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<!doctype html> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=utf-8"> <meta http-equiv="Cache-Control" content="no-cache, no-store, must-revalidate"/> <meta http-equiv="Pragma" content="no-cache"/> <meta http-equiv="Expires" content="0"/> <meta content="index,follow" name="Robots"/> <meta name="keywords" content="CRD, Centre for Reviews and Dissemination, NHSCRD, Systematic, Dissemination, Information, DARE, NHS EED, Economic Evaluation Database, medical, evidence-based medicine, EBM, clinical effectiveness, cost-effectiveness, HTA database, health technology assessment, promotion, Cochrane Library, Effective care bulletins, matters"> <meta name="description" content="The Centre for Reviews and Dissemination is a department of the University of York and is part of the National Institute for Health Research. CRD undertakes high quality systematic reviews that evaluate the effects of health and social care interventions and the delivery and organisation of health care."> <meta charset="utf-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"/> <meta name="apple-mobile-web-app-capable" content="yes"> <meta name="apple-mobile-web-app-status-bar-style" content="black"> <meta name="viewport" content="width=device-width, initial-scale=1, maximum-scale=1"> <link rel="apple-touch-icon" href="images/iosicon.png"> <link rel="shortcut icon" href="images/favicon.ico">  <link rel="stylesheet" type="text/css" href="jquery/jquery.mobile-1.4.5.min.css?v=2165790"> <link rel="stylesheet" type="text/css" href="jquery/jquery-ui.css?v=2165790"> <link rel="stylesheet" type="text/css" href="themes/jquery.css?v=2165790"> <link rel="stylesheet" type="text/css" href="css/record.css?v=2165790"> <link rel="stylesheet" type="text/css" href="icons/flaticon.css?v=2165790">   <script src="jquery/jquery-1.11.3.min.js?v=2165790"></script> <script src="jquery/jquery-1.11.0.min.js?v=2165790"></script>  <script src="sitedefinitions.js?v=2165790"></script> <script src="record.js?v=2165790"></script> <script src="jquery/jquery.mobile-1.4.5.min.js?v=2165790"></script> <script src="jquery.ui.touch-punch.js?v=2165790"></script> </head> <body> <div style="display: none" id="recordtype"></div>  <div id="displaydocument"> <div id="documentheader"> <div id="documentheadericons"> <div id="documentheaderuniicon"></div> <div id="documentheadernihricon"><a href="http://www.nihr.ac.uk" target="_blank" class="floatright ui-link" tabindex="-1"><img src="images/nihr-master-logo-325px.png" alt=""> </a></div> </div> <div id="documentheadertext"><a href="" onclick="GoHome()" tabindex="-1" style="font-weight:bold" class="ui-link"> PROSPERO<br> <span style="font-size:0.85em">International prospective register of systematic reviews</span></a></div> </div> <div id="documentControls"> <div class="documentControlsLeft"></div> <div class="documentControlsRight"> <div class="documentControlsButton"><span class="flaticon flaticon-print" onclick="print()" title="Print this review"> Print </span> | <span class="exportpdf flaticon flaticon-pdf" onclick="getPDF();"> PDF </span></div> </div> </div> <div id="documenttitles"> <div id="documenttitlestitle"></div> <div id="documenttitlesauthor"></div> <div id="documenttitlesversion"></div> </div> <div class="content-details"> <div id="documentpublishingnote"></div> <div id="documentamendmentnote"></div> <div id="documentcitation"> <p id="citationdetails"></p> </div> <div id="documentfields"></div> </div> <div id="documentfooter"><p>PROSPERO</p><p>This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.</p></div> </div> <div class="questions" style="display: none"> <div class="questionsScroll"> <ul id="PROSPERO_Clinical_questionlist" data-role="listview" data-inset="true" data-theme="a" data-divider-theme="a" data-corners="true" data-icon="false"> <li data-wmax="50" data-qtype="text_2"><a class="mandatory" href="#question1">1. * Review title.</a> </li> <li data-wmax="50" data-qtype="text_2"><a href="#question2">2. Original language title.</a> </li> <li data-qtype="date"><a class="mandatory" href="#question3">3. * Anticipated or actual start date.</a> </li> <li data-qtype="date"><a class="mandatory" href="#question4">4. * Anticipated completion date.</a> </li> <li data-qtype="q5"><a class="mandatory" href="#question5">5. * Stage of review at time of this submission.