Key findings
The comparison of expected uptake to the actual volume of medicines used in the NHS in England is available in the national level medicine groupings interactive dashboard.
You can find the dashboard on the online web platform.
The expected uptake is shown where it has been possible to estimate the range of expected usage in the NHS in England for high level conditions within the areas below, for the medicines listed.
High level conditions
 Cancer
 Cardiovascular conditions
 Genetic disorder
 Infections
 Lifestyle
 Neurological conditions
 Respiratory conditions
Medicines
 Abiraterone acetate
 Afatinib
 Alemtuzumab
 Alirocumab
 Apalutamide
 Apixaban
 Benralizumab
 Cabazitaxel
 Cladribine
 Dabigatran etexilate
 Dacomitinib
 Dimethyl fumarate
 Diroximel fumarate
 Edoxaban
 Elbasvir–grazoprevir
 Enzalutamide
 Eptinezumab
 Erenumab
 Erlotinib
 Evolocumab
 Fingolimod
 Fremanezumab
 Galcanezumab
 Gefitinib
 Glatiramer acetate
 Glecaprevir–pibrentasvir
 Icosapent ethyl
 Inclisiran
 Interferon beta1a
 Interferon beta1b
 Ivacaftor (branded as Kalydeco)
 Ivacaftor–tezacaftor–elexacaftor (branded as Kaftrio)
 Ledipasvir–sofosbuvir
 Lumacaftor–ivacaftor (branded as Orkambi)
 Mepolizumab
 Natalizumab
 Ocrelizumab
 Ofatumumab
 Omalizumab
 Ombitasvir–paritaprevir–ritonavir
 Osimertinib
 Peginterferon beta1a
 Ponesimod
 Reslizumab
 Rimegepant
 Rivaroxaban
 Siponimod
 Sofosbuvir
 Sofosbuvir–velpatasvir
 Sofosbuvir–velpatasvir–voxilaprevir
 Teriflunomide
 Tezacaftor–ivacaftor (branded as Symkevi)
 Varenicline
 Warfarin
Interpretation
The interactive dashboard, where possible, compares the expected usage of National Institute for Health and Care Excellence (NICE) recommended medicines to the actual volume of medicines used in the NHS in England. The choice to use the medicine should occur only when the clinician concludes and the patient agrees that the recommended medicine is the most appropriate to use. This choice is based on a discussion of all available treatments and informed patient choice. In interpreting these figures, it is important to note that the expected and observed use may differ for a variety of reasons and they should not be assumed to definitely indicate either ‘under’ or ‘over’ prescribing.
Potential explanations for variation between actual and expected volumes include:
 clinical judgement and patient choice
 the availability of alternative treatment options that have not been appraised by NICE
 changes in prevalence or incidence
 the time taken for the population to present to services
 assumptions about the average length of treatment used to develop predictions of use
 known gaps in the medicine utilisation data, such as supplies made directly to patients via the homecare route or by outsourced dispensing
Estimate calculations
The sections below set out the calculation steps for each group of medicines where it has been possible to estimate the range of expected usage in the NHS in England. Expected usage is stated as the expected number of Assumed Daily Doses (ADDs) per 100,000 population for the time period. More information on ADDs can be found in the ADD methodology chapter of this publication. Links have been included to the NICE guidance and Summaries of Product Characteristics (SmPC) for each medicine.
Atrial fibrillation, pulmonary embolism or deep vein thrombosis
Apixaban, dabigatran, edoxaban, rivaroxaban and warfarin are recommended by NICE for treating atrial fibrillation, pulmonary embolism or deep vein thrombosis. These were published between 2012 and 2015.
Apixaban
Dabigatran etexilate
Edoxaban
Rivaroxaban
Atrial fibrillation, pulmonary embolism or deep vein thrombosis: estimate calculation
Only use of apixaban, dabigatran etexilate, edoxaban, rivaroxaban and warfarin in primary care is estimated.
1. Population who meet SmPC
The Summaries of Product Characteristics (SmPC) states that these medicines are mostly indicated for an adult population. However due to prevalence data in step 2, the starting population is the whole population in England in 2022.
Measure  Point estimate  Reference 

England population  57,106,398  1 
2. Prevalence of atrial fibrillation
Primary care GP registry Quality and Outcomes Framework (QOF) reported 2.1% of the England population in 2021/22 have diagnosed atrial fibrillation. Not all people with atrial fibrillation (AF) who are eligible to receive medication will be diagnosed.
Given this potential unknown population we have used Public Health England’s (2017) estimate of prevalence (and 95% confidence intervals); 2.5% (95% CI 2.4% to 2.6%), which estimates the diagnosed and undiagnosed population. This prevalence estimate is based on a Swedish study and is for the whole population.
This figure has been applied to the whole population in England in step 1.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with atrial fibrillation  1,427,660  1,370,554  1,484,766  2 
3. Proportion of people with atrial fibrillation eligible to receive treatment with apixaban, dabigatran etexilate, edoxaban, rivaroxaban or warfarin
Not all people with atrial fibrillation will be suitable to receive these medications. Reasons for not receiving medicine include lower thromboembolic risk score and weight.
The Quality and Outcomes Framework indicator AF007 records the number of people with diagnosed atrial fibrillation with a record of a CHA2DS2VASc score of 2 or more, who are treated with anticoagulation drug therapy, as 89%. This has been used to estimate the proportion of people with atrial fibrillation who are eligible to receive treatment.
This has been applied to the estimate and upper and lower confidence intervals calculated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with disease  1,270,617  1,219,793  1,321,442  3 
4. People with PE/DVT (VTE) provoked and unprovoked incidence
The incidence (and 95% confidence intervals) of provoked and unprovoked VTE for the whole population have been reported by Martinez (2013) as 131.5 per 100,000 person years (95% CI 130.2 to 132.9).
These proportions have been applied to the population identified in step 1.
Measure  Point estimate  Lower range  Upper range  Reference 

Incidence of VTE  75,380  74,238  75,952  4 
5. People with PE/DVT (VTE) and cancer
The estimated incidence of provoked and unprovoked VTE with active cancer is reported by Martinez (2013) as: 18.6%. The inverse of this figure has been used to calculate the proportion of people with VTE who are not known to have cancer.
These figures have been applied to the estimate and upper and lower range calculated in step 4.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people with VTE and active cancer  14,021  13,808  14,127  4 
Number of people with VTE not known to have cancer  61,359  60,430  61,825  4 
6. People with recurrent PE/DVT (VTE)
Martinez calculated 58.1% of people will have unprovoked VTE. This has been used as a proxy for the proportion of the VTE population that should receive long term anticoagulant treatment.
These figures have been applied to the estimate and upper and lower range calculated in step 4.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people likely to receive treatment with recurrent PE/DVT (VTE)  43,796  43,132  44,128  4 
7. Treatment duration
The duration of treatment is taken from the British National Formulary (2020). The treatment duration applied here is 3 months for incident VTE, 6 months for incident VTE with cancer, and lifelong for both AF and recurrent VTE.
These treatment durations have been used to estimate the number of people who will receive treatment in a year. For example, if treatment duration is 6 months, the eligible population has been multiplied by 0.5. Where the treatment duration is 3 months, the treatment population has been multiplied by 0.25.
These figures have been applied to the estimate and upper and lower range calculated in steps 3, 5 and 6.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people with VTE and active cancer and receiving treatment  7,011  6,904  7,064  5 
Number of people with VTE not known to have cancer and receiving treatment  15,340  15,108  15,456  5 
Number of people with recurrent VTE and receiving treatment  43,796  43,132  44,128  5 
Number of people with AF and receiving treatment  1,270,617  1,219,793  1,321,442  5 
8. Estimated population in England with atrial fibrillation, pulmonary embolism or deep vein thrombosis expected to receive one of apixaban, dabigatran, edoxaban, rivaroxaban and warfarin
The figures calculated in step 7 have been summed together to get a total.
Measure  Point estimate  Lower range  Upper range 

Estimated number of people likely to receive treatment  1,336,764  1,284,937  1,388,090 
9. Estimated volume
The number of people estimated to receive apixaban, dabigatran, edoxaban, rivaroxaban or warfarin was calculated in step 8. This number has then been multiplied by the number of days in a year to give the annual usage in Assumed Daily Doses (ADD).
Measure  Point estimate  Lower range  Upper range 

Estimated annual usage (ADDs) 365 days  487,918,860  469,002,005  506,652,850 
10. Estimated usage by quarter per 100,000 population
The estimated annual ADD usage calculated in step 9 was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 9.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  213,601  205,319  221,802  1 
References
1. Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
2. PHE (2017) Technical document for subnational English atrial fibrillation prevalence estimates: https://www.gov.uk/government/publications/atrialfibrillationprevalenceestimatesforlocalpopulations [Accessed 11/09/2020].
3. Quality and outcomes framework 202122 (2022). NHS Digital. Available from https://digital.nhs.uk/dataandinformation/publications/statistical/qualityandoutcomesframeworkachievementprevalenceandexceptionsdata/202122 [Accessed: 03/01/2023].
4. Martinez (2013). Epidemiology of first and recurrent venous thromboembolism: A populationbased cohort study in patients without active cancer https://pdfs.semanticscholar.org/a72e/a02e5d50b2ef7d9f854fb7cdc82d98d59c50.pdf?_ga=2.261870413.1733460998.16028380891477011522.1602838089 [Accessed: 11/09/2020].
Chronic hepatitis C
Elbasvir–grazoprevir, glecaprevir–pibrentasvir, ledipasvir–sofosbuvir, ombitasvir–paritaprevir–ritonavir, sofosbuvir, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir are recommended by NICE for treating chronic hepatitis C in adults. These were published between 2015 and 2018.
Elbasvir–grazoprevir
Glecaprevir–pibrentasvir
Ledipasvir–sofosbuvir
Ombitasvir–paritaprevir–ritonavir
Sofosbuvir–velpatasvir
Sofosbuvir–velpatasvir–voxilaprevir
Chronic hepatitis C: estimate calculation
1. Population who meet SmPC
The Summaries of Product Characteristics (SmPC) for elbasvir–grazoprevir, glecaprevir–pibrentasvir, ledipasvir–sofosbuvir, ombitasvir–paritaprevir–ritonavir, sofosbuvir, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir show they are mostly indicated for an adult population, although some are indicated for people aged 3 years and older. As most patients are likely to be over 18 years the starting population is for this age.
Measure  Point estimate  Reference 

