NICE Technology Appraisals in the NHS in England (Innovation Scorecard) To June 2021

• Cancer
• Cardiovascular conditions
• Chronic kidney disease
• Genetic disorder
• Infections
• Lifestyle
• Respiratory conditions

• 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

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).

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

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.

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).

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.

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.

Transient attacks of cerebral ischaemia.

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.

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 in adolescents aged 12 to <18 years.

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 above.

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:

N/A

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 above.

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.

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

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

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.

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.

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.

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

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.

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 (see section 2.3 for details).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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:

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.

4. People with PE/DVT (VTE) provoked and unprovoked incidence

The incidence (and 95% confidence intervals) of provoked and unprovoked VTE for the whole population have been reported by Martinez (2013) as 131.5 per 100,000 person years (95% CI 130.2 to 132.9).

These proportions have been applied to the population identified in step 1.

5. People with PE/DVT (VTE) and cancer

The estimated incidence of provoked and unprovoked VTE with active cancer is reported by Martinez (2013) as: 18.6%. The inverse of this figure has been used to calculate the proportion of people with VTE who are not known to have cancer.

These figures have been applied to the estimate and upper and lower range calculated in step 4.

6. People with recurrent PE/DVT (VTE)

Martinez calculated 58.1% of people will have unprovoked VTE. This has been used as a proxy for the proportion of the VTE population that should receive long term anti-coagulant treatment.

These figures have been applied to the estimate and upper and lower range calculated in step 4.

7. Treatment duration

The duration of treatment is taken from the British National Formulary (2020). The treatment duration applied here is 3 months for incident VTE, 6 months for incident VTE with cancer, and lifelong for both AF and recurrent VTE.

These treatment durations have been used to estimate the number of people who will receive treatment in a year. For example, if treatment duration is 6 months, the eligible population has been multiplied by 0.5. Where the treatment duration is 3 months, the treatment population has been multiplied by 0.25. 

These figures have been applied to the estimate and upper and lower range calculated in steps 3, 5 and 6.

8. Estimated population in England with atrial fibrillation, pulmonary embolism or deep vein thrombosis expected to receive one of apixaban, dabigatran, edoxaban, rivaroxaban and warfarin

These figures calculated in step 7 are summed below:

9. 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.

 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].

1. Population who meet SmPC

The Summaries of Product Characteristics (SmPC) for elbasvir–grazoprevir, glecaprevir–pibrentasvir, ledipasvir–sofosbuvir, ombitasvir–paritaprevir–ritonavir, sofosbuvir, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir show they are mostly indicated for an adult population, although some are indicated for people aged 3 years and older. As most patients are likely to be over 18 years the starting population is for this age.

2. Prevalence of chronic hepatitis C

In the resource tool costing template for ombitasvir–paritaprevir–ritonavir (TA365), NICE assume a prevalence rate of 0.4% of the population in England aged 18 and over.

As the population size at the time (ONS mid-year 2014 estimate) was 41,766,418, this gave a prevalent population of 167,066. If the prevalence rate remained the same, given the population increase for the age group, the prevalent population for chronic hepatitis C would now be 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.

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 rate of 9%, based on a company submission by Abbvie. This estimate has been applied to the prevalent populations in step 2:

4. Number of people to receive treatment

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

5. Volume of treatment

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

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].

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, people aged 15 and younger and 16 to 40, people of all ages can have the condition. Therefore, we have used the England population for all ages as the starting point for this estimate.

2. Prevalence of cystic fibrosis

The UK cystic fibrosis registry has collected prevalence data since 2009.

The prevalence of cystic fibrosis is 0.018% across all age groups and 0.031% in the those 40 years and younger. The 0.018% prevalence rate has been added to the total of step 1. 

3. Number of people eligible to be treated

NHS England and NHS Improvement (NHSEI) applied for bespoke data from the UK cystic fibrosis registry for people in England by genotype. The licensed population is 68% of the prevalent population as shown below. 

