rhDNase as an example of recurrent event analysis

Stat Med. 1997 Sep 30;16(18):2029-47. doi: 10.1002/(sici)1097-0258(19970930)16:18<2029::aid-sim637>3.0.co;2-h.


We consider counting process methods for analysing time-to-event data with multiple or recurrent outcomes, using the models developed by Anderson and Gill, Wei, Lin and Weissfeld and Prentice, Williams and Peterson. We compare the methods, and show how to implement them using popular statistical software programs. By analysing three data sets, we illustrate the strengths and pitfalls of each method. The first example is simulated and involves the effect of a hidden covariate. The second is based on a trial of gamma interferon, and behaves remarkably like the first. The third and most interesting example involves both multiple events and discontinuous intervals at risk, and the three approaches give dissimilar answers. We recommend the AG and marginal models for the analysis of this type of data.

MeSH terms

  • Adult
  • Analysis of Variance
  • Child
  • Cystic Fibrosis / drug therapy*
  • Data Collection / statistics & numerical data
  • Deoxyribonuclease I / therapeutic use*
  • Double-Blind Method
  • Expectorants / therapeutic use*
  • Granulomatous Disease, Chronic / therapy*
  • Humans
  • Interferon-gamma / therapeutic use*
  • Mathematical Computing*
  • Models, Statistical*
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Recombinant Proteins / therapeutic use
  • Risk
  • Software*
  • Survival Analysis*
  • Treatment Outcome


  • Expectorants
  • Recombinant Proteins
  • Interferon-gamma
  • DNASE1 protein, human
  • Deoxyribonuclease I