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PubMed1989

Meta-analysis: whither narrative review?

Meta-analysis refers to methodologies that are used to integrate related empirical research to arrive at conclusions not possible by reviewing individual studies, or to improve generalizations of individual studies. It is distinguished from the traditional narrative review in that statistical methodologies are applied to derive more objective conclusions than those that typify narrative reviews. Meta-analysis has been slow to appear in the literature of clinical medicine, however, particularly when viewed in the context of the exponential expansion of literature and the availability of computer technology to facilitate its conduct.

Clinical Medicine↗

PubMed1995

The effects of endurance training on functional capacity in the elderly: a meta-analysis.

In this investigation, meta-analysis was used to delineate exercise induced changes in the VO2max of older individuals and test a null hypothesis of no significant training effects. Parameters included in the analysis were age of the subjects, length of the training regimen, frequency and duration of exercise bouts, pretraining VO2max, posttraining VO2max, and the difference between pretraining and posttraining VO2max (delta VO2max). Effect size for training-induced improvements in VO2max was calculated, corrected for bias, weighted, and analyzed according to contemporary meta-analysis procedures. The mean effect size was found to be 0.65 standard deviation units, representing an improvement in oxygen consumption of 22.8%. The mean effect size was also significantly different from 0 (P < 0.0001), and the null hypothesis was rejected. Stepwise regression analysis indicated that length of training, pretraining VO2max, and duration of training bouts accounted for 59% of the total variation in delta VO2max. In addition, age was found to be inversely correlated with pretraining VO2max (r = -0.56, P = 0.002), and delta VO2max (r = -0.56, P = 0.003). It was concluded that endurance training significantly increases functional capacity in the elderly, and that the increase is related to subject age, duration of exercise bouts, length of the training regimen, and pretraining VO2max.

Aged↗

PubMed1995

Guidelines for application of meta-analysis in environmental epidemiology. ISLI Risk Science Institute.

The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique. Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a meta-analysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results. Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when meta-analysis should or should not be used.

Environmental Exposure↗

PubMed2001

Risk of pancreatic cancer in workers exposed to chlorinated hydrocarbon solvents and related compounds: a meta-analysis.

This is a meta-analysis of occupational exposures to chlorinated hydrocarbon (CHC) solvents and pancreatic cancer, based primarily on studies that addressed exposure directly (agent studies) and secondarily on studies that reported data without verification of individual CHC exposures (job title studies), all of which were listed in databases for the period January 1969 to May 1998. Standardized extraction of data and double-checking of consistency of data extraction by five extractors were done. Simple random models estimated meta-relative risks. Suggestive weak excesses were found for trichloroethylene (meta-relative risk (MRR) = 1.24, 95% confidence interval (CI): 0.79, 1.97), polychlorinated biphenyls (MRR = 1.37, 95% CI: 0.56, 3.31), methylene chloride (MRR = 1.42, 95% CI: 0.80, 2.53), and vinyl chloride (MRR = 1.17, 95% CI: 0.71, 1.91) but not for carbon tetrachloride. One study addressed tetrachloroethylene (MRR = 3.08, 95% CI: 0.63, 8.99); another investigated chlorohydrin production (MRR = 4.92, 95% CI: 1.58, 11.4). Exposure-response meta-analyses for trichloroethylene and methylene chloride failed to reveal trends. Job title studies on metal degreasing and dry cleaning revealed significant MRRs (2.0 and 1.4, respectively). Publication bias was unlikely. Confounding may have remained insufficiently controlled. Unless the results are seriously biased by exposure or endpoint misclassification or by confounding, strong causal associations between CHC compounds and pancreatic cancer can be judged unlikely. Interactions between environmental and occupational agents, lifestyle factors, and genetic susceptibility remain a possibility, but the data for this meta-analysis did not address interactions.

Canada↗

PubMed1992

[Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies].

In the first part the statistical methods of meta-analysis are discussed. Meta-analysis is considered as a statistical tool for quantitatively summarizing the results of clinical trials with comparable aims (treatments) and designs. Meta-analysis can be based on the significance probabilities or effect values. The last procedure is preferable as it gives an estimate (and confidence interval) for the global effect of the treatment of interest, if homogeneity of the effects between the trials can be assumed. Such a homogeneity can be often achieved by a suitable standardization of the effect variables within the trials. In the second part the methods of meta-analysis are applied to controlled clinical trials with Ginkgo biloba extract EGb 761 in patients with peripheral arterial disease. Included were 5 placebo-controlled clinical trials with similar design and inclusion criteria. In all studies treatment effect was quantified by the increase of walking distance (measured in standardized treadmill exercise). The effect value of EGb 761 treatment was expressed by the standardized mean difference in walking distance increase between EGb 761 and placebo, standardized by the standard deviation. It could be shown that this effect value is homogeneous in all trials. The global effect size was estimated as 0.75. This means that the mean increase in walking distance achieved by EGb 761 is 0.75 times of the standard deviation higher than that achieved by placebo. This value is highly significant different from zero. So the meta-analysis revealed a highly significant therapeutic effect of EGb 761 for the treatment of peripheral arterial disease.

