Eton, D.T., & Cella, D. (2011). Do erythropoietic-stimulating agents relieve fatigue? A review of reviews. Cancer Treatment and Research, 157, 181–194. 

STUDY PURPOSE: To review findings of 10 systematic reviews of clinical trials of erythropoietic-stimulating agents (ESAs) in the five-year period spanning 2004–2008.

TYPE OF STUDY: Systematic review

TOTAL REFERENCES RETRIEVED: 10

• FINAL NUMBER OF STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW =  86,374
• SAMPLE RANGE ACROSS STUDIES: 1,949–21,378
• KEY SAMPLE CHARACTERISTICS: Inference that all patients included in reviews were patients with cancer, but report did not actually specify

PHASE OF CARE: Active treatment

10 reviews of effects of ESA treatment on symptoms and quality of life (QOL) were reviewed.

• (From authors) Overall evidence from studies seem to support  a symptom and QOL benefit from ESA treatment, which is unlikely to be due to chance alone.
• (From reviewer) Quality of studies presented in review, variability of instruments and ESAs used to measure variables of interest, missing data, and lack of description of sample populations in studies limits sufficient evidence for empirical benefit from ESA treatment in patients with cancer

• Focus of review was on patient-reported symptoms and QOL outcomes versus all risks (safety, survival, thrombosis) and benefits (transfusion use, hematologic response) of ESA use.
• Not all of the studies reviewed were placebo controlled or double blinded.
• Increased risk of placebo effect when outcome of interest is patient self-report.
• Many studies failed to report metrics needed for a more detailed analysis.
• Substantial loss of data and lack of documentation of how missing data were handled.
• Timing and conditions under which symptoms and QOL were measured were not described in many studies.

• Focus future studies on description of conditions for the safe use of ESAs.
• Determine empirically derived cutoff above which ESA therapy is contraindicated.
• Conduct detailed analysis of secondary data sources (meta-analysis).
• Need for inclusion of patient perspective of benefits and harms of ESA therapy.
• Development of patient education materials about relative risks and benefits of ESA use or lack thereof.