England population (aged 18+)  45,219,492  1 
2. Prevalence of chronic hepatitis C
In the resource tool costing template for ombitasvir–paritaprevir–ritonavir (TA365), NICE assume a prevalence rate of 0.4% of the population in England aged 18 and over.
As the population size at the time (ONS midyear 2014 estimate) was 41,766,418, this gave a prevalent population of 167,066. If the prevalence rate remained the same, given the population increase for the age group, the prevalent population for chronic hepatitis C would now be 180,878.
Public Health England (PHE) publish an annual report on hepatitis C in England. In the accompanying data table, published in 2020, they give the following prevalence figures in 2019 as 89,000. We have used both prevalence figures for an upper and lower range.
Measure  Point estimate  Reference 

Prevalent population (NICE, 2014)  180,878  2 
Prevalent population (PHE, 2019)  89,000  4 
3. Number of patients to be initiated with a new course of treatment
All the estimated prevalent population are eligible for treatment. However, the number who would be expected to be treated will depend on the rate at which people present to services or are identified for one of the NHS England hepatitis C programme initiatives.
TA365 guidance assumes a population treatment of 9%, based on a company submission by Abbvie. This estimate has been applied to the prevalent populations in step 2.
Measure  Unique people (annual)  Unique people (monthly) 

NICE (2014)  16,279  1,357 
PHE (2019)  8,010  668 
4. Number of people to receive treatment
The upper and lower bound calculated in step 3 and the midpoint have been applied to estimate the number of people who will receive treatment annually.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who will receive treatment  12,145  8,010  16,279   
5. Volume of treatment
The upper and lower bound and the point estimate calculated in step 4 has been multiplied by the number of treatment days. The lower bound multiplied by 56 days (treatment duration of 8 weeks multiplied by 7 days per week) and upper bound multiplied by 84 days (treatment duration of 12 weeks multiplied by 7 days per week). The point estimate is the midpoint between this range.
Assumed Daily Doses (ADD) were used to measure uptake.
Measure  Point estimate  Lower range  Upper range 

Estimated usage ADD  907,998  448,560  1,367,436 
6. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 5, was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  398  196  599  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 NICE (2015) Resource impact assessment template for Ombitasvir–paritaprevir–ritonavir with or without dasabuvir for treating chronic hepatitis C TA365. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta365.
 Public Health England (2020) Hepatitis C in the England: Annual Report. Available from: https://www.gov.uk/government/publications/hepatitiscintheuk
 Public Health England (2020) Hepatitis C in the England: Headline data table. Available from: https://www.gov.uk/government/publications/hepatitiscintheuk
 Datapharm Communications Ltd (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/ [Accessed: 16/06/2021].
Cystic fibrosis
Ivacaftor, ivacaftor–tezacaftor–elexacaftor, lumacaftor–ivacaftor and tezacaftor–ivacaftor for treating cystic fibrosis.
Ivacaftor, ivacaftor–tezacaftor–elexacaftor, lumacaftor–ivacaftor and tezacaftor–ivacaftor
Although NICE does not recommend lumacaftor–ivacaftor in the NICE guidance TA398 published in 2016, NHS England has said that it is now available on the NHS for treating cystic fibrosis.
NHS England has agreed combination therapy is available on the NHS for treating cystic fibrosis. Further information on the announcement of this agreement can be found on the NHS England website. The data collection agreement can be found on the NICE website. It enables eligible patients continued access to Vertex’s cystic fibrosis modulator therapies while further data is collected to inform a future NICE technology appraisal.
The SmPC therapeutic indications are:
Cystic fibrosis: estimate calculation
There are 4 treatment options for cystic fibrosis which have licensed indications linked to patient subgroups by genotype. These are:
 Ivacaftor (brand name Kalydeco)
 Ivacaftor–tezacaftor–elexacaftor (brand name Kaftrio)
 Lumacaftor–ivacaftor (brand name Orkambi)
 Tezacaftor–ivacaftor (brand name Symkevi)
1. Population who meet SmPC
While cystic fibrosis is associated with younger people, those aged 40 and under in particular, people of all ages can have the condition. Therefore, we have used the England population for all ages as the starting point for this estimate.
Measure  Point estimate  Reference 

England population (all ages)  57,106,398  1 
2. Prevalence of cystic fibrosis
The UK cystic fibrosis registry has collected prevalence data since 2009.
The prevalence of cystic fibrosis is 0.018% across all age groups and 0.031% in people aged 40 years and younger. The 0.018% prevalence rate has been added to the total of step 1.
Measure  Point estimate  Reference 

Prevalent population  10,279  2 
3. Number of people eligible to be treated
NHS England and NHS Improvement (NHSEI) applied for bespoke data from the UK cystic fibrosis registry for people in England by genotype. The licensed population is 68% of the prevalent population as shown below.
Measure  12+  611  25  02  Total 

Total licensed population  5,441  862  614  74  6,990 
Modelling by NHSEI of the licensed population suggests a rise in the number of people eligible for treatment in the next 4 years. The profile beyond this point will be subject to demographic changes.
Year 1  Year 2  Year 3  Year 4  

6,920  6,990  7,317  7,899  7,899 
4. Number of people to receive treatment
Clinical judgement suggests that the compliance/tolerance rate of the interventions may mean that the number of people receiving a course of treatment at any one time is approximately 81%. The 95% confidence interval around this estimated proportion has been calculated using the exact binomial method (Pezzullo, 2009).
The proportion receiving treatment and the confidence interval has been applied to the licenced population in year 4.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who will receive treatment (year 4)  6,399  6,320  6,478  3 
5. Estimated volume
The estimated number of people who will receive treatment has been multiplied by the number of days in the year to give the annual usage in Assumed Daily Doses (ADD).
Measure  Point estimate  Lower range  Upper range 

Annual volume (ADD) 365 days  2,335,485  2,306,652  2,364,318 
6. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 5, was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  1,022  1,010  1,035  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 UK Cystic Fibrosis Registry. Available from: https://www.cysticfibrosis.org.uk/
 Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html
Epidermal growth factor receptor EGFR nonsmallcell lung cancer
Afatinib, dacomitinib, erlotinib, and gefitinib are indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutationpositive nonsmallcell lung cancer (NSCLC).
Osimertinib is indicated for firstline treatment in people with stage Ib to stage IIIa EGFR positive NSCLC and secondline treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutationpositive NSCLC.
Erlotinib
Osimertinib
EGFR nonsmallcell lung cancer: estimate calculation
The following aims to estimate the expected usage of the NICE positively appraised medicines afatinib, dacomitinib, erlotinib and gefitinib in people with epidermal growth factor receptor (EGFR) positive stage 3b and stage 4 advanced nonsmallcell lung cancer (NSCLC), firstline treatment with osimertinib in people with stage Ib to stage IIIa EGFR positive NSCLC and second line use of osimertinib in people with T790 mutation positive EGFR positive NSCLC.
Where these medicines have a licenced indication not positively appraised by NICE, usage has not been estimated. While this usage is expected to be small, it may result in a lower expected usage when compared to observed usage.
1. Incidence of lung cancer
The SmPC states that these medicines are indicated in an adult population only.
Estimated incidence of lung cancer in adults aged 20 years or older was reported by the National Lung Cancer Audit (2023) for the year 2021 in England.
Measure  Point estimate  Reference 

Newly diagnosed lung cancers (C34 Malignant neoplasm of bronchus and lung)  34,478  1 
2. Estimated number of people with nonsmallcell lung cancer
The proportion of new cases of lung cancer that are nonsmallcell lung cancer (NSCLC) is reported in the National Lung Cancer Audit (2022) to be 72.2%. This proportion has been applied to the point estimate calculated in step 1.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with nonsmallcell lung cancer in England  24,893  1 
3. Proportion of people presenting with stage IIIb (advanced) and stage IV (metastatic) NSCLC
The proportion of new cases of NSCLC that are diagnosed stage IIIb (advanced), or stage IV (metastatic) is reported in the National Lung Cancer Audit as 55%. This proportion has been applied to the point estimate calculated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people presenting with stage IIIb or stage IV NSCLC  13,691  1 
4. Proportion of people successfully assessed for EGFR
The spotlight audit on molecular testing in advanced lung cancer (2020), shows, for EGFR, 92% or 92,000 per 100,000 of people with advanced lung adenocarcinoma were assessed. The 95% confidence interval around the reported proportion 95% CI (91,613 to 92,375) has been calculated using the exact binomial method (Pezzullo 2009).
The proportion and confidence interval has been applied to the adult population calculated in step 3.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people successfully assessed for EGFR  12,596  12,543  12,647  2, 3, 9 
The spotlight audit on molecular testing in advanced lung cancer (2020), shows, for EGFR, 8% of people with advanced lung adenocarcinoma were not assessed and have unidentified EGFR status. Patients in whom the disease has progressed after nontargeted chemotherapy may have erlotinib if their patient characteristics suggest that their tumour may be EGFR mutation positive. An element of clinical judgement is needed when identifying these patients and is not calculated here.
5. Proportion of people where molecular testing was successful
The spotlight audit on molecular testing in advanced lung cancer (2020), shows, for EGFR, 97.7% or 97,700 per 100,000 of people, molecular testing was successful, giving a positive or negative result. The 95% confidence interval around the reported proportion (95% CI 97,469 to 97,911) has been calculated using the exact binomial method (Pezzullo 2009).
The proportion and confidence interval has been applied to the adult population calculated in step 4.
Point estimate  Lower range  Upper range  Reference  

