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Publication, Part of

NICE Technology Appraisals in the NHS in England (Innovation Scorecard) to December 2021

Official statistics

Estimates Report

Key findings

The report sets out the calculation steps for each of the included medicines where it has been possible to estimate the range of expected usage in the NHS in England. The comparison of expected uptake to the actual volume of medicines used in the NHS in England is now available in the national level medicine groupings interactive dashboard.


Introduction

This report, where possible, compares the expected usage of 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, 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
High level conditions
  • Cancer
  • Cardiovascular conditions
  • Chronic kidney disease
  • Genetic disorder
  • Infections
  • Lifestyle
  • Respiratory conditions
Medicines
  • Abiraterone acetate
  • Afatinib
  • Alirocumab
  • Apixaban
  • Benralizumab
  • Cabazitaxel
  • Dabigatran
  • Edoxaban
  • Elbasvir–grazoprevir
  • Enzalutamide
  • Erlotinib
  • Etelcalcetide
  • Evolocumab
  • Gefitinib
  • Glecaprevir–pibrentasvir
  • Ivacaftor (branded as Kalydeco)
  • Ivacaftor–tezacaftor–elexacaftor (branded as Kaftrio)
  • Ledipasvir–sofosbuvir
  • Lumacaftor–ivacaftor (branded as Orkambi)
  • Mepolizumab
  • Omalizumab
  • Ombitasvir–paritaprevir–ritonavir
  • Osimertinib
  • Reslizumab
  • Rivaroxaban
  • Sofosbuvir
  • Sofosbuvir–velpatasvir
  • Sofosbuvir–velpatasvir–voxilaprevir
  • Tezacaftor–ivacaftor (branded as Symkevi)
  • Varenicline
  • Warfarin

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.

Apixaban

NICE guidance TA341 (2015)

Apixaban is recommended, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

NICE guidance TA275 (2013)

1.1 Apixaban is recommended as an option for preventing stroke and systemic embolism within its marketing authorisation, that is, in people with nonvalvular atrial fibrillation with 1 or more risk factors such as:

  • prior stroke or transient ischaemic attack
  • age 75 years or older
  • hypertension
  • diabetes mellitus
  • symptomatic heart failure.

1.2 The decision about whether to start treatment with apixaban should be made after an informed discussion between the clinician and the person about the risks and benefits of apixaban compared with warfarin, dabigatran etexilate and rivaroxaban. For people who are taking warfarin, the potential risks and benefits of switching to apixaban should be considered in light of their level of international normalised ratio (INR) control.

SmPC Therapeutic indications: Apixaban

Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA); age≥ 75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥ II).

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults (see section 4.4 for haemodynamically unstable PE patients).

Dabigatran etexilate

NICE guidance TA327 (2014)

Dabigatran etexilate is recommended, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

NICE guidance TA249 (2012)

1.1 Dabigatran etexilate is recommended as an option for the prevention of stroke and systemic embolism within its licensed indication, that is, in people with nonvalvular atrial fibrillation with one or more of the following risk factors:

  • previous stroke, transient ischaemic attack or systemic embolism
  • left ventricular ejection fraction below 40%
  • symptomatic heart failure of New York Heart Association (NYHA) class 2 or above
  • age 75 years or older
  • age 65 years or older with one of the following: diabetes mellitus, coronary artery disease or hypertension.

1.2 The decision about whether to start treatment with dabigatran etexilate should be made after an informed discussion between the clinician and the person about the risks and benefits of dabigatran etexilate compared with warfarin. For people who are taking warfarin, the potential risks and benefits of switching to dabigatran etexilate should be considered in light of their level of international normalised ratio (INR) control.

SmPC therapeutic indications: dabigatran etexilate

Primary prevention of venous thromboembolic events in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery.

Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors, such as prior stroke or transient ischemic attack (TIA); age ≥ 75 years; heart failure (NYHA Class ≥ II); diabetes mellitus; hypertension.

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.

Edoxaban

NICE guidance TA354 (2015)

Edoxaban is recommended, within its marketing authorisation, as an option for treating and for preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

NICE guidance TA355 (2015)

1.1 Edoxaban is recommended, within its marketing authorisation, as an option for preventing stroke and systemic embolism in adults with non‑valvular atrial fibrillation with one or more risk factors, including:

  • congestive heart failure
  • hypertension
  • diabetes
  • prior stroke or transient ischaemic attack
  • age 75 years or older.

1.2 The decision about whether to start treatment with edoxaban should be made after an informed discussion between the clinician and the person about the risks and benefits of edoxaban compared with warfarin, apixaban, dabigatran etexilate and rivaroxaban. For people considering switching from warfarin, edoxaban's potential benefits should be considered against its potential risks, taking into account the person's level of international normalised ratio (INR) control.

SmPC therapeutic indications: Lixiana

Lixiana is indicated in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA).

Lixiana is indicated in treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for the prevention of recurrent DVT and PE in adults (see section 4.4 for haemodynamically unstable PE patients).

Rivaroxaban

NICE guidance TA256 (2012)

1.1 Rivaroxaban is recommended as an option for the prevention of stroke and systemic embolism within its licensed indication, that is, in people with nonvalvular atrial fibrillation with one or more risk factors such as:

  • congestive heart failure
  • hypertension
  • age 75 years or older
  • diabetes mellitus,
  • prior stroke or transient ischaemic attack.

1.2 The decision about whether to start treatment with rivaroxaban should be made after an informed discussion between the clinician and the person about the risks and benefits of rivaroxaban compared with warfarin. For people who are taking warfarin, the potential risks and benefits of switching to rivaroxaban should be considered in light of their level of international normalised ratio (INR) control.

NICE guidance TA261 (2012)

Rivaroxaban is recommended as an option for treating deep vein thrombosis and preventing recurrent deep vein thrombosis and pulmonary embolism after a diagnosis of acute deep vein thrombosis in adults.

NICE guidance TA287 (2012)

Rivaroxaban is recommended as an option for treating pulmonary embolism and preventing recurrent deep vein thrombosis and pulmonary embolism in adults.

SmPC therapeutic indications: rivaroxaban

Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack.

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.

Warfarin

SmPC therapeutic indications: warfarin

Prophylaxis of systemic embolism in patients with rheumatic heart disease and atrial fibrillation.

Prophylaxis after insertion of prosthetic heart valves.

Prophylaxis and treatment of venous thrombosis and pulmonary embolism and for use in the treatment of these conditions to prevent their extension.


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.

Elbasvir–grazoprevir

 

NICE guidance TA413 (2016)

Elbasvir–grazoprevir is recommended, within its marketing authorisation, as an option for treating genotype 1 or 4 chronic hepatitis C in adults, only if the company provides the drug at the same price or lower than that agreed with the Commercial Medicines Unit.

SmPC therapeutic indication: ZEPATIER

ZEPATIER is indicated for the treatment of chronic hepatitis C (CHC) in adults.

Glecaprevir–pibrentasvir

NICE guidance TA499 (2018)

1.1 Glecaprevir–pibrentasvir is recommended, within its marketing authorisation, as an option for treating chronic hepatitis C in adults, only if the company provides the drug at the same price or lower than that agreed with the Commercial Medicines Unit.

1.2 It is recommended that the decision to treat and prescribing decisions are made by multidisciplinary teams in the operational delivery networks put in place by NHS England, to prioritise treatment for people with the highest unmet clinical need.

SmPC therapeutic indication: Maviret

Maviret is indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults and children aged 3 years and older.

Ledipasvir–sofosbuvir

NICE guidance TA363 (2015)

Ledipasvir–sofosbuvir is recommended as an option for treating chronic hepatitis C in adults.

SmPC Therapeutic indication: Harvoni

Harvoni is indicated for the treatment of chronic hepatitis C (CHC) in adult and paediatric patients aged 3 years and older.