Arteries↗

PubMed1998

Neonatal outcome and mode of delivery after epidural analgesia for labour with ropivacaine and bupivacaine: a prospective meta-analysis.

In this prospective meta-analysis, we have evaluated the effect of epidural analgesia with ropivacaine for pain in labour on neonatal outcome and mode of delivery compared with bupivacaine. In six randomized, double-blind studies, 403 labouring women, primigravidae and multiparae, received epidural analgesia with ropivacaine or bupivacaine 2.5 mg ml-1. The drugs were administered as intermittent boluses in four studies and by continuous infusion in two. Apgar scores, neurological and adaptive capacity scores (NACS), degree of motor block and mode of delivery were recorded. The studies were designed prospectively to fit meta-analysis of the pooled results. Results showed similar pain relief and consumption of the two drugs. In the vaginally delivered neonates, NACS scores were approximately equal for both groups at 2 h, but at 24 h there were fewer infants with NACS less than 35 in the ropivacaine compared with the bupivacaine group (2.8% vs 7.6%; P < 0.05). Spontaneous vaginal deliveries occurred more frequently overall with ropivacaine than with bupivacaine (58% vs 49%; P < 0.05) and instrumental deliveries (forceps and vacuum extraction) less frequently (27% vs 40%; P < 0.01), while the frequency of Caesarean section was similar between groups. The intensity of motor block was lower with ropivacaine. There were no significant differences in adverse events.

Adolescent↗

PubMed2002

Meta-analysis: the glass eye of evidence-based practice?

Meta-analysis was developed as a technique for combining the results of many different quantitative studies: it is often used to produce quantitative estimates of causal relations and/or association between variables. Meta-analysis is sometimes regarded as a central component of evidence-based practice. We draw attention to an incompatibility in the epistemology and methods of reasoning in quantitative meta-analysis and the epistemology and reasoning implicit in expert practice. We argue that this may be because the common perception of meta-analysis appeals to truth as correspondence; we suggest that rejecting the naive realism that underpins truth as correspondence allows meta-analysis to be understood in terms of truth as coherence. We can then develop an account of meta-analysis that does not depend upon reduction to a mathematical procedure but is an attempt to maximise coherence in beliefs about what works that is consistent with clinical reasoning in expert practice.

Decision Making↗

PubMed2003

Bulky DNA adducts and risk of cancer: a meta-analysis.

We present a meta-analysis to test the hypothesis that the presence of a high level of bulky DNA adducts in tissues is associated with an increased risk of cancer in humans. Seven articles were selected that matched the selection criteria, for a total of 691 cancer patients and 632 control subjects. In five studies the cases had lung cancer, in one oral cancer, and in one bladder cancer. Six studies measured adducts in WBCs and one in normal lung tissue around tumor tissue. Six were case-control investigations, and one was a case-control study on lung cancer nested within a cohort. Current smokers showed a statistically significant difference between cases and controls, with cases having 83% higher levels of adducts than controls (95% confidence interval, 0.44-1.22). Results were negative or contradictory in ex-smokers and nonsmokers. This observation was confirmed by sensitivity analyses. Publication bias does not seem to be a problem. Despite some methodological limitations, our meta-analysis shows that current smokers with high levels of adducts have an increased risk of lung and bladder cancers. This conclusion also suggests that similar (aromatic) compounds may be involved in the etiology of both types of cancer.

Biomarkers, Tumor↗

PubMed1995

Qualitative assessment of studies included in a meta-analysis: DES and the risk of pregnancy loss.

Meta-analysis, the qualitative and quantitative integration of available research information, is increasingly used in clinical research. This report examines the qualitative elements of meta-analysis through critical review of two published examples that assessed the effect of diethylstilboestrol (DES) on miscarriage and neonatal mortality, respectively. Our subjective review showed the internal validity of three of five trials aggregated in the former meta-analysis to be severely compromised. The remaining two trials (data from which were aggregated in the latter meta-analysis), while internally valid, studied different clinical populations. Therefore, pooling of their results may have been clinically inappropriate. In conclusion, meta-analysis involves substantial elements of subjective judgment. Qualitative assessment of studies is of pivotal importance, because the validity of any summary estimate of effect hinges on both the methodologic quality and the combinability of the aggregated studies.

