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Recurrent event analysis

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are popular models in social sciences and medical science to assess associations between variables and risk of recurrence, or to predict recurrent event outcomes. Many extensions of survival models based on the Cox proportional hazards approach have been proposed to handle recurrent event data. These
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The marginal means/rates model considers all recurrent events of the same subject as a single counting process and does not require time-varying covariates to reflect the past history of the process, which makes it a more flexible model. Instead, the full history of the counting process may influence
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The processes which generate events repeatedly over time are referred to as recurrent event processes, which are different from processes analyzed in time-to-event analysis: whereas time-to-event analysis focuses on the time to a single terminal event, individuals may be at risk for subsequent events
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is a popular model for recurrent event data, which models the number of recurrences that have occurred. Poisson regression assumes that the number of recurrences has a Poisson distribution with a fixed rate of recurrence over time. The logarithm of the expected number of recurrences is modeled by a
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that analyzes the time until recurrences occur, such as recurrences of traits or diseases. Recurrent events are often analyzed in social sciences and medical studies, for example recurring infections, depressions or cancer recurrences. Recurrent event analysis attempts to answer certain questions,
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In multi-state models, the recurrent event processes of individuals are described by different states. The different states may describe the recurrence number, or whether the subject is at risk of recurrence. A change of state is called a transition (or an event) and is central in this framework,
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Time to recurrence is often correlated within subjects, as some subjects can be more frail to experiencing recurrences. If the correlated nature of the data is ignored, the confidence intervals (CI) for the estimated rates could be artificially narrow, which may result in false positive results.
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In frailty models, a random effect is included in the recurrent event model which describes the individual excess risk that can not be explained by the included covariates. The frailty term induces dependence among the recurrence times within subjects.
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When a heterogeneous group of individuals or processes is considered, the assumption of a common event intensity is no longer plausible. Greater generality can be achieved by incorporating fixed or time-varying covariates in the intensity function.
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It is possible to use robust 'sandwich' estimators for the variance of regression coefficients. Robust variance estimators are based on a jackknife estimate, which anticipates correlation within subjects and provides robust standard errors.
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which is fully characterized through estimation of transition probabilities between states and transition intensities that are defined as instantaneous hazards of progression to one state, conditional on occupying another state.
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Well-known examples of Cox-based recurrent event models are the Andersen and Gill model, the Prentice, Williams and Petersen model and the Wei–Lin–Weissfeld model
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such as: how many recurrences occur on average within a certain time interval? Which factors are associated with a higher or lower risk of recurrence?
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Models for recurrent events can be specified by considering the probability distribution for the number of recurrences in short intervals
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R. L. Prentice, B. J. Williams, A. V. Peterson, On the regression analysis of multivariate failure time data,
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Determining the relationship of fixed covariates, treatments, and time-varying factors to event occurrence
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records the cumulative number of events generated by the process; specifically,
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10.1002/(sici)1097-0258(20000115)19:1<13::aid-sim279>3.0.co;2-5
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Identifying and characterizing variation across a population of processes
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describes the instantaneous probability of an event occurring at time
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after the first in recurrent event analysis, until they are censored.
