Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

Simon Thompson; Stephen Kaptoge; Ian White; Angela Wood; Philip Perry; John Danesh; Emerging Risk Factors Collaboration The Emerging Risk Factors Collaboration; S. G. Thompson; S. Kaptoge; I. R. White; A. M. Wood; P. L. Perry; J. Danesh; R. W. Tipping; C. E. Ford; L. M. Simpson; G. Walldius; I. Jungner; L. E. Chambless; D. B. Panagiotakos; C. Pitsavos; C. Chrysohoou; C. Stefanadis; M. Knuiman; U. Goldbourt; M. Benderly; D. Tanne; P. H. Whincup; S. G. Wannamethee; R. W. Morris; J. Willeit; S. Kiechl; P. Santer; A. Mayr; D. A. Lawlor; J. W G Yarnell; J. Gallacher; E. Casiglia; V. Tikhonoff; P. J. Nietert; S. E. Sutherland; D. L. Bachman; J. E. Keil; M. Cushman; R. P. Tracy; A. Tybjærg-Hansen; B. G. Nordestgaard; M. Benn; R. Frikke- Schmidt; S. Giampaoli; L. Palmieri; S. Panico; D. Vanuzzo; A. Gómez de la Cámara; J. A. Gómez- Gerique; L. Simons; J. McCallum; Y. Friedlander; F. G R Fowkes; A. J. Lee; J. Taylor; J. M. Guralnik; R. Wallace; J. Guralnik; D. G. Blazer; J. M. Guralnik; J. M. Guralnik; K. T. Khaw; H. Brenner; E. Raum; H. Müller; D. Rothenbacher; J. H. Jansson; P. Wennberg; A. Nissinen; C. Donfrancesco; S. Giampaoli; V. Salomaa; K. Harald; P. Jousilahti; E. Vartiainen; M. Woodward; R. B. D'Agostino; R. S. Vasan; M. J. Pencina; E. M. Bladbjerg; T. Jørgensen; L. Møller; J. Jespersen; R. Dankner; A. Chetrit; F. Lubin; A. Rosengren; G. Lappas; C. Björkelund; L. Lissner; C. Bengtsson; P. Cremer; D. Nagel; R. S. Tilvis; T. E. Strandberg; Y. Kiyohara; H. Arima; Y. Doi; T. Ninomiya; B. Rodriguez; J. M. Dekker; G. Nijpels; C. D A Stehouwer; E. Rimm; J. K. Pai; S. Sato; H. Iso; A. Kitamura; H. Noda; U. Goldbourt; V. Salomaa; K. Harald; P. Jousilahti; E. Vartiainen; J. T. Salonen; T. P. Tuomainen; D. J H Deeg; J. L. Poppelaars; T. W. Meade; J. A. Cooper; B. Hedblad; G. Berglund; G. Engstrom; W. M M Verschuren; A. Blokstra; M. Cushman; S. Shea; A. Döring; W. Koenig; C. Meisinger; W. Mraz; W. M M Verschuren; A. Blokstra; H. Bas Bueno-de-Mesquita; A. Rosengren; G. Lappas; L. H. Kuller; G. Grandits; R. Selmer; A. Tverdal; W. Nystad; R. Gillum; M. Mussolino; E. Rimm; S. Hankinson; J. E. Manson; J. K. Pai; T. W. Meade; J. A. Cooper; C. Knottenbelt; J. A. Cooper; K. A. Bauer; S. Sato; A. Kitamura; Y. Naito; H. Iso; I. Holme; R. Selmer; A. Tverdal; W. Nystad; H. Nakagawa; K. Miura; P. Ducimetiere; X. Jouven; C. J. Crespo; M. R. Garcia Palmieri; P. Amouyel; D. Arveiler; A. Evans; J. Ferrieres; H. Schulte; G. Assmann; J. Shepherd; C. J. Packard; N. Sattar; I. Ford; B. Cantin; J. P. Després; G. R. Dagenais; E. Barrett-Connor; D. L. Wingard; R. Bettencourt; V. Gudnason; T. Aspelund; G. Sigurdsson; B. Thorsson; M. Trevisan; J. Witteman; I. Kardys; M. Breteler; A. Hofman; H. Tunstall-Pedoe; R. Tavendale; G. D O Lowe; M. Woodward; Y. Ben-Shlomo; G. Davey-Smith; B. V. Howard; Y. Zhang; J. Umans; A. Onat; T. W. Meade; T. Wilsgaard; E. Ingelsson; L. Lind; V. Giedraitis; L. Lannfelt; J. M. Gaziano; P. Ridker; J. M. Gaziano; P. Ridker; H. Ulmer; G. Diem; H. Concin; A. Tosetto; F. Rodeghiero; S. Wassertheil-Smoller; J. E. Manson; M. Marmot; R. Clarke; R. Collins; E. Brunner; M. Shipley; P. Ridker; J. Buring; J. Shepherd; S. M. Cobbe; I. Ford; M. Robertson; Y. He; A. Marín Ibañez; E. J M Feskens; D. Kromhout; R. Collins; E. Di Angelantonio; S. Erqou; S. Kaptoge; S. Lewington; L. Orfei; L. Pennells; P. L. Perry; K. K. Ray; N. Sarwar; M. Alexander; A. Thompson; S. G. Thompson; M. Walker; S. Watson; F. Wensley; I. R. White; A. M. Wood; J. Danesh

