4 Consideration of the evidence

4.1 The Appraisal Committee reviewed the data available on the clinical and cost effectiveness of ocriplasmin having considered evidence on the nature of vitreomacular traction and the value placed on the benefits of ocriplasmin by people with the condition, those who represent them, and clinical specialists. It also took into account the effective use of NHS resources.

4.2 The Committee considered the current management of vitreomacular traction and the likely place of ocriplasmin in clinical practice; noting that the scope of the appraisal and the marketing authorisation for ocriplasmin is 'indicated in adults for the treatment of vitreomacular traction, including when associated with macular hole of diameter less than or equal to 400 microns'. The clinical specialists explained that vitreomacular traction was managed differently depending on whether or not a stage II macular hole was present.

  • They said that patients who presented with a stage II macular hole would be listed for surgery because delaying surgery could lead to poorer outcomes for these patients and stage II macular holes rarely resolve spontaneously. The Committee heard from the clinical specialists that if ocriplasmin was recommended for use, patients with a stage II macular hole would still be listed for surgery, without delay, and ocriplasmin would be administered to patients during the period before surgery (in UK clinical practice this can be a number of weeks or months).

  • The clinical specialists stated that for patients who have vitreomacular traction without a macular hole, or with a stage I macular hole, delaying surgery in general does not have an impact on long‑term outcomes and that many of these patients will not need surgery. The clinical specialists explained that some patients would need surgery and in these patients if ocriplasmin was available it would be offered as an alternative to surgery. Furthermore, they commented that some patients would have severe distressing symptoms (such as metamorphopsia [distorted vision in which straight lines appear wavy] and low visual acuity), but would not be eligible for surgery, and that if ocriplasmin was available it would be offered to these patients instead of 'watch and wait'. The Committee acknowledged that about 80% of the patients in the trials had an expected need for vitrectomy at baseline, and therefore the patients in the trials were those with severe distressing symptoms and/or those who were eligible for surgery.

  • The Committee concluded that the treatment pathway varies depending on the presence or absence of a stage II macular hole. If a stage II macular hole is present, ocriplasmin would be used during the wait for surgery, without delaying surgery. If a stage II macular hole is not present, ocriplasmin would be used as an alternative to surgery, or as an alternative to 'watch and wait' for people who have severe distressing symptoms.

4.3 The Committee discussed vitrectomy surgery in UK clinical practice. The clinical specialists explained that there were risks involved with the surgery, including the potential to damage the eye and reduce visual acuity. Clinical specialists stated that a treatment that could avoid vitrectomy surgery would be beneficial for patients. The Committee also heard from the patient expert who described her experience of vitrectomy surgery and the anxiety and trauma it could cause. The patient expert explained that the recovery period after surgery was worse than the surgery itself because she had to lie in a face down position for up to a week. She described this as being very difficult and uncomfortable, and said that it felt suffocating. She commented that she would choose a treatment that involved an injection over vitrectomy surgery. The Committee recognised this, but also understood that face down positioning for recovery is being used less often, and for shorter periods. The Committee acknowledged that, although vitrectomy surgery was effective in resolving vitreomacular traction and the recovery time after surgery was short, the recovery was an unpleasant process for patients, and surgery also had risks and could damage the eye. The Committee concluded that an alternative treatment for vitreomacular traction would be welcomed by clinicians and patients.

4.4 The Committee considered the impact of vitreomacular traction on the everyday life of patients. It heard from the patient expert about the problems associated with vitreomacular traction, including difficulties with reading, cooking, watching television and driving that prevented them from enjoying these activities. The Committee understood from the patient expert that the effects of metamorphopsia and macular holes were very disturbing. The patient described seeing straight lines as wavy, and objects disappearing from view. The Committee concluded that resolving vitreomacular traction without the need for surgery would be beneficial to the wellbeing of patients with vitreomacular traction.

