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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="3.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">PLoS ONE</journal-id>
      <journal-id journal-id-type="publisher-id">plos</journal-id>
      <journal-id journal-id-type="pmc">plosone</journal-id>
      <journal-title-group>
        <journal-title>PLoS ONE</journal-title>
      </journal-title-group>
      <issn pub-type="epub">1932-6203</issn>
      <publisher>
        <publisher-name>Public Library of Science</publisher-name>
        <publisher-loc>San Francisco, USA</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">PONE-D-12-40674</article-id>
      <article-id pub-id-type="doi">10.1371/journal.pone.0058777</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Article</subject>
        </subj-group>
        <subj-group subj-group-type="Discipline-v2">
          <subject>Mathematics</subject>
          <subj-group>
            <subject>Statistics</subject>
            <subj-group>
              <subject>Biostatistics</subject>
              <subject>Contingency tables</subject>
              <subject>Statistical methods</subject>
            </subj-group>
          </subj-group>
        </subj-group>
        <subj-group subj-group-type="Discipline-v2">
          <subject>Medicine</subject>
          <subj-group>
            <subject>Clinical research design</subject>
            <subj-group>
              <subject>Case-control studies</subject>
              <subject>Epidemiology</subject>
              <subject>Retrospective studies</subject>
              <subject>Statistical methods</subject>
            </subj-group>
          </subj-group>
          <subj-group>
            <subject>Epidemiology</subject>
            <subj-group>
              <subject>Epidemiological methods</subject>
            </subj-group>
          </subj-group>
        </subj-group>
        <subj-group subj-group-type="Discipline-v2">
          <subject>Social and behavioral sciences</subject>
          <subj-group>
            <subject>Psychology</subject>
            <subj-group>
              <subject>Psychometrics</subject>
            </subj-group>
          </subj-group>
        </subj-group>
        <subj-group subj-group-type="Discipline">
          <subject>Public Health and Epidemiology</subject>
          <subject>Epidemiology</subject>
          <subject>Mathematics</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Effect Sizes for 2×2 Contingency Tables</article-title>
        <alt-title alt-title-type="running-head">Effect Sizes for 2×2 Contingency Tables</alt-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Olivier</surname>
            <given-names>Jake</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="cor1">
            <sup>*</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author" xlink:type="simple">
          <name name-style="western">
            <surname>Bell</surname>
            <given-names>Melanie L.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <addr-line>School of Mathematics and Statistics, University of New South Wales, Sydney, Australia</addr-line>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <addr-line>Psycho-Oncology Co-Operative Research Group, School of Psychology, University of Sydney, Sydney, Australia</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor" xlink:type="simple">
          <name name-style="western">
            <surname>Rapallo</surname>
            <given-names>Fabio</given-names>
          </name>
          <role>Editor</role>
          <xref ref-type="aff" rid="edit1"/>
        </contrib>
      </contrib-group>
      <aff id="edit1">
        <addr-line>University of East Piedmont, Italy</addr-line>
      </aff>
      <author-notes>
        <corresp id="cor1">* E-mail: <email xlink:type="simple">j.olivier@unsw.edu.au</email></corresp>
        <fn fn-type="conflict">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
        <fn fn-type="con">
          <p>Analyzed the data: JO MLB. Wrote the paper: JO MLB.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2013</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>7</day>
        <month>3</month>
        <year>2013</year>
      </pub-date>
      <volume>8</volume>
      <issue>3</issue>
      <elocation-id>e58777</elocation-id>
      <history>
        <date date-type="received">
          <day>19</day>
          <month>12</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>6</day>
          <month>2</month>
          <year>2013</year>
        </date>
      </history>
      <permissions>
        <copyright-year>2013</copyright-year>
        <copyright-holder>Olivier and Bell</copyright-holder>
        <license xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>Sample size calculations are an important part of research to balance the use of resources and to avoid undue harm to participants. Effect sizes are an integral part of these calculations and meaningful values are often unknown to the researcher. General recommendations for effect sizes have been proposed for several commonly used statistical procedures. For the analysis of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e001" xlink:type="simple"/></inline-formula> tables, recommendations have been given for the correlation coefficient <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e002" xlink:type="simple"/></inline-formula> for binary data; however, it is well known that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e003" xlink:type="simple"/></inline-formula> suffers from poor statistical properties. The odds ratio is not problematic, although recommendations based on objective reasoning do not exist. This paper proposes odds ratio recommendations that are anchored to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e004" xlink:type="simple"/></inline-formula> for fixed marginal probabilities. It will further be demonstrated that the marginal assumptions can be relaxed resulting in more general results.</p>
      </abstract>
      <funding-group>
        <funding-statement>The authors have no support or funding to report.</funding-statement>
      </funding-group>
      <counts>
        <page-count count="7"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="s1">
      <title>Introduction</title>
      <p>Sample size calculations are an integral part of scientifically useful and ethical research <xref ref-type="bibr" rid="pone.0058777-Lewis1">[1]</xref>. A study which is too small may not answer the research question, wasting resources and potentially putting participants at risk for no purpose <xref ref-type="bibr" rid="pone.0058777-Halpern1">[2]</xref>. Studies which are too large can also waste resources and expose participants to the potential harms of research needlessly, as well as delaying results and their translation into practice. The computation of sample size <italic>a priori</italic> is usually dependent upon predetermined values for power and level of significance, an estimate of the expected variability in the sample and an effect size of practical or clinical importance. By convention, the choice of power and level of significance is usually at least <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e005" xlink:type="simple"/></inline-formula> and no more than <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e006" xlink:type="simple"/></inline-formula> respectively. When a practically important effect size is unknown, there are several recommendations in the literature to guide the researcher. In his seminal paper, Cohen <xref ref-type="bibr" rid="pone.0058777-Cohen1">[3]</xref> gives operationally defined small, medium and large effect sizes for various, common significance tests. The use of effect size recommendations should not replace differences of clinical or practical importance <xref ref-type="bibr" rid="pone.0058777-Lenth1">[4]</xref> and may not be appropriate for all disciplines. In basic science research, for example, large effect sizes by Cohen's criteria are common and, therefore, require small sample sizes. On the other hand, clinical and epidemiological research often deals with small effect sizes and often requires large, population-based studies. While there are some approaches to estimating a minimum important effect <xref ref-type="bibr" rid="pone.0058777-King1">[5]</xref>, there are instances where this information is simply not known. Thus, effect size recommendations assist with the balance between overly small and overly large sample sizes.</p>
