Evidence Table 3, Data abstraction of systematic reviews - Drug Class Review: Drugs for Fibromyalgia

Author Year Country	Aims	Time period covered	Eligibility criteria	Number of patients	Characteristics of identified articles: study designs	Characteristics of identified articles: populations	Characteristics of identified articles: interventions	Main results	Subgroups	Adverse events
Hauser, 2010 Germany	To give physicians and patients an orientation on FDA approved pharmacological treatment options of fibromyalgia syndrome	Through May 2009	An RCT design with a head-to-head comparison of at least 2 drugs or an RCT design with duloxetine, milnacipran or pregabalin with a pharmacological placebo control group or uncontrolled open label extension studies with these drugs Outcomes of at least 1 key domain of fibromyalgia syndrome (pain, sleep, fatigue, depressed mood, health related quality of life and data on harms) Data published as full paper or data on file in the public databases All studies included patients diagnosed with fibromyalgia according to 1990 ACR criteria	6388	Duloxetine: 4 RCTs, 2 uncontrolled open label extension studies, and 1 open label/double blind study Milnacipran: 5 RCTs and 1 uncontrolled open-label extension study Pregabalin: 5 RCTs and 3 uncontrolled open label extension studies	All studies included patients with Fibromyalgia according to ACR 1990 criteria, patients recruited from America, Europe, Australia, Asia with Americans in the majority. 4508 on active drug, 1880 on placebo Median duration of randomized phase of trials: 24 weeks Median age: 49 years (range 47–51) Median % women: 95% (range 88–100%) Caucasians: 90% (range 76–94%)	Pregabalin, Milnacipran, Duloxetine	Standardized mean difference [95% CI], p of test for overall effect, I ² (%): Duloxetine Pain −0.33 (−0.43 to −0.23), p<0.0001, I²: 15 Fatigue: −0.10 (−0.21 to 0.01), p=0.06, I²: 0 Sleep: −0.31 (−0.50 to −0.13, p=0.0007, I²:0 Depressed mood: −0.27 (−0.39 to −0.16)p<0.0001, I ²: 0 HRQOL: −0.25 (−0.42, −0.08), p=0.05, I²:69 Milnacipran Pain: −0.19 (−0.26 to −0.11), p<0.0001, I²:0 Fatigue: −0.13 (−0.21 to −0.06), p=0.006, I²: 0 Sleep: −0.05 (−0.12 to .03), p=0.23, I²:0 Depressed mood: −0.11(−0.19 to −0.04), p=0.003, I ²:0 HRQOL: −0.17(−0.25 to −0.10), p<0.0001, I²:0 Pregabalin Pain: −0.27 (−0.35 to −0.19), p<0.0001, I²: 36 Fatigue: −0.16 (−0.23 to −0.09), p<0.0001, I²:26 Sleep: −0.37 (−0.46 to −0.28), p<0.0001, I²: 0 Depressed mood: 0.01 (−0.07 to 0.10), p=0.75, I²=0 HRQOL:−0.25 (−0.36 to −0.13), p<0.0001, I²=0 NNTs for 30% pain reduction: Duloxetine 7.2 (95% CI 5.2 to 11.4), Milnacipran 19 (95% CI 7.4 to 20.5) and Pregabalin 8.6 (95% CI 6.4 to 12.9) NNHs for dropout due to lack of efficacy: Duloxetine 14.9 (95% CI 9.1 to 41.4), Milnacipran 7.6 (95% CI 6.2 to 9.9) and Pregabalin 7.6 (95% CI 6.3 to 9.4)	NR	NNH (95% CI), RR (95% CI, I2 (%), p-value: Nausea: Duloxetine: 5.6 (4.5 to 7.2), 2.54 (1.92 to 3.37), 0%, p<0.0001, Milnacipran: 5.1 (4.3 to 6.3), 1.84 (1.55 to 2.18), 0%, p<0.0001, Pregabalin: −96.3 (−24.4 to 49.6), 0.97 (0.64 to 1.48), 0%, p=0.89 Headache: Duloxetine: 12.5 (8.4 to 23.8), 1.61 (1.20 to 2.17), 0%, p=0.01, Milnacipran: 25.0 (19.7 to 144), 1.30 (1.04 to 1.64), 0%, p=0.02, Duloxetine: 17.7(−32.1 to 11.6), 0.72 (0.57 to 0.91), 0%, p=0.007 Dry mouth: Duloxetine:7.9 (6.3 to 10.5), 3.16 (2.11 to 4.72), 0%, p<0.001, Milnacipran: 25.5 (14.8 to 92.3), 2.46 (1.06 to 5.69), 0%, p=0.04, Pregabalin: 15.3 (12.4 to 19.9), 4.98 (2.72 to 9.10), 0%, p<0.0001 Insomnia: Duloxetine:18.7 (11.5 to 51.0), 2.47 (0.57 to 10.71), 40%, p=0.23, Milnacipran: 38.8 (18.8 to 45.3), 1.35 (1.01 to 1.79), 0% p=0.04 Constipation: duloxetine:10.1 (7.9 to 13.9, 3.50 (2.23 to 5.79), 0%, p<0.0001, Milnacipran: 8.1 (6.8 to 10.0), 4.47 (2.91 to 6.86), 0%, p=0.04, Pregabalin: 24.3 (14.1 to 83.6), 3.94 (0.50 to 30.74), 74%, 0.19 Hyperhidrosis: Duloxetine 11.8 (9.4 to 15.8), 5.71 (2.34 to 13.95), 0%, p=0.0001, Milnacipran: 14.4 (11.5 to 19.2), 5.00 (2.64 to 9.47), 0%, p<0.0001 Dizziness: Duloxetine:23.6 (13.9 to 79.0), 2.62 (1.53 to 4.50), 27%; p=0.004, Milnacipran: 19.4 (13.4 to 35.5), 1.94 (1.34 to 2.81), 0%, p=0.0004, Pregabalin: 3.5 (3.2 to 3.9), 3.87 (3.06 to 4.89), 0%, p<0.0001 Diarrhea: Duloxetine:26.6 (14.5 to 147), 1.59 (1.11 to 2.29), 8%, p=0.01, Milnacipran: −5.7 (−25.3 to 29.1), 0.72 (0.49 to 1.05), Pregabalin: −64.6 (−117 to 26.9), 0.79 (0.42 to 1.48), 40%, p=0.46 Fatigue: Duloxetine: 13.5 (9.4 to 23.8), 2.07 (1.47 to 2.91), 0%, p<0.0001, Milnacipran: NR, Pregabalin(fatigue/asthenia): 32.1 (19.8 to 84.8), 1.67 (1.15 to 2.43), 0%,p<0.0001 Somnolence: Duloxetine: 14.7 (10.9 to 22.8), 2.66 (1.78 to 3.96), 0%,p<0.0001, Milnacipran: NR, Pregabalin: 6.4 (5.5 to 7.5), 4.21 (2.96 to 5.94), 0%, p<0.0001 Weight gain: Pregabalin: 11.5 (9.9 to 14.5), 4.58 (2.44 to 6.82), 0%,p<0.0001, peripheral edema:20.5 (15.5 to 30.1), 3.52 (2.01 to 6.18),0%,p<0.0001
Moore 2010 U.K.	To assess the analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain	1990 through May 2009	Adults aged ≥18 years who reported pain in acute pain setting or were studied in situations where pain was anticpated, had one or more of a wide range of chronic or neuropathic pains including diabetic neuropathy, post herpetic neuralgia, phantom limb pain, Guillain barre and spinal cord injury and had any other chronic painful condition.	2294 patients in 4 trials 1 trial had 1051 patients analyzed seperately as it used complete EERW design.	