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Publication, Part of

NICE Technology Appraisals in the NHS in England (Innovation Scorecard) - To September 2019

Official statistics

Estimates Report

Key findings

This report includes medicines where it has been possible to estimate the number of patients to be treated with the medicine or combination of medicines. It compares expected uptake to the actual volume of medicines used in the NHS in England.

For the 12 month period from October 2018 to September 2019 :

  • Medicine use for 4 of the 9 estimates is lower than expected
  • Medicine use for 3 estimates is within the expected range
  • Medicine use for 2 estimates are higher than expected

This is based on the methodology applied to derive the estimates.

 

 


Introduction

This report, where possible, compares the expected usage of NICE recommended medicines to the actual volume of medicines used in the NHS in England.

The choice to use the medicine should occur only when the clinician concludes and the patient agrees that the recommended medicine is the most appropriate to use, based on a discussion of all available treatments and informed patient choice.

In interpreting these figures it is important to note that the expected and observed use may differ for a variety of reasons and they should not be assumed to definitely indicate either ‘under’ or ‘over’ prescribing. Potential explanations for variation between actual and expected volumes include:

  • Clinical judgement and patient choice
  • The availability of alternative treatment options that have not been appraised by NICE
  • Changes in prevalence or incidence
  • The time taken for the population to present to services
  • Assumptions about the average length of treatment used to develop predictions of use
  • Known gaps in the medicine utilisation data, such as supplies made directly to patients via the homecare route or by outsourced dispensing
High level conditions
  • Cancer
  • Cardiovascular conditions
  • Chronic kidney disease
  • Digestive tract conditions
  • Liver conditions
  • Neurological conditions
  • Respiratory conditions
Conditions and diseases
  • Crohn’s disease and ulcerative colitis
  • Heart failure
  • Hypercholesterolaemia
  • Metastatic castration-resistant prostate cancer
  • Metastatic colorectal cancer
  • Non-small-cell lung cancer
  • Overt hepatic encephalopathy
  • Relapsing-remitting multiple sclerosis
  • Secondary hyperpara-thyroidism
Medicines
  • abiraterone
  • alirocumab
  • afatinib
  • cabazitaxel
  • dimethyl fumarate
  • enzalutamide
  • erlotinib
  • etelcalcetide
  • evolocumab
  • gefitinib
  • osimertinib
  • rifaximin
  • sacubitril valsartan
  • teriflunomide
  • trifluridine–tipiracil
  • vedolizumab

 

 


Chronic heart failure

Sacubitril valsartan is recommended by NICE for the treatment of symptomatic chronic heart failure with reduced ejection fraction.

Sacubitril valsartan

NICE guidance: TA388 (2016)

1.1 Sacubitril valsartan is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction, only in people:

  • with New York Heart Association (NYHA) class II to IV symptoms and
  • with a left ventricular ejection fraction of 35% or less and
  • who are already taking a stable dose of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).

1.2 Treatment with sacubitril valsartan should be started by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be performed by the most appropriate team member as defined in NICE's guideline on chronic heart failure in adults: management.

SmPC therapeutic indication: Entresto

Entresto is indicated in adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction.

 

For the 12 month period from October 2018 to September 2019 , the tables below show the expected and observed use and the ratio between them. Defined Daily Doses (DDDs) were not available for this formulation, so tablets were used to measure uptake. The annual volume of medicine used was between 49% and 58% lower than expected. 

Table: Observed and expected use of sacubitril valsartan

The observed and expected number of tablets prescribed in primary and secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

2,319,443

6,308,256

5,657,080 to 6,955,752

2. Jan 19-Mar 19

2,612,086

6,171,120

5,534,100 to 6,804,540

3. Apr 19-Jun 19

3,055,559

6,239,688

5,595,590 to 6,880,146

4. Jul 19-Sep 19

3,522,588

6,308,256

5,657,080 to 6,955,752

Total (Oct 18-Sep 19)

11,509,676

25,027,320

22,443,850 to 27,596,190

 

 

 


Crohn’s disease and ulcerative colitis

Vedolizumab is recommended by NICE for the treatment of Crohn’s disease and ulcerative colitis.

Vedolizumab

NICE guidance TA342 (2015)

1.1 Vedolizumab is recommended, within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults only if the company provides vedolizumab with the discount agreed in the patient access scheme.

1.2 Vedolizumab should be given until it stops working or surgery is needed. At 12 months after the start of treatment, people should be reassessed to see whether treatment should continue. Treatment should only continue if there is clear evidence of ongoing clinical benefit. For people in complete remission at 12 months, consider stopping vedolizumab, resuming treatment if there is a relapse. People who continue vedolizumab should be reassessed at least every 12 months to see whether continued treatment is justified.

NICE guidance TA352 (2015)

1.1 Vedolizumab is recommended as an option for treating moderately to severely active Crohn's disease only if:

  • a tumour necrosis factor alpha inhibitor has failed (that is, the disease has responded inadequately or has lost response to treatment) or
  • a tumour necrosis factor alpha inhibitor cannot be tolerated or is contraindicated.

1.2 Vedolizumab should be given as a planned course of treatment until it stops working or surgery is needed, or until 12 months after the start of treatment, whichever is shorter. At 12 months, people should be reassessed to determine whether treatment should continue. Treatment should only continue if there is clear evidence of ongoing clinical benefit. For people in complete remission at 12 months, consider stopping vedolizumab, resuming treatment if there is a relapse. People who continue vedolizumab should be reassessed at least every 12 months to decide whether continued treatment is justified.

SmPC therapeutic indication: Entyvio

Ulcerative Colitis:

  • Entyvio is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

Crohn's Disease:

  • Entyvio is indicated for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

 

For the 12 month period from October 2018 to September 2019 , the tables below show the expected and observed medicine use and the ratio between them. Defined Daily Doses (DDDs) were used, as defined by the World Health Organisation (WHO). The annual volume of medicine used was between 8% lower and 50% higher than expected. The expected values are based on predictions for use in 2018. 

Table: Observed and expected use of vedolizumab
The observed and expected DDDs, and the ratio between them, prescribed in secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

593,956

560,096

435,436 to 711,712

2. Jan 19-Mar 19

613,404

547,920

425,970 to 696,240

3. Apr 19-Jun 19

652,556

554,008

430,703 to 703,976

4. Jul 19-Sep 19

734,170

560,096

435,436 to 711,712

Total (Oct 18-Sep 19)

2,594,086

2,222,120

1,727,545 to 2,823,640

 

 

 


Non-small-cell lung cancer

Afatinib, erlotinib and gefitinib are indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

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

Afatinib

NICE guidance TA310 (2014)

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

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

SmPC therapeutic indication: Giotrif

Giotrif as monotherapy is indicated for the treatment of:

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

NICE guidance TA258 (2012)

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

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

NICE guidance TA374 (2015)

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

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

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

1.3 Erlotinib is not recommended for treating locally advanced or metastatic nonsmallcell lung cancer that has progressed after nontargeted chemotherapy in people with tumours that are EGFRTK mutationnegative.

1.4 Gefitinib is not recommended for treating locally advanced or metastatic nonsmallcell lung cancer that has progressed after nontargeted chemotherapy in people with tumours that are EGFRTK mutationpositive.

SmPC therapeutic indication: Tarceva

Non-Small Cell Lung Cancer (NSCLC):

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

Pancreatic cancer:

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

NICE guidance TA192 (2010)

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

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

SmPC therapeutic indication: Iressa

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

Osimertinib

NICE guidance TA416 (2016)

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

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

SmPC therapeutic indication: Tagrisso

TAGRISSO as monotherapy is indicated for:

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

 

For the 12 month period from October 2018 to September 2019 , the tables below show the expected and observed medicine use and the ratio between them. Defined Daily Doses (DDDs) were not available, so daily doses were used to measure uptake. These are the daily doses recommended in the summary of product characteristics (SmPC). The annual volume of medicine used was within the expected range.

