Abstract:
Introduction: WHO treatment guidelines are widely recommended for guiding
treatment for millions of children with pneumonia every year across multiple lowincome and middle-income countries. Guidelines are based on synthesis of available
evidence that provides moderate certainty in evidence of effects for forms of pneumonia
that can result in hospitalisation. However, trials have included fewer children from
Africa than other settings, and it is suggested that African children with pneumonia have
higher mortality. Thus, despite improving access to recommended treatments and
deployment with high coverage of childhood vaccines, pneumonia remains one of the top
causes of mortality for children in Kenya. Establishing whether there are benefits of
alternative treatment regimens to help reduce mortality would require pragmatic clinical
trials. However, these remain relatively expensive and time consuming. This protocol
describes an approach to using secondary analysis of a new, large observational dataset
as a potentially cheaper and quicker way to examine the comparative effectiveness of
penicillin versus penicillin plus gentamicin in treatment of indrawing pneumonia.
Addressing this question is important, as although it is now recommended that this form
of pneumonia is treated with oral medication as an outpatient, it remains associated with
non-trivial mortality that may be higher outside trial populations.
Methods and analysis: We will use a large observational dataset that captures data on
all admissions to 13 Kenyan county hospitals. These data represent the findings of
clinicians in practice and, because the system was developed for large observational
research, pose challenges of non-random treatment allocation and missing data. To
overcome these challenges, this analysis will use a rigorous approach to study design,
propensity score methods and multiple imputation to minimise bias.
Ethics and dissemination: The primary data are held by hospitals participating in the
Kenyan Clinical Information Network project with de-identifed data shared with the
Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme for
agreed analyses. The use of data for the analysis described received ethical clearance
from the KEMRI scientific and ethical review committee. The findings of this analysis
will be published.