Clinical effectiveness

4.5 The Committee considered the evidence presented by the manufacturer on the clinical effectiveness of ocriplasmin. The Committee acknowledged that 3 subgroups were presented by the manufacturer (VMT without ERM [vitreomacular traction without an epiretinal membrane], VMT with ERM [vitreomacular traction with an epiretinal membrane], and VMT with MH [vitreomacular traction with a stage II macular hole]). It noted that the evidence was from the TG‑MV‑006 and TG‑MV‑007 trials and it discussed the outcomes in these trials. The Committee acknowledged that the outcomes presented by the manufacturer were in line with the scope issued by NICE, and that they included vitreomacular traction resolution, posterior vitreous detachment (PVD), vitrectomy, visual acuity changes and macular hole closure. The Committee noted that although there was a statistically significant benefit with ocriplasmin compared with placebo in terms of vitreomacular traction resolution and total PVD at day 28 in the VMT without ERM and VMT with MH subgroups, this did not translate into a statistically significant visual acuity benefit (see 3.7 and 3.9). The clinical specialists explained that visual acuity was not a complete or accurate measure of the vision impairment experienced with vitreomacular traction. This is because measured visual acuity may not be affected by the presence of a macular hole or metamorphopsia: although the patient has distorted vision, they may still be able to read a letter on an eye chart successfully. The clinical specialists therefore explained that anatomical measures such as vitreomacular traction resolution or total PVD were a better way to measure the benefit of the treatment, and that from their experience approximately 70–80% of metamorphopsia resolved with vitreomacular traction resolution. The Committee accepted that the anatomical outcomes of vitreomacular traction resolution and total PVD were appropriate measures for assessing the effectiveness of ocriplasmin.

4.6 The Committee considered the results from the trials in the manufacturer's submission. The Committee noted that the efficacy of ocriplasmin was not the same for all the subgroups evaluated. The Committee acknowledged that ocriplasmin was associated with a statistically significant improvement in vitreomacular traction resolution and total PVD at 28 days in the VMT without ERM (see 3.7) and VMT with MH (see 3.9) subgroups. However, in the VMT with ERM subgroup, the effect of ocriplasmin in terms of these outcomes was small and not statistically significant (see 3.8). The Committee heard from the clinical specialists that they did not consider ocriplasmin to have a place in the treatment of patients with vitreomacular traction and an epiretinal membrane because it was not clinically effective in these patients. The Committee recognised that the VMT with MH group included people with ERM, and that because of the small sample size of this group (n=23) analyses had not been presented by the manufacturer. The Committee took into account the data from the VMT with ERM subgroup and the opinion of the clinical specialists and concluded that ocriplasmin was unlikely to be clinically effective in people with ERM in any of the subgroups, including VMT with MH. The Committee concluded that ocriplasmin was clinically effective, in terms of vitreomacular traction resolution and total PVD at 28 days in the subgroups VMT without ERM and VMT with MH, but not in the subgroup VMT with ERM, and it was unlikely to be clinically effective in terms of these outcomes in the VMT with MH subgroup who had ERM.

4.7 The Committee discussed whether the comparator arm in the clinical trials was relevant to clinical practice in the UK. It noted that a placebo injection was used in the trials instead of the UK clinical practice of 'watch and wait'. It heard from clinical specialists that an injection of saline into the eye sometimes resolves vitreomacular traction, and that it could also provoke macular hole development. Therefore it was likely that the placebo injection could lead to total PVD, or to the creation of a macular hole. The clinical specialists commented that this was supported by the spontaneous resolution rates observed in the placebo arm of the trials (approximately 10%) because they were much higher than they observe in clinical practice (approximately 2–5%). The Committee concluded that the placebo injection in the clinical trials was not equivalent to 'watch and wait' and that it was plausible that the efficacy of ocriplasmin would have been greater if it had been compared with the UK clinical practice of 'watch and wait'.

4.8 The Committee considered the differences between the trials and clinical practice in the UK. The clinical specialists noted that access to surgery may have been quicker in the trials than in clinical practice. It discussed that patients in the trials may be operated on immediately, while in clinical practice there could be a waiting time of several weeks or months. The Committee agreed that this difference could lead to an underestimation of the benefit of ocriplasmin because the wait for surgery can result in a poorer outcome for patients in clinical practice than observed in the trial. The Committee concluded that the benefit of ocriplasmin may have been underestimated because there was a shorter waiting period for vitrectomy in the clinical trials.

4.9 The Committee considered the impact of ocriplasmin on all of the outcomes measured in the trials. The Committee noted that the trial results were limited to 6 months after the injection and therefore the long‑term impact was unknown. However, it heard from clinical specialists that once traction was relieved the condition was generally stable, and therefore it was plausible that any benefits relating to ocriplasmin would be expected to last beyond the 6‑month clinical trial period. The Committee concluded that the clinical effectiveness of ocriplasmin was likely to be durable in the long term.