Table: Observed and expected use of afatinib, erlotinib, gefitinib and osimertinib
The observed and expected daily doses, and the ratio between them, prescribed in primary and secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Ratio

1. Oct 18-Dec 18

108,513

184,539

101,027 to 290,840

2. Jan 19-Mar 19

105,842

180,526

98,830 to 284,517

3. Apr 19-Jun 19

109,475

182,532

99,928 to 287,678

4. Jul 19-Sep 19

113,698

184,538

101,026 to 290,839

Total (Oct 18-Sep 19)

437,528

732,135

400,811 to 1,153,874

 

Note: Erlotinib has licensed indications that have not been appraised or recommended by NICE and it has not been possible to establish proportional usage by indication. Therefore, the actual volume of medicine used for the indications recommended by NICE may be lower than the total observed.

 

 


Castration-resistant prostate cancer

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

Abiraterone

NICE guidance TA259 (2012)

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

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

NICE guidance TA387 (2016)

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

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

SmPC therapeutic indication: Zytiga

ZYTIGA is indicated with prednisone or prednisolone for:

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

NICE guidance TA391 (2016)

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

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

In addition, cabazitaxel is recommended only if:

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

Enzalutamide

NICE guidance TA316 (2014)

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

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

NICE guidance TA377 (2016)

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

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

SmPC therapeutic indication: Xtandi

Xtandi is indicated for:

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

 

For the 12 month period from October 2018 to September 2019 , the tables below show the expected and observed medicine use and the ratio between them. Defined Daily Doses (DDDs) were not available for cabazitaxel, so daily doses were used to measure uptake. For abiraterone and enzalutamide, these are the daily doses recommended in the summary of product characteristics (SmPC). For cabazitaxel a daily dose was calculated using the recommended dose stated in the SmPC and an estimated average body surface area for men with cancer. The annual volume of medicine used was between 8% and 89% higher than expected.

Table: Observed and expected use of abiraterone, cabazitaxel and enzalutamide
The observed and expected daily doses, and the ratio between them, prescribed in primary and secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

551,523

413,420

301,698 to 525,287

2. Jan 19-Mar 19

554,900

404,433

295,140 to 513,868

3. Apr 19-Jun 19

563,129

408,927

298,419 to 519,578

4. Jul 19-Sep 19

588,370

413,420

301,698 to 525,287

Total (Oct 18-Sep 19)

2,257,922

1,640,200

1,196,955 to 2,084,020

 

 

 


Colorectal cancer

Trifluridine–tipiracil is recommended by NICE for the treatment of metastatic colorectal cancer.

Trifluridine–tipiracil

NICE guidance TA405 (2016)

Trifluridine–tipiracil is recommended, within its marketing authorisation, as an option for treating metastatic colorectal cancer, that is:

  • in adults who have had previous treatment with available therapies including fluoropyrimidine-, oxaliplatin- or irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) agents and anti-epidermal growth factor receptor (EGFR) agents, or when these therapies are not suitable, and
  • only when the company provides trifluridine–tipiracil with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Lonsurf

Lonsurf is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.

 

For the 12 month period from October 2018 to September 2019 , the table below shows the expected and observed use and the ratio between them. Defined Daily Doses (DDDs) were not available for this formulation, so milligrams were used to measure uptake. The annual volume of medicine used was 32% to 39% lower than expected. 

Table: Observed and expected use of trifluridine–tipiracil
The observed and expected milligrams, and the ratio between them, prescribed in secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

1,362,371

2,296,642

2,169,083 to 2,426,544

2. Jan 19-Mar 19

1,468,162

2,246,714

2,121,929 to 2,373,793

3. Apr 19-Jun 19

1,490,742

2,271,678

2,145,506 to 2,400,169

4. Jul 19-Sep 19

1,510,744

2,296,641

2,169,083 to 2,426,544

Total (Oct 18-Sep 19)

5,832,019

9,111,675

8,605,600 to 9,627,050

 

 

 


Overt hepatic encephalopathy

Rifaximin (550mg) is recommended by NICE for preventing episodes of overt hepatic encephalopathy in adults.

Rifaximin (550mg)

NICE guidance TA337 (2015)

Rifaximin is recommended, within its marketing authorisation, as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in people aged 18 years or older.

SmPC therapeutic indication: Targaxan

TARGAXAN is indicated for the reduction in recurrence of episodes of overt hepatic encephalopathy in patients ≥ 18 years of age.

 

For the 12 month period from October 2018 to September 2019, the tables below show the expected and observed medicine use and the ratio between them. Defined Daily Doses (DDDs) were not available for this formulation, so daily doses were used to measure uptake. These are the daily doses recommended in the summary of product characteristics (SmPC). The annual volume of medicine used was within the expected range.

Table: Observed and expected use of rifaximin (550mg)
The observed and expected daily doses, and the ratio between them, prescribed in primary and secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

467,391

419,244

323,564 to 521,548

2. Jan 19-Mar 19

470,863

410,130

316,530 to 510,210

3. Apr 19-Jun 19

499,275

414,687

320,047 to 515,879

4. Jul 19-Sep 19

524,416

419,244

323,564 to 521,548

Total (Oct 18-Sep 19)

1,961,945

1,663,305

1,283,705 to 2,069,185

 

 

 


Primary hypercholesterolaemia and mixed dyslipidaemia

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

Alirocumab

NICE guidance TA393 (2016)

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

  • Low density lipoprotein concentrations are persistently above the thresholds specified in table 1 despite maximal tolerated lipid lowering therapy. That is, either the maximum dose has been reached or further titration is limited by intolerance (as defined in NICE's guideline on familial hypercholesterolaemia: identification and management).
  • The company provides alirocumab with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Praluent

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

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

NICE guidance TA394 (2016)

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

  • The dosage is 140 mg every 2 weeks.
  • Low-density lipoprotein concentrations are persistently above the thresholds specified in table 1 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.

 

For the 12 month period from October 2018 to September 2019, the tables below show the expected and observed medicine use and the ratio between them. Actual Daily Doses (ADDs) were used. The annual volume of medicine used was between 65% and 72% lower than expected.

Table: Observed and expected use of alirocumab and evolocumab
The observed and expected ADDs, and the ratio between them, prescribed in primary and secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

292,591

1,064,624

958,088 to 1,171,068

2. Jan 19-Mar 19

303,126

1,041,480

937,260 to 1,145,610

3. Apr 19-Jun 19

324,535

1,053,052

947,674 to 1,158,339

4. Jul 19-Sep 19

392,856

1,064,624

958,088 to 1,171,068

Total (Oct 18-Sept 19)

1,313,108

4,223,780

3,801,110 to 4,646,085

 

 

 


Relapsing-remitting multiple sclerosis

Dimethyl fumarate and teriflunomide are recommended by NICE for treating relapsing-remitting multiple sclerosis (RRMS) in adults.

Dimethyl fumarate

NICE guidance TA320 (2014)

Dimethyl fumarate is recommended as an option for treating adults with active relapsing-remitting multiple sclerosis (normally defined as 2 clinically significant relapses in the previous 2 years), only if:

  • they do not have highly active or rapidly evolving severe relapsing-remitting multiple sclerosis and
  • the manufacturer provides dimethyl fumarate with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Tecfidera

Tecfidera is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis.

Teriflunomide

NICE guidance TA303 (2014)

Teriflunomide is recommended as an option for treating adults with active relapsing–remitting multiple sclerosis (normally defined as 2 clinically significant relapses in the previous 2 years), only if:

  • they do not have highly active or rapidly evolving severe relapsing–remitting multiple sclerosis and
  • the manufacturer provides teriflunomide with the discount agreed in the patient access scheme.

SmPC therapeutic indication: Aubagio

Aubagio is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis (MS).

 

For the 12 month period from October 2018 to September 2019 , the tables below show the expected and observed medicine use and the ratio between them. Daily doses were used to measure uptake. These are the daily doses recommended in the summary of product characteristics (SmPC). The annual volume of medicine used was between 1% and 39% higher than expected.

Table: Observed and expected use of dimethyl fumarate and teriflunomide
The observed and expected daily doses, and the ratio between them, prescribed in primary and secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected (range)

1. Oct 18-Dec 18

687,027

613,180

517,224 to 712,816

2. Jan 19-Mar 19

723,223

599,850

505,980 to 697,320

3. Apr 19-Jun 19

689,933

606,515

511,602 to 705,068

4. Jul 19-Sep 19

759,360

613,180

517,224 to 712,816

Total (Oct 18-Sep 19)

2,859,543

2,432,725

2,052,030 to 2,828,020

 

 

 


Secondary hyperparathyroidism

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

Etelcalcetide

NICE guidance TA448 (2017)

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

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

SmPC therapeutic indication: Parsabiv

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

 

For the 12 month period from October 2018 to September 2019 , the table below shows the expected and observed use and the ratio between them. Defined Daily Doses (DDDs) were used, as defined by the World Health Organisation (WHO). The annual volume of medicine used was between 56% and 87% lower than expected.