Estimated number of people successfully assessed for EGFR  12,306  12,226  12,383  2, 3 
6. Proportion of people who test positive for EGFR mutation
The spotlight audit on molecular testing in advanced lung cancer (2020), reported 10% or 10,000 per 100,000 have the EGFR mutation present. The 95% confidence interval around the reported proportion (95% CI 9,562 to 10,451) has been calculated using the exact binomial method (Pezzullo 2009).
The reported proportion and confidence interval has been applied to the upper and lower range and the point estimate for people successfully assessed, calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people expected to have a positive EGFR mutation  1,231  1,169  1,294  2, 3 
7. Proportion of people who receive first line afatinib, dacomitinib, erlotinib, gefitinib or osimertinib
The spotlight audit on molecular testing in advanced lung cancer (2020), 75% of patients with an EGFR mutation received a firstline tyrosine kinase inhibitor (TKI).
The reported proportion has been applied to the upper and lower range and the point estimate for people successfully assessed, calculated in step 6.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who receive first line afatinib, dacomitinib, erlotinib, gefitinib or osimertinib  923  877  971  2, 3 
8. Proportion of people who progress following first line treatment with afatinib, dacomitinib, erlotinib or gefitinib (previously treated EGFRpositive)
The resource impact tool for TA654 (NICE 2020) states that in year 1, 20% of first line treatment will be with osimertinib. Of the remaining 80% who received firstline treatment with afatinib, dacomitinib, erlotinib or gefitinib, the disease will progress in 65% of cases (TA416, NICE 2016) and will then be eligible for osimertinib. These proportions (80% and 65%) have been applied successively to the point estimate and the lower and upper range in step 7.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who progress following first line treatment second line osimertinib  480  456  505  4, 5 
9. Proportion of people who harbour T790M mutation at progression (previously treated EGFRpopulation)
Based on genomic analysis, progression on a firstline EGFR TKI is characterised by an acquired secondary EGFR kinase domain mutation labelled T790M, causing resistance to the firstline EGFR TKI. The proportion of people who harbour T790M mutation at progression is reported in Mazza (2017) to be between 50% and 60%. The midpoint (55%) has been applied to the point estimate and the proportions (50% and 60%) applied respectively to the lower and upper range calculated in step 8.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who harbour T790M mutation at progression and are eligible for osimertinib  264  228  303  6, 10 
10a. Proportion of people with Ib to IIIa NSCLC who had tumour resection surgery
The NICE technology appraisal TA761 published in January 2022 and recommended an additional population of people eligible to receive osimertinib for stage Ib to IIIa NSCLC who had tumour resection surgery.
The national lung cancer audit 2022 reports the number of people with NSCLC who had tumour resection surgery as 20%. This proportion has been applied to the point estimate calculated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with Ib to IIIa NSCLC who had tumour resection surgery  4,979  1 
10b. Proportion of people with Ib to IIIa NSCLC who had tumour resection surgery and were EGFR positive
The spotlight audit on molecular testing in advanced lung cancer (2020), reported 10% or 10,000 per 100,000 have the EGFR mutation present. The reported proportion and confidence interval has been applied to the point estimate for people who had tumour resection surgery, calculated in step 10a.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with stage Ib to IIIa NSCLC who had tumour resection surgery and were EGFR positive  498  2 
10c. Proportion of people with stage Ib to IIIa NSCLC who had tumour resection surgery and were EGFR positive with exon 19 deletions or exon 21 L858R mutations
Based on data reviewed in Zhang (2016), it is estimated that 90% of people who are EGFR positive have exon 19 deletions or exon 21 L858R mutations. This has been applied to the point estimate for people who had tumour resection surgery and were EGFR positive, calculated in step 10b.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with stage Ib to IIIa NSCLC who had tumour resection surgery and were EGFR positive with exon 19 deletions or exon 21 L858R mutations  448  448  448  8 
11a. Treatment population for afatinib, dacomitinib, erlotinib, gefitinib and osimertinib
The total treatment population for first line afatinib, dacomitinib, erlotinib, gefitinib or osimertinib has been taken from step 7 and step 9 and added to the treatment population for second line osimertinib.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated treatment population afatinib, dacomitinib, erlotinib, gefitinib and osimertinib  1,635  1,553  1,722   
11b. Calculate estimated usage volume – afatinib, erlotinib and gefitinib
The total estimated treatment population for first line afatinib, erlotinib, gefitinib has been taken from step 7. It has been assumed here that treatment will be for 12 months, and use of each medicine in step 7 is evenly split across the treatment population.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated treatment population first line afatinib, dacomitinib, erlotinib, gefitinib  554  526  583   
Estimated median progressionfree survival (days)  365  365  365  4, 11 
Total estimated annual usage (ADDs)  202,137  192,063  212,649 
11c. Calculate estimated usage volume – dacomitinib
The total estimated treatment population for dacomitinib has been taken from step 7. It has been assumed that treatment will be for 12 months.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated treatment population dacomitinib  185  175  194   
Estimated median progressionfree survival (days)  365  365  365  4, 11 
Total estimated annual usage (ADDs)  67,379  64,021  70,883 
11d. Calculate estimated usage volume – first and second line osimertinib
The total estimated treatment population for first line osimertinib has been taken from step 7 and step 10c. Secondline osimertinib is taken from step 9. It has been assumed that treatment will be for 21 months (639 days) and usage will be spread evenly.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated treatment population for first or secondline osimertinib  897  851  945   
Estimated median progressionfree survival (days)  639  639  639  4, 11 
Total estimated annual usage (ADDs)  572,927  544,045  603,983 
11e. Total treatment volume – afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib
The total treatment volume (ADD) for afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib has been summed from steps 11b, 11c and 11d.
Measure  Point estimate  Lower range  Upper range  Reference 

Total estimated annual usage (ADDs) for afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib  842,443  800,129  887,515   
12. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 11f.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  369  350  389  12 
References
 Royal College of Physicians. National Lung Cancer Audit (2023) Newly diagnosed lung cancers 2021, England. London: RCP, 2022. Available from: NLCA [Accessed: 20/12/2023].
 Spotlight audit on molecular testing in advanced lung cancer (2020). Available from: https://www.rcplondon.ac.uk/projects/outputs/spotlightauditmoleculartestingadvancedlungcancer2019diagnoses2017 [Accessed: 08/11/2021].
 Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from: https://statpages.org/confint.html [Accessed: 09/11/2021].
 TA654 (NICE 2020). Osimertinib for untreated EGFR mutationpositive nonsmallcell lung cancer. Available from: https://www.nice.org.uk/guidance/ta654 [Accessed: 02/11/2021].
 TA416 (NICE 2016). Manufacturers submission (AstraZeneca 2016). Available from: https://www.nice.org.uk/guidance/ta416/evidence [Accessed: 29/01/2018].
 Mazza V, Cappuzzo F. Treating EGFR mutation resistance in nonsmall cell lung cancer – role of osimertinib. The Application of Clinical Genetics. 2017; 10:4956. doi:10.2147/TACG.S103471.
 TA761 (NICE 2022). Osimertinib for adjuvant treatment of EGFR mutationpositive nonsmallcell lung cancer after complete tumour resection. Available from https://www.nice.org.uk/guidance/ta761 [Accessed: 28/06/2022].
 Zhang et al (2016). The prevalence of EGFR mutation in patients with nonsmall cell lung cancer: a systematic review and metaanalysis. Oncotarget. 2016 Nov 29; 7(48): 78985–78993.
 TA374 (2015) Erlotinib and gefitinib for treating nonsmallcell lung cancer that has progressed after prior chemotherapy. Final appraisal determination, section 4.3.6. Available from: https://www.nice.org.uk/guidance/ta374 [Accessed: 29/01/2018].
 Cappuzzo F, Ciuleanu T, Stelmakh L (2010). Erlotinib as maintenance treatment in advanced nonsmallcell lung cancer: a multicentre, randomised, placebocontrolled phase 3 study. The Lancet Oncology. Volume 11, Issue 6, June 2010, Pages 521529.
 Datapharm Communications Limited (2017). The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/ [Accessed: 10/11/2021].
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
Icosapent ethyl
Icosapent ethyl is recommended by NICE with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides.
Icosapent ethyl
Icosapent ethyl: estimate calculation
1. Population who meet SmPC
The Summary of Product Characteristics (SmPC) states that the medicine is indicated for an adult population only. Office for national statistics population data for England has been used to establish the number of people aged 18 and over (ONS 2022).
Measure  Point estimate  Reference 

Adult population England (18+)  45,219,492  1, 2 
2. Secondary prevention of cardiovascular disease
The CVDPREVENT third annual audit report (2023) states the prevalence of GP recorded cardiovascular disease in England for people aged 18 and over is 6%. This includes people with a coded diagnosis of at least one of the following cardiovascular diseases (CVD):
 stroke or transient ischaemic attack
 coronary heart disease (CHD) (including myocardial infarction (MI) and acute coronary syndrome)
 heart failure (HF)
 abdominal aortic aneurysm (AAA)
 peripheral arterial disease (PAD)
This proportion has been applied to the England adult population in step 1.
Measure  Point estimate  Reference 

CVD population  2,713,170  3 
3. Number of people suitable for treatment with statins
Estimates on the proportion of people with CVD who are receiving or who have previously received statins varies. Here we have used a range of between 79% (Steen, 2017) and 90% (Bilitou, 2020). These have been applied to the population identified in step 2 to calculate the upper and lower range and midpoint (point estimate).
Measure  Point estimate  Lower range  Upper range  Reference 

Suitable for treatment with statins  2,292,628  2,143,404  2,441,853  4, 5 
4. Lowdensity lipoprotein cholesterol concentrations
The estimated number of people who have had at least one recorded instance of a cardiovascular event and whose lowdensity lipoprotein cholesterol concentrations are above 2.5mmol/L is reported by Danese (2018) to be 21.5%. The remaining 78.5% has been used here as the proportion below 2.5mmol/L. Due to available data the threshold is not an exact match for the threshold stated in the NICE guidance. This threshold has been applied to the point estimate and upper and lower bounds calculated in step 3.
Measure  Point estimate  Lower range  Upper range  Reference 

Lowdensity lipoprotein cholesterol concentration  1,799,713  1,682,572  1,916,854  6 
5. Number of people with raised triglycerides
The proportion of people with raised triglycerides (150 mg/dL [1.7 mmol/litre] or more) used here is 20%. This is taken from the resource impact template published alongside the technology appraisal (NICE, 2022). This has been applied to the point estimate and upper and lower bounds calculated in step 4.
Measure  Point estimate  Lower range  Upper range  Reference 

People with raised triglycerides  359,943  336,514  383,371  7 
6. Number of people who will receive treatment with icosapent ethyl
The resource impact template published alongside the technology appraisal (NICE, 2022) estimates that 1% of the eligible population (step 5) will receive treatment with icosapent ethyl in year 1 rising to 5% in year 5. For the period of this report it is estimated that 2% will receive treatment. This has been applied to the point estimate and upper and lower bounds calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who will receive treatment  7,199  6,730  7,667  7 
7. Calculate estimated usage volume (ADD)
The number of people who are estimated to receive treatment with icosapent ethyl has been multiplied by days in a year to produce an expected volume of medicine per year in Assumed Daily Doses (ADD).
Measure  Point estimate  Lower range  Upper range  Reference 

