Systematic Reviews and Meta-analysis Understanding the Best Evidence in Primary Healthcare
Customs child wellness, public wellness, and epidemiology
Understanding systematic reviews and meta-analysis
Abstruse
This review covers the basic principles of systematic reviews and meta-analyses. The bug associated with traditional narrative reviews are discussed, equally is the function of systematic reviews in limiting bias associated with the assembly, critical appraisal, and synthesis of studies addressing specific clinical questions. Important issues that need to be considered when appraising a systematic review or meta-assay are outlined, and some of the terms used in the reporting of systematic reviews and meta-analyses—such as odds ratio, relative run a risk, confidence interval, and the forest plot—are introduced.
- RCT, randomised controlled trial
- systematic review
- meta-analysis
- narrative review
- critical appraisal
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- RCT, randomised controlled trial
- systematic review
- meta-analysis
- narrative review
- critical appraisal
Health care professionals are increasingly required to base their practice on the best available evidence. In the start article of the series, I described basic strategies that could be used to search the medical literature.one After a literature search on a specific clinical question, many articles may be retrieved. The quality of the studies may be variable, and the individual studies might accept produced conflicting results. It is therefore of import that health care decisions are not based solely on one or two studies without account existence taken of the whole range of research data bachelor on that topic.
Health care professionals have always used review articles as a source of summarised show on a item topic. Review manufactures in the medical literature have traditionally been in the form of "narrative reviews" where experts in a detail field provide what is supposed to exist a "summary of prove" in that field. Narrative reviews, although still very common in the medical field, have been criticised considering of the high risk of bias, and "systematic reviews" are preferred.two Systematic reviews employ scientific strategies in ways that limit bias to the associates, a disquisitional appraisal, and synthesis of relevant studies that address a specific clinical question.2
THE PROBLEM WITH TRADITIONAL REVIEWS
The validity of a review article depends on its methodological quality. While traditional review articles or narrative reviews can be useful when conducted properly, there is evidence that they are unremarkably of poor quality. Authors of narrative reviews frequently use breezy, subjective methods to collect and interpret studies and tend to be selective in citing reports that reinforce their preconceived ideas or promote their ain views on a topic.3, 4 They are as well rarely explicit near how they selected, assessed, and analysed the primary studies, thereby not allowing readers to assess potential bias in the review procedure. Narrative reviews are therefore frequently biased, and the recommendations made may be inappropriate.v
WHAT IS A SYSTEMATIC REVIEW?
In contrast to a narrative review, a systematic review is a form of research that provides a summary of medical reports on a specific clinical question, using explicit methods to search, critically assess, and synthesise the world literature systematically.6 It is particularly useful in bringing together a number of separately conducted studies, sometimes with alien findings, and synthesising their results.
By providing in a clear explicit mode a summary of all the studies addressing a specific clinical question,4 systematic reviews allow us to have account of the whole range of relevant findings from inquiry on a particular topic, and non just the results of ane or ii studies. Other advantages of systematic reviews have been discussed by Mulrow.seven They tin can be used to establish whether scientific findings are consequent and generalisable across populations, settings, and treatment variations, or whether findings vary significantly past detail subgroups. Moreover, the explicit methods used in systematic reviews limit bias and, hopefully, will better reliability and accuracy of conclusions. For these reasons, systematic reviews of randomised controlled trials (RCTs) are considered to be evidence of the highest level in the hierarchy of research designs evaluating effectiveness of interventions.eight
METHODOLOGY OF A SYSTEMATIC REVIEW
The demand for rigour in the training of a systematic review ways that there should be a formal procedure for its comport. Figure i summarises the process for conducting a systematic review of RCTs.9 This includes a comprehensive, exhaustive search for main studies on a focused clinical question, selection of studies using clear and reproducible eligibility criteria, critical appraisal of primary studies for quality, and synthesis of results according to a predetermined and explicit method.3, 9
WHAT IS A META-Analysis?
Post-obit a systematic review, data from individual studies may be pooled quantitatively and reanalysed using established statistical methods.10 This technique is called meta-analysis. The rationale for a meta-analysis is that, by combining the samples of the individual studies, the overall sample size is increased, thereby improving the statistical power of the analysis equally well as the precision of the estimates of treatment effects.11
Meta-analysis is a ii stage procedure.12 The starting time stage involves the adding of a measure of treatment result with its 95% confidence intervals (CI) for each individual written report. The summary statistics that are unremarkably used to measure treatment consequence include odds ratios (OR), relative risks (RR), and take a chance differences.