Modelling by NHSEI of the licensed population suggests a rise in the number of people eligible for treatment in the next 4 years. The profile beyond this point will be subject to demographic changes.

4. Number of people to receive treatment

Clinical judgement suggests that the compliance/tolerance rate of the interventions may mean that the number of people receiving a course of treatment at any one time is approximately 81%. The 95% confidence interval around this estimated proportion has been calculated using the exact binomial method (Pezzullo, 2009).

The proportion receiving treatment and the confidence interval has been applied to the licenced population in year 1:

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.

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. 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

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

Where these medicines have a licenced indication not positively appraised by NICE, usage has not been estimated. While this usage is expected to be small it may result in a lower expected usage when compared to observed usage.

1. Incidence of lung cancer

The SmPC states that these medicines are indicated in an adult population only.

Estimated incidence of lung cancer in adults aged 20 years or older was reported by the Office for National Statistics (2019), 2017 Cancer Registration Statistics for England.

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

The proportion of new cases of lung cancer that are non-small-cell lung cancer (NSCLC) is reported in the national lung cancer audit (2020) information sheet to be 88.2%. This proportion has been used to inform the upper and lower range and applied to the point estimate calculated in step 1.

3. Proportion of people presenting with stage IIIb (advanced) and stage IV (metastatic) NSCLC

The proportion of new cases of NSCLC that are diagnosed stage IIIb (advanced) or stage IV (metastatic) is reported in the national lung cancer audit information sheet to be 57%. This figure has been used to inform the upper and lower range. This proportion has been applied to the point estimate calculated in step 2.

4. Estimated proportion with stage IIIb/IV and PS 0–1 who receive systemic anticancer treatment

The proportion of people with good performance status (PS 0-1) and advanced or metastatic NSCLC who receive systemic anticancer treatment (SACT) in England is reported in the national lung cancer audit report (2020) to be 66%. This proportion has been used to inform the upper and lower range and applied to the point estimate calculated in step 3.

5. Proportion of people with sufficient and insufficient sample for genotyping

The final appraisal determination produced for TA374 (NICE 2015) states that, to successfully test for EGFR mutation status, an adequate tissue sample and sufficient quality DNA is required. Zer (2014) estimated that between 15% and 35% of patients may not have sufficient samples for genotyping.

To calculate the proportion of people with sufficient samples for genotyping the inverse of these proportions has been applied. The midpoint (75%) has been applied to the point estimate and the proportions (65% and 85%) applied to the upper and lower range calculated in step 4.

6. Proportion of people who test positive for EGFR mutation

The proportion who test EGFR mutation positive was reported in Li et al (2013). Li reported that between 10% and 20% of people defined by the authors as ‘white’ had tumours that were EGFR mutation positive.

The reported proportions have been applied to the upper and lower range and the midpoint (15%) applied to the point estimate for people with sufficient samples for genotyping calculated in step 5.

7. Proportion of people who receive first line afatinib, erlotinib or gefitinib

It is expected that all the population in step 6 who test EGFR mutation positive will receive first line treatment with the tyrosine kinase inhibitors (TKIs) afatinib, erlotinib or gefitinib.

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

The proportion of people who have disease progression after first-line treatment with afatinib, erlotinib or gefitinib is stated in the manufacturer’s submission for osimertinib TA416 (AstraZeneca 2016) to be 65% of the incident population. This proportion has been applied as a scaling factor to the point estimate and the lower and upper range summed in step 7.

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

Based on genomic analysis, progression on a first-line EGFR TKI is characterised by an acquired secondary EGFR kinase domain mutation labelled T790M, causing resistance to the first-line EGFR TKI. The proportion of people who harbour T790M mutation at progression is reported in Mazza (2017) to be between 50% and 60%. The midpoint (55%) has been applied to the point estimate and the proportions (50% and 60%) applied to the upper and lower range calculated in step 8.

10. Proportion of people who receive osimertinib (previously treated EGFR-population)

It is assumed that all the people who harbour T790M mutation at progression (step 9) will receive osimertinib.

