Key conclusion (sections 1.1, 3.4, 3.15, 3.16, 4.5, 4.6, 4.9, 4.19)
Ranibizumab is recommended as an option for treating choroidal neovascularisation associated with pathological myopia when the manufacturer provides ranibizumab with the discount agreed in the patient access scheme.
The clinical evidence from RADIANCE, which compared ranibizumab with vPDT, showed that ranibizumab was associated with a greater improvement than vPDT in BCVA between baseline and months 1 to 3, although there is uncertainty about the efficacy after 3 months. The Committee concluded that ranibizumab is a clinically effective treatment option for visual impairment caused by choroidal neovascularisation associated with pathological myopia.
The key drivers of the cost‑effectiveness analysis included the unit cost of ranibizumab and vPDT, the number of ranibizumab injections in the first and second year, the starting age of the patient group, the discount rate for benefits and the maximum utility gain in the worse‑seeing eye. The manufacturer's base‑case cost‑effectiveness analysis showed that ranibizumab dominated vPDT, resulting in more QALYs and lower costs. The Committee concluded that the uncertainties associated with the key drivers in the model were unlikely to have an effect on the overall cost‑effectiveness results. The Committee therefore recommended ranibizumab as a cost‑effective use of NHS resources.
Current practice
Clinical need of patients, including the availability of alternative treatments (sections 4.2 to 4.4)
The Committee heard that visual impairment caused by choroidal neovascularisation seriously impairs quality of life.
The Committee heard that the current standard treatment for choroidal neovascularisation secondary to pathological myopia is vPDT. However, it is not effective in most patients and its use is diminishing because of anti‑VEGF treatments.
The Committee heard from a clinical specialist that the non‑licensed use of bevacizumab in the NHS is not routine or best practice. However, written statements from the Royal College of Ophthalmologists, the Royal College of Pathologists, and the Macular Society suggested considerable use of bevacizumab in the NHS for this indication.
The Committee heard from the patient expert and the clinical specialist that there are often delays in agreements to fund ranibizumab or bevacizumab.
The technology
Proposed benefits of the technology; how innovative is the technology in its potential to make a significant and substantial impact on health-related benefits? (section 4.20)
The Committee agreed that anti‑VEGF treatments (such as ranibizumab) were a substantial improvement over previous treatments.
It was not aware of any substantial benefits of ranibizumab over its comparators that were not already captured in the QALY estimation in the modelling.
What is the position of the treatment in the pathway of care for the condition? (section 4.5)
The Committee assessed the clinical effectiveness of ranibizumab compared with vPDT for treating visual impairment caused by choroidal neovascularisation associated with pathological myopia.
Adverse reactions (section 4.8)
The Committee was aware that the main adverse events listed in the summary of product characteristics were eye pain, ocular hyperaemia, increased intraocular pressure, vitritis, and vitreous detachment. The Committee agreed that the evidence suggested manageable adverse events with ranibizumab, and concluded that ranibizumab was safe and well tolerated in patients with visual impairment caused by choroidal neovascularisation associated with pathological myopia.
Evidence for clinical effectiveness
Availability, nature and quality of evidence (sections 4.4 to 4.5)
The Committee acknowledged that the evidence presented by the manufacturer was primarily from RADIANCE, which compared ranibizumab with vPDT. This evidence was complemented by data from the ranibizumab arm of 2 other randomised trials.
The Committee was aware that the scope of the appraisal listed bevacizumab as a comparator. It noted that the ERG identified only 2 small trials that compared ranibizumab and bevacizumab. The Committee concluded that there was currently insufficient evidence to allow bevacizumab to be included with confidence in a clinical and cost‑effectiveness analysis.
Relevance to general clinical practice in the NHS (section 4.2)
The Committee heard that the current standard treatment for visual impairment caused by choroidal neovascularisation secondary to pathological myopia is vPDT. However, it is not effective in most patients and its use is diminishing because of anti VEGF treatments, such as ranibizumab and bevacizumab.