Table: Observed and expected use of etelcalcetide
The observed and expected DDDs, and the ratio between them, prescribed in secondary care from October 2018 to September 2019 

Time period

Observed

Expected

Expected )ratio)

1. Oct 18-Dec 18

20,529

112,056

52,900 to 184,460

2. Jan 19-Mar 19

19,696

109,620

51,750 to 180,450

3. Apr 19-Jun 19

25,444

110,838

52,325 to 182,455

4. Jul 19-Sep 19

27,534

112,056

52,900 to 184,460

Total (Oct 18-Sept 19)

93,203

444,570

209,875 to 731,825

 

 

 


Methodology and limitations

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

Estimates of the treatment population

NICE resource impact assessments were used as the starting point to develop the estimates presented.

Resource impact templates are provided by NICE to support the implementation of most technology appraisal guidance when the resource impact is expected to be significant (greater than £5 million for England). The templates are an aid for financial planning purposes and enable users to estimate the local resource impact of implementing guidance at the time of publication. However, the template can be used to further develop and establish assumptions around an eligible population and an estimated treatment population.

The assumptions used to generate the resource impact templates are based on peer reviewed literature, data sources, expert opinion and other information. Data were sought from several different sources to refine the population numbers for the indications and circumstances detailed in the NICE technology appraisal guidance. The data reviewed included: epidemiological data such as the prevalence of a disease, proportions of patients at a stage of a disease, and their likely treatment history. For some medicines additional information was required, for example, the proportion of patients likely to discontinue treatment or choose an alternative.

NICE do not produce a resource impact template where the cost impact of a technology is not considered to be significant, or when estimating the cost impact is not possible. In the absence of a resource impact template an estimate was constructed using a stepwise process similar to that used to develop a resource impact template. The process involved:

  1. A review of the available literature on the epidemiology of the indication(s) for the medicine.
  2. Where appropriate, the use of primary data sources such as Hospital Episode Statistics (HES) and The Health Improvement Network (THIN) database (containing pseudonymous patient information extracted from a sample of GP practice clinical systems).
  3. Consultation with clinical experts and consideration of expert opinion used in other templates/sources of evidence for the same therapeutic area.

For medicines with multiple indications, only those recommended by NICE were identified. Eligible populations were developed on an indication by indication basis. The separate indication estimates were then combined to produce an overall estimate. Indications not appraised or recommended by NICE were excluded from the estimate of the eligible population. Where a medicine has an indicated use not appraised or recommended by NICE this could give the impression of over usage, even if this is not the case.

Estimates of usage (volume)

Treatment population estimates were used to calculate the total expected volume of medicine at a national level. Where available, Defined Daily Doses (DDDs) as defined by the World Health Organisation (WHO) were used. For those medicines where DDDs were not available, or were developed for a different indication, an alternative measure such as daily dose or actual daily dose (ADD) was used.

The daily dose is the daily maintenance dose calculated from the recommended dosage as set out in the summary of product characteristics. The ADD is a prescribing measure developed for the Innovation Scorecard. ADDs assign a unique value for each presentation of a medicine based on units (such as tablets, capsules, patches) and the recommended frequency of daily use. For more information on ADD please refer to the Medicine Groupings Specification

The annual estimated usage volume was proportionally allocated to each quarter based on the number of days in a quarter.

Range

Ranges for the estimate of the treatment population and the estimate of usage have been calculated for each estimate. The range provides an indication of the level of uncertainty in the estimate. They are calculated from confidence intervals and other specified measures at each step where available.

Manufacturer input to NICE estimates

Manufacturer input was requested for new estimates or those where a material change had been made to the estimated treatment population calculation. The draft estimates were sent to the relevant manufacturers with a request for comments and feedback on the estimate calculations and the supporting data. Company feedback was then critically appraised and where appropriate, the draft estimate was updated. Where data used in the estimate is taken from a source that is routinely updated, such as the Quality and Outcomes Framework or population statistics, updating the estimate to reflect the latest publication is not considered to be a material change.

Observed use

Data for observed use of the medicines under consideration were obtained by NHS Digital through its routine access to Prescribing Analysis and Cost Tabulation (PACT) data on primary care prescribing (supplied by the NHS BSA) and Hospital Pharmacy Audit Index (HPAI) data on secondary care prescribing (supplied by IQVIA, formerly IMS Health and Quintiles). Usage data were converted where appropriate, for example to DDDs or daily doses, to allow comparison with the estimates.

Although the secondary care database captures some data for drugs supplied through homecare services, it is incomplete. Therefore, the actual volume of medicine used may be higher than the volume reported in the observed use. This applies to all medicines in this report, which are prescribed as follows:

  • Sacubitril valsartan: primary and secondary care
  • Vedolizumab: secondary care only
  • Afatinib, erlotinib, gefitinib and osimertinib: predominantly used in secondary care, but a very small volume of medicine is prescribed in primary care
  • Abiraterone, cabazitaxel and enzalutamide: predominantly used in secondary care, but a small volume of medicine is prescribed in primary care
  • Trifluridine–tipiracil: secondary care only
  • Rifaximin (550mg): primary and secondary care
  • Alirocumab and evolocumab: primary and secondary care
  • Dimethyl fumarate and teriflunomide: predominantly used in secondary care, but a small volume of medicine is prescribed in primary care
  • Etelcalcetide: secondary care

Comparison of expected and observed use

Observed use is compared with the estimated use to indicate whether use is higher or lower than expected. The estimated treatment population is calculated with an upper and lower range, to address the uncertainty in the underlying analyses. The ratio of observed to expected volume, and the upper and lower range, is calculated. Where the observed use is within the upper and lower estimate range, the use is as expected.

Limitations

Several assumptions are made in order to develop the expected volume of medicine to be prescribed. This approach is due to limitations, which include:

  • Lack of prevalence and incidence data at national level
  • Some medicines have multiple indications of which one or more indications have not been recommended by NICE
  • Medicines recommended as one of several options for treatment

Usage data are limited in coverage and quality. Problems include:

  • Multiple indications for a single medicine (usage data give no information on the condition being treated)
  • Failure of some hospitals to contribute data to the IQVIA data collection or are unable to provide full datasets
  • Lack of available data from some mental health trusts
  • Reporting of medicines supplied via the homecare route or by outsourced dispensing is not recorded in pharmacy systems
  • Medicines that need to be diluted or manipulated to the individual patient’s requirements in specialist units; the way these are recorded in the pharmacy systems often does not allow calculation of the actual amount of drug used and sometimes these medicines are not recorded at all by the pharmacy

These limitations mean that caution must be exercised in interpreting the figures in the report as providing evidence of under or overuse of the medicines reviewed.

 

 


Estimate calculations

Chronic heart failure with reduced ejection fraction – sacubitril valsartan

1. Population who meet SmPC

The SmPC states that sacubitril valsartan is indicated for the treatment of symptomatic chronic heart failure with reduced ejection fraction.

 

Point estimate

Reference

England population

55,619,430

(1)

2. Prevalence of heart failure

The quality and outcomes framework (QOF) reported the number of people on the heart failure register (NHS Digital 2018). It is estimated that 832 people per 100,000 population have heart failure. The 95% confidence interval around the reported prevalence (95% CI 829 to 834) has been calculated using the exact binomial method (Pezzullo 2009).

