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Commit 68fffbee authored by Rachel Heyard's avatar Rachel Heyard
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some random changes (not done yet).

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......@@ -82,6 +82,20 @@
journal = {Frontiers in Psychology}
}
@article {Chalmers1002,
author = {Chalmers, Iain},
title = {Proposal to outlaw the term {\textquotedblleft}negative trial{\textquotedblright}},
volume = {290},
number = {6473},
pages = {1002--1002},
year = {1985},
doi = {10.1136/bmj.290.6473.1002},
publisher = {BMJ Publishing Group Ltd},
issn = {0267-0623},
URL = {https://www.bmj.com/content/290/6473/1002.1},
journal = {BMJ}
}
@Article{Bayarri2003,
doi = {10.1016/s0378-3758(02)00282-3},
year = {2003},
......@@ -1388,6 +1402,18 @@ Visualizing Intersecting Sets},
journal = {{eLife}}
}
@article{Errington2021b,
doi = {10.7554/elife.73430},
url = {https://doi.org/10.7554/elife.73430},
year = {2021},
month = dec,
publisher = {{eLife} Sciences Publications, Ltd},
volume = {10},
author = {Timothy M Errington and Alexandria Denis and Anne B Allison and Renee Araiza and Pedro Aza-Blanc and Lynette R Bower and Jessica Campos and Heidi Chu and Sarah Denson and Cristine Donham and Kaitlyn Harr and Babette Haven and Elizabeth Iorns and Jennie Kwok and Elysia McDonald and Steven Pelech and Nicole Perfito and Amanda Pike and Darryl Sampey and Michael Settles and David A Scott and Vidhu Sharma and Todd Tolentino and Angela Trinh and Rachel Tsui and Brandon Willis and Joshua Wood and Lisa Young},
title = {Experiments from unfinished Registered Reports in the Reproducibility Project: Cancer Biology},
journal = {{eLife}}
}
@article{Bretz2009,
doi = {10.1002/sim.3538},
year = {2009},
......@@ -2831,6 +2857,20 @@ Discrimination},
journal = {Statistics in Medicine}
}
@article{Berner2022,
doi = {10.1111/jeb.14009},
url = {https://doi.org/10.1111/jeb.14009},
year = {2022},
month = may,
publisher = {Wiley},
volume = {35},
number = {6},
pages = {777--787},
author = {Daniel Berner and Valentin Amrhein},
title = {Why and how we should join the shift from significance testing to estimation},
journal = {Journal of Evolutionary Biology}
}
@book{Senn2008,
title={Statistical issues in drug development},
......
......@@ -24,7 +24,7 @@
bottom=25mm,
}
\title{\bf Replication studies and absence of evidence}
\title{\bf Meta-research: Replication studies and absence of evidence}
\author{{\bf Rachel Heyard, Charlotte Micheloud, Samuel Pawel, Leonhard Held} \\
Epidemiology, Biostatistics and Prevention Institute \\
Center for Reproducible Science \\
......@@ -116,7 +116,15 @@ formatBF <- Vectorize(FUN = formatBF.)
some sort of mantra in statistics and medical lectures. The
misinterpretation of non-significant results as ``null-findings'' is
however still common and has important consequences for the
interpretation of replication projects and alike.
interpretation of replication projects and alike. In many replication
attempts and large replication projects, failure to reject the null
hypothesis in the replication study is interpreted as successfully
replicating or even proving a null-effect. Methods to adequately summarize
the evidence for the null have been proposed. With this paper we want to
highlight the consequences of the ``absence of evidence'' fallacy in the
replication setting and want to guide the readers and hopefully future
authors of replication studies to the correct methods to design and
analyse their replication attempts.
} \\
\rule{\textwidth}{0.5pt} \emph{Keywords}: Bayesian hypothesis testing,
equivalence test, non-inferiority test, null hypothesis, replication
......@@ -127,8 +135,6 @@ formatBF <- Vectorize(FUN = formatBF.)
\section{Introduction}
The general misconception that statistical non-significance indicates evidence
for the absence of an effect is unfortunately widespread \citep{Altman1995}. A
well-designed study is constructed in a way that a large enough sample (of
......@@ -136,41 +142,62 @@ participants, n) is used to achieve an 80-90\% power of correctly rejecting the
null hypothesis. This leaves us with a 10-20\% chance of a false negative.
Somehow this fact from ``Hypothesis Testing 101'' is all too often forgotten and
studies showing an effect with a p-value larger than the conventionally used
significance level of 0.05 is doomed to be ``negative study'' or showing a
``null effect''. Some have even pleaded for abolishing the term ``negative
study'', as every well-designed and conducted study is a ``positive contribution
to knowledge'', regardless it’s results [REF]. \todo[inline]{Some more from
https://onlinelibrary.wiley.com/doi/full/10.1111/jeb.14009}
More specifically, turning to the replication context, the misconception
significance level of $\alpha = 0.05$ is doomed to be a ``negative study'' or showing a
``null effect''. Some have even called to abolish the term ``negative
study'' altogether, as every well-designed and conducted study is a ``positive
contribution to knowledge'', regardless it’s results \citep{Chalmers1002}. Others
suggest to shift away from significance testing because of the many misconceptions
of $p$-values and significance \citep{Berner2022}.
