Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study
Objective To examine the presence and extent of small study effects in clinical osteoarthritis research.Design Meta-epidemiological study.Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control i...
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| Veröffentlicht in: | BMJ 2010-07, Vol.341 (7766), p.241-241 |
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| creator | Nüesch, Eveline Trelle, Sven Reichenbach, Stephan Rutjes, Anne W S Tschannen, Beatrice Altman, Douglas G Egger, Matthias Jüni, Peter |
| description | Objective To examine the presence and extent of small study effects in clinical osteoarthritis research.Design Meta-epidemiological study.Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients’ reported pain as an outcome.Methods We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials.Results On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes −0.21, 95% confidence interval −0.34 to −0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates.Conclusions Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed. |
| doi_str_mv | 10.1136/bmj.c3515 |
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| fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2905513</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>20734961</jstor_id><sourcerecordid>20734961</sourcerecordid><originalsourceid>FETCH-LOGICAL-b578t-d36bce65f35683fa7708b168a13d43e4fb94d1b9f9a6f91b9baa1e1cc77690133</originalsourceid><addsrcrecordid>eNqF0l2L1DAUBuAgijuMe-EPUIoK4kXXpCefXggy-MmiF-qKVyFt092MbTMmqTj_3sx2HFZhFQIJvA-HcHgRukvwCSHAn9bD-qQBRtgNtCCUy5JJgJtogRVTpSQgj9BxjGuMcQVCKs5uo6MKc1CVogv09eNg-r6IaWq3he0626RYuLEYbDKlGU2_jTYWvit8TNabkC6CSy4WKTjTx2ezsxvX2sH53p-7xuyn3UG3ukzs8f5eos-vXn5avSlPP7x-u3pxWtZMyFS2wOvGctYB4xI6IwSWNeHSEGgpWNrVirakVp0yvFP5URtDLGkaIbjCBGCJns9zN1M92LaxYwqm15vgBhO22hun_0xGd6HP_Q9dKczY5YDH-wHBf59sTHpwsbF9b0brp6gFo4RWglf_lwBKSkZ3Mx_8Jdd-CnmdGVHOlKKCZfTwOkQUwYKKCqp_KiEkBg75LNGTWTXBxxhsd1gAwXrXE517oi97ku39qxs7yN-tyODeDNYx-XAlF0AVJzkv59zlUvw85CZ801yAYPr92UrTL1Uu2zumz7J_NPvdH67_1y84u9x8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1778036336</pqid></control><display><type>article</type><title>Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study</title><source>Applied Social Sciences Index & Abstracts (ASSIA)</source><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><creator>Nüesch, Eveline ; Trelle, Sven ; Reichenbach, Stephan ; Rutjes, Anne W S ; Tschannen, Beatrice ; Altman, Douglas G ; Egger, Matthias ; Jüni, Peter</creator><creatorcontrib>Nüesch, Eveline ; Trelle, Sven ; Reichenbach, Stephan ; Rutjes, Anne W S ; Tschannen, Beatrice ; Altman, Douglas G ; Egger, Matthias ; Jüni, Peter</creatorcontrib><description>Objective To examine the presence and extent of small study effects in clinical osteoarthritis research.Design Meta-epidemiological study.Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients’ reported pain as an outcome.Methods We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials.Results On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes −0.21, 95% confidence interval −0.34 to −0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates.Conclusions Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.</description><edition>International edition</edition><identifier>ISSN: 0959-8138</identifier><identifier>ISSN: 0959-8146</identifier><identifier>ISSN: 0959-535X</identifier><identifier>EISSN: 1468-5833</identifier><identifier>EISSN: 1756-1833</identifier><identifier>DOI: 10.1136/bmj.c3515</identifier><identifier>PMID: 20639294</identifier><identifier>CODEN: BMJOAE</identifier><language>eng</language><publisher>England: British Medical Journal Publishing Group</publisher><subject>Arthritis ; Attention deficit disorder ; Bias ; Clinical trials ; Data processing ; Degenerative Joint Disease ; Epidemiology ; Experimentation ; Hip ; Humans ; Intervention ; Knee ; Meta-analysis ; Musculoskeletal Syndromes ; Osteoarthritis ; Osteoarthritis, Hip - therapy ; Osteoarthritis, Knee - therapy ; Pain ; Pain (Neurology) ; Pain - prevention & control ; Quality ; Randomized