Total estimated annual usage (ADDs) 365 days  2,627,581  2,456,555  2,798,607 
8. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 7, was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 7.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  1,150  1,075  1,225  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 Datapharm Communications Limited (2015) The electronic Medicines Compendium. Available from: https://www.medicines.org.uk/emc/ [Accessed: April 2023]
 The CVDPREVENT third annual audit report (2023) available from https://www.nhsbenchmarking.nhs.uk/cvdpreventoutputs [Accessed: April 2023]
 Dylan L Steen, Irfan Khan, David Ansell, Robert J Sanchez, Kausik K Ray. Retrospective examination of lipidlowering treatment patterns in a realworld highrisk cohort in the UK in 2014: comparison with the National Institute for Health and Care Excellence (NICE) 2014 lipid modification guidelines. BMJ Open 2017. Available from: https://bmjopen.bmj.com/content/bmjopen/7/2/e013255.full.pdf [Accessed: April 2023]
 A Bilitou, A Rabe, L Inema, G Alamgir, K Dunton, The prevalence and patient outcomes of adult primary hypercholesterolaemia and dyslipidaemia in the UK: a longitudinal retrospective study using a primary care dataset from 2008 to 2018, European Heart Journal, Volume 41, Issue Supplement_2, November 2020, ehaa946.3559, https://doi.org/10.1093/ehjci/ehaa946.3559
 Danese MD, Sidelnikov E, Kutikova L. The prevalence, lowdensity lipoprotein cholesterol levels, and treatment of patients at very high risk of cardiovascular events in the United Kingdom: a crosssectional study. Curr Med Res Opin. 2018 Aug;34(8):14411447. doi: 10.1080/03007995.2018.1463211. Epub 2018 Apr 20. PMID: 29627994.
 Resource impact template, Icosapent ethyl with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides, NICE, 2022. Available from: https://www.nice.org.uk/guidance/ta805 [Accessed: April 2023]
Metastatic castrationresistant prostate cancer
Abiraterone, apalutamide, cabazitaxel and enzalutamide are recommended by NICE for the treatment of metastatic castrationresistant prostate cancer.
Abiraterone
Apalutamide
Enzalutamide
Metastatic castrationresistant prostate cancer: estimate calculation
Apalutamide and enzalutamide are also indicated (SmPC) for some nonmetastatic prostate cancer. That population has not been calculated here. It is expected that this may underestimate the expected treatment population for abiraterone, apalutamide, enzalutamide and cabazitaxel by less than 5%.
1. Population
The Office for National Statistics (ONS) estimates that the male population in England in 2022 was 27,983,290. Public Health England’s report on "cancer prevalence in England 2020", reported the prevalence of prostate cancer in males to be 1.54%.
A prevalence of 1.54% has been applied to the male population to give the estimated number of people with prostate cancer in England.
Measure  Point estimate  Reference 

Estimated prevalence of prostate cancer, in England  431,180  1, 2 
2. Diagnosed metastatic prostate cancer
A large modelbased study of the number of prevalent prostate cancer patients at different clinical stages in an Italian setting (Spandonaro, 2021), estimated 5.2% of the prevalent population were diagnosed with metastatic disease. The 95% confidence interval around the reported prevalence has been calculated using the exact binomial method (Pezzullo et al, 2009).
This has been applied to the point estimate and upper and lower range of the prevalence of prostate cancer in England (step 1).
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people diagnosed with metastatic prostate cancer in England  22,594  22,239  22,925  3, 4 
3. Hormone sensitive and hormonerelapsed metastatic prostate cancer
A large modelbased study of the number of prevalent prostate cancer patients at different clinical stages in an italian setting (Spandonaro, 2021), estimated, for metastatic disease, 33.9% were hormone sensitive and 66.1% were hormonerelapsed.
The 95% confidence interval around the reported prevalence has been calculated using the exact binomial method (Pezzullo 2009). This has been applied to the point estimate and the upper and lower range calculated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

3a. Hormonesensitive metastatic prostate cancer  7,659  7,539  7,772  3, 4 
3b. Hormonerelapsed metastatic prostate cancer  14,935  14,700  15,153  3, 4 
Hormonesensitive metastatic prostate cancer
4. Proportion of people who have hormone sensitive metastatic prostate cancer that are expected to receive treatment with apalutamide or enzalutamide
Apalutamide or enzalutamide plus ADT offers an option for people with hormonesensitive metastatic prostate cancer, especially for people who cannot have docetaxel. It is taken by mouth so is more convenient than docetaxel, which is an intravenous treatment.
Of the people diagnosed with metastatic prostate cancer, it is estimated 15% (TA712, 2021) will receive treatment with apalutamide or enzalutamide in the first year, rising to 30% in subsequent years. This has been applied to the upper and lower range and the midpoint (22.5%) applied to the point estimate calculated in step 3a.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people who have hormonesensitive metastatic prostate cancer that are expected to receive treatment with apalutamide or enzalutamide  1,723  1,131  2,331  5 
Hormonerelapsed metastatic prostate cancer
5. Proportion of people who have hormonerelapsed metastatic prostate cancer that are expected to receive treatment with abiraterone or enzalutamide before treatment with docetaxel chemotherapy is indicated
Abiraterone and enzalutamide are indicated before chemotherapy in people with hormonerelapsed metastatic prostate cancer. Using pain as a proxy, the proportion of people with metastatic prostate cancer who have not had chemotherapy and report no or mild symptoms was reported in Autio (2013) as 62%.
Expert opinion suggests that 80% of these patients will receive treatment with abiraterone or enzalutamide. The reported proportion and estimated percentage to receive treatment have been applied to the point estimate and upper and lower range calculated in step 3b.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number that receive treatment with abiraterone or enzalutamide  7,407  7,291  7,516  6, 7 
6. Proportion of people that require further treatment after abiraterone or enzalutamide
Expert opinion suggests that treatment with abiraterone or enzalutamide provides clinical benefit in 65% of patients. For the remaining 35% of patients, expert opinion suggests that 55% will require further treatment and go on to receive docetaxel chemotherapy.
Of those that receive chemotherapy at that stage, it is estimated that 30% will subsequently receive treatment with cabazitaxel. The estimated number to receive treatment has been applied to the point estimate and upper and lower range calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number that receive cabazitaxel after chemotherapy  428  421  434  7 
7. Proportion of people who have hormonerelapsed metastatic prostate cancer that are expected to receive treatment with abiraterone, cabazitaxel or enzalutamide after treatment with firstline docetaxel chemotherapy
Abiraterone, cabazitaxel and enzalutamide are also indicated for use after docetaxel chemotherapy in patients whose disease has progressed during or after docetaxel chemotherapy. Around 20% will receive treatment with firstline docetaxel chemotherapy.
Of those receiving firstline treatment with docetaxel chemotherapy, expert opinion suggests that for 55% of patients, treatment will not be successful and that 75% of those patients will then go on to have further treatment with abiraterone, cabazitaxel or enzalutamide.
The estimated number to receive treatment (20% * 55% * 75%) has been applied to the point estimate and upper and lower range calculated in step 3b.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number that receive abiraterone, cabazitaxel or enzalutamide after chemotherapy  1,232  1,213  1,250  7 
8. Calculate estimated usage volume
The number of people who have hormonerelapsed or hormone sensitive metastatic prostate cancer or likely to receive treatment with abiraterone or enzalutamide has been multiplied by days in a year then multiplied by the Assumed Daily Doses (ADD) to produce an expected volume of medicine per year in ADDs.
It has not been possible to identify the proportional split of people who will receive treatment with apalutamide, abiraterone, cabazitaxel or enzalutamide after treatment with firstline docetaxel chemotherapy (calculated in step 7), therefore this total patient group has been assumed to receive treatment for 365 days in a year. This may overestimate the total number of ADDs as the shorter treatment duration of cabazitaxel is not reflected in this calculation.
TA391 (NICE 2016) states that treatment with cabazitaxel is stopped when the disease progresses or after a maximum of 10 cycles (whichever happens first). Ten cycles have been calculated as 210 days (SmPC). The number of people who have metastatic hormonerelapsed prostate cancer likely to receive treatment with cabazitaxel after treatment with abiraterone or enzalutamide and subsequent docetaxel chemotherapy (calculated in step 6) has been multiplied by 210 (suggested treatment duration in days), then multiplied by the ADD to produce an expected volume of medicine per year in ADDs.
Measure  Point estimate  Lower range  Upper range 

