Outcomes in Clinical Trials of Inhaled Corticosteroids for Children with Asthma Are Narrowly Focussed on Short Term Disease Activity

Background

Little work has been done to determine which outcomes should be measured in randomised controlled trials (RCTs) in children with asthma. Drug regulatory authorities require that short term disease activity is measured, but other outcome domains are not mandatory for licensing and marketing purposes. We aimed to identify whether any domains were underrepresented in RCTs of regular therapies for children with asthma over a 20 year period, and to examine what consistency there was between RCTs in the outcomes used to assess the domains.

Methodology/Principal Findings

By searching the Cochrane Central Register of Controlled Trials in January 2008, we identified all parallel-group RCTs, published between January 1988 and December 2007, which assessed inhaled corticosteroids (ICS) as regular therapy for children with asthma. We evaluated how frequently RCTs measured the following pre-defined domains: disease activity; disease damage; functional status; quality of life; health resource utilisation; and adverse effects of therapy. Our initial search identified 1668 abstracts, of which 412 were retrieved in full. 159 RCTs, of which 115 involved only children and 44 involved children and adults, were included in the review. Disease activity was measured in 157 RCTs, adverse effects of ICS in 135, functional status in 25, quality of life in 21, and health resource utilisation in 17. No RCT measured long term disease damage, although two used FEV1 as a measure of ‘lung growth’. RCTs were inconsistent in the outcomes used to measure the domains.

Conclusions

Short term disease activity is the most frequently measured outcome domain in RCTs in children with asthma. Effects of regular therapies on functional status, quality of life, and long term consequences of asthma are infrequently assessed. A core set of outcomes, developed using consensus techniques, would standardise the measurement of appropriate outcomes in these RCTs. Involving patients would identify outcomes which are most relevant from their perspective.