Uncertainties generated by the evidence (section 4.6)
The Committee noted that the primary end point of RADIANCE was the mean average change in BCVA between baseline and months 1 to 3. The Committee heard from a clinical specialist that 3 months was not a long time period to assess the longer-term benefits of ranibizumab. The Committee concluded that, because the clinical effectiveness of ranibizumab was not compared with vPDT after 3 months, there is uncertainty about the long‑term efficacy of ranibizumab for choroidal neovascularisation associated with pathological myopia.
Are there any clinically relevant subgroups for which there is evidence of differential effectiveness?
None.
Estimate of the size of the clinical effectiveness including strength of supporting evidence (section 4.5)
The Committee noted that ranibizumab was associated with a greater improvement than vPDT in BCVA between baseline and months 1 to 3. The Committee concluded that ranibizumab is a clinically effective treatment option for visual impairment caused by choroidal neovascularisation associated with pathological myopia.
Evidence for cost effectiveness
Availability and nature of evidence (sections 4.9 to 4.10)
The Committee considered the manufacturer's economic model and the critique and exploratory analyses performed by the ERG. It accepted the model structure, but was concerned by some of the uncertainties about the assumptions used by the manufacturer.
The Committee noted that the manufacturer had not included bevacizumab as a comparator in its economic model.
The Committee considered the larger proportion of patients with subfoveal involvement in the VIP trial, which provided the vPDT data after 3 months. However, it concluded that the imbalance between RADIANCE and VIP was unlikely to have a large impact on the manufacturer's model.
The Committee considered the manufacturer's assumption that the average BCVA gain at the end of year 1 would continue indefinitely. It concluded that the duration of treatment benefit was likely to be less than the manufacturer's assumption of an indefinite duration, but that ranibizumab dominated vPDT when the duration of effect was reduced.
The Committee discussed whether the manufacturer's assumption about the number of ranibizumab injections that people would receive in clinical practice was too low. It concluded that the number of injections included in the manufacturer's base case could be an underestimate, and that even if the number of injections was increased, the base‑case analysis would not be affected.
The Committee discussed whether the costs of blindness used in the manufacturer's model were too high. The Committee noted that the ERG presented lower costs of blindness in their report. The Committee concluded that the ERG's assumptions about the costs of blindness were likely to be more realistic than those used by the manufacturer, and that any changes were unlikely to have a large impact on the base‑case analysis.
The Committee discussed whether the administration costs of ranibizumab used in the manufacturer's model were an underestimate. It concluded that the NHS costs were uncertain, but the uncertainty was not great enough to affect the base‑case analysis.
The Committee discussed whether the mortality multipliers used in the manufacturer's economic model were appropriate. It concluded that the manufacturer's rationale for some of the mortality multipliers in the model was unclear, and that any changes to them were unlikely to change the base‑case analysis.
The Committee discussed whether the method used in the manufacturer's model to account for the possibility of the treated eye changing from being the better‑seeing eye to the worse‑seeing eye as patients change health states was appropriate. It concluded that the modelling may have had an impact on the base‑case analysis, but the level of impact was unclear.
The Committee considered that EQ‑5D data were collected in RADIANCE, but were not used in the manufacturer's economic model. It concluded that using the EQ‑5D data from RADIANCE was unlikely to change the overall results of the base‑case analysis.
Are there specific groups of people for whom the technology is particularly cost effective?
None.
What are the key drivers of cost effectiveness? (section 3.16)
The manufacturer's sensitivity analyses showed that the cost effectiveness of ranibizumab was sensitive to changes in the unit cost of ranibizumab and vPDT, the number of ranibizumab injections in the first and second year, the starting age of the patient group, the discount rate for benefits, and the maximum utility gain in the worse‑seeing eye.
Most likely cost-effectiveness estimate (given as an ICER; sections 4.9, 4.11 to 4.19)
The Committee noted that manufacturer's base-case analysis showed that ranibizumab dominated vPDT (that is, it was more effective and less costly), resulting in more QALYs (13.18 compared with 12.75) and lower costs (£9694 compared with £12,455). The Committee considered the uncertainties in the manufacturer's model and noted that they were unlikely to have an effect on the overall results of the base-case analysis, which showed that ranibizumab dominated vPDT.