Abortion, Spontaneous↗

PubMed1997

The design and analysis of paired cluster randomized trials: an application of meta-analysis techniques.

The statistical issues in clinical trials where clusters, communities or groups rather than individuals are randomized are often not fully appreciated. In this paper we discuss the design and analysis of trials in which pairs of clusters are randomized in the context of one recent trial, the British Family Heart Study. Both sample size calculations and the analysis strategy need to take account of the between-cluster component of variance. The analysis can be considered as a random effects meta-analysis across cluster pairs, and can usefully be presented as such. Techniques developed in the context of meta-analysis can then be used in the analysis, for example using a profile likelihood method to derive a confidence interval for the overall treatment effect which takes into account the variability in the estimate of the between-cluster variance. The methods presented here are contrasted with previously published methods for cluster randomized trials.

Adult↗

PubMed1997

Strengths and limitations of meta-analysis: larger studies may be more reliable.

Meta-analysis of randomized controlled trials combines information from independent studies that address a similar question to provide more reliable estimates of treatment effects. At the present time, the methodology and usefulness of meta-analysis is under scrutiny. In the first part of this paper, we summarize the limitations of meta-analysis and make suggestions for improvements. In the second part, we illustrate strengths and limitations using examples of meta-analyses and subsequent large trials that address the same question. We develop the hypothesis that the size of the meta-analysis may be a useful measure of reliability. Small meta-analyses (i.e., those with less than 200 outcome events) may only be useful for summarizing the available information and generating hypotheses for future research. The results of small meta-analyses should be regarded with caution, even if the p value shows extreme statistical significance. Larger meta-analyses (i.e., those with several hundred events) are likely to be more reliable and may be clinically useful. Well-conducted meta-analyses of large trials using individual patient data may provide the best estimates of treatment effects in the cohort overall and in clinically important subgroups.

Bias↗

PubMed1997

Systematic reviews of medical evidence: the use of meta-analysis in obstetrics and gynecology.

OBJECTIVE: To review the technique of meta-analysis and its uses and limitations in obstetrics and gynecology. DATA SOURCES: We reviewed four major journals in obstetrics and gynecology (American Journal of Obstetrics and Gynecology, Fertility and Sterility, Journal of Reproductive Medicine, and Obstetrics & Gynecology). METHODS OF STUDY SELECTION: Journals were reviewed to determine frequency of meta-analysis as a method of systematic review in obstetrics and gynecology. We also summarized objectives and scientific guidelines for performing a meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Meta-analysis is used with increased frequency in obstetrics and gynecology as a way of systematically reviewing medical evidence. This technique is an attempt to improve on traditional methods of narrative review by an expert and as a framework for evidence-based medicine and developing practice guidelines. By combining data from replicate studies, a meta-analysis can increase statistical power, more precisely estimate the typical effect size of treatment or risk factor, and attempt to resolve controversies in the medical literature. Meta-analysis is a retrospective look at data already collected and is therefore subject to the biases of all retrospective studies. CONCLUSIONS: The technique of meta-analysis requires all the scientific rigor of a randomized clinical trial with careful attention to study design, including a formal protocol for literature search strategies, quality assessment of candidate studies, specific inclusion and exclusion criteria, issues of sampling and publication bias, statistical tests of homogeneity, and sensitivity analysis.

Evidence-Based Medicine↗

PubMed2002

Quantifying heterogeneity in a meta-analysis.

The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.