11. Number of people with insufficient sample for genotyping (unidentified EGFR status)

The final appraisal determination produced for TA374 (NICE 2015) states that, to successfully test for EGFR mutation status, an adequate tissue sample and sufficient quality DNA is required. Zer (2014) estimated that between 15% and 35% of patients may not have sufficient samples for genotyping.

To calculate the proportion with inadequate tissue sample, the midpoint (25%) has been applied to the point estimate and the proportions (15% and 35%) applied to the upper and lower range calculated in step 4.

12. Proportion of people who will receive second line therapy (unidentified EGFR status)

The proportion of the population expected to receive any second line therapy was stated in Zer (2014) to be between 30% and 50% of the eligible population. These proportions have been used to inform the upper and lower range and a mid-point (40%) has been applied to the point estimate calculated in step 11.

The final appraisal determination produced for TA374 (NICE 2015) states that an element of clinical judgement is needed when treating these patients. Patients in whom the disease has progressed after non-targeted chemotherapy may have erlotinib if their patient characteristics suggest that their tumour may be mutation-positive (for example, people who have never smoked or are light smokers, women, people of Asian family origin and people with adenocarcinoma histology). The proportion that will be identified is uncertain and is not calculated here. In clinical practice this may reduce the expected treatment population.

13. Treatment population for afatinib, erlotinib, gefitinib and osimertinib

The total treatment population for first line afatinib, erlotinib or gefitinib has been taken from step 7. The treatment population for second line osimertinib has been taken from step 10. The treatment population for second line erlotinib has been taken from step 12.

14. Calculate estimated usage volume

For these medicines, the calculated ADD is 1 tablet of afatinib, erlotinib (excluding erlotinib 100 mg tablets), gefitinib or osimertinib. The estimated treatment population (calculated in step 13) has been multiplied by estimated median progression-free survival per year to produce an expected volume of medicine per year in ADDs.

14a. Calculate estimated usage volume – first line afatinib, erlotinib and gefitinib

The total estimated treatment population for first line afatinib, erlotinib and gefitinib has been taken from step 13. Scluier et al (2015) reported that across 6 RCTs assessing the TKIs afatinib, erlotinib and gefitinib, compared with chemotherapy in people with NSCLC with active EGFR mutations, median progression free survival ranged between 9.2 and 13.1 months. To develop this estimate, the midpoint between this range was calculated (11 months) and applied to estimate the median progression free survival per year (11 months x 365/12 = 335 days).

14b. Calculate estimated usage volume – subsequent osimertinib

The total estimated treatment population for subsequent osimertinib use has been taken from step 13. The committee for TA416 (NICE 2016) noted the pooled AURA dataset (AURA extension and AURA2) for people having osimertinib as second and later lines of treatment. It noted that the estimate of median progression-free survival from this analysis was 11.0 months (335 days).

14c. Calculate estimated usage volume – second line erlotinib

The total treatment population for second line erlotinib has been taken from step 13. Cappuzzo (2010) reported a multicentre, randomised, placebo-controlled phase 3 study on second line erlotinib. Progression free survival was reported as 12.3 weeks (86 days).

14d. Total estimated usage volume – afatinib, erlotinib, gefitinib and osimertinib

The total volume in daily doses for afatinib, erlotinib, gefitinib and osimertinib has been summed from steps 14a, 14b and 14c.

