Estimates Report

• Cancer
• Cardiovascular conditions
• Genetic disorder
• Infections
• Lifestyle
• Neurological conditions
• Respiratory conditions

• 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 beta-1a
• Interferon beta-1b
• 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 beta-1a
• Ponesimod
• Reslizumab
• Rimegepant
• Rivaroxaban
• Siponimod
• Sofosbuvir
• Sofosbuvir–velpatasvir
• Sofosbuvir–velpatasvir–voxilaprevir
• Teriflunomide
• Tezacaftor–ivacaftor (branded as Symkevi)
• Varenicline
• Warfarin

NICE guidance TA341 (2015)
NICE guidance TA275 (2013)
SmPC therapeutic indications: apixaban

NICE guidance TA327 (2014)
NICE guidance TA249 (2012)
SmPC therapeutic indications: dabigatran etexilate

NICE guidance TA354 (2015)
NICE guidance TA355 (2015)
SmPC therapeutic indications: Lixiana

NICE guidance TA256 (2012)
NICE guidance TA261 (2012)
NICE guidance TA287 (2012)
SmPC therapeutic indications: rivaroxaban

SmPC therapeutic indications: warfarin

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.

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.

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 CHA2DS2-VASc score of 2 or more, who are treated with anti-coagulation 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.

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.

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.

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 anti-coagulant treatment.

These figures have been applied to the estimate and upper and lower range calculated in step 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.

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.

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).

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.

References

1.    Office for National Statistics (2023) Annual Mid-year 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 sub-national English atrial fibrillation prevalence estimates: https://www.gov.uk/government/publications/atrial-fibrillation-prevalence-estimates-for-local-populations [Accessed 11/09/2020].
3.    Quality and outcomes framework 2021-22 (2022). NHS Digital. Available from https://digital.nhs.uk/data-and-information/publications/statistical/quality-and-outcomes-framework-achievement-prevalence-and-exceptions-data/2021-22 [Accessed: 03/01/2023].
4.    Martinez (2013). Epidemiology of first and recurrent venous thromboembolism: A population-based cohort study in patients without active cancer https://pdfs.semanticscholar.org/a72e/a02e5d50b2ef7d9f854fb7cdc82d98d59c50.pdf?_ga=2.261870413.1733460998.1602838089-1477011522.1602838089  [Accessed: 11/09/2020].

NICE guidance TA413 (2016)
SmPC therapeutic indication: ZEPATIER

NICE guidance TA499 (2018)
SmPC therapeutic indication: Maviret

NICE guidance TA363 (2015)
SmPC therapeutic indication: Harvoni

NICE guidance TA365 (2015)

NICE guidance TA330 (2015)
SmPC therapeutic indication: Sovaldi

NICE guidance TA430 (2017)
SmPC therapeutic indication: Epclusa

NICE guidance TA507 (2018)
SmPC therapeutic indication: Vosevi

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.

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 mid-year 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.

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.

4. Number of people to receive treatment

The upper and lower bound calculated in step 3 and the mid-point have been applied to estimate the number of people who will receive treatment annually.

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. 

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. 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.
3. Public Health England (2020) Hepatitis C in the England: Annual Report. Available from: https://www.gov.uk/government/publications/hepatitis-c-in-the-uk
4. Public Health England (2020) Hepatitis C in the England: Headline data table. Available from: https://www.gov.uk/government/publications/hepatitis-c-in-the-uk
5. Datapharm Communications Ltd (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/ [Accessed: 16/06/2021].

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:

• Ivacaftor (Kalydeco) tablets 
• Ivacaftor (Kalydeco) granules
• Ivacaftor–tezacaftor–elexacaftor (Kaftrio) tablets 
• Lumacaftor–ivacaftor (Orkambi) tablets 
• Lumacaftor–ivacaftor (Orkambi) granules
• Tezacaftor–ivacaftor (Symkevi) tablets

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.

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. 

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. 

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.

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.

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).