</a> </li>  <li data-qtype="text_1"><a class="mandatory" href="#question6">6. * Named contact.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="named_contact"></div> <div data-qtype="text_1" data-subid="named_contact_salutation">Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence:</div> </div> </li> <li data-qtype="text_1"><a class="mandatory" href="#question7">7. * Named contact email.</a> </li> <li data-qtype="text_5"><a href="#question8">8. Named contact address<span class="Q8nb" style="font-size: 0.6em"><br>PLEASE NOTE this information will be published in the PROSPERO record so please do not enter private information, i.e. personal home address</span></a> </li> <li data-qtype="text_1"><a href="#question9">9. Named contact phone number.</a> </li> <li data-qtype="text_1"><a class="mandatory" href="#question10">10. * Organisational affiliation of the review.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="org_affil"></div> <div data-qtype="text_1" data-subid="org_affil_web">Organisation web address:</div> </div> </li> <li data-qtype="reviewteam"><a class="mandatory" href="#question11">11. * Review team members and their organisational affiliations.</a> </li>  <li data-wmax="300" data-qtype="text_8"><a class="mandatory" href="#question12">12. * Funding sources/sponsors.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="funding"></div> <div data-qtype="text_1" data-subid="grantnumber">Grant number(s)<br><span style="font-size: 14px">State the funder, grant or award number and the date of award</span></div> </div> </li> <li data-qtype="conflict"><a class="mandatory" href="#question13">13. * Conflicts of interest.</a> </li> <li data-qtype="reviewteam"><a href="#question14">14. Collaborators.</a> </li>  <li data-wmax="250" data-qtype="text_8"><a class="mandatory" href="#question15">15. * Review question.</a> </li> <li data-wmax="300" data-qtype="text_8"><a class="mandatory" href="#question16">16. * Searches.</a> </li> <li data-qtype="url_search"><a href="#question17">17. URL to search strategy.</a> </li> <li data-wmax="200" data-qtype="text_8"><a class="mandatory" href="#question18">18. * Condition or domain being studied.</a> </li> <li data-wmax="200" data-qtype="text_3"><a class="mandatory" href="#question19">19. * Participants/population.</a> </li> <li data-wmax="200" data-qtype="text_5"><a class="mandatory" href="#question20">20. * Intervention(s), exposure(s).</a> </li> <li data-wmax="200" data-qtype="text_3"><a class="mandatory" href="#question21">21. * Comparator(s)/control.</a> </li> <li data-wmax="150" data-qtype="text_3"><a class="mandatory" href="#question22">22. * Types of study to be included.</a> </li> <li data-wmax="250" data-qtype="text_8"><a href="#question23">23. Context.</a> </li> <li data-wmax="200" data-qtype="text_8"><a class="mandatory" href="#question24">24. * Main outcome(s).</a> <div class="subhead"> <div data-qtype="text_1" data-subid="outcomes"></div> <div data-qtype="text_1" data-subid="timing" data-help="Please specify the effect measure(s) for you main outcome(s) e.g. relative risks, odds ratios, risk difference, and/or 'number needed to treat.">Measures of effect</div> </div> </li> <li data-wmax="300" data-qtype="text_8"><a class="mandatory" href="#question25">25. * Additional outcome(s).</a> <div class="subhead"> <div data-qtype="text_1" data-subid="outcomes"></div>  <div data-qtype="text_1" data-subid="timing" data-help="Please specify the effect measure(s) for you additional outcome(s) e.g. relative risks, odds ratios, risk difference, and/or 'number needed to treat.">Measures of effect</div> </div> </li> <li data-wmax="300" data-qtype="text_8"><a class="mandatory" href="#question26">26. * Data extraction (selection and coding).</a> </li> <li data-wmax="200" data-qtype="text_8"><a class="mandatory" href="#question27">27. * Risk of bias (quality) assessment.</a> </li> <li data-wmax="400" data-qtype="text_8"><a class="mandatory" href="#question28">28. * Strategy for data synthesis.</a> </li> <li data-wmax="250" data-qtype="text_8"><a class="mandatory" href="#question29">29. * Analysis of subgroups or subsets.</a> </li>  <li data-qtype="methods"><a class="mandatory" href="#question30">30. * Type and method of review.</a> </li> <li data-qtype="language"><a href="#question31">31. Language.</a> </li> <li data-qtype="country"><a class="mandatory" href="#question32">32. * Country.