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Statistics
Jonas Ranstam PhD
Statistics
A scientific report

The idea is to try and give all the information to help
others to judge the value of your contributions, not just
the information that leads to judgment in one particular
direction or another.

                                     Richard P. Feynman
Statistics
Description of observed data

mean, median, mode (central tendency)
standard deviation, range (dispersion)

Presentation of uncertainty

p-value, statistical significance (hypothesis testing)
confidence interval, SEM (interval estimation)
Statistics
What uncertainty?

Generalization uncertainty, for example:

-   From one sample of rats to all rats (the uncertainty
    caused by biological variability)

-   From a single measurement on a single rat to all
    measurements of the same kind on the same rat
    (the uncertainty caused by using imperfect
    measurement instruments, i.e. reliability)
Statistics
What determines the degree of uncertainty?

1. The number of observations

2. The variability
Statistics
What is important when presenting results?

1. The number of observations

2. The variability
Reported mean concentration with ±SD (bar chart)
Observed mean concentration (dotplot)
Estimated mean concentration with 95% confidence intervals
Statistics
Why use CI instead of SEM?

Because the CI is the better measure of uncertainty

  n        SEM       CI (for a mean value)

  2         ±1       50%
  3         ±1       58%
  4         ±1       63%
  6         ±1       64%
  7         ±1       65%
  ∞         ±1       68%
Statistics
Other problems related to generalization uncertainty

1. Independence of observations

2. Gaussian probability distribution

3. Multiplicity
Statistics
1. Independent observations (2 treatments, 4 rats, n = ?)



                                        n=4


                                        n=8



                                        n = 96
Statistics
Independent observations

Distinguish between:

1. Biological variation

2. Measurement reliability



Describe the sources of variation clearly in the manuscript!
How many animals, repeated observations, technical
replicates, etc. have been analyzed?
Statistics
Recommended reading

Churchill GA. Fundamentals of experimental design for
cDNA microarrays. Nature Genetics 2002;32S:490-495.
2. Gaussian distribution
Statistics
Are your results empirically supported?

Or do they rely on your assumptions?

- Student's t-test (Gaussian, identical variance)

- Mann-Whitney U-test (identical shape and variance)
Statistics
Did you check if the assumptions were fulfilled?

-   How did you do it?

-   What was the result?



Describe it in the manuscript!
Statistics
3. Multiplicity

With more than one tested null hypothesis the real
significance level will differ from the nominal
Statistics
3. Multiplicity

-   Multiplicity corrections correct the type-1 error rate

-   Multiplicity corrections increase the type-2 error rate
Statistics
3. Multiplicity

-   Bonferroni is not a good method, several better
    exist, for example the methods developed
    by Holm and Hochberg

-   P-value corrections within endpoints do not solve
    the problem of testing multiple endpoints
Statistics
3. Multiplicity

What is your strategy for dealing with multiplicity? Are
Bonferroni corrections necessary? Are all multiplicity
issues addressed?



Describe it in the manuscript!
Statistics
Summary

As an author of a scientific report your task is to
perform an adequate evaluation and presentation of
the uncertainty and limitations of your findings.

This involves more than just calculating a p-value.
Statistics
Summary

When a well-done trial or experiment or observational
study is fairly, honestly, and thoroughly reported, it will
have so many warts, footnotes, and exceptions that it
may be hard for the uninitiated to believe that the work
was of high quality.


                                         Frederick Mosteller
Thank you for your attention!

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