Sum treatment population abiraterone, apalutamide & enzalutamide (step 4, step 5 and step 7)  10,362  9,635  11,097 
Estimated treatment population cabazitaxel (step 6)  428  421  434 
Estimated annual usage apalutamide, abiraterone & enzalutamide (treatment population x 365 days x 1 ADD)  3,782,130  3,516,775  4,050,405 
Estimated annual usage cabazitaxel (treatment population x 210 days x 1 ADD)  89,880  88,410  91,140 
Total estimated annual usage 365 days (ADDs)  3,872,010  3,605,185  4,141,545 
9. Estimated usage by quarter per 100,000 population
Estimated annual Assumed Daily Doses (ADD) usage calculated in step 8, was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 8.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  1,695  1,578  1,813  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 The National Cancer Registration and Analysis Service. Public Health England’s cancer prevalence in England 2020. Available from https://www.cancerdata.nhs.uk/ [Accessed: 14/09/2023].
 Spandonaro F, D’Angela D, Polistena B et al. (2021) Prevalence of Prostate Cancer at Different Clinical Stages in Italy: Estimated Burden of Disease Based on a Modelling Study.
 Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html [Accessed: 09/11/2021].
 Enzalutamide for treating hormonesensitive metastatic prostate cancer. NICE TA712, RIA template (2021). Available from: https://www.nice.org.uk/guidance/ta712/resources [Accessed: 04/11/2021].
 Autio K, Bennett A, Jia X et al. (2013) Prevalence of pain and analgesic use in men with metastatic prostate cancer using a patientreported outcome measure.
 NICE Adoption and Impact Programme Reference Panel (2016), clinical experts with an interest in metastatic castrationresistant prostate cancer.
 Cabazitaxel for hormonerelapsed metastatic prostate cancer treated with docetaxel. NICE TA391, RIA template (2016). Available from: https://www.nice.org.uk/guidance/ta391 [Accessed: 04/11/2021].
 Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/, [Accessed: 07/12/2021].
Migraine
Eptinezumab, erenumab, galcanezumab, fremanezumab and rimegepant are types of human monoclonal antibodies that bind to the calcitonin generelated peptide (CGRP) ligand, inhibiting the function of CGRP at its receptor. They are recommended as options for treating migraine.
Rimegepant
Migraine: estimate calculation
The estimated treatment population is calculated for the Calcitonin GeneRelated Peptide (CGRP) receptor antagonists eptinezumab, erenumab, fremanezumab, galcanezumab and rimegepant, for treating episodic and chronic migraine. An upper and lower range is calculated, to address the uncertainty in the underlying analyses.
The SmPC states eptinezumab, erenumab, fremanezumab, galcanezumab and rimegepant are preventative treatments for adults in England who have at least 4 migraine days per month, for whom at least 3 previous preventative drug treatments have failed.
This estimate has been updated for the April 2024 publication and the medicine rimegepant (TA906) has been added to the group. Rimegepant is also indicated for the acute treatment of migraine (TA919). Due to the complexities in calculating the acute treatment duration and dosing, and the expectation that the acute treatment population is small (<10% of the treatment population), the acute treatment population has not been included in this estimate at this stage but will continue to be reviewed.
1. Prevalence of migraine
To calculate the prevalence of migraine in England, two sources have been used to calculate the lower and upper range and the point estimate. For the lower range, Steiner et al., 2003 study was used. It estimates that the overall oneyear prevalence of migraine in adults in England is 14.3%. Applying this to the adult population (18+) of England, 45,219,492 (ONS, 2022), an estimated 7,584,355 adults in England have migraine.
For the upper range we will use the prevalence number as reported by the Global Burden of Disease Collaborative Network (2019) for those in England aged 20+ to represent the adult population, which is 8,702,324. For the point estimate, we used the midpoint between the lower and upper range. This can be seen in the table below.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with migraine in England  7,584,355  6,466,387  8,702,324  1, 2, 3 
1.1. Prevalence of episodic migraine
The migraine definitions used across NICE TA’s are based on the International Classification of Headache Disorders 3rd edition (NICE, 2023). They define episodic migraine (EM) as the occurrence of headaches on less than 15 days per month (International Headache Society, 2018).
As a criterion for the use of eptinezumab, erenumab, fremanezumab, galcanezumab and rimegepant is that a minimum of 4 migraine days a month is needed, EM is therefore defined in this estimate as between 4 and 15 migraine days a month.
It has been reported that 23.2% of people with migraine are cases of EM based a survey by Lundbeck in collaboration with Migraine Trust of active migraine sufferers (NICE, 2023).
This figure has been applied to the point estimate and upper and lower ranges in step 1.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with EM in England  1,759,570  1,500,202  2,018,939  4 
1.2. Prevalence of chronic migraine
Chronic migraine (CM) is defined as having 15 or more migraine days a month for more than 3 months, which, on at least 8 days of the month, has the features of migraine headache (International Headache Society, 2018).
The prevalence of CM is greater than EM with CM being reported to make up 45.6% of migraine cases using the same survey source used for EM (NICE, 2023).
This figure has been applied to the point estimate and upper and lower ranges in step 1.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with CM in England  3,458,466  2,948,673  3,968,260  4 
2. Number of people who have preventative therapy for migraine
2.1 Number of people who have preventative therapy for episodic migraine
Bloudek, et al., 2012 study found that within the UK, 28% of people with EM reported using preventative medication. This figure is reinforced by other studies (Ferrari, et al., 2007; Blumefeld, et al., 2013; Sanderson, et al., 2013).
This figure has been applied to the point estimate and upper and lower range calculated in step 1.1.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with EM in England that take preventative therapy  492,680  420,057  565,303  6, 7, 8, 9 
2.2 Number of people who have preventative therapy for chronic migraine
Studies suggest that there is a higher percentage of those with CM that take preventive medication than there are for EM. Bloudek, et al., 2012 study found that, within the UK, 32% of people with CM reported using preventive medication. This figure is reinforced by other studies which cite a similar percentage (Ferrari, et al., 2007; Blumefeld, et al., 2013; Sanderson, et al., 2013).
This figure has been applied to the point estimate and upper and lower range calculated in step 1.2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with CM in England that take preventative therapy  1,106,709  943,575  1,269,843  6, 7, 8, 9 
3. Number of people who have had 3 or more prior treatment failures
A criterion for the use of eptinezumab, erenumab, galcanezumab, fremanezumab or rimegepan is that at least three preventative drugs treatments have failed.
3.1 Number of people with episodic migraine who have had 3 or more prior treatment failures
Sanderson, et al., 2013 states that 9% of those on preventive therapy for EM have had 3 or more treatment failures in the UK. This figure has been applied to the point estimate and upper and lower range from step 2.1 which can be seen below.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with EM in England that take preventative therapy and have had 3 or more prior treatment failures  44,341  37,805  50,877  9 
3.2 Number of people with chronic migraine who have had 3 or more prior treatment failures
In comparison to EM, the proportion of people with CM who have had preventative therapy and 3 or more prior treatment failures is substantially greater. Sanderson, et al., 2013 found that 28% of people with CM have had 3 or more treatment failures in the UK. This figure has been applied to the point estimate and upper and lower range from step 2.2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of adults with CM in England that take preventative therapy and have had 3 or more prior treatment failures  309,879  264,201  355,556  9 
4. Total eligible population for eptinezumab, erenumab, fremanezumab, galcanezumab and rimegepant
The total eligible population for eptinezumab, erenumab, fremanezumab, galcanezumab and rimegepant is calculated by summing the two values from step 3.1 and 3.2.
Measure  Point estimate  Lower range  Upper range  Reference 

Total eligible population  354,220  302,006  406,433   
5. Treatment population
This step takes the expected usage of people receiving the medicines based on the estimated growth rate in usage, with the same usage split applied proportionately, which is 49% for these medicines with the remaining 51% taking botulinum toxin A (TA871, NICE 2023). This figure has been applied to the total treatment population from step 4.
Measure  Point estimate  Lower range  Upper range  Reference 

Total treatment population for CGRP receptor antagonists  173,568  147,983  199,152  4 
6. Number of people who continue treatment after 12 weeks
It is expected that a proportion of people receiving treatment with eptinezumab, erenumab, fremanezumab, galcanezumab and rimegepant will discontinue treatment. Within each of the drug’s TA’s it specifies to stop treatment after 12 weeks if the frequency does not reduce by at least 50% for EM, and the frequency does not reduce by at least 30% for CM.
Discontinuation is similar across these medicines, thus for simplicity an average is used which is 52%, leaving 48% continuing treatment (TA871, NICE 2023). This figure has been applied to the treatment population from step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people who continue treatment with CGRP receptor antagonists after 12 weeks  83,312  71,032  95,593  4 
7. Estimated annual volume
The number of people estimated to receive these medicines and continue treatment calculated in step 6 was multiplied by the number of days in a year (365) to give the annual usage in ADDs.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated annual usage (ADDs) 365 days  30,409,056  25,926,624  34,891,488 
8. Estimated usage by quarter per 100,000 population
Estimated annual Actual Daily Doses (ADD) usage calculated in step 7 was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population (57,106,398) and multiplied by 100,000 to give an estimated usage per 100,000 population. This was applied to the point estimate and upper and lower range calculated in step 7.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  13,312  11,350  15,275  2 
References
 Steiner, T. et al., 2003. The Prevalence and Disability Burden of Adult Migraine in England and their Relationships to Age, Gender and Ethnicity. Cephalalgia, 23(7), pp. 519527.
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 Global Burden of Disease Collaborative Network 2019 Global Burden of Disease Study 2019 (GBD 2019). Seattle, United States: Institute for Health Metrics and Evaulation (IHME). Available from: https://vizhub.healthdata.org/gbdresults/ [Accessed: 30/5/22]
 NICE, 2023. Technology Appraisal: Eptinezumab for preventing migraine (TA871). NICE
 International Headache Society, 2018. International Classification of Headache Disorders 3rd edition. s.l.:Cephalagia.
 Bloudek, L. et al., 2012. Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS). Journal of Headache Pain, 13(5), pp. 361378.
 Ferrari, A. et al., 2007. Similarities and Differences Between Chronic Migraine and Episodic Migraine. Headache, 47(1), pp. 6572.
 Blumefeld, A. M. et al., 2013. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMSII). Headache, 53(4), pp. 644655.
 Sanderson, J. C. et al., 2013. Headacherelated health resource utilisation in chronic and episodic migraine across six countries. Journal of Neurology, Neurosurgery, and Psychiatry, 84(12), pp. 13091317
Multiple sclerosis
Alemtuzumab, cladribine, dimethyl fumarate, diroximel fumarate, fingolimod, glatiramer acetate, interferon beta1a, interferon beta1b, natalizumab, ocrelizumab, ofatumumab, peginterferon beta1a, ponesimod, siponimod, or teriflunomide are recommended by NICE for the treatment of multiple sclerosis.
Dimethyl fumarate
Diroximel fumarate
Glatiramer acetate
Interferon beta1a
Interferon beta1b
Ocrelizumab
Peginterferon beta1a
Multiple sclerosis: estimate calculation
The following steps estimate the population of adults with multiple sclerosis who receive treatment with one of the following NICEapproved medicines: alemtuzumab, cladribine, dimethyl fumarate, diroximel fumarate, fingolimod, glatiramer acetate, interferon beta1a, interferon beta1b, natalizumab, ocrelizumab, ofatumumab, peginterferon beta1a, ponesimod, siponimod, or teriflunomide.
1. England Population
The SmPC states that all of the above medicines are indicated for an adult population. The following medicines are also indicated for adolescent and paediatric populations: dimethyl fumarate (aged 13+), glatiramer acetate (aged 12+), interferon beta1a (aged 2+, Rebif only), interferon beta1b (aged 1217), and teriflunomide (aged 10+).
The starting population for this estimate is the total population of England.
Measure  Point estimate  Reference 

