Draft guidance recommends clinical trial for severe COPD drug

Draft guidance recommends clinical trial for severe COPD drug
New draft guidance from NICE recommends the use of roflumilast (Daxas, Merck, Sharp & Dohme) in the context of research, as part of a clinical trial for adults with severe chronic obstructive pulmonary disease[1], associated with chronic bronchitis, as an add on to bronchodilator treatment for people with a history of frequent exacerbations.[2]

After carefully considering the evidence, NICE's independent appraisal committee concluded there was great uncertainty about the effect of roflumilast on reducing the rate of exacerbations as an add-on to triple[3] or dual therapy[4] for people with severe COPD. For that reason, the draft guidance recommends setting up a trial to assess its clinical effectiveness for this indication. The draft guidance also recommends that it should be compared with theophylline[5] in people for whom this drug might be suitable.

In line with the technology appraisals process this draft guidance has now been issued for consultation: NICE has not yet published final guidance to the NHS. Final guidance is expected in January 2012.

There are currently 1 million people with COPD in England and Wales, and it is estimated that almost 200,000 would be eligible for treatment with roflumilast by 2015. Likely treatment duration would be many years.

Commenting on NICE's draft recommendation, Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: "The independent appraisal committee concluded that roflumilast was most likely to be used in addition to triple therapy, but the committee was concerned about the lack of clinical evidence available on the use of roflumilast in that way. As there was great uncertainty about how well the treatment works alongside triple therapy, the committee could not establish that it would be good value for money.

"As a result, the committee discussed whether it was appropriate to recommend the set up of a research trial to determine the clinical effectiveness of roflumilast on top of triple or dual therapy. In this case, the committee felt that the benefits and costs of carrying out the research would be favourable to the NHS.

"While we recognise it is important for people with severe COPD to have a range of options, NICE has to ensure that the NHS provides treatments which are effective and value for money. We hope a clinical study would generate robust evidence so that we can be clear about the benefits roflumilast brings for these patients.

"We encourage Merck, Sharp & Dohme, patient organisations and other relevant third parties to comment on this preliminary recommendation during this public consultation period so that they can contribute to the development of this guidance."


Notes to Editors
About the guidance
1. The appraisal consultation document (ACD) will be available from Friday 9 September 2011 at http://guidance.nice.org.uk/TA/Wave24/13. Consultation will take place between 9 - 30 September.

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 £37.71 for a 30-tablet pack and £113.14 for a 90-tablet 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 the manufacturer (Merck, Sharp & Dohme) funds a clinical trial (including the cost of the drug) designed to address the remaining uncertainty about the effectiveness of the drug when used in combination with currently recommended treatment regimens.

About NICE
1. The National Institute for Health and Clinical 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 sectorhealth technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHSclinical 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 servicesQuality 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. NICEprovides 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.




[1] Severe chronic obstructive pulmonary disease is defined as forced expiratory volume in 1 second [FEV1] post-bronchodilator less than 50% predicted

[2] 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.

[3] Triple therapy is defined as long-acting muscarinic antagonists (LAMA) plus long-acting beta2 agonists (LABA) plus inhaled corticosteroids (ICS).

[4] Dual therapy is defined as LAMA plus LABA for those people who are intolerant to, or decline, ICS.

[5] Theophylline is an option for people with severe COPD who have had a trial of short-acting bronchodilators and long-acting bronchodilators, or who cannot use inhaled therapy.

This page was last updated: 08 September 2011