Nordström 1997.

Methods	1. Design: parallel‐design (2 arms) 2. Country: Sweden (7 sites) 3. Intention‐to‐treat analysis: no 4. Follow‐up period: 12 weeks 5. Unit of randomization: patient 6. Unit of analysis: patient
Participants	1. Randomized: 46 (Quote "three active, one placebo") (page 68) Erythropoietin (EPO) group: 36 Placebo group: 10 2. Patients receiving drug: 46 EPO group: 36 (78.2%) Placebo group: 10 (21.7%) 3. Analyzed patients: EPO group: 26 (72.2%) Placebo group: 9 (90%) Imbalance between groups: 17.8% 4. Age (years; mean±SD; range) EPO group: 56.1±12.7; 25 to 76 Placebo group: 56.9±12.7; 29 to 79 5. Gender (female): Overall: 85% (39/46) EPO group: 80.5% (29/36) Placebo group: 100% (10/10) 6. Inclusion criteria: Clinical diagnosis of rheumatoid arthritis by American College of Rheumatology (ACR) criteria. Independent of disease activity with stable disease. The Disease‐Modifying Anti‐rheumatic Drugs (DMARDs) regimens unchanged during the treatment. Hemoglobin concentrations below ≤ 100 g/L (women) and ≤ 110 g/L (men). Hemoglobin concentrations during iron supplementations did not increase by more than 15 g/L. 7. Exclusion criteria: Hemorrhage. Hemolysis. Folic acid deficiency. Vitamin B12 deficiency. Uncontrolled hypertension. Kidney disease. Liver disease. High doses of corticosteroids (exceeding 10 mg of prednisone or equivalent).
Interventions	Interventional group: recombinant human erythropoietin (rHuEPO; Express 10,000 U/ml, Cilag AB Sweden), 150 IU/ kg subcutaneous injected twice weekly. Duration: 12 weeks. Placebo: subcutaneous injection twice weekly for 12 weeks. Nature of placebo: not given. Co‐intervention: oral iron supplementations at a median dose of 200 mg elemental iron per day.
Outcomes	Outcomes were not defined explicitly as primary or secondary: An adequate response was defined as reaching an Hb≥ 120 g/L at least once after the study start (page 68). Elevation of energy level (page 70). Safety (page 71).
Notes	1. Sample size calculation a priori: not reported. 2. Sponsor: Cilag AB Sweden. 3. Roll of sponsor: not specified. 4. Conflict of interest: not described.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Randomization was carried out in blocks of four patients (three active, one placebo) and allocation within each block was in random order” (page 68). Insufficient information to consider 'low risk' or 'high risk'. Comment: there is an imbalance in gender and duration of disease variables (page 69, table 1).
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgment of 'low risk' or 'high risk'.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient information to permit judgment of 'low risk' or 'high risk'. This trial was reported as double‐blind.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgment of 'low risk' or 'high risk'. This trial was reported as double‐blind.
Incomplete outcome data (attrition bias) All outcomes	High risk	1. Lost postrandomization: 24% (11/46). EPO group: 38.4% (10/26). Placebo group: 11.1% (1/9). 2. Imbalance between comparison groups: 27.3% Quote: "(5 patients excluded due to entering the extension study, 5 drop‐outs) patients receiving rHuEPO over 9 patients receiving placebo (one drop out)" (page 70) 3. Comment: potentially inappropriate application of simple imputation. 4. Comment: For continuous outcome data, plausible effects size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size and potentially inappropriate application of simple imputation.
Selective reporting (reporting bias)	High risk	Quote: "A significant rise in Hb was noted in 26 (5 patients excluded due to entering the extension study, 5 drop‐outs) patients receiving rHuEPO over 9 patients receiving placebo (one drop‐out) (Hb elevation from 95 g/L to 107 g/L vs 93 g/L to 97 g/L, P < 0.05), from week 10 onwards that lasted throughout the study. A significant elevation of red blood cells was noted already from 4 weeks onward (P = 0.02) and Hct levels at week 12 (P = 0.009)" (page 70) Quote: "only 14.6% (N = 6) of the patients were considered responders according to the preset criteria of Hb level equaling or exceeding 120 g/l" (page 70). Quote "A significant elevation of energy (NHP variable) was noted at the end of the study after week 12 (P = 0.004). Otherwise, HAQ scores, NHP scores, classification of functional class or joint score index scores did not differ significantly between the two groups". (page 70). Comment: one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis.
Other bias	High risk	Comments: 1. There is imbalance between comparison groups regarding gender, duration of disease (years) and medication for treating ARA variables (page 69). 2. There was a potential source of bias related to the specific study design used, with extreme baseline imbalance.