STATISTICAL SIGNIFICANCE IN BIOLOGY
Conventions, Abstractions, and the Future
Erik Kusch
erik.kusch@uni-leipzig.de
Behavioural Ecology Research Group
University of Leipzig
18/06/2019
University of Leipzig Excursions into Biostatistics 1 / 14
1 The Reproducibility Crisis
What crisis?
Why are we in this crisis?
2 The p-Value Conundrum
Background
Alternatives
3 Finding A Solution
Summary
Discussion
University of Leipzig Excursions into Biostatistics 2 / 14
The Reproducibility Crisis
1 The Reproducibility Crisis
What crisis?
Why are we in this crisis?
2 The p-Value Conundrum
Background
Alternatives
3 Finding A Solution
Summary
Discussion
University of Leipzig Excursions into Biostatistics 3 / 14
The Reproducibility Crisis What crisis?
Irreproducible research
Reproducibility analyses have shown that only a surprisingly small portion of
studies can be replicated.
Nuzzo (2015). FOOLING OURSELVES. Nature.
This manifests in:
Large sample-to-sample variations of the p-value
Halsey et al. (2015). The fickle P value generates irreproducible results. Nature Methods.
Ambiguity in data handling procedures
Peng & Leek (2015). P values are just the tip of the iceberg. Nature.
Difficulty in establishing meta-analyses
Cumming (2014). The New Statistics: Why and How. Psychological Science.
Thus, our studies become solitary glances behind the curtain.
University of Leipzig Excursions into Biostatistics 4 / 14
The Reproducibility Crisis What crisis?
Irreproducible research
Reproducibility analyses have shown that only a surprisingly small portion of
studies can be replicated.
Nuzzo (2015). FOOLING OURSELVES. Nature.
This manifests in:
Large sample-to-sample variations of the p-value
Halsey et al. (2015). The fickle P value generates irreproducible results. Nature Methods.
Ambiguity in data handling procedures
Peng & Leek (2015). P values are just the tip of the iceberg. Nature.
Difficulty in establishing meta-analyses
Cumming (2014). The New Statistics: Why and How. Psychological Science.
Thus, our studies become solitary glances behind the curtain.
University of Leipzig Excursions into Biostatistics 4 / 14
The Reproducibility Crisis What crisis?
Irreproducible research
Reproducibility analyses have shown that only a surprisingly small portion of
studies can be replicated.
Nuzzo (2015). FOOLING OURSELVES. Nature.
This manifests in:
Large sample-to-sample variations of the p-value
Halsey et al. (2015). The fickle P value generates irreproducible results. Nature Methods.
Ambiguity in data handling procedures
Peng & Leek (2015). P values are just the tip of the iceberg. Nature.
Difficulty in establishing meta-analyses
Cumming (2014). The New Statistics: Why and How. Psychological Science.
Thus, our studies become solitary glances behind the curtain.
University of Leipzig Excursions into Biostatistics 4 / 14
The Reproducibility Crisis What crisis?
Irreproducible research
Reproducibility analyses have shown that only a surprisingly small portion of
studies can be replicated.
Nuzzo (2015). FOOLING OURSELVES. Nature.
This manifests in:
Large sample-to-sample variations of the p-value
Halsey et al. (2015). The fickle P value generates irreproducible results. Nature Methods.
Ambiguity in data handling procedures
Peng & Leek (2015). P values are just the tip of the iceberg. Nature.
Difficulty in establishing meta-analyses
Cumming (2014). The New Statistics: Why and How. Psychological Science.
Thus, our studies become solitary glances behind the curtain.
University of Leipzig Excursions into Biostatistics 4 / 14
The Reproducibility Crisis What crisis?
Irreproducible research
Reproducibility analyses have shown that only a surprisingly small portion of
studies can be replicated.
Nuzzo (2015). FOOLING OURSELVES. Nature.
This manifests in:
Large sample-to-sample variations of the p-value
Halsey et al. (2015). The fickle P value generates irreproducible results. Nature Methods.
Ambiguity in data handling procedures
Peng & Leek (2015). P values are just the tip of the iceberg. Nature.
Difficulty in establishing meta-analyses
Cumming (2014). The New Statistics: Why and How. Psychological Science.
Thus, our studies become solitary glances behind the curtain.
University of Leipzig Excursions into Biostatistics 4 / 14
The Reproducibility Crisis Why are we in this crisis?
Reasons for the reproducibility crisis
Some select phenomena that brought us here:
Dichotomy of p-values
Arbitrary .05 significance cut-off
generates a false dichotomy of
’false’ or ’true’ conclusions
Significant effect are not
necessarily biologically relevant
Burnham et al. (2011). AIC model selection and multimodel inference in
behavioral ecology: Some background, observations, and comparisons.
Behavioral Ecology and Sociobiology.
