Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights

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

doi:10.1186/s13063-022-06977-4

Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights

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^*

^*Corresponding author for this work

Metabolism and Systems Research

Research output: Contribution to journal › Review article › peer-review

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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.

Original language	English
Article number	1037
Number of pages	10
Journal	Trials
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s13063-022-06977-4
Publication status	Published - 21 Dec 2022

Bibliographical note

Funding Information:
We are very grateful for the comments and support from Guadalupe Gomez and Jordi Cortés. We also want to thank Carmen Bernal Soriano, Marta Puig, Diego San José, Ana Pastor Moreno, Celia Fátima Gómez, Shandra Fuentes, Iñigo Sanz, and Eñaut Aguirre for their support during the systematic reviewing process.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Composite endpoints
Correlation
MACE
Sample size

ASJC Scopus subject areas

Medicine (miscellaneous)
Pharmacology (medical)

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Cite this

Marsal, J. R., Urreta-Barallobre, I., Ubeda-Carrillo, M., Osorio, D., Lumbreras, B., Lora, D., Fernández-Felix, B. M., Oristrell, G., Ródenas-Alesina, E., Herrador, L., Ballesteros, M., Zamora, J., Pijoan, J. I., Ribera, A., & Ferreira-González, I. (2022). Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights. Trials, 23(1), Article 1037. https://doi.org/10.1186/s13063-022-06977-4

@article{fce069701d2645989d97192eb10a2a7f,

title = "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 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.",

keywords = "Composite endpoints, Correlation, MACE, Sample size",

author = "Marsal, {Josep Ramon} and Iratxe Urreta-Barallobre and Marimar Ubeda-Carrillo and Dimelza Osorio and Blanca Lumbreras and David Lora and Fern{\'a}ndez-Felix, {Borja M.} and Gerard Oristrell and Eduard R{\'o}denas-Alesina and Lorena Herrador and M{\'o}nica Ballesteros and Javier Zamora and Pijoan, {Jose I.} and Aida Ribera and Ignacio Ferreira-Gonz{\'a}lez",

note = "Funding Information: We are very grateful for the comments and support from Guadalupe Gomez and Jordi Cort{\'e}s. We also want to thank Carmen Bernal Soriano, Marta Puig, Diego San Jos{\'e}, Ana Pastor Moreno, Celia F{\'a}tima G{\'o}mez, Shandra Fuentes, I{\~n}igo Sanz, and E{\~n}aut Aguirre for their support during the systematic reviewing process. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

day = "21",

doi = "10.1186/s13063-022-06977-4",

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Marsal, JR, Urreta-Barallobre, I, Ubeda-Carrillo, M, Osorio, D, Lumbreras, B, Lora, D, Fernández-Felix, BM, Oristrell, G, Ródenas-Alesina, E, Herrador, L, Ballesteros, M, Zamora, J, Pijoan, JI, Ribera, A & Ferreira-González, I 2022, 'Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights', Trials, vol. 23, no. 1, 1037. https://doi.org/10.1186/s13063-022-06977-4

TY - JOUR

T1 - Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE)

T2 - new insights

AU - Marsal, Josep Ramon

AU - Urreta-Barallobre, Iratxe

AU - Ubeda-Carrillo, Marimar

AU - Osorio, Dimelza

AU - Lumbreras, Blanca

AU - Lora, David

AU - Fernández-Felix, Borja M.

AU - Oristrell, Gerard

AU - Ródenas-Alesina, Eduard

AU - Herrador, Lorena

AU - Ballesteros, Mónica

AU - Zamora, Javier

AU - Pijoan, Jose I.

AU - Ribera, Aida

AU - Ferreira-González, Ignacio

N1 - Funding Information: We are very grateful for the comments and support from Guadalupe Gomez and Jordi Cortés. We also want to thank Carmen Bernal Soriano, Marta Puig, Diego San José, Ana Pastor Moreno, Celia Fátima Gómez, Shandra Fuentes, Iñigo Sanz, and Eñaut Aguirre for their support during the systematic reviewing process. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/21

Y1 - 2022/12/21

N2 - 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.

AB - 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.

KW - Composite endpoints

KW - Correlation

KW - MACE

KW - Sample size

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U2 - 10.1186/s13063-022-06977-4

DO - 10.1186/s13063-022-06977-4

M3 - Review article

C2 - 36539800

AN - SCOPUS:85144303178

SN - 1745-6215

VL - 23

JO - Trials

JF - Trials

IS - 1

M1 - 1037

ER -

Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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