      <p>When the researcher is interested in <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e007" xlink:type="simple"/></inline-formula> contingency tables, a common measure of effect size is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e008" xlink:type="simple"/></inline-formula> which, in this instance, is equivalent to Pearson's correlation coefficient <xref ref-type="bibr" rid="pone.0058777-DavenportJr1">[6]</xref>. Cohen <xref ref-type="bibr" rid="pone.0058777-Cohen1">[3]</xref> recommends effect sizes of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e009" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e010" xlink:type="simple"/></inline-formula> for small, medium and large effect sizes respectively and are identical to his recommendations for the correlation coefficient. Although Cohen <xref ref-type="bibr" rid="pone.0058777-Cohen1">[3]</xref> denotes this statistic as <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e011" xlink:type="simple"/></inline-formula>, much of the literature uses <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e012" xlink:type="simple"/></inline-formula> <xref ref-type="bibr" rid="pone.0058777-DavenportJr1">[6]</xref>–<xref ref-type="bibr" rid="pone.0058777-Ferguson2">[10]</xref> and the remainder of this manuscript follows this convention. To support his recommended effect sizes for correlation coefficients, Cohen <xref ref-type="bibr" rid="pone.0058777-Cohen2">[11]</xref> chose equivalent values for the difference in two means through the connection with point biserial correlation. Additionally, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e013" xlink:type="simple"/></inline-formula> is applicable to logistic regression since it can be converted to an odds ratio (<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e014" xlink:type="simple"/></inline-formula>) when the row (or column) marginal probabilities of the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e015" xlink:type="simple"/></inline-formula> table are fixed. For example, when the marginal probabilities are uniform (i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e016" xlink:type="simple"/></inline-formula> for row and column probabilities), Cohen's recommended effect sizes are equivalent to odds ratios of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e017" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e018" xlink:type="simple"/></inline-formula>. It will be demonstrated that the connection between the odds ratio and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e019" xlink:type="simple"/></inline-formula> is largely dependent on the marginal probabilities and these <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e020" xlink:type="simple"/></inline-formula> values should not be used in general.</p>
      <p>A problem arises when using the effect size <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e021" xlink:type="simple"/></inline-formula> for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e022" xlink:type="simple"/></inline-formula> tables as the full range of correlation coefficients are only possible under very restrictive circumstances and are not justified in general <xref ref-type="bibr" rid="pone.0058777-Haddock1">[12]</xref>. On the other hand, odds ratios are valid effect size measures that are not constrained by the marginal probabilities. Ferguson <xref ref-type="bibr" rid="pone.0058777-Ferguson2">[10]</xref> recommends small, medium, and large odds ratio effect sizes of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e023" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e024" xlink:type="simple"/></inline-formula>, but urges caution in their use as they are not “anchored” to Pearson's correlation coefficient. Although many have pointed out problems with <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e025" xlink:type="simple"/></inline-formula> as an association measure and advocate the use of odds ratios as an alternative, effect size recommendations for odds ratios do not exist in general.</p>
      <p>It is common in randomised controlled trials and case-control studies to fix one of the marginal probabilities in the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e026" xlink:type="simple"/></inline-formula> table as it directly relates to the ratio of participant allocation. For instance, a marginal probability of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e027" xlink:type="simple"/></inline-formula> corresponds to a 1:1 case-control ratio while a 2:1 ratio is a marginal probability of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e028" xlink:type="simple"/></inline-formula> (or equivalently <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e029" xlink:type="simple"/></inline-formula> for 1:2).</p>
      <p>The aims of this paper are to demonstrate: (1) the equivalence of effect size measures for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e031" xlink:type="simple"/></inline-formula> contingency tables, in particular the relationship between <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e032" xlink:type="simple"/></inline-formula> and the odds ratio; (2) that recommended odds ratio effect sizes can be derived from Cohen's work using the maximum value of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e033" xlink:type="simple"/></inline-formula> as a guideline for fixed marginal probabilities; (3) the shortcomings of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e034" xlink:type="simple"/></inline-formula> and the strength of the odds ratio as an effect size measure; and (4) that conservative odds ratio effect size recommendations can be derived without relying on fixed margins. We provide an example that investigates the association between helmet wearing by bicyclists and overtaking distance by automobiles.</p>
    </sec>
    <sec id="s2">
      <title>Equivalence of Effect Size Measures for 2×2 Contingency Tables</title>
      <sec id="s2a">
        <title><inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e035" xlink:type="simple"/></inline-formula> Contingency tables</title>
        <p>The two-way classification or contingency table is a common method for summarising the relationship between two binary variables, say <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e036" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e037" xlink:type="simple"/></inline-formula>. <xref ref-type="table" rid="pone-0058777-t001">Table 1</xref> gives the joint probability distribution of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e038" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e039" xlink:type="simple"/></inline-formula> when their individual outcomes are from the set <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e040" xlink:type="simple"/></inline-formula>.</p>
        <table-wrap id="pone-0058777-t001" position="float">
          <object-id pub-id-type="doi">10.1371/journal.pone.0058777.t001</object-id>
          <label>Table 1</label>
          <caption>
            <title>2×2contingency table of probabilities.</title>
          </caption>
