The Spectra Optia® apheresis system provides automated red blood cell exchange for people with chronic symptomatic sickle cell disease. It is operationally more efficient than manual red blood cell exchange, resulting in improved clinical and patient outcomes and improved regulation of iron levels. |
The paucity of clinical evidence to support the Spectra Optia system largely reflects a lack of clinical equipoise. Limited observational evidence and expert opinion suggest the system provides long-term savings to the National Health Service, primarily through a reduction in the requirement for iron chelation therapy. |
With the correct service provision, the Spectra Optia system could also reduce geographical inequalities in the management of sickle cell disease. |
1 Introduction
2 Background to the Condition and Technology
3 Decision Problem (Scope)
3.1 Population
3.2 Intervention
3.3 Comparator
3.4 Outcomes
4 Review of Clinical Effectiveness Evidence
4.1 Company’s Review of Clinical Effectiveness Evidence
4.2 EAC Critique of Clinical Effectiveness Evidence
Primary study referencea, study design, country of origin | Population | Intervention (I) and comparator (C) | EAC comment on methodological qualityb and usefulness |
---|---|---|---|
Comparative studies included by the company and EAC | |||
Cabibbo et al. [18], retrospective observational study, Italy | Adults and children with SCD (n = 20) at high risk for recurrent complications who had been hospitalised more than twice per year | I: aRBCx (3 different technologies) C: mRBCx | Very poor methodology and reporting. Not possible to attribute results to technology |
Dedeken et al. [19], retrospective longitudinal ‘before-and-after’ study, Belgium | Older children (n = 10) with SCD receiving long-term exchange, previously treated with manual exchange | I: Spectra Optia C: mRBCx (historical) | Poor methodology and reporting (conference abstract). Difficult to interpret |
Duclos et al. [20], retrospective matched case series, France | Children with SCD (n = 10) treated by long-term RBCx | I: Cobe Spectra C: mRBCx (different centre) | Good methodology and reporting. Low patient numbers, but important comparative study |
Fasano et al. [21], retrospective observational study, USA | Children with SCD (n = 36) on iron chelation and long-term transfusion (3-way comparison) | I: Spectra Optia) C: mRBCx and TUT | Poor methodology and reporting (conference abstract). Interpretation difficult because of mixed comparators |
Kuo et al. [22], retrospective observational study, UK | Adults with SCD (n = 51) and >1 RBCx over 1 year | I: Spectra Optia C: mRBCx (different centre) | Good methodology and reporting (although not peer reviewed). Key comparative study |
Woods et al. [23], retrospective observational study, USA | Children and teenagers with SCD (n = 38) receiving regular RBCx for stroke prevention | I: Spectra Optia C: mRBCX (patients received mixed modalities over course of the study) | Poor methodology and reporting (conference abstract). Not possible to disaggregate and interpret results |
Single-armed studies selected by EAC (fully published and peer-reviewed studies only) | |||
Bavle et al. [24], retrospective observational study (matched controls), USA | Children with SCD (n = 35) receiving RBCx for >1 year | Cobe Spectra | Medium methodological quality and reporting. Outcomes peripheral to decision problem |
Billard et al. [25], retrospective case series, France | Children with SCD (n = 18) | Cobe Spectra | Medium methodological quality with descriptive reporting. Aim of study to assess efficacy of indwelling catheter rather than aRBCx |
Kalff et al. [26], retrospective case series, Australia | Adults with SCD (n = 13) | Cobe Spectra | Poor methodological quality, sufficient reporting but missing data. No analytical data reported |
Masera et al. [27], retrospective data review, Italy | Children with SCD (n = 34) at high risk for vaso-occlusive complications | Cobe Spectra | Medium methodological quality but poorly reported. Results poorly generalisable |
Quirolo et al. [28], retrospective observational study, USA | Adults and older children with SCD (n = 60) | I: Spectra Optia C: Spectra Optia (dRBCx) (Subgroup analysis) | High quality with good reporting. Key paper in determining Spectra Optia resource use |
Sarode et al. [29], retrospective observational study, USA | Adults with SCA (n = 20), stable with history of thrombotic stroke | I: Cobe Spectra (dRBCx) C: Cobe Spectra (standard) (Historic controls) | Medium methodology with good reporting. Comparative data peripheral to decision problem |
Shrestha et al. [30], retrospective observational study, USA | Adults with SCD (n = 29) on scheduled RBCx | Cobe Spectra | Medium methodological quality with poor reporting. Aim was comparison of two types of venous access |
Clinical outcome (from scope) | Direction of effect in clinical evidence compared with manual RBCx | Magnitude of effect in clinical evidence | Relation to company’s claimed benefitsa
|
---|---|---|---|
Primary outcomes | |||
HbS levels (%) | No consistent evidence of effect | N/A | Claim 4: increased efficiency resulting in reduced complications is not substantiated |