In the second stage of meta-analysis, an overall treatment upshot is calculated every bit a weighted average of the private summary statistics. Readers should note that, in meta-assay, data from the private studies are not simply combined as if they were from a single report. Greater weights are given to the results from studies that provide more information, considering they are probable to be closer to the "truthful effect" we are trying to approximate. The weights are often the changed of the variance (the square of the standard fault) of the handling result, which relates closely to sample size.12 The typical graph for displaying the results of a meta-analysis is called a "forest plot".13
The forest plot
The plot shows, at a glance, data from the private studies that went into the meta-analysis, and an estimate of the overall results. Information technology too allows a visual cess of the corporeality of variation between the results of the studies (heterogeneity). Figure two shows a typical forest plot. This figure is adapted from a recent systematic review and meta-analysis which examined the efficacy of probiotics compared with placebo in the prevention and treatment of diarrhoea associated with the utilize of antibiotics.14
Description of the wood plot
In the forest plot shown in fig ii, the results of nine studies have been pooled. The names on the left of the plot are the first authors of the chief studies included. The blackness squares represent the odds ratios of the individual studies, and the horizontal lines their 95% conviction intervals. The area of the blackness squares reflects the weight each trial contributes in the meta-analysis. The 95% confidence intervals would contain the true underlying effect in 95% of the occasions if the report was repeated once more and over again. The solid vertical line corresponds to no effect of treatment (OR = 1.0). If the CI includes 1, and so the difference in the effect of experimental and control treatment is not significant at conventional levels (p>0.05).fifteen The overall treatment result (calculated equally a weighted average of the private ORs) from the meta-analysis and its CI is at the bottom and represented equally a diamond. The middle of the diamond represents the combined treatment effect (0.37), and the horizontal tips stand for the 95% CI (0.26 to 0.52). If the diamond shape is on the Left of the line of no effect, then Less (fewer episodes) of the outcome of involvement is seen in the handling group. If the diamond shape is on the Right of the line, then moRe episodes of the event of interest are seen in the treatment group. In fig 2, the diamond shape is found on the left of the line of no outcome, pregnant that less diarrhoea (fewer episodes) was seen in the probiotic grouping than in the placebo group. If the diamond touches the line of no issue (where the OR is 1) then there is no statistically significant difference between the groups being compared. In fig 2, the diamond shape does non affect the line of no upshot (that is, the conviction interval for the odds ratio does non include 1) and this means that the deviation found between the two groups was statistically significant.
APPRAISING A SYSTEMATIC REVIEW WITH OR WITHOUT META-Analysis
Although systematic reviews occupy the highest position in the hierarchy of evidence for manufactures on effectiveness of interventions,8 information technology should not be assumed that a study is valid merely because it is stated to be an systematic review. Simply as in RCTs, the main issues to consider when appraising a systematic review can be condensed into iii of import areas8:
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The validity of the trial methodology.
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The magnitude and precision of the treatment outcome.
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The applicability of the results to your patient or population.
Box 1 shows a listing of 10 questions that may exist used to appraise a systematic review in all three areas.16
Box 1: Questions to consider when appraising a systematic reviewsixteen
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Did the review address a clearly focused question?
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Did the review include the right blazon of study?
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Did the reviewers try to place all relevant studies?
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Did the reviewers assess the quality of all the studies included?
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If the results of the study have been combined, was it reasonable to do so?
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How are the results presented and what are the main results?
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How precise are the results?
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Can the results exist applied to your local population?
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Were all important outcomes considered?
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Should practice or policy alter every bit a result of the evidence contained in this review?
ASSESSING THE VALIDITY OF TRIAL METHODOLOGY
Focused enquiry question
Similar all enquiry reports, the authors should clearly country the research question at the outset. The research question should include the relevant population or patient groups beingness studied, the intervention of interest, any comparators (where relevant), and the outcomes of involvement. Keywords from the research question and their synonyms are ordinarily used to place studies for inclusion in the review.
Types of studies included in the review
The validity of a systematic review or meta-analysis depends heavily on the validity of the studies included. The authors should explicitly state the type of studies they accept included in their review, and readers of such reports should determine whether the included studies have the advisable written report design to respond the clinical question. In a contempo systematic review which adamant the effects of glutamine supplementation on morbidity and weight proceeds in preterm babies the investigators based their review simply on RCTs.17
Search strategy used to identify relevant articles
There is evidence that single electronic database searches lack sensitivity and relevant articles may be missed if merely 1 database is searched. Dickersin et al showed that only 30–eighty% of all known published RCTs were identifiable using MEDLINE.18 Even if relevant records are in a database, it can exist hard to call up them hands. A comprehensive search is therefore important, not only for ensuring that every bit many studies as possible are identified but also to minimise choice bias for those that are institute. Relying exclusively on one database may call up a ready of studies that are unrepresentative of all studies that would have been identified through a comprehensive search of multiple sources. Therefore, in club to retrieve all relevant studies on a topic, several different sources should be searched to place relevant studies (published and unpublished), and the search strategy should not exist express to the English language language. The aim of an extensive search is to avoid the trouble of publication bias which occurs when trials with statistically significant results are more than probable to exist published and cited, and are preferentially published in English language journals and those indexed in Medline.
In the systematic review referred to higher up, which examined the effects of glutamine supplementation on morbidity and weight gain in preterm babies, the authors searched the Cochrane controlled trials register, Medline, and Embase,17 and they likewise hand searched selected journals, cross referencing where necessary from other publications.