References

1. Office for National Statistics (2019) Cancer Registration Statistics, England: 2017. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancerregistrationstatisticscancerregistrationstatisticsengland [Accessed: 26/01/2021]
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. 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]
4. Zer A, Natasha B. Leigh l. Second-Line Therapy in Non–Small-Cell Lung Cancer: The DELTA Between Different Genotypes Widens. Journal of Clinical Oncology 32, no. 18 (June 2014) 1874-1881.
5. Li T, Kung H, Mack P et al. (2013). Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies. Journal of clinical oncology. Vol 31, number 8. March 2013.
6. TA416 (NICE 2016). Manufacturers submission (AstraZeneca 2016) Available from https://www.nice.org.uk/guidance/ta416/evidencehttps://www.nice.org.uk/guidance/ta416 [Accessed 29/01/2018]
7. Mazza V, Cappuzzo F. Treating EGFR mutation resistance in non-small cell lung cancer – role of osimertinib. The Application of Clinical Genetics. 2017; 10:49-56. doi:10.2147/TACG.S103471.
8. Scluier J, Berghmans T, Meert A (2015) Advances in target therapy in lung cancer. European respiratory review 24: 23-29. Journal of Clinical Oncology 32, no. 18 (June 2014) 1874-1881.
9. 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
10. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: http://www.whocc.no/atc_ddd_index/, [Accessed: 17/01/2018]
11. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 17/01/2018]

1. Population who meet SmPC

The SmPC states that abiraterone, cabazitaxel and enzalutamide are indicated for an adult male population only. Therefore, the starting population is adult male new registrations for prostate cancer diagnosis in England.

The Office for National Statistics (ONS) publishes new adult cancer registrations for England. This estimate uses the number of new registrations for diagnosis code ICD-10 C61, malignant neoplasm of prostate, in 2017 (ONS, 2019).

2. Prevalence of metastatic hormone-relapsed prostate cancer

It is estimated that between 11.2% (Morgan 2010) and 19.5% (Stevenson 2011) of people with prostate cancer have metastatic hormone-relapsed cancer. These estimates have been used to develop the upper and lower range. The midpoint of the two figures, 15.35%, has been applied to the point estimate.

The prevalence figure and reported range has been applied to the adult population with new prostate cancer in England:

3. Proportion of people who have metastatic hormone relapsed 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 patients with no or mild symptoms. Autio (2013) estimated that 75% of patients with metastatic hormone relapsed prostate cancer have no or mild symptoms and are therefore eligible for treatment with abiraterone or enzalutamide. Expert opinion suggests that 80% of these patients will receive treatment with abiraterone or enzalutamide. The reported proportion and estimated number to receive treatment have been applied to the point estimate and upper and lower range calculated in step 2.

4. 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 3.

5. Proportion of people who have metastatic hormone relapsed 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. Expert opinion suggests that for 55% of patients, first-line treatment with docetaxel chemotherapy 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 has been applied to the point estimate and upper and lower range calculated in step 4.

6. 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.

The number of people who have metastatic hormone relapsed prostate cancer likely to receive treatment with abiraterone or enzalutamide before treatment with docetaxel chemotherapy (calculated in step 3) has been multiplied by days in a year then multiplied by the ADD to produce an expected volume of medicine per year in ADDs.

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 4) 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.

It has not been possible to identify the proportional split of people who will receive treatment with abiraterone, cabazitaxel or enzalutamide after treatment with first-line docetaxel chemotherapy (calculated in step 5), 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.

References

1. Office for National Statistics (2019) Cancer Registration Statistics, England: 2017. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancerregistrationstatisticscancerregistrationstatisticsengland [Accessed: 26/01/2021]
2. Kirby M, Hirst C and Crawford E (2011) Characterising the castration-resistant prostate cancer population: a systematic review
3. Morgan C, McEwan P, Chamberlain G et al. (2010) Castration-resistant prostate cancer (CRPC): a UK epidemiology study
4. Stevenson M, Jones M, Kearns B et al. (2011) Cabazitaxel for the second line treatment of hormone refractory, metastatic prostate cancer: A Single Technology Appraisal.  ScHARR, the University of Sheffield
5. 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
6. NICE Adoption and Impact Programme Reference Panel (2016), clinical experts with an interest in metastatic castration-resistant prostate cancer.
7. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 16/02/2017].

1. Adult population England

The following estimates the population of adults with primary hypercholesterolaemia (familial and non-familial), or mixed dyslipidaemia who are eligible for treatment with a PCSK9 inhibitor (alirocumab or evolocumab).