Duration of procedure | Strong evidence of reduced duration | Spectra Optia: 1.5–2.5 h Manual RBCx: 4–6 h | Claim 2: substantiates claim that Spectra Optia results in shorter procedures, but not by magnitude of original claim |
Frequency of treatment | Strong evidence of reduced frequency | Spectra Optia: 6–7 weeks Manual RCBx: 4–5 weeks | Claim 1: substantiates claim that Spectra Optia results in reduced frequency of treatment, but not by magnitude of original claim |
Patient haematocrit | No evidence of difference | N/A | Claim 5: improved maintenance of haematocrit to prevent iron overloading is not substantiated |
Iron overload and requirement for chelation therapy | Some uncertainty whether ferritin levels are reduced | At least equivalent magnitude of any reduction in ferritin unknown | Claim 3: reduced iron overload leading to reduced chelation therapy is not fully substantiated through reported changes in ferritin levels |
Clinical outcomes | None reported | N/A | Claim 4: improved outcomes, including reduced incidence of stroke, reduced frequency and severity of painful crises, and reduced incidence of acute chest syndrome, have not been substantiated Claim 7: reduced complications leading to reduced hospitalisation has not been substantiated |
Quality of life | Not reported | N/A | Claim 4: improvements in general quality of life have not been substantiated |
Length of hospital stay | Not reported directly, but reduced hospital stay highly likely | Not known | Claim 6: reduced hospital stay [outpatients] highly plausible |
Staff time and staff group/grade | Not reported | N/A | Claim 6: substitution of doctors with nurses, or nurses at lower pay grades, is not substantiated |
Frequency of top-up transfusion required to treat sickle cell complications | Unclear | N/A | Does not affect claims |
Secondary outcomes | |||
Ease of venous access, bruising and haematoma | Peripheral venous access more difficult using Spectra Optia system | Not known | Does not affect claims |
Device-related adverse events | Weak evidence for increased catheter-related complications in Spectra Optia, resulting in some patients transitioning to manual RBCx and some requiring hospital readmission | Dependent on site of vascular access, greater magnitude for femoral or implantable double lumen large-bore ports | Claim 7: reduced complications leading to reduced hospitalisations is refuted when femoral access is used for Spectra Optia |
Hospital admissions | Possible reduction, but comparative data absent | N/A | Claim 7: reduced complications leading to reduced hospitalisations unsubstantiated (lack of data) |
Donor blood usage | Strong evidence of increased requirement | Some uncertainty, but probably double RBC requirement for Spectra Optia | Claim 8: depletion–exchange protocol makes better use of donor blood is unsubstantiated |
BMI and growth in children | No direct evidence to support improved BMI and growth in children | N/A | Claim 4: improved body mass index and growth in paediatric patients not substantiated |
Alloimmunisationb
| Consistent findings of no clinically significant difference in alloimmunisation rates between manual and automated RBCx | No difference demonstrated when red cell antigen matching protocols are performed prior to transfusion | N/A—no claim made in this regard |
5 Economic Evidence
5.1 Company’s Economic Submission
5.2 Critique of Economic Evidence
Population | Option | No overloada
| Mild overload | Moderate overload | Severe overload |
---|---|---|---|---|---|
Adults | Auto vs. manual | Generally, Spectra Optia is cost saving, except where extreme assumptions are used | Spectra Optia is comfortably cost saving over manual | Spectra Optia is cost saving over manual where the less conservative assumptions are used | Spectra Optia is always more costly than manual |
Auto vs. TUT | Spectra Optia is comfortably cost saving over TUT | Spectra Optia is comfortably cost saving over TUT | Spectra Optia is cost saving over manual where the less conservative assumptions are used | Spectra Optia is always more costly than manual | |
Paediatric secondary prevention | Auto vs. manual | Spectra Optia is cost saving over manual where the less conservative assumptions are used | Spectra Optia is comfortably cost saving over manual | Spectra Optia is always more costly than manual | Spectra Optia is always more costly than manual |
Auto vs. TUT | Spectra Optia is comfortably cost saving over TUT | Spectra Optia is comfortably cost saving over manual | Spectra Optia is always more costly than manual | Spectra Optia is always more costly than manual | |
Paediatric primary prevention | Auto vs. manual | Spectra Optia is cost saving over manual where the less conservative assumptions are used | Spectra Optia is comfortably cost saving over manual | Spectra Optia is always more costly than manual | Spectra Optia is always more costly than manual |
Auto vs. TUT | Generally, Spectra Optia is cost saving, except where extreme assumptions are used | Generally, Spectra Optia is cost saving, except where extreme assumptions are used | Spectra Optia is always more costly than manual | Spectra Optia is always more costly than manual |