          <alternatives>
            <graphic id="pone-0058777-t001-1" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0058777.t001" xlink:type="simple"/>
            <table>
              <colgroup span="1">
                <col align="left" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
              </colgroup>
              <thead>
                <tr>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"><italic>X = </italic>0</td>
                  <td align="left" rowspan="1" colspan="1"><italic>X = </italic>1</td>
                  <td align="left" rowspan="1" colspan="1">
                    <italic>Total</italic>
                  </td>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="1" colspan="1"><italic>Y = </italic>0</td>
                  <td align="left" rowspan="1" colspan="1">π<sub>00</sub></td>
                  <td align="left" rowspan="1" colspan="1">π<sub>01</sub></td>
                  <td align="left" rowspan="1" colspan="1">π<sub>0+</sub></td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1"><italic>Y = </italic>1</td>
                  <td align="left" rowspan="1" colspan="1">π<sub>10</sub></td>
                  <td align="left" rowspan="1" colspan="1">π<sub>11</sub></td>
                  <td align="left" rowspan="1" colspan="1">π<sub>1+</sub></td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">
                    <italic>Total</italic>
                  </td>
                  <td align="left" rowspan="1" colspan="1">π<sub>+0</sub></td>
                  <td align="left" rowspan="1" colspan="1">π<sub>+1</sub></td>
                  <td align="left" rowspan="1" colspan="1">1.0</td>
                </tr>
              </tbody>
            </table>
          </alternatives>
        </table-wrap>
        <p>In this formulation, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e041" xlink:type="simple"/></inline-formula>, for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e042" xlink:type="simple"/></inline-formula>, is the joint probability of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e043" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e044" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e045" xlink:type="simple"/></inline-formula> is the marginal probability of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e046" xlink:type="simple"/></inline-formula>, and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e047" xlink:type="simple"/></inline-formula> is the marginal probability of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e048" xlink:type="simple"/></inline-formula>. Under an assumption of independence between <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e049" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e050" xlink:type="simple"/></inline-formula>, the product of the marginal probabilities equals the cell probabilities, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e051" xlink:type="simple"/></inline-formula>. Alternatively, the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e052" xlink:type="simple"/></inline-formula> table could be represented by the frequency of observations so that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e053" xlink:type="simple"/></inline-formula> where <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e054" xlink:type="simple"/></inline-formula>. Similarly, the marginal frequencies are <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e055" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e056" xlink:type="simple"/></inline-formula>. Note that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e057" xlink:type="simple"/></inline-formula> is assumed to be the population proportion as the focus of this paper is the use of effect sizes as a planning tool and not statistical inference per se. In a case-control study, for example, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e058" xlink:type="simple"/></inline-formula> may indicate the presence or absence of disease while <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e059" xlink:type="simple"/></inline-formula> is an indication of exposure. Thus, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e060" xlink:type="simple"/></inline-formula> would represent the joint probability of being diseased and exposed.</p>
      </sec>
      <sec id="s2b">
        <title>Effect size <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e063" xlink:type="simple"/></inline-formula> and Equivalences for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e064" xlink:type="simple"/></inline-formula> Tables</title>
        <p>There are many association measures applicable to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e065" xlink:type="simple"/></inline-formula> tables which, with the exception of the odds ratio and relative risk, are equivalent or similar to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e066" xlink:type="simple"/></inline-formula>. The equivalence of some of these association measures is outlined below.</p>
        <p>For the random sample <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e067" xlink:type="simple"/></inline-formula>, Pearson's correlation coefficient is<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e068" position="float" xlink:type="simple"/></disp-formula>where <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e069" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e070" xlink:type="simple"/></inline-formula> are the sample means of the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e071" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e072" xlink:type="simple"/></inline-formula> respectively. Although used primarily as a measure of linear association, Pearson's correlation coefficient can be applied to binary variables and is often given the notation <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e073" xlink:type="simple"/></inline-formula>. For the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e074" xlink:type="simple"/></inline-formula> table case, we get</p>
        <p>
          <disp-formula>
            <graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e075" position="float" xlink:type="simple"/>
          </disp-formula>
          <disp-formula>
            <graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e076" position="float" xlink:type="simple"/>
          </disp-formula>
          <disp-formula>
            <graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e077" position="float" xlink:type="simple"/>
          </disp-formula>
        </p>
        <p>So, Pearson's correlation coefficient for binary random variables <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e078" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e079" xlink:type="simple"/></inline-formula> is<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e080" position="float" xlink:type="simple"/></disp-formula></p>
        <p>Since <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e081" xlink:type="simple"/></inline-formula> under the hypothesis of independence, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e082" xlink:type="simple"/></inline-formula> can be interpreted as measuring the departure from independence between <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e083" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e084" xlink:type="simple"/></inline-formula>. Note that Cramér's <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e085" xlink:type="simple"/></inline-formula> is equivalent to this equation for the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e086" xlink:type="simple"/></inline-formula> table case <xref ref-type="bibr" rid="pone.0058777-Cohen2">[11]</xref> as well as the square root of Goodman and Kruskal's <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e087" xlink:type="simple"/></inline-formula> <xref ref-type="bibr" rid="pone.0058777-Agresti1">[13]</xref>.</p>
