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. Author manuscript; available in PMC: 2017 Jan 1.
Published in final edited form as: Clin Ther. 2015 Nov 11;38(1):162–179.e6. doi: 10.1016/j.clinthera.2015.10.010

Table 2.

Summary of the rating results regarding the quality of evidence

Pramipexole compared with placebo for primary moderate to severe restless leg syndrome
Patient or population: primary moderate to severe restless leg syndrome, according the International Restless Legs Syndrome Study Group criteria; 18 years
or older
Settings: Outpatient settings in Europe, North America, China, Japan
Intervention: Pramipexole
Comparison: Placebo
Outcomes Illustrative comparative risks* (95% CI)
 Relative
effect
(95%
CI)		 No of
participants
(studies)		 Quality of
the
evidence
(GRADE)		 Comments
Assumed risk Corresponding risk
Placebo Pramipexole
Change in the IRLS20,22–25,27–29
International Restless Leg
Syndrome Study Group Rating
Scale. Scale from 0 to 40.
Follow-up: 3–26 weeks		 The mean change on IRLS
ranged across control
groups from
-5.7 to −11.35 points		 The mean change on IRLS
in pramipexole groups was
4.64 lower
(5.95 to 3.33 lower)		 - 2420
(8 studies)		 ⊕⊕⊝⊝
low1, 2 		The difference in the treatment
duration was the main cause of
the heterogeneity
Responder rates for the IRLS
score22–29
Count
Follow-up: 3–26 weeks		 38 per 100 60 per 100
(55 to 66)		 RR 1.57
(1.43 to
1.73)		 2188
(8 studies)		 ⊕⊕⊕⊝
moderate2 		-
Responder rates for the
CGI-I20,22–31
Count
Follow-up: 3–26 weeks		 44 per 100 66 per 100
(58 to 74)		 RR 1.48
(1.31 to
1.66)		 3234
(11
studies)		 ⊕⊕⊝⊝
low1, 2 		BI248.61620 was the main
contributor for heterogeneity.
Responder rates for the
PGI20,22–29
Count
Follow-up: 3–26 weeks		 41 per 100 63 per 100
(54 to 74)		 RR 1.54
(1.31 to
1.81)		 2568
(9 studies)		 ⊕⊕⊝⊝
low1, 2 		BI248.61620 was the main
contributor for heterogeneity.
Change in quality of life23,25,27,28
The Johns Hopkins RLS Quality
of Life questionnaire score
Follow-up: 12–26 weeks		 The mean change in
quality of life ranged
across control groups
from
12.3 to 14.5 points		 The mean change in quality
of life in pramipexole
groups was
5.39 higher
(2.28 to 8.5 higher)		 - 1397
(4 studies)		 ⊕⊕⊝⊝
low1, 2 		Hogl et al.27 was the main
contributor for heterogeneity.
Quality of sleep30,31
Quality of sleep with a
Questionnaire
Follow-up: mean 12 weeks		 The mean quality of sleep
ranged across control
groups from
6–57.7 points		 The mean quality of sleep
in pramipexole groups was
0.51 higher
(0.03 lower to 1.06 higher)		 - 685
(2 studies)		 ⊕⊕⊕⊝
moderate2 		-
Change in daytime
tiredness24,25,27,28
Medical Outcomes Study sleep
disturbance score; RLS-6 item
scores
Follow-up: 6–26 weeks		 The mean change in
daytime tiredness ranged
across control groups
from
−0.8 to −1.3 points		 The mean change in
daytime tiredness in
pramipexole groups was
0.61 lower
(1.21 to 0.01 lower)		 - 1411
(4 studies)		 ⊕⊕⊝⊝
low1, 2 		The differences in treatment
duration and the proportion of
female patients in placebo group
might be the main cause of
heterogeneity.
Change in periodic limb
movements per hour of
sleep21,22,26
Epworth Sleepiness Scale; The
Pittsburgh Sleep Quality Index
Follow-up: 3–8 weeks		 The mean change in
periodic limb movements
in sleep per hour of sleep
ranged across control
groups from
−1.54 to −7.21 points		 The mean change in
periodic limb movements in
sleep per hour of sleep in
pramipexole groups was
35.95 lower
(56.42 to 15.48 lower)		 - 168
(3 studies)		 ⊕⊝⊝⊝
very low1, 2, 3 		The difference in the drug
dosage might be responsible for
heterogeneity.
Change in quality of sleep22–26,28
Medical Outcomes Study sleep
scale; Epworth Sleepiness Scale;
the Pittsburgh Sleep Quality
Index; RLS-6 rating scales
Follow-up: 3–12 weeks		 The mean change in
quality of sleep ranged
across control groups
from
0.4 to 25.9 points		 The mean change in quality
of sleep in pramipexole
groups was
3.60 higher
(1.69 to 5.5 higher)		 - 1574
(6 studies)		 ⊕⊕⊝⊝
low1, 2 		The difference in the evaluation
tool of quality of sleep might be
responsible for heterogeneity.
*

The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio; IRLS: International RLS Study Group Rating Scale; CGI-I: Clinical Global Impression of Improvement Scale; PGI: Patient Global Impression Scale; RLS-6: RLS six-item questionnaire; RLS: Restless legs syndrome.

GRADE working group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

1

The variation in point estimates among different trials was relatively large, and the heterogeneity test showed results of p<0.10 and I2 >40%.

2

All of the trials were supported by pharmaceutical companies.

3

The sample size was small.