As part of our ongoing seminar series, the Centre of Excellence in Severe Asthma hosted Dr. Robert Niven, for a webinar on “Clinical Trials Endpoints for Severe Asthma” on 08 March, 2017.
Presentation Summary:
A range of clinical trial endpoints are used when assessing therapies for severe asthma. These include lung function, exacerbations, health status, quality of life, bronchial hyperreactivity, airway inflammation and steroid-sparing effects. Different outcomes measures provide different information about the effects of treatment. The use of different clinical trials endpoints for different treatments makes it difficult to compare trials. The relative benefits and drawbacks of clinical trial endpoints are discussed.
Careful selection of endpoint measures is critical. Clinical trial endpoints have largely been selected based on the predicted treatment response for each individual drug. As a result, different outcome measures are assessed for different drugs. Dr. Niven argues that endpoint measures must consider the treatment approach and relevant patient outcomes.
Key Points:
- A range of clinical trial endpoint measures can be used as the primary endpoint in clinical trials of asthma interventions
- What treatment outcomes matter most is different between patients, healthcare providers, payers and pharmaceutical companies
- Historically, lung function measurements (e.g. FEV1) have been used to assess treatment efficacy
- For example, combined low-dose ICS and LABA treatment improved lung function
- Exacerbation rates are now frequently used as the clinical endpoint
- In contract to lung function findings, high-dose ICS treatment was required to reduce severe exacerbations
- Peak flow measurement is not typically used as a clinical trial endpoint, partially due to the subjective nature of testing
- Health status or quality of life questionnaires (e.g. ACQ, AQLQ) provide information on patient perception of symptoms
- Large placebo effects have been observed using questionnaires, particularly when interventions are invasive (e.g. i.v. injections or bronchoscopy)
- Bronchial hyperreactivity measures are unchanged following targeted therapy, potentially due to the amount of time required to cause changes (e.g. months to years)
- Quantification of eosinophils or airway inflammation is objective, but changes may not reflect changes in outcomes relevant to patients
- Patients express a preference for steroid-sparing outcomes, which allow reductions in oral corticosteroid use and reduce associated side effects
- Assessing for steroid-sparing effects in blinded clinical trials can be difficult
- Outcomes based on healthcare utilisation (e.g. hospitalisations) may be useful to provide justification for the use of expensive add-on therapies
- Monoclonal antibody therapies must be targeted to appropriate patient populations and do not improve outcomes in unselected patient populations
- Clinical trials of monoclonal antibodies have been performed using primary outcomes most relevant to each drug, rather than the outcomes most relevant to patients
About Dr. Robert Niven:
Dr. Robert Niven runs a supra-regional service for severe asthma. He has assessed over 2,000 severe asthma patients, with around 50% of these referrals being for patients on maintenance oral steroids. He is a core member of the UK National Severe Asthma Network, with nearly 1,000 patients entered onto a national database from multiple centres, with Manchester a core contributor.
He has published over 100 peer-reviewed papers and 5 book chapters. Areas of interest have included occupational lung disease, environmental epidemiology and clinical practice in severe asthma. His research has assessed hypertonic saline for bronchiectasis therapy, awareness and diagnosis of dysfunctional breathing patterns, the role of antifungal therapy in severe asthma with fungal sensitisation and trials of bronchial thermoplasty and new biologics.
