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PubMed2006

Surgical versus non-surgical treatment of chronic low back pain: a meta-analysis of randomised trials.

We performed a meta-analysis of randomised controlled trials to investigate the effectiveness of surgical fusion for the treatment of chronic low back pain compared to non-surgical intervention. Several electronic databases (MEDLINE, EMBASE, CINAHL and Science Citation Index) were searched from 1966 to 2005. The meta-analysis comparison was based on the mean difference in Oswestry Disability Index (ODI) change from baseline to the specified follow-up of patients undergoing surgical versus non-surgical treatment. Of the 58 articles identified, three studies were eligible for primary analysis and one study for sensitivity analysis, with a total of 634 patients. The pooled mean difference in ODI between the surgical and non-surgical groups was in favour of surgery (mean difference of ODI: 4.13, 95%CI: -0.82 to 9.08, p = 0.10, I(2) = 44.4%). Surgical treatment was associated with a 16% pooled rate of early complication (95%CI: 12-20, I(2) = 0%). Surgical fusion for chronic low back pain favoured a marginal improvement in the ODI compared to non-surgical intervention. This difference in ODI was not statistically significant and is of minimal clinical importance. Surgery was found to be associated with a significant risk of complications. Therefore, the cumulative evidence at the present time does not support routine surgical fusion for the treatment of chronic low back pain.

Chronic Disease↗

PubMed2005

Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible protocol.

A meta-analysis was conducted to investigate whether flexible gonadotrophin-releasing hormone (GnRH) antagonist administration according to follicular size would be more beneficial than starting on a fixed day. Only randomized controlled trials were included after a comprehensive search strategy. The data were combined for meta-analysis with RevMan software. Eleven trials were identified, but only four randomized controlled trials met the inclusion criteria. There was no statistically significant difference in pregnancy rate per woman randomized, although there was a trend towards a higher pregnancy rate with the fixed protocol, especially with delayed administration beyond day 8 [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.45-1.1]. There was no premature LH surge in any participant in either protocol. However, there was a statistically significant reduction both in number of antagonist ampoules (OR -1.2 95%, CI -1.26 to -1.15) and amount of gonadotrophin (OR 95.5 IU, 95% CI 74.8-116.1) used in the flexible protocol. In conclusion, there was no statistically significant difference in pregnancy rate between flexible and fixed protocols. There was a statistically significant reduction in the amount of recombinant FSH with the flexible protocol.

Female↗

PubMed1991

[Meta-analysis: an alternative method in clinical research].

Meta-analysis is a research method which allows for the grouping of results from different studies relating to the same topic. Its main objective is to increase the precision surrounding the original research problem and provide a possibility to answer to different questions. This method has been developed in the areas of physics and the social sciences and has been widely accepted within the medical field. Its main use in medicine is in relation to the evaluation of therapeutic measures, yet its application has extended to the evaluation of diagnostic tests, etiological and prognostic factors. In spite of its development, there are still persisting problems in research difficult to solve because of the heterogeneity of the grouped studies, the identification of the size of the relevant effect and of the application of the results in clinical practice. The growing use of this research method within the medical field calls for its comprehension, as well as the recognition of its advantages and limitations in order for its users to be capable of judging the validity of individual meta-analysis.

Meta-Analysis as Topic↗

PubMed2006

Genome-wide meta-analysis for rheumatoid arthritis.

Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142-S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927-936, 2001; Jawaheer et al. in Arthritis Rheum 48:906-916, 2003), one study from the UK (MacKay et al. in Arthritis Rheum 46:632-639, 2001) and one from France (Cornelis et al. in Proc Natl Acad Sci USA 95:10746-10750, 1998). For each study, we obtained NPL scores by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et al. in Am J Hum Genet 58:1347-1363, 1996; Markianos et al. in Am J Hum Genet 68:963-977, 2001). The marker maps differed among the three consortium groups, therefore, the marker maps were aligned after the interval mapping was completed and the NPL scores that were within 1 cM of each other were combined using the method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142-S147, 2001) by calculating the weighted average of the NPL score. This approach avoids some problems in analysis encountered by using GeneHunter2 when some markers in the sample are not genotyped. This procedure provided marginal evidence (P<0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6.

