PMID- 25867124
OWN - NLM
STAT- MEDLINE
DCOM- 20160411
LR  - 20210112
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 156
IP  - 7
DP  - 2015 Jul
TI  - Development and preliminary validation of an integrated efficacy-tolerability 
      composite measure for the evaluation of analgesics.
PG  - 1357-1365
LID - 10.1097/j.pain.0000000000000186 [doi]
AB  - The goal of this analysis was to develop and evaluate integrated measures of 
      benefit and tolerability of analgesic drugs in clinical trials. We evaluated an 
      efficacy-tolerability composite (ETC) measure combining different cutoff values 
      for daily pain reduction (>/=20%, >/=30%, or >/=50% pain reduction) and adverse events 
      (AEs) (no AE, no or mild AEs, no or mild drug-related AEs). Nine ETC cutoff 
      values (3 x 3) were tested using data from a randomized double-blind trial 
      comparing tapentadol extended release (ER) (n = 310), oxycodone controlled 
      release (CR) (n = 322), and placebo (n = 314) in subjects with chronic low back 
      pain. Efficacy-tolerability composite scores were calculated as the mean number 
      of days a subject met the ETC criterion divided by the number of days the subject 
      was expected to be in study; ETC scores were then averaged in each treatment 
      group. For all 9 ETC measures, validity was demonstrated by significant 
      correlation of ETC scores with patients' Global Impression of change and with 
      change from baseline in pain scores. Tapentadol ER ETC scores were statistically 
      significantly higher than oxycodone CR ETC scores for 4 of the ETC measures. 
      "No/mild drug-related AE and >/=20% pain reduction" demonstrated the best overall 
      validity (correlation with patients' global impression of change) and 
      responsiveness (discrimination between treatment groups), yielding a higher 
      standardized effect size for tapentadol ER compared with placebo (0.19 [95% 
      confidence interval: 0.031-0.346]) and with oxycodone CR (0.23 [95% confidence 
      interval: 0.070-0.383]) than other cutoff values. Thus, we have identified herein 
      a composite measure that seems to be a valid and responsive measure of the 
      overall efficacy and tolerability of analgesics in clinical trials.
FAU - Katz, Nathaniel P
AU  - Katz NP
AD  - Analgesic Solutions, Natick, MA, USA Tufts University School of Medicine, Boston, 
      MA, USA Janssen Scientific Affairs, Titusville, NJ, USA Janssen Research and 
      Development, Titusville, NJ, USA Johnson & Johnson, New Brunswick, NJ, USA.
FAU - Mou, Joy
AU  - Mou J
FAU - Trudeau, Jeremiah
AU  - Trudeau J
FAU - Xiang, Jim
AU  - Xiang J
FAU - Vorsanger, Gary
AU  - Vorsanger G
FAU - Orman, Camille
AU  - Orman C
FAU - Kim, Myoung
AU  - Kim M
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Analgesics)
RN  - 0 (Phenols)
RN  - H8A007M585 (Tapentadol)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Analgesics/pharmacology/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pain/diagnosis/*drug therapy
MH  - Pain Measurement/*drug effects/*standards
MH  - Phenols/pharmacology/*therapeutic use
MH  - Tapentadol
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2015/04/14 06:00
MHDA- 2016/04/12 06:00
CRDT- 2015/04/14 06:00
PHST- 2015/04/14 06:00 [entrez]
PHST- 2015/04/14 06:00 [pubmed]
PHST- 2016/04/12 06:00 [medline]
AID - 00006396-201507000-00023 [pii]
AID - 10.1097/j.pain.0000000000000186 [doi]
PST - ppublish
SO  - Pain. 2015 Jul;156(7):1357-1365. doi: 10.1097/j.pain.0000000000000186.