Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review.
BACKGROUND
Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials.


OBJECTIVE
In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported.


METHODS
We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen.


RESULTS
We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good.


CONCLUSIONS
Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.
Johnston
Bradley C
BC
Department of Clinical Epidemiology and Biostatistics, McMaster University, Health Sciences Centre, Hamilton, Ontario, Canada. bjohnst@mcmaster.ca
Shamseer
Larissa
L
da Costa
Bruno R
BR
Tsuyuki
Ross T
RT
Vohra
Sunita
S
D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000175:diagnosis* / Q000628:therapy*; D003968:Diarrhea, Infantile / Q000175:diagnosis / Q000628:therapy; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States