PMID- 16526008
OWN - NLM
STAT- MEDLINE
DCOM- 20070220
LR  - 20091103
IS  - 0277-6715 (Print)
IS  - 0277-6715 (Linking)
VI  - 25
IP  - 23
DP  - 2006 Dec 15
TI  - Non-parametric inference of adverse events under informative censoring.
PG  - 3981-4003
AB  - In long-term treatments or in treatments associated with frequent severe adverse 
      events (AEs) such as those for oncology, it is important to know the probability 
      of occurrence of AEs over time and their severity. However, some patients 
      discontinue treatment and drop out of the clinical trial. Assumption that the 
      drop-outs are non-informative is not always true and are not validated by data. 
      We propose a method of applying competing risk analysis by defining events of 
      'occurrence of AE' and 'drop-out prior to AE'. We focus on one AE at a time. We 
      distinguish obvious non-informative censoring from other censorings that may not 
      be non-informative. Therefore, our approach does not need an independent 
      assumption for drop-outs. The cumulative incidence function estimator (CIFE) for 
      the AE by severity can be obtained by treating the degree of severity as a 
      competing risk within the AE. We also propose a non-parametric estimator of CIF 
      for sequential occurrence of the same AE by forming a subset of subjects with 
      prior occurrence(s) of the same AE and by applying Wang and Wells' estimator. We 
      give a very simple formulation of the cumulative joint incidence function 
      estimator (CJIFE) for subjects who drop out of the clinical trial after having 
      suffered from the AE at least one time. We evaluate the performance of Pepe's 
      variance estimator for CJIFE with small samples by simulations. We find that it 
      works well with a sample size more than 100. A useful graphical presentation for 
      CIFEs and CJIFE is shown.
FAU - Nishikawa, Masako
AU  - Nishikawa M
AD  - Department of Technology Assessment and Biostatistics, National Institute of 
      Public Health, 3-6, Minami 2 chome, Wako, Saitama-Ken, Japan. 
      mnishikawa@niph.go.jp
FAU - Tango, Toshiro
AU  - Tango T
FAU - Ogawa, Makiko
AU  - Ogawa M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Stat Med
JT  - Statistics in medicine
JID - 8215016
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Clinical Trials as Topic/adverse effects/*methods
MH  - Computer Simulation
MH  - *Data Interpretation, Statistical
MH  - Humans
MH  - Neoplasms/drug therapy
MH  - Patient Dropouts
MH  - Risk Assessment/*methods
EDAT- 2006/03/10 09:00
MHDA- 2007/02/21 09:00
CRDT- 2006/03/10 09:00
PHST- 2006/03/10 09:00 [pubmed]
PHST- 2007/02/21 09:00 [medline]
PHST- 2006/03/10 09:00 [entrez]
AID - 10.1002/sim.2511 [doi]
PST - ppublish
SO  - Stat Med. 2006 Dec 15;25(23):3981-4003. doi: 10.1002/sim.2511.