4.10 The Committee considered the adverse events that were associated with ocriplasmin. It noted that adverse events were mainly ocular events and that the incidence of serious adverse events was similar between ocriplasmin and placebo. The Committee acknowledged that the most common serious adverse event reported in the study eye was macular hole, which was more common in the placebo group than in the ocriplasmin group. The Committee understood that most adverse events were non-serious, mild in intensity and generally resolved. It concluded that ocriplasmin was similar to placebo in terms of adverse events.

Cost effectiveness

4.11 The Committee considered the cost‑effectiveness evidence presented in the manufacturer's submission, including the base‑case incremental cost‑effectiveness ratios (ICERs), the sensitivity and scenario analyses, the Evidence Review Group's (ERG's) critique of the manufacturer's evidence, and comments raised during consultation on the appraisal consultation document (ACD). The Committee considered the 3 subgroups presented by the manufacturer in turn, as detailed below.

4.12 The Committee considered the available cost‑effectiveness evidence for ocriplasmin in the VMT without ERM subgroup. The Committee discussed the potential for ocriplasmin to be used earlier than surgery would normally be used, in patients with distressing symptoms (for example metamorphopsia or low visual acuity), and was satisfied that this was captured in the model. It discussed the manufacturer's base‑case ICER of £18,500 per quality‑adjusted life year (QALY) gained. It noted that in the ERG's exploratory analysis (see 3.37–3.41) the ICERs were in the range of £17,700 to £20,200 per QALY gained, and that the ERG base-case ICER was £20,900 per QALY gained. The Committee recognised that this subgroup represents people with vitreomacular traction without an epiretinal membrane or a stage II macular hole who would be eligible for vitrectomy surgery, or people with severe distressing symptoms who would not be eligible for surgery. The Committee concluded that ocriplasmin was a cost‑effective option for the treatment of people with vitreomacular traction without an epiretinal membrane, and without a stage II macular hole.

4.13 The Committee considered the available cost‑effectiveness evidence of ocriplasmin in the VMT with ERM subgroup. The Committee noted that ocriplasmin was not associated with a statistically significant improvement in vitreomacular traction resolution and total PVD at 28 days in the VMT with ERM subgroup (see 3.8), and that any differences observed between ocriplasmin and placebo were small. Taking into account these data and the view of the clinical specialists that ocriplasmin was not effective in patients with ERM, the Committee concluded that the use of ocriplasmin in people with vitreomacular traction with an epiretinal membrane, but without a stage II macular hole, was not a cost‑effective use of NHS resources.

4.14 The Committee considered the cost effectiveness of ocriplasmin in the VMT with MH subgroup. It noted the manufacturer's base‑case ICER of £21,600 per QALY gained. It discussed the manufacturer's sensitivity and scenario analysis (see 3.25–3.30), and the ERG critique of the manufacturer's model. It noted the uncertainties in the model, which had potentially substantial impacts on the manufacturer's ICER:

  • The impact of combining vitrectomy and cataract surgery (see 4.15).

  • The rate of cataracts (see 4.16).

  • The macular hole vitrectomy success rate (see 4.17).

  • The metamorphopsia utility value (see 4.18).

    The Committee also discussed additional comments that were raised during ACD consultation (see 4.19) and that could impact on the ICER, including:

  • The number of optical coherence tomography (OCT) and follow‑up visits post‑vitrectomy.

  • The retinal detachment rate.

  • The retinal tear rate.

  • The rate of visual decline not accounting for a macular hole.

    The Committee's discussion and conclusion are summarised in the paragraphs below.

4.15 The Committee considered the VMT and MH subgroup and the assumption in the manufacturer's model that vitrectomy and cataract surgery would not be performed at the same time. The Committee heard from clinical specialists that combining vitrectomy surgery and cataract surgery into one procedure is common practice in the UK. It noted that the risk of cataracts forming after vitrectomy surgery is greater than 90%. However, the clinical specialists explained that the main driver for performing the 2 operations at the same time was constrained capacity in hospital eye departments rather than improved outcomes. The Committee agreed that combining vitrectomy and cataract surgery was done in clinical practice, and therefore should be included in the model. It noted that combining vitrectomy and cataract surgery increased the ICER for the VMT with MH subgroup from £21,600 to approximately £30,500 per QALY gained. The Committee noted that no disutility had been applied by the manufacturer to the model to account for the addition of cataract removal to vitrectomy surgery, and concluded that applying a disutility would reduce the ICER marginally to under £30,500 per QALY gained.