</a> </li> <li data-wmax="50" data-qtype="text_5"><a href="#question33">33. Other registration details.</a> </li> <li data-qtype="url_published"><a href="#question34">34. Reference and/or URL for published protocol.</a> </li> <li data-wmax="100" data-qtype="dissemination"><a href="#question35">35. Dissemination plans.</a> </li> <li data-qtype="text_8"><a href="#question36">36. Keywords.</a> </li> <li data-wmax="50" data-qtype="text_8"><a href="#question37">37. Details of any existing review of the same topic by the same authors.</a> </li> <li data-qtype="status"><a class="mandatory" href="#question38">38. * Current review status.</a> </li> <li data-qtype="text_5"><a href="#question39">39. Any additional information.</a> </li> <li data-wmax="100" data-qtype="final"><a href="#question40">40. Details of final report/publication(s) or preprints if available.</a> </li> <li data-wmax="100" class="managementquestion" data-qtype="mesh"><a href="#question41"> * MeSH headings.</a> </li> </ul> <ul id="PROSPERO_Animal_questionlist" data-role="listview" data-inset="true" data-theme="a" data-divider-theme="a" data-corners="true" data-icon="false"> <li data-qtype="text_2"><a class="mandatory" href="#question1">1. * Review title.</a> </li> <li data-qtype="text_2"><a href="#question2">2. Original language title.</a> </li> <li data-qtype="date"><a class="mandatory" href="#question3">3. * Anticipated or actual start date.</a> </li> <li data-qtype="date"><a class="mandatory" href="#question4">4. * Anticipated completion date.</a> </li> <li data-qtype="q5" class="summary"><a class="mandatory" href="#question5">5. * Stage of review at time of this submission.</a> </li>  <li data-qtype="text_1"><a class="mandatory" href="#question6">6. * Named contact.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="named_contact"></div> <div data-qtype="text_1" data-subid="named_contact_salutation">Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence:</div> </div> </li> <li data-qtype="text_1"><a class="mandatory" href="#question7">7. * Named contact email.</a> </li> <li data-qtype="text_5"><a class="mandatory" href="#question8">8. * Named contact address.<br><span class="Q8nb" style="font-size: 0.6em">PLEASE NOTE this information will be published in the PROSPERO record so please do not enter private information</span></a> </li> <li data-qtype="text_1"><a href="#question9">9. Named contact phone number</a> </li> <li data-qtype="text_1"><a class="mandatory" href="#question10">10. * Organisational affiliation of the review.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="org_affil"></div> <div data-qtype="text_1" data-subid="org_affil_web">Organisation web address:</div> </div> </li> <li data-qtype="reviewteam"><a class="mandatory" href="#question11">11. * Review team members and their organisational affiliations.</a> </li>  <li data-wmax="300" data-qtype="text_8"><a class="mandatory" href="#question12">12. * Funding sources/sponsors.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="funding"></div> <div data-qtype="text_1" data-subid="grantnumber">Grant number(s)</div> </div> </li> <li data-qtype="conflict"><a class="mandatory" href="#question13">13. * Conflicts of interest.</a> </li> <li data-qtype="reviewteam"><a href="#question14">14. Collaborators.</a> </li>  <li data-qtype="text_8"><a class="mandatory" href="#question15">15. * Review question.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="reviewq"></div> <div data-qtype="text_1" data-subid="reviewq_context" data-help="Provide a brief description of the context and rationale of the review, including information on the relevance of your review for human health (max 250 words).">Context and rationale</div> </div> </li> <li data-qtype="text_8"><a class="mandatory" href="#question16">16. * Searches.</a> </li> <li data-qtype="url_search"><a href="#question17">17. URL to search strategy.</a> </li> <li data-qtype="text_8"><a class="mandatory" href="#question18">18. * Human disease modelled.</a> </li> <li data-qtype="text_3"><a class="mandatory" href="#question19">19. * Animals/population.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="population_included">Inclusion criteria:</div> <div data-qtype="text_1" data-subid="population_excluded">Exclusion criteria:</div> </div> </li> <li data-qtype="text_5"><a class="mandatory" href="#question20">20. * Intervention(s), exposure(s).