doi:10.1093/ije/dyq063

Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

Simon Thompson, Stephen Kaptoge, Ian White, Angela Wood, Philip Perry, John Danesh, Emerging Risk Factors Collaboration The Emerging Risk Factors Collaboration, S. G. Thompson, S. Kaptoge, I. R. White, A. M. Wood, P. L. Perry, J. Danesh, R. W. Tipping, C. E. Ford, L. M. Simpson, G. Walldius, I. Jungner, L. E. Chambless, D. B. PanagiotakosC. Pitsavos, C. Chrysohoou, C. Stefanadis, M. Knuiman, U. Goldbourt, M. Benderly, D. Tanne, P. H. Whincup, S. G. Wannamethee, R. W. Morris, J. Willeit, S. Kiechl, P. Santer, A. Mayr, D. A. Lawlor, J. W G Yarnell, J. Gallacher, E. Casiglia, V. Tikhonoff, P. J. Nietert, S. E. Sutherland, D. L. Bachman, J. E. Keil, M. Cushman, R. P. Tracy, A. Tybjærg-Hansen, B. G. Nordestgaard, M. Benn, R. Frikke- Schmidt, S. Giampaoli, L. Palmieri, S. Panico, D. Vanuzzo, A. Gómez de la Cámara, J. A. Gómez- Gerique, L. Simons, J. McCallum, Y. Friedlander, F. G R Fowkes, A. J. Lee, J. Taylor, J. M. Guralnik, R. Wallace, J. Guralnik, D. G. Blazer, J. M. Guralnik, J. M. Guralnik, K. T. Khaw, H. Brenner, E. Raum, H. Müller, D. Rothenbacher, J. H. Jansson, P. Wennberg, A. Nissinen, C. Donfrancesco, S. Giampaoli, V. Salomaa, K. Harald, P. Jousilahti, E. Vartiainen, M. Woodward, R. B. D'Agostino, R. S. Vasan, M. J. Pencina, E. M. Bladbjerg, T. Jørgensen, L. Møller, J. Jespersen, R. Dankner, A. Chetrit, F. Lubin, A. Rosengren, G. Lappas, C. Björkelund, L. Lissner, C. Bengtsson, P. Cremer, D. Nagel, R. S. Tilvis, T. E. Strandberg, Y. Kiyohara, H. Arima, Y. Doi, T. Ninomiya, B. Rodriguez, J. M. Dekker, G. Nijpels, C. D A Stehouwer, E. Rimm, J. K. Pai, S. Sato, H. Iso, A. Kitamura, H. Noda, U. Goldbourt, V. Salomaa, K. Harald, P. Jousilahti, E. Vartiainen, J. T. Salonen, T. P. Tuomainen, D. J H Deeg, J. L. Poppelaars, T. W. Meade, J. A. Cooper, B. Hedblad, G. Berglund, G. Engstrom, W. M M Verschuren, A. Blokstra, M. Cushman, S. Shea, A. Döring, W. Koenig, C. Meisinger, W. Mraz, W. M M Verschuren, A. Blokstra, H. Bas Bueno-de-Mesquita, A. Rosengren, G. Lappas, L. H. Kuller, G. Grandits, R. Selmer, A. Tverdal, W. Nystad, R. Gillum, M. Mussolino, E. Rimm, S. Hankinson, J. E. Manson, J. K. Pai, T. W. Meade, J. A. Cooper, C. Knottenbelt, J. A. Cooper, K. A. Bauer, S. Sato, A. Kitamura, Y. Naito, H. Iso, I. Holme, R. Selmer, A. Tverdal, W. Nystad, H. Nakagawa, K. Miura, P. Ducimetiere, X. Jouven, C. J. Crespo, M. R. Garcia Palmieri, P. Amouyel, D. Arveiler, A. Evans, J. Ferrieres, H. Schulte, G. Assmann, J. Shepherd, C. J. Packard, N. Sattar, I. Ford, B. Cantin, J. P. Després, G. R. Dagenais, E. Barrett-Connor, D. L. Wingard, R. Bettencourt, V. Gudnason, T. Aspelund, G. Sigurdsson, B. Thorsson, M. Trevisan, J. Witteman, I. Kardys, M. Breteler, A. Hofman, H. Tunstall-Pedoe, R. Tavendale, G. D O Lowe, M. Woodward, Y. Ben-Shlomo, G. Davey-Smith, B. V. Howard, Y. Zhang, J. Umans, A. Onat, T. W. Meade, T. Wilsgaard, E. Ingelsson, L. Lind, V. Giedraitis, L. Lannfelt, J. M. Gaziano, P. Ridker, J. M. Gaziano, P. Ridker, H. Ulmer, G. Diem, H. Concin, A. Tosetto, F. Rodeghiero, S. Wassertheil-Smoller, J. E. Manson, M. Marmot, R. Clarke, R. Collins, E. Brunner, M. Shipley, P. Ridker, J. Buring, J. Shepherd, S. M. Cobbe, I. Ford, M. Robertson, Y. He, A. Marín Ibañez, E. J M Feskens, D. Kromhout, R. Collins, E. Di Angelantonio, S. Erqou, S. Kaptoge, S. Lewington, L. Orfei, L. Pennells, P. L. Perry, K. K. Ray, N. Sarwar, M. Alexander, A. Thompson, S. G. Thompson, M. Walker, S. Watson, F. Wensley, I. R. White, A. M. Wood, J. Danesh