The prevalence and confidence interval have been applied to the adult population in England:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with heart failure in England

 462,754

 461,085

 463,866

(2,3)

3. Proportion of people with heart failure and reduced left ventricular systolic dysfunction

The national heart failure audit (National Institute for Cardiovascular Outcomes Research 2016) reported that 70.2% of patients who were admitted for heart failure had left ventricular systolic dysfunction. This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 2.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with heart failure and reduced left ventricular ejection fraction

 324,853

 323,682

 325,634

(4)

4. Proportion of people with New York Heart Association (NYHA) class II to IV symptoms

The manufacturer’s submission for TA388 (Novartis Pharmaceuticals UK Ltd 2015) reported that 89% of people with heart failure had a New York Heart Association (NYHA) heart failure classification symptom between II to IV. This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with New York Heart Association (NYHA) class II to IV symptoms

 289,119

 288,077

 289,814

(5)

5. Proportion of people with a left ventricular ejection fraction of 35% or less

The resource impact assessment template for sacubitril valsartan estimates that 59.5% people with heart failure have a left ventricular ejection of 35% or less (NICE 2016). This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 4.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with a left ventricular ejection fraction of 35% or less

 172,026

 171,406

 172,439

(6)

6. Proportion of people taking a stable dose of angiotensinconverting enzyme (ACE) inhibitors or angiotensin II receptorblockers (ARBs)

The quality and outcomes framework heart failure register report the number of people taking a stable dose of angiotensinconverting enzyme (ACE) inhibitor or angiotensin II receptorblocker (ARB). It was reported that 83.04% of people on the register are taking a stable dose of either (NHS Digital 2018). This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 5.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with heart failure who are taking a stable dose of ACE inhibitors or ARBs

 142,850

 142,336

 143,193

(3)

7. Estimated treatment population

The resource impact assessment template for sacubitril valsartan projects the uptake of this medicine over time (NICE 2016). The projected uptake in 2017-18 is expected to be 24%; this figure has been adjusted +/- 10% to create a range (21.6% - 26.4%). These proportions have been applied as a scaling factor to the point estimate and the upper and lower ranges calculated in step 6.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people treated with sacubitril valsartan

 34,284

 30,745

 37,803

(6)

8. Calculate estimated usage volume

The number of people likely to receive treatment with sacubitril valsartan (calculated in step 7) has been multiplied by the number of tablets taken per day, and then by the number of days in a year (365 days).

 

Point estimate

Lower range

Upper range

Estimated number of people treated with sacubitril valsartan

 34,284

 30,745

 37,803

Number of tablets daily (x 2)

 68,568

 61,490

 75,606

Total estimated annual usage (tablets)

 25,027,320

 22,443,850

 27,596,190

References

  1. Office for National Statistics (2018) Annual Mid-year Population Estimates, 2017 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed: 06/11/2018].
  2. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html [Accessed 17/06/2016].
  3. NHS Digital (2017). Quality and Outcomes Framework (QOF) for April 2017 - March 2018, England. Available from: https://digital.nhs.uk/data-and-information/publications/statistical/quality-and-outcomes-framework-achievement-prevalence-and-exceptions-data [Accessed 26/10/2018].
  4. National Institute of Cardiovascular Outcomes Research (2016). National Heart Failure Audit, April 2014- March 2015. Available from: http://www.bsh.org.uk/resources/national-heart-failure-audit/ [Accessed: 17/11/2016].
  5. Novartis Pharmaceuticals UK Ltd (2015). The manufacturer’s submission for NICE technology appraisal 388. Available from: https://www.nice.org.uk/guidance/ta388/evidence [Accessed: 17/08/2016].
  6. NICE (2016) Resource impact assessment template for TA388. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta388/resources [Accessed: 17/08/2016]. Additional expert clinical opinion was used to inform steps 5 and 7.

 

Crohn’s disease and ulcerative colitis – vedolizumab

1. Population who meet SmPC

The SmPC states that the medicine is indicated for an adult population only. Therefore, the starting population is adults aged 18 years and over in England.

 

Point estimate

Reference

England population aged 18 years and over

43,752,473

(1)

2. Prevalence of ulcerative colitis (UC) and Crohn’s disease (CD)

Rubin et al (2000) have reported the prevalence of ulcerative colitis and Crohn’s disease in the United Kingdom (UK). This study was carried out in 15 GP practices in North Tees and represented a population of 135,723 people. The prevalence figures were adjusted for age and sex and were reported as:

Prevalence of UC per 100,000 UK pop in 1995: 243.4 (95% CI 217.4 to 269.4)

Prevalence of CD per 100,000 UK pop in 1995: 144.8 (95% CI 124.8 to 168.8)

The prevalence figures and associated confidence intervals have been applied to the adult population in England:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with ulcerative colitis aged 18 years and over in England

 106,494

 95,118

 117,869

(2)

Estimated number of people with Crohn’s disease aged 18 years and over in England

 63,354

 54,603

 73,854

(2)

3. Proportion of people with moderately to severely active disease

The manufacturer’s submission (Takeda 2014a) has reported that 52% of people with ulcerative colitis in the UK have moderately to severely active disease. Dretzke et al (2015) has reported that 40% of people with Crohn’s disease have moderately to severely active disease. These proportions have been applied as a scaling factor to the relevant point estimates and the upper and lower ranges calculated in step 2.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with moderately to severely active ulcerative colitis

 55,377

 49,461

 61,292

(4)

Estimated number of people with moderately to severely active Crohn’s disease

 25,342

 21,841

 29,542

(3)

4. Proportion of people whose disease failed to respond to conventional therapy and are treated with a biologic

The proportion of people whose disease failed to respond to conventional therapy and are treated with a biologic has been estimated using data from the national clinical audit of biological therapies (Royal College of Physicians 2015).

To develop this estimate, the data reported in the flow diagram of people included in the audit from 2011 to 2015 was used to estimate that 10% of people with ulcerative colitis are treated with a biologic. This has been referred to as the ‘estimated number of people who are eligible for treatment’ because vedolizumab is a treatment option for people with ulcerative colitis which has failed to respond to conventional therapy (see SmPC and technology appraisal recommendations). The same data (Royal College of Physicians 2015) has been used to estimate that 56% of people have Crohn’s disease which has failed to respond to conventional therapy and have been treated with a biologic. The 95% confidence intervals around the audit data have been calculated, using the exact binomial method (Pezzullo 2009). Therefore 10% (95% CI 9.5 to 10.9%) of people with ulcerative colitis and 56% (95% CI 54.5 to 56.8%) of people with Crohn’s disease are estimated to be treated with a biologic. These figures have been applied to the point estimates and the upper and lower ranges calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with ulcerative colitis eligible to receive treatment

 5,538

 4,699

 6,681

(5,9)

Estimated number of people with moderately to severely active Crohn’s disease which has failed to respond to conventional therapy and are treated with a biologic

 14,192

 11,903

 16,780

(5,9)

5. Proportion of people with Crohn’s disease who stop treatment with or whose disease has failed to respond to a tumour necrosis factor-alpha (TNFα) antagonist

The national clinical audit of biological therapies (Royal College of Physicians 2015) has reported the proportion of people with Crohn’s disease which has failed to respond to a TNFα antagonist. The audit reported follow-up treatment outcomes at 3, 6 and 12 months. Three month data has been used because the SmPC for biologics such as infliximab and adalimumab suggest that continued treatment beyond 4 to 12 weeks is not recommended unless people have a clinical response. Therefore, people are most likely to stop treatment in the first 3 months of starting therapy and this data would provide the most accurate figure of those eligible for treatment with vedolizumab. It is estimated that at 3 months, approximately 7% (95% CI 5.4 to 8.1%) of people with Crohn’s disease stopped treatment with adalimumab or infliximab either because of loss of response, poor response or side effects and 32% (95% CI 29.5 to 34.6%) of people did not experience clinical remission. To develop this estimate, the 95% confidence intervals around the audit data have been calculated, using the exact binomial method (Pezzullo 2009).

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with Crohn’s disease who stop treatment with a tumour necrosis factor-alpha (TNFα) antagonist

 993

 643

 1,359

(5,9)

Estimated number of people with Crohn’s disease who do not achieve clinical remission with a tumour necrosis factor-alpha (TNFα) antagonist

 4,541

 3,511

 5,806

(5,9)

6. Number of people eligible to receive treatment with vedolizumab

The number of people estimated to be eligible for treatment with vedolizumab are based on steps 4 and 5 above. For ulcerative colitis, the figures from step 4 have been used because vedolizumab is a treatment option following conventional therapy.

 

Point estimate

Lower range

Upper range

Estimated number of people with ulcerative colitis eligible to receive treatment

5,538

4,699

6,681

For Crohn’s disease, the sum of the point estimates and the upper and lower ranges calculated in step 5 have been used.