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. UK Cystic Fibrosis Registry. Available from: https://www.cysticfibrosis.org.uk/
3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html

NICE guidance TA310 (2014)
SmPC therapeutic indication: Giotrif

NICE guidance TA595 (2019)
SmPC therapeutic indication: Vizimpro

NICE guidance TA258 (2012)
NICE guidance TA374 (2015)
SmPC therapeutic indication: Tarceva

NICE guidance TA192 (2010)
SmPC therapeutic indication: Iressa

NICE guidance TA653 (2020)
NICE guidance TA654 (2020)
NICE guidance TA761 (2022)
SmPC therapeutic indication: Tagrisso

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 non-small-cell lung cancer (NSCLC), first-line 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.

2. Estimated number of people with non-small-cell lung cancer

The proportion of new cases of lung cancer that are non-small-cell 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.

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.

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.

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 non-targeted 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.

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.

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 first-line 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.

8. Proportion of people who progress following first line treatment with afatinib, dacomitinib, erlotinib or gefitinib (previously treated EGFR-positive)

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 first-line 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.

9. Proportion of people who harbour T790M mutation at progression (previously treated EGFR-population)

Based on genomic analysis, progression on a first-line EGFR TKI is characterised by an acquired secondary EGFR kinase domain mutation labelled T790M, causing resistance to the first-line 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.

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.

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.

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.

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.

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.

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.

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. Second-line 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.

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.

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.

References

1. 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].
2. Spotlight audit on molecular testing in advanced lung cancer (2020). Available from: https://www.rcplondon.ac.uk/projects/outputs/spotlight-audit-molecular-testing-advanced-lung-cancer-2019-diagnoses-2017 [Accessed: 08/11/2021].
3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from: https://statpages.org/confint.html [Accessed: 09/11/2021].
4. TA654 (NICE 2020). Osimertinib for untreated EGFR mutation-positive non-small-cell lung cancer. Available from: https://www.nice.org.uk/guidance/ta654 [Accessed: 02/11/2021].
5. TA416 (NICE 2016). Manufacturers submission (AstraZeneca 2016). Available from: https://www.nice.org.uk/guidance/ta416/evidence [Accessed: 29/01/2018].
6. Mazza V, Cappuzzo F. Treating EGFR mutation resistance in non-small cell lung cancer – role of osimertinib. The Application of Clinical Genetics. 2017; 10:49-56. doi:10.2147/TACG.S103471.
7. TA761 (NICE 2022). Osimertinib for adjuvant treatment of EGFR mutation-positive non-small-cell lung cancer after complete tumour resection. Available from https://www.nice.org.uk/guidance/ta761 [Accessed: 28/06/2022].
8. Zhang et al (2016). The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016 Nov 29; 7(48): 78985–78993.
9. TA374 (2015) Erlotinib and gefitinib for treating non-small-cell 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].
10. Cappuzzo F, Ciuleanu T, Stelmakh L (2010). Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. The Lancet Oncology. Volume 11, Issue 6, June 2010, Pages 521-529.
11. Datapharm Communications Limited (2017). The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/ [Accessed: 10/11/2021].
12. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].

NICE guidance TA805 (2022)
SmPC therapeutic indication: Vazkepa

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).

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.

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).

4. Low-density lipoprotein cholesterol concentrations

The estimated number of people who have had at least one recorded instance of a cardiovascular event and whose low-density 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.

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.

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.

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).

