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Questions for meta-analysis.

In spite of an abundance of data, the empirical evidence as yet does not make clear whether meta-analysis will bring about progress in psychological science. Therefore, it is still useful and desirable to engage in rational analysis of the methodology. Such analysis is done in the present essay by posing five questions that go to the logical and conceptual foundation of meta-analysis. The questions are (a) What are the grounds for believing that the review of the literature, even a quantitative one, will bring about scientific discovery? (b) Why is the individual study devalued when the history of successful science seems largely the story of the success of the individual study? (c) What is the rationale for believing that data analysis by itself can markedly improve the fortunes of psychological science? (d) Is there a basis for claims made on behalf of meta-analysis that it is more accurate than either the traditional literature review or the individual study? (e) Is there justification for the claim that de facto meta-analysis has been used effectively in physical science?

Humans↗

Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes.

Meta-analysis of binary data involves the computation of a weighted average of summary statistics calculated for each trial. The selection of the appropriate summary statistic is a subject of debate due to conflicts in the relative importance of mathematical properties and the ability to intuitively interpret results. This paper explores the process of identifying a summary statistic most likely to be consistent across trials when there is variation in control group event rates. Four summary statistics are considered: odds ratios (OR); risk differences (RD) and risk ratios of beneficial (RR(B)); and harmful outcomes (RR(H)). Each summary statistic corresponds to a different pattern of predicted absolute benefit of treatment with variation in baseline risk, the greatest difference in patterns of prediction being between RR(B) and RR(H). Selection of a summary statistic solely based on identification of the best-fitting model by comparing tests of heterogeneity is problematic, principally due to low numbers of trials. It is proposed that choice of a summary statistic should be guided by both empirical evidence and clinically informed debate as to which model is likely to be closest to the expected pattern of treatment benefit across baseline risks. Empirical investigations comparing the four summary statistics on a sample of 551 systematic reviews provide evidence that the RR and OR models are on average more consistent than RD, there being no difference on average between RR and OR. From a second sample of 114 meta-analyses evidence indicates that for interventions aimed at preventing an undesirable event, greatest absolute benefits are observed in trials with the highest baseline event rates, corresponding to the model of constant RR(H). The appropriate selection for a particular meta-analysis may depend on understanding reasons for variation in control group event rates; in some situations uncertainty about the choice of summary statistic will remain.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of recombinant erythropoietin on "late" transfusions in the neonatal intensive care unit: a meta-analysis.

OBJECTIVES: Using the approach of a meta-analysis, we sought to determine whether the administration of recombinant erythropoietin (rEpo) to very low birth weight (VLBW) infants, after the first week of life, results in fewer "late" transfusions. STUDY DESIGN AND METHODS: The guidelines set forth by the Cochrane Neonatal Review Group were used to identify all relevant studies. Medline was searched from January 1990 to November of 2000. Studies that used a randomized, placebo-controlled, and double-masked design were deemed acceptable. RESULTS: Eight studies meet the inclusion criteria. These involved 357 VLBW neonates: 183 rEpo and 174 placebo recipients. The neonates in the rEpo group received fewer erythrocyte transfusions during the study period than did those in the placebo group; the common odds ratio (OR)=0.33; 95% confidence interval (CI) 0.21-0.51. Furthermore, the rEpo effect size was a function of the dose of rEpo administered (p=0.0001). CONCLUSION: A meta-analysis of the most scientifically rigorous studies on this topic indicates that administration of rEpo to VLBW infants reduces "late" erythrocyte transfusions in a dose-dependent manner.

Blood Transfusion↗

Occupational trichloroethylene exposure and non-Hodgkin's lymphoma: a meta-analysis and review.

METHODS: Meta-analysis and review of 14 occupational cohort and four case-control studies of workers exposed to trichloroethylene (TCE) to investigate the relation between TCE exposure and the risk of non-Hodgkin's lymphoma (NHL). Studies were selected and categorised based on a priori criteria, and results from random effects meta-analyses are presented. RESULTS: The summary relative risk estimates (SRRE) for the group of cohort studies that had more detailed information on TCE exposure was 1.29 (95% CI 1.00 to 1.66) for the total cohort and 1.59 (95% CI 1.21 to 2.08) for the seven studies that identified a specific TCE exposed sub-cohort. SRREs for three studies with cumulative exposure information were 1.8 (95% CI 0.62 to 5.26) for the lowest exposure category and 1.41 (95% CI 0.61 to 3.23) for the highest category. Comparison of SRREs by levels of TCE exposure did not indicate exposure-response trends. The remaining cohort studies that identified TCE exposure but lacked detailed exposure information had an SRRE of 0.843 (95% CI 0.72 to 0.98). Case-control studies had an SRRE of 1.39 (95% CI 0.62 to 3.10). Statistically significant findings for the Group 1 studies were driven by the results from the subgroup of multiple industry cohort studies (conducted in Europe) (SRRE = 1.86; 95% CI 1.27 to 2.71). The SRRE for single industry cohort studies was not significantly elevated (SRRE = 1.25; 95% CI 0.87 to 1.79). CONCLUSIONS: Interpretation of overall findings is hampered by variability in results across the Group 1 studies, limited exposure assessments, lack of evidence of exposure response trends, lack of supportive information from toxicological and mechanistic data, and absence of consistent findings in epidemiologic studies of exposure and NHL. Although a modest positive association was found in the TCE sub-cohort analysis, a finding attributable to studies that included workers from multiple industries, there is insufficient evidence to suggest a causal link between TCE exposure and NHL.