England population  57,106,398  1 
2. Estimated prevalence of multiple sclerosis
The proportion of people with multiple sclerosis has been estimated from a study using a representative sample of primary care records in England from The Health Improvement Network (THIN) dataset. The prevalence of multiple sclerosis in England was estimated as 0.19% of the population.
However, had incomplete records not been excluded from this study, the estimated prevalence would have been 0.205%. To account for this uncertainty, both of these prevalence figures have been applied to the population identified in step 1 to create an estimate range.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with multiple sclerosis in England  108,502  108,502  117,068  2 
3. People with an Expanded Disability Status Scale (EDSS) score of less than 7
All medicines for multiple sclerosis should be discontinued once a person develops an EDSS score of 7 (an inability to walk) that persists for longer than 6 months. The UK Multiple Sclerosis Register collects clinical data from MS treatment centres, including individuals EDSS score. According to this register 82.42% of people with multiple sclerosis have an EDSS score of less than 7 (correct as of 9/5/2023). To account for error in this estimation, a range between 80% and 85% has been applied to the population identified in step 2 to create an upper and lower estimate.
This proportion has been applied to the population stated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with an EDSS score of less than 7  89,427  86,802  99,508  3 
4. Estimated treatment population
Despite evidence that early treatment and adherence to disease modifying therapies results in better outcomes (reduced relapse rates and disease progression), some people with MS may choose to not receive treatment.
A study investigating MS medicine compliance in a Canadian population found that 31.3% of people declined treatment. A similar study on a French population found that 10% of people declined treatment. Some of the most common reasons for this decision were: personal preference, lack of disease activity, wanting to use alternative medicines, or wishing to adopt a conservative approach to treatment. It should be noted that these figures may not directly reflect MS medicine compliance in a UK population.
To account for these factors when estimating the current treatment population, adherence estimates of 70%, 80% and 90% have been applied to the lower, point and higher estimate, respectively.
Measure  Point estimate  Lower range  Upper range 

Total treatment population  71,542  60,761  89,557 
5. Calculate estimated usage volume (ADD)
The number of people who are estimated to receive treatment with MS medicines has been multiplied by days in a year to produce an expected volume of medicine per year in ADDs.
Measure  Point estimate  Lower range  Upper range 

Total estimated annual usage (ADDs) 365 days  26,112,823  22,177,841  32,688,345 
6. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 5, was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  11,432  9,709  14,310  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 Public Health England (2020) Multiple sclerosis: prevalence, incidence and smoking status  data briefing. Available from: https://www.gov.uk/government/publications/multiplesclerosisprevalenceincidenceandsmokingstatus/multiplesclerosisprevalenceincidenceandsmokingstatusdatabriefing [Accessed: 30/06/2022].
 UK MS Register Data (2023) Stats at a glance. Available at: https://ukmsregister.org/Research/OurData [Accessed: 09/05/2023].
 Zekkat et al., (2012) Multiple sclerosis without treatment: characteristic features of 70 untreated patients in a cohort of 1187 patients. Revue Neurologique. DOI: 10.1016/j.neurol.2011.08.018.

Stratos et al., (2020) Noncompliance with disease modifying therapies in patients with Multiple Sclerosis: A qualitative analysis. Multiple Sclerosis and Related Disorders. https://doi.org/10.1016/j.msard.2020.102016.
Primary hypercholesterolaemia and mixed dyslipidaemia
Alirocumab, evolocumab or inclisiran are recommended by NICE for the treatment of primary hypercholesterolaemia and mixed dyslipidaemia.
Primary hypercholesterolaemia and mixed dyslipidaemia: estimate calculation
The following estimates the population of adults with primary hypercholesterolaemia (familial and nonfamilial), or mixed dyslipidaemia who receive treatment with a PCSK9 inhibitor (alirocumab or evolocumab) or inclisiran.
1. Adult population England
The SmPC states that alirocumab, evolocumab and inclisiran are indicated for an adult population. Evolocumab is also indicated in adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipidlowering therapies. Due to data availability, the eligible adolescent population has not been calculated, however this is not expected to significantly alter the estimated treatment population.
The starting population for this estimate is adults aged 18 years or older in England.
Measure  Point estimate  Reference 

England population aged 18 years and over  45,219,492  1, 2 
2. Primary hypercholesterolaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia
The proportion of people with primary nonfamilial hypercholesterolaemia or mixed dyslipidaemia has been estimated from an analysis of primary care practices across the UK. The prevalence of hypercholesterolaemia/mixed dyslipidaemia in the UK was estimated as 24.1% of the adult population. This proportion has been applied to the population identified in step 1.
Measure  Point estimate  Reference 

Primary nonfamilial hypercholesterolaemia or mixed dyslipidaemia  10,897,898  3 
3. Estimated number of people receiving or who have previously received lipid lowering therapy
The proportion of people with primary nonfamilial hypercholesterolaemia or mixed dyslipidaemia who are receiving or who have previously received lipid lowering therapy is estimated at over 90%. To account for error in this estimation, a range between 85% and 95% has been applied to the population identified in step 2 to create an upper and lower estimate.
This proportion has been applied to the adult population stated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people received or receiving lipid lowering therapy  9,808,108  9,263,213  10,353,003  3, 4 
4. People who have had at least one recorded instance of a cardiovascular event, angina or peripheral arterial disease (secondary prevention)
The proportion of people who have had at least one recorded instance of a cardiovascular event or angina is estimated to be almost 15.9%. This has been applied to the populations calculated in step 3.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated eligible population  1,559,489  1,472,851  1,646,127  3 
5. Lowdensity lipoprotein cholesterol concentrations
The estimated number of people who have had at least one recorded instance of a cardiovascular event and whose lowdensity lipoprotein cholesterol concentrations are between 2.5mmol/L and 3.49mmol/L is reported to be 21.5%. Lowdensity lipoprotein cholesterol concentrations between 3.5mmol/L and 3.99mmol/L is reported to be 3.3% and 3.1% for above 4mmol/L.
Due to available data the thresholds are not an exact match for the thresholds stated in the NICE guidance. These thresholds have been applied to the populations calculated in step 4.
Measure  Point estimate  Lower range  Upper range  Reference 

5a. Estimated number of people with lowdensity lipoprotein cholesterol concentrations between 2.5mmol/L and 3.495mmol/L  335,290  316,663  353,917  5 
5b. Estimated number of people with lowdensity lipoprotein cholesterol concentrations between 3.5mmol/L and 3.995mmol/L  51,463  48,604  54,322  5 
5c. Estimated number of people with lowdensity lipoprotein cholesterol concentrations above 4 mmol/L  48,344  45,658  51,030  5 
5d. Summed total lowdensity lipoprotein cholesterol concentrations are persistently above 2.5mmol/L  435,097  410,925  459,269  sum of 5a, 5b, and 5c 
5e. Summed total lowdensity lipoprotein cholesterol concentrations are persistently above 3.5mmol/L  99,807  94,262  105,352  sum of 5b and 5c 
6. Estimated treatment population
There is considerable uncertainty estimating a treatment population for this group of medicines. Based on figures used in the AHSN data toolkit, the trajectory of uptake of inclisiran is estimated to be 9.3% of the eligible population in year 1, 43.9% in year 2 and 61.7% in year 3. The year 3 trajectory has been applied to the point estimate and the upper and lower range calculated in step 5d.
The treatment population for alirocumab and evolocumab is calculated here as the remaining population following year 3 uptake of inclisiran (10061.7=38.3). This has been applied to the total lowdensity lipoprotein cholesterol concentrations above 3.5mmol/L calculated in step 5e, for the point estimate and the upper and lower range.
Measure  Point estimate  Lower range  Upper range  Reference 

6a. Estimated treatment population for inclisiran  268,455  253,541  283,369  6 
6b. Estimated treatment population for alirocumab and evolocumab  38,226  36,103  40,350  6 
6c. Total treatment population  306,681  289,644  323,719 
7. Calculate estimated usage volume (ADD)
The number of people who are estimated to receive treatment with alirocumab, evolocumab or inclisiran (step 6c) has been multiplied by days in a year to produce an expected volume of medicine per year in Assumed Daily Doses (ADD).
Measure  Point estimate  Lower range  Upper range 

Number of people estimated to receive treatment with alirocumab or evolocumab or inclisiran  306,681  289,644  323,719 
Total estimated annual usage (ADDs) 365 days  111,938,678  105,719,882  118,157,473 
8. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 7, was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 7.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  49,004  46,282  51,727  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc [Accessed: 01/11/2021].
 A Bilitou, A Rabe, L Inema, G Alamgir, K Dunton, The prevalence and patient outcomes of adult primary hypercholesterolaemia and dyslipidaemia in the UK: a longitudinal retrospective study using a primary care dataset from 2008 to 2018, European Heart Journal, Volume 41, Issue Supplement_2, November 2020, ehaa946.3559, https://doi.org/10.1093/ehjci/ehaa946.3559.
 Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia, TA733, based on estimate provided by NHSE/I, 2021. Available from: https://www.nice.org.uk/guidance/ta733/evidence [Accessed: 01/11/2021].
 Danese MD, Sidelnikov E, Kutikova L. The prevalence, lowdensity lipoprotein cholesterol levels, and treatment of patients at very high risk of cardiovascular events in the United Kingdom: a crosssectional study. Curr Med Res Opin. 2018 Aug;34(8):14411447. doi: 10.1080/03007995.2018.1463211. Epub 2018 Apr 20. PMID: 29627994.
 Calculation based on data supplied to the AHSN data toolkit by the inclisiran medicine manufacturer (Novartis), 2021.
Severe asthma
Benralizumab, mepolizumab, omalizumab and reslizumab are recommended by NICE for treating severe asthma.
Omalizumab
Severe asthma: estimate calculation
Benralizumab, mepolizumab and reslizumab are addon therapies, and are recommended by NICE as options for treating severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with highdose inhaled corticosteroids and longacting betaagonists.
Omalizumab is recommended by NICE as an optional addon therapy for treating severe persistent confirmed allergic IgE mediated asthma as an add on to optimised standard therapy. The Summary of Product Characteristics (SmPC) states omalizumab is indicated for allergic asthma, chronic rhinosinusitis with nasal polyps and chronic spontaneous urticaria. Only usage for allergic asthma has been calculated here. This will mean we have underestimated total use of omalizumab.
Tezepelumab (TA880, 2023) and dupilumab (TA751, 2021) will be considered for inclusion in the estimate in a future update.
1. Population aged 6 years and older
Measure  Point estimate  Reference 

