MRI-based clinical trials in relapsing–remitting MS: new sample size calculations based on a longitudinal model
Background: Sample sizes for magnetic resonance imaging (MRI)-based clinical trials in multiple sclerosis (MS) generally assume that lesion counts are reasonably described by the negative binomial (NB) model. Objective: This study aimed to assess the appropriateness of the NB model for lesion count...
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| Veröffentlicht in: | Multiple sclerosis 2012-11, Vol.18 (11), p.1600-1608 |
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| container_title | Multiple sclerosis |
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| creator | Altman, RM Petkau, AJ Vrecko, D Smith, A |
| description | Background:
Sample sizes for magnetic resonance imaging (MRI)-based clinical trials in multiple sclerosis (MS) generally assume that lesion counts are reasonably described by the negative binomial (NB) model.
Objective:
This study aimed to assess the appropriateness of the NB model for lesion count data and to provide sample sizes for placebo-controlled, MRI-based clinical trials in relapsing–remitting MS using a more realistic model.
Methods:
The fit of the NB model in each arm of five MS clinical trials was assessed using Pearson’s chi-squared statistic. Required sample sizes associated with various tests of treatment effect were estimated by simulating data from a new, longitudinal model for repeated lesion count data on individual patients.
Results:
Evidence (p < 0.05) against the NB model was found in at least one arm of four of the five trials. If a trial is designed using this model but the resulting clinical data do not follow its assumptions then this trial can be seriously under-powered for assessing differences in mean lesion counts.
Conclusion:
Sample sizes based on the longitudinal model are more realistic and often smaller than those previously reported using the NB model. |
| doi_str_mv | 10.1177/1352458512444326 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1115530725</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458512444326</sage_id><sourcerecordid>2818918621</sourcerecordid><originalsourceid>FETCH-LOGICAL-c395t-80e462b32db7b93ec2a7b63d79ba15634b641755caf6ff52f219df46146b148a3</originalsourceid><addsrcrecordid>eNp1kd9KHDEUh4NU3NX23isJSMGb0fzPxjsRq4IiaHs9JJnMkiWT2U1mKO2V79A39EnMstsqQq9y4Hy_L4dzADjE6BRjKc8w5YTxGceEMUaJ2AFTzKSskJLoU6lLu1r3J2A_5wVCSErK98CEEKa4YrMpWN0_3lZGZ9dAG3z0Vgc4JK9Dhj7C5IJeZh_nL89_kuv8MJQa3j-dw-h-wqy7ZXAw-98Olpwdgx58HzPc-PoINQx9nPthbHws4q5vXPgMdtuid1-27wH48e3q--VNdfdwfXt5cVdZqvhQzZBjghhKGiONos4SLY2gjVRGYy4oM4JhybnVrWhbTlqCVdMygZkwmM00PQAnG-8y9avR5aHufLYuBB1dP-YaY8w5RZLwgh5_QBf9mMrEa0oigQVTslBoQ9nU55xcWy-T73T6VWO05mT98RwlcrQVj6Zzzb_A3_0X4OsW0LmssE06Wp_fOMGlUJQUrtpwWc_du-n-9_ErJmyfJQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1170616497</pqid></control><display><type>article</type><title>MRI-based clinical trials in relapsing–remitting MS: new sample size calculations based on a longitudinal model</title><source>MEDLINE</source><source>SAGE Complete</source><creator>Altman, RM ; Petkau, AJ ; Vrecko, D ; Smith, A</creator><creatorcontrib>Altman, RM ; Petkau, AJ ; Vrecko, D ; Smith, A</creatorcontrib><description>Background:
Sample sizes for magnetic resonance imaging (MRI)-based clinical trials in multiple sclerosis (MS) generally assume that lesion counts are reasonably described by the negative binomial (NB) model.
Objective:
This study aimed to assess the appropriateness of the NB model for lesion count data and to provide sample sizes for placebo-controlled, MRI-based clinical trials in relapsing–remitting MS using a more realistic model.
Methods:
The fit of the NB model in each arm of five MS clinical trials was assessed using Pearson’s chi-squared statistic. Required sample sizes associated with various tests of treatment effect were estimated by simulating data from a new, longitudinal model for repeated lesion count data on individual patients.