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is the number of events occurring over the time interval
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Understanding and describing individual event processes
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models can be characterized by four model components:
242: 508: 440: 420: 396: 355: 320: 307:{\textstyle N(t)=\sum _{k=1}^{\infty }I(T_{k}\leq t)} 195: 172: 145: 93: 67: 390:, given the history of event occurrence before time 857:Kelly, Patrick J.; Lim, Lynette L-Y. (2000-01-15). 948:, Volume 68, Issue 2, August 1981, Pages 373–379, 630: 494: 426: 402: 382: 338: 306: 228: 178: 158: 131: 79: 61:For a single recurrent event process starting at 542: 39:Objectives of recurrent event analysis include: 975:Journal of the American Statistical Association 798:Amorim, Leila DAF; Cai, Jianwen (2014-12-09). 132:{\displaystyle 0\leq T_{1}<T_{2}<\dots } 691:Extended Cox proportional hazards (PH) models 669:linear combination of explanatory variables. 8: 763:The Statistical Analysis of Recurrent Events 489: 456: 223: 196: 904:Andersen, P. K.; Gill, R. D. (1982-12-01). 766:. Statistics for Biology and Health. 2007. 655:Statistical models for recurrent event data 502:, then the intensity is formally defined as 495:{\displaystyle H(t)=\{N(s):0\leq s<t\}} 921: 833: 815: 713:Correction for within-subject correlation 560: 545: 518: 507: 439: 419: 395: 354: 319: 289: 273: 262: 241: 194: 171: 150: 144: 117: 104: 92: 66: 753: 678:the mean function of recurrent events. 721:Correlated event times within subjects 804:International Journal of Epidemiology 7: 793: 791: 643:Description of recurrent event data 616: 581: 546: 371: 274: 14: 229:{\displaystyle \{N(t),0\leq t\}} 987:10.1080/01621459.1989.10478873 697:Cox proportional hazard models 611: 602: 596: 587: 572: 566: 552: 535: 532: 526: 519: 512: 468: 462: 450: 444: 383:{\displaystyle [t,t+\Delta t)} 377: 356: 333: 321: 301: 282: 252: 246: 208: 202: 139:denote the event times, where 1: 49:Comparing groups of processes 16:Branch of survival analysis 1031: 673:Marginal means/rates model 772:10.1007/978-0-387-69810-6 186:th event. The associated 965:Wei, L. J.; Lin, D. Y.; 910:The Annals of Statistics 647:As a counterpart of the 20:Recurrent event analysis 954:10.1093/biomet/68.2.373 57:Notation and frameworks 923:10.1214/aos/1176345976 863:Statistics in Medicine 632: 496: 428: 404: 384: 340: 308: 278: 230: 180: 160: 133: 81: 633: 497: 429: 405: 385: 341: 309: 258: 231: 181: 161: 159:{\displaystyle T_{k}} 134: 82: 506: 438: 418: 394: 353: 318: 240: 193: 170: 143: 91: 65: 166:is the time of the 80:{\displaystyle t=0} 981:(408): 1065–1073. 817:10.1093/ije/dyu222 695:Extensions of the 649:Kaplan–Meier curve 628: 559: 492: 424: 412:intensity function 400: 380: 336: 304: 226: 176: 156: 129: 77: 1015:Survival analysis 781:978-0-387-69809-0 682:Multi-state model 623: 541: 427:{\displaystyle t} 403:{\displaystyle t} 179:{\displaystyle k} 24:survival analysis 1022: 999: 998: 962: 956: 942: 936: 935: 925: 901: 895: 894: 854: 848: 847: 837: 819: 795: 786: 785: 758: 637: 635: 634: 629: 624: 622: 614: 561: 558: 522: 501: 499: 498: 493: 433: 431: 430: 425: 409: 407: 406: 401: 389: 387: 386: 381: 345: 343: 342: 339:{\displaystyle } 337: 313: 311: 310: 305: 294: 293: 277: 272: 235: 233: 232: 227: 188:counting process 185: 183: 182: 177: 165: 163: 162: 157: 155: 154: 138: 136: 135: 130: 122: 121: 109: 108: 86: 84: 83: 78: 1030: 1029: 1025: 1024: 1023: 1021: 1020: 1019: 1005: 1004: 1003: 1002: 964: 963: 959: 943: 939: 903: 902: 898: 856: 855: 851: 797: 796: 789: 782: 760: 759: 755: 750: 741: 732: 730:Robust variance 723: 707:Baseline hazard 693: 684: 675: 662: 657: 645: 615: 562: 504: 503: 436: 435: 416: 415: 392: 391: 351: 350: 316: 315: 285: 238: 237: 191: 190: 168: 167: 146: 141: 140: 113: 100: 89: 88: 63: 62: 59: 37: 22:is a branch of 17: 12: 11: 5: 1028: 1026: 1018: 1017: 1007: 1006: 1001: 1000: 957: 937: 896: 849: 810:(1): 324–333. 