</a> <div class="subhead"> <div data-qtype="text_1" data-subid="intervention_included">Inclusion criteria:</div> <div data-qtype="text_1" data-subid="intervention_excluded">Exclusion criteria:</div> </div> </li> <li data-qtype="text_3"><a class="mandatory" href="#question21">21. * Comparator(s)/control.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="comparator_included">Inclusion criteria:</div> <div data-qtype="text_1" data-subid="comparator_excluded">Exclusion criteria:</div> </div> </li> <li data-qtype="text_3"><a class="mandatory" href="#question22">22. * Study designs to be included.</a> <div class="subhead"> <div data-qtype="text_1" data-subid="type_included">Inclusion criteria:</div> <div data-qtype="text_1" data-subid="type_excluded">Exclusion criteria:</div> </div> </li> <li data-qtype="text_8"><a href="#question23">23. Other selection criteria or limitations applied.</a> </li> <li data-qtype="text_8"><a class="mandatory" href="#question24">24. * Outcome measure(s).</a> <div class="subhead"> <div data-qtype="text_1" data-subid="outcome_included">Inclusion criteria:</div> <div data-qtype="text_1" data-subid="outcome_excluded">Exclusion criteria:</div> </div> </li> <li data-qtype="na"><a href="#question25">25. N/A.</a> </li> <li data-qtype="text_16"><a class="mandatory" href="#question26">26. * Study selection and data extraction.</a> <div class="subhead"> <div data-qtype="text_5" data-subid="da_study_selection" data-help="Give the procedure for selecting studies for the review, including the screening phases (title and/or title-abstract and/or full-text), the number of researchers involved, and how discrepancies will be resolved.<span class='showHelpextra'> <b>Example:</b> Screening will be performed in two phases, namely initial screening based on title and abstract, followed by full-text screening of the eligible articles for final inclusion. In each phase, 2 observers will independently assess each article. Discrepancies will be resolved through discussion, or by consulting a third investigator.</span>">Procedure for study selection</div> <div data-qtype="text_5" data-subid="da_screening" data-help="Multiple exclusion criteria may apply to an abstract/paper, which can cause discrepancies between reviewers in the reason for exclusion recorded. To avoid this, it is helpful to prioritize the exclusion criteria (e.g. 1) not an animal study; 2) not a myocardial infarction model, etc.) and record the highest ranking applicable criterion as the reason for exclusion. Please sort the exclusion criteria defined in questions 19 to 24. If applicable, do so for each screening phase.<span class='showHelpextra'><b>Example</b>:<br>Title-abstract screening: <br>1. Not an original full research paper (e.g. review, editorial) <br>2. Not an in vivo animal study <br>3. No metastases/ only primary tumor <br>4. No control group <br>5. Combination therapy or contamination <br>6. Not about analgesics used in the clinic<br><br>Full text-screening: <br>As above, with the addition of:<br>7. No relevant outcome measure reported</span>">Prioritise the exclusion criteria</div> <div data-qtype="text_5" data-subid="da_extraction" data-help="Describe methods for data extraction, including the number of reviewers performing data extraction, extraction of data from text and/or graphs, whether and how authors of eligible studies will be contacted to provide missing or additional data, etc.<span class='showHelpextra'><b>Example:</b> Two reviewers will independently extract data from each article. We first try to extract numerical data from tables, text or figures. If these are not reported, we will extract data from graphs using digital ruler software. In case data are not reported or unclear, we will attempt to contact authors by e-mail (max. 2 attempts). In case an outcome is measured at multiple time points, data from the time point where efficacy is highest will be included.</span>">Methods for data extraction</div> <div data-qtype="text_5" data-subid="da_study_design" data-help="Specify the data to be extracted related to characteristics of the study design, e.g. controlled versus cross-over, number of experimental groups, etc.<span class='showHelpextra'><b>Example:</b> Experimental groups, control group(s) and number of animals per group.</span>">Data to be extracted: study design</div> <div data-qtype="text_5" data-subid="da_animal_model" data-help="Specify the data to be extracted related to characteristics of the animal model, e.g. species, sex of the animals, etc.