Clinical effectiveness questions
Main question: is it clinically effective to use epoetinum alfa in the management of adults with non-iron-deficient anaemia prior to major elective orthopaedic surgery?
To answer this question the following sub-questions will be addressed:
- What is the standard comparator treatment or practice used in studies identified in the literature evidence base? Can this be generalised to standard practice within Scotland? Are there treatments for which comparisons to epoetinum alfa are unavailable?
- Which patients are most suitable for treatment with epoetinum alfa and are there any special cases? For example can patients with Hb levels of below 10 g/dl in particular circumstances (eg elderly or malnourished patients unable to retain iron, or patients with rheumatoid arthritis) be safely treated?
- Does clinical effectiveness vary within particular patient subgroups (eg the elderly, patients requiring repeated or revision surgery, low weight patients)?
- Is effectiveness influenced by pre-surgery Hb level, eg <8, 8-10,10-13 g/dl?
- What are the relevant clinical outcome measures for patients (short and long term)? The relevant clinical outcomes per patient included:
- avoidance of risk of allogeneic transfusion
- net volume of blood savedchange in Hb
- able to pre-donate autologous blood
- volume of autologous blood pre-donated
- time in hospital
- measures of speed of recovery
- health related quality of life
- outcome of surgery
- adverse events (epoetinum alfa related, for example in patients with predisposition for development of deep vein thrombosis, and transfusion related) and their timescale.
Cost-effectiveness questions
Main question: is it cost effective to add epoetinum alfa to standard care in the management of adults with moderate anaemia who are not iron deficient, prior to major elective orthopaedic surgery?
The economic evaluation will undertake a cost-consequences analysis, to identify the changes in costs and benefits associated with using epoetinum alfa compared to standard care (as defined by clinical effectiveness analysis). It is anticipated that the analysis will be developed to calculate the cost per QALY gained from adding epoetinum alfa to standard care. The utility measure should include any utility gain from reduction in adverse events in comparison with current practice. Secondary outcomes are likely to include value of transfusions avoided, for example longer hospital stays and cost of adverse events avoided. No survival benefit is anticipated.
The major costs are likely to be the unit costs of epoetinum alfa, the estimated costs to administer it, to include in pre-assessment clinics, and cost of adverse events. These could include cancelled or deferred operations if appropriate. An NHS perspective will be used to value costs and benefits.
Budget impact
If epoetinum alfa is found to be clinically and cost effective then an assessment of budget impact will be conducted to estimate the changes in resource use, costs and patient outcomes from moving from standard care to a regime with epoetinum alfa added.
Organisational issues
To inform the cost-effectiveness analysis, the organisational issues associated with identifying patients who might benefit from the therapy and with administering the drug will be assessed. No other organisational issues will be considered until answers to the clinical and cost-effectiveness questions are available.
Patient issues
It is anticipated that issues of importance to the patient will relate to the safety and acceptability of epoetinum alfa versus allogenic blood transfusions. Examples include:
- the risks of allogenic blood transfusion include transfusion transmitted infections (eg HIV and vCJD), transfusion reactions and procedural error
- side effects of epoetinum alfa can include hypertension and deep vein thrombosis
- a weekly subcutaneous injection of erythropoietin is given for three weeks prior to surgery and on the day of surgery. Patients should be given adequate iron supplementation throughout the course of erythropoietin therapy. Furthermore, patients receiving epoetinum alfa should have weekly haematocrit checks. Would compliance be problematic?
There are specific groups of patients for whom administration of epoetinum alfa may be a high priority, for example patients who:
- are Jehovah s Witnesses
- have multiple antibodies
- have serious anxieties about the transfusion of allogenic blood.
HTA exclusions
The HTA will not consider other indications in renal or cancer therapy or possible wider uses within this indication, for example use pre-operatively for cardiac surgery. This is because the contra-indications include use in patients with recent myocardial infarction.