England population (aged 6 years and older)  53,387,730  1 
2. Prevalence of asthma
The Quality and Outcomes Framework (QOF) reported the number of people on the asthma register (NHS Digital, 2022) as 3,745,077. The 95% confidence interval around the reported prevalence has been calculated using the exact binomial method (Pezzullo et al, 2009).
The prevalence and confidence interval has been applied to the population in England in step 1.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with asthma in England  3,785,190  3,779,851  3,790,529  2, 3 
3. Proportion of people with asthma and a blood eosinophil count of 300 cells per microlitre or more
NICE (2019) reports 14.2% of people with asthma have a blood eosinophil count of 300 cells per microlitre or more. This proportion has been applied to the point estimate and lower and upper range calculated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with asthma and blood eosinophil count of 300 cells per microlitre or more  539,011  538,251  539,771  4 
4. Proportion of people with a blood eosinophil count of 300 cells per microlitre or more and 4 or more exacerbations in the last 12 months
NICE (2019) reports 7.5% of people with blood eosinophil count of 300 cells per microlitre or more will have had 4 or more exacerbations in the last 12 months.
This proportion has been applied to the point estimate and lower and upper range calculated in step 3.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with asthma and blood eosinophil count of 300 cells per microlitre or more and 4 or more exacerbations in the last 12 months  40,426  40,369  40,483  4 
5. Proportion of people with asthma and blood eosinophil count of 400 cells per microlitre or more
NICE (2019) reports 8.3% of people with asthma have a blood eosinophil count of 400 cells per microlitre or more. This proportion has been applied to the point estimate and lower and upper range calculated in step 2.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with asthma and blood eosinophil count of 400 cells per microlitre or more  314,171  313,728  314,614  4 
6. Proportion of people with asthma and a blood eosinophil count of 400 cells per microlitre or more and 3 or more exacerbations in the last 12 months
NICE (2019) reports 3.7% of people with blood eosinophil count of 400 cells per microlitre or more will have had 3 or more exacerbations in the last 12 months.
This proportion has been applied to the point estimate and lower and upper range calculated in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

Estimated number of people with asthma and blood eosinophil count of 400 cells per microlitre or more and 3 or more exacerbations in the last 12 months  11,624  11,608  11,641  4 
7. Total eligible population for benralizumab, mepolizumab and reslizumab
Total eligible population for benralizumab, mepolizumab and reslizumab summed from steps 4 and 6.
Measure  Point estimate  Lower range  Upper range  Reference 

Total eligible population for benralizumab, mepolizumab and reslizumab  52,050  51,977  52,124   
8. Overlap with omalizumab for benralizumab, mepolizumab and reslizumab
The IDEAL study (Albers, 2018) estimates that around 25% of the eligible population for omalizumab will overlap with other treatment options. Total eligible population for benralizumab, mepolizumab and reslizumab (step 7) and the eligible population for omalizumab (step 12) have each been reduced by 12.5% to adjust for this overlap.
Measure  Point estimate  Lower range  Upper range  Reference 

Adjustment for overlap  45,544  45,480  45,609  9 
9. Treatment population for benralizumab, mepolizumab and reslizumab
Benralizumab, mepolizumab and reslizumab are add on therapies that are initiated in secondary care, requiring clinical consultation, where capacity may act as a barrier to treatment initiation.
NICE resource impact template for TA565 (benralizumab, 2019) estimates the proportion of the eligible population (step 8) that will receive treatment with benralizumab to be 4%.
NICE resource impact template for TA431 (mepolizumab, 2017) estimates the proportion of the eligible population (step 8) that will receive treatment with mepolizumab to be 15%. Alternatively, NICE resource impact template for TA565 (benralizumab, 2019) estimates the proportion of the eligible population (step 8) that will receive treatment with mepolizumab to be 6%. These have been used to inform the lower and upper range and midpoint (10.5%) the point estimate.
NICE resource impact template for TA479 (reslizumab, 2017) estimates the proportion of the eligible population (step 8) that will receive treatment with reslizumab to be 10%. Alternatively NICE resource impact template for TA565 (benralizumab, 2019) estimates the proportion of the eligible population (step 8) that will receive treatment with reslizumab to be 1%. These have been used to inform the lower and upper range and midpoint (5.5%) the point estimate.
These proportions have been applied to the point estimate and lower and upper range calculated in step 8.
Measure  Point estimate  Lower range  Upper range  Reference 

People treated with benralizumab  1,822  1,819  1,824  4, 5, 6 
People treated with mepolizumab  4,782  2,729  6,841  
People treated with reslizumab  2,505  455  4,561  
Total treatment population for benralizumab, mepolizumab and reslizumab  9,109  5,003  13,226   
10. Proportion discontinuing benralizumab, mepolizumab and reslizumab each year
The proportion of people discontinuing addon therapy each year is reported in the manufacturer’s submission to NICE for benralizumab (TA565) to be 11.8% for benralizumab, mepolizumab and reslizumab.
This proportion has been subtracted from the point estimate and lower and upper range calculated in step 9.
Measure  Point estimate  Lower range  Upper range  Reference 

Treatment population for benralizumab, mepolizumab and reslizumab following adjustment for discontinuation  8,034  4,413  11,665  7 
11. Proportion of people with severe asthma
The number of people with severe asthma in the United Kingdom is reported to be around 200,000 people (Asthma UK, 2020). This equates to around 169,000 people in England (84.5% of UK population is England). The QOF for 2019/20 reports 3,916,000 people on the asthma register, therefore it is calculated that 4.3% of the asthma population has severe asthma.
This has been applied to the point estimate and the lower and upper range calculated in step 2 (prevalence of asthma).
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people with severe asthma  162,763  162,534  162,993  1, 2, 8 
12. Eligible for omalizumab
The IDEAL study (Albers, 2018) estimates that 30.6% (CI 27.1 – 34.2%) of people with severe asthma will be eligible for omalizumab. This proportion has been applied to the point estimate and lower and upper range calculated in step 11.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people eligible for omalizumab  49,805  44,047  55,744  9 
13. Overlap with benralizumab, mepolizumab and reslizumab for omalizumab
The IDEAL study (Albers, 2018) estimates that around 25% of the eligible population for omalizumab will overlap with other treatment options. Total eligible population benralizumab, mepolizumab and reslizumab (see step 7) and the eligible population omalizumab (step 12) have each been reduced by 12.5% to adjust for this overlap.
Measure  Point estimate  Lower range  Upper range  Reference 

Adjustment for overlap  43,579  38,541  48,776  9 
14. Treatment population for omalizumab
The NICE resource impact report for omalizumab for treating severe persistent allergic asthma (2013), estimated that around 2,000 people would receive omalizumab for treating severe persistent allergic asthma. This is around 4% of the eligible population.
This proportion has been applied to the point estimate and lower and upper range calculated in step 13.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of people receiving treatment  1,992  1,762  2,230  10 
15. Treatment population for benralizumab, mepolizumab, reslizumab and omalizumab
The treatment population for benralizumab, mepolizumab, reslizumab and omalizumab has been summed from steps 10 and 14.
Measure  Point estimate  Lower range  Upper range 

Total estimated treatment population  10,026  6,175  13,895 
16. Calculate estimated usage volume
The number of people estimated to receive benralizumab, mepolizumab, reslizumab and omalizumab (calculated in step 15) has been multiplied by the number of days in a year to give the annual usage in Assumed Daily Doses (ADD).
Measure  Point estimate  Lower range  Upper range 

Total estimated annual usage (ADDs) 365 days  3,659,490  2,253,875  5,071,675 
17. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 16 was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 16.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  1,602  987  2,220  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 Quality and outcomes framework 202223 (2023), 202122 (2022) and 2019/20 (2020). NHS Digital. Available from https://digital.nhs.uk/dataandinformation/publications/statistical/qualityandoutcomesframeworkachievementprevalenceandexceptionsdata/ [Accessed: 08/09/2022]
 Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html.
 NICE (2019) Resource impact assessment template for TA565 benralizumab (2019). Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta565. [Accessed: 23/10/2019].
 NICE (2017) Resource impact assessment template for TA431 mepolizumab (2017). Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta431. [Accessed: 23/10/2019].
 NICE (2017) Resource impact assessment template for TA479 reslizumab (2017). Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta479. [Accessed: 23/10/2019].
 NICE (2019) committee papers for TA565 benralizumab. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta565/evidence/appraisalconsultation1committeepaperspdf6715489645 [Accessed: 06/11/2019].
 Asthma UK (2020) Do no harm. Available from: https://www.asthmaandlung.org.uk/sites/default/files/202303/severeasthma_report_final.pdf [Accessed 11/01/2021].
 Frank C. Albers, Hana Müllerová, Necdet B. Gunsoy, JiYeon Shin, Linda M. Nelsen, Eric S. Bradford, Sarah M. Cockle & Robert Y. Suruki (2018) Biologic treatment eligibility for realworld patients with severe asthma: The IDEAL study, Journal of Asthma, 55:2, 152160, DOI: 10.1080/02770903.2017.1322611 Available from https://doi.org/10.1080/02770903.2017.1322611 [Accessed: 07/01/2021).
 NICE (2013) Resource impact assessment report for Omalizumab for treating severe persistent allergic asthma. TA278. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta278. Based on manufacturer submission to NICE for TA278 (TA133TA201) https://www.nice.org.uk/guidance/ta278/documents/asthmaseverepersistentpatientsaged6adultsomalizumabrevta133ta201novartis2 [Accessed: 11/10/2020].
 Datapharm Communications Limited (2016) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/. [Accessed: 31/08/2016].
 Kerkhof, M (et al) Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population. Available from https://abdn.pure.elsevier.com/en/publications/healthcareresourceuseandcostsofsevereuncontrolledeosinoph.
Smoking cessation
Varenicline is recommended by NICE for smoking cessation.
Smoking cessation: estimate calculation
Varenicline is not currently available in the UK. It has been withdrawn as a precaution, because of an impurity found in the medicine. It may be unavailable longterm.
In this estimate we have only used varenicline in this assessment because bupropion is prescribed less often, and the uncertainty surrounding our estimate is large enough to cover the low level of prescribing of the alternative treatment.
The NHS Long Term Plan states that by 2023/24, all people admitted to hospital who smoke will be offered NHSfunded tobacco treatment services. The approach was piloted in Wythenshawe Hospital Manchester between October 2018 and March 2019. Hospital inpatients who were admitted for at least one night were screened for their smoking status. People who smoke were asked on an optout basis to take part in a programme to help them to stop smoking. Varenicline was included in the range of pharmacotherapies available to help people quit smoking.
This estimate is concerned with the prescribing of varenicline that was initiated in secondary care. This will be compared with observed prescribing of secondary care varenicline and linked primary care varenicline prescribing.
Smoking is legal in the UK from age 18. Although some people smoke below that age, the estimate is based on adults aged 18 and over.
1. Population who meet SmPC
The SmPC states varenicline is indicated for an adult population only. Therefore, the starting population is people aged 18 and over in England.
Measure  Point estimate  Reference 