Ombitasvir–paritaprevir–ritonavir

NICE guidance TA365 (2015)

Ombitasvir–paritaprevir–ritonavir with or without dasabuvir is recommended, within its marketing authorisation, as an option for treating genotype 1 or 4 chronic hepatitis C in adults, only if the company provides ombitasvir–paritaprevir–ritonavir and dasabuvir at the same price or lower than that agreed with the Commercial Medicines Unit.

SmPC therapeutic indication: Ombitasvir–paritaprevir–ritonavir

N/A

Sofosbuvir

NICE guidance TA330 (2015)

Sofosbuvir is recommended as an option for treating chronic hepatitis C in adults.

SmPC therapeutic indication: Sovaldi

Sovaldi is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults and paediatric patients aged 3 years and older.

Sofosbuvir–velpatasvir

NICE guidance TA430 (2017)

Sofosbuvir–velpatasvir is recommended as an option for treating chronic hepatitis C in adults, only if the company provides the drug with the discount agreed in the simple discount agreement.

SmPC therapeutic indication: Epclusa

Epclusa is indicated for the treatment of chronic hepatitis C virus (HCV) infection in patients aged 6 years and older and weighing at least 17 kg.

Sofosbuvir–velpatasvir–voxilaprevir

NICE guidance TA507 (2018)

Sofosbuvir–velpatasvir–voxilaprevir is recommended as an option for treating chronic hepatitis C in adults, and the company provides the drug at the same price or lower than that agreed with the Commercial Medicines Unit.

SmPC Therapeutic indication: Vosevi

Vosevi is indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults


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 (NICE guidance TA398 (2016)), NHS England has said that it is now available on the NHS for treating cystic fibrosis.

NHS England and NHS Improvement has agreed combination therapy is available on the NHS for treating cystic fibrosis. The data collection agreement enables eligible patients continued access to Vertex’s cystic fibrosis modulator therapies while further data is collected to inform a future NICE technology appraisal.

SmPC therapeutic indications:

Ivacaftor (Kalydeco) tablets are indicated:

• As monotherapy for the treatment of adults, adolescents, and children aged 6 years and older and weighing 25 kg or more with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

• In a combination regimen with tezacaftor/ivacaftor tablets for the treatment of adults, adolescents, and children aged 6 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.

• In a combination regimen with ivacaftor /tezacaftor /elexacaftor tablets for the treatment of adults and adolescents aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation in the CFTR gene or heterozygous for F508del and have a minimal function (MF) mutation in the CFTR gene.

Ivacaftor (Kalydeco) granules are indicated for the treatment of infants aged at least 4 months, toddlers and children weighing 5 kg to less than 25 kg with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

Ivacaftor–tezacaftor–elexacaftor (Kaftrio) tablets are indicated in a combination regimen with ivacaftor 150 mg tablets for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or heterozygous for F508del in the CFTR gene with a minimal function (MF) mutation. 

Lumacaftor–ivacaftor (Orkambi) tablets are indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Lumacaftor–ivacaftor (Orkambi) granules are indicated for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Tezacaftor–ivacaftor (Symkevi) tablets are indicated in a combination regimen with ivacaftor tablets for the treatment of patients with cystic fibrosis (CF) aged 6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T


EGFR Non-small-cell 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) mutation-positive non-small-cell lung cancer (NSCLC).

Osimertinib is indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC.

Afatinib

NICE guidance TA310 (2014)

Afatinib is recommended as an option, within its marketing authorisation, for treating adults with locally advanced or metastatic non-small-cell lung cancer only if:

  • the tumour tests positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and
  • the person has not previously had an EGFR-TK inhibitor and
  • the manufacturer provides afatinib with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Giotrif

Giotrif as monotherapy is indicated for the treatment of:

  • Epidermal Growth Factor Receptor (EGFR) TKI-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s).
  • Adult patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy.
Dacomitinib

NICE guidance TA595 (2019)

Dacomitinib is recommended, within its marketing authorisation, as an option for untreated locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in adults. It is recommended only if the company provides it according to the commercial arrangement.

SmPC therapeutic indication: Vizimpro

Vizimpro, as monotherapy, is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations.

Erlotinib

NICE guidance TA258 (2012)

Erlotinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if:

  • they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and
  • the manufacturer provides erlotinib at the discounted price agreed under the patient access scheme (as revised in 2012).

NICE guidance TA374 (2015)

1.1 Erlotinib is recommended as an option for treating locally advanced or metastatic non-small cell lung cancer that has progressed in people who have had non targeted chemotherapy because of delayed confirmation that their tumour is epidermal growth factor receptor tyrosine kinase (EGFR TK) mutation positive, only if the company provides erlotinib with the discount agreed in the patient access scheme revised in the context of NICE technology appraisal guidance 258.

1.2 Erlotinib is recommended as an option for treating locally advanced or metastatic non-small cell lung cancer that has progressed after non targeted chemotherapy in people with tumours of unknown EGFR TK mutation status, only if:

  • the result of an EGFR TK mutation diagnostic test is unobtainable because of an inadequate tissue sample or poor quality DNA and
  • the treating clinician considers that the tumour is very likely to be EGFR TK mutation positive and
  • the person's disease responds to the first 2 cycles of treatment with erlotinib and
  • the company provides erlotinib with the discount agreed in the patient access scheme revised in the context of NICE technology appraisal guidance 258.

1.3 Erlotinib is not recommended for treating locally advanced or metastatic non‑small‑cell lung cancer that has progressed after non‑targeted chemotherapy in people with tumours that are EGFR‑TK mutation‑negative.

1.4 Gefitinib is not recommended for treating locally advanced or metastatic non‑small‑cell lung cancer that has progressed after non‑targeted chemotherapy in people with tumours that are EGFR‑TK mutation‑positive.

SmPC therapeutic indication: Tarceva

Non-Small Cell Lung Cancer (NSCLC):

  • Tarceva is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR activating mutations.
  • Tarceva is also indicated for switch maintenance treatment in patients with locally advanced or metastatic NSCLC with EGFR activating mutations and stable disease after first-line chemotherapy.
  • Tarceva is also indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. In patients with tumours without EGFR activating mutations, Tarceva is indicated when other treatment options are not considered suitable.

Pancreatic cancer:

  • Tarceva in combination with gemcitabine is indicated for the treatment of patients with metastatic pancreatic cancer.
Gefitinib

NICE guidance TA192 (2010)

Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if:

  • they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and
  • the manufacturer provides gefitinib at the fixed price agreed under the patient access scheme.

SmPC therapeutic indication: Iressa

IRESSA is indicated as monotherapy for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR-TK.

Osimertinib

NICE guidance TA416 (2016)

Osimertinib is recommended as an option for use within the Cancer Drugs Fund for treating locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small-cell lung cancer in adults whose disease has progressed only:

  • after first-line treatment with an EGFR tyrosine kinase inhibitor and
  • if the conditions in the managed access agreement for osimertinib are followed.

SmPC therapeutic indication: Tagrisso

TAGRISSO as monotherapy is indicated for:

  • The first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.
  • The treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC.
  • The first-line treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR mutations

Metastatic castration-resistant prostate cancer

Abiraterone, apalutamide, cabazitaxel and enzalutamide are recommended by NICE for the treatment of metastatic castration-resistant prostate cancer.

Abiraterone

NICE guidance TA259 (2012)

Abiraterone in combination with prednisone or prednisolone is recommended as an option for the treatment of castration resistant metastatic prostate cancer in adults, only if:

  • their disease has progressed on or after one docetaxel containing chemotherapy regimen, and
  • the manufacturer provides abiraterone in accordance with the commercial access arrangement as agreed with NHS England.

NICE guidance TA387 (2016)

Abiraterone in combination with prednisone or prednisolone is recommended, within its marketing authorisation, as an option for treating metastatic hormone-relapsed prostate cancer:

  • in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated
  • only when the company provides abiraterone in accordance with the commercial access arrangement as agreed with NHS England.