Controlled Trials as Topic - methods ; Randomized Controlled Trials as Topic - statistics & numerical data ; Sample Size ; Therapeutic applications ; Treatment Outcome</subject><ispartof>BMJ, 2010-07, Vol.341 (7766), p.241-241</ispartof><rights>Nüesch et al 2010</rights><rights>2010 BMJ Publishing Group Ltd</rights><rights>Copyright: 2010 © Nüesch et al 2010</rights><rights>Copyright BMJ Publishing Group Jul 31, 2010</rights><rights>Nüesch et al 2010 2010 Nüesch et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b578t-d36bce65f35683fa7708b168a13d43e4fb94d1b9f9a6f91b9baa1e1cc77690133</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://bmj.com/content/341/bmj.c3515.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttp://bmj.com/content/341/bmj.c3515.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>114,115,230,314,776,780,799,881,3183,23550,27901,27902,30976,30977,57992,58225,77343,77374</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20639294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nüesch, Eveline</creatorcontrib><creatorcontrib>Trelle, Sven</creatorcontrib><creatorcontrib>Reichenbach, Stephan</creatorcontrib><creatorcontrib>Rutjes, Anne W S</creatorcontrib><creatorcontrib>Tschannen, Beatrice</creatorcontrib><creatorcontrib>Altman, Douglas G</creatorcontrib><creatorcontrib>Egger, Matthias</creatorcontrib><creatorcontrib>Jüni, Peter</creatorcontrib><title>Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study</title><title>BMJ</title><addtitle>BMJ</addtitle><description>Objective To examine the presence and extent of small study effects in clinical osteoarthritis research.Design Meta-epidemiological study.Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients’ reported pain as an outcome.Methods We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials.Results On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes −0.21, 95% confidence interval −0.34 to −0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates.Conclusions Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.</description><subject>Arthritis</subject><subject>Attention deficit disorder</subject><subject>Bias</subject><subject>Clinical trials</subject><subject>Data processing</subject><subject>Degenerative Joint Disease</subject><subject>Epidemiology</subject><subject>Experimentation</subject><subject>Hip</subject><subject>Humans</subject><subject>Intervention</subject><subject>Knee</subject><subject>Meta-analysis</subject><subject>Musculoskeletal Syndromes</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis, Hip - therapy</subject><subject>Osteoarthritis, Knee - therapy</subject><subject>Pain</subject><subject>Pain (Neurology)</subject><subject>Pain - prevention & control</subject><subject>Quality</subject><subject>Randomized Controlled Trials as Topic - methods</subject><subject>Randomized Controlled Trials as Topic - statistics & numerical data</subject><subject>Sample Size</subject><subject>Therapeutic applications</subject><subject>Treatment Outcome</subject><issn>0959-8138</issn><issn>0959-8146</issn><issn>0959-535X</issn><issn>1468-5833</issn><issn>1756-1833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>ACMMV</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>7QJ</sourceid><recordid>eNqF0l2L1DAUBuAgijuMe-EPUIoK4kXXpCefXggy-MmiF-qKVyFt092MbTMmqTj_3sx2HFZhFQIJvA-HcHgRukvwCSHAn9bD-qQBRtgNtCCUy5JJgJtogRVTpSQgj9BxjGuMcQVCKs5uo6MKc1CVogv09eNg-r6IaWq3he0626RYuLEYbDKlGU2_jTYWvit8TNabkC6CSy4WKTjTx2ezsxvX2sH53p-7xuyn3UG3ukzs8f5eos-vXn5avSlPP7x-u3pxWtZMyFS2wOvGctYB4xI6IwSWNeHSEGgpWNrVirakVp0yvFP5URtDLGkaIbjCBGCJns9zN1M92LaxYwqm15vgBhO22hun_0xGd6HP_Q9dKczY5YDH-wHBf59sTHpwsbF9b0brp6gFo4RWglf_lwBKSkZ3Mx_8Jdd-CnmdGVHOlKKCZfTwOkQUwYKKCqp_KiEkBg75LNGTWTXBxxhsd1gAwXrXE517oi97ku39qxs7yN-tyODeDNYx-XAlF0AVJzkv59zlUvw85CZ801yAYPr92UrTL1Uu2zumz7J_NPvdH67_1y84u9x8</recordid><startdate>20100716</startdate><enddate>20100716</enddate><creator>Nüesch, Eveline</creator><creator>Trelle, Sven</creator><creator>Reichenbach, Stephan</creator><creator>Rutjes, Anne W S</creator><creator>Tschannen, Beatrice</creator><creator>Altman, Douglas G</creator><creator>Egger, Matthias</creator><creator>Jüni, Peter</creator><general>British