Real-world service costs for neovascular-AMD clinics in the United Kingdom: structured literature review and scenario analysis

Figures & data

Table 1. Approved posology and administration for anti-VEGF treatments licensed for use in nAMD in the UK.

	Aflibercept (Eylea)	Brolucizumab (Beovu)	Faricimab (Vabysmo)	Ranibizumab (Lucentis)
Loading	1 × 2 mg injection/4 weeks for 3 doses	1 × 6 mg injection/month for 3 doses	1 × 6 mg injection/month for 4 doses	1 × 0.5 mg injection/month until stable or maximum visual acuity
Maintenance	1 × 2 mg injection/2 months	Treatment interval of 8 or 12 weeks based on disease activity (visual/anatomic outcomes)^b	–	Treatment interval determined by physician based on disease activity (visual/anatomic outcomes)
T&E interval (min-max)	4 weeks-4 months^a 2- or 4-week increments	No T&E regimen specified	21 days–16 weeks^a 4-week increments	4 weeks-maximum not specified 2-week increments
Monitoring	None required	Monitoring for disease activity suggested at 16 weeks after treatment start	Monitoring between injections scheduled based on patient status at physician discretion	Monitoring for disease activity may include clinical examination, functional testing or imaging techniques
Monitoring interval	None required	Not specified	Not specified	Not specified
Administration	Adults: qualified healthcare professional experienced in intravitreal injection	Qualified ophthalmologist experienced in intravitreal injections	Qualified healthcare professional trained in intravitreal injections	Qualified ophthalmologist

^aTreatment dosing intervals not studied under 4 weeks/over 4 months (Eyelea), under 21 days (Faricimab). b: 8 weeks (disease activity), 12 weeks (no disease activity).

Data obtained from the Medicines and Healthcare products Regulatory Agency^22–25.

Table 2. Population, concept and context inclusion and exclusion criteria.

Criteria	Inclusion	Exclusion
Population	Patients receiving anti-VEGF treatment for licensed UK ophthalmic indications Patients with nAMD receiving monitoring or other intervention delivered by a UK NHS ophthalmic service Caregivers of included patient populations Medical and non-medical healthcare providers of NHS retina services	Dry AMD Patients with licensed UK indications for anti-VEGF treatments receiving treatments other than anti-VEGF References with mixed populations were only included if data for included populations was reported separately
Concept	Cost burdens of nAMD and nAMD treatment and monitoring service delivery from patient, caregiver, healthcare provider perspectives	Treatment drug costs Clinical trials Cited data from clinical trials was not extracted
Context	Provision of retina services in NHS primary and secondary care and in the community in the UK A secondary context of NHS ophthalmology services under strain was recognized	References reporting non-UK settings
Searching	Published and unpublished qualitative and quantitative studies Grey literature Studies published in English	Studies published before 2006 Studies reporting pre-2006 data Conference abstracts Studies published in other languages without available English translations

Figure 1. Modified preferred reporting items for systematic reviews and meta-analysis (PRISMA) flow chart adapted from Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi:10.1136/bmj.n71. For more information, visit: http://www.prisma-statement.org/.

Figure 2. Clinic cost misclassification plot showing false negative and false positive rates for HTAmin and HTAmax at 20%, 50% and 80% prevalence. Minimum: HTAmin; Maximum: HTAmax. False positive rate = 0, following specificity results.

Table 3. Neutrality analysis for HTAmin and HTAmax.

		nAMD Service Non-Drug Cost Instrument
		Included items	Excluded items	Neutrality (%)
HTAmin	Included items	4	0
	Excluded items	213	22
	Total	217	22
	S, C	0.02	1.00	1.02 (50.1%)
HTAmax	Included	153	0
	Excluded	64	22
	Total	217	22
	S, C	0.71	1	1.71 (85.5%)

Abbreviations: S, Sensitivity; C, Specificity; Neutrality, S + C (% accuracy).

Figure 3. Comparative cost-effectiveness decision-making from HTA perspective showing estimated drug acquisition cost magnitudes for hypothetical drug 1 (A) and drug 2 (B): D1, D2: anti-VEGF drug acquisition cost; Items 1–3: non-anti-VEGF drug acquisition costs. Shaded bars show differentiating cost items.

Figure 4. Comparative cost-effectiveness decision-making using the nAS, illustrating the impact of strain costs on two hypothetical nAMD anti-VEGF treatments. This figure shows that the lower cost drug (D1) incurs higher costs of strain, despite its lower acquisition cost. This is attributed to the higher frequency of treatments and monitoring required to maintain its efficacy, which increases operational costs during periods of clinic strain. The higher cost drug (D2), while more expensive upfront, demands fewer clinic visits, thereby incurring lower strain-related costs. This visualization underscores the importance of considering visit frequency and operational strain in total treatment cost assessments. The list of cost items is provided in Appendix 7: Supplemental Table 7.