Abstract
Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within-and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1345-1359 |
| Number of pages | 15 |
| Journal | International journal of epidemiology |
| Volume | 39 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2010 |
Bibliographical note
Funding Information:Methodological work in the ERFC has been supported by specific grants from the UK Medical Research Council. The ERFC Coordinating Centre is underpinned by a programme grant from the British Heart Foundation and supported by the BUPA Foundation and unrestricted educational grants from GlaxoSmithKline. Various sources have supported recruitment, follow-up and laboratory measurements in the cohorts contributing to the ERFC. Investigators of several of these studies have contributed to a list naming some of these funding sources, which can be found at http://www.phpc.cam.ac.uk/MEU/.
Publisher Copyright:
© The Author 2010; all rights reserved.
Keywords
- Epidemiological studies
- Individual participant data
- Meta-analysis
- Statistical methods
- Survival analysis
Access
Other files and links
Fingerprint Dive into the research topics of 'Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies'. Together they form a unique fingerprint.
Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies. / Thompson, Simon; Kaptoge, Stephen; White, Ian; Wood, Angela; Perry, Philip; Danesh, John; The Emerging Risk Factors Collaboration, Emerging Risk Factors Collaboration; Thompson, S. G.; Kaptoge, S.; White, I. R.; Wood, A. M.; Perry, P. L.; Danesh, J.; Tipping, R. W.; Ford, C. E.; Simpson, L. M.; Walldius, G.; Jungner, I.; Chambless, L. E.; Panagiotakos, D. B.; Pitsavos, C.; Chrysohoou, C.; Stefanadis, C.; Knuiman, M.; Goldbourt, U.; Benderly, M.; Tanne, D.; Whincup, P. H.; Wannamethee, S. G.; Morris, R. W.; Willeit, J.; Kiechl, S.; Santer, P.; Mayr, A.; Lawlor, D. A.; Yarnell, J. W G; Gallacher, J.; Casiglia, E.; Tikhonoff, V.; Nietert, P. J.; Sutherland, S. E.; Bachman, D. L.; Keil, J. E.; Cushman, M.; Tracy, R. P.; Tybjærg-Hansen, A.; Nordestgaard, B. G.; Benn, M.; Frikke- Schmidt, R.; Giampaoli, S.; Palmieri, L.; Panico, S.; Vanuzzo, D.; Gómez de la Cámara, A.; Gómez- Gerique, J. A.; Simons, L.; McCallum, J.; Friedlander, Y.; Fowkes, F. G R; Lee, A. J.; Taylor, J.; Guralnik, J. M.; Wallace, R.; Guralnik, J.; Blazer, D. G.; Guralnik, J. M.; Guralnik, J. M.; Khaw, K. T.; Brenner, H.; Raum, E.; Müller, H.; Rothenbacher, D.; Jansson, J. H.; Wennberg, P.; Nissinen, A.; Donfrancesco, C.; Giampaoli, S.; Salomaa, V.; Harald, K.; Jousilahti, P.; Vartiainen, E.; Woodward, M.; D'Agostino, R. B.; Vasan, R. S.; Pencina, M. J.; Bladbjerg, E. M.; Jørgensen, T.; Møller, L.; Jespersen, J.; Dankner, R.; Chetrit, A.; Lubin, F.; Rosengren, A.; Lappas, G.; Björkelund, C.; Lissner, L.; Bengtsson, C.; Cremer, P.; Nagel, D.; Tilvis, R. S.; Strandberg, T. E.; Kiyohara, Y.; Arima, H.; Doi, Y.; Ninomiya, T.; Rodriguez, B.; Dekker, J. M.; Nijpels, G.; Stehouwer, C. D A; Rimm, E.; Pai, J. K.; Sato, S.; Iso, H.; Kitamura, A.; Noda, H.; Goldbourt, U.; Salomaa, V.; Harald, K.; Jousilahti, P.; Vartiainen, E.; Salonen, J. T.; Tuomainen, T. P.; Deeg, D. J H; Poppelaars, J. L.; Meade, T. W.; Cooper, J. A.; Hedblad, B.; Berglund, G.; Engstrom, G.; Verschuren, W. M M; Blokstra, A.; Cushman, M.; Shea, S.; Döring, A.; Koenig, W.; Meisinger, C.; Mraz, W.; Verschuren, W. M M; Blokstra, A.; Bas Bueno-de-Mesquita, H.; Rosengren, A.; Lappas, G.; Kuller, L. H.; Grandits, G.; Selmer, R.; Tverdal, A.; Nystad, W.; Gillum, R.; Mussolino, M.; Rimm, E.; Hankinson, S.; Manson, J. E.; Pai, J. K.; Meade, T. W.; Cooper, J. A.; Knottenbelt, C.; Cooper, J. A.; Bauer, K. A.; Sato, S.; Kitamura, A.; Naito, Y.; Iso, H.; Holme, I.; Selmer, R.; Tverdal, A.; Nystad, W.; Nakagawa, H.; Miura, K.; Ducimetiere, P.; Jouven, X.; Crespo, C. J.; Garcia Palmieri, M. R.; Amouyel, P.; Arveiler, D.; Evans, A.; Ferrieres, J.; Schulte, H.; Assmann, G.; Shepherd, J.; Packard, C. J.; Sattar, N.; Ford, I.; Cantin, B.; Després, J. P.; Dagenais, G. R.; Barrett-Connor, E.; Wingard, D. L.; Bettencourt, R.; Gudnason, V.; Aspelund, T.; Sigurdsson, G.; Thorsson, B.; Trevisan, M.; Witteman, J.; Kardys, I.; Breteler, M.; Hofman, A.; Tunstall-Pedoe, H.; Tavendale, R.; Lowe, G. D O; Woodward, M.; Ben-Shlomo, Y.; Davey-Smith, G.; Howard, B. V.; Zhang, Y.; Umans, J.; Onat, A.; Meade, T. W.; Wilsgaard, T.; Ingelsson, E.; Lind, L.; Giedraitis, V.; Lannfelt, L.; Gaziano, J. M.; Ridker, P.; Gaziano, J. M.; Ridker, P.; Ulmer, H.; Diem, G.; Concin, H.; Tosetto, A.; Rodeghiero, F.; Wassertheil-Smoller, S.; Manson, J. E.; Marmot, M.; Clarke, R.; Collins, R.; Brunner, E.; Shipley, M.; Ridker, P.; Buring, J.; Shepherd, J.; Cobbe, S. M.; Ford, I.; Robertson, M.; He, Y.; Marín Ibañez, A.; Feskens, E. J M; Kromhout, D.; Collins, R.; Di Angelantonio, E.; Erqou, S.; Kaptoge, S.; Lewington, S.; Orfei, L.; Pennells, L.; Perry, P. L.; Ray, K. K.; Sarwar, N.; Alexander, M.; Thompson, A.; Thompson, S. G.; Walker, M.; Watson, S.; Wensley, F.; White, I. R.; Wood, A. M.; Danesh, J.
In: International journal of epidemiology, Vol. 39, No. 5, 2010, p. 1345-1359.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies
AU - Thompson, Simon
AU - Kaptoge, Stephen
AU - White, Ian
AU - Wood, Angela
AU - Perry, Philip
AU - Danesh, John
AU - The Emerging Risk Factors Collaboration, Emerging Risk Factors Collaboration
AU - Thompson, S. G.
AU - Kaptoge, S.
AU - White, I. R.
AU - Wood, A. M.
AU - Perry, P. L.
AU - Danesh, J.
AU - Tipping, R. W.
AU - Ford, C. E.
AU - Simpson, L. M.
AU - Walldius, G.
AU - Jungner, I.
AU - Chambless, L. E.
AU - Panagiotakos, D. B.
AU - Pitsavos, C.
AU - Chrysohoou, C.
AU - Stefanadis, C.
AU - Knuiman, M.
AU - Goldbourt, U.
AU - Benderly, M.
AU - Tanne, D.
AU - Whincup, P. H.
AU - Wannamethee, S. G.
AU - Morris, R. W.
AU - Willeit, J.
AU - Kiechl, S.