Results:
Evidence (p < 0.05) against the NB model was found in at least one arm of four of the five trials. If a trial is designed using this model but the resulting clinical data do not follow its assumptions then this trial can be seriously under-powered for assessing differences in mean lesion counts.
Conclusion:
Sample sizes based on the longitudinal model are more realistic and often smaller than those previously reported using the NB model.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458512444326</identifier><identifier>PMID: 22495948</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Biological and medical sciences ; Brain - pathology ; Chi-Square Distribution ; Computer Simulation ; Controlled Clinical Trials as Topic - methods ; Controlled Clinical Trials as Topic - statistics & numerical data ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Endpoint Determination ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; Medical sciences ; Models, Statistical ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Multiple Sclerosis, Relapsing-Remitting - diagnosis ; Multiple Sclerosis, Relapsing-Remitting - pathology ; Multiple Sclerosis, Relapsing-Remitting - therapy ; Neurology ; Predictive Value of Tests ; Sample Size ; Time Factors ; Treatment Outcome</subject><ispartof>Multiple sclerosis, 2012-11, Vol.18 (11), p.1600-1608</ispartof><rights>The Author(s) 2012</rights><rights>2015 INIST-CNRS</rights><rights>SAGE Publications © Nov 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-80e462b32db7b93ec2a7b63d79ba15634b641755caf6ff52f219df46146b148a3</citedby><cites>FETCH-LOGICAL-c395t-80e462b32db7b93ec2a7b63d79ba15634b641755caf6ff52f219df46146b148a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458512444326$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458512444326$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26576932$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22495948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Altman, RM</creatorcontrib><creatorcontrib>Petkau, AJ</creatorcontrib><creatorcontrib>Vrecko, D</creatorcontrib><creatorcontrib>Smith, A</creatorcontrib><title>MRI-based clinical trials in relapsing–remitting MS: new sample size calculations based on a longitudinal model</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background:
Sample sizes for magnetic resonance imaging (MRI)-based clinical trials in multiple sclerosis (MS) generally assume that lesion counts are reasonably described by the negative binomial (NB) model.
Objective:
This study aimed to assess the appropriateness of the NB model for lesion count data and to provide sample sizes for placebo-controlled, MRI-based clinical trials in relapsing–remitting MS using a more realistic model.
Methods:
The fit of the NB model in each arm of five MS clinical trials was assessed using Pearson’s chi-squared statistic. Required sample sizes associated with various tests of treatment effect were estimated by simulating data from a new, longitudinal model for repeated lesion count data on individual patients.
Results:
Evidence (p < 0.05) against the NB model was found in at least one arm of four of the five trials. If a trial is designed using this model but the resulting clinical data do not follow its assumptions then this trial can be seriously under-powered for assessing differences in mean lesion counts.
Conclusion:
Sample sizes based on the longitudinal model are more realistic and often smaller than those previously reported using the NB model.</description><subject>Biological and medical sciences</subject><subject>Brain - pathology</subject><subject>Chi-Square Distribution</subject><subject>Computer Simulation</subject><subject>Controlled Clinical Trials as Topic - methods</subject><subject>Controlled Clinical Trials as Topic - statistics & numerical data</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Endpoint Determination</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Magnetic Resonance Imaging</subject><subject>Medical sciences</subject><subject>Models, Statistical</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - diagnosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - pathology</subject><subject>Multiple Sclerosis, Relapsing-Remitting - therapy</subject><subject>Neurology</subject><subject>Predictive Value of Tests</subject><subject>Sample Size</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kd9KHDEUh4NU3NX23isJSMGb0fzPxjsRq4IiaHs9JJnMkiWT2U1mKO2V79A39EnMstsqQq9y4Hy_L4dzADjE6BRjKc8w5YTxGceEMUaJ2AFTzKSskJLoU6lLu1r3J2A_5wVCSErK98CEEKa4YrMpWN0_3lZGZ9dAG3z0Vgc4JK9Dhj7C5IJeZh_nL89_kuv8MJQa3j-dw-h-wqy7ZXAw-98Olpwdgx58HzPc-PoINQx9nPthbHws4q5vXPgMdtuid1-27wH48e3q--VNdfdwfXt5cVdZqvhQzZBjghhKGiONos4SLY2gjVRGYy4oM4JhybnVrWhbTlqCVdMygZkwmM00PQAnG-8y9avR5aHufLYuBB1dP-YaY8w5RZLwgh5_QBf9mMrEa0oigQVTslBoQ9nU55xcWy-T73T6VWO05mT98RwlcrQVj6Zzzb_A3_0X4OsW0LmssE06Wp_fOMGlUJQUrtpwWc_du-n-9_ErJmyfJQ</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>Altman, RM</creator><creator>Petkau, AJ</creator><creator>Vrecko, D</creator><creator>Smith, A</creator><general>SAGE Publications</general><general>Sage Publications</general><general>Sage Publications Ltd</general><scope>IQODW</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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20121101</creationdate><title>MRI-based clinical trials in relapsing–remitting MS: new sample size calculations based on a longitudinal model</title><author>Altman, RM ; Petkau, AJ ; Vrecko, D ; Smith, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-80e462b32db7b93ec2a7b63d79ba15634b641755caf6ff52f219df46146b148a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Biological and medical sciences</topic><topic>Brain - pathology</topic><topic>Chi-Square Distribution</topic><topic>Computer Simulation</topic><topic>Controlled Clinical Trials as Topic - methods</topic><topic>Controlled Clinical Trials as Topic - statistics & numerical data</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Endpoint Determination</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Magnetic Resonance Imaging</topic><topic>Medical sciences</topic><topic>Models, Statistical</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - diagnosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - pathology</topic><topic>Multiple Sclerosis, Relapsing-Remitting - therapy</topic><topic>Neurology</topic><topic>Predictive Value of Tests</topic><topic>Sample Size</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Altman, RM</creatorcontrib><creatorcontrib>Petkau, AJ</creatorcontrib><creatorcontrib>Vrecko, D</creatorcontrib><creatorcontrib>Smith, A</creatorcontrib><collection>Pascal-Francis</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>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>MEDLINE - Academic</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Altman, RM</au><au>Petkau, AJ</au><au>Vrecko, D</au><au>Smith, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MRI-based clinical trials in relapsing–remitting MS: new sample size calculations based on a longitudinal model</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2012-11-01</date><risdate>2012</risdate><volume>18</volume><issue>11</issue><spage>1600</spage><epage>1608</epage><pages>1600-1608</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>Background:
Sample sizes for magnetic resonance imaging (MRI)-based clinical trials in multiple sclerosis (MS) generally assume that lesion counts are reasonably described by the negative binomial (NB) model.
Objective:
This study aimed to assess the appropriateness of the NB model for lesion count data and to provide sample sizes for placebo-controlled, MRI-based clinical trials in relapsing–remitting MS using a more realistic model.
Methods:
The fit of the NB model in each arm of five MS clinical trials was assessed using Pearson’s chi-squared statistic. Required sample sizes associated with various tests of treatment effect were estimated by simulating data from a new, longitudinal model for repeated lesion count data on individual patients.
Results:
Evidence (p < 0.05) against the NB model was found in at least one arm of four of the five trials. If a trial is designed using this model but the resulting clinical data do not follow its assumptions then this trial can be seriously under-powered for assessing differences in mean lesion counts.
Conclusion:
Sample sizes based on the longitudinal model are more realistic and often smaller than those previously reported using the NB model.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>22495948</pmid><doi>10.1177/1352458512444326</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1352-4585 |
| ispartof | Multiple sclerosis, 2012-11, Vol.18 (11), p.1600-1608 |
| issn | 1352-4585 1477-0970 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1115530725 |
| source | MEDLINE; SAGE Complete |
| subjects | Biological and medical sciences Brain - pathology Chi-Square Distribution Computer Simulation Controlled Clinical Trials as Topic - methods Controlled Clinical Trials as Topic - statistics & numerical data Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Endpoint Determination Humans Longitudinal Studies Magnetic Resonance Imaging Medical sciences Models, Statistical Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Multiple Sclerosis, Relapsing-Remitting - diagnosis Multiple Sclerosis, Relapsing-Remitting - pathology Multiple Sclerosis, Relapsing-Remitting - therapy Neurology Predictive Value of Tests Sample Size Time Factors Treatment Outcome |
| title | MRI-based clinical trials in relapsing–remitting MS: new sample size calculations based on a longitudinal model |
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