Peer-review shortcommings
Reluctancy to make corrections
No clear guidelines on where to
direct criticism towards
No standard process for data and
code access
Allison (2016). A tragedy of errors. Nature.
Research integrity
Research questions often
formulated post-hoc leading to
multiple testing issue
Sloppy reporting of data handling
procedures
Lack of data and code repository
guidelines
Lack in pre-specification of
research
Cumming (2014). The New Statistics: Why and How. Psychological
Science.
University of Leipzig Excursions into Biostatistics 5 / 14
The Reproducibility Crisis Why are we in this crisis?
Reasons for the reproducibility crisis
Some select phenomena that brought us here:
Dichotomy of p-values
Arbitrary .05 significance cut-off
generates a false dichotomy of
’false’ or ’true’ conclusions
Significant effect are not
necessarily biologically relevant
Burnham et al. (2011). AIC model selection and multimodel inference in
behavioral ecology: Some background, observations, and comparisons.
Behavioral Ecology and Sociobiology.
Peer-review shortcommings
Reluctancy to make corrections
No clear guidelines on where to
direct criticism towards
No standard process for data and
code access
Allison (2016). A tragedy of errors. Nature.
Research integrity
Research questions often
formulated post-hoc leading to
multiple testing issue
Sloppy reporting of data handling
procedures
Lack of data and code repository
guidelines
Lack in pre-specification of
research
Cumming (2014). The New Statistics: Why and How. Psychological
Science.
University of Leipzig Excursions into Biostatistics 5 / 14
The Reproducibility Crisis Why are we in this crisis?
Reasons for the reproducibility crisis
Some select phenomena that brought us here:
Dichotomy of p-values
Arbitrary .05 significance cut-off
generates a false dichotomy of
’false’ or ’true’ conclusions
Significant effect are not
necessarily biologically relevant
Burnham et al. (2011). AIC model selection and multimodel inference in
behavioral ecology: Some background, observations, and comparisons.
Behavioral Ecology and Sociobiology.
Peer-review shortcommings
Reluctancy to make corrections
No clear guidelines on where to
direct criticism towards
No standard process for data and
code access
Allison (2016). A tragedy of errors. Nature.
Research integrity
Research questions often
formulated post-hoc leading to
multiple testing issue
Sloppy reporting of data handling
procedures
Lack of data and code repository
guidelines
Lack in pre-specification of
research
Cumming (2014). The New Statistics: Why and How. Psychological
Science.
University of Leipzig Excursions into Biostatistics 5 / 14
The Reproducibility Crisis Why are we in this crisis?
Reasons for the reproducibility crisis
Some select phenomena that brought us here:
Dichotomy of p-values
Arbitrary .05 significance cut-off
generates a false dichotomy of
’false’ or ’true’ conclusions
Significant effect are not
necessarily biologically relevant
Burnham et al. (2011). AIC model selection and multimodel inference in
behavioral ecology: Some background, observations, and comparisons.
Behavioral Ecology and Sociobiology.
Peer-review shortcommings
Reluctancy to make corrections
No clear guidelines on where to
direct criticism towards
No standard process for data and
code access
Allison (2016). A tragedy of errors. Nature.
Research integrity
Research questions often
formulated post-hoc leading to
multiple testing issue
Sloppy reporting of data handling
procedures
Lack of data and code repository
guidelines
Lack in pre-specification of
research
Cumming (2014). The New Statistics: Why and How. Psychological
Science.
University of Leipzig Excursions into Biostatistics 5 / 14
The p-Value Conundrum
1 The Reproducibility Crisis
What crisis?
Why are we in this crisis?
2 The p-Value Conundrum
Background
Alternatives
3 Finding A Solution
Summary
Discussion
University of Leipzig Excursions into Biostatistics 6 / 14
The p-Value Conundrum Background
What is the p-value and why is it isnufficient?
"The p-value is the probability of randomly obtaining an effect at least as
extreme as the one in your sample data, given the null hypothesis."
Misconceptions
The p-value is not designed to tell
us whether something is strictly
true or false
It is not the probability of the null
hypothesis being true
The size of p does not yield any
information about the strength of
an observed effect
Mathematical Quirks
It varies strongly from
sample-to-sample (depending on
statistical power of the set-up)
If the sample size is big enough,
the
p
value will always be below the
.05 cut-off, no matter the
magnitude of the effect
University of Leipzig Excursions into Biostatistics 7 / 14
The p-Value Conundrum Background
What is the p-value and why is it isnufficient?
"The p-value is the probability of randomly obtaining an effect at least as
extreme as the one in your sample data, given the null hypothesis."
