Our recent work for NICE

In the past months, iMTA and the HTA department of ESHPM have worked on six projects as External Assessment Group (EAG) in relation to the appraisal of specific technologies under the NICE Single Technology Appraisal (STA) programme. Published guidance on three of these projects can be found below. External assessment groups are independent academic centres commissioned by NICE to technically review the company’s evidence submission and prepare a so-called EAG report. Our NICE team consists of Maiwenn Al, Venetia Qendri and Eline Krijkamp, from the HTA department of ESHPM, and Isaac Corro Ramos, from iMTA. In this period, the team was supported by four colleagues of the HTA department of ESHPM, Seamus Kent, Annemieke Leunis-van Dongen, Mehlika Toy and Marten Poley, and one iMTA colleague, Stavros Anagnostopoulos.

In addition, our previous work for NICE has led to two publications in PharmacoEconomics. Key learnings from these assessments and a link to the full papers can be found below.

 

PharmacoEconomics – Key Learnings From NICE Single Technology Appraisals

When Evidence Falls Short—Belzutifan for Treating Tumours Associated with von Hippel-Lindau Disease: An External Assessment Group Perspective on a NICE Single Technology Appraisal

Key learnings from this work were the following:

• In the absence of comparative study data, EAGs need to be alert to biases due to a mismatch between the DP/ scope/MA and any trial populations. Such biases can be mitigated by making best use of individual patient data, adjusted to better match the correct population.
• EAGs also need to ensure that patients in the economic model are treated as if from this same population regardless of whether in receipt of the intervention or comparator.
• Sometimes most of the uncertainties identified in the company submission cannot be resolved with the current evidence. Considering this, the current model structure and the available data, the EAG might prefer not to define a new base case; any alternative base-case scenario would still be subjected to too many uncertainties, its results would be unreliable and could give the wrong impression that it would be appropriate for the current DP.
• Nevertheless, EAGs need to explore additional scenario analyses to highlight key uncertainty areas and assess the impact of relevant assumptions on the current CE results.

Read the full article HERE.

 

Cost Comparisons in NICE Technology Appraisals: An External Assessment Group Perspective

Key learnings from this work were the following:

• Cost comparisons can play a valuable role in NICE TAs when there is evidence of at least similar efficacy and safety, promoting an optimal balance between the need for empirical evidence and the goal of providing timely access to new technologies. This resembles practices in other countries: for example, in Australia, cost-minimisation analysis has a recognized role in the decision-making process of the Pharmaceutical Benefits Advisory Committee for medicines.
• In cost comparisons, demonstrating equivalence does not require RCTs designed for this purpose. A lack of statistically significant difference or overlapping 95% CIs for multiple outcomes can suffice.
• Cost-comparison models are simpler than cost-effectiveness models: clinical benefits are not modelled; only cost differences are considered.
• EAGs must remain alert to methodological challenges that can arise in cost-comparison analyses, as appeared from the case studies discussed in this article. These challenges include the choice of comparator, establishing equivalence in efficacy and safety, the types of costs to be included, and the time horizon (including considerations of treatment discontinuation). For example, there is a risk of omitting some comparators, which might be more effective or cheaper. To give another example, although the cost of managing adverse events should be captured in a cost comparison, if there are substantial differences between technologies in the costs associated with adverse events, then the cost- comparison approach might be unsuitable, and a CUA could be more appropriate.
• Validation of the economic model remains crucial, although it is less time-consuming than for a full CUA.
• Cost comparisons typically require less work from EAGs (e.g. EAG reports are generally shorter, by following the NICE cost-comparison template).

Read the full article HERE.

 

Completed NICE Appraisals

Linzagolix for treating symptoms of endometriosis

Linzagolix with hormonal add-back therapy can be used within its marketing authorisation as an option to treat symptoms of endometriosis in adults of reproductive age who have had medical or surgical treatment for their endometriosis.

Treatments for endometriosis aim to manage its symptoms but do not resolve the underlying condition. Options include surgery, gonadotropin-releasing hormone agonists (such as leuprorelin acetate) and relugolix–estradiol–norethisterone acetate (relugolix combination therapy [CT]).