Albumins↗

PubMed2025

The Impact of Nutritional Status on Oral Health Outcomes and Management in Older Adults: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis evaluated the relationship between nutritional status and the oral health of older adults (aged 75 years or older). The PECO focus question was, 'What is the occurrence, association and impact of nutritional state on the oral health outcomes and its management in older adults?' METHODS: A comprehensive literature search was performed across MEDLINE (PubMed), Embase and the Cochrane Library. Publications up to April 2025 were considered, yielding 3324 records for initial screening. Quality assessment of the included studies predominantly revealed a low to moderate risk of bias. RESULTS: Eighty-three studies were included for data analysis. Meta-analyses demonstrated that older adults at risk of malnutrition had fewer teeth (SMD = -0.29; 95% CI: -0.46, -0.11; p = 0.002). Those with < 20 teeth and who were not rehabilitated with dentures were more likely to be malnourished (OR = 4.00; 95% CI: 1.21, 13.18; p = 0.02). Malnutrition was associated with self-reported chewing problems (OR = 2.38; 95% CI: 1.74, 3.26; p < 0.0001), swallowing problems (OR = 3.18; 95% CI: 2.20, 4.61; p < 0.0001) or dry mouth (OR = 2.35; 95% CI: 1.91, 2.88; p < 0.0001). Conversely, those with oral pain showed lower odds of malnutrition risk (OR = 0.68; 95% CI: 0.52, 0.89; p = 0.005). CONCLUSIONS: Fewer teeth, existing chewing or swallowing problems, dry mouth and the absence of removable dentures where needed, were associated with malnutrition in care-dependent older adults. The current lack of longitudinal studies and proof of causality for malnutrition affecting oral health outcomes underscores the need for further research to better clarify the complex relationship between oral health and nutrition in older populations. TRIAL REGISTRATION: PROSPERO Registration: CRD420251003549.

Humans↗

PubMed1992

Meta-analysis for descriptive research.

Although nurses have begun to use meta-analysis, a review of the nursing literature demonstrates that its use has not been maximized. Meta-analysis can be employed to synthesize descriptive as well as experimental research, yet attention in nursing has focused almost exclusively on meta-analysis techniques for, and meta-analytic studies of, experimental research. Furthermore, nursing literature has emphasized use of the effect size index (d) rather than the correlation index (r); the latter may, in some cases, be the more suitable metric, particularly with meta-analysis of correlational studies. An argument is made for the value of meta-analysis as a technique for integrating descriptive research, and an overview of different meta-analytic approaches to data analysis using the correlational index with descriptive research is provided.

Humans↗

PubMed1999

Meta-analysis: formulating, evaluating, combining, and reporting.

Meta-analysis involves combining summary information from related but independent studies. The objectives of a meta-analysis include increasing power to detect an overall treatment effect, estimation of the degree of benefit associated with a particular study treatment, assessment of the amount of variability between studies, or identification of study characteristics associated with particularly effective treatments. This article presents a tutorial on meta-analysis intended for anyone with a mathematical statistics background. Search strategies and review methods of the literature are discussed. Emphasis is focused on analytic methods for estimation of the parameters of interest. Three modes of inference are discussed: maximum likelihood; restricted maximum likelihood, and Bayesian. Finally, software for performing inference using restricted maximum likelihood and fully Bayesian methods are demonstrated. Methods are illustrated using two examples: an evaluation of mortality from prophylactic use of lidocaine after a heart attack, and a comparison of length of hospital stay for stroke patients under two different management protocols.

Anti-Arrhythmia Agents↗

PubMed1990

Meta-analysis for dermatologists.

Meta-analysis is a relatively new statistical technique that is attracting a great deal of attention in the medical and social science literature. This technique is discussed in terms of its tenants, advantages, rudiments, and controversies.

Dermatology↗

PubMed1996

Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis.

We conducted a two-part meta-analysis to assess the effectiveness of fluoroquinolones for preventing bacterial infections in granulocytopenic patients who are receiving chemotherapy for malignancies. Overall, 19 randomized studies met selection criteria and were included in this meta-analysis of 2,112 patients. Thirteen studies that compared the fluoroquinolones alone with control regimens (co-trimoxazole, oral nonabsorbable antibiotics, or placebo) and six studies that compared the fluoroquinolones plus prophylaxis for bacteremia due to gram-positive bacteria with control regimens (fluoroquinolones or oral nonabsorbable antibiotics) were included in the two meta-analyses. The results of the first meta-analysis indicate that fluoroquinolones alone are effective in preventing gram-negative bacteremia (overall odds ratio [OR], 0.09; 95% confidence interval [CI], 0.05-0.16; P < .001), but not gram-positive bacteremia (OR, 1.05; 95% CI, 0.76-1.45; P = .7), fever-related morbidity (OR, 0.76; 95% CI, 0.56-1.04; P = .09), and infection-related mortality (OR, 0.79; 95% CI, 0.47-1.34; P = .4). The results of the second meta-analysis indicate that a combination of fluoroquinolones plus prophylaxis for gram-positive bacteremia (penicillin, vancomycin, or macrolides) significantly reduces the occurrence of gram-positive bacteremia (OR, 0.46; CI, 0.33-0.63; P < .001) without affecting the incidence of fever-related morbidity (OR, 0.83; 95% CI, 0.62-1.13; P = .2) and infection-related mortality (OR, 0.74; 95% CI, 0.40-1.38; P = .3)

Anti-Bacterial Agents↗