Predictors of placebo response in pooled lamotrigine neuropathic pain clinical trials.
OBJECTIVE
One limitation of neuropathic pain clinical trials is the often large and variable extent of response in the placebo group, possibly obscuring true medication effects. We pooled data from 252 individuals in the placebo arms of 3 clinical trials of lamotrigine in patients with neuropathic pain to examine the relationship of baseline patient and study site characteristics with 12-week change in the Pain Intensity Numerical Rating Scale score (DeltaPI-NRS). The 574 patients in the pooled lamotrigine treatment arms were used as a replication dataset.


METHODS
We performed univariable and multivariable regression analysis of predictors of DeltaPI-NRS. Clinical factors examined were baseline pain intensity score (mean daily PI-NRS over the week prior to randomization), age, sex, diagnosis, prior and concurrent gabapentin use, prior and concurrent tricyclic antidepressant use, pain duration, variability of daily pain scores during the baseline week, and slope of daily pain scores over the baseline week. Site factors evaluated were study site, US geographic region, recruitment rate, and recruitment period.


RESULTS
Baseline PI-NRS and site recruitment rate were independent predictors of the 12-week DeltaPI-NRS in the last observation carried forward, observed case, and repeated measures analyses. Patients with higher baseline PI-NRS scores had a significantly greater 12-week reduction in pain intensity than patients with lower baseline scores. Patients within sites with a faster recruitment rate also had a significantly greater reduction of pain intensity than those in sites with slower recruitment.


CONCLUSIONS
These results suggest that both patient and study site characteristics can influence the response in the placebo arms of neuropathic pain studies.
Irizarry
Michael C
MC
WW Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA. michael.c.irizarry@gsk.com
Webb
David J
DJ
Ali
Zahid
Z
Chizh
Boris A
BA
Gold
Michael
M
Kinrade
Frances J
FJ
Meisner
Paul D
PD
Blum
David
D
Silver
Marianne T
MT
Weil
John G
JG
D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009437:Neuralgia / Q000188:drug therapy* / Q000523:psychology; D018710:Pain Clinics; D015990:Placebo Effect; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D013997:Time Factors; D014227:Triazines / Q000627:therapeutic use*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine