Table 2.
Summary of findings
| Recombinant human erythropoietin vs placebo | ||||||
| Patient or population: male and female patients with no comorbidities between the age of 18 and 65. Setting: track or gym. Intervention: rHuEPO administered at low, medium or high doses. Comparison: placebo. | ||||||
| Outcomes* | Duration | Intervention† | Participants (n) (studies)‡ |
Quality of the evidence§¶ (GRADE) |
||
| rHuEPO, low-dose (<6875 IU/week) | rHuEPO, medium-dose (6876–13 750 IU/week) | rHuEPO, high-dose (>13 750 IU/week) | ||||
| Borg Scale Rating of Perceived Exhaustion | Immediate | No statistically significant improvement (NS) in 1 study, n=20 (13) | NS, n=20 (13) | Significant improvement in 1 study (p<0.05; n=7) (22); NS, n=20 (13) | ||
| Short | NS, n=20 (13) | NS, n=20 (13) | NS, n=20 (13) | |||
| Time to exhaustion | Immediate | NS, n=20 (13) | NS, n=20 (13) | NS, n=20 (13) | ||
| Short | NS, n=20 (13) | Heterogeneity: I2=0% (13 19) Test for overall effect: Z=2.46 (p=0.01) SMD (95% CI): 0.87 (0.18 to 1.56) |
Significant improvement using a submaximal exercise test in 2 studies (p<0.05, p=0.04; n=40) (13 18) |
Medium-dose 36 (2) (13 19) |
Medium-dose ⊕⊕○○ Low Limitations 0 Imprecision −1** Inconsistency −1†† Indirectness 0 Other 0 |
|
| Training load | Short | N/A | NS, n=39 (20 21 24) | N/A | ||
| Maximum power output | Immediate | NS, n=20 (13) | NS, n=20 (13) | NS, n=20 (13) | ||
| Short | Heterogeneity: I2=0% (6 13 15) Test for overall effect: Z=2.82 (p=0.005) SMD (95% CI): 0.63 (0.19 to 1.07) |
Heterogeneity: I2=0% (13 20) Test for overall effect: Z=0.97 (p=0.33) SMD (95% CI): 0.33 (−0.33 to 0.99) |
Significant improvement in 1 study (p<0.01; n=20) (13) |
Low-dose 86 (3) (6 13 15) |
Low-dose ⊕⊕○○ Low Limitations 0 Imprecision −1** Inconsistency −1†† Indirectness 0 Other 0 |
|
|
Medium-dose 36 (2) (13 20) |
Medium-dose ⊕⊕○○ Low Limitations 0 Imprecision −1** Inconsistency −1†† Indirectness 0 Other 0 |
|||||
| Submaximal power output | Short | NS, n=48 (6) | N/A | N/A | ||
| Total work | Immediate | N/A | N/A | NS, n=7 (22) | ||
| Mont Ventoux race time | Short | NS, n=48 (6) | N/A | N/A | ||
| Haematocrit percentage | Immediate | NS, n=20 (13) | Heterogeneity: I2=0% (13 23) Test for overall effect: Z=1.17 (p=0.24) SMD (95% CI): 0.40 (−0.27 to 1.07) |
Heterogeneity: I2=0% (13 22) Test for overall effect: Z=2.58 (p=0.010) SMD (95% CI): 1.09 (0.26 to 1.93) |
Medium-dose 35 (2) (13 23) |
Medium-dose ⊕⊕○○ Low Limitations 0 Imprecision −2** Inconsistency 0 Indirectness 0 Other 0 |
|
High-dose 27 (2) (13 22) |
High-dose ⊕⊕⊕○ Moderate Limitations 0 Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|||||
| Short | Heterogeneity: I2=42% (6 13 15) Test for overall effect: Z=5.67 (p<0.00001) SMD (95% CI): 2.33 (1.53 to 3.14) |
Heterogeneity: I2=0% (13 19–21 23 24) Test for overall effect: Z=6.28 (p<0.00001) SMD (95% CI): 1.60 (1.10 to 2.09) |
Significant improvement in 1 study (p<0.001; n=20) (13) |
Low-dose 86 (3) (6 13 15) |
Low-dose ⊕⊕⊕○ Moderate Limitations 0 Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|
|
Medium-dose 90 (6) (13 19–21 23 24) |
Medium-dose ⊕⊕○○ Low Limitations −1‡‡ Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|||||