Clinical trial evidence shows that linzagolix with hormonal add-back therapy reduces dysmenorrhoea (painful periods) and non-menstrual pelvic pain compared with placebo. Indirect comparisons suggest that linzagolix with hormonal add-back therapy gives similar pain relief to leuprorelin acetate and relugolix CT.

The cost-effectiveness estimates for linzagolix with hormonal add-back therapy compared with surgery, leuprorelin acetate and relugolix CT are within the range that NICE considers an acceptable use of NHS resources. So, linzagolix with hormonal add-back therapy can be used.

Read the full recommendation HERE.

 

Betula verrucosa for treating moderate to severe allergic rhinitis or conjunctivitis caused by tree pollen

Betula verrucosa can be used as an option to treat moderate to severe allergic rhinitis or conjunctivitis caused by pollen from the birch homologous group of trees in adults with: symptoms despite using symptom-relieving medicines and a positive sensitisation test (skin prick test or specific immunoglobulin E) to a member of the birch homologous group.

For this evaluation, betula verrucosa was considered only for use in adults. This does not include everyone who it is licensed for.

Usual treatment for moderate to severe allergic rhinitis and conjunctivitis caused by pollen from the birch homologous group of trees includes symptom-relieving medicines such as antihistamine tablets and corticosteroid nasal sprays.

Clinical trial evidence shows that betula verrucosa reduces the severity of allergic rhinitis and conjunctivitis symptoms compared with placebo (both when given with symptom-relieving medicines).

There is uncertainty in the economic model about how many healthcare appointments would be saved by using betula verrucosa. But even when taking this into account, the likely cost-effectiveness estimates are all within the range that NICE considers an acceptable use of NHS resources. So, betula verrucosa can be used.

Read the full recommendation HERE.

 

Vanzacaftor-tezacaftor-deutivacaftor for treating cystic fibrosis with 1 or more F508del mutations in the CFTR gene in people 6 years and over

Vanzacaftor-tezacaftor-deutivacaftor (Vnz-Tez-Diva) can be used as an option to treat cystic fibrosis in people 6 years and over who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Vnz-Tez-Diva can only be used if the company provides it according to the commercial arrangement.

Usual treatment for cystic fibrosis with at least 1 F508del mutation in the CFTR gene is Iva-Tez-Elx, which is licensed for people 2 years and over. Vnz-Tez-Diva works in a similar way and is licensed for people 6 years and over.

Clinical trial evidence shows that Vnz-Tez-Diva is as effective as Iva-Tez-Elx in people 12 years and over at improving lung function, growth and weight gain and reducing the number of lung infections. It has not been directly compared with Iva-Tez-Elx in people aged 6 to 11 years but is likely to work as well in these people.

A cost comparison of Vnz-Tez-Diva and Iva-Tez-Elx in people 6 years and over suggests that the costs are similar. But Iva-Tez-Elx is licensed for people with at least 1 F508del mutation and no other responsive mutation. So, Vnz-Tez-Diva can only be used in people 6 years and over who have at least 1 F508del mutation in the CFTR gene.

Read the full recommendation HERE

 

Other publications

For undermentioned research, the team was supported by three colleagues of the HTA department of ESHPM, Annemieke Leunis-van Dongen, Mehlika Toy and Marten Poley.

 

Relugolix–estradiol–norethisterone for treating symptoms of endometriosis

Relugolix–estradiol–norethisterone (relugolix combination therapy [CT]) can be used, within its marketing authorisation, as an option for treating symptoms of endometriosis in adults of reproductive age who have had medical or surgical treatment for endometriosis.

After pain relief and hormonal treatment, usual treatment options for endometriosis are gonadotropin-releasing hormone (GnRH) agonists and surgery. There is no cure for endometriosis, and there is an unmet need for long-term and non-invasive (nonsurgical and not injected) treatments for its symptoms. Clinical trial evidence shows that relugolix CT reduces pain compared with placebo. Relugolix CT has not been directly compared in a clinical trial with usual treatment. Indirect comparisons suggest that it is likely to reduce pelvic pain almost as well as GnRH agonists. But it is unclear how well relugolix CT works compared with surgery. The cost-effectiveness estimates for relugolix CT compared with GnRH agonists and surgery are within the range that NICE considers an acceptable use of NHS resources. So, relugolix CT is recommended.