Case-Control Studies↗

Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data.

A meta-analysis of 8 randomized trials (1792 patients, 2947 patient-years of follow-up) showed that acyclovir (> or = 3200 mg/day) offered a significant survival benefit (P = .006 by log-rank test) in human immunodeficiency virus (HIV) infection. The treatment effect did not vary significantly in patient subgroups of different CD4 cell counts, hemoglobin levels, age, race, and sex, and with or without AIDS diagnosis. Acyclovir treatment (hazard ratio, 0.78; 95% confidence interval [CI], 0.65-0.93), higher CD4 cell count (P < .001), higher hemoglobin level (P < .001), and younger age (P < .001) reduced the hazard of mortality. Acyclovir decreased herpes simplex virus infections (odds ratio [OR], 0.28; 95% CI, 0.21-0.37) and varicella-zoster virus infections (OR, 0.29; 95% CI, 0.13-0.63) but not cytomegalovirus disease or mortality from lymphoma or Kaposi's sarcoma. A survival advantage was seen specifically in studies with high incidence of clinical herpesvirus infections (> or = 25% per year). Given the wide confidence intervals, the small effect in low-risk patients, and recent changes in HIV therapeutics, the results should be interpreted cautiously, but the meta-analysis supports the importance of pathogenetic interactions between herpesviruses and HIV.

Acyclovir↗

Meta-analysis of local metronidazole in the treatment of chronic periodontitis.

BACKGROUND: Meta-analysis was used to assess the effectiveness of local delivery of metronidazole alone or as an adjunct to mechanical therapy in patients with chronic periodontitis. METHODS: Studies were identified using MEDLINE and other sources. Meta-analyses were performed on the basis of probing depth (PD) at baseline and experimental and control regimens studied (i.e., metronidazole plus scaling and root planing [SRP] versus SRP and metronidazole versus SRP); the effect of local metronidazole on PD and attachment level (AL) was evaluated for follow-up times of 4, 8, 12, 24, and 36 weeks. The DerSimonian & Laird random effects model was used. RESULTS: Twelve studies that met inclusion criteria were entered into the meta-analysis. A significant mean reduction in PD for the combined metronidazole and SRP was observed in all comparisons with initial PD > or = 4 mm (0.38 mm at 8 weeks to 0.6 mm at 12 weeks); whereas, with initial PD > or = 5 mm a significant mean reduction was observed from 12 weeks (0.29 to 0.48 mm at 24 and 36 weeks, respectively). Meta-analysis could be performed for AL to test the effectiveness of metronidazole as an adjunct to SRP and a significant AL improvement was found in all analyses (0.2 mm at 4 weeks to 0.29 mm at 24 and 36 weeks). Meta-analyses were performed including two to four studies. CONCLUSION: Our results demonstrated the effectiveness of metronidazole as an adjunct to SRP in the treatment of chronic adult periodontitis, but clinical significance and dissemination of antibiotics should be taken into account in the evaluation of metronidazole as an alternative to SRP.

Administration, Topical↗

Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis.

OBJECTIVE: The researchers reviewed published clinical trials and performed a meta-analysis to assess if therapy with adrenergic beta-antagonists (beta-blockers) reduces the risk of mortality in patients with systolic dysfunction. STUDY DESIGN: A systematic review was performed with meta-analysis where appropriate. Clinical trials were reviewed with respect to the quality of the research methods, including patient population and end points. Two independent reviewers calculated relative risk, relative risk reduction, absolute risk reduction, and number needed to treat for the total mortality end point reported in each trial. A meta-analysis was performed. DATA SOURCES: The study team searched pertinent indexing services and references from published articles for relevant literature. The selected clinical trials were randomized, double-blinded, and controlled, and included patients with systolic heart failure. