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Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically

Identifieur interne : 001796 ( Ncbi/Merge ); précédent : 001795; suivant : 001797

Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically

Auteurs : Emily S. Sena [Royaume-Uni, Australie] ; Gillian L. Currie [Royaume-Uni] ; Sarah K. Mccann [Australie] ; Malcolm R. Macleod [Royaume-Uni] ; David W. Howells [Australie]

Source :

RBID : PMC:4013765

Abstract

The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular diseases. Empirical evidence suggests that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. The aim of this review is to describe the concepts of systematic review and meta-analysis and consider how these tools may be used to provide empirical evidence to spur the field to improve the rigor of the conduct and reporting of preclinical research akin to their use in improving the conduct and reporting of randomized controlled trials in clinical research. As with other research domains, systematic reviews are subject to bias. Therefore, we have also suggested guidance for their conduct, reporting, and critical appraisal.


Url:
DOI: 10.1038/jcbfm.2014.28
PubMed: 24549183
PubMed Central: 4013765

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PMC:4013765

Le document en format XML

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<author>
<name sortKey="Kilkenny, C" uniqKey="Kilkenny C">C Kilkenny</name>
</author>
<author>
<name sortKey="Browne, Wj" uniqKey="Browne W">WJ Browne</name>
</author>
<author>
<name sortKey="Cuthill, Ic" uniqKey="Cuthill I">IC Cuthill</name>
</author>
<author>
<name sortKey="Emerson, M" uniqKey="Emerson M">M Emerson</name>
</author>
<author>
<name sortKey="Altman, Dg" uniqKey="Altman D">DG Altman</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Landis, Sc" uniqKey="Landis S">SC Landis</name>
</author>
<author>
<name sortKey="Amara, Sg" uniqKey="Amara S">SG Amara</name>
</author>
<author>
<name sortKey="Asadullah, K" uniqKey="Asadullah K">K Asadullah</name>
</author>
<author>
<name sortKey="Austin, Cp" uniqKey="Austin C">CP Austin</name>
</author>
<author>
<name sortKey="Blumenstein, R" uniqKey="Blumenstein R">R Blumenstein</name>
</author>
<author>
<name sortKey="Bradley, Ew" uniqKey="Bradley E">EW Bradley</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Egan, Kj" uniqKey="Egan K">KJ Egan</name>
</author>
<author>
<name sortKey="Sena, Es" uniqKey="Sena E">ES Sena</name>
</author>
<author>
<name sortKey="Vesterinen, Hm" uniqKey="Vesterinen H">HM Vesterinen</name>
</author>
<author>
<name sortKey="Macleod, Mr" uniqKey="Macleod M">MR Macleod</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
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<author>
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<author>
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</author>
<author>
<name sortKey="Macleod, Mr" uniqKey="Macleod M">MR Macleod</name>
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</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Frantzias, J" uniqKey="Frantzias J">J Frantzias</name>
</author>
<author>
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</author>
<author>
<name sortKey="Salman, Ra S" uniqKey="Salman R">RA-S Salman</name>
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</analytic>
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<biblStruct>
<analytic>
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<author>
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<biblStruct>
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</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Cereb Blood Flow Metab</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Cereb. Blood Flow Metab</journal-id>
<journal-title-group>
<journal-title>Journal of Cerebral Blood Flow & Metabolism</journal-title>
</journal-title-group>
<issn pub-type="ppub">0271-678X</issn>
<issn pub-type="epub">1559-7016</issn>
<publisher>
<publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">24549183</article-id>
<article-id pub-id-type="pmc">4013765</article-id>
<article-id pub-id-type="pii">jcbfm201428</article-id>
<article-id pub-id-type="doi">10.1038/jcbfm.2014.28</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically</article-title>
<alt-title alt-title-type="running">Systematic review and meta-analysis: why and how?</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Sena</surname>
<given-names>Emily S</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
<xref ref-type="corresp" rid="caf1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Currie</surname>
<given-names>Gillian L</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McCann</surname>
<given-names>Sarah K</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Macleod</surname>
<given-names>Malcolm R</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Howells</surname>