Misconceptions
The p-value is not designed to tell
us whether something is strictly
true or false
It is not the probability of the null
hypothesis being true
The size of p does not yield any
information about the strength of
an observed effect
Mathematical Quirks
It varies strongly from
sample-to-sample (depending on
statistical power of the set-up)
If the sample size is big enough,
the
p
value will always be below the
.05 cut-off, no matter the
magnitude of the effect
University of Leipzig Excursions into Biostatistics 7 / 14
The p-Value Conundrum Background
What is the p-value and why is it isnufficient?
"The p-value is the probability of randomly obtaining an effect at least as
extreme as the one in your sample data, given the null hypothesis."
Misconceptions
The p-value is not designed to tell
us whether something is strictly
true or false
It is not the probability of the null
hypothesis being true
The size of p does not yield any
information about the strength of
an observed effect
Mathematical Quirks
It varies strongly from
sample-to-sample (depending on
statistical power of the set-up)
If the sample size is big enough,
the
p
value will always be below the
.05 cut-off, no matter the
magnitude of the effect
University of Leipzig Excursions into Biostatistics 7 / 14
The p-Value Conundrum Alternatives
Effect sizes
"A measure of the magnitude of a statistical effect within the data (i.e.
values calculated from test statistics)."
Nakagawa & Cuthill (2007). Effect size, confidence interval and statistical significance: A practical guide for biologists. Biological Reviews.
Intuitive to interpret and often what we are interested in
Three types for most situations:
r statistics (correlations)
d statistics (comparisons of values)
OR (odds ratio) statistics (risk measurements)
These are point estimates
Need to be reported alongside some information of credibility
These are usually standardised thus enabling meta-studies
In R: https://cran.r-project.org/web/packages/compute.es/compute.es.pdf and
https://cran.r-project.org/web/packages/effsize/effsize.pdf
University of Leipzig Excursions into Biostatistics 8 / 14
The p-Value Conundrum Alternatives
Confidence Intervals
"Confidence intervals (CIs) answer the questions: ’How strong is the
effect’ and ’How accurate is that estimate of the population effect’."
Halsey (2019). The reign of the p-value is over: what alternative analyses could we employ to fill the power vacuum? Biology Letters.
Intuitive to interpret
Answers the questions we are most interested in
Does not require additional information of statistical certainty
Combines point estimates and range estimates
Removes some of the pressure of the "file drawer problem"
Shares the same mathematical framework as the p-value calculation
Especially useful in data visualisation
In R, many functions come with in-built ways of establishing CIs.
University of Leipzig Excursions into Biostatistics 9 / 14
The p-Value Conundrum Alternatives
Akaike Information Criterion (AIC)
The Akaike Information Criterion (AIC) is a indicator of model fit.
Burnham et al. (2011). AIC model selection and multimodel inference in behavioral ecology: Some background, observations, and comparisons.
Behavioral Ecology and Sociobiology.
Used for model selection and comparison
Lower AICs indicate better model fit
One can establish contrasting models adhering to different hypothesis and
identify which model suits the data best
A proper hypothesis selection tool
Model selection often comes with some degree of uncertainty
Can be misused in step-wise model building procedures
In R, most model outputs can be assessed using the AIC() function.
University of Leipzig Excursions into Biostatistics 10 / 14
The p-Value Conundrum Alternatives
Bayes Factor
" The minimum Bayes factor is simply the exponential of the difference
between the log-likelihoods of two competing models."
Goodman (2001). Of P-Values and Bayes: A Modest Proposal. Epidemiology.
Intuitive to interpret (Bayes Factor of 1/10 means that our study
decreased the relative odds of the null hypothesis being true tenfold)
Uses prior information to establish expected likelihoods thus enabling a
progression in science
In R: https://cran.r-project.org/web/packages/BayesFactor/BayesFactor.pdf or direct Bayesian
Statistics using JAGS or STAN (for example)
University of Leipzig Excursions into Biostatistics 11 / 14
Finding A Solution
1 The Reproducibility Crisis
What crisis?
Why are we in this crisis?
2 The p-Value Conundrum
Background
Alternatives
3 Finding A Solution
Summary
Discussion
University of Leipzig Excursions into Biostatistics 12 / 14
Finding A Solution Summary
Research Integrity
1 Distinguish between prespecified (answering a question) and
exploratory (formulating a question) studies.
2 Express research question in terms of expectations of effect sizes
3 Identify the effect sizes best suited to answer these questions
4 Report full study plan before commencing data collection
5 Calculate measures of statistical meaning that enable meta-studies
(e.g. effect sizes and CIs)
6 Make sure to correctly interpret the results outside of the p-value
dichotomy of true and false
7 Report the findings in a meta-analytic context
University of Leipzig Excursions into Biostatistics 13 / 14
Finding A Solution Discussion
Where do we go from here?
"Treat statistics as a science, and not a
recipe"
Andrew Vickers
"The numbers are where the scientific
discussion should start, not end!"
Regina Nuzzo
University of Leipzig Excursions into Biostatistics 14 / 14