        <p>For the analysis of contingency tables, in general (not just the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e088" xlink:type="simple"/></inline-formula> table case) the effect size formula for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e089" xlink:type="simple"/></inline-formula> total cells is<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e090" position="float" xlink:type="simple"/></disp-formula>where <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e091" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e092" xlink:type="simple"/></inline-formula> are cell probabilities under the null and alternative hypotheses respectively. Note that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e093" xlink:type="simple"/></inline-formula> is related to the usual chi-square statistic <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e094" xlink:type="simple"/></inline-formula> by <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e095" xlink:type="simple"/></inline-formula> and is sometimes called the contingency coefficient. Using this formula, Cohen <xref ref-type="bibr" rid="pone.0058777-Cohen1">[3]</xref> recommends <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e096" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e097" xlink:type="simple"/></inline-formula> for small, medium and large effect sizes. Making note that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e098" xlink:type="simple"/></inline-formula> is the probability of each cell (<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e099" xlink:type="simple"/></inline-formula>) and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e100" xlink:type="simple"/></inline-formula> is the cell probability under an independence assumption (so that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e101" xlink:type="simple"/></inline-formula>), we can then write the effect size formula for the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e102" xlink:type="simple"/></inline-formula> table as follows</p>
        <p>
          <disp-formula>
            <graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e103" position="float" xlink:type="simple"/>
          </disp-formula>
        </p>
        <p>Simple arithmetic demonstrates the equivalence of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e104" xlink:type="simple"/></inline-formula> with <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e105" xlink:type="simple"/></inline-formula>. The <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e106" xlink:type="simple"/></inline-formula> function is used to give the appropriate sign since the chi-square statistic is inherently non-directional.</p>
      </sec>
      <sec id="s2c">
        <title>The relationship of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e107" xlink:type="simple"/></inline-formula> to the odds ratio</title>
        <p>The odds ratio for the association between <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e108" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e109" xlink:type="simple"/></inline-formula> is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e110" xlink:type="simple"/></inline-formula>. When the marginal probabilities are held constant and the cell probability <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e111" xlink:type="simple"/></inline-formula> is known, the remaining cell probabilities can be written as<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e112" position="float" xlink:type="simple"/></disp-formula><disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e113" position="float" xlink:type="simple"/></disp-formula><disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e114" position="float" xlink:type="simple"/></disp-formula></p>
        <p>Therefore, when the marginal probabilities are fixed, the odds ratio can be computed directly from <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e115" xlink:type="simple"/></inline-formula>, which can then be expressed as<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e116" position="float" xlink:type="simple"/></disp-formula></p>
        <p>It is clear from the above formula that the odds ratio will be greater than one (or less than one) precisely when the joint probability <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e117" xlink:type="simple"/></inline-formula> is greater (or less) than expected under an assumption of independence, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e118" xlink:type="simple"/></inline-formula>. Additionally, the formula for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e119" xlink:type="simple"/></inline-formula> can be rearranged to solve for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e120" xlink:type="simple"/></inline-formula>, i.e.,<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e121" position="float" xlink:type="simple"/></disp-formula></p>
        <p>Although mathematically unattractive, it is clear the odds ratio can then be computed from <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e122" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e123" xlink:type="simple"/></inline-formula>, and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e124" xlink:type="simple"/></inline-formula>. Note that when <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e125" xlink:type="simple"/></inline-formula> (i.e., no correlation), we get <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e126" xlink:type="simple"/></inline-formula> (i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e127" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e128" xlink:type="simple"/></inline-formula> are independent) and the odds ratio is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e129" xlink:type="simple"/></inline-formula>. When <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e130" xlink:type="simple"/></inline-formula>, the term <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e131" xlink:type="simple"/></inline-formula> is then a measure of the departure from independence.</p>
      </sec>
    </sec>
    <sec id="s3">
      <title>Maximum <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e132" xlink:type="simple"/></inline-formula> and Modified Effect Sizes</title>
      <p>When the marginal probabilities are fixed constants, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e133" xlink:type="simple"/></inline-formula> is an increasing linear function of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e134" xlink:type="simple"/></inline-formula>. Further, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e135" xlink:type="simple"/></inline-formula> is bounded by<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e136" position="float" xlink:type="simple"/></disp-formula></p>
