Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights
Abstract Background The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-022-06977-4 |
| _version_ | 1828086983908392960 |
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| author | Josep Ramon Marsal Iratxe Urreta-Barallobre Marimar Ubeda-Carrillo Dimelza Osorio Blanca Lumbreras David Lora Borja M. Fernández-Felix Gerard Oristrell Eduard Ródenas-Alesina Lorena Herrador Mónica Ballesteros Javier Zamora Jose I. Pijoan Aida Ribera Ignacio Ferreira-González |
| author_facet | Josep Ramon Marsal Iratxe Urreta-Barallobre Marimar Ubeda-Carrillo Dimelza Osorio Blanca Lumbreras David Lora Borja M. Fernández-Felix Gerard Oristrell Eduard Ródenas-Alesina Lorena Herrador Mónica Ballesteros Javier Zamora Jose I. Pijoan Aida Ribera Ignacio Ferreira-González |
| author_sort | Josep Ramon Marsal |
| collection | DOAJ |
| description | Abstract Background The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). Methods A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015–2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. Results Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between − 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. Conclusions The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE. |
| first_indexed | 2024-04-11T05:04:42Z |
| format | Article |
| id | doaj.art-df8c4375dbed4faeb3f4743b3ac6a7eb |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-11T05:04:42Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-df8c4375dbed4faeb3f4743b3ac6a7eb2022-12-25T12:28:14ZengBMCTrials1745-62152022-12-0123111010.1186/s13063-022-06977-4Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insightsJosep Ramon Marsal0Iratxe Urreta-Barallobre1Marimar Ubeda-Carrillo2Dimelza Osorio3Blanca Lumbreras4David Lora5Borja M. Fernández-Felix6Gerard Oristrell7Eduard Ródenas-Alesina8Lorena Herrador9Mónica Ballesteros10Javier Zamora11Jose I. Pijoan12Aida Ribera13Ignacio Ferreira-González14Cardiovascular Epidemiology and Research Unit, Vall d’Hebron Institut de Recerca (VHIR)CIBER Epidemiology and Public HealthOsakidetza Basque Health Service, Donostialdea Integrated Health Organisation, Donostia University Hospital, Library ServiceCIBER Epidemiology and Public HealthCIBER Epidemiology and Public HealthCIBER Epidemiology and Public HealthCIBER Epidemiology and Public HealthCardiology Department, Vall d’Hebron University HospitalCardiology Department, Vall d’Hebron University HospitalCardiology Department, Vall d’Hebron University HospitalCIBER Epidemiology and Public HealthCIBER Epidemiology and Public HealthCIBER Epidemiology and Public HealthCardiovascular Epidemiology and Research Unit, Vall d’Hebron Institut de Recerca (VHIR)Cardiovascular Epidemiology and Research Unit, Vall d’Hebron Institut de Recerca (VHIR)Abstract Background The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). Methods A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015–2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. Results Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between − 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. Conclusions The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE.https://doi.org/10.1186/s13063-022-06977-4Composite endpointsSample sizeCorrelationMACE |
| spellingShingle | Josep Ramon Marsal Iratxe Urreta-Barallobre Marimar Ubeda-Carrillo Dimelza Osorio Blanca Lumbreras David Lora Borja M. Fernández-Felix Gerard Oristrell Eduard Ródenas-Alesina Lorena Herrador Mónica Ballesteros Javier Zamora Jose I. Pijoan Aida Ribera Ignacio Ferreira-González Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights Trials Composite endpoints Sample size Correlation MACE |
| title | Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights |
| title_full | Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights |
| title_fullStr | Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights |
| title_full_unstemmed | Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights |
| title_short | Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights |
| title_sort | sample size requirement in trials that use the composite endpoint major adverse cardiovascular events mace new insights |
| topic | Composite endpoints Sample size Correlation MACE |
| url | https://doi.org/10.1186/s13063-022-06977-4 |
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