787: 780: 752: 751: 749: 746: 740: 739:Frailty models 737: 731: 728: 722: 719: 715: 714: 711: 708: 705: 704:Risk intervals 692: 689: 683: 680: 674: 671: 661: 658: 656: 653: 644: 641: 627: 621: 618: 613: 610: 607: 604: 601: 598: 595: 592: 589: 586: 583: 580: 577: 574: 571: 568: 565: 557: 554: 551: 548: 544: 540: 537: 534: 531: 528: 525: 521: 517: 514: 511: 491: 488: 485: 482: 479: 476: 473: 470: 467: 464: 461: 458: 455: 452: 449: 446: 443: 423: 399: 379: 376: 373: 370: 367: 364: 361: 358: 335: 332: 329: 326: 323: 303: 300: 297: 292: 288: 284: 281: 276: 271: 268: 265: 261: 257: 254: 251: 248: 245: 225: 222: 219: 216: 213: 210: 207: 204: 201: 198: 175: 153: 149: 128: 125: 120: 116: 112: 107: 103: 99: 96: 76: 73: 70: 58: 55: 54: 53: 50: 47: 44: 36: 33: 15: 13: 10: 9: 6: 4: 3: 2: 1027: 1016: 1013: 1012: 1010: 996: 992: 988: 984: 980: 976: 972: 968: 967:Weissfeld, L. 961: 958: 955: 951: 947: 941: 938: 933: 929: 924: 919: 915: 911: 907: 900: 897: 892: 888: 884: 880: 876: 872: 868: 864: 860: 853: 850: 845: 841: 836: 831: 827: 823: 818: 813: 809: 805: 801: 794: 792: 788: 783: 777: 773: 769: 765: 764: 757: 754: 747: 745: 738: 736: 729: 727: 720: 718: 712: 709: 706: 703: 702: 701: 698: 690: 688: 681: 679: 672: 670: 667: 666:Poisson model 660:Poisson model 659: 654: 652: 650: 642: 640: 625: 619: 608: 605: 599: 593: 590: 584: 578: 575: 569: 563: 555: 549: 538: 529: 523: 515: 509: 486: 483: 480: 477: 474: 471: 465: 459: 453: 447: 441: 421: 413: 397: 374: 368: 365: 362: 359: 347: 330: 327: 324: 298: 295: 290: 286: 279: 269: 266: 263: 259: 255: 249: 243: 220: 217: 214: 211: 205: 199: 189: 173: 151: 147: 126: 123: 118: 114: 110: 105: 101: 97: 94: 74: 71: 68: 56: 51: 48: 45: 42: 41: 40: 34: 32: 28: 25: 21: 978: 974: 960: 945: 940: 913: 909: 899: 869:(1): 13–33. 866: 862: 852: 807: 803: 762: 756: 742: 733: 724: 716: 694: 685: 676: 663: 646: 411: 348: 187: 60: 38: 35:Introduction 29: 19: 18: 946:Biometrika 748:References 995:0162-1459 932:0090-5364 883:0277-6715 826:1464-3685 617:Δ 591:− 582:Δ 553:↓ 547:Δ 510:λ 478:≤ 372:Δ 296:≤ 275:∞ 260:∑ 218:≤ 127:… 98:≤ 1009:Category 969:(1989). 891:10623910 844:25501468 710:Risk set 835:4339761 993:  930:  889:  881:  842:  832:  824:  778:  410:. 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Index

survival analysis
Kaplan–Meier curve
Poisson model
Cox proportional hazard models
The Statistical Analysis of Recurrent Events
doi
10.1007/978-0-387-69810-6
ISBN
978-0-387-69809-0


"Modelling recurrent events: a tutorial for analysis in epidemiology"
doi
10.1093/ije/dyu222
ISSN
1464-3685
PMC
4339761
PMID
25501468
<13::aid-sim279>3.0.co;2-5 "Survival analysis for recurrent event data: an application to childhood infectious diseases"
doi
10.1002/(sici)1097-0258(20000115)19:1<13::aid-sim279>3.0.co;2-5
ISSN
0277-6715
PMID
10623910
"Cox's Regression Model for Counting Processes: A Large Sample Study"
doi
10.1214/aos/1176345976

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