More specifically, turning to the replication context, ``the absence of evidence'' fallacy
appeared in the definitions of replication success in some of the large-scale
replication projects. The Replication Project Cancer Biology (RPCB [REF]) and
the RP in Experimental Philosophy (RPEP [REF]) explicitly define a replication
of a non-significant original effect as successful if the effect in the
replication projects. The Replication Project Cancer Biology \citep[RPCB]{Errington2021}
and the RP in Experimental Philosophy \citep[RPEP]{Cova2018} explicitly define a
replication of a non-significant original effect as successful if the effect in the
replication study is also non-significant. While the authors of the RPEP warn
the reader that the use of p-values as criterion for success is problematic when
applied to replications of original non-significant findings, the authors of the
RPCB do not. The RP in Psychological Science [REF], on the other hand, excluded
the ``original nulls'' when deciding replication success based on significance and
the Social Science RP [REF] as well as the RP in Experimental Economics [REF]
did not include original studies without a significant finding.
RPCB do not. The RP in Psychological Science \citep{Opensc2015}, on the other hand,
excluded the ``original nulls'' when deciding replication success based on significance and
the Social Science RP \citep{Camerer2018} as well as the RP in Experimental Economics
\cite{Camerer2016} did not include original studies without a significant finding.
\section{To replicate or not to replicate (a ``null'')?}
\textbf{To replicate or not to replicate an original ``null'' finding?}
Because of the previously presented fallacy, original studies with
non-significant effects are seldom replicated. Given the cost of replication
studies, it is also unwise to advise replicating a study that has low changes of
successful replication. To help deciding what studies are worth repeating,
efforts to predict which studies have a higher chance to replicate successfully
emerged [REF]. Of note is that the chance of a successful replication
emerged \citep{Altmejd2019, Pawel2020}. Of note is that the chance of a successful replication
intrinsically depends on the definition of replication success. If for a
successful replication we need a ``significant result in the same direction in
both the original and the replication study'' (i.e. the two-trials rule),
both the original and the replication study'' (i.e. the two-trials rule, \cite{Senn2008}),
replicating a non-significant original result does indeed not make any sense.
However, the use of significance as sole criterion for replication success has
its shortcomings .....
\todo[inline]{SP: look and discuss the papers from \citet{Anderson2016, Anderson2017}}
\section{Example: ``Null findings'' from the Reproducibility Project: Cancer
its shortcomings.
\citet{Anderson2016} summarized the goals of replications and recommended analyses and
success criterion. Interestingly they recommended using the two-trials rule only if
the goal is to infer the \textit{existence and direction} of a statistical significant
effect, while the replicating researchers are not interested in the size of this effect.
A successful replication attempt would result in a small $p$-value, while a large $p$-value
in the replication would only mean that the
On the contrary, if the goal is to infer a null effect \cite{Anderson2016} write that,
in this case, evidence for the null hypothesis has to be provided. To achieve this
goal equivalence tests or Bayesian methods to quantify the evidence for the null
hypothesis can be used. In the following, we will illustrate how to accurately
interpret the potential replication of original non-significant results in the
Cancer Biology Replication Project.
% \todo[inline]{SP: look and discuss the papers from \citet{Anderson2016, Anderson2017}}
\todo[inline]{RH: Note sure what to cite from \citet{Anderson2017}}
In general a non-significant original finding does not mean that the underlying
true effect is zero nor that it does not exist. This is especially true if the
original study is under-powered. \todo[inline]{RH: for myself, more blabla on
under-powered original studies}
\section{Example: ``Null findings'' from the Replication Project Cancer
Biology}
Of the 158 effects presented in 23 original studies that were repeated in the
cancer biology RP \citep{Errington2021} 14\% (22) were interpreted as ``null
......@@ -179,7 +206,7 @@ effects''.
% presented in Lu et al. (2014) and replicated by Richarson et al (2016).
Note that the attempt to replicate all the experiments from the original study
was not completed because of some unforeseen issues in the implementation (see
Errington et al (2021) for more details on the unfinished registered reports in
\cite{Errington2021b} for more details on the unfinished registered reports in
the RPCB). Figure~\ref{fig:nullfindings} shows effect estimates with confidence
intervals for the original ``null findings'' (with $p_{o} > 0.05$) and their
replication studies from the project.
......@@ -315,18 +342,19 @@ ggplot(data = rpcbNull) +
\label{fig:nullfindings}
\end{figure}
\section{Equivalence Design}
\section{Dealing with original non-significant findings in replication projects}
\subsection{Equivalence Design}
For many years, equivalence designs have been used in clinical trials to
understand whether a new drug, which might be cheaper or have less side effects
is equivalent to a drug already on the market [some general REF]. Essentially,
this type of design tests whether the difference between the effects of both
treatments or interventions is smaller than a predefined margin/threshold.
Turning back to the replication contexts and our example ....
% \todo[inline]{fix margin:
% to 0.25??}
\section{Bayesian Hypothesis Testing}
\subsection{Bayesian Hypothesis Testing}
Bayesian hypothesis testing is a hypothesis testing framework in which the
distinction between absence of evidence and evidence of absence is more natural.
The central quantity is the Bayes factor \citep{Jeffreys1961, Good1958,
......
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