5 PCTs of fibromyalgia	NR	Pregabalin in any dose and by any route Placebo or any active control	Proportion of patients with at least 30% pain relief (Results from 4 studies) Pregabalin 150mg vs placebo: 31% vs 27%, Relative benefit 1.1, 95%CI (0.8 to 1.7), NNT not calculated Pregabalin 300mg vs placebo: 39% vs 28%, Relative benefit 1.4, 95% CI (1.2 to 1.6), NNT 9.2, 95% CI (6.3 to 17) Pregabalin 450mg vs placebo: 43% vs 28%, Relative benefit 1.5, 95% CI (1.3 to 1.8), NNT 6.6 (5.0 to 9.8) Pregabalin 600mg vs placebo: 39% vs 28%, Relative benefit 1.4, 95% CI (1.2 to 1.6), NNT 9.1 (6.1 to 18) Proportion of patients with atleast 50% pain relief (Results from 4 studies) Pregabalin 150mg vs placebo: 13% vs 13%, Relative benefit 1.0, 95% CI (0.5 to 1.9), NNT not calculated Pregabalin 300mg vs placebo: 21% vs 14%, Relative benefit 1.5, 95% CI (1.2 to 1.9), NNT 14, 95% CI (9.0 to 33) Pregabalin 450mg vs placebo:25% vs 14%, Relative benefit 1.7, 95% CI (1.4 to 2.1), NNT 9.8, 95% CI (7.0 to 16) Pregabalin 600mg vs placebo: 24% vs 15%, Relative benefit 1.6, 95% CI (1.3 to 2.1), NNT 11, 95% CI (7.1 to 21) Proportion of patients with PGIC much or very much improved (Results from 4 studies) Pregabalin 150mg vs placebo: 32% vs 27%, Relative benefit 1.2, 95% CI (0.8 to 1.8), NNT not calculated Pregabalin 300mg vs placebo: 36% vs 28%, Relative benefit 1.5, 95% CI (1.2 to 1.9), NNT 11, 95% CI (7.3 to 26) Pregabalin 450mg vs placebo: 42% vs 28%, Relative benefit 1.5, 95% CI (1.3 to 1.8), NNT 6.8, 95% CI (6.1 to 1.0) Pregabalin 600mg vs placebo: 41% vs 28%, Relative benefit 1.5, 95% CI (1.2 to 1.7), NNT 7.7, 95% CI (5.4 to 13) Effficacy results from 1 EERW study : DB phase % of patients experiencing loss of therapeutic response: Pregabalin vs placebo: 32% vs 61%, NNT 3.5, 95% CI (2.8 to 4.9)	NR	% of patients with AE discontinuation Pregabalin 150mg vs placebo: 8% vs 8%, RR 1.1, 95% CI(0.5 to 2.5), NNH not calculated Pregabalin 300mg vs placebo: 16% vs 10%, RR 1.6, 95% CI (1.2 to 2.1), NNH 17, 95% CI (11 to 43) Pregabalin 450mg vs placebo: 20% vs 10%, RR 1.9, 95% CI 1.5 to 2.5), NNH 11, 95% CI (7.6 to 18) Pregabalin 600mg vs placebo: 28% vs 11%, RR 2.5, 95% CI (1.9 to 3.3), NNH 5.9, 95% CI (4.6 to 8.0) % of patients with Somnolence Pregabalin 150 mg vs placebo: 16% vs 5%, RR 3.5, 95% CI (1.5 to 8.3), NNH 8.8, 95 % CI (5.4 to 24) Pregabalin 300mg vs placebo: 32% vs 10%, RR 3.1, 95% CI 2.8 to 5.8), NNH 6.7, 95% CI (5.5 to 8.7) Pregabalin 450mg vs placebo: 21% vs 5%, RR 4.2, 95% CI 2.9 to 6.0), NNH 6.4, 95% CI (5.2 to 8.1) Pregabalin 600mg vs placebo: 23% vs 5%, RR 4.5, 95% CI 3.1 to 6.7), NNH 5.7, 95% CI (4.6 to 7.3) % of patients with dizziness Pregabalin 150mg vs placebo: 13% vs 10%, RR 1.3, 95% CI (0.8 to 2.1), NNH not calculated Pregabalin 300mg vs placebo: 32% vs 10%, RR 3.1, 95% CI (2.4 to 3.9), NNH 4.6, 95% CI 3.9 to 5.7) Pregabalin 450mg vs placebo 43% vs 10%, RR 4.1, 95% CI (3.2 to 5.2), NNH 3.1, 95% CI (2.8 to 3.6) Pregabalin 600mg vs placebo 46% vs 10%, RR 4.4, 95% CI (3.4 to 5.8), NNH 2.8, 95% CI (2.5 to 3.2) Results from EERW study DB phase % of patients with any adverse event placebo 45%, pregabalin 300mg 59% vs pregabalin 600mg 62%