The SmPC states that alirocumab and evolocumab 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. The starting population for this estimate is adults aged 20 years or older in England; this was because of the prevalence data available. Excluding those aged 18 to 19 may underestimate the eligible population.

2. People with LDL-C of 4 mmol/litre or over and at high risk of CVD

The number of people with primary non-familial hypercholesterolaemia or mixed dyslipidaemia has been estimated through CVD risk and LDL-C levels. The number of people at high CVD risk and with LDL-C of 4 mmol/litre or over was estimated in the manufacturer submission to NICE for alirocumab (Sanofi/ Regeneron 2016) to be 0.19% of the adult population. This proportion has been applied to the population identified in step 1.

3. People with LDL-C of 3.5 mmol/litre or over and a very high risk of CVD

The number of people with primary non-familial hypercholesterolaemia or mixed dyslipidaemia has been estimated through CVD risk and LDL-C levels. The number of people at very high risk of CVD with LDL-C of 3.5 mmol/litre or over was estimated in the manufacturer submission to NICE for alirocumab (Sanofi/ Regeneron 2016) to be 0.17% of the adult population. This proportion has been applied to the adult population stated in step 1.

4. Total at high risk or very high risk of CVD with specified LDL-C levels

The estimated number of people at high risk or very high risk of CVD with specified LDL-C levels from steps 2 and 3 is summed below.

5. Maximal tolerated lipid‑lowering therapy

It is expected that people would reach third line therapy following maximal tolerated lipid-lowering therapy being reached.

A retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data (Danese 2017), reported on the management of lipid-lowering therapy in approximately 24,000 patients with cardiovascular events in the UK. It suggests that 20% of patients are receiving high intensity statins 12 months after their cardiovascular event. In addition to this another 2% of patients are similarly treated with a combination of statins plus ezetimibe.

This proportion (22%) has been applied to the point estimate in step 4.

6. Estimated treatment population for alirocumab or evolocumab

The proportion of this population at high risk or very high risk of CVD with specified LDL-C levels to be treated (uptake) with alirocumab or evolocumab is estimated in the NICE resource impact template for alirocumab (NICE 2016) to be 100% in year 5 (2020), increasing from 88% in year 3 (2018). This figure has been adjusted to create a range (90% to 100%). These proportions have been applied as a scaling factor to the point estimate in step 5.

7. Primary heterozygous familial hypercholesterolaemia with LDL-C of 5 mmol/litre or over and no history of CVD

The number of people with primary heterozygous familial hypercholesterolaemia and no history of CVD with LDL-C of 5 mmol/litre or over was estimated in the manufacturer submission to NICE for alirocumab (Sanofi/ Regeneron 2016) to be 0.01% of the adult population. This proportion has been applied to the adult population stated in step 1.

8. Primary familial heterozygous hypercholesterolaemia with LDL-C of 3.5 mmol/litre or over and a history of CVD

The number of people with primary heterozygous familial hypercholesterolaemia and a history of CVD with LDL-C of 3.5 mmol/litre or over was estimated in the manufacturer submission to NICE for alirocumab (Sanofi/ Regeneron 2016) to be 0.02% of the adult population. This proportion has been applied to the adult population stated in step 1.

9. Total primary heterozygous familial hypercholesterolaemia

The estimated number of people with primary heterozygous familial hypercholesterolaemia and at high risk or very high risk of CVD with specified LDL-C levels has been summed from steps 7 and 8.

10. Maximal tolerated lipid‑lowering therapy primary heterozygous familial hypercholesterolaemia

It is expected that people would reach third line therapy following maximal tolerated lipid-lowering therapy being reached.

A retrospective cohort study using Clinical Practice Research Datalink records linked with Hospital Episode Statistics data (Danese 2017), reported on the management of lipid-lowering therapy in approximately 24,000 patients with cardiovascular events in the UK. It suggests that 20% of patients are receiving high intensity statins 12 months after their cardiovascular event. In addition to this another 2% of patients are similarly treated with a combination of statins plus ezetimibe.

