Appendix B
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Proposed Technology Appraisal
Colistimethate sodium powder for inhaler device for the treatment of Pseudomonas aeruginosa lung
infection in cystic fibrosis
Draft scope (Pre-referral)
Draft remit/appraisal objective
To appraise the clinical and cost effectiveness of colistimethate sodium powder for inhaler device within its licensed
indication for the treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis.
Background
Cystic fibrosis is an inherited condition characterised by abnormal transport of chloride and sodium across the epithelium
in all exocrine tissues, leading to thick viscous secretions in the lungs, pancreas, liver, intestine, and reproductive tract,
and an increase in the salt content in sweat gland secretions.
Cystic fibrosis has an incidence of 1 in 2500 live births. In 2007, there were 8080 people with cystic fibrosis registered
with the Cystic Fibrosis Trust in the UK, and more than half were older than 16 years of age. About 1 in 25 people in the
UK of white European decent are carriers of the cystic fibrosis gene. It is much less common in Afro-Caribbean and Asian
people. Although cystic fibrosis is a progressive condition, it has an improving prognosis leading to a rapidly increasing
number of adult patients with inevitably more severe problems. In 2005, 97 deaths from cystic fibrosis were recorded in
England and Wales, of which 56 had pulmonary manifestations.
While cystic fibrosis is a multi system disease, the primary cause of death in people with cystic fibrosis is respiratory
failure resulting from chronic pulmonary infection. Pseudomonas aeruginosa, is a bacterium which is the most frequent
cause of lung infection in early childhood. The length and quality of life for people with cystic fibrosis is thought to be
strongly influenced by the success or failure to eradicate Pseudomonas aeruginosa in early childhood and by subsequent
antibiotic treatment of respiratory infective exacerbations. In 2003, the age-specific prevalence of Pseudomonas
aeruginosa in pre-school aged children with cystic fibrosis was 9% rising to 32% for 10 to 15 year olds.
Management of Pseudomonas aeruginosa lung infection in cystic fibrosis involves treatment with antibiotics to suppress
bacterial growth. Current treatment options include the use of inhaled antibiotics (such as nebulised colistimethate
sodium or tobramycin) effective against Pseudomonas aeruginosa. Inhaled antibiotic therapy may also be combined with
oral antibiotics (such as ciprofloxacin) to eradicate first or intermittent Pseudomonas aeruginosa colonisation.
Intermittent administration of intravenous anti-pseudomonal antibiotics may also be given for chronic infection.
The technology
Colistimethate sodium powder for inhalation (Colobreathe, Forest Laboratories UK) belongs to the polymixins class of
antibacterials and works by disrupting the structure of the bacterial cell membrane, leading to bacterial death. It is active
against Gram-negative organisms including Pseudomonas aeruginosa, Acinetobacter baumanii, and Klebsiella
pneumoniae. It is supplied as hard capsules which are administered using a ‘Turbospin’ inhaler device.
Colistimethate sodium powder for inhalation does not currently have UK marketing authorisation for the treatment of
Pseudomonas aeruginosa lung infection in cystic fibrosis. It has been studied in a clinical trial in people with Pseudomonas
aeruginosa lung infection (including colonisation) in cystic fibrosis compared to nebulised tobramycin.
National Institute for Health and Clinical Excellence
Draft scope for the proposed appraisal of colistimethate sodium powder for inhaler device for the treatment of Pseudomonas
aeruginosa lung infection in cystic fibrosis
Intervention(s)
Colistimethate sodium powder inhaler (Colobreathe)
Population(s)
People with cystic fibrosis and Pseudomonas aeruginosa lung infection
(including colonisation)
Colistimethate sodium for inhalation with a nebuliser and other
nebulised antibiotics effective against Pseudomonas aeruginosa
Comparators
Outcomes
The outcome measures to be considered include:
 mortality
 lung function
 respiratory symptoms
 reduction in hospital admissions
 adverse effects of treatment
 health-related quality of life
The reference case stipulates that the cost effectiveness of treatments
should be expressed in terms of incremental cost per quality-adjusted
life year.
The reference case stipulates that the time horizon for estimating
clinical and cost effectiveness should be sufficiently long to reflect any
differences in costs or outcomes between the technologies being
compared.
Costs will be considered from an NHS and Personal Social Services
perspective.
Guidance will only be issued in accordance with the marketing
authorisation.
If evidence allows, colistimethate sodium resistance of Pseudomonas
aeruginosa will be considered.
Economic analysis
Other considerations
Related
recommendations
NICE
Related Guidelines:
Clinical Guideline No. 69, July 2008, ‘Prescribing of antibiotics for selflimiting respiratory tract infections in adults and children in primary
care’. Review date: July 2011
Questions for consultation
What are the most appropriate antibiotics used for the treatment of Pseudomonas aeruginosa lung infection in cystic
fibrosis? Can they be nebulised?
Are there any subgroups of people in whom the technology is expected to be more clinically effective and cost effective
or other groups that should be examined separately?
Are there any issues that require special attention in light of the duty to have due regard to the need to eliminate
unlawful discrimination and promote equality?
NICE intends to appraise this technology through its Single Technology Appraisal (STA) Process. We welcome comments
on the appropriateness of appraising this topic through this process. (Information on the Institute’s Technology Appraisal
processes is available at
http://www.nice.org.uk/aboutnice/howwework/devnicetech/technologyappraisalprocessguides/technology_appraisal_p
rocess_guides.jsp)
National Institute for Health and Clinical Excellence
Draft scope for the proposed appraisal of colistimethate sodium powder for inhaler device for the treatment of Pseudomonas
aeruginosa lung infection in cystic fibrosis
Appendix C
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Proposed Single Technology Appraisal (STA)
Colistimethate sodium powder for inhaler device for the treatment of Pseudomonas aeruginosa
lung infection in cystic fibrosis
Provisional matrix of consultees and commentators
Consultees
Commentators (no right to submit or appeal)
Manufacturers/sponsors