Author
Year
Country

Aims

Time period covered

Eligibility criteria

Number of patients

Characteristics of identified articles: study designs

Characteristics of identified articles: populations

Characteristics of identified articles: interventions

Main results

Subgroups

Adverse events

Hauser, 2010
Germany

To give physicians and patients an orientation on FDA approved pharmacological treatment options of fibromyalgia syndrome

Through May 2009

An RCT design with a head-to-head comparison of at least 2 drugs or an RCT design with duloxetine, milnacipran or pregabalin with a pharmacological placebo control group or uncontrolled open label extension studies with these drugs
Outcomes of at least 1 key domain of fibromyalgia syndrome (pain, sleep, fatigue, depressed mood, health related quality of life and data on harms)
Data published as full paper or data on file in the public databases

All studies included patients diagnosed with fibromyalgia according to 1990 ACR criteria

6388

Duloxetine: 4 RCTs, 2 uncontrolled open label extension studies, and 1 open label/double blind study Milnacipran: 5 RCTs and 1 uncontrolled open-label extension study
Pregabalin: 5 RCTs and 3 uncontrolled open label extension studies

All studies included patients with Fibromyalgia according to ACR 1990 criteria, patients recruited from America, Europe, Australia, Asia with Americans in the majority.
4508 on active drug, 1880 on placebo
Median duration of randomized phase of trials: 24 weeks
Median age: 49 years (range 47–51)
Median % women: 95% (range 88–100%)
Caucasians: 90% (range 76–94%)

Pregabalin, Milnacipran, Duloxetine

Standardized mean difference [95% CI], p of test for overall effect, I ² (%):
Duloxetine
Pain −0.33 (−0.43 to −0.23), p<0.0001, I²: 15
Fatigue: −0.10 (−0.21 to 0.01), p=0.06, I²: 0
Sleep: −0.31 (−0.50 to −0.13, p=0.0007, I²:0
Depressed mood: −0.27 (−0.39 to −0.16)p<0.0001, I ²: 0
HRQOL: −0.25 (−0.42, −0.08), p=0.05, I²:69
Milnacipran
Pain: −0.19 (−0.26 to −0.11), p<0.0001, I²:0
Fatigue: −0.13 (−0.21 to −0.06), p=0.006, I²: 0
Sleep: −0.05 (−0.12 to .03), p=0.23, I²:0
Depressed mood: −0.11(−0.19 to −0.04), p=0.003, I ²:0
HRQOL: −0.17(−0.25 to −0.10), p<0.0001, I²:0
Pregabalin
Pain: −0.27 (−0.35 to −0.19), p<0.0001, I²: 36
Fatigue: −0.16 (−0.23 to −0.09), p<0.0001, I²:26
Sleep: −0.37 (−0.46 to −0.28), p<0.0001, I²: 0
Depressed mood: 0.01 (−0.07 to 0.10), p=0.75, I²=0
HRQOL:−0.25 (−0.36 to −0.13), p<0.0001, I²=0
NNTs for 30% pain reduction: Duloxetine 7.2 (95% CI 5.2 to 11.4), Milnacipran 19 (95% CI 7.4 to 20.5) and Pregabalin 8.6 (95% CI 6.4 to 12.9)
NNHs for dropout due to lack of efficacy: Duloxetine 14.9 (95% CI 9.1 to 41.4), Milnacipran 7.6 (95% CI 6.2 to 9.9) and Pregabalin 7.6 (95% CI 6.3 to 9.4)