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. Datapharm Communications Limited (2015) The electronic Medicines Compendium. Available from: https://www.medicines.org.uk/emc/ [Accessed: April 2023]
3. The CVDPREVENT third annual audit report (2023) available from https://www.nhsbenchmarking.nhs.uk/cvdprevent-outputs [Accessed: April 2023]
4. Dylan L Steen, Irfan Khan, David Ansell, Robert J Sanchez, Kausik K Ray. Retrospective examination of lipid-lowering treatment patterns in a real-world high-risk 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]
5. 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
6. Danese MD, Sidelnikov E, Kutikova L. The prevalence, low-density lipoprotein cholesterol levels, and treatment of patients at very high risk of cardiovascular events in the United Kingdom: a cross-sectional study. Curr Med Res Opin. 2018 Aug;34(8):1441-1447. doi: 10.1080/03007995.2018.1463211. Epub 2018 Apr 20. PMID: 29627994.
7. 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]

NICE guidance TA259 (2012)
NICE guidance TA387 (2016)
SmPC therapeutic indication: Zytiga

NICE guidance TA741 (2021)
NICE guidance TA740 (2021)
SmPC therapeutic indication: Erleada

NICE guidance TA391 (2016)
SmPC therapeutic indication: cabazitaxel

NICE guidance TA316 (2014)
NICE guidance TA377 (2016)
SmPC therapeutic indication: Xtandi

Apalutamide and enzalutamide are also indicated (SmPC) for some non-metastatic 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.

2. Diagnosed metastatic prostate cancer

A large model-based 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).

3. Hormone sensitive and hormone-relapsed metastatic prostate cancer

A large model-based 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 hormone-relapsed.

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.

Hormone-sensitive 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 hormone-sensitive 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 mid-point (22.5%) applied to the point estimate calculated in step 3a.

Hormone-relapsed metastatic prostate cancer

5. Proportion of people who have hormone-relapsed 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 hormone-relapsed 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.

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.

7. Proportion of people who have hormone-relapsed metastatic prostate cancer that are expected to receive treatment with abiraterone, cabazitaxel or enzalutamide after treatment with first-line 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 first-line docetaxel chemotherapy.

Of those receiving first-line 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.

8. Calculate estimated usage volume

The number of people who have hormone-relapsed 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 first-line 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 hormone-relapsed 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.

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. 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].
3. 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.
4. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html [Accessed: 09/11/2021].
5. Enzalutamide for treating hormone-sensitive metastatic prostate cancer. NICE TA712, RIA template (2021). Available from: https://www.nice.org.uk/guidance/ta712/resources [Accessed: 04/11/2021].
6. Autio K, Bennett A, Jia X et al. (2013) Prevalence of pain and analgesic use in men with metastatic prostate cancer using a patient-reported outcome measure.
7. NICE Adoption and Impact Programme Reference Panel (2016), clinical experts with an interest in metastatic castration-resistant prostate cancer.
8. Cabazitaxel for hormone-relapsed metastatic prostate cancer treated with docetaxel. NICE TA391, RIA template (2016). Available from: https://www.nice.org.uk/guidance/ta391 [Accessed: 04/11/2021].
9. Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/, [Accessed: 07/12/2021].

NICE guidance TA871 (2023)
SmPC therapeutic indication: VYEPTI

NICE guidance TA682 (2021)
SmPC therapeutic indication: Aimovig

NICE guidance TA764 (2022)
SmPC therapeutic indication: AJOVY

NICE guidance TA659 (2020)
SmPC therapeutic indication: Emgality

NICE guidance TA906 (2023)
NICE guidance TA919 (2023)
SmPC therapeutic indication: Vydura

The estimated treatment population is calculated for the Calcitonin Gene-Related 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 one-year 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.

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. 

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.

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.

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.

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. 

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.

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.

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.

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. 

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.

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.  

References

1. 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. 519-527.
2. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023].
3. 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/gbd-results/ [Accessed: 30/5/22] 
4. NICE, 2023. Technology Appraisal: Eptinezumab for preventing migraine (TA871). NICE
5. International Headache Society, 2018. International Classification of Headache Disorders 3rd edition. s.l.:Cephalagia.
6. 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. 361-378.
7. Ferrari, A. et al., 2007. Similarities and Differences Between Chronic Migraine and Episodic Migraine. Headache, 47(1), pp. 65-72.
8. 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 (IBMS-II). Headache, 53(4), pp. 644-655.
9. Sanderson, J. C. et al., 2013. Headache-related health resource utilisation in chronic and episodic migraine across six countries. Journal of Neurology, Neurosurgery, and Psychiatry, 84(12), pp. 1309-1317

