This is often referred to as the "evidence pyramid". It is used to illustrate the evolution of the literature. The base of the pyramid is where information usually starts with an idea or laboratory research. As these ideas turn into drugs and diagnostic tools they are tested in laboratories models, then in animals, and finally in humans. The human testing may begin with volunteers and go through several phases of clinical trials before the drug or diagnostic tool can be authorized for use within the general population. Randomized controlled trials are then done to further test the effectiveness and efficacy of a drug or therapy. As you move up the pyramid the amount of available literature decreases, but increases in its relevance to the clinical setting. Meta-Analysis takes the systematic review (see below) a step further by using statistical techniques to combine the results of several studies as if they were one large study. Systematic Reviews usually focus on a clinical topic and answer a specific question. Extensive literature searches are conducted to identify studies with sound methodology. The studies are reviewed, assessed, and summarized according to the predetermined criteria of the review question. Randomized Controlled Trials are carefully planned projects that study the effect of a therapy or test on real patients. They include methodologies that reduce the potential for bias and that allow for comparison between intervention groups and control groups (no intervention). Evidence for questions of diagnosis is found in prospective trials which compare tests with a reference or "gold standard" test. Cohort Studies take a large population and follow patients who have a specific condition or receive a particular treatment over time and compare them with another group that is similar but has not been affected by the condition being studied. Cohort studies are not as reliable as randomized controlled studies, since the two groups may differ in ways other than in the variable under study. Case Control Studies are studies in which patients who already have a specific condition are compared with people who do not. These types of studies are often less reliable than randomized controlled trials and cohort studies because showing a statistical relationship does not mean than one factor necessarily caused the other. Case Series consist of collections of reports on the treatment of individual patients. Case Report is a report on a single patient. Because they are reports of cases and use no control groups with which to compare outcomes, they have no statistical validity . Practice Guidelines are systematically developed statements to assist practitioner and patient make decisions about appropriate health care for specific clinical circumstances. Guidelines review and evaluate the evidence and then make explicit recommendations for practice. The pyramid serves as a guideline to the hierarchy of evidence available. You may not always find the best level of evidence to answer your question. In the absence of the best evidence, you then need to consider moving down the pyramid to other types of studies.
evdience based management of nec
Evidence-BasedManagement of NEC Alaa Eldemerdash, MD, FAAP Consultant and Head of Neonatology Latifa ( formerlyAl Wasl) Hospital, Dubai, UAE
QuestionDo you Use evidence in your management of NEC?Yes
What are the types of Evidence? Textbooks Learned it from my professor Conferences My own experience What we did in residency Published studies Others
Evidence Pyramid Type of Study Meta-Analysis Systematic Review Randomized Controlled Trial Cohort studies Case Control studies Case Series/Case Reports Expert Opinion/ Animal research
generation synthesis policy application 5 decisions 4 2 3 1 Knowledge Translation Steps from evidence generation to clinical application1. generation of evidence from research; 2. evidence summary and synthesis; 3.forming clinical policy; 4. application of policy; 5. individual clinical decisions, includinga) patient’s circumstances, b) patient’s wishes, and c) evidence
Level of Evidence and Grades ofRecommendationUSPSTF: United States Preventive Services Task ForceSORT: Strength of Recommendation TaxonomyCEBM: Center for Evidence Based MedicineGRADE systemMany others
CEBM: Levels of Evidence (LOE) Therapy/Prevention Prognosis Diagnosis DDx/ Symptom Economic and Etiology/Harm prevalence Decision analysis1a SR (with homogeneity) of RCTs1b RCT with narrow CI1c All or none2a SR (with homogeneity) of cohort studies2b Individual cohort study or low quality RCT2c “Outcomes” research3a SR (with homogeneity) case control studies3b Individual case-control study4 Case series/low quality cohort and case-control5 Expert opinion/bench research
CEBM: Grades of Recommendation (GOR)Used to grade a clinical recommendation based on a body of evidence:A: consistent Level 1 studiesB: consistent Level 2 or 3 studies, or extrapolation from Level 1 studiesC: Level 4 studies, or extrapolation from Level 2 or 3 studiesD: Level 5 studies, or troublingly inconsistent or inconclusive studies from any level
GRADE System: Individual StudiesUses four tiers for grading quality of evidence in a study for a particular outcome…High: further research unlikely to change our certainty or the effect sizeModerate: further research is likely to change our certainty and perhaps the effect sizeLow: further research likely to change our certainty and our estimate of the effect sizeVery low: estimate of effect is uncertain
GRADE System: Individual StudiesStart: RCT=3, observational study=1, other evidence=0Subtract: -1 or -2 for quality problems, -1 for reporting bias, -1 for sparse data, -1 or -2 for problems with applicability, etc.Add: +1 for evidence of dose response effect, +1 if plausible co- founders should have been in opposite direction, +1 or +2 for evidence of “association,” etc.
METHODSA retrospective analysis was conducted on VLBW infants (birth weight less than 1500 g) managed at 2 institutionsThe NICUs at both institutions follow an identical strategy for respiratory management of VLBW infants
ConclusionAuthors’ Conclusion:Initial respiratory support with ENCPAP seems to be a safe alternative to routine intubation and mechanical ventilation in premature infants
Formula milk versus maternal breast milk for feeding preterm or low birth weight infants Ginny Henderson, Mary Y Anthony, William McGuireCochrane Database of Systematic Reviews, Issue 4, 2009
Authors’ conclusionsThere are no data from randomised trials of formula milk versus maternal breast milk for feeding preterm or low birth weight infants.
Prevention of NECBreast milkTrophic feedsAdvancing feedsUse of H2 BlockersArginine and Glutamine supplementationOral AntibioticsOral IVIGProbiotics
H2 Blockers and NEC Ronnie Guillet, MD, PhDa, Barbara J. Stoll, MDb, C. Michael Cotten, MDc, Marie Gantz, PhDd, Scott McDonald, BSd,W. Kenneth Poole, PhDd, Dale L. Phelps, MDa, for members of the National Institute of Child Health and Human Development Neonatal Research Network PEDIATRICS Volume 117, Number 2, February 2006 Case-control study was conducted, and the results were analyzed with conditional logistic regression. Infants of 401 to 1500 g in birth weight who were cared for in 1 of the 19 (NICHD) Neonatal Research Network centers from September1998 to December 2001.
H2 Blockers and NECThree controls were matched to each NEC case on the basis of birth-weight category (401–750, 751–1000, 1001–1250,and 1251–1500 g), race , and center.Either enteral or parenteral ranitidine (Zantac), famotidine (Pepcid), or cimetidine (Tagamet) before 120 days of age, death, or discharge.
Ranitidine is Associated With Infections,Necrotizing Enterocolitis, and Fatal Outcomein NewbornsNewborns with birth weight ranging between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in 4 Italian NICUs MEAP 2012 Terrin et al Pediatrics 2012;129;e40
Strategies for Prevention of NecrotizingEnterocolitis.
SummaryMeta-analysis and RCTs are best evidence ( sometimes not possible)Look at other important outcomesLook at guidelines and analysis in secondary publications and EBM organizations