Article in The Guardian

 

Selpercatinib for advanced thyroid cancer with RET alterations untreated with a targeted cancer drug in people 12 years and over

Selpercatinib is recommended as an option for treating advanced RET fusion-positive thyroid cancer that is refractory to radioactive iodine (if radioactive iodine is appropriate) and advanced RET-mutant medullary thyroid cancer. It is for people 12 years and over and is recommended only if the cancer has not been treated with a targeted cancer drug, and the company provides it according to the commercial arrangement.

Its evaluation focused on RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer that has not been treated with a targeted cancer drug. People may have surgery to remove all or part of the thyroid before starting drug treatments. Usual treatments for RET-mutant medullary thyroid cancer include cabozantinib (a targeted cancer drug) and best supportive care (routine care and monitoring). Usual treatments for RET fusion-positive thyroid cancer that is refractory to radioactive iodine include targeted cancer drugs (lenvatinib or sorafenib) and best supportive care. Selpercatinib is a targeted cancer drug. The main clinical trial supporting this evaluation did not directly compare selpercatinib with usual treatment. Indirect comparisons suggest that people having selpercatinib have longer before their cancer gets worse and live longer than people having usual treatment. But this is uncertain. The most likely cost-effectiveness estimates are below what NICE considers an acceptable use of NHS resources. So selpercatinib is recommended.

Read the article HERE

 

Ruxolitinib for treating acute graft versus host disease refractory to corticosteroids in people aged 12 and over

Final Draft Guidance established that Ruxolitinib is recommended, within its marketing authorisation, as an option for treating acute graft versus host disease (GvHD) that has an inadequate response to corticosteroids in people 12 years and over. Ruxolitinib is only recommended if the company provides it according to the commercial arrangement.https://www.nice.org.uk/guidance/indevelopment/gid-ta11512

First-line standard care for acute GvHD is corticosteroids. If corticosteroids have not worked well enough, second-line standard care can include extracorporeal photopheresis, mycophenolate mofetil, etanercept and infliximab. Ruxolitinib is an alternative to these second-line treatments. Clinical trial evidence shows that acute GvHD is more likely to improve with ruxolitinib than with standard care. Treatment failure (that is, need for another treatment, relapse of the underlying disease that led to the need for a transplant, or death) may also be less likely in people who have ruxolitinib. The most likely cost-effectiveness estimate for ruxolitinib is within the range that NICE considers an acceptable use of NHS resources. So, ruxolitinib is recommended.

Read the article HERE

 

Efanesoctocog alfa for treating and preventing bleeding episodes in haemophilia A in people 2 years and over

Efanesoctocog alfa is recommended as an option for treating and preventing bleeding episodes in people 2 years and over with haemophilia A (congenital factor VIII deficiency), only if they have a factor VIII activity level of less than 1% (severe haemophilia A) and the company provides it according to the commercial arrangement.

For this evaluation, efanesoctocog alfa was only considered for people with severe haemophilia A, in line with the evidence provided by the company. This does not include everyone who it is licensed for. Current treatment options for severe haemophilia A include ongoing treatment with factor VIII replacement therapies (including standard half-life and extended half-life therapies) or emicizumab to prevent bleeding. On-demand factor VIII replacement therapies are used to treat bleeding. The results from a clinical trial suggest that there may be fewer bleeding episodes with ongoing efanesoctocog than with previous ongoing factor VIII replacement therapy, but this is uncertain. There is limited clinical-effectiveness evidence directly comparing efanesoctocog alfa with currently available treatments for severe haemophilia A, and there are substantial limitations with the available indirect comparisons. So, it is uncertain how well efanesoctocog alfa works compared with other haemophilia A treatments. Because of uncertainties in the clinical-effectiveness evidence and the economic model, the cost-effectiveness estimates are uncertain. But, when considering all the available evidence and economic analyses, efanesoctocog alfa is a cost-effective use of NHS resources. So, it is recommended.

Read the article HERE

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