SmPC therapeutic indication: Zytiga

ZYTIGA is indicated with prednisone or prednisolone for:

  • The treatment of newly diagnosed high risk metastatic hormone sensitive prostate cancer (mHSPC) in adult men in combination with androgen deprivation therapy (ADT).
  • The treatment of metastatic castration resistant prostate cancer (mCRPC) in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.
  • The treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.
Apalutamide

NICE guidance TA741 (2021)

Apalutamide plus androgen deprivation therapy (ADT) is recommended as an option for treating hormone-sensitive metastatic prostate cancer in adults, only if:

 

docetaxel is not suitable

 

  • the company provides apalutamide according to the commercial arrangement.

NICE guidance TA741 (2021)

Apalutamide plus androgen deprivation therapy (ADT) is recommended, within its marketing authorisation, as an option for treating hormone‑relapsed non‑metastatic prostate cancer that is at high risk of metastasising in adults. High risk is defined as a blood prostate-specific antigen (PSA) level that has doubled in 10 months or less on continuous ADT. It is recommended only if the company provides apalutamide according to the commercial arrangement.

SmPC therapeutic indication: Erleada

Erleada is indicated:• in adult men for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.• in adult men for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).

Cabazitaxel

NICE guidance TA391 (2016)

Cabazitaxel in combination with prednisone or prednisolone is recommended as an option for treating metastatic hormone relapsed prostate cancer in people whose disease has progressed during or after docetaxel chemotherapy, only if:

  • the person has an eastern cooperative oncology group (ECOG) performance status of 0 or 1
  • the person has had 225 mg/m2 or more of docetaxel
  • treatment with cabazitaxel is stopped when the disease progresses or after a maximum of 10 cycles (whichever happens first).

In addition, cabazitaxel is recommended only if:

  • the company provides cabazitaxel with the discount in the patient access scheme agreed with the Department of Health, and
  • NHS trusts purchase cabazitaxel in accordance with the commercial access agreement between the company and NHS England, either:
    • in pre prepared intravenous infusion bags, or
    • in vials, at a reduced price that includes a further discount reflecting the average cost of waste per patient 

SmPC therapeutic indication: Jevtana

JEVTANA in combination with prednisone or prednisolone is indicated for the treatment of adult patients with metastatic castration resistant prostate cancer previously treated with a docetaxel-containing regimen.

Enzalutamide

NICE guidance TA316 (2014)

1.1 Enzalutamide is recommended within its marketing authorisation as an option for treating metastatic hormone relapsed prostate cancer in adults whose disease has progressed during or after docetaxel-containing chemotherapy, only if the manufacturer provides enzalutamide with the discount agreed in the patient access scheme.

1.2 The use of enzalutamide for treating metastatic hormone-relapsed prostate cancer previously treated with abiraterone is not covered by this guidance.

NICE guidance TA377 (2016)

Enzalutamide is recommended, within its marketing authorisation, as an option for treating metastatic hormone relapsed prostate cancer:

  • in people who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated
  • and only when the company provides it with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Xtandi

Xtandi is indicated for:

  • The treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer.
  • The treatment of adult men with metastatic castration-resistant prostate cancer (CRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.
  • The treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy.
  • The treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy.

Primary hypercholesterolaemia and mixed dyslipidaemia

Alirocumab,  evolocumab or inclisiran are recommended by NICE for the treatment of primary hypercholesterolaemia and mixed dyslipidaemia.

Alirocumab

 

NICE guidance TA393 (2016)

Alirocumab is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only if:

  • low density lipoprotein concentrations are persistently above specified thresholds despite maximal tolerated lipid lowering therapy. That is, either the maximum dose has been reached or further titration is limited by intolerance (as defined in NICE's guideline on familial hypercholesterolaemia: identification and management).
  • the company provides alirocumab with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Praluent

Praluent is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

  • in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or,
  • alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
Evolocumab

 

NICE guidance TA394 (2016)

Evolocumab is recommended as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only if:

  • the dosage is 140 mg every 2 weeks.
  • low-density lipoprotein concentrations are persistently above specified thresholds despite maximal tolerated lipid-lowering therapy. That is, either the maximum dose has been reached, or further titration is limited by intolerance (as defined in NICE's guideline on familial hypercholesterolaemia).
  • the company provides evolocumab with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Repatha

Hypercholesterolaemia and mixed dyslipidaemia:

Repatha is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

  • in combination with a statin or statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or,
  • alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.

Homozygous familial hypercholesterolaemia:

Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipid-lowering therapies.

Established atherosclerotic cardiovascular disease:

Repatha is indicated in adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors:

  • in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or,
  • alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.
Inclisiran

NICE guidance TA733 (2021)

Inclisiran is recommended as an option for treating primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet in adults. It is recommended only if:

  • there is a history of any of the following cardiovascular events:
  • acute coronary syndrome (such as myocardial infarction or unstable angina needing hospitalisation)
  • coronary or other arterial revascularisation procedures
  • coronary heart disease
  • ischaemic stroke or
  • peripheral arterial disease, and
  • low-density lipoprotein cholesterol (LDL-C) concentrations are persistently 2.6 mmol/l or more, despite maximum tolerated lipid-lowering therapy, that is:
  • maximum tolerated statins with or without other lipid-lowering therapies or,
  • other lipid-lowering therapies when statins are not tolerated or are contraindicated, and
  • the company provides inclisiran according to the commercial arrangement.

SmPC therapeutic indication: Leqvio

Leqvio is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:

  • in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin, or
  • alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.

Secondary hyperparathyroidism

Etelcalcetide is indicated for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on haemodialysis therapy.

Etelcalcetide

NICE guidance TA448 (2017)

Etelcalcetide is recommended as an option for treating secondary hyperparathyroidism in adults with chronic kidney disease on haemodialysis, only if:

  • treatment with a calcimimetic is indicated but cinacalcet is not suitable and
  • the company provides etelcalcetide with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Parsabiv

Parsabiv is indicated for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on haemodialysis therapy.


Severe asthma

Benralizumab, mepolizumab, omalizumab and reslizumab are recommended by NICE for treating severe asthma.

Benralizumab

NICE guidance TA565 (2019)

1.1 Benralizumab, as an add-on therapy, is recommended as an option for treating severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with high-dose inhaled corticosteroids and long-acting beta-agonists, only if:

  • the person has agreed to and followed the optimised standard treatment plan and
  • the blood eosinophil count has been recorded as 300 cells per microlitre or more and the person has had 4 or more exacerbations needing systemic corticosteroids in the previous 12 months, or has had continuous oral corticosteroids of at least the equivalent of prednisolone 5 mg per day over the previous 6 months (that is, the person is eligible for mepolizumab) or
  • the blood eosinophil count has been recorded as 400 cells per microlitre or more with 3 or more exacerbations needing systemic corticosteroids in the past 12 months (that is, the person is eligible for reslizumab).
  • Benralizumab is recommended only if the company provides it according to the commercial arrangement.

1.2 If benralizumab, mepolizumab or reslizumab are equally suitable, start treatment with the least expensive option (taking into account drug and administration costs).

1.3 At 12 months:

  • stop benralizumab if the asthma has not responded adequately or
  • continue benralizumab if the asthma has responded adequately and assess response each year.

An adequate response is defined as:

  • a clinically meaningful reduction in the number of severe exacerbations needing systemic corticosteroids or
  • a clinically significant reduction in continuous oral-corticosteroid use while maintaining or improving asthma control.

SmPC Therapeutic indication: Fasenra

Fasenra is indicated as an add-on maintenance treatment in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus long-acting β-agonists.

Mepolizumab

NICE Guidance TA671 (2021)

1.1 Mepolizumab, as an add-on therapy, is recommended as an option for treating severe refractory eosinophilic asthma, only if:

  • it is used for adults who have agreed to and followed the optimised standard treatment plan and
  • the blood eosinophil count has been recorded as 300 cells per microlitre or more and the person has had at least 4 exacerbations needing systemic corticosteroids in the previous 12 months, or has had continuous oral corticosteroids of at least the equivalent of prednisolone 5 mg per day over the previous 6 months or
  • the blood eosinophil count has been recorded as 400 cells per microlitre or more and the person has had at least 3 exacerbations needing systemic corticosteroids in the previous 12 months (so they are also eligible for either benralizumab or reslizumab).