This proportion (22%) has been applied to the point estimates and the upper and lower ranges calculated in step 9.

11. Estimated treatment population for alirocumab or evolocumab primary heterozygous familial hypercholesterolaemia

The proportion of this population to be treated (uptake) with alirocumab or evolocumab is estimated in the NICE resource impact template for alirocumab (NICE 2016) to be 100% in year 5 (2020), increasing from 55% in year 3 (2018). This figure has been adjusted to create a range (90% to 100%). These proportions have been applied as a scaling factor to the point estimate calculated in step 10.

12. Calculate estimated usage volume (ADD)

The number of people who are estimated to receive treatment with alirocumab or evolocumab (summed from steps 6 and 11) 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.

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 [Accessed: 26/01/2021].
2. Alirocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia, TA393, manufacturer’s submission (Sanofi/Regeneron), 2016. Available from: https://www.nice.org.uk/guidance/ta393/evidence [Accessed: 27/06/2017].
3. Danese, M.D., Gleeson, M., Kutikova, L., Griffiths, R.I., Khunti, K., Seshasai, S.R.K. and Ray, K.K., 2017. Management of lipid-lowering therapy in patients with cardiovascular events in the UK: a retrospective cohort study. BMJ open, 7(5), p.e013851.
4. NICE (2016) Costing template: TA394. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta394/resources, [Accessed: 01/09/2017].
5. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: http://www.whocc.no/atc_ddd_index/, [Accessed: 01/09/2017]
6. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 01/09/2017].

1. Population in England

Etelcalcetide is recommended for use in adults only.

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).

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.

4. Less the proportion of adults having 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.

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.

Fernandez-Martin et al, as part of the COSMOS study, which surveyed European haemodialysis centres (including the UK), 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%).

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.

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%).

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 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%).

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.

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.

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).

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 [Accessed: 26/01/2021].
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 20^th 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]

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

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, 2009).

The prevalence and confidence interval has been applied to the population in England in step 1:

3. Proportion of people with asthma and a blood eosinophil count of 300 cells per microlitre or more

NICE (2019) reports 14.2% of people with asthma have a blood eosinophil count of 300 cells per microlitre or more. This proportion has been applied to the point estimate and lower and upper range calculated in step 2:

4. Proportion of people with a blood eosinophil count of 300 cells per microlitre or more and 4 or more exacerbations in the last 12 months

NICE (2019) reports 7.5% of people with blood eosinophil count of 300 cells per microlitre or more and will have 4 or more exacerbations in the last 12 months.

This proportion has been applied to the point estimate and lower and upper range calculated in step 3:

5. Proportion of people with asthma and blood eosinophil count of 400 cells per microlitre or more

NICE (2019) reports 8.3% of people with asthma have a blood eosinophil count of 400 cells per microlitre or more. This proportion has been applied to the point estimate and lower and upper range calculated in step 2:

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

This proportion has been applied to the point estimate and lower and upper range calculated in step 5:

7. Total eligible population for benralizumab, mepolizumab and reslizumab

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

8. Overlap with omalizumab for benralizumab, mepolizumab and reslizumab

The IDEAL study (Albers, 2018) estimates that around 25% of the eligible population for omalizumab will overlap with other treatment options. Total eligible population benralizumab, mepolizumab and reslizumab (step 7) and the eligible population omalizumab (step 12) have each been reduced by 12.5% to adjust for this overlap.

9. Treatment population 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%. 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%. NICE resource impact template for TA565 (benralizumab, 2019) estimates the proportion of the eligible population (step 8) that will receive treatment with reslizumab to be 1%. These have been used to inform the lower and upper range and midpoint (5.5%) the point estimate.

These proportions have been applied to the point estimate and lower and upper range calculated in step 8:

10. Proportion discontinuing benralizumab, mepolizumab and reslizumab each year

The proportion of people discontinuing add-on therapy each year is reported in the manufacturers submission to NICE for benralizumab (TA565), to be 11.8%, for benralizumab, mepolizumab and reslizumab.