 

Point estimate

Lower range

Upper range

Estimated number of people with Crohn’s disease eligible to receive treatment

 5,534

 4,154

 7,165

7. Proportion of people likely to receive treatment with vedolizumab

The manufacturer’s submission for ulcerative colitis (Takeda 2014a) and the NICE costing report for Crohn’s disease (NICE 2015) have reported the projected uptake of vedolizumab. The proportions reported in the manufacturer’s submission are based on current uptake of medicines and market share assumptions. The projected uptake of vedolizumab in 2018 is estimated to be 30% for ulcerative colitis and 80% for Crohn’s disease. The uptake for people with Crohn’s disease is assumed to be higher because there has been previous intolerance or failure with biologics such as infliximab and adalimumab. These proportions have been applied as a scaling factor to the point estimates and the upper and lower ranges calculated in step 6.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with ulcerative colitis likely to receive treatment

1,661

1,410

2,004

(4)

Estimated number of people with Crohn’s disease likely to receive treatment

4,427

3,323

5,732

(8)

Total estimated number of people treated with vedolizumab

6,088

4,733

7,736

 

8. Calculate estimated usage volume

The number of people expected to be treated with vedolizumab calculated in step 7 has been multiplied by the number of days in a year (365 days) to produce an expected volume of medicine per year in DDDs.

 

Point estimate

Lower range

Upper range

Estimated number of people likely to receive treatment with vedolizumab

6,088

4,733

7,736

Total estimated annual usage (DDDs)

2,222,120

1,727,545

2,823,640

The DDD for vedolizumab is reported as 5.4mg/day (WHO 2015) and may underestimate the number of people receiving treatment.

References

  1. Office for National Statistics (2018) Annual Mid-year Population Estimates, 2017 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed: 06/11/2018].
  2. Rubin GP, Hungin, APS, Kelly PJ et al. (2000) Inflammatory bowel disease: Epidemiology and management in an English general practice population. Alimentary Pharmacology and Therapeutics 14: 1553-1559
  3. Dretzke J, Edlin R, Round J et al. (2011) Use of tumour necrosis factor alpha (TNF α) inhibitors adalimumab and infliximab for Crohn’s disease. Systematic review and economic evaluation. Health Technology Assessment No 15.6. Available from: https://www.journalslibrary.nihr.ac.uk/hta/hta15060
  4. Takeda (2014a) Manufacturer’s submission for NICE technology appraisal guidance 342. Available from: https://www.nice.org.uk/guidance/ta342/history [Accessed: 28/10/15]
  5. Royal College of Physicians (2015). National clinical audit of biological therapies: adult report. UK inflammatory bowel disease (IBD) audit. London: Royal College of Physicians. Available from: https://www.rcplondon.ac.uk/projects/outputs/national-clinical-audit-report-biological-therapies-adult-report-2015 [Accessed: 01/10/2015]
  6. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: https://www.whocc.no/atc_ddd_index/ [Accessed: 16/02/17]
  7. Datapharm Communications Ltd (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 16/02/2017].
  8. NICE (2015). Costing report for vedolizumab for treating moderately to severely active Crohn's disease after prior therapy. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta352/history [Accessed: 28/10/2015]
  9. Pezzullo (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from: https://statpages.info/confint.html [Accessed 14/01/2016]

 

Locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer – afatinib, erlotinib, gefitinib and osimertinib

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 (2018), 2016 Cancer Registration Statistics for England.

 

Point estimate

Reference

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

38,352

(1)

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

The proportion of new cases of lung cancer that are non-small-cell lung cancer (NSCLC) in England is reported in the national lung cancer audit (2018) information sheet to be 88.4%. This proportion has been used to inform the upper and lower range and applied to the point estimate calculated in step 1.

 

Point estimate

Lower range

Upper range

Reference

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

33,903

33,903

33,903

(2)

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

The proportion of new cases of NSCLC that are diagnosed stage IIIb (advanced) or stage IV (metastatic) is reported in the national lung cancer audit for England information sheet to be 57.8%. 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.

 

Point estimate

Lower range

Upper range

Reference

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

19,596

19,596

19,596

(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 (2018) to be 62.5%. This proportion has been used to inform the upper and lower range and applied to the point estimate calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with stage IIIB/IV and PS 0–1 who receive SACT

 12,248

 12,248

 12,248

(2)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with sufficient samples for genotyping.

 9,186

 7,961

 10,411

(3,4)

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.

 

Point estimate

Lower range

Upper range

Reference

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

 1,378

 796

 2,082

(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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who receive afatinib, erlotinib or gefitinib

 1,378

 796

 2,082

(-)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who progress following first line treatment

 896

 517

 1,353

(6)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who harbour T790M mutation at progression

 493

 259

 812

(7)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people receiving osimertinib

 493

 259

 812

(-)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with inadequate tissue sample or unsuccessful DNA test

 3,062

 1,837

4,287

(3,4)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with inadequate tissue sample or unsuccessful DNA test

1,225

551

2,144

(3,4)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population first line afatinib, erlotinib, gefitinib

 1,378

 796

 2,082

(-)

Estimated treatment population second line osimertinib

 493

 259

 812

 

Estimated treatment population second line erlotinib

1,225

551

2,144

 

14. Calculate estimated usage volume

Defined Daily Doses (DDDs) were not available for afatinib, erlotinib, gefitinib and osimertinib so daily doses calculated from the SmPC have been used.

The SmPC recommended daily dose for afatinib is 40mg, for erlotinib is 150mg, for gefitinib is 250mg and for osimertinib is 80mg. 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 daily doses.

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).

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population first line afatinib, erlotinib, gefitinib

 1,378

 796

 2,082

(-)

Estimated median progression-free survival (days)

 335

 335

 335

(8)

Total estimated annual usage (daily doses)

 461,630

266,660

697,470

 

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).

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population subsequent osimertinib

 493

 259

 812

(-)

Estimated median progression-free survival (days)

 335

 335

 335

(6)

Total estimated annual usage (daily doses)

 165,155

 86,765

272,020

 

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).

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population second line erlotinib

1,225

551

2,144

(-)

Estimated median progression-free survival (days)

 86

 86

 86

(9)

Total estimated annual usage (daily doses)

 105,350

 47,386

184,384

 

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.

 

Point estimate

Lower range

Upper range

Reference

Total estimated annual usage (daily doses)

 732,135

 400,811

 1,153,874

(-)

References

  1. Office for National Statistics (2018) Cancer Registration Statistics, England: 2016. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancerregistrationstatisticscancerregistrationstatisticsengland [Accessed: 12/03/2018]
  2. National Cancer Registration and Analysis Service (2018). Royal College of Physicians. National lung cancer audit 2018 (for the audit period 2016). London: RCP, 2017. Available from https://www.rcplondon.ac.uk/projects/outputs/nlca-annual-report-2017 [Accessed 03/04/2018]
  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/chapter/3-Evidence [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: https://www.whocc.no/atc_ddd_index/ [Accessed: 17/01/2018]
  11. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 17/01/2018]

 

Metastatic castration-resistant prostate cancer – abiraterone, cabazitaxel and enzalutamide

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 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 2016 (ONS, 2018).

 

Point estimate

Reference

New cases of prostate cancer (C61), adults, England

40,486

(1)

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:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who have metastatic hormone relapsed prostate cancer in England

6,215

4,534

7,895

(2,3,4)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who have metastatic hormone relapsed prostate cancer who have no or mild symptoms

4,661

3,401

5,921

(5)

Estimated number that receive treatment with abiraterone or enzalutamide

3,729

2,721

4,737

(6)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who do not receive clinical benefit from abiraterone or enzalutamide

1,305

952

1,658

(6)

Estimated number that go on to receive docetaxel chemotherapy after abiraterone or enzalutamide treatment

718

524

912

(6)

Estimated number that receive cabazitaxel after chemotherapy

215

157

274

(6)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with metastatic hormone relapsed prostate cancer who receive first-line docetaxel chemotherapy (step 2 minus step 3)

1,554

1,134

1,974

(6)

Estimated number in which first-line chemotherapy is unsuccessful

855

624

1,086

(6)

Estimated number that receive abiraterone, cabazitaxel or enzalutamide after chemotherapy

641

468

815

(6)

6. Calculate estimated usage volume

The daily dose for abiraterone has been reported as 1,000mg (WHO 2016) and the daily dose for enzalutamide as 160mg (WHO 2016). The recommended dose of cabazitaxel is 25 mg/m2 every 3 weeks (SmPC 2016). The average body surface area of adult male cancer patients in the UK is reported to be 1.91 m2 (Sacco 2010). Therefore, the daily dose for cabazitaxel has been calculated as 2.27mg. These medicines are used in primary and secondary care; therefore the observed mgs have been extracted for primary and secondary care.