Mepolizumab is recommended only if the company provides it according to the commercial arrangement.

1.2 If mepolizumab, benralizumab or reslizumab are equally suitable, start treatment with the least expensive option (taking into account drug and administration costs).

1.3 At 12 months:

  • stop mepolizumab if the asthma has not responded adequately or
  • continue mepolizumab if the asthma has responded adequately and assess response each year.

An adequate response is defined as:

  • a clinically meaningful reduction in the number of severe exacerbations needing systemic corticosteroids or
  • a clinically significant reduction in continuous oral corticosteroid use while maintaining or improving asthma control.

SmPC therapeutic indication: Nucala

Nucala is indicated as an add-on treatment for severe refractory eosinophilic asthma in adults, adolescents and children aged 6 years and older.

Omalizumab

NICE Guidance TA278 (2013)

1.1 Omalizumab is recommended as an option for treating severe persistent confirmed allergic IgE mediated asthma as an add on to optimised standard therapy in people aged 6 years and older:

•  who need continuous or frequent treatment with oral corticosteroids (defined as 4 or more courses in the previous year), and

•  only if the manufacturer makes omalizumab available with the discount agreed in the patient access scheme.

1.2 Optimised standard therapy is defined as a full trial of and, if tolerated, documented compliance with inhaled high dose corticosteroids, long acting beta2 agonists, leukotriene receptor antagonists, theophyllines, oral corticosteroids, and smoking cessation if clinically appropriate.

NICE Guidance TA339 (2015)

1.1 Omalizumab is recommended as an option as add‑on therapy for treating severe chronic spontaneous urticaria in adults and young people aged 12 years and over only if:

  • the severity of the condition is assessed objectively, for example, using a weekly urticaria activity score of 28 or more
  • the person's condition has not responded to standard treatment with H1‑antihistamines and leukotriene receptor antagonists
  • omalizumab is stopped at or before the fourth dose if the condition has not responded
  • omalizumab is stopped at the end of a course of treatment (6 doses) if the condition has responded, to establish whether the condition has gone into spontaneous remission, and is restarted only if the condition relapses
  • omalizumab is administered under the management of a secondary care specialist in dermatology, immunology or allergy
  • the company provides omalizumab with the discount agreed in the patient access scheme.

SmPC therapeutic indications: Xolair

Allergic asthma: Xolair is indicated in adults, adolescents and children (6 to <12 years of age). Xolair treatment should only be considered for patients with convincing IgE (immunoglobulin E) mediated asthma

Adults and adolescents (12 years of age and older): Xolair is indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and who have reduced lung function (FEV1 <80%) as well as frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily high-dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist.

Children (6 to <12 years of age): Xolair is indicated as add-on therapy to improve asthma control in patients with severe persistent allergic asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and frequent daytime symptoms or night-time awakenings and who have had multiple documented severe asthma exacerbations despite daily high-dose inhaled corticosteroids, plus a long-acting inhaled beta2-agonist.

Chronic rhinosinusitis with nasal polyps (CRSwNP): Xolair is indicated as an add-on therapy with intranasal corticosteroids (INC) for the treatment of adults (18 years and above) with severe CRSwNP for whom therapy with INC does not provide adequate disease control.

Chronic spontaneous urticaria (CSU): Xolair is indicated as add-on therapy for the treatment of chronic spontaneous urticaria in adult and adolescent (12 years and above) patients with inadequate response to H1 antihistamine treatment.

Reslizumab

NICE Guidance TA479 (2017)

1.1 Reslizumab, as an add-on therapy, is recommended as an option for the treatment of severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with high-dose inhaled corticosteroids plus another drug, only if:

  • the blood eosinophil count has been recorded as 400 cells per microlitre or more
  • the person has had 3 or more severe asthma exacerbations needing systemic corticosteroids in the past 12 months and
  • the company provides reslizumab with the discount agreed in the patient access scheme.

1.2 At 12 months:

  • stop reslizumab if the asthma has not responded adequately or
  • continue reslizumab if the asthma has responded adequately and assess response each year.

An adequate response is defined as:

  • a clinically meaningful reduction in the number of severe exacerbations needing systemic corticosteroids or
  • a clinically significant reduction in continuous oral corticosteroid use while maintaining or improving asthma control.

SmPC therapeutic indication: Cinqaero

CINQAERO is indicated as add-on therapy in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus another medicinal product for maintenance treatment.


Smoking cessation

Varenicline is recommended by NICE for smoking cessation.

Varenicline

NICE guidance TA123 (2007)

1.1 Varenicline is recommended within its licensed indications as an option for smokers who have expressed a desire to quit smoking.

1.2 Varenicline should normally be prescribed only as part of a programme of behavioural support.

SmPC therapeutic indication: CHAMPIX

CHAMPIX is indicated for smoking cessation in adults.


Methodology and limitations

The estimate approach compares estimated predicted use (calculated using the estimated treatment population, the average dose and average length of treatment) with observed use.

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 (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:

  1. A review of the available literature on the epidemiology of the indication(s) for the medicine.
  2. 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).
  3. 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 actual 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 estimate calculations.

Where an ADD was not available, Defined Daily Doses (DDDs) as defined by the World Health Organisation (WHO) or an alternative measure such as milligrams (mgs) was used.

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 Rx-info). Usage data were converted where appropriate, for example 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 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 (usage data give no information on the condition being treated)
  • Failure of some hospitals to contribute data to the Rx-info data collection or are unable to 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 systems
  • Medicines that need to be diluted or manipulated to the individual patient’s requirements in specialist units; the way these are recorded in the pharmacy systems often does not allow calculation of the actual amount of drug used and 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.


Estimate calculations

Atrial fibrillation, pulmonary embolism or deep vein thrombosis: apixaban, dabigatran, edoxaban, rivaroxaban and warfarin

Only use of apixaban, dabigatran, 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.

 

Point estimate

Reference

England population

56,286,961

(1)

 

2. Prevalence of atrial fibrillation

Not all people with atrial fibrillation (AF) who are eligible to receive medication will be diagnosed. Primary care GP registry Quality and Outcomes Framework (QOF) reported 2.1% of the England population in 2019/20 have diagnosed atrial fibrillation.

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, step 1:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with atrial fibrillation

1,407,174

1,350,887

1,463,461

(2)

 

3. Proportion of people with atrial fibrillation eligible to receive treatment with apixaban, dabigatran, 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 eligible to be treated with anti-coagulation drug therapy, as 1,001,702. The total number of people on the QOF atrial fibrillation register is 1,239,401. From this the proportion of people on the register eligible for treatment has been calculated as 80.8%. 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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with disease

 1,136,997

 1,091,517

 1,182,476

(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.

 

Point estimate

Lower range

Upper range

Reference

Incidence of VTE

 74,299

 73,173

 74,862

(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.

 

Point estimate

Lower range

Upper range

Reference

Number of people with VTE and active cancer

 13,820

 13,610

 13,924

(4)

Number of people with VTE not known to have cancer

 60,479

 59,563

 60,938

(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.

 

Point estimate

Lower range

Upper range

Reference

Number of people likely to receive treatment with recurrent PE/DVT (VTE)

 43,168

 42,514

 43,495

(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.