Forest Laboratories UK (colistimethate sodium
powder; ‘Turbospin’ inhaler device)
General

Board of Community Health Councils in Wales

British National Formulary

Commissioning Support Appraisals Service

Department of Health, Social Services and Public Safety
for Northern Ireland

Medicines and Healthcare products Regulatory Agency

National Association of Primary Care

National Public Health Service for Wales

NHS Alliance

NHS Confederation

NHS Purchasing and Supply Agency

NHS Quality Improvement Scotland

Scottish Medicines Consortium
Patient/carer groups

Action for Children

Action for Sick Children

Afiya Trust

Association for Children with Life Threatening or
Terminal Conditions

Black Health Agency

British Lung Foundation

Carers UK

Children’s Society

Chinese National Healthy Living Centre

Cystic Fibrosis Trust

Equalities National Council

Muslim Council of Great Britain

Muslim Health Network

National Children’s Bureau

National Parent Partnership Network

South Asian Health Foundation

Specialised Healthcare Alliance

WellChild
Professional groups

Association of Respiratory Nurse Specialists

British Thoracic Society

General Practice Airways Group

Royal College of General Practitioners

Royal College of Nursing

Royal College of Paediatrics & Child Health

Royal College of Pathologists

Royal College of Physicians

Royal Pharmaceutical Society

Royal Society of Medicine – Intellectual Disabilities
Forum

United Kingdom Clinical Pharmacy Association
Others

Department of Health

NHS Westminster

Vale of Glamorgan LHB

Welsh Assembly Government
Possible comparator manufacturer(s)

Actavis UK (tobramycin)

Chiesi (tobramycin)

Flynn Pharma (tobramycin)

Forest Laboratories UK (colistin sulphate, colistimethate
sodium)

Hospira UK (tobramycin)

King Pharmaceuticals (tobramycin)

Novartis Pharmaceuticals (tobramycin

Profile Pharma (colistimethate sodium)

Teva UK (tobramycin)
Relevant research groups

Cochrane Airways Group

MRC Clinical Trials Unit

National Institute for Health Research
Evidence Review Group

Evidence Review Group tbc

National Institute for Health Research
Health Technology Assessment Programme
Associated Guideline Groups

National Clinical Guidelines Centre

National Collaborating Centre for Women and Children’s
Health
Associated Public Health Groups

tbc
NICE is committed to promoting equality and eliminating unlawful discrimination. Please let us know if we have missed
any important organisations from the lists contained within the matrix and which organisations we should include who
have a particular focus on relevant equality issues.
National Institute for Health and Clinical Excellence Provisional matrix for the proposed technology appraisal of colistimethate sodium
powder for inhaler device for the treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis
Definitions:
Consultees
Organisations that accept an invitation to participate in the appraisal; the manufacturer(s) or sponsor(s) of the
technology; national professional organisations; national patient organisations; the Department of Health and the
Welsh Assembly Government and relevant NHS organisations in England.
The manufacturer/sponsor of the technology is invited to make an evidence submission, respond to consultations and
has the right to appeal against the Final Appraisal Determination (FAD).
All non-manufacturer/sponsor consultees are invited to submit a statement 1, respond to consultations, nominate
clinical specialists or patient experts and have the right to appeal against the Final Appraisal Determination (FAD).
Commentators
Organisations that engage in the appraisal process but that are not asked to prepare an evidence submission or
statement, are able to respond to consultations and they receive the FAD for information only, without right of appeal.
These organisations are: manufacturers of comparator technologies; NHS Quality Improvement Scotland; the relevant
National Collaborating Centre (a group commissioned by the Institute to develop clinical guidelines); other related
research groups where appropriate (for example, the Medical Research Council [MRC], National Cancer Research
Institute); other groups (for example, the NHS Confederation, NHS Information Authority and NHS Purchasing and
Supplies Agency, and the British National Formulary.
All non-manufacturers/sponsors commentators are invited to nominate clinical specialists or patient experts.
Evidence Review Group (ERG)
An independent academic group commissioned by the National Institute for Health Research (NIHR) Health Technology
Assessment Programme (HTA Programme) to assist the Appraisal Committee in reviewing the manufacturer/sponsor
evidence submission to the Institute.
1
Non manufacturer consultees are invited to submit statements relevant to the group they are representing.