English Mike, Karumbi Jamlick, Maina Michuki, Aluvaala Jalemba, Gupta Archna, Zwarenstein Merrick, Opiyo Newton
KEMRI-Wellcome Trust Research Programme, P.O. Box 43640, Nairobi, 00100, Kenya.
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
BMC Med. 2016 Jan 18;14:5. doi: 10.1186/s12916-016-0556-z.
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.
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.
实用随机试验旨在检验干预措施在接受常规护理的临床医生所诊治的各类患者中的效果。此类试验应与实施许多看似有前景但有效性证据有限的干预措施的努力并行开展。我们以低收入和中等收入国家（LMIC）降低新生儿住院死亡率的基本干预措施为例来说明这一需求，但认为这些观点适用于大多数临床领域。
基于现有证据，已确定了一组基本干预措施，如果在LMIC的地区和社区医院大规模成功实施，可大幅降低早期新生儿死亡。然而，我们表明，在指导许多新生儿住院干预措施的实施方面，现有证据仍存在许多空白，现有证据往往来自高收入环境，且常常表明效果估计的幅度甚至方向存在不确定性。此外，将结果推广到LMIC存在问题，因为那里的情况包括患者与工作人员比例非常高、甚至缺乏基本技术以及主要依赖经验性管理。在不同背景下或在可能在常规护理环境中接受干预的广泛人群中，干预措施的有效性存在此类不确定性时，应越来越多地采用既能保持内部有效性又能提高外部有效性的实用试验。许多干预措施在引入时，没有充分证据证明其在引入的常规环境中的有效性。需要全球努力支持实用研究，以确定许多旨在降低LMIC死亡率或发病率的干预措施在常规护理中的有效性。此类研究应被视为优化实施工作的补充。
