NICE do not recommend fluocinolone implant for chronic diabetic macular oedema in final draft guidance
In final draft guidance published today (30 November) by the healthcare guidance body, NICE, fluocinolone acetonide intravitreal implant (Iluvien, Alimera Sciences) is not recommended within its marketing authorisation, that is, for the treatment of chronic diabetic macular oedema (DMO) considered insufficiently responsive to available therapies.
The macula is the central part of the retina responsible for colour vision and perception of fine detail. DMO occurs as a result of changes in retinal blood vessels in people with diabetes. A reduction in the number of connective tissues around capillaries and an increased amount of a protein called vascular endothelial growth factor (VEGF) causes the blood retinal barrier to become more permeable. This leads to leakage of plasma constituents in the surrounding retina, causing a build-up of excess fluid (oedema) which disrupts the fovea, the area responsible for sharp vision. It can lead to severe visual impairment in the affected eye.
Fluocinolone acetonide intravitreali implant is a corticosteroidii which has anti-inflammatory and anti-vascular endothelial growth factor (anti-VEGF) properties. Fluocinolone can decrease the oedema and limit visual loss and/or improve vision. The implant releases fluocinolone acetonide for up to 3 years.
The independent Appraisal Committee concluded that, despite the manufacturer providing an updated economic model following consultation on the previous draft guidance, this model underestimated the incremental cost-effectiveness ratio (ICER) for fluocinolone intravitreal implant compared with optimised standard of care, resulting in an ICER of £19,300 per QALY gained. The Committee concluded that the most plausible ICER was likely to be at least £47,600 per QALY gained and that fluocinolone acetonide intravitreal implant exceeded the range that NICE considers an effective use of NHS resources.
For example, the Committee concluded that the manufacturer's model did not take into account the possible negative effects of fluocinolone intravitreal implant such as cataract, and glaucoma, and subsequently, the operations, procedures, and hospital attendances associated with these.
The Committee also concluded that the evidence submitted by the manufacturer did not accurately reflect current clinical practice. For example, the people involved in the trials submitted as evidence may not have been as severely affected by chronic diabetic macular oedema as those patients who would receive fluocinolone intravitreal implant in routine clinical practice, and results from the clinical trials might be better than what would be seen in clinical practice.
In response to the ACD consultation, the manufacturer also proposed a pseudophakiciii subgroup in its modelling. The Committee accepted that the subgroup was reasonable, but that the comparatively small numbers of patients in the evidence submitted led to uncertainty in the estimates of clinical effectiveness for this group and, thus, in the estimates from the economic modeling. The Committee agreed that from the evidence submitted, the most plausible ICER for this subgroup was towards the upper end of the range of £29,700 to £50,600 per QALY gained, and therefore, the technology could not be recommended for treating people who are pseudophakic and have chronic diabetic macular oedema that is insufficiently responsive to available therapies.
Sir Andrew Dillon, Chief Executive of NICE said: "The independent Appraisal Committee is aware of the significant impact that chronic diabetic macular oedema can have on those with the condition and their carers. However, when NICE recommends any drug or treatment, we have to be sure that it is both clinically and cost effective, because money has to be diverted from elsewhere in the health service to pay for it. Unfortunately, in this case, despite additional information on a pseudophakic subgroup and updated economic modeling from the manufacturer, the Committee concluded that the evidence provided did not show that the benefits fluocinolone intravitreal implantprovides to patients justify the price the NHS is being asked to pay."
NICE has not yet issued final guidance to the NHS; registered stakeholders now have the opportunity to appeal against these draft recommendations and consequently they may change in the event of an appeal being received.
Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its guidance on a technology it replaces local recommendations across the country.
Notes to Editors
i. Intravitreal refers to the treatment being administered through the eye.
ii. A corticosteroid is a type of medication that contains steroids.
iii. When an eye is pseudophakic, the natural lens has been surgically removed and replaced by an artificial lens.