Arthritis, Rheumatoid↗

PubMed2026

Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-Response Relationships and Moderating Factors.

OBJECTIVE: This meta-analysis evaluated the efficacy of behavioral activation (BA) in adolescents with subthreshold depression (SD) or major depressive disorder (MDD), exploring dose-response relationships and moderating factors. METHOD: We searched PubMed, EMBASE, Web of Science, EBSCO, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) through December 31, 2024. Risk of bias was assessed using RoB-2, and evidence quality with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Analyses were performed with R, using standardized mean difference (SMD) for continuous variables and meta-regression for dose-response relationships. Subgroup analyses included symptom severity, intervention setting, delivery format, and parental involvement. The primary outcome was the reduction in depressive symptoms (PROSPERO: CRD42023444273). RESULTS: A total of 14 studies were included (11 RCTs meta-analyzed, comprising 572 participants). BA demonstrated a moderate effect size compared to treatment-as-usual (SMD = -0.42) and a large effect size compared to no-treatment controls (SMD = -0.87). BA was more effective for mild depressive symptoms (SMD = -0.93) than severe symptoms (SMD = -0.43), with significant efficacy in university settings (SMD = -0.94). Intervention without parental involvement exhibited significantly larger effects than those with parental participation (SMD = -0.94 vs -0.38; p < .0001), although this finding was likely confounded by age, symptom severity, and intervention setting. BA moderately improved both behavioral activation levels and functioning (SMD = 0.49). CONCLUSION: Short-term, school-based BA is significantly beneficial for older adolescents with mild depressive symptoms. Findings provide practical guidance for optimizing BA implementation and highlight directions for future research, including the need for larger sample sizes, standardized follow-up assessments, and more representative samples. PLAIN LANGUAGE SUMMARY: This meta-analysis evaluated the effectiveness of behavioral activation (BA), a therapeutic approach focused on improving positive activities, in adolescents with subthreshold depression or major depressive disorder. Based on 14 included studies and 572 participants, BA was found to be more effective for subthreshold compared to major depression. These findings suggest a promising role for BA as an early intervention tool in adolescent depression. STUDY REGISTRATION INFORMATION: Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-response Relationships and Moderating Factors; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023444273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group.

Humans↗

PubMed1997

Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis.

Several reports have evaluated the correlation between cathepsin-D and overall survival or disease-free survival in node-negative breast cancer patients. Because conflicting data have so far been reported, a meta-analysis was conducted to clarify this problem. Eleven studies were included in our meta-analysis (total of 2690 patients). A specific meta-analytical methodology for censored data was used, and disease-free survival was the primary end point. Patients with low cathepsin-D levels had a significantly better disease-free survival than patients with high cathepsin-D values (meta-analytical odds ratio from 0.59 to 0.60 over the interval from 1 to 7 years). A secondary meta-analysis conducted exclusively on the data from eight studies based on cytosol assay gave substantially similar results. One limitation of our study is that the cut-off values to define high and low cathepsin-D concentrations were not identical in the various studies included in our meta-analysis (range from 20 to 78 pmol mg(-1) protein), thus introducing a possible bias in the statistical analysis of the data. However, a simulation based on the well-accepted method of the so-called publication bias showed that more than 100 null studies would be required to lead our results to a statistical level of non-significance. Considering the results of our meta-analysis, we conclude that the data presently available confirm a statistically significant association between high cathepsin-D values and poor disease-free survival in node-negative breast cancer patients.

Breast Neoplasms↗

PubMed1995

A quality-adjusted survival meta-analysis of adjuvant chemotherapy for premenopausal breast cancer. International Breast Cancer Study Group.