NICE guidance TA312 (2014)
SmPC therapeutic indication: LEMTRADA

NICE guidance TA616 (2019)
SmPC therapeutic indication: MAVENCLAD

NICE guidance TA320 (2014)
SmPC therapeutic indication: Tecfidera

NICE guidance TA794 (2022)
SmPC therapeutic indication: Vumerity

NICE guidance TA254 (2012)
SmPC therapeutic indication

NICE guidance TA527 (2018)
SmPC therapeutic indication

NICE guidance TA527 (2018)
SmPC therapeutic indication

NICE guidance TA527 (2018)
SmPC therapeutic indication

NICE guidance TA127 (2007)
SmPC therapeutic indication: TYSABRI

NICE guidance TA533 (2018)
NICE guidance TA585 (2019)
SmPC therapeutic indication: OCREVUS

NICE guidance TA699 (2021)
SmPC therapeutic indication: Kesimpta

NICE guidance TA624 (2020)
SmPC therapeutic indication: Plegridy

NICE guidance TA767 (2022)
SmPC therapeutic indication: Ponvory

NICE guidance TA656 (2020)
SmPC therapeutic indication: Mayzent

NICE guidance TA303 (2014)
SmPC therapeutic indication: AUBAGIO

The following steps estimate the population of adults with multiple sclerosis who receive treatment with one of the following NICE-approved medicines: alemtuzumab, cladribine, dimethyl fumarate, diroximel fumarate, fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b, natalizumab, ocrelizumab, ofatumumab, peginterferon beta-1a, 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 beta-1a (aged 2+, Rebif only), interferon beta-1b (aged 12-17), and teriflunomide (aged 10+). 

The starting population for this estimate is the total population of England.
 

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.  

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.

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.

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.

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. Public Health England (2020) Multiple sclerosis: prevalence, incidence and smoking status - data briefing. Available from: https://www.gov.uk/government/publications/multiple-sclerosis-prevalence-incidence-and-smoking-status/multiple-sclerosis-prevalence-incidence-and-smoking-status-data-briefing [Accessed: 30/06/2022].
3. UK MS Register Data (2023) Stats at a glance. Available at: https://ukmsregister.org/Research/OurData [Accessed: 09/05/2023].
4. 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.

5. Stratos et al., (2020) Non-compliance 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.

NICE guidance TA393 (2016)
SmPC therapeutic indication: Praluent

NICE guidance TA394 (2016)
SmPC therapeutic indication: Repatha

NICE guidance TA733 (2021)
SmPC therapeutic indication: Leqvio

The following estimates the population of adults with primary hypercholesterolaemia (familial and non-familial), 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 lipid-lowering 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.

2. Primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia

The proportion of people with primary non-familial 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.

3. Estimated number of people receiving or who have previously received lipid lowering therapy

The proportion of people with primary non-familial 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.

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.

5. Low-density lipoprotein cholesterol concentrations

The estimated number of people who have had at least one recorded instance of a cardiovascular event and whose low-density lipoprotein cholesterol concentrations are between 2.5mmol/L and 3.49mmol/L is reported to be 21.5%. Low-density 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.

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 (100-61.7=38.3). This has been applied to the total low-density lipoprotein cholesterol concentrations above 3.5mmol/L calculated in step 5e, for the point estimate and the upper and lower range.

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).

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc [Accessed: 01/11/2021].
3. 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.
4. 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].
5. Danese MD, Sidelnikov E, Kutikova L. The prevalence, low-density lipoprotein cholesterol levels, and treatment of patients at very high risk of cardiovascular events in the United Kingdom: a cross-sectional study. Curr Med Res Opin. 2018 Aug;34(8):1441-1447. doi: 10.1080/03007995.2018.1463211. Epub 2018 Apr 20. PMID: 29627994.
6. Calculation based on data supplied to the AHSN data toolkit by the inclisiran medicine manufacturer (Novartis), 2021.