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 365 (days in a year) then multiplied by the recommended daily dose to produce an expected volume of medicine per year in daily doses.

TA391 (NICE 2016) states that treatment with cabazitaxel is stopped when the disease progresses or after a maximum of 10 cycles (whichever happens first). 10 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 recommended daily dose to produce an expected volume of medicine per year in daily doses.

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 daily doses as the shorter treatment duration of cabazitaxel is not reflected in this calculation.

 

Point estimate

Lower range

Upper range

Estimated treatment population abiraterone & enzalutamide (including cabazitaxel at step 5)

4,370

3,189

5,552

Estimated treatment population cabazitaxel

215

157

274

Estimated annual usage abiraterone & enzalutamide (including cabazitaxel at step 5) (treatment population x 365 days x 1 daily dose)

1,595,050

1,163,985

2,026,480

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

45,150

32,970

57,540

Total estimated annual usage (daily doses)

1,640,200

1,196,955

2,084,020

References

  1. Office for National Statistics (2018) Cancer Registration Statistics, England: 2016. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancerregistrationstatisticscancerregistrationstatisticsengland [Accessed: 06/11/2018]
  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. Sacco J, Botten J, Macbeth F et al (2010) The average body surface area of adult cancer patients in the UK: a multicentre retrospective study
  8. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: https://www.whocc.no/atc_ddd_index/ [Accessed: 16/02/2017]
  9. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 16/02/2017].

 

Metastatic colorectal cancer – trifluridine–tipiracil

1. Incidence of colorectal cancer

The SmPC states that trifluridine–tipiracil for previously treated metastatic colorectal cancer is indicated in an adult population only. Therefore, the starting population is adults aged 18 years or older in England with colorectal cancer.

Estimated incidence of colorectal cancer for adult males and females was reported by the Office for National Statistics (2018), 2016 Cancer Registration Statistics for England.

 

Point estimate

Reference

Estimated number of adult females with colon or rectal cancer

15,323

(1)

Estimated number of adult males with colon or rectal cancer

19,557

(1)

2. Proportion of new cases diagnosed as metastatic colorectal cancer (stage 4)

The proportion of new cases of colorectal cancer that are diagnosed as metastatic (stage 4) in England has been published by Public Health England (22%). This is cancer diagnosis by stage (where known). To develop this estimate, the 95% confidence intervals around the data have been calculated using the exact binomial method (Pezzullo 2009). These figures have been used to inform the upper (22.34% males, 22.39% females) and lower (21.66% males, 21.62% females) range. These proportions have been applied to the point estimate calculated in step 1.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adult females with metastatic colorectal cancer (stage 4)

3,371

3,313

3,431

(2,3)

Estimated number of adult males with metastatic colorectal cancer (stage 4)

4,303

4,236

4,369

(2,3)

3. Proportion of new cases that are diagnosed as colorectal cancer (stage 2 or 3)

The proportion of new cases of colorectal cancer that are diagnosed at stage 2 or 3 in England has been published by Public Health England (47%). This is cancer diagnosis by stage (where known). To develop this estimate, the 95% confidence intervals around the data have been calculated using the exact binomial method (Pezzullo 2009). These figures have been used to inform the upper (47.41% males, 47.47% females) and lower (46.59% males, 46.53% females) range. These proportions have been applied to the point estimate calculated in step 1.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adult females with colorectal cancer (stage 2 or 3)

7,202

7,130

7,274

(2,3)

Estimated number of adult males with colorectal cancer (stage 2 or 3)

9,192

9,112

9,272

(2,3)

4. Proportion of people diagnosed with stage 2 or 3 colorectal cancer that progresses to metastatic (stage 4) disease following diagnosis

The proportion of people diagnosed with stage 2 or 3 colorectal cancer that progresses to metastatic (stage 4) disease following diagnosis is between 50% and 60% (Kish 2016). These figures have been used to inform the upper and lower range. A midpoint (55%) has been used to calculate the point estimate. These proportions have been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Number of females diagnosed with stage 2 or 3 colorectal cancer that progresses to metastatic (stage 4) disease following diagnosis

3,961

3,601

4,321

(4)

Number of males diagnosed with stage 2 or 3 colorectal cancer that progresses to metastatic (stage 4) disease following diagnosis

5,056

4,596

5,515

(4)

5. Number of people with metastatic colorectal cancer (stage 4)

The number of males and females with metastatic disease has been calculated by summing those diagnosed at stage 4 with those diagnosed at stage 2 or 3 whose disease then progresses to stage 4 (steps 2 and 4).

 

Point estimate

Lower range

Upper range

Reference

Number of females with metastatic disease

7,332

6,914

7,752

(-)

Number of males with metastatic disease

9,359

8,832

9,884

(-)

6. Proportion with metastatic colorectal cancer who have first-line and second-line treatments

The proportion of people with metastatic colorectal cancer who receive first-line and second-line treatments (42.5%) has been taken from the manufacturer’s submission for TA405 (Servier Laboratories Ltd 2016). This proportion has been applied as a scaling factor to the point estimate and the lower and upper range calculated in step 5.

 

Point estimate

Lower range

Upper range

Reference

Number of females with metastatic colorectal cancer who receive first-line and second-line treatments

3,116

2,938

3,295

(5)

Number of males with metastatic colorectal cancer who receive first-line and second-line treatments

3,978

3,754

4,201

(5)

7. Proportion of people with metastatic colorectal cancer who are eligible for treatment after other available therapies

The proportion of people with metastatic colorectal cancer who are eligible for treatment after other available therapies (33%) has been taken from table 83 of the manufacturer’s submission for TA405 (Servier Laboratories Ltd 2016). This proportion has been applied as a scaling factor to the point estimate and the lower and upper range calculated in step 6.

 

Point estimate

Lower range

Upper range

Reference

Number of females with metastatic colorectal cancer who are eligible for treatment after other available therapies

1,028

970

1,087

(5)

Number of males with metastatic colorectal cancer who are eligible for treatment after other available therapies

1,313

1,239

1,386

(5)

8. Proportion of the eligible population who will receive treatment with trifluridine–tipiracil

The proportion of the eligible population who will receive treatment with trifluridine–tipiracil has been estimated as 40% in year 3, based on the manufacturer’s submission for TA405 (Servier Laboratories Ltd 2016). This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 7.

 

Point estimate

Lower range

Upper range

Reference

Number of females who will receive treatment with trifluridine–tipiracil

411

388

435

(5)

Number of males who will receive treatment with trifluridine–tipiracil

525

496

554

(5)

9. Calculate estimated usage volume

The recommended starting dose of trifluridine–tipiracil in adults is 35 mg/m2/dose administered orally twice daily on days 1 to 5 and days 8 to 12 of each 28-day cycle (SmPC 2017). The average body surface area for people with colorectal cancer is 1.96m2 in males and 1.71m2 in females (Sacco 2010). A body surface area of 1.96m2 equates to a total daily dose of 130mg and a body surface area of 1.71m2 equates to a total daily dose of 120mg (SmPC 2017). In a 28 day period the average dose is calculated as 1,300mg (10 x 130mg) for males and 1,200mg (10 x 120mg) for females.

A phase 3 trial (Mayer 2015) to assess the efficacy and safety of trifluridine–tipiracil in a global population of 800 patients reported median overall survival of 7.1 months (217 days).

To calculate the annual use, the 28 day use has been multiplied by 7.75 (217/28). This equates to usage of 10,075mg for males and 9,300mg for females. This has been applied to the eligible population calculated in step 8, applied as a scaling factor to the point estimate and the upper and lower range.