 

Point estimate

Lower range

Upper range

Reference

Number of people with VTE and active cancer and receiving treatment

 6,910

 6,805

 6,962

(5)

Number of people with VTE not known to have cancer and receiving treatment

 15,120

 14,891

 15,235

(5)

Number of people with recurrent VTE and receiving treatment

 43,168

 42,514

 43,495

(5)

Number of people with AF and receiving treatment

 1,136,997

 1,091,517

 1,182,476

(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

These figures calculated in step 7 are summed below:

 

Point estimate

Lower range

Upper range

Estimated number of people likely to receive treatment

1,202,195

1,155,727

1,248,168

 

  1. Estimated volume

The number of people estimated to receive apixaban, dabigatran, edoxaban, rivaroxaban or warfarin (calculated in step 8) has been multiplied by the number of days in a year to give the annual usage in ADDs:

For these medicines, the calculated ADD is:

  • two tablets of apixaban (2.5mg or 5mg tablets), or
  • two tablets of dabigatran (110mg or 150mg tablets), or
  • one tablet of edoxaban (15mg or 30mg or 60mg tablets), or
  • two 15mg tablets of rivaroxaban, or
  • one 20mg tablet of rivaroxaban, or
  • 1.75 tablets of rivaroxaban initiation pack (15mg and 20mg tablets), or
  • 7.5mg of warfarin.

 

 

Point estimate

Lower range

Upper range

Estimated annual usage (ADDs) 365 days

438,801,175

421,840,355

455,581,320

Estimated annual usage (ADDs) 366 days

440,003,370

422,996,082

456,829,488

 

10. Estimated usage by quarter per 100,000 population

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 193,981

 186,483

 201,399

(7)

 

 References

  1. Office for National Statistics (2020) Annual Mid-year Population Estimates 2019. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates  [Accessed: 11/09/2020].
  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 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/2019-20 (Accessed 11/09/2020)
  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].
  5. British National Formulary. Available from https://bnf.nice.org.uk/treatment-summary/venous-thromboembolism.html (Accessed 11/09/2020)
  6. Datapharm Communications Limited (2016) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/ [Accessed: 11/09/2020].
  7. Office for National Statistics (2021) population estimate England 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
Chronic hepatitis C: elbasvir–grazoprevir, glecaprevir–pibrentasvir, ledipasvir–sofosbuvir, ombitasvir–paritaprevir–ritonavir, sofosbuvir, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir
  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.

 

 

Point estimate

Reference

England population (aged 18+)

44,263,393

(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 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 177,054.

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.

 

Point estimate

Reference

Prevalent population (NICE, 2014)

177,054

(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:

 

Unique people (annual)

Unique people (monthly)

NICE (2014)

15,935

1,328

PHE (2019)

8,010

668

 

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.

 

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who will receive treatment

11,973

 8,010

 15,935

(-)

 

5. Volume of treatment

The upper and lower bound and the point estimate calculated in step 4 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.

Actual Daily Doses (ADD) were used to measure uptake. For these medicines, the calculated ADD is:

  • 1 tablet of elbasvir-grazoprevir or ledipasvir-sofosbuvir or sofosbuvir or sofosbuvir-velpatasvir, or
  • 3 tablets of glecaprevir-pibrentasvir, or
  • 2 tablets of ombitasvir-paritaprevir-ritonavir, or
  • 1 tablet of sofosbuvir–velpatasvir–voxilaprevir.

 

 

Point estimate

Lower range

Upper range

Estimated usage ADD

 893,550

 448,560

 1,338,540

 

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 395

 198

 592

(6)

 

References

  1. Office for National Statistics (2020) Annual Mid-year Population Estimates, 2019. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland
  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: http://www.medicines.org.uk/emc/, [Accessed: 16/06/2021].
  6. Office for National Statistics (2021) population estimate England 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
Cystic fibrosis: ivacaftor, ivacaftor–tezacaftor–elexacaftor, lumacaftor–ivacaftor and tezacaftor–ivacaftor

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.

 

Point estimate

Reference

England population (all ages)

56,552,138

(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. 

 

Point estimate

Reference

Prevalent population

10,070

(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. 

 

12+

6-11

2-5

0-2

Total

Total licensed population

5,317

842

600

72

6,831

 

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

Total licensed population

6,831

7,151

7,720

7,720

 

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 1:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who will receive treatment (year 1)

5,533

 5,486

 5,596

(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 ADDs.

For these medicines, the calculated ADD is:

  • two 150mg tablets of ivacaftor, or
  • 2 sachets of ivacaftor granules (50mg or 75mg sachets), or
  • one tablet of ivacaftor–tezacaftor–elexacaftor (75mg or 50mg or 100mg)
  • 4 lumacaftor–ivacaftor tablets (100mg/125mg or 200mg/125mg tablets), or
  • 2 sachets of lumacaftor–ivacaftor granules (100mg/125mg or 150mg/188mg sachets), or
  • one 100mg/150mg tablet of tezacaftor–ivacaftor.

 

 

Point estimate

Lower range

Upper range

Annual volume (ADD) 365 days

2,019,545

2,002,390

2,042,540

Annual volume (ADD) 366 days

2,025,078

2,007,876

2,048,136

 

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 893

 885

 903

(1)

 

References

  1. Office for National Statistics (2021) population estimate England 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
  2. UK Cystic Fibrosis Registry. Available from: https://www.cysticfibrosis.org.uk/
  3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from http://statpages.org/confint.html
EGFR Non-small-cell lung cancer: afatinib, dacomitinib, erlotinib, gefitinib and osimertinib

The following aims to estimate the expected first line use of the NICE positively appraised medicines afatinib, dacomitinib, erlotinib, gefitinib and osimertinib in people with epidermal growth factor receptor (EGFR) positive advanced non-small-cell lung cancer (NSCLC) and second line use in people who are T790 mutation positive.

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 Office for National Statistics (2020), 2018 Cancer Registration Statistics for England.

 

Point estimate

Reference

Newly diagnosed lung cancers (C34 Malignant neoplasm of bronchus and lung)

39,260

(1)

 

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 National Lung Cancer Audit information sheet (2020) to be 88.2%. This proportion has been used to inform the point estimate calculated in step 1.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with non-small-cell lung cancer in England

34,627

 

 

(2)

 

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 information sheet to be 57%. This proportion has been applied to the point estimate calculated in step 2.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people presenting with stage IIIb or stage IV NSCLC

19,737

 

 

(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 prevalence (95% CI 91,613 to 92,375) has been calculated using the exact binomial method (Pezzullo 2009).

The prevalence and confidence interval has been applied to stage IIIb and stage IV, population calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people successfully assessed for EGFR.

 18,158

 18,082

 18,232

(3,4,5)

 

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 are 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.

17,740

17,624

17,851

(3,4)

 

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 prevalence (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 4b.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people expected to have a positive EGFR mutation status

 1,774

 1,685

 1,866

(3,4)

 

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.

The reported proportion has been applied to the upper and lower range and the point estimate who tested EGFR mutation positive calculated in step 6.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who receive afatinib, dacomitinib, erlotinib, gefitinib or osimertinib

 1,331

 1,264

 1,400

(3)

 

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

The RIA for TA654 (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 2016) and will then be eligible for osimertinib. These proportions (80% and 65%) have been applied as a scaling factor to the point estimate and the lower and upper range summed in step 7.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who progress following first line treatment

 692

 657

 728

(6,7)

 

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 to the upper and lower range calculated in step 7.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who harbour T790M mutation at progression and eligible for osimertinib

 381

 329

 437

(7,8)

 

10. 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 added to the treatment population for second line osimertinib, step 9.

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib

 1,712

 1,677

 1,746

(-)

 

11. Calculate estimated usage volume – first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib

For these medicines, the calculated ADD is 1 tablet of afatinib, dacomitinib, erlotinib (excluding erlotinib 100 mg tablets), gefitinib or osimertinib. The estimated treatment population has been used to calculate an expected annual volume of medicine per year in ADDs.

11a. 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 that treatment will be for 12 months and usage will be spread evenly. 

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population first line afatinib, erlotinib, gefitinib

 799

 758

 840

(-)

Estimated median progression-free survival (days)

                             365

                             365

                             365

(6,9)

Total estimated annual usage (ADDs)

 291,489

 276,816

 306,600

 

 

11b. 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 and usage will be spread evenly. 