NNH (95% CI), RR (95% CI, I2 (%), p-value:
Nausea: Duloxetine: 5.6 (4.5 to 7.2), 2.54 (1.92 to 3.37), 0%, p<0.0001, Milnacipran: 5.1 (4.3 to 6.3), 1.84 (1.55 to 2.18), 0%, p<0.0001, Pregabalin: −96.3 (−24.4 to 49.6), 0.97 (0.64 to 1.48), 0%, p=0.89
Headache: Duloxetine: 12.5 (8.4 to 23.8), 1.61 (1.20 to 2.17), 0%, p=0.01, Milnacipran: 25.0 (19.7 to 144), 1.30 (1.04 to 1.64), 0%, p=0.02, Duloxetine: 17.7(−32.1 to 11.6), 0.72 (0.57 to 0.91), 0%, p=0.007
Dry mouth: Duloxetine:7.9 (6.3 to 10.5), 3.16 (2.11 to 4.72), 0%, p<0.001, Milnacipran: 25.5 (14.8 to 92.3), 2.46 (1.06 to 5.69), 0%, p=0.04, Pregabalin: 15.3 (12.4 to 19.9), 4.98 (2.72 to 9.10), 0%, p<0.0001
Insomnia: Duloxetine:18.7 (11.5 to 51.0), 2.47 (0.57 to 10.71), 40%, p=0.23, Milnacipran: 38.8 (18.8 to 45.3), 1.35 (1.01 to 1.79), 0% p=0.04
Constipation: duloxetine:10.1 (7.9 to 13.9, 3.50 (2.23 to 5.79), 0%, p<0.0001, Milnacipran: 8.1 (6.8 to 10.0), 4.47 (2.91 to 6.86), 0%, p=0.04, Pregabalin: 24.3 (14.1 to 83.6), 3.94 (0.50 to 30.74), 74%, 0.19
Hyperhidrosis: Duloxetine 11.8 (9.4 to 15.8), 5.71 (2.34 to 13.95), 0%, p=0.0001, Milnacipran: 14.4 (11.5 to 19.2), 5.00 (2.64 to 9.47), 0%, p<0.0001
Dizziness: Duloxetine:23.6 (13.9 to 79.0), 2.62 (1.53 to 4.50), 27%; p=0.004, Milnacipran: 19.4 (13.4 to 35.5), 1.94 (1.34 to 2.81), 0%, p=0.0004, Pregabalin: 3.5 (3.2 to 3.9), 3.87 (3.06 to 4.89), 0%, p<0.0001
Diarrhea: Duloxetine:26.6 (14.5 to 147), 1.59 (1.11 to 2.29), 8%, p=0.01, Milnacipran: −5.7 (−25.3 to 29.1), 0.72 (0.49 to 1.05), Pregabalin: −64.6 (−117 to 26.9), 0.79 (0.42 to 1.48), 40%, p=0.46
Fatigue: Duloxetine: 13.5 (9.4 to 23.8), 2.07 (1.47 to 2.91), 0%, p<0.0001, Milnacipran: NR, Pregabalin(fatigue/asthenia): 32.1 (19.8 to 84.8), 1.67 (1.15 to 2.43), 0%,p<0.0001
Somnolence: Duloxetine: 14.7 (10.9 to 22.8), 2.66 (1.78 to 3.96), 0%,p<0.0001, Milnacipran: NR, Pregabalin: 6.4 (5.5 to 7.5), 4.21 (2.96 to 5.94), 0%, p<0.0001
Weight gain: Pregabalin: 11.5 (9.9 to 14.5), 4.58 (2.44 to 6.82), 0%,p<0.0001, peripheral edema:20.5 (15.5 to 30.1), 3.52 (2.01 to 6.18),0%,p<0.0001

Moore 2010
U.K.

To assess the analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain

1990 through May 2009

Adults aged ≥18 years who reported pain in acute pain setting or were studied in situations where pain was anticpated, had one or more of a wide range of chronic or neuropathic pains including diabetic neuropathy, post herpetic neuralgia, phantom limb pain, Guillain barre and spinal cord injury and had any other chronic painful condition.

2294 patients in 4 trials
1 trial had 1051 patients analyzed seperately as it used complete EERW design.

5 PCTs of fibromyalgia

Pregabalin in any dose and by any route
Placebo or any active control

Proportion of patients with at least 30% pain relief (Results from 4 studies)
Pregabalin 150mg vs placebo: 31% vs 27%, Relative benefit 1.1, 95%CI (0.8 to 1.7), NNT not calculated
Pregabalin 300mg vs placebo: 39% vs 28%, Relative benefit 1.4, 95% CI (1.2 to 1.6), NNT 9.2, 95% CI (6.3 to 17)
Pregabalin 450mg vs placebo: 43% vs 28%, Relative benefit 1.5, 95% CI (1.3 to 1.8), NNT 6.6 (5.0 to 9.8)
Pregabalin 600mg vs placebo: 39% vs 28%, Relative benefit 1.4, 95% CI (1.2 to 1.6), NNT 9.1 (6.1 to 18)

