Clinically Relevant Outcomes for New Asthma Therapies
Clinically Relevant Outcomes for New Asthma Therapies
Symptoms, medication needs, quality of life (QOL) questionnaires and exacerbations are commonly used to assess the effects of new medications.
Asthmatic patients usually consult for symptoms, and clinicians mainly base their treatment on these last. Symptoms are a direct representation asthma control, and although quite subjective, they are cheap and easy to record. Most symptoms are nonspecific and relate to the perception of patients. Symptoms-based treatment strategies have been successfully used in randomized clinical studies. Asthma symptoms can be recorded in diaries (paper/electronic) and time of occurrence (morning/evening/night), intensity (different scales) and sometimes impact on activities can be recorded. A visual analogue score can be used to assess overall or specific symptoms. Few validated instruments are however available and several authors consider symptoms-free periods as an adequate measure of symptoms.
Asthma control composite score tools have been used in most recent clinical studies. Questionnaires, with or without physiologic measures such as forced expiratory flows in one second (FEV1) or peak expiratory flows (PEFs) or, on a single occasion, with airway inflammation measures, capture the multifaceted picture of asthma control. Most of these former instruments, including the new RAND Asthma Control Measure, have been validated. Bousquet et al. stressed that the best for asthma control tests would be to associate old methods with newer e-health technologies (e.g. using smartphones), while keeping the questionnaires simple and user-friendly.
The use of fast-acting inhaled bronchodilators, a marker of asthma control and a predictor of exacerbations when increased, reflects asthma variability and airway obstruction reversibility and is included in most composite control scores. The use of fast-acting inhaled bronchodilators as a preventive treatment before an asthma trigger (e.g. exercise) or in combination with inhaled corticosteroids (ICS), both as maintenance and rescue therapy, would however benefit from a reassessment of this outcome measure as a control criterion.
Exacerbations are usually defined as an event requiring a change in treatment, while the need for a short course of systemic corticosteroids usually defines a severe exacerbation. To keep them simple, most definitions avoid adding an objective measurement of the worsening lung function, such as a fall in either PEF or FEV1. A recent lack of control, increased PEF fluctuations, significant airway inflammation and poor adherence to anti-inflammatory treatments are predictors of exacerbations. Time to the first exacerbation and number, duration, onset and resolution time of exacerbations are often used as key outcomes to assess treatments, including recently developed biologics such as anti-interleukin-5 (IL5) or bronchial thermoplasty.
They have been many attempts to consider pharmaco-economic data as potential outcomes in asthma, particularly when severe. Indeed, severe asthma represents the major component of healthcare resources use. Furthermore, new therapies, such as biologics, by essence expensive, require an assessment of their potential cost–benefit. The results of such studies are heterogeneous, considering the populations investigated, the databases, the different parameters and the broad range of disease severity.
Health-related quality of life (HRQOL) is a patient-related outcome used to assess the perceived burden of asthma. Quality of life questionnaires have been validated and compared. They are easy to use and have been translated in various languages. They are more difficult to use in a routine clinical setting and have been shown to be less susceptible to change in severe asthma. HRQOL and asthma control improve in parallel and the former has been used in many clinical trials as a surrogate marker of control. Several questionnaires have been extensively used such as the AQLQ and the St Georges respiratory questionnaires. Some advocate for a combined use of generic and disease-specific QOL questionnaires, which may better assess the intangible costs of asthma and may allow comparison with other chronic disorders.
HRQOL takes into account not only the impact of asthma control and severity but also the impact of comorbid conditions and the potential additional burden of treatment side effects. They should be used according to the patient language and the cultural background and not modified from the validated form. They have been mainly used as a research tool in academic and drug-sponsored studies, but they can be used in pragmatic studies.
Clinical Outcomes
Symptoms, medication needs, quality of life (QOL) questionnaires and exacerbations are commonly used to assess the effects of new medications.
Symptoms
Asthmatic patients usually consult for symptoms, and clinicians mainly base their treatment on these last. Symptoms are a direct representation asthma control, and although quite subjective, they are cheap and easy to record. Most symptoms are nonspecific and relate to the perception of patients. Symptoms-based treatment strategies have been successfully used in randomized clinical studies. Asthma symptoms can be recorded in diaries (paper/electronic) and time of occurrence (morning/evening/night), intensity (different scales) and sometimes impact on activities can be recorded. A visual analogue score can be used to assess overall or specific symptoms. Few validated instruments are however available and several authors consider symptoms-free periods as an adequate measure of symptoms.
Composite Scores
Asthma control composite score tools have been used in most recent clinical studies. Questionnaires, with or without physiologic measures such as forced expiratory flows in one second (FEV1) or peak expiratory flows (PEFs) or, on a single occasion, with airway inflammation measures, capture the multifaceted picture of asthma control. Most of these former instruments, including the new RAND Asthma Control Measure, have been validated. Bousquet et al. stressed that the best for asthma control tests would be to associate old methods with newer e-health technologies (e.g. using smartphones), while keeping the questionnaires simple and user-friendly.
Use of Rescue Bronchodilators
The use of fast-acting inhaled bronchodilators, a marker of asthma control and a predictor of exacerbations when increased, reflects asthma variability and airway obstruction reversibility and is included in most composite control scores. The use of fast-acting inhaled bronchodilators as a preventive treatment before an asthma trigger (e.g. exercise) or in combination with inhaled corticosteroids (ICS), both as maintenance and rescue therapy, would however benefit from a reassessment of this outcome measure as a control criterion.
Exacerbations
Exacerbations are usually defined as an event requiring a change in treatment, while the need for a short course of systemic corticosteroids usually defines a severe exacerbation. To keep them simple, most definitions avoid adding an objective measurement of the worsening lung function, such as a fall in either PEF or FEV1. A recent lack of control, increased PEF fluctuations, significant airway inflammation and poor adherence to anti-inflammatory treatments are predictors of exacerbations. Time to the first exacerbation and number, duration, onset and resolution time of exacerbations are often used as key outcomes to assess treatments, including recently developed biologics such as anti-interleukin-5 (IL5) or bronchial thermoplasty.
Costs of Asthma
They have been many attempts to consider pharmaco-economic data as potential outcomes in asthma, particularly when severe. Indeed, severe asthma represents the major component of healthcare resources use. Furthermore, new therapies, such as biologics, by essence expensive, require an assessment of their potential cost–benefit. The results of such studies are heterogeneous, considering the populations investigated, the databases, the different parameters and the broad range of disease severity.
Health-related Quality of Life
Health-related quality of life (HRQOL) is a patient-related outcome used to assess the perceived burden of asthma. Quality of life questionnaires have been validated and compared. They are easy to use and have been translated in various languages. They are more difficult to use in a routine clinical setting and have been shown to be less susceptible to change in severe asthma. HRQOL and asthma control improve in parallel and the former has been used in many clinical trials as a surrogate marker of control. Several questionnaires have been extensively used such as the AQLQ and the St Georges respiratory questionnaires. Some advocate for a combined use of generic and disease-specific QOL questionnaires, which may better assess the intangible costs of asthma and may allow comparison with other chronic disorders.
HRQOL takes into account not only the impact of asthma control and severity but also the impact of comorbid conditions and the potential additional burden of treatment side effects. They should be used according to the patient language and the cultural background and not modified from the validated form. They have been mainly used as a research tool in academic and drug-sponsored studies, but they can be used in pragmatic studies.
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