<span class='showHelpextra'><b>Example:</b> Species, sex, weight, age, co‐morbidity, anaesthetic agent used, method of induction of cardiac ischemia, duration of ischemia and duration of reperfusion (if applicable).</span>">Data to be extracted: animal model</div> <div data-qtype="text_5" data-subid="da_study_intervention" data-help="Specify the data to be extracted related to characteristics of the intervention of interest, e.g. dose, timing, etc.<span class='showHelpextra'><b>Example:</b> Dose, timing of administration, frequency of administration, route of administration, vehicle.</span>">Data to be extracted: intervention of interest</div> <div data-qtype="text_5" data-subid="da_study_primary" data-help="Define the primary outcome measure(s). For each outcome measure, specify in which format data will be extracted, including the eligible units of measurement, and data type (continuous/dichotomous). A description of any other manipulation or transformation of the extracted data that is planned may be included.<span class='showHelpextra'><b>Example:</b> Serum creatinine; continuous; umol/L (may be recalculated from mg/dL).</span>">Data to be extracted: primary outcome(s)</div> <div data-qtype="text_5" data-subid="da_study_secondary" data-help="Define the secondary outcome measure(s). For each outcome measure, specify in which format data will be extracted, including the eligible units of measurement, and data type (continuous/dichotomous). A description of any other manipulation or transformation of the extracted data that is planned may be included.<span class='showHelpextra'><b>Example:</b> Blood urea nitrogen; continuous; mmol/L (may be recalculated from mg/dL); Renal histological damage as assessed by Jablonski scale; continuous; Jablonski score.</span>">Data to be extracted: secondary outcome(s)</div> <div data-qtype="text_5" data-subid="da_other" data-help="Specify any other data or study characteristics to be extracted, e.g. bibliographical details, such as author, year and language.<span class='showHelpextra'><b>Example:</b> 1st author, year of publication, language, journal.</span>">Data to be extracted: other</div> </div> </li> <li data-qtype="syrcle_rob"><a class="mandatory" href="#question27">27. * Risk of bias and/or quality assessment.</a> </li> <li data-qtype="text_8"><a class="mandatory" href="#question28">28. * Strategy for data synthesis.</a> <div class="subhead"> <div data-qtype="text_5" data-subid="syn_approach" data-help="For each outcome measure, specify whether a quantitative or narrative synthesis is planned and how this decision will be made.<span class='showHelpextra'><a href='http://ilarjournal.oxfordjournals.org/content/55/3/418.full' target='_blank' tabindex='-1'>An introduction</a> as well as a <a href='http://www.dcn.ed.ac.uk/camarades/files/Vesterinen2014_JNeurosciMethods.pdf' target='_blank' tabindex='-1'>practical guide</a> to meta-analysis of pre-clinical studies are available.<br><br><b>Example:</b> A meta‐analysis will be performed for all outcome measures reported in 10 or more articles. For subgroup analysis a minimum of 8 studies per subgroup is required. If meta‐analysis is not possible, data will be reported through a descriptive summary.</span>">Planned approach</div> <div data-qtype="na" data-subid="syn_meta_analysis" data-help="<b>If a meta-analysis is planned</b>, please specify the following:"></div> <div data-qtype="text_5" data-subid="syn_measure" data-help="For each outcome measure, specify the effect measure to be used (e.g. mean difference, odds ratio etc.).<span class='showHelpextra'><b>Example:</b> number of metastases: standardized mean difference; incidence of metastasis: risk ratio.</span>">Effect measure</div> <div data-qtype="text_5" data-subid="syn_model" data-help="For each outcome measure, specify the statistical model of analysis (e.g. random-effects or fixed-effect model).