      <p>These bounds are due to all cell probabilities being non-negative and the relationship of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e137" xlink:type="simple"/></inline-formula> with the other cell probabilities given above. As a result, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e138" xlink:type="simple"/></inline-formula> is bounded as well and attains its maximum when <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e139" xlink:type="simple"/></inline-formula>. Using the upper bound of the above inequality, it can be shown that<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e140" position="float" xlink:type="simple"/></disp-formula>where <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e141" xlink:type="simple"/></inline-formula> to ensure <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e142" xlink:type="simple"/></inline-formula>. It is clear from the formula for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e143" xlink:type="simple"/></inline-formula> that the full range of correlation coefficients, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e144" xlink:type="simple"/></inline-formula>, is attainable only when the marginal probabilities are equal, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e145" xlink:type="simple"/></inline-formula> or <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e146" xlink:type="simple"/></inline-formula>. This has an intuitive appeal as perfect correlation for two binary variables is only possible when two cell probabilities are zero. For example, when all observations are in either the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e147" xlink:type="simple"/></inline-formula> or <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e148" xlink:type="simple"/></inline-formula> cells, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e149" xlink:type="simple"/></inline-formula>. However, it would appear highly unlikely both marginal probabilities will be equal in practice. For example, in a 1:1 case-control study with mortality as the primary outcome, half of all patients would need to die for perfect correlation to be possible. On the other hand, if <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e150" xlink:type="simple"/></inline-formula> of all patients die, the maximum correlation possible is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e151" xlink:type="simple"/></inline-formula> which is near a medium recommended effect size. So, in this situation, all estimates of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e152" xlink:type="simple"/></inline-formula>, computed from observed proportions, are bounded by</p>
      <p>
        <disp-formula>
          <graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e153" position="float" xlink:type="simple"/>
        </disp-formula>
      </p>
      <p>Importantly, odds ratios are not bounded with possible values of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e154" xlink:type="simple"/></inline-formula> as <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e155" xlink:type="simple"/></inline-formula> varies on the interval <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e156" xlink:type="simple"/></inline-formula>. In fact, as <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e157" xlink:type="simple"/></inline-formula> approaches <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e158" xlink:type="simple"/></inline-formula>, the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e159" xlink:type="simple"/></inline-formula> increases without bound. <xref ref-type="fig" rid="pone-0058777-g001">Figure 1</xref> demonstrates this relationship. Importantly, this indicates <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e160" xlink:type="simple"/></inline-formula> has serious limitations as a measure of association and that these limitations are not applicable to the odds ratio.</p>
      <fig id="pone-0058777-g001" position="float">
        <object-id pub-id-type="doi">10.1371/journal.pone.0058777.g001</object-id>
        <label>Figure 1</label>
        <caption>
          <title>Relationship between the odds ratio and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e030" xlink:type="simple"/></inline-formula> for unequal marginal probabilities.</title>
        </caption>
        <graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0058777.g001" position="float" xlink:type="simple"/>
      </fig>
    </sec>
    <sec id="s4">
      <title>Effect Sizes Relative to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e161" xlink:type="simple"/></inline-formula></title>
      <p>In many practical instances, the marginal probabilities are not equal, making the full range of values for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e162" xlink:type="simple"/></inline-formula> impossible with the potential of making Cohen's recommended effect sizes unusable for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e163" xlink:type="simple"/></inline-formula> tables. Although not equivalent to perfect correlation, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e164" xlink:type="simple"/></inline-formula> can be interpreted as the maximum possible correlation given the marginal probabilities. In fact, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e165" xlink:type="simple"/></inline-formula>/<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e166" xlink:type="simple"/></inline-formula> has been proposed as an association measure with the interpretation as the proportion of observed correlation relative to the maximum attainable with fixed marginal probabilities <xref ref-type="bibr" rid="pone.0058777-Ferguson1">[7]</xref>, although the researcher is cautioned when the marginal probabilities diverge <xref ref-type="bibr" rid="pone.0058777-DavenportJr1">[6]</xref>. Note that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e167" xlink:type="simple"/></inline-formula> is not equivalent to Cohen's similarity/agreement measure <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e168" xlink:type="simple"/></inline-formula>. However, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e169" xlink:type="simple"/></inline-formula> suffers from the same boundary problems as <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e170" xlink:type="simple"/></inline-formula> and the two are equivalent when scaled to their maximum values, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e171" xlink:type="simple"/></inline-formula>/<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e172" xlink:type="simple"/></inline-formula>/<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e173" xlink:type="simple"/></inline-formula>, making the two measures similar <xref ref-type="bibr" rid="pone.0058777-DavenportJr1">[6]</xref>.</p>
      <sec id="s4a">
        <title>Recommended effect sizes in terms of the odds ratio</title>
        <p>As an alternative to Cohen's recommendations, increments of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e174" xlink:type="simple"/></inline-formula> can be related to the odds ratio, say <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e175" xlink:type="simple"/></inline-formula>, where <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e176" xlink:type="simple"/></inline-formula>. Note that values of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e177" xlink:type="simple"/></inline-formula> or <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e178" xlink:type="simple"/></inline-formula> coincide with Cohen's usual recommendations when <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e179" xlink:type="simple"/></inline-formula>. The relationship between <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e180" xlink:type="simple"/></inline-formula> and the odds ratio can be simplified by choosing marginal probabilities for commonly used participant allocations. As an example, <xref ref-type="fig" rid="pone-0058777-g002">Figures 2</xref> and <xref ref-type="fig" rid="pone-0058777-g003">3</xref> demonstrate the relationship between <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e181" xlink:type="simple"/></inline-formula> and odds ratios for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e182" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e183" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e184" xlink:type="simple"/></inline-formula> for 1:1 and 1:2 allocations respectively. Note that the minimal odds ratios, and therefore most conservative when used to compute sample size, occur when <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e185" xlink:type="simple"/></inline-formula> tends to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e186" xlink:type="simple"/></inline-formula>. Although the odds ratio does not exist when <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e187" xlink:type="simple"/></inline-formula>, the limit exists and is<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e188" position="float" xlink:type="simple"/></disp-formula></p>
