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Table e-1. Study characteristics of randomized clinical trials of efficacious medications for neuropathic pain (n = 106 treatment groups)Age in years (n=102), mean (SD) / 60.3(8.6)
Duration of pain in years (n=33) , mean (SD) / 4.1 (1.7)
Baseline pain (n=89) , mean (SD) / 60.4 (9.6)
% male (n=97) , mean (SD) / 55.8 (15.9)
% Caucasian (n=64) , mean (SD) / 84.7 (15.3)
Number of study sites (n=93), median (IQR) / 22 (1-45)
Number of patients enrolled (n=105) , median (IQR) / 158 (50-325)
Treatment period in days, mean (SD) / 53.5 (26.3)
Titration period in days, median (IQR) / 14 (6-28)
Year of publication, median (IQR) / 2005 (2003-2008)
Pain measure (%)
NRS / 76 (71.7)
VAS / 12 (11.3)
Other / 18 (17.0)
Design, no. (%)
Parallel / 78 (73.6)
Crossover / 28 (26.4)
Minimum duration of chronic pain, no. (%)
≤ 3 months / 47 (44.3)
> 3 months / 38 (35.9)
Missing / 21 (19.8)
Minimum baseline pain, no. (%)
30 / 9 (8.5)
40 / 53 (50.0)
50-60 / 7 (6.6)
Missing / 37 (34.9)
Number of study sites, no. (%)
1 / 27 (25.5)
> 1 / 70 (66.0)
Missing / 9 (8.5)
Number of treatment arms including placebo, no. (%)
2 / 50 (47.2)
> 2 / 56 (52.8)
Dosage regimen of active therapy, no. (%)
Fixed / 46 (43.4)
Flexible / 56 (52.8)
Missing / 4 (3.8)
Rescue medication allowed, no. (%)
No / 66 (62.3)
Yes / 34 (32.1)
Missing / 6 (5.7)
Concomitant analgesics allowed, no. (%)
No / 38 (35.9)
Yes / 41 (38.7)
Missing / 27 (25.5)
Quality score, no. (%)
2-3 / 15 (14.2)
4 / 29 (27.4)
5 / 41 (38.7)
Missing / 21 (19.8)
Countries, no. (%)
US and Canada only / 46 (43.4)
Other countries / 55 (51.9)
Missing / 5 (4.7)
Type of neuropathic pain, no. (%)
PHN / 31 (29.2)
DPN or other peripheral neuropathy / 52 (49.1)
Other / 23 (21.7)
Active medication
Antidepressant medications (TCAs; SSNRIs)
Antiepileptic medications (gabapentin,
pregabalin, carbamazepine)
Opioid analgesics and tramadol
Topical lidocaine
High-concentration capsaicin / 23 (21.7)
57 (53.8)*
14 (13.2)
6 (5.7)
6 (5.7)
IQR = interquartile range; NRS = numerical rating scale; SD = standard deviation; SSNRI = selective serotonin and reuptake inhibitor; TCA = tricyclic antidpressant; VAS = visual analogue scale.
* Two trials examined combinations of an antiepileptic medication and an opioid analgesic.
Table e-2. Study characteristics of all randomized clinical trials of medications for neuropathic pain (n = 223 treatment groups)Age in years (n=207), mean (SD) / 58.4(8.3)
Duration of pain in years (n=85) , mean (SD) / 4.0 (1.5)
Baseline pain (n=180) , mean (SD) / 61.5 (10.4)
% male (n=199) , mean (SD) / 55.4 (17.2)
% Caucasian (n=117) , mean (SD) / 85.8 (13.1)
Number of study sites (n=185), median (IQR) / 10 (1-41)
Number of patients enrolled (n=222) , median (IQR) / 126 (41-302)
Treatment period in days, mean (SD) / 61.1 (35.6)
Titration period in days, median (IQR) / 10 (0-28)
Year of publication, median (IQR)
Pain measure (%)
NRS
VAS
Other / 2005 (2002-2008)
122 (54.7)
42 (18.8)
59 (26.5)
Design, no. (%)
Parallel / 168 (75.3)
Crossover / 55 (24.7)
Minimum duration of chronic pain, no. (%)
≤ 3 months / 86 (38.6)
> 3 months / 80 (35.9)
Missing / 57 (25.6)
Assigned efficacy of active therapy, no. (%)
No / 117 (52.5)
Yes / 106 (47.5)
Minimum baseline pain, no. (%)
≤ 30 / 19 (8.5)
40 / 102 (45.7)
50-60 / 16 (7.2)
Missing / 86 (38.6)
Number of study sites, no. (%)
1 / 69 (30.9)
> 1 / 126 (56.5)
Missing / 28 (12.7)
Number of treatment arms including placebo, no. (%)
2 / 103 (46.2)
> 2 / 120 (53.8)
Dosage regimen of active therapy, no. (%)
Fixed / 117 (52.5)
Flexible / 95 (42.6)
Missing / 11 (4.9)
Rescue medication allowed, no. (%)
No / 126 (56.5)
Yes / 87 (39.0)
Missing / 10 (4.5)
Concomitant analgesics allowed, no. (%)
No / 98 (44.0)
Yes / 72 (32.3)
Missing / 53 (23.8)
Quality score, no. (%)
2-3 / 41 (18.4)
4 / 74 (33.2)
5 / 80 (35.9)
Missing / 28 (12.6)
Countries, no. (%)
US and Canada only / 105 (47.1)
Other countries / 95 (42.6)
Missing / 23 (10.3)
Type of neuropathic pain, no. (%)
PHN / 43 (19.3)
DPN or other peripheral neuropathy / 144 (64.6)
Other / 36 (16.1)
IQR = interquartile range; SD = standard deviation.