Biostatistics

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

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	https://doi.org/10.1093/ije/dyq063
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1093/ije/dyq063

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Thompson, S., Kaptoge, S., White, I., Wood, A., Perry, P., Danesh, J., The Emerging Risk Factors Collaboration, E. R. F. C., 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., ... Danesh, J. (2010). Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies. International journal of epidemiology, 39(5), 1345-1359. https://doi.org/10.1093/ije/dyq063

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

Thompson, S, Kaptoge, S, White, I, Wood, A, Perry, P, Danesh, J, The Emerging Risk Factors Collaboration, ERFC, Thompson, SG, Kaptoge, S, White, IR, Wood, AM, Perry, PL, Danesh, J, Tipping, RW, Ford, CE, Simpson, LM, Walldius, G, Jungner, I, Chambless, LE, Panagiotakos, DB, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Knuiman, M, Goldbourt, U, Benderly, M, Tanne, D, Whincup, PH, Wannamethee, SG, Morris, RW, Willeit, J, Kiechl, S, Santer, P, Mayr, A, Lawlor, DA, Yarnell, JWG, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, PJ, Sutherland, SE, Bachman, DL, Keil, JE, Cushman, M, Tracy, RP, Tybjærg-Hansen, A, Nordestgaard, BG, Benn, M, Frikke- Schmidt, R, Giampaoli, S, Palmieri, L, Panico, S, Vanuzzo, D, Gómez de la Cámara, A, Gómez- Gerique, JA, Simons, L, McCallum, J, Friedlander, Y, Fowkes, FGR, Lee, AJ, Taylor, J, Guralnik, JM, Wallace, R, Guralnik, J, Blazer, DG, Guralnik, JM, Guralnik, JM, Khaw, KT, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, JH, Wennberg, P, Nissinen, A, Donfrancesco, C, Giampaoli, S, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, RB, Vasan, RS, Pencina, MJ, Bladbjerg, EM, 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, RS, Strandberg, TE, Kiyohara, Y, Arima, H, Doi, Y, Ninomiya, T, Rodriguez, B, Dekker, JM, Nijpels, G, Stehouwer, CDA, Rimm, E, Pai, JK, Sato, S, Iso, H, Kitamura, A, Noda, H, Goldbourt, U, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Salonen, JT, Tuomainen, TP, Deeg, DJH, Poppelaars, JL, Meade, TW, Cooper, JA, Hedblad, B, Berglund, G, Engstrom, G, Verschuren, WMM, Blokstra, A, Cushman, M, Shea, S, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Verschuren, WMM, Blokstra, A, Bas Bueno-de-Mesquita, H, Rosengren, A, Lappas, G, Kuller, LH, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Rimm, E, Hankinson, S, Manson, JE, Pai, JK, Meade, TW, Cooper, JA, Knottenbelt, C, Cooper, JA, Bauer, KA, 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, CJ, Garcia Palmieri, MR, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, CJ, Sattar, N, Ford, I, Cantin, B, Després, JP, Dagenais, GR, Barrett-Connor, E, Wingard, DL, 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, GDO, Woodward, M, Ben-Shlomo, Y, Davey-Smith, G, Howard, BV, Zhang, Y, Umans, J, Onat, A, Meade, TW, Wilsgaard, T, Ingelsson, E, Lind, L, Giedraitis, V, Lannfelt, L, Gaziano, JM, Ridker, P, Gaziano, JM, Ridker, P, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Wassertheil-Smoller, S, Manson, JE, Marmot, M, Clarke, R, Collins, R, Brunner, E, Shipley, M, Ridker, P, Buring, J, Shepherd, J, Cobbe, SM, Ford, I, Robertson, M, He, Y, Marín Ibañez, A, Feskens, EJM, Kromhout, D, Collins, R, Di Angelantonio, E, Erqou, S, Kaptoge, S, Lewington, S, Orfei, L, Pennells, L, Perry, PL, Ray, KK, Sarwar, N, Alexander, M, Thompson, A, Thompson, SG, Walker, M, Watson, S, Wensley, F, White, IR, Wood, AM & Danesh, J 2010, 'Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies', International journal of epidemiology, vol. 39, no. 5, pp. 1345-1359. https://doi.org/10.1093/ije/dyq063

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. / Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies. In: International journal of epidemiology. 2010 ; Vol. 39, No. 5. pp. 1345-1359.

@article{582a0caac2d946598dec165758828f61,

title = "Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies",

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.",

keywords = "Epidemiological studies, Individual participant data, Meta-analysis, Statistical methods, Survival analysis",

author = "Simon Thompson and Stephen Kaptoge and Ian White and Angela Wood and Philip Perry and John Danesh and {The Emerging Risk Factors Collaboration}, {Emerging Risk Factors Collaboration} and Thompson, {S. G.} and S. Kaptoge and White, {I. R.} and Wood, {A. M.} and Perry, {P. L.} and J. Danesh and Tipping, {R. W.} and Ford, {C. E.} and Simpson, {L. M.} and G. Walldius and I. Jungner and Chambless, {L. E.} and Panagiotakos, {D. B.} and C. Pitsavos and C. Chrysohoou and C. Stefanadis and M. Knuiman and U. Goldbourt and M. Benderly and D. Tanne and Whincup, {P. H.} and Wannamethee, {S. G.} and Morris, {R. W.} and J. Willeit and S. Kiechl and P. Santer and A. Mayr and Lawlor, {D. A.} and Yarnell, {J. W G} and J. Gallacher and E. Casiglia and V. Tikhonoff and Nietert, {P. J.} and Sutherland, {S. E.} and Bachman, {D. L.} and Keil, {J. E.} and M. Cushman and Tracy, {R. P.} and A. Tybj{\ae}rg-Hansen and Nordestgaard, {B. G.} and M. Benn and {Frikke- Schmidt}, R. and S. Giampaoli and L. Palmieri and S. Panico and D. Vanuzzo and {G{\'o}mez de la C{\'a}mara}, A. and {G{\'o}mez- Gerique}, {J. A.} and L. Simons and J. McCallum and Y. Friedlander and Fowkes, {F. G R} and Lee, {A. J.} and J. Taylor and Guralnik, {J. M.} and R. Wallace and J. Guralnik and Blazer, {D. G.} and Guralnik, {J. M.} and Guralnik, {J. M.} and Khaw, {K. T.} and H. Brenner and E. Raum and H. M{\"u}ller and D. Rothenbacher and Jansson, {J. H.} and P. Wennberg and A. Nissinen and C. Donfrancesco and S. Giampaoli and V. Salomaa and K. Harald and P. Jousilahti and E. Vartiainen and M. Woodward and D'Agostino, {R. B.} and Vasan, {R. S.} and Pencina, {M. J.} and Bladbjerg, {E. M.} and T. J{\o}rgensen and L. M{\o}ller and J. Jespersen and R. Dankner and A. Chetrit and F. Lubin and A. Rosengren and G. Lappas and C. Bj{\"o}rkelund and L. Lissner and C. Bengtsson and P. Cremer and D. Nagel and Tilvis, {R. S.} and Strandberg, {T. E.} and Y. Kiyohara and H. Arima and Y. Doi and T. Ninomiya and B. Rodriguez and Dekker, {J. M.} and G. Nijpels and Stehouwer, {C. D A} and E. Rimm and Pai, {J. K.} and S. Sato and H. Iso and A. Kitamura and H. Noda and U. Goldbourt and V. Salomaa and K. Harald and P. Jousilahti and E. Vartiainen and Salonen, {J. T.} and Tuomainen, {T. P.} and Deeg, {D. J H} and Poppelaars, {J. L.} and Meade, {T. W.} and Cooper, {J. A.} and B. Hedblad and G. Berglund and G. Engstrom and Verschuren, {W. M M} and A. Blokstra and M. Cushman and S. Shea and A. D{\"o}ring and W. Koenig and C. Meisinger and W. Mraz and Verschuren, {W. M M} and A. Blokstra and {Bas Bueno-de-Mesquita}, H. and A. Rosengren and G. Lappas and Kuller, {L. H.