Original Title: Eisentherapie bei eisenmangel ohne anämie

Authors' objectives: The definition and the indication for the treatment of iron deficiency without anaemia (iron deficiency no anaemia, IDNA) are controversially discussed in Switzerland. In a first step the aim was to assess the clinical effectiveness of iron therapy (irrespective of the route of administration) compared to any other intervention including placebo or no therapy in IDNA populations having symptoms such as fatigue, depression, restless legs syndrome (RLS), sleep disorders, hair loss, brittle nails, attention-deficit hyperactivity disorder, and cognitive deficit. In addition to this step, an individual patient data meta-analysis of trials comparing iron therapy versus control was conducted to identify any subgroups (e.g. baseline ferritin level) in women with IDNA and fatigue who would particularly benefit from iron therapy. In the second step, a health economic evaluation of parenteral versus oral iron therapy in symptomatic IDNA populations benefiting from iron therapy was conducted.

Authors' results and conclusions: In the clinical effectiveness assessment, three symptomatic IDNA populations were identified. Eight RCTs investigated adults with restless legs syndrome (RLS), four RCTs women with fatigue and one RCT children with attention-deficit hyperactivity disorder (ADHD). In patients with RLS (eight RCTs), iron therapy compared to control let to a statistically significant reduction of RLS symptom severity and a statistically significant improvement in RLS treatment response. A potential “placebo effect” cannot be excluded in six out of seven trials reporting on RLS symptom severity. For the outcomes sleep, sleepiness, quality of life, global impression, depression and fatigue no statistically significant effect for iron therapy compared to control was found. In women with IDNA and fatigue (four RCTs), iron therapy compared to control statistically significantly improved fatigue severity (measured as a continuous variable), improved subscores for mental and physical health quality of life and anxiety. A potential “placebo effect” cannot be excluded in the trials reporting on fatigue severity. For the outcomes fatigue improvement (measured as binary variable), quality of life total scores, and depression scores no statistically significant effect was found for iron therapy compared to control. Although the overall quality of evidence from trials in patients with IDNA and fatigue or RLS was judged to be very low, it is likely that a substantial proportion of patients may experience a reduction in fatigue severity or RLS symptom severity from iron therapy (irrespective of the route of administration).

Authors' methods: For the clinical effectiveness a systematic literature search was conducted in Medline and CENTRAL to identify relevant randomised controlled trials (RCTs). The systematic review was conducted according to principles of the Cochrane Handbook. Quality of Evidence was evaluated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). For the economic evaluation, it was decided to restrict the evaluation to a cost-comparison analysis, rather than a cost-effectiveness analysis, and a budget impact analysis from a health care payer perspective because no data from RCTs with a direct comparison of parenteral and oral iron therapy could be identified and because no reliable estimation of differential effects can be expected from an indirect comparison of the available RCT data from the clinical effectiveness assessment (step one). For the cost-comparison, the medical costs of all health care services of the different routes of iron administration were modelled with a decision tree over a time horizon of one year reflecting the current clinical practice in Switzerland. The model was parametrized primarily with empirical evidence from the clinical trials identified in step one of this HTA report, from additional clinical literature and from opinions of clinical experts. The budget impact analysis was based on the results from the cost-comparison analysis, epidemiological data available for Switzerland and expert opinions.

Project Status: Completed

URL for project: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-projekte/eisentherapie.html

Year Published: 2020

URL for published report: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0002eisn-hta-report.pdf.download.pdf/h0002eisn-hta-report.pdf

URL for additional information: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-programm.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Switzerland

Organisation Name: Swiss Federal Office of Public Health (FOPH)

Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland

Contact Name: Stephanie Vollenweider

Contact Email: hta@bag.admin.ch

Copyright: Swiss Federal Office of Public Health