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Table e-3. Univariate analyses of relationships between study characteristics and standardized effect size (n = 223 treatment groups)SES / Group Difference or Coefficient* / 95% CI / P value / R2**
Design
Crossover (reference) / 0.43 / 0
Parallel / 0.34 / -0.09 / -0.21 / 0.03 / 0.163
Assigned efficacy of active therapy
No / 0.29 / 0.035
Yes / 0.43 / 0.14 / 0.03 / 0.24 / 0.013
Minimum duration of chronic pain
≤ 3 months (reference) / 0.40 / 0.004
> 3 months / 0.38 / -0.02 / -0.16 / 0.11 / 0.736
Missing / 0.28 / -0.12 / -0.26 / 0.01 / 0.082
Minimum baseline pain
30 (reference) / 0.27 / 0
40 / 0.42 / 0.15 / 0.01 / 0.29 / 0.038
50-60 / 0.35 / 0.08 / -0.14 / 0.29 / 0.49
Missing / 0.31 / 0.04 / -0.11 / 0.19 / 0.606
Number of study sites
1 (reference) / 0.40 / 0.012
> 1 / 0.35 / -0.05 / -0.2 / 0.1 / 0.513
Missing / 0.3 / -0.1 / -0.31 / 0.12 / 0.365
Number of treatment arms including placebo
2 (reference) / 0.38 / 0
> 2 / 0.32 / -0.06 / -0.17 / 0.06 / 0.328
Dosage regimen of active therapy
Fixed (reference) / 0.37 / 0
Flexible / 0.35 / -0.02 / -0.13 / 0.1 / 0.786
Missing / 0.48 / 0.11 / -0.18 / 0.4 / 0.463
Rescue medication allowed
No (reference) / 0.39 / 0.005
Yes / 0.35 / -0.04 / -0.15 / 0.07 / 0.492
Missing / 0.19 / -0.2 / -0.68 / 0.29 / 0.426
Concomitant analgesics allowed
No (reference) / 0.38 / 0.004
Yes / 0.40 / 0.02 / -0.11 / 0.15 / 0.761
Missing / 0.26 / -0.12 / -0.27 / 0.02 / 0.106
Jadad quality rating
2-3 (reference) / 0.37 / 0.008
4 / 0.39 / 0.02 / -0.17 / 0.22 / 0.806
5 / 0.38 / 0.01 / -0.19 / 0.2 / 0.948
Missing / 0.27 / -0.1 / -0.3 / 0.09 / 0.294
Countries
Other countries (reference) / 0.43 / 0.047
US and Canada only (reference) / 0.32 / -0.11 / -0.22 / 0.01 / 0.072
Missing / 0.17 / -0.26 / -0.42 / -0.11 / 0.001
Type of neuropathic pain
PHN (reference) / 0.41 / 0.003
DPN & other peripheral neuropathy / 0.35 / -0.06 / -0.22 / 0.1 / 0.459
Duration of pain in years / - / 0.03 / -0.02 / 0.08 / 0.226 / 0
Baseline pain / - / 0.03 / -0.03 / 0.08 / 0.384 / 0.001
Age (10-year increment) / - / 0.07 / 0.01 / 0.14 / 0.076 / 0.014
% male / - / 0 / 0 / 0.01 / 0.259 / 0
% Caucasian / - / 0.01 / 0 / 0.01 / 0.014
0.068
Number of patients enrolled (100 patient increment) / - / -0.04 / -0.08 / -0.01 / 0.011 / 0.037
Treatment period in days (7 day increment) / - / -0.01 / -0.02 / -0.00 / 0.004 / 0.055
Titration period in days (7 day increment) / - / -0.02 / -0.04 / -0.00 / 0.032 / 0.025
Year of publication / - / -0.04 / -0.16 / 0.07 / 0.459 / 0.007
CI = confidence interval; SES = standardized effect size.
* Difference in SES between the referent group and the non-referent group for categorical variables or the coefficient for a continuous variable.
** R2 equals the proportion of the true variance accounted for by the covariate; 0 indicates that the estimated value is less than or equal to 0.