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population dacomitinib

 266

 253

 280

(-)

Estimated median progression-free survival (days)

                             365

                             365

                             365

(6,9)

Total estimated annual usage (ADDs)

 97,163

 92,272

 102,200

 

 

11c. Calculate estimated usage volume – first and second line osimertinib

The total estimated treatment population for first line osimertinib has been taken from step 7. It has been assumed that treatment will be for 21 months (639 days) and usage will be spread evenly.  Second line osimertinib is taken from step 9.

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population first or second line osimertinib

 647

 582

 717

(-)

Estimated median progression-free survival (days)

 639

 639

 639

(6,9)

Total estimated annual usage (ADDs)

 413,561

 371,770

 458,163

 

 

11d. 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 11a, 11b and 11c.

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population first line afatinib, dacomitinib, erlotinib, gefitinib and first or second line osimertinib

 802,213

 740,858

 866,963

(-)

 

12. Estimated usage by quarter per 100,000 population

Estimated annual ADD usage calculated in step 11d, 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 11d.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 355

 328

 383

(10)

 

References

  1. Office for National Statistics (2020) Cancer Registration Statistics, England: 2018. ONS: Newport. Available from: https://www.gov.uk/government/statistics/cancer-registration-statistics-england-2018-final-release  [Accessed: 03/11/2021]
  2. National Cancer Registration and Analysis Service (2020). Royal College of Physicians. National lung cancer audit 2020 (for the audit period 2018). London: RCP, 2020. Available from https://www.hqip.org.uk/resource/national-lung-cancer-audit-annual-report-for-the-audit-period-2018/#.YBADg-j7SUk  [Accessed 21/01/2021]
  3. 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]
  4. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from http://statpages.org/confint.html [Accessed 09/11/2021].
  5. 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]
  6. 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]
  7. TA416 (NICE 2016). Manufacturers submission (AstraZeneca 2016) Available from https://www.nice.org.uk/guidance/ta416/evidence [Accessed 29/01/2018]
  8. 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
  9. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 10/11/2021]
  10. Office for National Statistics (2021) population estimate England 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
Metastatic castration-resistant prostate cancer: abiraterone, apalutamide, cabazitaxel and enzalutamide

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 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 2020 was 27,982,818. Public Health England’s ‘cancer prevalence in England 2018’, reported the prevalence of prostate cancer in males to be 1.43%.

A prevalence of 1.43% has been applied to the male population to give the estimated number of people with prostate cancer in England.

 

 

Point estimate

Reference

Estimated prevalence of prostate cancer, in England

400,154

 

(1,2)

 

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):

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people diagnosed with metastatic prostate cancer in England

20,968

20,642

21,272

(3,4)

 

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.

 

Point estimate

Lower range

Upper range

Reference

3a. Hormone-sensitive metastatic prostate cancer

 7,108

 6,998

 7,211

(3,4)

3b. Hormone-relapsed metastatic prostate cancer

 13,860

 13,644

 14,061

(3,4)

 

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who have hormone-sensitive metastatic prostate cancer that are expected to receive treatment with apalutamide or  enzalutamide

1,599

1,050

2,163

(5)

 

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number that receive treatment with abiraterone or enzalutamide

6,874

6,768

6,974

(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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number that receive cabazitaxel after chemotherapy

397

391

403

(7)

 

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number that receive abiraterone, cabazitaxel or enzalutamide after chemotherapy

1,144

1,126

1,160

(7)

 

8. Calculate estimated usage volume

For these medicines, the calculated ADD is:

  • four 250mg tablets or two 500mg tablets of abiraterone, or
  • 2.857mg of cabazitaxel, or
  • four 40mg tablets of enzalutamide, or
  • 240mg of apalutamide

The number of people who have hormone-relapsed or hormonse 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 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.

 

Point estimate

Lower range

Upper range

Sum treatment population abiraterone, apalutamide & enzalutamide (step 4, step 5 and step 7).

9,617

8,944

10,297

Estimated treatment population cabazitaxel (step 6)

397

391

403

Estimated annual usage apalutamide, abiraterone & enzalutamide (treatment population x 365 days x 1 ADD)

3,510,205

3,264,560

3,758,405

Estimated annual usage cabazitaxel (treatment population x 210 days x 1 ADD)

83,370

82,110

84,630

Total estimated annual usage 365 days (ADDs)

3,593,575

3,346,670

3,843,035

 

9. Estimated usage by quarter per 100,000 population

Estimated annual 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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 1,589

 1,479

 1,699

(10)

 

References

  1. Office for National Statistics (2020) Cancer Registration Statistics, England: 2018. ONS: Newport. Available from: https://www.gov.uk/government/statistics/cancer-registration-statistics-england-2018-final-release [Accessed: 03/11/2021]
  2. The National Cancer Registration and Analysis Service. Public Health England’s cancer prevalence in England 2018. Available from https://www.cancerdata.nhs.uk/ [Accessed 04/11/2021]
  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 http://statpages.org/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: http://www.medicines.org.uk/emc/, [Accessed: 07/12/2021]

Office for National Statistics (2021) population estimate England 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]

Primary hypercholesterolaemia and mixed dyslipidaemia: alirocumab and evolocumab or inclisiran

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.

 

Point estimate

Reference

England population aged 18 years and over

44,456,850

(1,2)

 

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 a database analysis covering 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.

 

Point estimate

Reference

primary non-familial hypercholesterolaemia or mixed dyslipidaemia

10,714,101

(3)

 

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 1 to create an upper and lower estimate.

 This proportion has been applied to the adult population stated in step 2.

 

Point estimate

Lower Estimate

Higher estimate

Reference

Estimated number of people received or receiving lipid lowering therapy

9,642,691

9,106,986

10,178,396

(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.

 

Point estimate

Lower Estimate

Higher estimate

Reference

Estimated eligible population

1,533,187

1,448,011

1,618,365

(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 above 4mmol/L 3.1%. 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.

 

Point estimate

Lower Estimate

Higher estimate

Reference

5a. Estimated number of people with low-density lipoprotein cholesterol concentrations between 2.5mmol/L and 3.495mmol/L

 329,635

 311,322

 347,948

(5)

5b. Estimated number of people with low-density lipoprotein cholesterol concentrations between 3.5mmol/L and 3.995mmol/L

 50,595

 47,784

 53,406

(5)

5c. Estimated number of people with low-density lipoprotein cholesterol concentrations are above 4 mmol/L

 47,529

 44,888

 50,169

(5)

5d. Summed total low-density lipoprotein cholesterol concentrations are persistently above 2.6mmol/L

 427,759

 403,994

 451,523

(sum of 5a, 5b, 5c)

5e. Summed total low-density lipoprotein cholesterol concentrations are persistently above 3.5mmol/L

 98,124

 92,672

 103,575

(sum of 5b, 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 1 trajectory has been here 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/ calculated in step 5e, for the point estimate and the upper and lower range.

 

Point estimate

Lower Estimate

Higher estimate

Reference

6a. Estimated treatment population inclisiran

 39,782

 37,572

 41,992

(6)

6b. Estimated treatment population alirocumab and evolocumab

 37,581

 35,493

 39,669

(6)

6c. Total treatment population

 77,363

 73,065

 81,661

 

 

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 ADDs.

For these medicines, the calculated ADD is:

  • 10.714mg of alirocumab 150mg solution, or
  • 5.357mg of alirocumab 75mg solution, or
  • 10mg of evolocumab 140mg solution or
  • 1.56mg of Inclisiran

 

Point estimate

Lower range

Upper range

Number of people estimated to receive treatment with alirocumab or evolocumab or inclisiran

77,363

73,065

81,661

Total estimated annual usage (ADDs) 365 days

28,237,524

26,668,659

29,806,215

Total estimated annual usage (ADDs) 366 days

28,314,887

26,741,723

29,887,876

 

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 12,483

 11,789

 13,176

(1)

 

References

  1. Office for National Statistics (2021) Annual Mid-year Population Estimates, 2020 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland  [Accessed: 01/11//2021].
  2. Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: http://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
Secondary hyperparathyroidism: etelcalcetide

1. Population in England

Etelcalcetide is recommended for use in adults only.