Quality assessment of included trials
The reviewers should state a predetermined method for assessing the eligibility and quality of the studies included. At least two reviewers should independently assess the quality of the included studies to minimise the risk of choice bias. There is evidence that using at least two reviewers has an important effect on reducing the possibility that relevant reports volition be discarded.19
Pooling results and heterogeneity
If the results of the private studies were pooled in a meta-analysis, it is of import to determine whether it was reasonable to practise so. A clinical judgement should be made about whether it was reasonable for the studies to be combined based on whether the private trials differed considerably in populations studied, interventions and comparisons used, or outcomes measured.
The statistical validity of combining the results of the various trials should be assessed by looking for homogeneity of the outcomes from the diverse trials. In other words, there should be some consistency in the results of the included trials. 1 fashion of doing this is to inspect the graphical brandish of results of the individual studies (forest plot, see higher up) looking for similarities in the management of the results. When the results differ profoundly in their direction—that is, if there is pregnant heterogeneity—then information technology may not be wise for the results to exist pooled. Some articles may likewise report a statistical exam for heterogeneity, but information technology should be noted that the statistical power of many meta-analyses is usually too low to allow the detection of heterogeneity based on statistical tests. If a study finds significant heterogeneity among reports, the authors should effort to offering explanations for potential sources of the heterogeneity.
Magnitude of the treatment event
Common measures used to report the results of meta-analyses include the odds ratio, relative take a chance, and mean differences. If the event is binary (for case, disease v no disease, remission v no remission), odds ratios or relative risks are used. If the outcome is continuous (for case, blood force per unit area measurement), mean differences may be used.
ODDS RATIOS AND RELATIVE RISKS
Odds and odds ratio
The odds for a group is divers as the number of patients in the group who attain the stated terminate point divided by the number of patients who practice not. For case, the odds of acne resolution during handling with an antibiotic in a group of x patients may be six to 4 (6 with resolution of acne divided by 4 without = 1.5); in a command group the odds may be 3 to 7 (0.43). The odds ratio, as the proper name implies, is a ratio of 2 odds. Information technology is but defined as the ratio of the odds of the treatment group to the odds of the control group. In our example, the odds ratio of treatment to control grouping would be 3.5 (1.v divided past 0.43).
Risk and relative risk
Adventure, as opposed to odds, is calculated as the number of patients in the group who achieve the stated terminate point divided by the total number of patients in the group. Chance ratio or relative gamble is a ratio of 2 "risks". In the instance in a higher place the risks would exist half dozen in 10 in the treatment grouping (half-dozen divided past 10 = 0.six) and 3 in x in the command group (0.3), giving a run a risk ratio, or relative risk of 2 (0.6 divided by 0.3).
Estimation of odds ratios and relative risk
An odds ratio or relative risk greater than one indicates increased likelihood of the stated upshot beingness accomplished in the treatment grouping. If the odds ratio or relative hazard is less than one, there is a decreased likelihood in the treatment group. A ratio of i indicates no difference—that is, the outcome is simply as probable to occur in the handling group as it is in the control group.11 Every bit in all estimates of treatment effect, odds ratios or relative risks reported in meta-analysis should exist accompanied past confidence intervals.
Readers should understand that the odds ratio will be close to the relative risk if the terminate betoken occurs relatively infrequently, say in less than xx%.15 If the outcome is more than common, then the odds ratio volition considerably overestimate the relative take a chance. The advantages and disadvantages of odds ratios v relative risks in the reporting of the results of meta-assay have been reviewed elsewhere.12
Precision of the treatment effect: confidence intervals
Every bit stated earlier, confidence intervals should accompany estimates of handling effects. I discussed the concept of conviction intervals in the second article of the series.8 Ninety five per cent confidence intervals are commonly reported, but other intervals such as 90% or 99% are as well sometimes used. The 95% CI of an estimate (for example, of odds ratios or relative risks) will be the range inside which we are 95% certain that the truthful population treatment effect will lie. The width of a confidence interval indicates the precision of the estimate. The wider the interval, the less the precision. A very long interval makes us less sure about the accuracy of a report in predicting the true size of the effect. If the conviction interval for relative risk or odds ratio for an estimate includes 1, then we have been unable to demonstrate a statistically pregnant departure between the groups being compared; if information technology does not include 1, and then we say that in that location is a statistically pregnant deviation.
APPLICABILITY OF RESULTS TO PATIENTS
Health intendance professionals should always make judgements about whether the results of a particular study are applicative to their ain patient or grouping of patients. Some of the issues that i need to consider before deciding whether to incorporate a particular piece of research evidence into clinical practice were discussed in the 2d article of the series.viii These include similarity of study population to your population, do good v impairment, patients preferences, availability, and costs.
CONCLUSIONS
Systematic reviews apply scientific strategies to provide in an explicit fashion a summary of all studies addressing a specific question, thereby allowing an account to be taken of the whole range of relevant findings on a particular topic. Meta-assay, which may accompany a systematic review, can increment power and precision of estimates of treatment effects. People working in the field of paediatrics and child health should sympathize the central principles of systematic reviews and meta-analyses, including the ability to apply critical appraisal not only to the methodologies of review manufactures, but also to the applicability of the results to their own patients.
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Copyright 2005 Archives of Affliction in Childhood
Source: https://adc.bmj.com/content/90/8/845
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