This proportion has been subtracted from the point estimate and lower and upper range calculated in step 9:

11. Proportion of people with severe asthma

The number of people with severe asthma in the United Kingdom is reported to be around 200,000 people (Asthma UK, 2020). This equates to around 169,000 people in England (84.5% of UK population is England). The QOF for 2019/20 reports 3,916,000 people on the asthma register, therefore it is calculated that 4.3% of the asthma population has severe asthma. 

This has been applied to the point estimate and the lower and upper range calculated in step 2 (prevalence of asthma):

12. Eligible for omalizumab

The IDEAL study (Albers, 2018) estimates that 30.6% (CI 27.1 – 34.2) of people with severe asthma will be eligible for omalizumab.  This proportion has been applied to the point estimate and lower and upper range calculated in step 11:

13. Overlap with benralizumab, mepolizumab and reslizumab for omalizumab

The IDEAL study (Albers, 2018) estimates that around 25% of the eligible population for omalizumab will overlap with other treatment options. Total eligible population benralizumab, mepolizumab and reslizumab (see step 8) and the eligible population omalizumab (step 12) have each been reduced by 12.5% to adjust for this overlap.

14. Treatment population for omalizumab

The NICE resource impact report for omalizumab for treating severe persistent allergic asthma (2013), estimated that around 2,000 people would receive omalizumab for treating severe persistent allergic asthma. This is around 4% of the eligible population.  

This proportion has been applied to the point estimate and lower and upper range calculated in step 13:

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

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

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.

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. 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

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.

2. Adult ordinary admissions to hospital as overnight inpatients for at least one night

To calculate the number of people who will be prescribed varenicline in hospital the number of admissions into hospital needs to be calculated.

The same person may be admitted more than once to hospital in a year. A total of 3,581,581 adults were associated with 7,353,667 ordinary admissions (excluding maternity, paediatrics and day cases) between 01 April 2019 and 31 March 2020. NHS Long Term Plan policy is that if people are admitted more than once and need support to stop smoking, they will be offered it. Therefore, the number of admissions is used. 

3. Smoking prevalence among adults admitted to hospital

The British Thoracic Society has conducted 2 national smoking cessation audits, the first in 2016 and the second in 2019. Smoking prevalence among adult inpatients was higher than smoking prevalence in the general adult population, with an estimate of around 23.85%. 

The estimate was based on a random sample of patient notes provided by 125 institutions, covering all adult inpatients in acute hospitals during the audit period of July and August 2019 (excluding maternity and mental health).

Given uncertainty in this estimate, confidence intervals alongside the point estimate, as applied to the population from step 2, were estimated as follows.

4. Proportion of adults admitted to hospital who smoke to be eligible for smoking cessation pharmacotherapy

The proportion of people screened during the pilot in Wythenshawe Hospital was 92%. This estimate has been applied to the estimate and upper and lower range calculated in step 3.

5. Proportion of adults admitted to hospital who smoke 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.

6. Proportion of adults admitted to hospital who smoke who receive varenicline

The final step of the Wythenshawe pilot was for people receiving pharmacotherapy the amount who received varenicline. This was 15% in the pilot which has been applied to point estimate and upper and lower range of those offered pharmacotherapy for smoking cessation.

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.

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. 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)

3. British Thoracic Society National Smoking Cessation Audit Report 2019, British Thoracic Society Reports, Vol 11, Issue 2, 2020 (June 2020)

4. ‘Feasibility, uptake and impact of a hospital-wide tobacco addiction treatment pathway: Results from the CURE project pilot’, Evison et al, Clinical Medicine 2020 Vol 20 No. 2 pp.196-202 (DOI: 10.7861/clinmed.2019-0336)
5. Datapharm Communications Limited (2021) The Electronic Medicines Compendium [WWW]. Available from: http://www.medicines.org.uk/emc/, [Accessed: 26/01/2021].