 

Point estimate

Reference

England population (18 years or over)

44,456,850

 

(1)

 

2. Proportion of adults having dialysis

In their 2017 annual report, the UK Renal Registry reported that, in 2016, 24,663 people in England were having dialysis. Based on the mid-year population estimate for England in that year (43,482,790), this was 56.7 per 100,000 of the adult population. This proportion has been applied to the population identified in step 1 and 95% confidence intervals were calculated (56.0 to 57.4 per 100,000) using the exact binomial method (Pezzullo 2009).

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults having dialysis

25,207

24,896

25,518

(3,4)

 

3. Proportion of adults having haemodialysis

The UK Renal Registry reported that 21,560 (87.4%) of those dialysis patients were on haemodialysis. This proportion has been applied to the dialysis population calculated in step 2 and 95% confidence intervals were calculated (87.0 to 87.8%) using the exact binomial method.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults having haemodialysis

 22,031

 21,660

 22,405

(3,4)

 

4. Excluding adults on home haemodialysis

Unlike most other treatments for secondary hyperparathyroidism, etelcalcetide is administered either during dialysis into the venous line at the end of treatment during rinse-back, or intravenously immediately after. This method of administration will be less suitable for those on home haemodialysis as they would need to visit the dialysis centre for administration of etelcalcetide 3 times a week, defeating the benefit of home haemodialysis.

The UK Renal Registry reported that, in 2016, 4.4% of all dialysis patients were on home haemodialysis. This proportion has been applied to the dialysis population reported in step 2 and then deducted from the haemodialysis population calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults having home haemodialysis

1,109

1,095

1,123

(4)

Estimated number of adults having haemodialysis excluding those on home haemodialysis

 20,922

 20,565

 21,282

Calculated

 

5. Proportion of adults with secondary hyperparathyroidism and uncontrolled parathyroid hormone levels

Treatment with a calcimimetic is commenced after patients have tried standard therapy (dietary control, phosphate binders and vitamin D analogues) and failed to attain either a satisfactory reduction in parathyroid hormone levels or to reach target levels, which current guidance recommends should be in the range of 2 to 9 times the upper limit of normal for patients with CKD G3a to G5.

At this stage, parathyroidectomy is an option – however, it is expected that most patients and their clinicians would prefer to opt for a minimally invasive pharmacological-therapy, before resorting to an invasive surgical procedure with its associated risks. Therefore, the number of patients having parathyroidectomy at this stage is likely to be negligible and not considered in this estimate.

The technology appraisal for cinacalcet recommends that treatment should only be initiated in patients with ‘very uncontrolled’ parathyroid hormone levels, defined as greater than 800pg/ml. However, it is expected that some clinicians may consider treatment with a calcimimetic when levels exceed the target upper limit of 9 times the upper limit of normal for patients with CKD G3a to G5, despite standard treatment. This translates approximately to 585 to 677pg/ml. Therefore, a literature search was undertaken to identify the number of dialysis patients who are reported to have parathyroid levels above 800pg/ml to inform the lower range and the number of patients with levels above 9 times the upper limit of normal to inform the upper range of patients who have uncontrolled hyperparathyroidism and are likely to receive treatment with cinacalcet.

As part of the COSMOS study, which surveyed European haemodialysis centres (including the UK), Fernandez-Martin et al. reported that 7.4% of haemodialysis patients had a parathyroid hormone level greater than 800pg/ml. This proportion has been applied to the population calculated in step 4 and used to estimate the lower limit.

The UK Renal Registry states that 18.5% of haemodialysis patients have a parathyroid hormone level above 677pg/ml (9 times the upper limit of normal). This proportion has been applied to the population calculated in step 4 and used to estimate the upper limit.

The point estimate is taken as the mean of the lower and upper proportions (13.0%).

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults with secondary hyperparathyroidism and uncontrolled parathyroid hormone levels

2,720

1,522

3,937

(4, 5)

 

6. Proportion of adults with an adjusted calcium level at or above the lower limit of normal

The SmPC for both etelcalcetide and cinacalcet advise that corrected serum calcium should be at or above the lower limit of the normal range prior to administration of first dose, a dose increase, or reinitiation after a dose stop.

The proportion of patients with an adjusted serum calcium greater than 2.2mmol/L, as reported by the UK Renal Registry (88.3%), was used to calculate the proportion of those patients estimated in step 5, who would be appropriate for initiating treatment with a calcimimetic.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults with Ca >2.2mmol/L

2,402

1,344

3,476

(3)

 

7. Proportion of adults for whom cinacalcet is not suitable

NICE recommends that etelcalcetide should only be used if a calcimimetic is indicated but cinacalcet is not suitable. It is expected that most patients will be considered for etelcalcetide if they cannot tolerate cinacalcet, their condition does not respond to it, or they are unlikely to adhere to the regimen. While other reasons for not being suitable for cinacalcet are possible (such as administration difficulties or absorption disorders), these are thought to be a small proportion and have not been considered in this estimate.

7a. Proportion of adults who do not tolerate cinacalcet

Withdrawals due to adverse events in published trial data were used to estimate the proportion of patients that may not tolerate cinacalcet and discontinue treatment. A literature search was undertaken to identify clinical trials which included a European or English population, which evaluated cinacalcet in patients on dialysis. Six studies were identified, and they reported a range of withdrawals due to adverse events from 4.0% to 18.1%. These figures have been used to estimate the range of proportions of people who may discontinue cinacalcet due to tolerability and a point estimate calculated from the mean of all values reported in all six papers (11.5%).

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults who do not tolerate cinacalcet

276

54

629

(6, 7, 8, 9, 10, 11)

 

7b. Proportion of adults whose condition does not respond to cinacalcet

NICE recommends that treatment with cinacalcet should only be continued if a reduction in parathyroid hormones of 30% is achieved. This was the measure used to estimate the proportion of patients whose condition does not respond to cinacalcet in this estimate. Using the same criteria as above, two trials were identified which reported this measure as an outcome, and they reported that 63 and 64% of patients achieved a 30% reduction in parathyroid hormone levels. This is translated into 37 and 36% of patients whose condition does not respond to cinacalcet and has been used to calculate an upper and lower range. The mean has been calculated as the point estimate (36.5%).

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults whose condition does not respond to cinacalcet

877

484

1,286

(6,7)

 

7c. Proportion of adults who do not adhere to cinacalcet

People with CKD are usually taking many oral medicines and non-adherence is acknowledged to be a concern in this population. In the EVOLVE trial, it was reported that 3.5% of people taking cinacalcet discontinued the trial due to ‘non-compliance’. Whilst adherence in a clinical trial is likely to be higher than in real-life, given the lack of data in the real-world setting, this proportion has been used to estimate the proportion of people who may not adhere to cinacalcet. This is likely to be an underestimation.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults who do not adhere to cinacalcet

84

47

122

(8)

 

8. Estimated treatment population

Adding together the number of people who do not tolerate cinacalcet (step 7a), those whose condition does not respond (step 7b) and those who do not adhere to the regimen (step 7c) gives the number of people who are eligible for treatment with etelcalcetide. Parathyroidectomy is an option at this stage; however, the numbers of patients opting for parathyroidectomy rather than a less-invasive pharmacological therapy is thought to be negligible. It has therefore been assumed that, once accounting for those in whom cinacalcet is not suitable, most patients will be prescribed etelcalcetide. Therefore, all those eligible to receive etelcalcetide are included in the estimated treatment population.

 

Point estimate

Lower range

Upper range

Estimated treatment population

1,237

585

2,037

 

9. Calculate estimated usage volume

The number of people estimated to receive etelcalcetide (calculated in step 8) has been multiplied by the number of days in a year to give the annual usage in DDDs.

The DDD for etelcalcetide is reported as 2.1mg (WHO 2017).

