A recent study is a perfect illustration of the difficulties physicians face in comparing one biological asthma drug to another, experts say.
Writing in the Lancet Respiratory Medicine Phillip Korenblat and James Wedner from the Washington School of Medicine say the diversity of statistical methods applied to studies of biologics in patients with asthma, and the differing outcome variables used, make the comparison of one drug to another “at times difficult if not impossible”.
A recently published phase 2 study on the safety and efficacy of tralokinumab is a case in point, they say.
The investigators chose an annual asthma exacerbation rate as the primary outcome variable in a group of adults with severe uncontrolled asthma who had had a minimum of two exacerbations in the year before entry into the study.
They based their αlpha level* of 0·1 on a conservative estimate of 1·2 exacerbations per year; however, the actual asthma exacerbation rate in the control population was less than one exacerbation per year.
This result was not changed by the study drug tralokinumab for either of the two dose regimens studied.
In order to indicate the sample size that would have been necessary to achieve significance the authors recalculated their αlpha level, which showed that a larger sample size would have been necessary to produce any change in the annual exacerbation rate.
However, the investigators interpreted their findings against the conventional αlpha level of 0·05.
According to Korenblat and Wedner this is where the confusion lies as to the significance of the outcomes.
The example illustrates a wider issue when evaluating outcome studies of biological drugs, they say.
“It would help the asthma practitioner and the pharmaceutical industry to have one well defined set of outcome variables by which to compare newly emerging therapies as well as head to head trials,” they concluded.
*αlpha level is a set value that when coupled with variability of the outcome measured determines the minimum sample size for the control population.