The purpose of this paper is to develop and apply a meta-analysis methodology, that does not require patient-level data, for comparing treatments in terms of quality-of-life-adjusted survival. As a motivating example, we considered adjuvant chemotherapy for breast cancer. This therapy has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but its acute toxic effects discourage some physicians from prescribing it. To determine whether the benefit of adjuvant chemotherapy treatment outweighs its costs in terms of toxic effects, we performed a meta-analysis of quality-adjusted survival based on data from 1229 patients, 49 years of age or younger, randomized in eight clinical trials that compared chemotherapy versus no adjuvant systemic therapy. We conducted the meta-analysis by performing a quality-adjusted survival analysis known as a Q-TWiST analysis on each trial. A Q-TWiST analysis allows one to make treatment comparisons that incorporate differences in quality of life associated with various health states. In this analysis, we define as health states the periods of time patients spend: (i) with subjective toxic effects of chemotherapy; (ii) without symptoms of recurrence and toxicity, and (iii) following disease recurrence. We assigned weights to each health state which reflect their relative value in terms of quality of life and allowed them to vary in a sensitivity analysis. We then combined the individual trial results in a meta-analysis, using a multivariate regression model, in such a way that we could easily perform an overall sensitivity analysis. Individual patient-level data are not required to perform this meta-analysis methodology if the individual Q-TWiST analysis results for each trial are available.

Adult↗

PubMed1998

Detecting and describing heterogeneity in meta-analysis.

The investigation of heterogeneity is a crucial part of any meta-analysis. While it has been stated that the test for heterogeneity has low power, this has not been well quantified. Moreover the assumptions of normality implicit in the standard methods of meta-analysis are often not scrutinized in practice. Here we simulate how the power of the test for heterogeneity depends on the number of studies included, the total information (that is total weight or inverse variance) available and the distribution of weights among the different studies. We show that the power increases with the total information available rather than simply the number of studies, and that it is substantially lowered if, as is quite common in practice, one study comprises a large proportion of the total information. We also describe normal plots that are useful in assessing whether the data conform to a fixed effect or random effects model, together with appropriate tests, and give an application to the analysis of a multi-centre trial of blood pressure reduction. We conclude that the test of heterogeneity should not be the sole determinant of model choice in meta-analysis, and inspection of relevant normal plots, as well as clinical insight, may be more relevant to both the investigation and modelling of heterogeneity.

Adult↗

PubMed2001

The effect of family interventions on relapse and rehospitalization in schizophrenia--a meta-analysis.

Twenty-five intervention studies were meta-analytically examined regarding the effect of including relatives in schizophrenia treatment. The studies investigated family intervention programs to educate relatives and help them cope better with the patient's illness. The patient's relapse rate, measured by either a significant worsening of symptoms or rehospitalization in the first years after hospitalization, served as the main study criterion. The main result of the meta-analysis was that the relapse rate can be reduced by 20 percent if relatives of schizophrenia patients are included in the treatment. If family interventions continued for longer than 3 months, the effect was particularly marked. Furthermore, different types of comprehensive family interventions have similar results. The bifocal approach, which offers psychosocial support to relatives and schizophrenia patients in addition to medical treatment, was clearly superior to the medication-only standard treatment. The effects of family interventions and comprehensive patient interventions were comparable, but the combination did not yield significantly better results than did a treatment approach, which focused on either the patient or the family. This meta-analysis indicates that psychoeducational interventions are essential to schizophrenia treatment.

Adaptation, Psychological↗

PubMed2000

The effect of a probiotic milk product on plasma cholesterol: a meta-analysis of short-term intervention studies.