        <fig id="pone-0058777-g002" position="float">
          <object-id pub-id-type="doi">10.1371/journal.pone.0058777.g002</object-id>
          <label>Figure 2</label>
          <caption>
            <title>Odds ratios and marginal probability by small, medium and large effect sizes for 1:1 allocation.</title>
          </caption>
          <graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0058777.g002" position="float" xlink:type="simple"/>
        </fig>
        <fig id="pone-0058777-g003" position="float">
          <object-id pub-id-type="doi">10.1371/journal.pone.0058777.g003</object-id>
          <label>Figure 3</label>
          <caption>
            <title>Odds ratios and marginal probability by small, medium and large effect sizes for 1:2 allocation.</title>
          </caption>
          <graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0058777.g003" position="float" xlink:type="simple"/>
        </fig>
        <p>Additionally, the maximal odds ratio, and therefore most anti-conservative, occurs when the marginal probabilities are equal, as expected. Below is the maximum attainable odds ratio for equal margins <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e189" xlink:type="simple"/></inline-formula> for increments <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e190" xlink:type="simple"/></inline-formula> of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e191" xlink:type="simple"/></inline-formula>,<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e192" position="float" xlink:type="simple"/></disp-formula></p>
        <p>It is important to note that when <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e193" xlink:type="simple"/></inline-formula>, as is often true for case-control studies where cases are harder to identify or enrol than controls, the minimal odds ratio will be smallest for evenly allocated studies, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e194" xlink:type="simple"/></inline-formula>. Further, it is generally recommended to use 1:1 allocation as it is the most statistically efficient ratio, i.e., maximum power for a fixed overall sample size. So, odds ratios of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e195" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e196" xlink:type="simple"/></inline-formula> can be used as small, medium and large effect sizes without assumptions regarding marginal probabilities. Sample sizes computed using these odds ratios for 1:1 allocation are given in <xref ref-type="table" rid="pone-0058777-t002">Table 2</xref> for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e197" xlink:type="simple"/></inline-formula> power and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e198" xlink:type="simple"/></inline-formula> level of significance. A SAS macro that will compute sample sizes from given marginal probabilities for small, medium and large odds ratios has been provided as a supplementary file.</p>
        <table-wrap id="pone-0058777-t002" position="float">
          <object-id pub-id-type="doi">10.1371/journal.pone.0058777.t002</object-id>
          <label>Table 2</label>
          <caption>
            <title>Sample sizes calculated for small, medium and large effect sizes for 1:1 allocation, 80<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e061" xlink:type="simple"/></inline-formula> power and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e062" xlink:type="simple"/></inline-formula>.</title>
          </caption>
          <alternatives>
            <graphic id="pone-0058777-t002-2" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0058777.t002" xlink:type="simple"/>
            <table>
              <colgroup span="1">
                <col align="left" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
                <col align="center" span="1"/>
              </colgroup>
              <thead>
                <tr>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1">π<sub>1+</sub></td>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                  <td align="left" rowspan="1" colspan="1"/>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">Odds Ratio</td>
                  <td align="left" rowspan="1" colspan="1">0.1</td>
                  <td align="left" rowspan="1" colspan="1">0.2</td>
                  <td align="left" rowspan="1" colspan="1">0.3</td>
                  <td align="left" rowspan="1" colspan="1">0.4</td>
                  <td align="left" rowspan="1" colspan="1">0.5</td>
                  <td align="left" rowspan="1" colspan="1">0.6</td>
                  <td align="left" rowspan="1" colspan="1">0.7</td>
                  <td align="left" rowspan="1" colspan="1">0.8</td>
                  <td align="left" rowspan="1" colspan="1">0.9</td>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left" rowspan="1" colspan="1">1.22</td>
                  <td align="left" rowspan="1" colspan="1">8168</td>
                  <td align="left" rowspan="1" colspan="1">4688</td>
                  <td align="left" rowspan="1" colspan="1">3646</td>
                  <td align="left" rowspan="1" colspan="1">3254</td>
                  <td align="left" rowspan="1" colspan="1">3188</td>
                  <td align="left" rowspan="1" colspan="1">3386</td>
                  <td align="left" rowspan="1" colspan="1">3948</td>
                  <td align="left" rowspan="1" colspan="1">5282</td>
                  <td align="left" rowspan="1" colspan="1">9576</td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">1.86</td>
                  <td align="left" rowspan="1" colspan="1">724</td>
                  <td align="left" rowspan="1" colspan="1">436</td>
                  <td align="left" rowspan="1" colspan="1">354</td>
                  <td align="left" rowspan="1" colspan="1">330</td>
                  <td align="left" rowspan="1" colspan="1">338</td>
                  <td align="left" rowspan="1" colspan="1">374</td>
                  <td align="left" rowspan="1" colspan="1">454</td>
                  <td align="left" rowspan="1" colspan="1">632</td>
                  <td align="left" rowspan="1" colspan="1">1188</td>
                </tr>
                <tr>
                  <td align="left" rowspan="1" colspan="1">3.00</td>
                  <td align="left" rowspan="1" colspan="1">200</td>
                  <td align="left" rowspan="1" colspan="1">128</td>
                  <td align="left" rowspan="1" colspan="1">110</td>
                  <td align="left" rowspan="1" colspan="1">108</td>
                  <td align="left" rowspan="1" colspan="1">116</td>
                  <td align="left" rowspan="1" colspan="1">134</td>
                  <td align="left" rowspan="1" colspan="1">170</td>
                  <td align="left" rowspan="1" colspan="1">246</td>
                  <td align="left" rowspan="1" colspan="1">480</td>
                </tr>
              </tbody>
            </table>
          </alternatives>
        </table-wrap>