NICE guidance TA565 (2019)
SmPC therapeutic indication: Fasenra

NICE guidance TA671 (2021)
SmPC therapeutic indication: Nucala

NICE guidance TA278 (2013)
NICE guidance TA339 (2015)
SmPC therapeutic indications: Xolair

NICE guidance TA479 (2017)
SmPC therapeutic indication: Cinqaero

Benralizumab, mepolizumab and reslizumab are add-on therapies, and are recommended by NICE as options for treating severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with high-dose inhaled corticosteroids and long-acting beta-agonists.

Omalizumab is recommended by NICE as an optional add-on 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

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.

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.

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.

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.

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.

7. Total eligible population for benralizumab, mepolizumab and reslizumab

Total eligible population for benralizumab, mepolizumab and reslizumab summed from steps 4 and 6.

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.

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.

10. Proportion discontinuing benralizumab, mepolizumab and reslizumab each year

The proportion of people discontinuing add-on 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.

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).

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.

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.

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.

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.

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).

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. Quality and outcomes framework 2022-23 (2023), 2021-22 (2022) and 2019/20 (2020). NHS Digital. Available from https://digital.nhs.uk/data-and-information/publications/statistical/quality-and-outcomes-framework-achievement-prevalence-and-exceptions-data/  [Accessed: 08/09/2022]
3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html.
4. 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].
5. 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].
6. 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].
7. NICE (2019) committee papers for TA565 benralizumab. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta565/evidence/appraisal-consultation-1-committee-papers-pdf-6715489645 [Accessed: 06/11/2019].
8. Asthma UK (2020) Do no harm. Available from: https://www.asthmaandlung.org.uk/sites/default/files/2023-03/severe-asthma_report_final.pdf [Accessed 11/01/2021].
9. Frank C. Albers, Hana Müllerová, Necdet B. Gunsoy, Ji-Yeon Shin, Linda M. Nelsen, Eric S. Bradford, Sarah M. Cockle & Robert Y. Suruki (2018) Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study, Journal of Asthma, 55:2, 152-160, DOI: 10.1080/02770903.2017.1322611 Available from https://doi.org/10.1080/02770903.2017.1322611 [Accessed: 07/01/2021).
10. 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 (TA133-TA201) https://www.nice.org.uk/guidance/ta278/documents/asthma-severe-persistent-patients-aged-6-adults-omalizumab-rev-ta133-ta201-novartis2 [Accessed: 11/10/2020].
11. Datapharm Communications Limited (2016) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/. [Accessed: 31/08/2016].
12. 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/healthcare-resource-use-and-costs-of-severe-uncontrolled-eosinoph.

NICE guidance TA123 (2007)
SmPC therapeutic indication: CHAMPIX

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 long-term.

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 NHS-funded 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 opt-out 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.

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. 

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.

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.

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.

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.

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.

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.

References

1. Office for National Statistics (2023) Annual Mid-year Population Estimates, 2022 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/estimatesofthepopulationforenglandandwales [Accessed: 12/10/2023]. 
2. 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 hospital-wide tobacco addiction treatment pathway: Results from the CURE project pilot’, Evison et al, Clinical Medicine 2020 Vol 20 No. 2 pp.196-202 (DOI: 10.7861/clinmed.2019-0336).
3. British Thoracic Society National Smoking Cessation Audit Report 2019, British Thoracic Society Reports, Vol 11, Issue 2, 2020 (June 2020)
4. ‘Feasibility, uptake and impact of a hospital-wide tobacco addiction treatment pathway: Results from the CURE project pilot’, Evison et al, Clinical Medicine 2020 Vol 20 No. 2 pp.196-202 (DOI: 10.7861/clinmed.2019-0336).
5. Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk/emc/ [Accessed: 26/01/2021].