INTRODUCTION: Certain fermented dairy milk products may have beneficial effects on plasma cholesterol levels. However, a number of studies have produced conflicting results as to whether dietary supplementation by a probiotic dairy product containing the bacteria culture Causido(R) reduces plasma cholesterol. OBJECTIVE: To conduct a meta-analysis of intervention studies to evaluate the effect of the Causido(R) culture on plasma total cholesterol and low-density lipoprotein (LDL)-cholesterol. THE PROBIOTIC MILK PRODUCT: The yoghurt product Gaio(R) is fermented with Causido(R), composed of one strain of Enterococcus faecium (human species) with the proposed cholesterol-lowering effect, and two strains of Streptococcus thermophilus. STUDY INCLUSION AND DATA EXTRACTION: Six studies were identified from a literature search and from the yoghurt producer. All studies met the inclusion criteria. Summary data for plasma concentrations of total cholesterol and LDL-cholesterol were extracted from the original publications or by personal request to the authors. Data from 4-8 weeks of treatment duration was used. STATISTICAL ANALYSIS: We performed a traditional meta-analysis where mean differences between intervention and control of the pre-post changes in total cholesterol and LDL-cholesterol were calculated, as well as 95% confidence intervals (CIs). RESULTS: In the six studies included in the meta-analysis, the Gaio(R) interventions produced changes in total cholesterol above those of the control groups ranging from -0.02 to -1.02 mmol/l and in LDL-cholesterol ranging from -0.02 to -1.15 mmol/l. After inclusion of an open-label study, the meta-analysis of the double-blind studies showed that Gaio(R) as compared to the control group changed total cholesterol by -0.22 mmol/l (95% CI: -0.35 to -0.08, P<0.01) and LDL-cholesterol by -0.20 mmol/l (95% CI: -0.33 to -0.06, P<0.005). The outcome was essentially the same if all studies were included. CONCLUSIONS: The present meta-analysis of controlled short-term intervention studies shows that the fermented yoghurt product produced a 4% decrease in total cholesterol and a 5% decrease in LDL-cholesterol when the open-label study is excluded. To demonstrate sustained effects on blood lipids, long-term studies are required. SPONSORSHIP: MD Foods A/S, Denmark.

Adult↗

PubMed2004

Personality and transformational and transactional leadership: a meta-analysis.

This study was a meta-analysis of the relationship between personality and ratings of transformational and transactional leadership behaviors. Using the 5-factor model of personality as an organizing framework, the authors accumulated 384 correlations from 26 independent studies. Personality traits were related to 3 dimensions of transformational leadership--idealized influence-inspirational motivation (charisma), intellectual stimulation, and individualized consideration--and 3 dimensions of transactional leadership--contingent reward, management by exception-active, and passive leadership. Extraversion was the strongest and most consistent correlate of transformational leadership. Although results provided some support for the dispositional basis of transformational leadership--especially with respect to the charisma dimension--generally, weak associations suggested the importance of future research to focus on both narrower personality traits and nondispositional determinants of transformational and transactional leadership.

Humans↗

PubMedDate not supplied

The interpretation of random-effects meta-analysis in decision models.

This article shows that the interpretation of the random-effects models used in meta-analysis to summarize heterogeneous treatment effects can have a marked effect on the results from decision models. Sources of variation in meta-analysis include the following: random variation in outcome definition (amounting to a form of measurement error), variation between the patient groups in different trials, variation between protocols, and variation in the way a given protocol is implemented. Each of these alternatives leads to a different model for how the heterogeneity in the effect sizes previously observed might relate to the effect size(s) in a future implementation. Furthermore, these alternative models require different computations and, when the net benefits are nonlinear in the efficacy parameters, result in different expected net benefits. The authors' analysis suggests that the mean treatment effect from a random-effects meta-analysis will only seldom be an appropriate representation of the efficacy expected in a future implementation. Instead, modelers should consider either the predictive distribution of a future treatment effect, or they should assume that the future implementation will result in a distribution of treatment effects. A worked example, in a probabilistic, Bayesian posterior framework, is used to illustrate the alternative computations and to show how parameter uncertainty can be combined with variation between individuals and heterogeneity in meta-analysis.

Cholesterol↗

PubMed2004

Pantoprazole based therapies in Helicobacter pylori eradication: a systematic review and meta-analysis.

AIM: To perform a systematic review on the efficacy of pantoprazole based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of pantoprazole and other proton pump inhibitors (PPIs) when co-prescribed with antibiotics. METHODS: Studies evaluating pantoprazole combined with antibiotics were considered. Only randomized clinical trials comparing pantoprazole and other PPIs when co-prescribed with antibiotics, and differing only in the PPI (pantoprazole vs other), were eligible for inclusion in the meta-analysis. Bibliographical searches in several electronic databases, and manual search of abstracts from congresses, were conducted. The percentage (weighted mean) of patients with eradication success was calculated. Meta-analysis was performed combining the odds ratios (ORs) of the individual studies in a global OR. RESULTS: The mean eradication rate with pantoprazole plus clarithromycin for 14 days was 60%. Cure rates with 7 day pantoprazole based triple regimens were higher: pantoprazole, amoxicillin and clarithromycin (78%); pantoprazole, clarithromycin and nitroimidazole (84%); and pantoprazole, amoxicillin and nitroimidazole (74%). Twelve studies comparing pantoprazole and other PPIs were selected for the meta-analysis, including 534 and 603 patients, respectively. The mean eradication rate for H. pylori using pantoprazole plus antibiotics was 83%, and 81% when other PPIs were used (OR = 1; 95% confidence interval (CI) from 0.61 to 1.64). When sub-analysis was performed, including only studies comparing pantoprazole with omeprazole, or pantoprazole with lansoprazole, differences were also statistically non-significant. The meta-analysis of the six studies prescribing equivalent doses of all PPIs demonstrated similar results with pantoprazole and with other PPIs (OR = 1.07; 95% CI from 0.71 to 1.62), the results being statistically homogeneous. CONCLUSIONS: Pantoprazole achieves similar cure rates to those of omeprazole and lansoprazole when co-prescribed with antibiotics for the eradication of H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2005