 

Point estimate

Lower range

Upper range

Reference

Total estimated annual usage females (mg)

3,822,300

3,608,400

4,045,500

(6,7,8)

Total estimated annual usage males (mg)

5,289,375

4,997,200

5,581,550

(6,7,8)

Total estimated annual usage (mg)

9,111,675

8,605,600

9,627,050

(-)

References

  1. Office for National Statistics (2018) Cancer Registration Statistics, England: 2016. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancerregistrationstatisticscancerregistrationstatisticsengland [Accessed: 06/11/2018]
  2. Public health England. National Cancer Registration and Analysis Service (2016). Cancer survival by stage at diagnosis for England (experimental statistics): Adults diagnosed 2012, 2013 and 2014 and followed up to 2015. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/cancersurvivalbystageatdiagnosisforenglandexperimentalstatistics/adultsdiagnosed20122013and2014andfollowedupto2015 [Accessed 10/07/2017]
  3. Pezzullo (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from: https://statpages.info/confint.html [Accessed 14/01/2017]
  4. Kish T, Uppal P. (2016). Trifluridine/tipiracil (lonsurf) for the treatment of metastatic colorectal cancer. Pharmacy and Therapeutics, 41(5), p.314.
  5. Servier Laboratories Ltd (2016) The manufacturer’s submission for NICE technology appraisal 405. Available from: https://www.nice.org.uk/guidance/ta405 [Accessed: 24/01/2017].
  6. Sacco JJ, Botten J, Macbeth F, Bagust A, Clark P. The Average Body Surface Area of Adult Cancer Patients in the UK: A Multicentre Retrospective Study. Shea BJ, ed. PLoS ONE. 2010;5(1): e8933. doi:10.1371/journal.pone.0008933.
  7. Mayer RJ, Van Cutsem E, Falcone A, et al. (2015) Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909–1919. 
  8. Datapharm Communications Ltd (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 07/07/2017].

 

Overt hepatic encephalopathy – rifaximin (550mg)

1. Population who meet SmPC

The SmPC states that the medicine is indicated for an adult population only. Therefore, the starting population is adults aged 18 years and over in England.

 

Point estimate

Reference

England population aged 18 years and over

43,752,473

(1)

2. Prevalence of cirrhosis

Fleming et al (2008) has reported that the prevalence of cirrhosis for the whole population in the United Kingdom (UK) is 76.3 per 100,000 population.

To develop this estimate, the 95% confidence interval around this prevalence (95% CI 73.6 to 79.1) has been calculated using the exact binomial method (Pezzullo 2009).

The prevalence figure and calculated confidence interval has been applied to the adult population in England:

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with cirrhosis in England

 33,383

 32,202

 34,608

(2,3)

3. Proportion of people with cirrhosis where overt hepatic encephalopathy is present

Bajaj (2010) has reported that between 30% and 45% of people with cirrhosis have overt hepatic encephalopathy. The mid-point figure (37.5%) and reported range (30% to 45%) has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 2.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with cirrhosis where overt hepatic encephalopathy is present

 12,519

 9,661

 15,574

(4)

4. Proportion of people with overt hepatic encephalopathy who will receive treatment

The manufacturer’s submission for TA337 (Norgine 2013) has reported that 91% of people with overt hepatic encephalopathy will receive treatment for the condition. This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who will receive treatment

 11,392

 8,792

 14,172

(7)

5. Proportion of people likely to receive treatment with rifaximin

The manufacturer’s submission for TA337 (Norgine 2013) has reported that 40% of people are likely to receive treatment with rifaximin at year 5 in 2018 (rifaximin was first marketed in Jan 2013). This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 4 for all time periods.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people likely to receive treatment with rifaximin

 4,557

 3,517

 5,669

(7)

6. Calculate estimated usage volume

The SmPC reports that the recommended daily dose for rifaximin is 1,100mg (2 x 550mg tablets). The number of people likely to receive treatment with rifaximin (calculated in step 5) has been multiplied by 365 (days in a year) to produce an expected number of daily doses.

 

Point estimate

Lower range

Upper range

Estimated number of people likely to receive treatment with rifaximin (550mg)

 4,557

 3,517

 5,669

Total estimated annual usage (daily doses)

 1,663,305

 1,283,705

 2,069,185

References

  1. Office for National Statistics (2018) Annual Mid-year Population Estimates, 2017 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed: 06/11/2018].
  2. Fleming KM, Aithal GP, Solaymani-Dodaran M et al. (2008) Incidence and prevalence of cirrhosis in the United Kingdom, 1992-2001: a general population -based study. Journal of Hepatology 49: 732-8.
  3. Pezzullo. (2009) Exact Binomial and Poisson Confidence Intervals calculator. Available from https://statpages.info/confint.html [Accessed 14/01/2016]
  4. Bajaj J (2010) Review article: the modern management of hepatic. encephalopathy. Alimentary Pharmacology & Therapeutics 31: 537-547.
  5. Amodio P, Del Piccolo F, Petteno E (2001) Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. Journal of Hepatology 35: 37-45.
  6. Romero-Gomez M, Boza F, Garcia-Valdecasas MS (2001) Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. American Journal of Gastroenterology 96: 2718–23.
  7. Rifaximin (TARGAXAN® 550), Norgine Pharmaceuticals Ltd. Single technology appraisal (STA) Specification for manufacturer/sponsor submission of evidence (2013). Available from: https://www.nice.org.uk/guidance/ta337/resources [Accessed: 14/11/2016]
  8. Datapharm Communications Limited (2017) The electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 16/02/17]
  9. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: https://www.whocc.no/atc_ddd_index/ [Accessed: 16/02/2017]

 

Primary hypercholesterolaemia and mixed dyslipidaemia – alirocumab and evolocumab

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.

 

Point estimate

Reference

England population aged 20 years and over

42,450,335

(1)

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.

 

Point estimate

Reference

LDL-C of 4 mmol/litre or over and a high risk of CVD

 80,656

(2,4)

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.

 

Point estimate

Reference

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

 72,166

(2,4)

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.

 

Point estimate

Reference

High risk or very high risk of CVD with specified LDL-C levels

 152,822

N/A

5. Maximal tolerated lipidlowering 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.

 

Point estimate

Reference

Estimated eligible population

 33,621

(3)

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 31% in year 2 (2016). This figure has been adjusted +/- 10% to create a range (27.9% - 34.1%). These proportions have been applied as a scaling factor to the point estimate in step 5.

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population

 10,423

 9,380

 11,465

(4)

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.

 

Point estimate

Reference

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

 4,245

(2,4)

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.

 

Point estimate

Reference

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

 8,490

(2,4)

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.

 

Point estimate

Reference

Primary heterozygous familial hypercholesterolaemia total

 12,735

N/A

10. Maximal tolerated lipidlowering 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.

 

Point estimate

Reference

Maximal tolerated lipidlowering therapy

 2,802

(3)

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 41% in year 2 (2016). This figure has been adjusted +/- 10% to create a range (36.9% - 45.1%). These proportions have been applied as a scaling factor to the point estimate and the upper and lower ranges calculated in step 10.

 

Point estimate

Lower range

Upper range

Reference

Estimated treatment population

1,149

1,034

1,264

(4)

12. Calculate estimated usage volume (ADD)

The SmPC recommended dose for alirocumab is 75mg administered once every 2 weeks.  For those requiring a larger LDL-C reduction, a dose of 150mg once every 2 weeks or 300mg once every 4 weeks is recommended. The ADD for the 75mg/1ml solution for injection has been calculated as 5.4mg (75 x 26 / 365). The ADD for the 150mg/1ml solution for injection has been calculated as 10.7mg (150 x 26 / 365).

The SmPC recommended dose for evolocumab is 140mg every 2 weeks or 420mg once monthly. Evolocumab is recommended by NICE as an option for treating primary hypercholesterolaemia or mixed dyslipidaemia, only if the dosage is 140 mg every 2 weeks. The ADD has been calculated as 10mg (140 x 26 / 365). This is the same as the WHO DDD for evolocumab.

The number of people who are estimated to receive treatment with alirocumab or evolocumab (summed from step 6 and 11) has been multiplied by 365 (days in a year) to produce an expected volume of medicine per year in ADDs.