Medical Journal Publishing Group</general><general>British Medical Association</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><general>BMJ Publishing Group Ltd</general><scope>9YT</scope><scope>ACMMV</scope><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7QJ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100716</creationdate><title>Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study</title><author>Nüesch, Eveline ; Trelle, Sven ; Reichenbach, Stephan ; Rutjes, Anne W S ; Tschannen, Beatrice ; Altman, Douglas G ; Egger, Matthias ; Jüni, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b578t-d36bce65f35683fa7708b168a13d43e4fb94d1b9f9a6f91b9baa1e1cc77690133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Arthritis</topic><topic>Attention deficit disorder</topic><topic>Bias</topic><topic>Clinical trials</topic><topic>Data processing</topic><topic>Degenerative Joint Disease</topic><topic>Epidemiology</topic><topic>Experimentation</topic><topic>Hip</topic><topic>Humans</topic><topic>Intervention</topic><topic>Knee</topic><topic>Meta-analysis</topic><topic>Musculoskeletal Syndromes</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis, Hip - therapy</topic><topic>Osteoarthritis, Knee - therapy</topic><topic>Pain</topic><topic>Pain (Neurology)</topic><topic>Pain - prevention & control</topic><topic>Quality</topic><topic>Randomized Controlled Trials as Topic - methods</topic><topic>Randomized Controlled Trials as Topic - statistics & numerical data</topic><topic>Sample Size</topic><topic>Therapeutic applications</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nüesch, Eveline</creatorcontrib><creatorcontrib>Trelle, Sven</creatorcontrib><creatorcontrib>Reichenbach, Stephan</creatorcontrib><creatorcontrib>Rutjes, Anne W S</creatorcontrib><creatorcontrib>Tschannen, Beatrice</creatorcontrib><creatorcontrib>Altman, Douglas G</creatorcontrib><creatorcontrib>Egger, Matthias</creatorcontrib><creatorcontrib>Jüni, Peter</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMJ</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nüesch, Eveline</au><au>Trelle, Sven</au><au>Reichenbach, Stephan</au><au>Rutjes, Anne W S</au><au>Tschannen, Beatrice</au><au>Altman, Douglas G</au><au>Egger, Matthias</au><au>Jüni, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study</atitle><jtitle>BMJ</jtitle><addtitle>BMJ</addtitle><date>2010-07-16</date><risdate>2010</risdate><volume>341</volume><issue>7766</issue><spage>241</spage><epage>241</epage><pages>241-241</pages><issn>0959-8138</issn><issn>0959-8146</issn><issn>0959-535X</issn><eissn>1468-5833</eissn><eissn>1756-1833</eissn><coden>BMJOAE</coden><abstract>Objective To examine the presence and extent of small study effects in clinical osteoarthritis research.Design Meta-epidemiological study.Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients’ reported pain as an outcome.Methods We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials.Results On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes −0.21, 95% confidence interval −0.34 to −0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates.Conclusions Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.</abstract><cop>England</cop><pub>British Medical Journal Publishing Group</pub><pmid>20639294</pmid><doi>10.1136/bmj.c3515</doi><tpages>1</tpages><edition>International edition</edition><oa>free_for_read</oa></addata></record> |
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| subjects | Arthritis Attention deficit disorder Bias Clinical trials Data processing Degenerative Joint Disease Epidemiology Experimentation Hip Humans Intervention Knee Meta-analysis Musculoskeletal Syndromes Osteoarthritis Osteoarthritis, Hip - therapy Osteoarthritis, Knee - therapy Pain Pain (Neurology) Pain - prevention & control Quality Randomized Controlled Trials as Topic - methods Randomized Controlled Trials as Topic - statistics & numerical data Sample Size Therapeutic applications Treatment Outcome |
| title | Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study |
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