days)
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
MeanDiseaseScoreSEM
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Drug Not-Interesting?
Vehicle
Limp
tail
Hind Limb
Paralysis
Partial
Paralysis
Impaired
Righting
Reflex
Drug
Treatment
METHODS…continued
11. Allocating Animals to Experimental Groups

45. Reading Papers
METHODS…continued
13. Statistical methods
a. Provide details of the statistical methods used for each analysis.
b. Specify the unit of analysis for each dataset (e.g. single animal, group of
animals, single neuron).
c. Describe any methods used to assess whether the data met the assumption of
the statistical approach.

46. Reading Papers
DATA HANDLING
Mean = Average
Standard Deviation = Approximation of Variability 1.96SD contains 95% of sample
Standard Error (Square Root of SD) place were mean will occur in 95% of studies
Median = Middle Number
Range = Top – Bottom result
Quartile= 0, 25, 50, 75,100%
Percentile = 1-100th division
Confidence Interval 95% CI = 95% that mean will be with in limits
ANALYSIS
Proportions: Chi-Square
Two Groups: t test, Mann Whitney U, Wilcoxon Rank Test
Many Groups: ANOVA, kursall and Wallace
Is data Normally Distributed are the Variances Equal If not use non-parametic stats

47. Reading Papers
Baker D, et al. PLoS Biol. 2014; 12:e1001756.
Analysis of Non-Parametric Clinical Score Data with Parametric Statistics
55% (CI 46.7%-62.3%)39% (CI 32.5%-46.8%) 13% (CI 8.7%-18.58%)
CNS–infiltration to Clinical
Score is Not Linear
Gupta S et al. PLoS One. 2013 Oct 4;8(10):e76330.

48. Reading Papers
Figure legend. Clinical scores of two independent
EAE experiments at d23 post disease induction.
Individual scores as well as the mean score of two
independent experiments are shown. Control: n=10,
vehicle: n=13, xxxxx-345: n=11. Control versus
vehicle: P=0.620, control versus xxxxx-345: P=0.017,
vehicle versus xxxxx-345 P=0.029. * indicate P
values <0.05 and ** indicate P values <0.005 based
on a non-paired Student’s t test. Error bars are s.e.m
The assumptions of a t test (a) Data is normally
distributed. You test this and it passes the test
p=0.152,
(b) data groups have equal variances
Test for that and it fails P<0.05.
(c) Data is Parametric. Fail. It is non-parametric.
t test is not a valid test
Mann Whitney test.P=0.082.........Ooooops.

49. Reading Papers
RESULTS
14. Baseline data. For each experimental group, report relevant characteristics and health status of animals
(e.g. weight, microbiological status, and drug- or test-naïve) prior to treatment or testing (this information
can often be tabulated).
15. Numbers Analysed
Report the number of animals in each group included in each analysis.
Report absolute numbers (e.g. 10/20, not 50%).
b. If any animals or data were not included in the analysis, explain why.
16. Outcomes and Estimation
Report the results for each analysis carried out, with a measure of precision
(e.g. standard error or confidence interval).

50. Reading Papers
Time Post- Induction (Days)
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
MeanDiseaseScoreSEM
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Drug Not-Interesting?
Vehicle
RESULTS
Measure of Precision
Limp
tail
Hind Limb
Paralysis
Partial
Paralysis
Impaired
Righting
Reflex

51. Reading Papers
Time Post- Induction (Days)
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
MeanDiseaseScoreSEM
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Drug Not-Interesting?
Vehicle
RESULTS
Measure of Precision
Limp
tail
Hind Limb
Paralysis
Partial
Paralysis
Impaired
Righting
Reflex
How many
Animals Got Disease?
Severity Changed?
Skewing due to
Non-susceptibility?
Death/Endpoint?

52. Reading Papers
RESULTS…continued
16 (old 17) Animal Care & Monitoring
Describe methods to reduce suffering.
Increase the Dose Until it Does Something!
_________________________________
Treatment No.EAE/Total
_________________________________
Saline Amount 1 * 12/12
Saline Amount 2 11/12
Saline Amount 3 4/8
_________________________________
* = RDA
ARE THE DOSES IN THE TEST IN VITRO OR ANIMALS
RELEVANT TO THE HUMAN CONDITION?

53. Reading Papers
DISCUSSION
18. Interpretation/scientific implications
a. Interpret the results, taking into account the study objectives and hypotheses,
current theory and other relevant studies in the literature.
b. Comment on the study limitations including any potential sources of bias, any
limitations of the animal model, and the imprecision associated with the result.
c. Describe any implications of your experimental methods or findings for the
replacement, refinement or reduction (the 3Rs) of the use of animals in
research.

54. Reading Papers
DISCUSSION….Continued
18. (Previous 19) Generalisability/ translation
Comment on whether, and how, the findings of this study are likely to translate to other species or systems,
including any relevance to human biology.
A NEW POTENTIAL CURE COMES EVER WEEK?……..
WHILST JOURNALISTS MAY OVER-INTERPRET YOUR
FINDINGS,
REMEMBER, PEOPLE WITH SERIOUS DISEASES ARE
DESPERATE FOR THAT CURE……
BE REALISTIC &
DON’T CREATE TOO MANY FALSE HOPES!
Public Engagement

55. Reading Papers
19. PROTOCOL REGISTRATION
Was a protocol done before the work was done and where is it registered?
Human Trials are Registered at Clinical Trials.gov (USA), EudraCT (EU)
Perhaps may help limitation of repetition of animals work
Public Disclosure stops the capacity to file a patent

56. Reading Papers
NEW 20-DATA ACCESS STATEMENT
Consider deposition of Raw Data as a Supplementary file
• Help with review
• Allow further analysis and allow others to understand the data
• Provide data for sample size calculations
Levy Barazany et al Exp Neurol 2014: 255:63-70
Asychronous relapsing disease
Baker et al. Ann clin trans neurol 2019. doi: 10.1002/acn3.792
Myelin oligodendrocyte glycoprotein induced
disease in Non Obese Diabetic Mice
Asychronous relapsing disease

57. Reading Papers
NEW 21-CONFLICT OF INTEREST STATEMENT
Real and Perceived Conflicts of Interest
Funding (Previous 20) Todays Research Can Be Tomorrows Drug
June 2010

58. KNOWLEDGE IS THE KEY TO GAINING KNOWLEDGE
Allows You to Understand the Paper
Allows You to Interpret the Results
Allows you to Place the Work in Context of its Relevance
Allows you to see the flaws that may affect interpretation
Allows you to Judge the Value of the Work
Allows you to Exploit the Information from the work
Allows you to learn from yours and others mistakes
GIVES YOU THE CONFIDENCE
IN ALL OF THE ABOVE
Reading Papers

59. Thank you for Listening