NICE says more data needed on severe COPD drug
Final draft guidance from NICE on the use of roflumilast (Daxas, Merck Sharp & Dohme) recommends setting up a clinical trial to establish how effective it is for adults with severe chronic obstructive pulmonary disease, associated with chronic bronchitis, as an add-on to bronchodilator treatment for people with a history of frequent exacerbations.
Roflumilast is most likely to be used in addition to triple therapy, but there was no direct clinical trial evidence related to roflumilast used in this way. It is therefore not possible to know whether roflumilast is a cost-effective use of NHS resources. For that reason, NICE's independent Appraisal Committee concluded that a clinical trial providing robust data about its clinical and cost effectiveness at this point in the treatment pathway would be beneficial for the NHS.
The trial should be designed to consider how well roflumilast works, and its cost-effectiveness, as an add-on to triple or dual therapy.
There are currently 1 million people with COPD in England and Wales, and it is estimated that almost 88,000 would be eligible for treatment with roflumilast by 2015. Likely treatment duration would be many years.
Commenting on NICE's final draft recommendation, Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: "The Committee noted that, in usual practice, roflumilast was most likely to be used in addition to triple therapy, but there were no directly relevant clinical trial data on this treatment regimen for the Committee to consider. There are a lot of people with COPD, and those likely to be treated with roflumilast could receive treatment for a long time. This meant that a high degree of uncertainty about the clinical and cost effectiveness was not acceptable to the Committee.
"For this reason, the Committee has recommended a clinical trial of roflumilast in the same combination in which it would be used in clinical practice. It felt, on balance, the benefits and costs of conducting the research were justified. A new clinical trial is a good opportunity to gather robust evidence to help inform future clinical practice."
The final draft guidance (called a final appraisal determination) is now with interested third parties, who have the opportunity to appeal against it and highlight any factual errors.
If NICE does not receive any appeals then final guidance will be published in January 2012.
Until NICE issues its final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
Notes to Editors
About the guidance
1. The final appraisal determination will be available from Thursday 8 December at http://guidance.nice.org.uk/TA/Wave24/13. Please contact the press office for embargoed copies. Consultees have until Thursday 6 January to appeal this final draft guidance.
2. NICE is developing guidance on using roflumilast for the management of chronic obstructive pulmonary disease in the NHS in England and Wales.
3. Roflumilast (Daxas, Merck Sharp & Dohme) has a marketing authorisation for maintenance treatment of severe chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second [FEV1] post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment.
4. Roflumilast is an orally administered long-acting selective phosphodiesterase-4 (PDE4) enzyme inhibitor which targets cells and mediators in the body believed to be important in chronic obstructive pulmonary disease. Roflumilast relieves the symptoms of COPD through an anti-inflammatory effect. It has been shown to inhibit chemotaxis, leukocyte infiltration, and cytokine production in vitro and in animal models of COPD and reduced neutrophils and eosinophils in the airways of patients with COPD.
5. The recommended dose is one 500 micrograms tablet daily.
6. Roflumilast is priced at £37.31 for a 30-tab pack and £113.14 for a 90-tab pack (excluding VAT; ‘British national formulary' [BNF] edition 61). Costs may vary in different settings because of negotiated procurement discounts.
7. Before the Appraisal Committee can make an ‘only in research' recommendation, the following factors need to be considered:
- The intervention should have a reasonable prospect of providing benefits to patients in a cost-effective way.
- The research can realistically be set up, is already planned, or is already recruiting patients.
- There is a real prospect that the research will inform future NICE guidance.
- The broad balance of the benefits and costs of conducting the research are favourable.
8. The ‘only in research' recommendation means that NICE is recommending that a clinical trial is conducted to address the remaining uncertainty about the effectiveness of the drug when used in combination with currently recommended treatment regimens.
9. The Committee concluded that the research should be designed to generate relevant data about the benefits of roflumilast as an add on to long-acting muscarinic antagonists (LAMA) plus long-acting beta2 agonists (LABA) plus inhaled corticosteroids (ICS), known as triple therapy, or LAMA plus LABA for those people who are intolerant to, or decline, ICS, known as dual therapy.
1. 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.
2. 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.
3. NICE produces standards for patient care:
- 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.
4. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.
 Severe chronic obstructive pulmonary disease is defined as forced expiratory volume in 1 second [FEV1] post-bronchodilator less than 50% predicted
 An exacerbation is when a patient's symptoms become particularly severe and possibly very debilitating. Having frequent exacerbations is generally regarded as having two exacerbations or more in one year.
 Triple therapy is defined as long-acting muscarinic antagonists (LAMA) plus long-acting beta2 agonists (LABA) plus inhaled corticosteroids (ICS).
 Dual therapy is defined as LAMA plus LABA for those people who are intolerant to, or decline, ICS.
This page was last updated: 07 December 2011