<span class='showHelpextra'>The random-effects model is the typical model of choice for pre-clinical meta-analyses. This is because in the fixed-effect model, it is assumed that the differences in <i>observed</i> effect between studies is solely due to sampling error (i.e. differences in sample size), and that the <i>true</i> effect is the same (fixed) across all studies. However, this assumption is unlikely to hold true for data from animal studies, which generally include various species, strains and treatment regimes, for which different true effects are likely to exist. The random-effects model takes into account both the within-study (sampling error) and between-study (differences in the true effect size) variance. Should the excessive between-study variance be very low or zero, the random-effects model will yield the same results as the fixed-effect model. For further details, see the <a href='http://ilarjournal.oxfordjournals.org/content/55/3/418.full' target='_blank' tabindex='-1'>introduction</a> and <a href='http://www.dcn.ed.ac.uk/camarades/files/Vesterinen2014_JNeurosciMethods.pdf' target='_blank' tabindex='-1'>practical guide</a> to pre-clinical meta-analysis.<br><br><b>Example:</b> Because of the exploratory nature of animal studies, a random effects model will be used to account for anticipated heterogeneity.</span>">Effect models</div> <div data-qtype="text_5" data-subid="syn_heterogeneity" data-help="Specify the statistical methods to assess heterogeneity (e.g. I², Q). For further guidance please refer to the <a href='http://ilarjournal.oxfordjournals.org/content/55/3/418.full' target='_blank' tabindex='-1'>introduction</a> and <a href='http://www.dcn.ed.ac.uk/camarades/files/Vesterinen2014_JNeurosciMethods.pdf' target='_blank' tabindex='-1'>practical guide</a> to pre-clinical meta-analysis.<span class='showHelpextra'><b>Example:</b> Heterogeneity will be assessed using the (residual) I2 and adjusted R2 statistics.</span>">Heterogeneity</div> <div data-qtype="text_5" data-subid="syn_other" data-help="Specify other details of the meta-analysis methodology (e.g. correction for multiple testing, correction for multiple use of control group).<span class='showHelpextra'>For further guidance please refer to the <a href='http://ilarjournal.oxfordjournals.org/content/55/3/418.full' target='_blank' tabindex='-1'>introduction</a> and <a href='http://www.dcn.ed.ac.uk/camarades/files/Vesterinen2014_JNeurosciMethods.pdf' target='_blank' tabindex='-1'>practical guide</a> to pre-clinical meta-analysis.<br><br><b>Example:</b> Whenever a control group serves more than one experimental group, we will correct the total number of control animals in the meta-analysis by dividing the number of animals in the control group by the number of treatment groups served. Where applicable, Holm-Bonferroni correction for testing multiple subgroup analyses will be performed. If one or more subgroup analyses cannot be performed due to insufficient data, the p-value will be adjusted accordingly.</span>">Other</div> </div> </li> <li data-qtype="text_8"><a class="mandatory" href="#question29">29. * Analysis of subgroups or subsets.</a> <div class="subhead"> <div data-qtype="text_5" data-subid="sg_groups" data-help="Give any planned exploration of subgroups or subsets within the review. ‘None planned’ is a valid response if no subgroup analyses are planned.<span class='showHelpextra'>Subgroup analysis or meta-regression are used to explore between-study heterogeneity and can provide insight into the relationship between study characteristics (e.g. species, sex or drug class or dose) and effect size. They should be considered hypothesis-generating. Ideally, a threshold describing the number of studies per subgroup required for analysis should be specified. For further guidance please refer to the <a href='http://ilarjournal.oxfordjournals.org/content/55/3/418.full' target='_blank' tabindex='-1'>introduction</a> and <a href='http://www.dcn.ed.ac.uk/camarades/files/Vesterinen2014_JNeurosciMethods.pdf' target='_blank' tabindex='-1'>practical guide</a> to pre-clinical meta-analysis.<br><br><b>Example:</b> The following study characteristics will be examined as potential source of heterogeneity: species (stratified per species); sex (stratified per sex); duration of index ischemia (linear); stem cell dose (linear); blinding of outcome assessment reported (stratified yes vs no). For stratified analyses, a minimum number of 8 studies per subgroup is required.</span>">Subgroup analyses</div> <div data-qtype="text_5" data-subid="sg_sensitivity" data-help="For each outcome measure, specify any sensitivity analyses you propose to perform.