<given-names>David W</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<aff id="aff1">
<label>1</label>
<institution>Department of Clinical Neurosciences, University of Edinburgh</institution>
, Edinburgh,
<country>UK</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>Stroke Division, Florey Institute of Neuroscience and Mental Health</institution>
, Melbourne, Victoria,
<country>Australia</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="caf1">
<label>*</label>
<institution>Department of Clinical Neurosciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent</institution>
, Edinburgh EH16 4SB,
<country>UK</country>
. E-mail:
<email>emily.sena@ed.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>05</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>19</day>
<month>02</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>1</day>
<month>5</month>
<year>2014</year>
</pub-date>
<volume>34</volume>
<issue>5</issue>
<fpage>737</fpage>
<lpage>742</lpage>
<history>
<date date-type="received">
<day>11</day>
<month>12</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>21</day>
<month>01</month>
<year>2014</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2014 International Society for Cerebral Blood Flow & Metabolism, Inc.</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>International Society for Cerebral Blood Flow & Metabolism, Inc.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/">
<pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/</license-p>
</license>
</permissions>
<abstract>
<p>The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular diseases. Empirical evidence suggests that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. The aim of this review is to describe the concepts of systematic review and meta-analysis and consider how these tools may be used to provide empirical evidence to spur the field to improve the rigor of the conduct and reporting of preclinical research akin to their use in improving the conduct and reporting of randomized controlled trials in clinical research. As with other research domains, systematic reviews are subject to bias. Therefore, we have also suggested guidance for their conduct, reporting, and critical appraisal.</p>
</abstract>
<kwd-group>
<kwd>acute stroke</kwd>
<kwd>animal models</kwd>
<kwd>basic science</kwd>
<kwd>Biostatistics</kwd>
<kwd>experimental</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="fig1">
<label>Figure 1</label>
<caption>
<p>The effect of the mean sample size on the estimate of effect size for neurobehavioural score in models of encephalomyelitis. The horizontal gray bar represents the 95% confidence limits for the summary estimate of effect. The vertical error bars represent the 95% confidence intervals for the individual estimate. The widths of the bar represent the log of the number of animals contributing to that comparison.
<sup>
<xref ref-type="bibr" rid="bib11">11</xref>
</sup>
</p>
</caption>
<graphic xlink:href="jcbfm201428f1"></graphic>
</fig>
<fig id="fig2">
<label>Figure 2</label>
<caption>
<p>Publication bias. Plots describing (
<bold>A</bold>
) funnel plot, (
<bold>B</bold>
) Egger regression, and (
<bold>C</bold>
) trim-and-fill.
<sup>
<xref ref-type="bibr" rid="bib9">9</xref>
</sup>
</p>
</caption>
<graphic xlink:href="jcbfm201428f2"></graphic>
</fig>
<table-wrap id="tbl1">
<label>Table 1</label>
<caption>
<title>Number and percentages of studies across the modeling of different neurologic diseases reporting measures to reduce the risk of bias</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="char" char="."></col>
<col align="char" char="("></col>
<col align="char" char="("></col>
<col align="center"></col>
<col align="char" char="("></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" char="." charoff="50">
<italic>Number of publications</italic>
</th>
<th align="center" valign="top" char="(" charoff="50">
<italic>Masked assessment of outcome (%)</italic>
</th>
<th align="center" valign="top" char="(" charoff="50">
<italic>Random allocation to group (%)</italic>
</th>
<th align="center" valign="top" charoff="50">
<italic>Allocation concealment (%)</italic>
</th>
<th align="center" valign="top" char="(" charoff="50">
<italic>Sample size calculation (%)</italic>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">Alzheimer's disease
<sup>
<xref ref-type="bibr" rid="bib30">30</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">428</td>
<td align="char" valign="top" char="(" charoff="50">95 (22)</td>
<td align="char" valign="top" char="(" charoff="50">67 (16)</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="char" valign="top" char="(" charoff="50">0 (0)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Multiple sclerosis
<sup>
<xref ref-type="bibr" rid="bib11">11</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">1,117</td>
<td align="char" valign="top" char="(" charoff="50">178 (16)</td>
<td align="char" valign="top" char="(" charoff="50">106 (9)</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="char" valign="top" char="(" charoff="50">2 (<1)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Parkinson's disease
<sup>
<xref ref-type="bibr" rid="bib31">31</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">252</td>
<td align="char" valign="top" char="(" charoff="50">38 (15)</td>
<td align="char" valign="top" char="(" charoff="50">40 (16)</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="char" valign="top" char="(" charoff="50">1 (<1)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Intracerebral hemorrhage
<sup>
<xref ref-type="bibr" rid="bib32">32</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">88</td>
<td align="char" valign="top" char="(" charoff="50">43 (49)</td>
<td align="char" valign="top" char="(" charoff="50">27 (31)</td>
<td align="char" valign="top" char="(" charoff="50">7 (8)</td>
<td align="char" valign="top" char="(" charoff="50">0 (0)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="." charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
<td align="char" valign="top" char="(" charoff="50"> </td>
</tr>
<tr>
<td colspan="6" align="left" valign="top" charoff="50">
<italic>Focal ischemia</italic>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> NXY 059
<sup>
<xref ref-type="bibr" rid="bib13">13</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">9</td>
<td align="char" valign="top" char="(" charoff="50">4 (44)</td>
<td align="char" valign="top" char="(" charoff="50">3 (33)</td>
<td align="char" valign="top" char="(" charoff="50">5 (56)</td>
<td align="char" valign="top" char="(" charoff="50">2 (22)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Hypothermia
<sup>
<xref ref-type="bibr" rid="bib12">12</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">101</td>
<td align="char" valign="top" char="(" charoff="50">38 (38)</td>
<td align="char" valign="top" char="(" charoff="50">36 (36)</td>
<td align="char" valign="top" char="(" charoff="50">4 (4)</td>
<td align="char" valign="top" char="(" charoff="50">0 (0)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Erythropoietin
<sup>
<xref ref-type="bibr" rid="bib33">33</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">19</td>
<td align="char" valign="top" char="(" charoff="50">8 (42)</td>
<td align="char" valign="top" char="(" charoff="50">7 (37)</td>
<td align="char" valign="top" char="(" charoff="50">4 (21)</td>
<td align="char" valign="top" char="(" charoff="50">0 (0)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> Tirilazad
<sup>
<xref ref-type="bibr" rid="bib34">34</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">18</td>
<td align="char" valign="top" char="(" charoff="50">13 (72)</td>
<td align="char" valign="top" char="(" charoff="50">12 (67)</td>
<td align="char" valign="top" char="(" charoff="50">1 (6)</td>
<td align="char" valign="top" char="(" charoff="50">0 (0)</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> tPA
<sup>
<xref ref-type="bibr" rid="bib14">14</xref>
</sup>
</td>
<td align="char" valign="top" char="." charoff="50">113</td>
<td align="char" valign="top" char="(" charoff="50">24 (21)</td>
<td align="char" valign="top" char="(" charoff="50">42 (37)</td>
<td align="char" valign="top" char="(" charoff="50">23 (20)</td>
<td align="char" valign="top" char="(" charoff="50">8 (7)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1-fn1">
<p>NA, not applicable; tPA, tissue plasminogen activator.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tbl2">
<label>Table 2</label>
<caption>
<title>Guidelines for reporting systematic reviews and meta-analyses of animal studies</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="left"></col>
</colgroup>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">Title</td>
<td align="left" valign="top" charoff="50">Identify the report as a systematic review and/or meta-analysis of animal experiments.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Abstract</td>
<td align="left" valign="top" charoff="50">Provide a structured abstract covering the following: objectives, data sources, review methods, results, and conclusion.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Introduction</td>
<td align="left" valign="top" charoff="50">Clearly defined and focussed research question.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="left" valign="top" charoff="50"> </td>
</tr>
<tr>
<td colspan="2" align="left" valign="top" charoff="50">
<italic>Methods</italic>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Protocol</td>
<td align="left" valign="top" charoff="50">Indicate if a protocol exists and where it can be found (i.e., web address).</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Searching</td>