} and G. Grandits and R. Selmer and A. Tverdal and W. Nystad and R. Gillum and M. Mussolino and E. Rimm and S. Hankinson and Manson, {J. E.} and Pai, {J. K.} and Meade, {T. W.} and Cooper, {J. A.} and C. Knottenbelt and Cooper, {J. A.} and Bauer, {K. A.} and S. Sato and A. Kitamura and Y. Naito and H. Iso and I. Holme and R. Selmer and A. Tverdal and W. Nystad and H. Nakagawa and K. Miura and P. Ducimetiere and X. Jouven and Crespo, {C. J.} and {Garcia Palmieri}, {M. R.} and P. Amouyel and D. Arveiler and A. Evans and J. Ferrieres and H. Schulte and G. Assmann and J. Shepherd and Packard, {C. J.} and N. Sattar and I. Ford and B. Cantin and Despr{\'e}s, {J. P.} and Dagenais, {G. R.} and E. Barrett-Connor and Wingard, {D. L.} and R. Bettencourt and V. Gudnason and T. Aspelund and G. Sigurdsson and B. Thorsson and M. Trevisan and J. Witteman and I. Kardys and M. Breteler and A. Hofman and H. Tunstall-Pedoe and R. Tavendale and Lowe, {G. D O} and M. Woodward and Y. Ben-Shlomo and G. Davey-Smith and Howard, {B. V.} and Y. Zhang and J. Umans and A. Onat and Meade, {T. W.} and T. Wilsgaard and E. Ingelsson and L. Lind and V. Giedraitis and L. Lannfelt and Gaziano, {J. M.} and P. Ridker and Gaziano, {J. M.} and P. Ridker and H. Ulmer and G. Diem and H. Concin and A. Tosetto and F. Rodeghiero and S. Wassertheil-Smoller and Manson, {J. E.} and M. Marmot and R. Clarke and R. Collins and E. Brunner and M. Shipley and P. Ridker and J. Buring and J. Shepherd and Cobbe, {S. M.} and I. Ford and M. Robertson and Y. He and {Mar{\'i}n Iba{\~n}ez}, A. and Feskens, {E. J M} and D. Kromhout and R. Collins and {Di Angelantonio}, E. and S. Erqou and S. Kaptoge and S. Lewington and L. Orfei and L. Pennells and Perry, {P. L.} and Ray, {K. K.} and N. Sarwar and M. Alexander and A. Thompson and Thompson, {S. G.} and M. Walker and S. Watson and F. Wensley and White, {I. R.} and Wood, {A. M.} and J. Danesh",

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: {\textcopyright} The Author 2010; all rights reserved.",

year = "2010",

doi = "10.1093/ije/dyq063",

language = "English (US)",

volume = "39",

pages = "1345--1359",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "5",

}

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 - 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 -

Statistical methods for the time-to-event analysis of individual participant data from multiple epidemiological studies

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