 

Point estimate

Lower range

Upper range

Number of people estimated to receive treatment with alirocumab or evolocumab

 11,572

 10,414

12,729

Total estimated annual usage (ADDs) 365 days

 4,223,780

 3,801,110

 4,646,085

References

  1. Office for National Statistics (2018) Annual Mid-year Population Estimates 2017. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed: 06/11/2018].
  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: https://www.whocc.no/atc_ddd_index/ [Accessed: 01/09/2017]
  6. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 01/09/2017].

 

Relapsing-remitting multiple sclerosis – dimethyl fumarate and teriflunomide

1. Population who meet SmPC

The SmPC states that both medicines are indicated for an adult population only. Therefore, the starting population is males and females aged 18 years and over in England.

 

Point estimate

Reference

England population female aged 18 years and over

22,352,862

(1)

England population males aged 18 years and over

21,399,611

(1)

2. Prevalence of multiple sclerosis

Mackenzie et al (2013) has reported the prevalence (and 95% confidence intervals) of multiple sclerosis for the whole population in the United Kingdom (UK):

Female prevalence per 100,000 UK pop in 2010: 285.8 (95% CI 277.7 to 293.1)

Male prevalence per 100,000 UK pop in 2010: 113.1 (95% CI 108.6 to 117.7)

The relevant prevalence figure and associated 95% confidence interval has been applied to the adult population in England:

 

Point estimate

Lower range

Upper range

Reference

Estimated number females aged 18 years and over with multiple sclerosis in England

 63,884

 62,074

 65,516

(2)

Estimated number males aged 18 years and over with multiple sclerosis in England

 24,203

 23,240

 25,187

(2)

Estimated number of people with multiple sclerosis aged 18 years and over

 88,087

 85,314

 90,703

 

3. Proportion of people with relapsing-remitting multiple sclerosis

Kobelt et al (2006) has reported that 35.5% of patients with multiple sclerosis in the UK have relapsing-remitting disease. This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 2.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people with relapsing-remitting multiple sclerosis

 31,271

 30,286

 32,200

(3)

4. Proportion of people who have previously received, or are currently receiving disease modifying therapy

The NICE costing template for TA320 (NICE 2014) has estimated that around 38.75% of people have previously received or are currently receiving disease modifying therapy. This is based on a longitudinal study of multiple sclerosis in south west England (Zejicek 2010). The associated range (33.75% to 43.75%) has been reported as part of the sensitivity analysis in the NICE costing template (NICE 2014). These proportions have been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 3.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people who have previously received, or are currently receiving disease modifying therapy

 12,118

 10,222

 14,088

(4,5)

5. Proportion of people likely to receive treatment with dimethyl fumarate or teriflunomide

The NICE costing template for TA320 (NICE 2014) has estimated that 55% of people will receive treatment with either dimethyl fumarate or teriflunomide. This proportion has been applied as a scaling factor to the point estimate and the upper and lower range calculated in step 4.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people likely to receive treatment with dimethyl fumarate or teriflunomide

 6,665

 5,622

 7,748

(5)

6. Calculate estimated usage volume

The number of people who are likely to receive treatment with dimethyl fumarate or teriflunomide (calculated in step 5) has been multiplied by 365 (days in a year) to produce an expected volume of medicine per year in daily doses. The daily dose is taken from the WHO DDD for dimethyl fumarate (480mg) and teriflunomide (14mg).

 

Point estimate

Lower range

Upper range

Reference

Estimated number of people likely to receive treatment with dimethyl fumarate or teriflunomide

 6,665

 5,622

 7,748

 

Total estimated annual usage (daily doses)

2,432,725

2,052,030

2,828,020

(6)

References

  1. Office for National Statistics (2018) Annual Mid-year Population Estimates, 2017 ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed: 06/11/2018].
  2. Mackenzie IS, Morant SV, Bloomfield GA et al. (2013). Incidence and prevalence of multiple sclerosis in the UK 1990–2010: a descriptive study in the General Practice Research Database. Journal of Neurol Neurosurg Psychiatry 10: 1136.
  3. Kobelt G, Berg J, Lindren P (2006) Costs and quality of life of multiple sclerosis in the United Kingdom. European Journal of Health Economics 7: 96-104.
  4. Zajicek J, Ingram W, Vickery J et al. (2010) Patient-orientated longitudinal study of multiple sclerosis in south west England (The south west impact of multiple sclerosis project, SWIMS)1: protocol and baseline characteristics of cohort, BioMedCentral Neurology 10: 88.
  5. NICE (2014) Costing template: TA320. Manchester: NICE. Available from: https://www.nice.org.uk/guidance/ta320/resources [Accessed: 10/08/2015].
  6. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: https://www.whocc.no/atc_ddd_index/ [Accessed: 16/02/2017]
  7. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 16/02/2017].

 

Secondary hyperparathyroidism in chronic kidney disease – etelcalcetide

1. Population in England

Etelcalcetide is recommended for use in adults only.

 

Point estimate

Reference

England population (18 years or over)

43,752,473

(1)

2. Proportion of adults having dialysis

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

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults having dialysis

24,808

24,501

25,114

(3,4)

3. Proportion of adults having haemodialysis

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

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults having haemodialysis

21,682

21,316

22,050

(3,4)

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.

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults having home haemodialysis

1,092

1,078

1,105

(4)

Estimated number of adults having haemodialysis excluding those on home haemodialysis

20,590

20,238

20,945

Calculated

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

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

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

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

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%).

 

Point estimate

Lower range

Upper range

Reference

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

2,677

1,498

3,875

(4, 5)

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

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

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

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults with Ca >2.2mmol/L

2,364

1,323

3,422

(3)

7. Proportion of adults for whom cinacalcet is not suitable

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

7a. Proportion of adults who do not tolerate cinacalcet

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

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults who do not tolerate cinacalcet

272

53

619

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

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

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

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults whose condition does not respond to cinacalcet

863

476

1,266

(6,7)

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

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

 

Point estimate

Lower range

Upper range

Reference

Estimated number of adults who do not adhere to cinacalcet

83

46

120

(8)

8. Estimated treatment population

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

 

Point estimate

Lower range

Upper range

Estimated treatment population

1,218

575

2,005

9. Calculate estimated usage volume

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

The number of people estimated to receive etelcalcetide (calculated in step 8) has been multiplied by the number of days in a year (365) to give the annual usage in DDDs.

 

Point estimate

Lower range

Upper range

Estimated number of people treated with etelcalcetide

1,218

575

2,005

Total estimated annual usage (DDDs)

444,570

209,875

731,825

References

  1. Office for National Statistics (2018) Annual Mid-year Population Estimates 2017. ONS: Newport. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland [Accessed 06/11/2018]
  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 https://statpages.info/confint.html [Accessed 17/06/2016].
  4. Byrne C, Caskey F, Castledine C et al. (2018) UK Renal Registry 20th Annual Report of the Renal Association. Nephron 2018;137: Suppl.1
  5. Fernandez-Martin JL, Carrero JJ, Benedik M et al. (2013) COSMOS: the dialysis scenario of CKD-MBD in Europe. Nephrology Dialysis Transplantation 28: 1922- 1935
  6. Block GA, Martin KJ, de Francisco ALM et al. (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. New England Journal of Medicine 350: 1516-1525
  7. Urena-Torres P, Bridges I, Christiano C et al. (2013) Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism. Nephrology Dialysis Transplantation 28: 1241 - 1254
  8. The EVOLVE Trial Investigators (2012) Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. New England Journal of Medicine 367: 2482 - 2492
  9. Ketteler M, Martin KJ, Wolf M et al (2012) Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study. Nephrology Dialysis Transplantation 27: 3270 - 3278
  10. Messa P, Macario F, Yaqoob M et al (2008) The OPTIMA Study: Assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clinical Journal of the American Society of Nephrology 3: 36 – 45
  11. Raggi P, Chertow GM, Urena-Torres P et al (2011) The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on haemodialysis. Nephrology Dialysis Transplantation 26: 1327 – 1339
  12. WHO (2017) ATC/DDD Index 2017. [WWW] WHO. Available from: https://www.whocc.no/atc_ddd_index/ [Accessed: 10 May 18]
  13. Datapharm Communications Limited (2017) The Electronic Medicines Compendium [WWW]. Available from: https://www.medicines.org.uk:443/emc/ [Accessed: 10 May 18]

 


Last edited: 29 April 2020 6:14 pm