4.16 The Committee discussed the VMT and MH subgroup further, and the rate that was applied in the manufacturer's model for developing a cataract after vitrectomy. The Committee noted from the ERG's critique that as the rate of developing a post‑surgical cataract is reduced, the ICER for ocriplasmin increases. The Committee heard from clinical specialists that the overall chance of developing a cataract was likely to be greater than 90%. It commented further that the annual rate of 64.6% (estimating an ICER of £28,300 per QALY gained for the VMT and MH subgroup) modelled by the ERG was likely to be lower than observed in UK clinical practice, and that the rate modelled by the manufacturer (96% annual rate, ICER £21,600 per QALY gained for the VMT with MH subgroup) was likely to be higher than observed in UK clinical practice. The Committee concluded that the rate of developing a cataract in UK clinical practice was likely to be lower than the manufacturer's value.

4.17 The Committee discussed the success rates of macular hole vitrectomy applied to the VMT with MH subgroup in the manufacturer's model (82%) and applied in the ERG's exploratory analyses (95.8%). It noted that for the VMT with MH subgroup, applying the higher rate increased the ICER from £21,600 to £26,900 per QALY gained. The Committee heard from clinical specialists that the success rate generally ranged from 80 to 90% and acknowledged the comments raised during ACD consultation that supported the ERG's macular hole vitrectomy success rate. The Committee therefore considered the rate applied by the ERG to be the most appropriate. The Committee concluded that the macular hole vitrectomy success rate was likely to be higher than that modelled in the manufacturer's base case and that this would increase the ICER.

4.18 The Committee noted from the manufacturer's scenario analysis in the VMT with MH subgroup that changing the metamorphopsia utility value had an impact on the manufacturer's base‑case ICER. It understood that the manufacturer's base case applied a disutility value of 0.017 and that the manufacturer's scenario analysis, using a value of 0.14, reduced the ICER in all 3 subgroups substantially (see 3.29). The Committee heard from clinical specialists that the utility gained from resolving metamorphopsia could be equivalent to going up 2 visual acuity states. The Committee considered that this was equivalent to approximately 0.03 utilities, based on the utility values used in the manufacturer's model. The Committee concluded that the disutility value applied in the manufacturer's model underestimated the disutility of metamorphopsia and that applying a higher disutility value would reduce the ICER, although the level of impact remained unclear.

4.19 The Committee considered the comments that were received during ACD consultation. It noted that the number of OCT and follow‑up visits post‑vitrectomy may have been overestimated in the manufacturer's base case for the VMT with MH subgroup. The Committee was aware that the ERG had done a sensitivity analysis that reduced the number of OCT and follow‑up visits from 4 to 2, and that this increased the ICER by a small amount: from £21,600 to £22,500 per QALY gained. The Committee also discussed comments received during consultation that a retinal detachment rate of 13.23% in the manufacturer's base case seemed high and a rate of 5.4% was more representative of clinical practice. In addition, a retinal tear rate with ocriplasmin of 0.22% had been used in the manufacturer's base case rather than a rate of 1.3%, which has been published. The Committee considered the impact on the ICER of the different rates of retinal detachment and retinal tear and recognised that the ICER would increase by a small amount. Finally, the Committee also noted comments received during consultation that in the manufacturer's base case visual decline was assumed to be the same whether or not a macular hole was present. The Committee understood from the ERG that the ICER would reduce if visual decline was different for people with or without a macular hole. The Committee concluded that reducing the number of OCT and follow‑up visits and applying different rates for retinal detachment and retinal tear would lead to small increases in the ICER, but that accounting for a greater rate of visual decline with a macular hole would reduce the ICER.

4.20 The Committee considered whether an ocriplasmin injection is an innovative treatment. The Committee agreed with the clinical specialists and manufacturer that the ocriplasmin injection provided a step change in treating patients with vitreomacular traction compared with current practice in vitrectomy and 'watch and wait'. The Committee acknowledged that no significant or substantial health‑related benefits were identified that were not included in the economic model. Therefore the Committee agreed that the ocriplasmin injection was innovative and it would consider an ICER at the top end of the range that would normally be considered a cost effective use of NHS resources (£20,000–30,000 per QALY gained).