England population aged 18 and over  45,219,492  1 
2. Adult ordinary admissions to hospital as overnight inpatients for at least one night
To calculate the number of people who will be prescribed varenicline in hospital, the number of admissions into hospital needs to be calculated.
The same person may be admitted more than once to hospital in a year. A total of 3,581,581 adults were associated with 7,353,667 ordinary admissions (excluding maternity, paediatrics and day cases) between 01 April 2019 and 31 March 2020. NHS Long Term Plan policy is that if people are admitted more than once and need support to stop smoking, they will be offered it. Therefore, the number of admissions is used.
Measure  Point estimate  Reference 

Adult ordinary admissions to hospital as overnight inpatients (at least one night)  7,353,667  2 
3. Smoking prevalence among adults admitted to hospital
The British Thoracic Society has conducted 2 national smoking cessation audits, the first in 2016 and the second in 2019. Smoking prevalence among adult inpatients was higher than smoking prevalence in the general adult population, with an estimate of around 23.85%.
The estimate was based on a random sample of patient notes provided by 125 institutions, covering all adult inpatients in acute hospitals during the audit period of July and August 2019 (excluding maternity and mental health).
Given uncertainty in this estimate, confidence intervals alongside the point estimate, as applied to the population from step 2, were estimated as follows.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of ordinary hospital admissions for current smokers each year  1,753,494  1,616,825  1,890,164  3 
4. Proportion of adult smokers admitted to hospital who are identified and eligible for smoking cessation pharmacotherapy
The proportion of adult admissions screened during the pilot in Wythenshawe Hospital was 92%. This estimate has been applied to the estimate and upper and lower range calculated in step 3.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of adult smokers screened during an inpatient stay  1,613,215  1,487,479  1,738,950  4 
5. Proportion of adults admitted to hospital who smoke who are offered pharmacotherapy treatment
Of those screened and identified as people who smoke, 66% were offered pharmacotherapy in the Wythenshawe pilot. This has been applied to point estimate and upper and lower range above.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of adult smokers screened offered pharmacotherapy  1,064,722  981,736  1,147,707  4 
6. Proportion of adults admitted to hospital who smoke who receive varenicline
Of the adult smokers prescribed smoking cessation pharmacotherapy in the Wythenshawe pilot, 15% were given varenicline. This percentage has been applied to the point estimate and upper and lower range of those offered pharmacotherapy for smoking cessation in step 5.
Measure  Point estimate  Lower range  Upper range  Reference 

Number of adult smokers offered varenicline  159,708  147,260  172,156  4 
7. Estimated volume
The upper and lower bound and the point estimate calculated in step 6 been multiplied by the number of days in the year to estimate the number of people who will receive treatment annually. Assumed Daily Doses (ADD) were used to measure uptake.
Measure  Point estimate  Lower range  Upper range 

Treatment volume 365 days (ADD)  58,293,420  53,749,900  62,836,940 
8. Estimated usage by quarter per 100,000 population
Estimated annual ADD usage calculated in step 7 was divided by 4 to show quarterly ADD usage. This was then divided by the whole England population and multiplied by 100,000 to give an estimated usage per 100,000 population. This has been applied to the point estimate and upper and lower range calculated in step 7.
Measure  Point estimate  Lower range  Upper range  Reference 

ADD per 100,000 population England  25,520  23,531  27,509  1 
References
 Office for National Statistics (2023) Annual Midyear Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
 A count of distinct patients, from a SUS+ data extract 2019/20 of adult ordinary admissions to hospital, excluding maternity, day case and paediatrics between 1 April 2019 and 31 March 2020. The total count for Wythenshawe Hospital between 1 October 2018 and 31 March 2019 using this approach was 15,000 which was consistent with the count of 14,690 published in ‘Feasibility, uptake and impact of a hospitalwide tobacco addiction treatment pathway: Results from the CURE project pilot’, Evison et al, Clinical Medicine 2020 Vol 20 No. 2 pp.196202 (DOI: 10.7861/clinmed.20190336).
 British Thoracic Society National Smoking Cessation Audit Report 2019, British Thoracic Society Reports, Vol 11, Issue 2, 2020 (June 2020)
 ‘Feasibility, uptake and impact of a hospitalwide tobacco addiction treatment pathway: Results from the CURE project pilot’, Evison et al, Clinical Medicine 2020 Vol 20 No. 2 pp.196202 (DOI: 10.7861/clinmed.20190336).
 Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/ [Accessed: 26/01/2021].
Methodology and limitations
The estimate approach compares estimated predicted use with observed use. The estimated prediction use is calculated using the estimated treatment population, the average dose, and average length of treatment.
Estimates of the treatment population
NICE resource impact assessments were used as the starting point to develop the estimates presented.
Resource impact templates are provided by NICE to support the implementation of most technology appraisal guidance when the resource impact is expected to be significant. Resource impact is considered significant if it is expected to be greater than £5 million for England. The templates are an aid for financial planning purposes and enable users to estimate the local resource impact of implementing guidance at the time of publication. However, the template can be used to further develop and establish assumptions around an eligible population and an estimated treatment population.
The assumptions used to generate the resource impact templates are based on peer reviewed literature, data sources, expert opinion and other information. Data were sought from several different sources to refine the population numbers for the indications and circumstances detailed in the NICE technology appraisal guidance. The data reviewed included epidemiological data such as the prevalence of a disease, proportions of patients at a stage of a disease, and their likely treatment history. For some medicines, additional information was required, for example, the proportion of patients likely to discontinue treatment or choose an alternative.
NICE do not produce a resource impact template where the cost impact of a technology is not considered to be significant, or when estimating the cost impact is not possible. In the absence of a resource impact template, an estimate was constructed using a stepwise process similar to that used to develop a resource impact template. The process involved:
 a review of the available literature on the epidemiology of the indication(s) for the medicine
 where appropriate, the use of primary data sources such as Hospital Episode Statistics (HES) and The Health Improvement Network (THIN) database (containing pseudonymous patient information extracted from a sample of GP practice clinical systems)
 consultation with clinical experts and consideration of expert opinion used in other templates/sources of evidence for the same therapeutic area
For medicines with multiple indications, only those recommended by NICE were identified. Eligible populations were developed on an indication by indication basis. The separate indication estimates were then combined to produce an overall estimate. Indications not appraised or recommended by NICE were excluded from the estimate of the eligible population. Where a medicine has an indicated use not appraised or recommended by NICE, this could give the impression of over usage, even if this is not the case.
Estimates of usage (volume)
Treatment population estimates were used to calculate the total expected volume of medicine at a national level. Prescribing volumes are presented in Assumed Daily Doses (ADDs). The ADD is a prescribing measure developed for the Innovation Scorecard. ADDs assign a unique value for each presentation of a medicine based on units (such as tablets, capsules, patches) and the recommended frequency of daily use. For more information on ADD, please refer to the ADD methodology.
The daily dose is the daily maintenance dose calculated from the recommended dosage as set out in the summary of product characteristics. The annual estimated usage volume was proportionally allocated to each quarter based on the number of days in a quarter.
Range
Ranges for the estimate of the treatment population and the estimate of usage have been calculated for each estimate. The range provides an indication of the level of uncertainty in the estimate. They are calculated from confidence intervals and other specified measures at each step where available.
Manufacturer input to NICE estimates
Manufacturer input was requested for new estimates or those where a material change had been made to the estimated treatment population calculation. The draft estimates were sent to the relevant manufacturers with a request for comments and feedback on the estimate calculations and the supporting data.
Company feedback was then critically appraised and where appropriate, the draft estimate was updated. Where data used in the estimate is taken from a source that is routinely updated, such as the Quality and Outcomes Framework or population statistics, updating the estimate to reflect the latest publication is not considered to be a material change.
Observed use
Data for observed use of the medicines under consideration were obtained by NHS Digital through its routine access to Prescribing Analysis and Cost Tabulation (PACT) data on primary care prescribing (supplied by the NHS BSA) and Define data on secondary care prescribing (supplied by Rxinfo). Usage data were converted to ADDs to allow comparison with the estimates.
Although the secondary care database captures some data for drugs supplied through homecare services, it is incomplete. Therefore, the actual volume of medicine used may be higher than the volume reported in the observed use.
Comparison of expected and observed use
Observed use is compared with the estimated use to indicate whether use is higher or lower than expected. The estimated treatment population is calculated with an upper and lower range, to address the uncertainty in the underlying analyses. The ratio of observed to expected volume, and the upper and lower range, is calculated. Where the observed use is within the upper and lower estimate range, the use is considered to be as expected.
Limitations
Several assumptions are made in order to develop the expected volume of medicine to be prescribed. This approach is due to limitations, which include:
 lack of prevalence and incidence data at national level
 some medicines have multiple indications of which one or more indications have not been recommended by NICE
 medicines recommended as one of several options for treatment
Usage data are limited in coverage and quality. Problems include:
 multiple indications for a single medicine, as usage data give no information on the condition being treated
 failure of some hospitals to contribute data to the Rxinfo data collection or provide full datasets
 lack of available data from some mental health trusts
 reporting of medicines supplied via the homecare route or by outsourced dispensing is not recorded in pharmacy system
Medicines that need to be diluted or manipulated to the individual patient’s requirements in specialist units can also pose problems. The way these are recorded in pharmacy systems often does not allow calculation of the actual amount of drug used. Sometimes these medicines are not recorded at all by the pharmacy.
These limitations mean that caution must be exercised in interpreting the figures in the report as providing evidence of under or overuse of the medicines reviewed.
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Assumed Daily Dose (ADD) Methodology