<td align="left" valign="top" charoff="50">Describe the information sources in detail, including keywords, search strategy, any restrictions, and special efforts to include all available data.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Selection</td>
<td align="left" valign="top" charoff="50">Describe the inclusion and exclusion criteria.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Validity and quality assessment</td>
<td align="left" valign="top" charoff="50">Describe the criteria and process used to assess validity.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Data abstraction</td>
<td align="left" valign="top" charoff="50">Describe the process or processes used (e.g., completed independently, in duplicate).</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="left" valign="top" charoff="50">Describe whether aggregate data or individual animal data are abstracted.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Study characteristics</td>
<td align="left" valign="top" charoff="50">Describe the study characteristics relevant to your research question.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Quantitative data synthesis</td>
<td align="left" valign="top" charoff="50">Describe the principal measures of effect, method of combining results, handling of missing data; how statistical heterogeneity was assessed; and any assessment of publication bias—all in enough detail to allow replication.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="left" valign="top" charoff="50"> </td>
</tr>
<tr>
<td colspan="2" align="left" valign="top" charoff="50">
<italic>Results</italic>
</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Flow chart</td>
<td align="left" valign="top" charoff="50">A meta-analysis profile summarizing study flow giving total number of experiments in the meta-analysis.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Study characteristics</td>
<td align="left" valign="top" charoff="50">Descriptive data for each experiment.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold></bold>
Quantitative data synthesis</td>
<td align="left" valign="top" charoff="50">Present simple summary results (e.g., forest plot); identify sources of heterogeneity, impact of study quality, and publication bias.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Discussion</td>
<td align="left" valign="top" charoff="50">Summarize the main findings; discuss limitations; provide general interpretation of the results in the context of other findings, and implications for future research.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Funding</td>
<td align="left" valign="top" charoff="50">Describe sources of funding for the review and other support. The role of funders should be presented.</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Conflict of interest</td>
<td align="left" valign="top" charoff="50">Any potential conflict of interests should be reported.</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tbl3">
<label>Table 3</label>
<caption>
<title>Points to consider in the critical appraisal of systematic reviews and meta-analyses of animal studies</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th align="left" valign="top" charoff="50"> </th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">1. Does the study follow a pre-specified protocol?</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">2. Was the research question focused and clearly defined?</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">3. Are the inclusion criteria appropriate?</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">4. How comprehensive was the search strategy?</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">5. Was the data abstraction from each study appropriate?</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">6. Were the data pooled appropriately?</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Royaume-Uni</li>
</country>
</list>
<tree>
<country name="Royaume-Uni">
<noRegion>
<name sortKey="Sena, Emily S" sort="Sena, Emily S" uniqKey="Sena E" first="Emily S" last="Sena">Emily S. Sena</name>
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<name sortKey="Currie, Gillian L" sort="Currie, Gillian L" uniqKey="Currie G" first="Gillian L" last="Currie">Gillian L. Currie</name>
<name sortKey="Macleod, Malcolm R" sort="Macleod, Malcolm R" uniqKey="Macleod M" first="Malcolm R" last="Macleod">Malcolm R. Macleod</name>
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<name sortKey="Mccann, Sarah K" sort="Mccann, Sarah K" uniqKey="Mccann S" first="Sarah K" last="Mccann">Sarah K. Mccann</name>
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   |texte=   Systematic reviews and meta-analysis of preclinical studies: why perform them and how to appraise them critically
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