| Haemoglobin concentration | Immediate | Significant improvement in 1 study (p<0.01; n=20) (13) | Heterogeneity: I2=0% (13 23) Test for overall effect: Z=1.19 (p=0.24) SMD (95% CI): 0.41 (−0.27 to 1.08) |
Significant improvement in 1 study (p<0.05; n=20) (13) |
Medium-dose 35 (2) (13 23) |
Medium-dose ⊕⊕○○ Low Limitations 0 Imprecision-2** Inconsistency 0 Indirectness 0 Other 0 |
| Short | Significant improvements in 3 studies (p<0.01, p<0.0001, p<0.001; n=86) (6 13 15) | Heterogeneity: I2=0% (13 19–21 23 24) Test for overall effect: Z=5.98 (p<0.00001) SMD (95% CI): 1.48 (1.00 to 1.97) |
Heterogeneity: I2=47% (13 18) Test for overall effect: Z=3.23 (p=0.001) SMD (95% CI): 1.73 (0.68 to 2.78) |
Medium-dose 90 (6) (13 19–21 23 24) |
Medium-dose ⊕⊕○○ Low Limitations −1‡‡ Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|
|
High-dose 40 (2) (13 18) |
High-dose ⊕⊕○○ Low Limitations 0 Imprecision −1** Inconsistency −1†† Indirectness 0 Other 0 |
|||||
| Pulmonary ventilation | Immediate | N/A | N/A | Significant improvement using a submaximal exercise test in 1 study (p<0.01; n=7) (22) NS using a maximal exercise test (n=7) (22) |
||
| Absolute maximal oxygen consumption | Immediate | Significant improvement in 1 study (p<0.05; n=20) (13) | Significant improvement in 1 study (p<0.01; n=20) (13) | Significant improvement in 1 study (p<0.05; n=20) (13) | ||
| Short | Heterogeneity: I²=0% (6 13 15) Test for overall effect: Z=3.50 (p=0.0005) SMD (95% CI): 0.79 (0.35 to 1.23) |
Heterogeneity: I2=0%(13 19–21 24) Test for overall effect: Z=3.64 (p=0.0003) SMD (95% CI): 0.92 (0.42 to 1.41) |
Heterogeneity: I2=38% (13 18) Test for overall effect: Z=2.30 (p=0.02) SMD (95% CI): 1.01 (0.15 to 1.88) |
Low-dose 86 (3) (6 13 15) |
Low-dose ⊕⊕⊕○ Moderate Limitations 0 Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|
|
Medium-dose 75 (5) (13 19–21 24) |
Medium-dose ⊕⊕○○ Low Limitations −1‡‡ Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|||||
|
High-dose 40 (2) (13 18) |
High-dose ⊕⊕⊕○ Moderate Limitations 0 Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|||||
| Absolute submaximal oxygen consumption | Immediate | NS, n=20 (13) | NS, n=20 (13) | NS, n=20 (13) | ||
| Short | Heterogeneity: I2=31% (6 13) Test for overall effect: Z=1.48 (p=0.14) SMD (95% CI): 0.47 (−0.15 to 1.10) |
NS, n=20 (13) | NS, n=20 (13) |
Low-dose 68 (2) (6 13) |
Low-dose ⊕⊕⊕○ Moderate Limitations 0 Imprecision −1** Inconsistency 0 Indirectness 0 Other 0 |
|
*Outcomes were stratified by treatment duration (rows) and dosages (columns).
†Qualitative and quantitative findings for outcomes are summarised in the grey boxes.
‡Number of participants and studies for outcomes that underwent quantitative analysis were listed below. For outcomes that underwent qualitative analysis, number of participants and studies were listed in the grey boxes.
§A quality assessment (GRADE) was only given for outcomes that underwent quantitative analysis.
¶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.
**Small study group or wide CI.
††Heterogeneity of participants, interventions or outcomes.
‡‡Lack of allocation concealment or blinding.
GRADE, Grading of Recommendations Assessment Development and Education; N/A, not available; rHuEPO, recombinant human erythropoietin; SMD, standard mean difference; TTE, time to exhaustion.