4.21 In summary, the Committee considered the manufacturer's base‑case ICERs, the sensitivity and scenario analyses presented by the manufacturer, the ERG's critique and exploratory analyses, and comments raised during consultation for each of the subgroups presented that make up the marketing authorisation.

  • The Committee considered the use of ocriplasmin to treat vitreomacular traction without an epiretinal membrane or a stage II macular hole and concluded that the ICER was likely to be no greater than £20,900 per QALY gained (as presented by the ERG, see 3.41). It agreed therefore that ocriplasmin was a cost‑effective use of NHS resources for treating vitreomacular traction in people with vitreomacular traction without an epiretinal membrane.

  • The Committee considered the use of ocriplasmin to treat vitreomacular traction with an epiretinal membrane, but without a stage II macular hole, and recognised that ocriplasmin was not clinically effective or cost effective for these people (see 3.8 and 3.41). The Committee therefore concluded that ocriplasmin could not be considered a cost‑effective use of NHS resources for treating people with vitreomacular traction and an epiretinal membrane, without a stage II macular hole.

  • The Committee considered the use of ocriplasmin to treat vitreomacular traction with a stage II macular hole. The Committee agreed that the preferred assumption was to include combined cataract and vitrectomy surgery (see 4.15), and noted the associated ICER was approximately £30,500 per QALY gained. It considered that in clinical practice the effectiveness of ocriplasmin might be greater than that seen in the trials because patients would have to wait longer for surgery and would not benefit from a placebo injection (see 4.7). The Committee recognised that this would lower the ICER to below £30,500 per QALY gained. The Committee also considered that addressing uncertainties in the model could both increase and decrease the ICER (increase it by: increasing the macular hole vitrectomy success rate [see 4.17], reducing the post vitrectomy cataract rate [see 4.16], increasing the retinal tear rate with ocriplasmin [see 4.19], decreasing the retinal detachment rate with vitrectomy [see 4.19] and decreasing the post‑vitrectomy OCT and follow‑up visits [see 4.19]; decrease it by: accounting for greater disutility values associated with both metamorphopsia and combined surgery [see 4.15 and 4.18], accounting for a greater rate of visual decline with a macular hole [see 4.19], and accounting for the active placebo comparison [see 4.7]). The Committee recognised that ocriplasmin was unlikely to be clinically effective in patients who have an epiretinal membrane and a stage II macular hole (see 4.6). Having taken into account all of the evidence submitted (from the manufacturer and the ERG), and comments received during ACD consultation, the Committee concluded that on balance the ICER was likely to be lower than £30,500 per QALY gained and therefore ocriplasmin was a cost‑effective use of NHS resources for treating people with vitreomacular traction and a stage II macular hole without an epiretinal membrane.

4.22 The Committee discussed whether NICE's duties under the equalities legislation required it to alter or add to its recommendations in any way. No equality issues were raised during the appraisal process or at the Committee meetings, and therefore the Committee concluded that no alterations or additions to its recommendations were needed.

Summary of Appraisal Committee's key conclusions

TA297

Appraisal title: Ocriplasmin for treating vitreomacular traction

Section

Key conclusion

Ocriplasmin is recommended as an option for treating vitreomacular traction in adults, only if

  • an epiretinal membrane is not present

and

  • they have a stage II full-thickness macular hole with a diameter of 400 micrometres or less and/or

  • they have severe symptoms.

The Committee understood that the treatment pathway, and therefore the use of ocriplasmin, varies depending on the presence or absence of a stage II macular hole. If a stage II macular hole is present, the Committee acknowledged that ocriplasmin would be used during the wait for surgery, without delaying surgery. However, if a stage II macular hole is not present, the Committee recognised that ocriplasmin would be offered as an alternative to surgery, or as an alternative to 'watch and wait' for people who have severe distressing symptoms but are not eligible for surgery.

The Committee concluded that ocriplasmin was clinically and cost effective in the VMT without ERM (vitreomacular traction without an epiretinal membrane), and VMT with MH (vitreomacular traction with a stage II macular hole) subgroups.

