When has enough evidence accumulated to change neonatal practice?

Foglia, Elizabeth E.; DeMauro, Sara B.; Dysart, Kevin; Kirpalani, Haresh

doi:10.1016/j.siny.2015.09.003

Cited by 8 publications

(7 citation statements)

References 55 publications

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“…A major issue facing investigators undertaking such RCTs is recruiting sufficient numbers of infants to meet the statistical "sample size" requirements to detect modest but clinically relevant effects on uncommon outcomes (Table 2). An otherwise methodologically robust RCT is unlikely to be informative if it enrols too few participants to allow statistical analyses to generate estimates of effect that are precise enough to inform policy or practice decisions (13). Despite this requirement, historically, most published…”

Section: Sample Size Mattersmentioning

confidence: 99%

Randomised Controlled Trials for Informing Perinatal Care

2019

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Background: Randomised controlled trials provide the best evidence for the effects of interventions and are a key tool in the effort to improve the care and outcomes for newborn infants. Methods: We discuss the role of randomisation for minimising selection bias in clinical trials and describe examples of seminal trials that have shaped the development of modern perinatal care. We consider the challenges inherent in designing and delivering large, simple, and pragmatic trials, and the need for the development and adoption of core outcome sets to ensure that trials provide high-quality evidence of sufficient validity and applicability to guide policy and practice. Results: Since the earliest days of modern neonatology, the randomised controlled trial has been recognised as the best method for assessing treatments and practices. While many strategies that reduce mortality and morbidity have been introduced following randomised trials, there are, however, important examples of ineffective or potentially harmful practices that have been adopted in the absence of trial-based evidence. Typically, randomised controlled trials in perinatal care need to recruit several thousand participants to be able to detect modest but potentially important effects of new interventions on the most important but rare outcomes. Given the concerns about the financial burden and regulatory complexity of standard trial designs, innovative “efficient” trial designs are being evaluated to streamline processes while safeguarding participants. Conclusions: Well-conducted randomised controlled trials provide the most robust evaluation of interventions aimed at improving outcomes for newborn infants and their families. Increasingly, these trials will need to be large and multicentre (often international) and use a simple and pragmatic protocol, incorporating meticulous follow-up procedures and assessment of long-term outcomes.

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Section: Sample Size Mattersmentioning

confidence: 99%

Randomised Controlled Trials for Informing Perinatal Care

2019

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“…Finally we ask, what does it take to move a putative therapy from investigation to standard of care? 8 We applaud the effort of these authors to understand the complex interaction between genetics and response to therapy to prevent BPD. In diverse societies as ours, trial results should identify potential subsets of participants that might benefit more than others.…”

Section: To the Editormentioning

confidence: 99%

Moving beyond race and ethnicity to understand the effect of inhaled nitric oxide on bronchopulmonary dysplasia prevention

Hwang

Burris

Collins

et al. 2018

The Journal of Pediatrics

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In their study, Blaisdell et al conclude that diuretics do not "substantially improve the respiratory status of the infant born extremely premature." 1 I disagree with this interpretation. The main outcome measure of the study was "change in the respiratory status," defined on the basis of 5 very broad categories ("deceased," "endotracheal tube," "continuous positive airway pressure or nasal cannula >2 liters per minute," "nasal cannula <2 LPM," and "no support"; their Table II) that are not sensitive enough to detect the incremental improvement that may result from the use of diuretics. For example, improvement in lung compliance, which is supposed to be the primary beneficial effect, 2-4 could result in decreases in the peak inspiratory pressure required to ventilate the patients but not necessarily to extubation because the latter may be necessary for other reasons (eg, apnea). Thus, this improvement would be counted as a "failure" under the study criteria. Similarly, a significant decrease in the fraction of inspired oxygen would be counted as "failure" if the patient remained intubated or on continuous positive airway pressure. The authors interpret the fact that the treated group required increased respiratory support after the diuretics were started either as unnecessary care or as failure of the diuretic therapy. A more plausible explanation would be that these patients required more support because they were more premature and had been considerably sicker since birth (their Table I). Thus, in the beginning of the treatment, they already had injury (eg, barotrauma and/or oxygen toxicity) that cannot be expected to be reversed by the use of diuretics. Lastly, considering that the participating centers were not following a common protocol, it is possible that some of the results might have been influenced by the different practices regarding invasive ventilation and oxygen therapy, both of which are known causes of morbidity. I believe that the findings of the study do not warrant any change in the use of diuretics.

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“…They may also be affected by non-scientific considerations, such as potential legal concerns regarding harm and responsibility (2). However, recent approaches to adoption of new therapies into standard practice, nowadays often emphasize the degree of evidential-scientific rigor (3). Such an approach bases itself explicitly on the evidence-based pyramid, and prioritizes randomized evidence.…”

Section: Evidence and Standard Clinical Practicementioning

confidence: 99%

“…There is little debate that new or innovative therapies must fulfill certain imperatives of rigorous testing to conform to US Food and Drug Administration (FDA) and other agency norms before acceptance into standard of care (3). However, what is the situation for practices already embraced by clinicians, but based on low levels of evidence?…”

Section: Evidence and Standard Clinical Practicementioning

confidence: 99%

Recent controversies on comparative effectiveness research investigations: Challenges, opportunities, and pitfalls

Kirpalani

Truog

D’Angio

et al. 2016

Seminars in Perinatology

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The purpose of comparative effectiveness research (CER) is to improve health outcomes by developing and disseminating evidence-based information about which currently available interventions and practices are most effective for patients. While Randomized Controlled Trials (RCT) are the hallmark of scientific proof, when they have been used to compare interventions used in variable ways by different clinicians (Comparative Effectiveness RCTs, CER RCTs) they have at times, generated controversy. Usually the background for the CER RCT is a range of ‘standard therapy’ or ‘standard of care’. This may have been adopted on observational data alone, pilot data. At times, such prior data may derive from populations that differ from the population in which the widely variable standard approach is being applied. We believe controversies related to these CER-RCTs result from confusing ‘accepted’ therapies and ‘rigorously evaluated therapies”. We first define evidence based medicine, and consider how well neonatology conforms to that definition. We then contrast the approach of testing new therapies and those already existing and widely adopted, as in CER-RCTs. We next examine a central challenge in incorporating the control arm within CER, and aspects of the ‘titrated’ trial. We finally briefly consider some ethical issues that have arisen, and briefly discuss the wide range of neonatology practices that could be subject to CER-RCTs or alternative CER-based strategies that might inform practice in the absence of RCTs. Throughout, we emphasize the lack of awareness of the lay community, and indeed many researchers or commentators, in appreciating the wide variation of standard of care. There is a corresponding need to identify the best uses of available resources that will lead to the best outcomes for our patients. We conclude that CER is an essential methodology in modern neonatology to address many unanswered questions and test unproven therapies in newborn care.

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When has enough evidence accumulated to change neonatal practice?

Cited by 8 publications

References 55 publications

Randomised Controlled Trials for Informing Perinatal Care

Randomised Controlled Trials for Informing Perinatal Care

Moving beyond race and ethnicity to understand the effect of inhaled nitric oxide on bronchopulmonary dysplasia prevention

Recent controversies on comparative effectiveness research investigations: Challenges, opportunities, and pitfalls

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