Heterogeneity testing in meta-analysis of genome searches.

Genome searches for identifying susceptibility loci for the same complex disease often give inconclusive or inconsistent results. Genome Search Meta-analysis (GSMA) is an established non-parametric method to identify genetic regions that rank high on average in terms of linkage statistics (e.g., lod scores) across studies. Meta-analysis typically aims not only to obtain average estimates, but also to quantify heterogeneity. However, heterogeneity testing between studies included in GSMA has not been developed yet. Heterogeneity may be produced by differences in study designs, study populations, and chance, and the extent of heterogeneity might influence the conclusions of a meta-analysis. Here, we propose and explore metrics that indicate the extent of heterogeneity for specific loci in GSMA based on Monte Carlo permutation tests. We have also developed software that performs both the GSMA and the heterogeneity testing. To illustrate the concept, the proposed methodology was applied to published data from meta-analyses of rheumatoid arthritis (4 scans) and schizophrenia (20 scans). In the first meta-analysis, we identified 11 bins with statistically low heterogeneity and 8 with statistically high heterogeneity. The respective numbers were 9 and 6 for the schizophrenia meta-analysis. For rheumatoid arthritis, bins 6.2 (the HLA region that is a well-documented susceptibility locus for the disease) and 16.3 (16q12.2-q23.1) had both high average ranks and low between-study heterogeneity. For schizophrenia, this was seen for bin 3.2 (3p25.3-p22.1) and heterogeneity was still significantly low after adjusting for its high average rank. Concordance was high between the proposed metrics and between weighted and unweighted analyses. Data from genome searches should be synthesized and interpreted considering both average ranks and heterogeneity between studies.

Arthritis, Rheumatoid↗

PubMed1998

A case study comparing a meta-analysis and a pooled analysis of studies of sinonasal cancer among wood workers.

A pooled analysis of raw data from 12 case-control studies of sinonasal cancer has recently been conducted by the International Agency for Research on Cancer; the summary odds ratio for all wood-related occupations was 2.0 (95% confidence interval = 1.6-2.5). We have conducted a meta-analysis of the published results of 14 studies on the same topic, including 11 studies from the pooled analysis, and compared the results for several categories of wood workers. Usable results were available for 12 studies: male wood workers had a summary odds ratio of sinonasal cancer of 2.6 (95% confidence interval = 2.1-3.3). The corresponding value based only on the studies that were also included in the pooled analysis was 2.4 (95% confidence interval = 1.9-3.0). When our meta-analysis was based on a relatively large number of studies, results tended to be higher than those of the pooled analysis. As compared with the meta-analysis, the pooled analysis controlled the effect of publication bias by using data from studies for which no specific result was reported, and it reduced misclassification of exposure; the resources used in the pooled analysis, however, were one order of magnitude greater than those needed for the meta-analysis. Whether a pooled analysis of raw data or a meta-analysis should be carried out depends on the research question; we propose some criteria for this decision.

Case-Control Studies↗

PubMed2000

Cauda equina syndrome secondary to lumbar disc herniation: a meta-analysis of surgical outcomes.

