In draft recommendations published today (24 October), NICE has recommended tobramycin dry powder for inhalation (Tobi Podhaler, Novartis) as an option for treating pseudomonas lung infection in people with cystic fibrosis. The draft guidance recommends tobramycin if:

• nebulised tobramycin is considered an appropriate treatment, that is, when nebulised colistimethate is contraindicated, not tolerated or has not produced an adequate clinical response, and
• the manufacturer provides tobramycin dry powder with the discount agreed as part of the patient access scheme to primary, secondary and tertiary care in the NHS.

Colistimethate sodium dry powder for inhalation (Colobreathe, Forest

Laboratories UK) is not recommended for treating chronic pulmonary infection caused by P. aeruginosa in people with cystic fibrosis. People currently using colistimethate sodium dry powder for inhalation (DPI) should be able to continue treatment until they and their clinician consider it appropriate to stop.

Cystic fibrosis is one of the UK's most common life-threatening inherited diseases, and currently affects around 8,000 people. Over two million people in the UK carry the faulty gene that causes cystic fibrosis - around 1 in 25 of the population. For a baby to be born with cystic fibrosis, both parents must be carriers of the faulty gene. If two carriers have a child, the baby has a 1 in 4 chance of having cystic fibrosis. The condition affects the internal organs, especially the lungs and digestive system, by clogging them with thick, sticky secretions, making it hard to breathe and digest food. Symptoms of cystic fibrosis can include a troublesome cough, repeated chest infections, prolonged diarrhoea and poor weight maintenance. People with the condition are prone to lung infections by a range of pathogens including Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa and Burkholderia cepacia. This may be because the thick mucus makes it difficult for the body to clear inhaled bacteria, and because people with cystic fibrosis have an increased airway inflammatory response to pathogens. The condition can also lead to pulmonary disease as well as cystic fibrosis related diabetes, male infertility and it can cause the blockage of small ducts in the liver. At present, there is no cure.

The aim of treatment in adults with cystic fibrosis is to clear the respiratory secretions in order to maintain lung function, as well as to reduce inflammation and bacterial growth in the respiratory tract. Treatment includes regular physiotherapy, antibiotics, and inhaled mucolyticsⁱ through a nebuliser.

Tobramycin sodium dry powder for inhalation (DPI) is inhaled using a breath activated, hand-held device and works by decreasing the amount of bacteria (Pseudomonas aeruginosa) in the lungs. The main goal is to improve or maintain lung function.

Colistimethate sodium DPI is also inhaled with a breath activated, hand-held device. It works by disrupting the structure of bacterial cells, which kills the bacteria.

The Committee noted that there was no economic analysis which compared colistimethate sodium DPI with nebulised colistimethate, the preferred comparator, according to clinical specialists on UK clinical practice. The results of the Committee's preferred economic analysis showed that colistimethate sodium DPI was less effective and less costly than nebulised tobramycin. The Committee concluded that although the analysis showed potential for cost savings, the clinical evidence for colistimethate sodium DPI was not robust enough to conclusively show that it is a cost-effective use of NHS resources.

The Committee noted that the results of the economic analysis for tobramycin DPI compared with nebulised tobramycin showed that tobramycin DPI was cheaper and slightly more effective, although associated with some uncertainty. Despite the limitations of all the data and the uncertainty in the model, the Committee agreed that it was reasonable to conclude that tobramycin DPI was a cost effective use of NHS resources in people with cystic fibrosis who would otherwise have been treated with nebulised tobramycin.

Professor Carole Longson, Health Technology Evaluation Centre Director at NICE said: "The Committee is aware that cystic fibrosis can have a very significant effect on the quality of life of patients and their carers. The primary cause of death in people with cystic fibrosis is respiratory failure resulting from chronic pulmonary infection caused by Pseudomonas aeruginosa. We are therefore pleased to recommend tobramycin dry powder as an option for treating such infections in people with cystic fibrosis.

Professor Longson continued: "In order for NICE to recommend any drug or technology, we have to be sure that it is both clinically and cost effective. Unfortunately in the case of colistimethate sodium DPI, the Committee concluded that there were significant limitations and uncertainty in the evidence available, and was, therefore, not able to recommend it. These draft recommendations are now available for public consultation and the manufacturers and other consultees are able to consider and respond to concerns and comments made by the Appraisal Committee."

