PMID- 22658815
OWN - NLM
STAT- MEDLINE
DCOM- 20130109
LR  - 20181201
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Linking)
VI  - 46
IP  - 9
DP  - 2012 Sep
TI  - Classifying responders and non-responders; does it help when there is evidence of 
      differentially responding patient groups?
PG  - 1169-73
LID - 10.1016/j.jpsychires.2012.05.005 [doi]
AB  - INTRODUCTION: Continuous trial outcomes are often dichotomized into 'response' 
      and 'non-response' categories prior to statistical analysis. This facilitates the 
      interpretation of results, but generally reduces statistical power. Exceptions 
      may occur when response in the study population is heterogeneous, and outcomes 
      are bimodally distributed. We explore whether bimodality is present in 
      antidepressant trial data and whether dichotomizing then indeed results in more 
      powerful statistical tests. METHODS: The distributions of relative changes from 
      baseline (rCFB) on the Hamilton depression rating scale (HAM-D) were estimated 
      using pooled data from nine antidepressant trials. T-tests on rCFB scores and 
      chi-square tests on dichotomized outcomes were compared to assess the 
      consequences of dichotomization, using both the commonly applied cutoff (i.e. 
      rCFB > 50%) and an estimated cutoff that provided optimal separation of the 
      mixture of two normal distributions that best fitted the pooled placebo outcomes. 
      The power of both tests was also evaluated for simulated scenario's that varied 
      the degree of bimodality and the treatment effect and sample size. RESULTS: 
      Placebo and treatment groups showed evidence of bimodality. The estimated cutoff 
      closely matched the commonly applied cutoff. Nevertheless, t-tests generally 
      yielded smaller p-values than chi-square tests. Simulations showed that 
      dichotomization only provides superior power when bimodality was considerably 
      more marked than observed in the empirical data. CONCLUSION: Antidepressant trial 
      outcomes showed bimodality, suggesting differential response among patient 
      groups. This heterogeneity in outcome distributions should be reported more 
      often, since a comparison of means does not adequately summarize the differences 
      between treatment groups. However, simply dichotomizing outcomes is not an 
      appropriate alternative as it reduces statistical power.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Boessen, Ruud
AU  - Boessen R
AD  - Julius Center for Health Sciences and Primary Care, University Medical Center 
      Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. 
      R.Boessen-2@umcutrecht.nl
FAU - Groenwold, Rolf H H
AU  - Groenwold RH
FAU - Knol, Mirjam J
AU  - Knol MJ
FAU - Grobbee, Diederick E
AU  - Grobbee DE
FAU - Roes, Kit C B
AU  - Roes KC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120601
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Antidepressive Agents)
RN  - 1806D8D52K (Amitriptyline)
RN  - 250PJI13LM (Mianserin)
RN  - A051Q2099Q (Mirtazapine)
SB  - IM
MH  - Amitriptyline/*therapeutic use
MH  - Antidepressive Agents/*therapeutic use
MH  - Chi-Square Distribution
MH  - *Clinical Trials as Topic
MH  - Computer Simulation
MH  - Depressive Disorder/*drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Mianserin/*analogs & derivatives/therapeutic use
MH  - Mirtazapine
MH  - Models, Statistical
MH  - Psychiatric Status Rating Scales
MH  - Sample Size
MH  - Treatment Outcome
EDAT- 2012/06/05 06:00
MHDA- 2013/01/10 06:00
CRDT- 2012/06/05 06:00
PHST- 2011/11/16 00:00 [received]
PHST- 2012/05/02 00:00 [revised]
PHST- 2012/05/07 00:00 [accepted]
PHST- 2012/06/05 06:00 [entrez]
PHST- 2012/06/05 06:00 [pubmed]
PHST- 2013/01/10 06:00 [medline]
AID - S0022-3956(12)00147-1 [pii]
AID - 10.1016/j.jpsychires.2012.05.005 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2012 Sep;46(9):1169-73. doi: 10.1016/j.jpsychires.2012.05.005. 
      Epub 2012 Jun 1.