 

Point estimate

Lower range

Upper range

Estimated number of people treated with etelcalcetide

1,237

585

2,037

Total estimated annual usage 365 days (DDDs)

451,505

213,525

743,505

Total estimated annual usage 366 days (DDDs)

452,742

214,110

745,542

 

10. Estimated usage by quarter per 100,000 population

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 200

 94

 329

(1)

 

References

  1. Office for National Statistics (2021) Annual Mid-year Population Estimates, 2021 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
  2. Office for National Statistics (2017) Annual Mid-year Population Estimates 2016. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed 06/11/2018]
  3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from http://statpages.org/confint.html [Accessed 17/06/2016].
  4. Byrne C, Caskey F, Castledine C et al. (2018) UK Renal Registry 20th Annual Report of the Renal Association. Nephron 2018;137: Suppl.1
  5. Fernandez-Martin JL, Carrero JJ, Benedik M et al. (2013) COSMOS: the dialysis scenario of CKD-MBD in Europe. Nephrology Dialysis Transplantation 28: 1922- 1935
  6. Block GA, Martin KJ, de Francisco ALM et al. (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. New England Journal of Medicine 350: 1516-1525
  7. Urena-Torres P, Bridges I, Christiano C et al. (2013) Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism. Nephrology Dialysis Transplantation 28: 1241 - 1254
  8. The EVOLVE Trial Investigators (2012) Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. New England Journal of Medicine 367: 2482 - 2492
  9. Ketteler M, Martin KJ, Wolf M et al (2012) Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study. Nephrology Dialysis Transplantation 27: 3270 - 3278
  10. Messa P, Macario F, Yaqoob M et al (2008) The OPTIMA Study: Assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clinical Journal of the American Society of Nephrology 3: 36 – 45
  11. Raggi P, Chertow GM, Urena-Torres P et al (2011) The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on haemodialysis. Nephrology Dialysis Transplantation 26: 1327 – 1339
  12. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: http://www.whocc.no/atc_ddd_index/, [Accessed: 10 May 18]
  13. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 10 May 18]
Severe asthma: benralizumab, mepolizumab, omalizumab and reslizumab

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.

 1. Population aged 6 years or older

 

 

Point estimate

Reference

England population (aged 6 years and older)

52,621,501

(1)

 

2. Prevalence of asthma

The Quality and Outcomes Framework (QOF) reported the number of people on the asthma register (NHS Digital 2020) as 3,916,150. 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:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with asthma in England

 3,940,510

 3,857,156

 4,025,545

(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:

 

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with asthma and blood eosinophil count of 300 cells per microlitre or more

 561,129

 549,259

 573,238

(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 and 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:

 

 

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.

 

 42,085

 41,194

 42,993

(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:

 

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with asthma and blood eosinophil count of 400 cells per microlitre or more

 327,062

 320,144

 334,120

(4)

 

6. Proportion of people with asthma and a blood eosinophil count of 400 cells per microlitre or more and 3 exacerbations in the last 12 months

NICE (2019) reports 3.7% of people with blood eosinophil count of 400 cells per microlitre or more and 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:

 

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 exacerbations in the last 12 months.

 

 12,101

 11,845

 12,362

(4)

 

7. Total eligible population for benralizumab, mepolizumab and reslizumab

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

 

 

Point estimate

Lower range

Upper range

Reference

Total eligible population for benralizumab, mepolizumab and reslizumab.

 

 54,186

 53,039

 55,355

(-)

 

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.

 

 

Point estimate

Lower range

Upper range

Reference

Adjustment for overlap.

 

 47,413

 46,409

 48,436

(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:

 

Point estimate

Lower range

Upper range

Reference

People treated with mepolizumab

 4,978

 2,785

 7,265

(4,5,6)

People treated with reslizumab

 2,608

 464

 4,844

 

People treated with benralizumab

 1,897

 1,856

 1,937

 

Total treatment population for benralizumab, mepolizumab and reslizumab

 9,483

 5,105

 14,046

(-)

 

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:

 

 

Point estimate

Lower range

Upper range

Reference

Treatment population for benralizumab, mepolizumab and reslizumab following adjustment for discontinuation

 

 8,364

 4,503

 12,389

(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):

 

 

Point estimate

Lower range

Upper range

Reference

Number of people with severe asthma

 

 

 169,442

 165,858

 173,098

(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:

 

 

Point estimate

Lower range

Upper range

Reference

Number of people eligible for omalizumab

 51,849

 44,948

 59,200

(9)

 

13. Overlap between 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 8) and the eligible population omalizumab (step 12) have each been reduced by 12.5% to adjust for this overlap.

 

 

Point estimate

Lower range

Upper range

Reference

Adjustment for overlap.

 

 45,368

 39,330

 51,800

(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:

 

 

Point estimate

Lower range

Upper range

Reference

Number of people receiving treatment

 

 2,074

 1,798

 2,368

(10)

 

15. Treatment population for reslizumab, benralizumab, omalizumab and mepolizumab

The treatment population for benralizumab, mepolizumab, omalizumab and reslizumab has been summed from steps 10 and 14:

 

 

Point estimate

Lower range

Upper range

Total estimated treatment population

10,438

6,301

14,757

 

16. Calculate estimated usage volume

The number of people estimated to receive reslizumab, benralizumab, omalizumab or mepolizumab (calculated in step 15) has been multiplied by the number of days in a year to give the annual usage in ADDs.

 

For these medicines, the calculated ADD is:

  • 0.536mg of benralizumab, or
  • 3.571mg of mepolizumab, or
  • 16mg of omalizumab, or
  • 7.143mg of reslizumab.

 

 

Point estimate

Lower range

Upper range

Total estimated annual usage (ADDs) 365 days

3,809,870

2,299,865

5,386,305

Total estimated annual usage (ADDs) 366 days

3,820,308

2,306,166

5,401,062

 

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 1,684

 1,017

 2,381

(1)

 

References

  1. Office for National Statistics (2021) Annual Mid-year Population Estimates 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
  2. Quality and outcomes framework 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/2019-20  (Accessed 11/09/2020)
  3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from http://statpages.org/confint.html
  4. NICE (2019) Resource impact assessment template for benralizumab TA565 (2019). Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta565 . [Accessed: 23/10/2019].
  5. NICE (2017) Resource impact assessment template for Mepolizumab TA431 (2017). Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta431 . [Accessed: 23/10/2019].
  6. NICE (2017) Resource impact assessment template for reslizumabTA479. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta479 . [Accessed: 23/10/2019].
  7. NICE (2019) committee papers for TA565. 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.asthma.org.uk/418cbc36/globalassets/campaigns/publications/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: 7/01/2021).
  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: http://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
Smoking cessation: varenicline

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 Summary of Product Characteristics (SmPC) states varenicline is indicated for an adult population only. Therefore, the starting population is people aged 18 and over in England.

 

 

Point estimate

Reference

England population aged 18 and over

44,456,850

(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. 

 

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.

 

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.

 

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 to receive 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.

 

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 has been applied to point estimate and upper and lower range of those offered pharmacotherapy for smoking cessation in step 5.

 

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.

 

Actual Daily Doses (ADD) were used to measure uptake. For this medicine, the calculated ADD is:

  • 2 tablets (0.5mg or 1mg tablets), or
  • 1.796 tablets from the 2-week treatment initiation pack, or
  • 1.893 tablets from the 4-week treatment initiation pack.

 

 

Point estimate

Lower range

Upper range

Treatment volume 365 days (ADD)

58,293,420

53,749,900

62,836,940

Treatment volume 365 days (ADD)

 58,453,128

 53,897,160

 63,009,096

 

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.

 

Point estimate

Lower range

Upper range

Reference

ADD per 100,000 population England

 25,770

 23,761

 27,778

(1)

 

References

  1. Office for National Statistics (2021) Annual Mid-year Population Estimates 2021. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates [Accessed: 01/03/2022]
  1. A count of distinct patients, from a SUS+ data extract 20190/20 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)
  1. British Thoracic Society National Smoking Cessation Audit Report 2019, British Thoracic Society Reports, Vol 11, Issue 2, 2020 (June 2020)
  1. ‘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)
  2. Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 26/01/2021].


Last edited: 28 April 2022 9:31 am