The draft guidance (appraisal consultation document / ACD) can be found on the NICE website.

NICE has not yet issued final guidance to the NHS; these decisions may change after consultation.

Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments. Once NICE issues its guidance on a technology it replaces local recommendations across the country.

Final guidance is expected to be published in March 2013.

Ends

Notes to editors

References and explanation of terms

i. Mucolytics dissolve thick mucus and to help relieve respiratory difficulties.

About the guidance

1. The draft guidance (appraisal consultation document / ACD) can be found on the NICE website at: TA276

Closing date for comments is Tuesday 13 November. The second appraisal committee meeting is Tuesday 27 November.

2. Tobramycin DPI is administered twice daily, 28 days on and 28 days off (TOBI Podhaler, Novartis). It acts primarily by disrupting protein synthesis leading to altered cell membrane permeability, progressive disruption of the cell envelope and eventual cell death. Tobramycin inhibits protein synthesis of many gram-negative bacteria and it is active against P. aeruginosa.

3. Tobramycin DPI is administered using a TOBI Podhaler device and is indicated for the suppressive treatment of chronic pulmonary infection caused by P. aeruginosa in adults and children aged 6 years and older with cystic fibrosis.

4. The recommended dosage for tobramycin DPI is 112 mg tobramycin (4×28-mg capsules), administered twice daily for 28 days using the TOBI Podhaler device in alternating cycles of 28 days on treatment followed by 28 days off treatment. The price for a pack of 56 ×28-mg capsules and 1 Podhaler device is £447.50 (excluding VAT; ‘British National formulary' [BNF] edition 62). The list price cost for 56 days of treatment is therefore £1790 excluding VAT. Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of tobramycin DPI has agreed a patient access scheme with the Department of Health, details of which are confidential.

5. The Committee concluded that tobramycin DPI was cost effective at a threshold of £20,000 per QALY gained, and in combination with the associated patient access scheme could be considered an acceptable use of NHS resources.

6. Tobramycin dry powder is accepted for use within NHS Scotland.

7. Colistimethate sodium dry powder for inhalation (DPI), 125 mg capsules administered twice daily (Colobreathe, Forest Laboratories UK), is a formulation of colistimethate sodium supplied as hard capsules for use with an inhaler. It belongs to the polymixin class of antibacterials and works by disrupting the structure of the bacterial cell membrane, leading to bacterial death. It is active against aerobic gram-negative organisms including P. aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.

8. Colistimethate sodium DPI is administered using the ‘Turbospin' device, which is a breath-activated, reusable dry powder inhaler. Colistimethate sodium DPI is indicated for the management of chronic pulmonary infections caused by P. aeruginosa in patients with cystic fibrosis aged 6 years and older.

9. The recommended dosage for colistimethate sodium DPI is 1 capsule (approximately equal to 125 mg of colistimethate sodium) to be inhaled twice daily using the ‘Turbospin' inhaler device. The price for a 28-day pack is £968 (excluding VAT; price provided by the manufacturer). The list price cost for 56 days of treatment is therefore £1936 excluding VAT. Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of colistimethate sodium DPI has agreed a patient access scheme with the Department of Health, details of which are confidential.

10. The Committee noted that there was no clinical or cost-effectiveness evidence comparing colistimethate sodium DPI with the most appropriate comparator, nebulised colistimethate sodium. Based on the Assessment Group's analysis (preferred by the Committee), the ICER for colistimethate sodium DPI compared with nebulised tobramycin was £52,700 saved per QALY lost (that is, colistimethate sodium DPI is less effective but also less expensive than nebulised tobramycin). The Committee did not have sufficient confidence in the clinical-effectiveness results to be sure that the disutility was acceptable given the financial saving. An additional consideration was that, in the analysis using the E-MIT price for nebulised tobramycin, colistimethate sodium DPI was dominated by nebulised tobramycin; that is nebulised tobramycin was more effective and cost less.

11. Colistimethate sodium dry powder for inhalation has not yet been appraised by the Scottish Medicines Consortium.

Related NICE guidance

Under development

12. NICE technology appraisal on Mannitol dry powder for inhalation for treating cystic fibrosis.

About NICE

13. The National Institute for Health and Care Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health.

14. NICE produces guidance in three areas of health:

• public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

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• quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
• Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients.

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