<span class='showHelpextra'>A sensitivity analysis is conducted to assess the impact of decisions taken in the review process on the meta-analysis outcome. These decisions may have been made in various stages of the review, e.g. the decision to exclude certain disease models, the decision to pool certain units of measurement for an outcome, the choice of effect measure, how subgroup variables are stratified etc. In order to assess the robustness of the findings of the meta-analysis, the analyses are re-run using the alternative options for each decision. If the results of both meta-analyses are similar, the results seem robust. When the conclusions of a meta-analysis significantly change, this should be discussed.<br><br><b>Example:</b> To test the robustness of our findings when selecting the time point of greatest efficacy we will re-run the analysis with data from the latest possible time point (in studies reporting an outcome at multiple time points). We will test the robustness of linear regression of time-to-treatment by performing stratified analysis (treatment pre-ischemia vs during vs post-ischemia). We will assess the effect of our decision to pool all reported scales for histological damage by re-running the analyses using only data from studies using the Jablonski scale.</span>">Sensitivity</div> <div data-qtype="text_5" data-subid="sg_pub_bias" data-help="Specify whether an assessment of publication bias is planned. If applicable, specify the method for assessment of publication bias.<span class='showHelpextra'><br><b>Example: </b> For meta-analyses using the mean difference or risk ration as effect measure and containing at least 20 studies, we will produce funnel plots and assess publication bias using Egger’s regression test.</span>">Publication bias</div> </div> </li>  <li data-qtype="methods"><a class="mandatory" href="#question30">30. * Review type.</a> </li> <li data-qtype="language"><a href="#question31">31. Language.</a> </li> <li data-qtype="country" class="summary mandatory"><a href="#question32">32. * Country.</a> </li> <li data-qtype="text_5"><a href="#question33">33. Other registration details.</a> </li> <li data-qtype="url_published"><a href="#question34">34. Reference and/or URL for published protocol.</a> </li> <li data-qtype="dissemination"><a class="mandatory" href="#question35">35. Dissemination plans.</a> </li> <li data-qtype="text_8"><a class="mandatory" href="#question36">36. * Keywords.</a> </li> <li data-qtype="text_8"><a href="#question37">37. Details of any existing review of the same topic by the same authors.</a> </li> <li data-qtype="status"><a class="mandatory" href="#question38">38. * Current review status.</a> </li> <li data-qtype="text_5"><a href="#question39">39. Any additional information.</a> </li> <li data-qtype="final"><a href="#question40">40. Details of final report/publication(s) or preprints if available.</a> </li> <li class="managementquestion" data-qtype="mesh"><a href="#question41"> * MeSH headings.</a> </li> </ul> </div> </div><form id="pdfform" action="export_record_pdf.php" method="post" enctype="application/x-www-form-urlencoded" target="_blank"> <input type="text" name="html" id="pdfoutput" value=""/> <input type="text" name="pdftitle" id="pdftitle" value=""/> <input type="text" name="pdfauthors" id="pdfauthors" value=""/> <input type="text" name="pdfversions" id="pdfversions" value=""/> <input type="text" name="pdfdisclaimer" id="pdfdisclaimer" value=""/> <input type="hidden" name="pdfrecordid" id="pdfrecordid" value=""/> <input type="hidden" name="userID" value="0"/> </form> </body> <script> populateRecord(403467, 0, 'DISPLAY'); function getPDF() { //$("#pdfoutput").val($("#displaydocument .content-details").html()); var pdfcontent = $(".content-details").html().replace(/[\n\r]/g, ''); var pdftitle = "<h1>" + $("#documenttitlestitle").html().replace(/[\n\r]/g, '') + "</h1>"; // GD 2022-10-11 title was not displaying pdfcontent = pdftitle + pdfcontent; var pdfauthors = $("#documenttitlesauthor").html().replace(/[\n\r]/g, ''); var pdfversions = $("#documenttitlesversion").html().replace(/[\n\r]/g, ''); var pdfnotes = $("#documentpublishingnote").html().replace(/[\n\r]/g, ''); var pdfdisclaimer = $("#documentfooter").html().replace(/[\n\r]/g, ''); $("#pdfoutput").val(pdfcontent); $("#pdftitle").val(pdftitle); $("#pdfauthors").val(pdfauthors); $("#pdfversions").val(pdfversions); $("#pdfdisclaimer").val(pdfdisclaimer); $("#pdfform").submit(); } </script> </html>