The Committee recognised that in the VMT with ERM (vitreomacular traction with an epiretinal membrane) subgroup, the effect of ocriplasmin was small and not statistically significant. The Committee heard from the clinical specialists that they did not consider ocriplasmin to have a place in the treatment of patients with vitreomacular traction and an epiretinal membrane because it was not clinically effective in these patients. The Committee recognised that the VMT with MH group included people with an epiretinal membrane, and taking into account the data from the VMT with ERM subgroup and the opinion of the clinical specialists it concluded that ocriplasmin was unlikely to be clinically or cost effective in people with an epiretinal membrane in any of the subgroups, including VMT with MH.

1.1, 4.2, 4.6, 4.12, 4.13, 4.21

Current practice

Clinical need of patients, including the availability of alternative treatments

The Committee understood that vitreomacular traction is managed differently depending on whether or not a stage II macular hole is present; if a stage II macular hole is present, ocriplasmin would be used during the wait for surgery, without delaying surgery; if a stage II macular hole is not present, ocriplasmin would be used as an alternative to surgery, or as an alternative to 'watch and wait' for people who have severe distressing symptoms.

The Committee understood that, although vitrectomy surgery is effective in resolving vitreomacular traction and the recovery time after surgery is short, the recovery is an unpleasant process for patients, and that surgery has risks and could damage the eye. The Committee concluded that an alternative treatment for vitreomacular traction would be welcomed by clinicians and patients.

4.2, 4.3

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?

The Committee agreed with the clinical specialists that the ocriplasmin injection provided a step change in treating patients with vitreomacular traction because it provides an alternative to 'watch and wait' and/or surgery. The Committee concluded that it was innovative.

4.20

What is the position of the treatment in the pathway of care for the condition?

The Committee understood that in UK clinical practice patients who have a stage II macular hole would be listed for surgery and ocriplasmin would be administered during the period before surgery, without delaying surgery. For patients without a macular hole, ocriplasmin would be offered as an alternative to surgery, or as an alternative to 'watch and wait' for people who have severe distressing symptoms.

4.2

Adverse reactions

The Committee understood that adverse event rates were similar between placebo and ocriplasmin and that most were non‑serious, mild in intensity, and resolved, and therefore were not considered to be clinically significant.

3.11, 4.10

Evidence for clinical effectiveness

Availability, nature and quality of evidence

The Committee acknowledged that all the relevant evidence was likely to have been identified by the manufacturer and that the evidence to support the clinical effectiveness was from the TG‑MV‑006 and TG‑MV‑007 trials. The Committee understood that the evidence presented by the manufacturer matched the decision problem.

3.31, 4.5

Relevance to general clinical practice in the NHS

The Committee discussed the comparator arm in the trials and noted that a placebo injection was used in the trials instead of the UK clinical practice of 'watch and wait'. The Committee concluded that the placebo injection in the clinical trials was not equivalent to 'watch and wait' and that it was plausible that the efficacy of ocriplasmin would have been greater if it had been compared with the UK clinical practice of 'watch and wait'.

4.7

Uncertainties generated by the evidence

The Committee recognised 2 key uncertainties in the clinical evidence:

  • The comparator in the trials was a placebo injection rather than 'watch and wait'.

  • Patients may have had a shorter waiting period before vitrectomy in the clinical trial than would be expected in clinical practice.

The Committee concluded that the efficacy of ocriplasmin may have been underestimated because of these uncertainties.

4.7, 4.8

Are there any clinically relevant subgroups for which there is evidence of differential effectiveness?

The manufacturer presented 3 different subgroups, for which there was differential effectiveness. The Committee took into account the data from the VMT with ERM subgroup and the opinion of the clinical specialists and concluded that ocriplasmin was unlikely to be clinically effective in people with an epiretinal membrane in any of the subgroups, including VMT with MH. The Committee concluded that ocriplasmin was clinically effective in the subgroups VMT without ERM and VMT with MH, but not in the subgroup VMT with ERM, and was unlikely to be clinically effective in those in the VMT with MH subgroup who had an epiretinal membrane.

4.6

Estimate of the size of the clinical effectiveness including strength of supporting evidence

The Committee noted that there was a statistically significant benefit in terms of vitreomacular traction resolution and total posterior vitreous detachment at day 28 in the VMT without ERM and VMT with MH subgroups.

4.5

Evidence for cost effectiveness

Availability and nature of evidence

The Committee considered the cost‑effectiveness evidence presented in the manufacturer's submission, including the base‑case incremental cost-effectiveness ratios (ICERs), the sensitivity and scenario analyses, as well as the Evidence Review Group's (ERG) critique of the manufacturer's evidence. The Committee understood that the modelling approach presented by the manufacturer was appropriate and that the assumptions and data sources were reasonable.