        <p>Interestingly, Haddock et al. <xref ref-type="bibr" rid="pone.0058777-Haddock1">[12]</xref> as a rule of thumb consider odds ratios greater than <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e199" xlink:type="simple"/></inline-formula> large effect sizes, although there is no clear justification given. In a situation where an allocation ratio other than 1:1 is used, recommended odds ratios can be computed directly using the above formula. These results are also applicable for other values of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e200" xlink:type="simple"/></inline-formula> through its complement <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e201" xlink:type="simple"/></inline-formula>. This is equivalent to swapping the columns (or rows) and the researcher should be aware the recommended odds ratio effect sizes are now the reciprocals of those above, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e202" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e203" xlink:type="simple"/></inline-formula> for small, medium and large respectively.</p>
        <p>This approach can also be applied to the relative risk and risk difference. If <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e204" xlink:type="simple"/></inline-formula> is taken as the grouping variable and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e205" xlink:type="simple"/></inline-formula> as the outcome, the relative risk is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e206" xlink:type="simple"/></inline-formula>. Simple substitution of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e207" xlink:type="simple"/></inline-formula> and the marginal probabilities <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e208" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e209" xlink:type="simple"/></inline-formula> results in a relative risk identical to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e210" xlink:type="simple"/></inline-formula> for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e211" xlink:type="simple"/></inline-formula>, i.e.,<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e212" position="float" xlink:type="simple"/></disp-formula></p>
        <p>Therefore, recommendations can also be derived for relative risk and are identical to those given for the odds ratio above. This result is expected as the odds ratio converges to the relative risk as the incidence rate approaches <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e213" xlink:type="simple"/></inline-formula>.</p>
        <p>Instead of comparing the risk between two groups as a ratio, it is sometimes useful to compare their differences <xref ref-type="bibr" rid="pone.0058777-Greenberg1">[14]</xref>. Again taking <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e214" xlink:type="simple"/></inline-formula> as the grouping variable and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e215" xlink:type="simple"/></inline-formula> as the outcome, the risk difference can be written as<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e216" position="float" xlink:type="simple"/></disp-formula></p>
        <p>where <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e217" xlink:type="simple"/></inline-formula> to ensure <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e218" xlink:type="simple"/></inline-formula> as above. It is clear from the numerator in this representation that <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e219" xlink:type="simple"/></inline-formula> is a measure of the departure from independence, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e220" xlink:type="simple"/></inline-formula>. Simple substitution of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e221" xlink:type="simple"/></inline-formula> into <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e222" xlink:type="simple"/></inline-formula> yields<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e223" position="float" xlink:type="simple"/></disp-formula>where the subscript <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e224" xlink:type="simple"/></inline-formula> is used to distinguish between risk difference formulae. This formula can be simplified somewhat for 1:1 allocations, i.e., <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e225" xlink:type="simple"/></inline-formula>; however, a general result independent of the marginal probabilities is clearly not possible in this instance as <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e226" xlink:type="simple"/></inline-formula> and therefore <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e227" xlink:type="simple"/></inline-formula>.</p>
        <p>Alternatively, the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e228" xlink:type="simple"/></inline-formula> formula can be solved for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e229" xlink:type="simple"/></inline-formula> and compared to previously given odds ratio recommendations. In terms of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e230" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e231" xlink:type="simple"/></inline-formula>, we get<disp-formula><graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e232" position="float" xlink:type="simple"/></disp-formula></p>
        <p>When the allocation ratio is 1:1, this formula simplifies to <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e233" xlink:type="simple"/></inline-formula> which has a form identical to Yule's <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e234" xlink:type="simple"/></inline-formula> <xref ref-type="bibr" rid="pone.0058777-Liebetrau1">[15]</xref>. So, Ferguson's <xref ref-type="bibr" rid="pone.0058777-Ferguson2">[10]</xref> odds ratio recommendations of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e235" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e236" xlink:type="simple"/></inline-formula> therefore correspond to proportions of maximum correlation of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e237" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e238" xlink:type="simple"/></inline-formula>. This suggests Ferguson's recommendations have the potential to be anti-conservative from a sample size viewpoint.</p>
      </sec>
    </sec>
    <sec id="s5">
      <title>Example</title>
      <p>This paper was motivated by a reanalysis of passing distances for motor vehicles overtaking a bicyclist <xref ref-type="bibr" rid="pone.0058777-Walker1">[16]</xref>. One of the primary results of this study was a significant association between helmet wearing and less overtaking distance, supporting a theory of risk perception for motor vehicle drivers directed towards bicyclists. Prior to collecting data, Walker <xref ref-type="bibr" rid="pone.0058777-Walker1">[16]</xref> reported computing a sample size of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e239" xlink:type="simple"/></inline-formula> overtaking manoeuvres based on a <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e240" xlink:type="simple"/></inline-formula> fixed effects factorial ANOVA for a small effect size <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e241" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e242" xlink:type="simple"/></inline-formula> level of significance and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e243" xlink:type="simple"/></inline-formula> power. The factors for this study were helmet wearing (2 levels) and bicycle position relative to the kerb (5 levels). It has been noted, however, that passing distances are often recommended and sometimes legislated to one metre or more <xref ref-type="bibr" rid="pone.0058777-Olivier1">[17]</xref>. So, passing manoeuvres of at least a metre are considered safe and less than a metre unsafe, with the implication that large differences in passing distance are unimportant beyond one metre in terms of bicycle safety. When compared with helmet wearing, safe/unsafe passing distances can be analysed using a <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e244" xlink:type="simple"/></inline-formula> table. Since Walker's study was powered at an unusually high level with subsequent increased probability of a type I error, bootstrap standard errors were estimated for more reasonable values for power of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e245" xlink:type="simple"/></inline-formula>, <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e246" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e247" xlink:type="simple"/></inline-formula>. Operationally defined small, medium and large effect sizes were also used since a meaningful difference in overtaking distance is unknown.</p>
