Which Outcome Matters Most?
What then constitutes a successful treatment outcome? To address this question, it is instructive to look to our study's data set and consider the differing conclusions concerning the efficacy of amoxicillin-clavulanate that would result from applying to the data an array of different hypothetical criteria for defining clinical failure, each arguably plausible. Results of this exercise are summarized in Table 1 and bring to light the following relationships:
However clinical failure was defined, it was experienced by fewer children treated with amoxicillin-clavulanate than with placebo.
The magnitude of the difference in outcome between the amoxicillin-clavulanate and placebo groups varied substantially depending on the criteria used for defining clinical failure: absolute between-group differences in the percentage of children with clinical failure ranged from 35% to 12%; the number needed to treat thus ranged from 3 to 8.
The between-group difference was largest when a conclusion of clinical failure was based simply on persistence of TM bulging of any degree, whether or not any symptoms as reflected in children's AOM-SOS scores persisted (set 1).
Criteria for clinical failure that incorporated persistence of TM bulging as well as of symptoms (set 2), compared with criteria based only on comparable persistence of symptoms (set 3), resulted in smaller proportions of children in each treatment group meeting failure criteria. However, between-group differences in sets 2 and 3, respectively, were of generally similar magnitude.
As criteria for clinical failure that included TM bulging were increased in stringency and accordingly were met by fewer children (sets 1 and 2), between-group differences in the rate of treatment failure tended to narrow progressively; this tendency, however, was not apparent when the criteria for clinical failure concerned only symptoms (set 3).
Limiting symptoms of interest, in determining outcome, to persistent ear rubbing or tugging and/or fever (set 4)—as had been the case in a number of earlier studies—substantially reduced the number of children meeting criteria for clinical failure, when compared with considering the AOM-SOS scale in its entirety (set 3), but resulted in little or no change in the magnitude of absolute differences between the 2 treatment groups.
Taken together, these findings underscore the need to resolve the question of whether symptomatic response or response based on otoscopic findings is the more telling measure of disease outcome, and relatedly, whether young children in whom otoscopic evidence of infection persists after antimicrobial treatment (or after no treatment), but who are substantially free of symptoms, benefit sufficiently to warrant additional (or newly instituted) antimicrobial treatment.