AU - Santer, P.
AU - Mayr, A.
AU - Lawlor, D. A.
AU - Yarnell, J. W G
AU - Gallacher, J.
AU - Casiglia, E.
AU - Tikhonoff, V.
AU - Nietert, P. J.
AU - Sutherland, S. E.
AU - Bachman, D. L.
AU - Keil, J. E.
AU - Cushman, M.
AU - Tracy, R. P.
AU - Tybjærg-Hansen, A.
AU - Nordestgaard, B. G.
AU - Benn, M.
AU - Frikke- Schmidt, R.
AU - Giampaoli, S.
AU - Palmieri, L.
AU - Panico, S.
AU - Vanuzzo, D.
AU - Gómez de la Cámara, A.
AU - Gómez- Gerique, J. A.
AU - Simons, L.
AU - McCallum, J.
AU - Friedlander, Y.
AU - Fowkes, F. G R
AU - Lee, A. J.
AU - Taylor, J.
AU - Guralnik, J. M.
AU - Wallace, R.
AU - Guralnik, J.
AU - Blazer, D. G.
AU - Guralnik, J. M.
AU - Guralnik, J. M.
AU - Khaw, K. T.
AU - Brenner, H.
AU - Raum, E.
AU - Müller, H.
AU - Rothenbacher, D.
AU - Jansson, J. H.
AU - Wennberg, P.
AU - Nissinen, A.
AU - Donfrancesco, C.
AU - Giampaoli, S.
AU - Salomaa, V.
AU - Harald, K.
AU - Jousilahti, P.
AU - Vartiainen, E.
AU - Woodward, M.
AU - D'Agostino, R. B.
AU - Vasan, R. S.
AU - Pencina, M. J.
AU - Bladbjerg, E. M.
AU - Jørgensen, T.
AU - Møller, L.
AU - Jespersen, J.
AU - Dankner, R.
AU - Chetrit, A.
AU - Lubin, F.
AU - Rosengren, A.
AU - Lappas, G.
AU - Björkelund, C.
AU - Lissner, L.
AU - Bengtsson, C.
AU - Cremer, P.
AU - Nagel, D.
AU - Tilvis, R. S.
AU - Strandberg, T. E.
AU - Kiyohara, Y.
AU - Arima, H.
AU - Doi, Y.
AU - Ninomiya, T.
AU - Rodriguez, B.
AU - Dekker, J. M.
AU - Nijpels, G.
AU - Stehouwer, C. D A
AU - Rimm, E.
AU - Pai, J. K.
AU - Sato, S.
AU - Iso, H.
AU - Kitamura, A.
AU - Noda, H.
AU - Goldbourt, U.
AU - Salomaa, V.
AU - Harald, K.
AU - Jousilahti, P.
AU - Vartiainen, E.
AU - Salonen, J. T.
AU - Tuomainen, T. P.
AU - Deeg, D. J H
AU - Poppelaars, J. L.
AU - Meade, T. W.
AU - Cooper, J. A.
AU - Hedblad, B.
AU - Berglund, G.
AU - Engstrom, G.
AU - Verschuren, W. M M
AU - Blokstra, A.
AU - Cushman, M.
AU - Shea, S.
AU - Döring, A.
AU - Koenig, W.
AU - Meisinger, C.
AU - Mraz, W.
AU - Verschuren, W. M M
AU - Blokstra, A.
AU - Bas Bueno-de-Mesquita, H.
AU - Rosengren, A.
AU - Lappas, G.
AU - Kuller, L. H.
AU - Grandits, G.
AU - Selmer, R.
AU - Tverdal, A.
AU - Nystad, W.
AU - Gillum, R.
AU - Mussolino, M.
AU - Rimm, E.
AU - Hankinson, S.
AU - Manson, J. E.
AU - Pai, J. K.
AU - Meade, T. W.
AU - Cooper, J. A.
AU - Knottenbelt, C.
AU - Cooper, J. A.
AU - Bauer, K. A.
AU - Sato, S.
AU - Kitamura, A.
AU - Naito, Y.
AU - Iso, H.
AU - Holme, I.