      <p>The relevant observed data from Walker <xref ref-type="bibr" rid="pone.0058777-Walker1">[16]</xref> is given in <xref ref-type="table" rid="pone-0058777-t003">Table 3</xref>. The observed marginal proportions here are <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e248" xlink:type="simple"/></inline-formula> for helmet wearing and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e249" xlink:type="simple"/></inline-formula> for unsafe passing manoeuvres. Using the marginal probabilities, the maximum attainable effect size is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e250" xlink:type="simple"/></inline-formula> and the estimated correlation is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e251" xlink:type="simple"/></inline-formula>. A consequence is the effect size for the association between helmet wearing and safe passing distance is, at best, much less than a small effect size by Cohen's index. The corresponding small, medium and large odds ratio effect sizes using increments of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e252" xlink:type="simple"/></inline-formula> are <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e253" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e254" xlink:type="simple"/></inline-formula> for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e255" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e256" xlink:type="simple"/></inline-formula>. Note that these values are not much greater than the minimal recommended odds ratios mentioned in the previous section, further suggesting the association between safe/unsafe passing distance and helmet wearing is, at best, a small effect size. In fact, the unadjusted odds ratio is <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e257" xlink:type="simple"/></inline-formula> and non-significant by the chi-square test (<inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e258" xlink:type="simple"/></inline-formula>). Conversely, sample sizes for a future study can be computed from the observed probabilities using G*Power for logistic regression with a single binomially distributed predictor for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e259" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e260" xlink:type="simple"/></inline-formula> power <xref ref-type="bibr" rid="pone.0058777-Faul1">[18]</xref> resulting in <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e261" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e262" xlink:type="simple"/></inline-formula> observations for small, medium and large odds ratios. To put these sample size computations into perspective, a future study would need to extend the sampling period by a factor greater than seven to detect a significant association between helmet wearing and safe/unsafe overtaking distance given a small effect size and identical marginal probabilities.</p>
      <table-wrap id="pone-0058777-t003" position="float">
        <object-id pub-id-type="doi">10.1371/journal.pone.0058777.t003</object-id>
        <label>Table 3</label>
        <caption>
          <title>Observed proportion of helmet use and safe passing manoeuvres from Walker (2007).</title>
        </caption>
        <alternatives>
          <graphic id="pone-0058777-t003-3" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0058777.t003" xlink:type="simple"/>
          <table>
            <colgroup span="1">
              <col align="left" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
              <col align="center" span="1"/>
            </colgroup>
            <thead>
              <tr>
                <td align="left" rowspan="1" colspan="1"/>
                <td align="left" rowspan="1" colspan="1">No Helmet</td>
                <td align="left" rowspan="1" colspan="1">Helmet</td>
                <td align="left" rowspan="1" colspan="1">Total</td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left" rowspan="1" colspan="1">Safe</td>
                <td align="left" rowspan="1" colspan="1">0.491</td>
                <td align="left" rowspan="1" colspan="1">0.462</td>
                <td align="left" rowspan="1" colspan="1">0.953</td>
              </tr>
              <tr>
                <td align="left" rowspan="1" colspan="1">Unsafe</td>
                <td align="left" rowspan="1" colspan="1">0.021</td>
                <td align="left" rowspan="1" colspan="1">0.026</td>
                <td align="left" rowspan="1" colspan="1">0.047</td>
              </tr>
              <tr>
                <td align="left" rowspan="1" colspan="1">Total</td>
                <td align="left" rowspan="1" colspan="1">0.512</td>
                <td align="left" rowspan="1" colspan="1">0.488</td>
                <td align="left" rowspan="1" colspan="1"/>
              </tr>
            </tbody>
          </table>
        </alternatives>
      </table-wrap>
    </sec>
    <sec id="s6">
      <title>Discussion</title>
      <p>We present a demonstration that many contingency table correlation measures are equivalent for the <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e263" xlink:type="simple"/></inline-formula> case and their use is limited due to constraints created by fixed marginal probabilities. The odds ratio, which is a function of these measures for fixed marginal probabilities, is not problematic, is regularly used in statistical analyses and has a direct application to logistic regression. Recommended odds ratios have been proposed from Cohen's small, medium and large effect sizes for <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e264" xlink:type="simple"/></inline-formula> relative to the maximum attainable correlation <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e265" xlink:type="simple"/></inline-formula>. Further, minimal odds ratios can be computed with only knowledge of participant allocation.</p>
      <p>The use of effect size recommendations should be avoided in situations in which clinical or practical differences are known. However, they can help the researcher balance between overly large or overly small sample size calculations when such information is unknown. In these situations, conservative estimates for odds ratio effect sizes can be derived from only the allocation ratio leading to a general result and, when a 1:1 allocation is chosen for optimal power, odds ratios of <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e266" xlink:type="simple"/></inline-formula> and <inline-formula><inline-graphic xlink:href="info:doi/10.1371/journal.pone.0058777.e267" xlink:type="simple"/></inline-formula> correspond to small, medium and large effect sizes.</p>
    </sec>
    <sec id="s7">
      <title>Supporting Information</title>
      <supplementary-material id="pone.0058777.s001" mimetype="text/plain" xlink:href="info:doi/10.1371/journal.pone.0058777.s001" position="float" xlink:type="simple">
        <label>File S1</label>
        <caption>
          <p>
            <bold>SAS Macro to compute sample sizes from marginal probabilities for small, medium and large odds ratios.</bold>
          </p>
          <p>(SAS)</p>
        </caption>
      </supplementary-material>
    </sec>
  </body>
  <back>
    <ack>
      <p>The authors would like to thank Warren May, David Warton and Jakub Stoklosa for their help in the preparation of this manuscript.</p>
    </ack>
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