Proportion of patients with atleast 50% pain relief (Results from 4 studies)
Pregabalin 150mg vs placebo: 13% vs 13%, Relative benefit 1.0, 95% CI (0.5 to 1.9), NNT not calculated
Pregabalin 300mg vs placebo: 21% vs 14%, Relative benefit 1.5, 95% CI (1.2 to 1.9), NNT 14, 95% CI (9.0 to 33)
Pregabalin 450mg vs placebo:25% vs 14%, Relative benefit 1.7, 95% CI (1.4 to 2.1), NNT 9.8, 95% CI (7.0 to 16)
Pregabalin 600mg vs placebo: 24% vs 15%, Relative benefit 1.6, 95% CI (1.3 to 2.1), NNT 11, 95% CI (7.1 to 21)

Proportion of patients with PGIC much or very much improved (Results from 4 studies)
Pregabalin 150mg vs placebo: 32% vs 27%, Relative benefit 1.2, 95% CI (0.8 to 1.8), NNT not calculated
Pregabalin 300mg vs placebo: 36% vs 28%, Relative benefit 1.5, 95% CI (1.2 to 1.9), NNT 11, 95% CI (7.3 to 26)
Pregabalin 450mg vs placebo: 42% vs 28%, Relative benefit 1.5, 95% CI (1.3 to 1.8), NNT 6.8, 95% CI (6.1 to 1.0)
Pregabalin 600mg vs placebo: 41% vs 28%, Relative benefit 1.5, 95% CI (1.2 to 1.7), NNT 7.7, 95% CI (5.4 to 13)

Effficacy results from 1 EERW study : DB phase
% of patients experiencing loss of therapeutic response: Pregabalin vs placebo: 32% vs 61%, NNT 3.5, 95% CI (2.8 to 4.9)

% of patients with AE discontinuation
Pregabalin 150mg vs placebo: 8% vs 8%, RR 1.1, 95% CI(0.5 to 2.5), NNH not calculated
Pregabalin 300mg vs placebo: 16% vs 10%, RR 1.6, 95% CI (1.2 to 2.1), NNH 17, 95% CI (11 to 43)
Pregabalin 450mg vs placebo: 20% vs 10%, RR 1.9, 95% CI 1.5 to 2.5), NNH 11, 95% CI (7.6 to 18)
Pregabalin 600mg vs placebo: 28% vs 11%, RR 2.5, 95% CI (1.9 to 3.3), NNH 5.9, 95% CI (4.6 to 8.0)

% of patients with Somnolence
Pregabalin 150 mg vs placebo: 16% vs 5%, RR 3.5, 95% CI (1.5 to 8.3), NNH 8.8, 95 % CI (5.4 to 24)
Pregabalin 300mg vs placebo: 32% vs 10%, RR 3.1, 95% CI 2.8 to 5.8), NNH 6.7, 95% CI (5.5 to 8.7)
Pregabalin 450mg vs placebo: 21% vs 5%, RR 4.2, 95% CI 2.9 to 6.0), NNH 6.4, 95% CI (5.2 to 8.1)
Pregabalin 600mg vs placebo: 23% vs 5%, RR 4.5, 95% CI 3.1 to 6.7), NNH 5.7, 95% CI (4.6 to 7.3)

% of patients with dizziness
Pregabalin 150mg vs placebo: 13% vs 10%, RR 1.3, 95% CI (0.8 to 2.1), NNH not calculated
Pregabalin 300mg vs placebo: 32% vs 10%, RR 3.1, 95% CI (2.4 to 3.9), NNH 4.6, 95% CI 3.9 to 5.7)
Pregabalin 450mg vs placebo 43% vs 10%, RR 4.1, 95% CI (3.2 to 5.2), NNH 3.1, 95% CI (2.8 to 3.6)
Pregabalin 600mg vs placebo 46% vs 10%, RR 4.4, 95% CI (3.4 to 5.8), NNH 2.8, 95% CI (2.5 to 3.2)

Results from EERW study DB phase
% of patients with any adverse event placebo 45%, pregabalin 300mg 59% vs pregabalin 600mg 62%

From: Evidence Tables

Cover of Drug Class Review: Drugs for Fibromyalgia

Drug Class Review: Drugs for Fibromyalgia: Final Original Report [Internet].

Smith B, Peterson K, Fu R, et al.

Portland (OR): Oregon Health & Science University; 2011 Apr.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Evidence Table 3Data abstraction of systematic reviews