AU - Selmer, R.
AU - Tverdal, A.
AU - Nystad, W.
AU - Nakagawa, H.
AU - Miura, K.
AU - Ducimetiere, P.
AU - Jouven, X.
AU - Crespo, C. J.
AU - Garcia Palmieri, M. R.
AU - Amouyel, P.
AU - Arveiler, D.
AU - Evans, A.
AU - Ferrieres, J.
AU - Schulte, H.
AU - Assmann, G.
AU - Shepherd, J.
AU - Packard, C. J.
AU - Sattar, N.
AU - Ford, I.
AU - Cantin, B.
AU - Després, J. P.
AU - Dagenais, G. R.
AU - Barrett-Connor, E.
AU - Wingard, D. L.
AU - Bettencourt, R.
AU - Gudnason, V.
AU - Aspelund, T.
AU - Sigurdsson, G.
AU - Thorsson, B.
AU - Trevisan, M.
AU - Witteman, J.
AU - Kardys, I.
AU - Breteler, M.
AU - Hofman, A.
AU - Tunstall-Pedoe, H.
AU - Tavendale, R.
AU - Lowe, G. D O
AU - Woodward, M.
AU - Ben-Shlomo, Y.
AU - Davey-Smith, G.
AU - Howard, B. V.
AU - Zhang, Y.
AU - Umans, J.
AU - Onat, A.
AU - Meade, T. W.
AU - Wilsgaard, T.
AU - Ingelsson, E.
AU - Lind, L.
AU - Giedraitis, V.
AU - Lannfelt, L.
AU - Gaziano, J. M.
AU - Ridker, P.
AU - Gaziano, J. M.
AU - Ridker, P.
AU - Ulmer, H.
AU - Diem, G.
AU - Concin, H.
AU - Tosetto, A.
AU - Rodeghiero, F.
AU - Wassertheil-Smoller, S.
AU - Manson, J. E.
AU - Marmot, M.
AU - Clarke, R.
AU - Collins, R.
AU - Brunner, E.
AU - Shipley, M.
AU - Ridker, P.
AU - Buring, J.
AU - Shepherd, J.
AU - Cobbe, S. M.
AU - Ford, I.
AU - Robertson, M.
AU - He, Y.
AU - Marín Ibañez, A.
AU - Feskens, E. J M
AU - Kromhout, D.
AU - Collins, R.
AU - Di Angelantonio, E.
AU - Erqou, S.
AU - Kaptoge, S.
AU - Lewington, S.
AU - Orfei, L.
AU - Pennells, L.
AU - Perry, P. L.
AU - Ray, K. K.
AU - Sarwar, N.
AU - Alexander, M.
AU - Thompson, A.
AU - Thompson, S. G.
AU - Walker, M.
AU - Watson, S.
AU - Wensley, F.
AU - White, I. R.
AU - Wood, A. M.
AU - Danesh, J.
N1 - Funding Information: Methodological work in the ERFC has been supported by specific grants from the UK Medical Research Council. The ERFC Coordinating Centre is underpinned by a programme grant from the British Heart Foundation and supported by the BUPA Foundation and unrestricted educational grants from GlaxoSmithKline. Various sources have supported recruitment, follow-up and laboratory measurements in the cohorts contributing to the ERFC. Investigators of several of these studies have contributed to a list naming some of these funding sources, which can be found at http://www.phpc.cam.ac.uk/MEU/. Publisher Copyright: © The Author 2010; all rights reserved.
PY - 2010
Y1 - 2010
N2 - Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within-and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.
AB - Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure-risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure-risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure-risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within-and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.
KW - Epidemiological studies
KW - Individual participant data
KW - Meta-analysis
KW - Statistical methods
KW - Survival analysis
UR - http://www.scopus.com/inward/record.url?scp=78149260793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149260793&partnerID=8YFLogxK
U2 - 10.1093/ije/dyq063
DO - 10.1093/ije/dyq063
M3 - Article
C2 - 20439481
AN - SCOPUS:78149260793
VL - 39
SP - 1345
EP - 1359
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
SN - 0300-5771
IS - 5
ER -