STUDY DESIGN: A meta-analysis of surgical outcomes of cauda equina syndrome secondary to lumbar disc herniation. OBJECTIVES: To determine the relationship between time to decompression after onset of cauda equina syndrome and clinical outcome, and to identify preoperative variables that were associated with outcomes. SUMMARY OF BACKGROUND DATA: The timing of surgical decompression for cauda equina syndrome is controversial. Although most surgeons recommend emergent decompression, results in certain studies show that delayed surgery may provide a satisfactory outcome. METHODS: A meta-analysis was performed to determine the correlation between timing of decompression and clinical outcome. One hundred four citations were reviewed, and 42 met the inclusion criteria. Preoperative and postoperative data were recorded. Length of time to surgery was broken down into five groups: less than 24 hours, 24-48 hours, 2-10 days, 11 days to 1 month, and more than 1 month. Logistic regression was used to determine the association between preoperative variables and postoperative outcomes. RESULTS: Outcomes were analyzed in 322 patients. Preoperative chronic back pain was associated with poorer outcomes in urinary and rectal function, and preoperative rectal dysfunction was associated with worsened outcome in urinary continence. In addition, increasing age was associated with poorer postoperative sexual function. No significant improvement in surgical outcome was identified with intervention less than 24 hours from the onset of cauda equina syndrome compared with patients treated within 24-48 hours. Similarly, no difference in outcome occurred in patients treated more than 48 hours after the onset of symptoms. Significant differences, however, were found in resolution of sensory and motor deficits as well as urinary and rectal function in patients treated within 48 hours compared with those treated more than 48 hours after onset of symptoms. CONCLUSIONS: There was a significant advantage to treating patients within 48 hours versus more than 48 hours after the onset of cauda equina syndrome. A significant improvement in sensory and motor deficits as well as urinary and rectal function occurred in patients who underwent decompression within 48 hours versus after 48 hours.

Adult↗

PubMed2002

Orthodontics and temporomandibular disorder: a meta-analysis.

As the importance of evidence-based health care has grown, meta-analysis has become more widely used in the medical and dental fields. In this meta-analysis, the relationship between traditional orthodontic treatment, including the specific type of appliance used and whether extractions were performed, and the prevalence of temporomandibular disorders (TMD) was investigated. After an exhaustive literature search of 960 articles, we found 31 that met the inclusion criteria (18 cross-sectional studies or surveys and 13 longitudinal studies). We divided and extracted data from the 31 articles according to study designs, symptoms, signs, or indexes. Due to severe heterogeneity, the results were summarized without further statistical analysis. The heterogeneous result might originate from lack of a universal diagnostic system and the variability of TMD. Because of heterogeneity, a definitive conclusion cannot be drawn. The data included in this comprehensive meta-analysis do not indicate that traditional orthodontic treatment increased the prevalence of TMD. It is apparent that a reliable and valid diagnostic classification system for TMD is needed for future research.

Adolescent↗

PubMed2004

Sensitivity analyses allowed more appropriate and reliable meta-analysis conclusions for multiple outcomes when missing data was present.

OBJECTIVE: A major problem for meta-analysis of multiple outcomes is the unavailability of some estimates from published and unpublished studies. Dissemination bias, in how and what outcomes are reported or published, may be causing this incompleteness. This article illustrates these problems and presents possible sensitivity analyses to allow the most reliable conclusions. STUDY DESIGN AND SETTING: In a systematic review of prognostic marker MYC-N in neuroblastoma, meta-analysis for overall survival (OS) and disease-free survival (DFS) was of interest. Only 17 published studies enabled extraction of both outcome estimates, 25 enabled only DFS, 39 enabled only OS, and 70 enabled neither outcome. Unidentified unpublished studies may also exist. We assessed the robustness of the pooled estimates to the problem of missing information. Because OS and DFS estimates seemed to be related, we used the known outcome estimates to predict estimates known to be missing, and combined this approach with existing methods for assessing dissemination bias. RESULTS: The results of the sensitivity analyses suggested that the original meta-analysis results were likely to be an overestimate of the true OS and DFS effect-sizes but strengthened the belief that MYC-N is a potentially important prognostic marker in neuroblastoma. CONCLUSION: Sensitivity analyses in meta-analysis allow more appropriate and reliable conclusions when problems such as unavailable estimates and dissemination bias are present.

Biomarkers, Tumor↗