title: The need for pragmatic clinical trials in low and middle income settings - taking essential neonatal interventions delivered as part of inpatient care as an illustrative example.
abstract: BACKGROUND
  Pragmatic randomized trials aim to examine the effects of interventions in the full spectrum of patients seen by clinicians who receive routine care. Such trials should be employed in parallel with efforts to implement many interventions which appear promising but where evidence of effectiveness is limited. We illustrate this need taking the case of essential interventions to reduce inpatient neonatal mortality in low and middle income countries (LMIC) but suggest the arguments are applicable in most clinical areas.
  
  
  CONCLUSIONS
  A set of basic interventions have been defined, based on available evidence, that could substantially reduce early neonatal deaths if successfully implemented at scale within district and sub-district hospitals in LMIC. However, we illustrate that there remain many gaps in the evidence available to guide delivery of many inpatient neonatal interventions, that existing evidence is often from high income settings and that it frequently indicates uncertainty in the magnitude or even direction of estimates of effect. Furthermore generalizing results to LMIC where conditions include very high patient staff ratios, absence of even basic technologies, and a reliance on largely empiric management is problematic. Where there is such uncertainty over the effectiveness of interventions in different contexts or in the broad populations who might receive the intervention in routine care settings pragmatic trials that preserve internal validity while promoting external validity should be increasingly employed. Many interventions are introduced without adequate evidence of their effectiveness in the routine settings to which they are introduced. Global efforts are needed to support pragmatic research to establish the effectiveness in routine care of many interventions intended to reduce mortality or morbidity in LMIC. Such research should be seen as complementary to efforts to optimize implementation.
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 43640, Nairobi, 00100, Kenya. menglish@kemri-wellcome.org.|Nuffield Department of Medicine, University of Oxford, Oxford, UK. menglish@kemri-wellcome.org.
authors.forename: Mike
authors.initials: M
authors.lastname: English
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 43640, Nairobi, 00100, Kenya. karumbij@gmail.com.|Ministry of Health, Nairobi, Kenya. karumbij@gmail.com.
authors.forename: Jamlick
authors.initials: J
authors.lastname: Karumbi
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 43640, Nairobi, 00100, Kenya. MMaina@kemri-wellcome.org.
authors.forename: Michuki
authors.initials: M
authors.lastname: Maina
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 43640, Nairobi, 00100, Kenya. jaluvaala@kemri-wellcome.org.|Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya. jaluvaala@kemri-wellcome.org.
authors.forename: Jalemba
authors.initials: J
authors.lastname: Aluvaala
authors.affiliation: Centre for Studies in Family Medicine, Schulich School of Medicine & Dentistry, Western University, Western Centre for Public Health and Family Medicine, London, Canada. archnagupta@gmail.com.
authors.forename: Archna
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Centre for Studies in Family Medicine, Schulich School of Medicine & Dentistry, Western University, Western Centre for Public Health and Family Medicine, London, Canada. merrick.zwarenstein@ices.on.ca.
authors.forename: Merrick
authors.initials: M
authors.lastname: Zwarenstein
authors.affiliation: KEMRI-Wellcome Trust Research Programme, P.O. Box 43640, Nairobi, 00100, Kenya. newtonpiyoo@gmail.com.
authors.forename: Newton
authors.initials: N
authors.lastname: Opiyo
mesh_terms: D000328:Adult; D005260:Female; D006301:Health Services Needs and Demand / Q000191:economics; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007182:Income; D007223:Infant; D007224:Infant Care / Q000191:economics / Q000458:organization & administration / Q000706:statistics & numerical data; D007226:Infant Mortality; D007231:Infant, Newborn; D007297:Inpatients; D011203:Poverty / Q000706:statistics & numerical data*; D064792:Pragmatic Clinical Trials as Topic / Q000191:economics / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000706:statistics & numerical data; D035501:Uncertainty