3.35

Uncertainties around and plausibility of assumptions and inputs in the economic model

The Committee considered important areas of uncertainty in the model:

  • The assumption that vitrectomy and cataract surgery would be completed separately, and that when the model accounted for combined surgery a disutility value to account for the addition of cataract removal to surgery was not added.

  • The cataract rate.

  • The macular hole vitrectomy success rate.

  • The metamorphopsia disutility value.

  • The number of optical coherence tomography and follow‑up visits post‑vitrectomy.

  • The retinal detachment and retinal tear rate.

  • The rate of visual decline not accounting for a macular hole.

4.14, 4.15, 4.16, 4.17, 4.18

Incorporation of health‑related quality‑of‑life benefits and utility values

Have any potential significant and substantial health‑related benefits been identified that were not included in the economic model, and how have they been considered?

The Committee agreed with clinical specialists that the ocriplasmin injection provided a step change in treating patients with vitreomacular traction because it provides an alternative to 'watch and wait' and/or surgery. The Committee concluded that it was innovative. The Committee recognised that the benefit of this may not have been captured in the quality-adjusted life year (QALY) calculation.

4.20

Are there specific groups of people for whom the technology is particularly cost effective?

The Committee understood that there was not a group of people for whom ocriplasmin was particularly cost effective. However, it recognised that ocriplasmin was not clinically effective (in terms of total posterior vitreous detachment [PVD] and vitreomacular traction resolution by day 28) for patients with vitreomacular traction and epiretinal membrane, without a stage II macular hole. In addition, it concluded, taking into account the views of clinical specialists and the data from the VMT with ERM subgroup, that ocriplasmin was unlikely to be clinically effective (in terms of total PVD and vitreomacular traction resolution by day 28) for patients with vitreomacular traction, an epiretinal membrane and a stage II macular hole. It therefore concluded that ocriplasmin was not cost effective for these groups.

3.8, 3.9, 4.6, 4.13, 4.21

What are the key drivers of cost effectiveness?

For the VMT without ERM and VMT with ERM subgroups the model outcomes were most sensitive to the inputs determining non‑surgical resolution of vitreomacular traction at 6 months and 28 days. The QALY discount rate was also an important driver for these subgroups. For the VMT with MH subgroup, the model outcomes were most sensitive to the inputs that determined non‑surgical macular hole closure, cataract disutility and the change of macular hole closure post‑vitrectomy.

3.26

Most likely cost‑effectiveness estimate (given as an ICER)

The Committee considered the use of ocriplasmin to treat vitreomacular traction without an epiretinal membrane or a stage II macular hole and concluded that the ICER was likely to be no greater than £20,900 per QALY gained (as presented by the ERG). It agreed therefore that ocriplasmin was a cost-effective use of NHS resources for treating vitreomacular traction in people without an epiretinal membrane.

The Committee considered the use of ocriplasmin to treat vitreomacular traction with an epiretinal membrane but without a stage II macular hole and recognised that ocriplasmin was not clinically effective or cost effective for these people. The Committee therefore concluded that ocriplasmin could not be considered a cost-effective use of NHS resources for treating people with vitreomacular traction and an epiretinal membrane, without a stage II macular hole.

The Committee considered the use of ocriplasmin to treat vitreomacular traction with a stage II macular hole. The Committee agreed that the preferred assumption was to include combined cataract and vitrectomy surgery, and noted the associated ICER was approximately £30,500 per QALY gained. The Committee also considered that addressing uncertainties in the model could both increase and decrease the ICER. The Committee recognised that ocriplasmin was unlikely to be clinically effective in patients who have an epiretinal membrane and a stage II macular hole. Having taken into account all of the evidence submitted (from the manufacturer and the ERG), and comments received during consultation, the Committee concluded that on balance the ICER was likely to be lower than £30,500 per QALY gained and therefore ocriplasmin was a cost-effective use of NHS resources for treating people with vitreomacular traction and a stage II macular hole without an epiretinal membrane.

4.21

Additional factors taken into account

Equalities considerations and social value judgements

No equality issues within the scope of this appraisal were raised during the appraisal process or at the Committee meetings.

  • National Institute for Health and Care Excellence (NICE)