About the guidance
1. The final draft guidance (final appraisal determination / FAD ) can be found from 09:00hrs on Friday 30 November on the NICE website at: http://guidance.nice.org.uk/TA/Wave25/10
2. Fluocinolone acetonide intravitreal implant has a marketing authorisation for the treatment of vision impairment associated with chronic diabetic macular oedema considered insufficiently responsive to available therapies
3. Each fluocinolone acetonide intravitreal implant contains 190 micrograms of fluocinolone acetonide, releasing 0.2 micrograms/day for up to 36 months.
4. The summary of product characteristics states that the recommended dose of fluocinolone acetonide is 1 implant in the affected eye every 3 years. Only patients whose disease has been insufficiently responsive to treatment with laser photocoagulation or other available therapies for diabetic macular oedema should be treated. Administration in both eyes concurrently is not recommended.
5. An additional implant may be administered after 12 months if the patient experiences decreased vision or an increase in retinal thickness secondary to recurrent or worsening diabetic macular oedema.
6. The Committee concluded that fluocinolone intravitreal acetonide implant showed greater efficacy compared with sham injection in people with chronic diabetic macular oedema.
7. The Committee noted that the clinical effectiveness of fluocinolone acetonide intravitreal implant on the subgroup of people who were pseudophakic before treatment (as proposed by the manufacturer in response to the ACD consultation) in terms of 15-letter gain in visual acuity was numerically worse than that in the total population (albeit with wide confidence intervals). Furthermore, it heard from the ERG that when the trial data were modelled, some variations in efficacy results became apparent, particularly in terms of response in the optimised standard of care group.
8. The manufacturer's submission states that the acquisition cost of a fluocinolone acetonide intravitreal implant is £5500 (excluding VAT) per 190-microgram implant (source: Alimera Sciences). Costs may vary in different settings because of negotiated procurement discounts.
9. The Committee concluded that the ICER was likely to be at least £47,600 per QALY gained for people with chronic diabetic macular oedema and in the upper end of the range of £29,700 to £50,600 per QALY gained for people with chronic diabetic macular oedema who are pseudophakic.
10. A patient access scheme has not been submitted by the manufacturer.
11. Approximately 14% (336,000) of people in the UK with diabetes have DMO and prevalence increases to 29% (696,000) for people with diabetes who use insulin for more than 20 years.
12. NICE recommends further research to resolve uncertainties about the cost-effectiveness of fluocinolone acetonide intravitreal implant for the treatment of chronic diabetic macular oedema. This should focus on a group of patients whose condition is unresponsive to other available therapies, and include measures of efficacy and health-related quality of life.
13. Research recommendations are all unanswered research questions that emerge during the development of NICE guidance.
14. The SMC has yet to publish advice on fluocinolone acetonide intravitreal implant for chronic diabetic macular oedema.
15. In draft guidance published in October 2012, NICE recommended ranibizumab (Lucentis, Novartis) as an option for treating visual impairment caused by diabetic macular oedema (DMO). NICE is currently conducting a rapid review of the original guidance, (TA237), because the manufacturer submitted a revised Patient Access Scheme, together with updated analyses.
16. In July 2011, NICE recommended dexamethasone (Ozurdex, Allergan) intravitreal implant for the treatment of macular oedema following central retinal vein occlusion (CRVO).
17. Further details on NICE technology appraisals.
Related NICE guidance
1. Ranibizumab for the treatment of diabetic macular oedema. NICE technology appraisal guidance 237 (2011).
2. Dexamethasone intravitreal implant for the treatment of macular oedema secondary to retinal vein occlusion. NICE technology appraisal guidance 229 (2011).
3. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration. NICE technology appraisal guidance 155 (2008).
4. Type 2 diabetes - newer agents (partial update of CG66). NICE clinical guideline 87 (2008).
5. Type 1 diabetes: diagnosis and management of type 1 diabetes in children, young people and adults. NICE clinical guideline 15 (2004).
6. There is no NICE guidance related specifically to treating chronic diabetic macular oedema.
8. Aflibercept solution for injection for the treatment of wet age-related macular degeneration. NICE technology appraisal guidance (publication expected August 2013).
9. Ranibizumab for the treatment of macular oedema caused by retinal vein occlusion. NICE technology appraisal guidance (publication date to be confirmed).
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This page was last updated: 29 November 2012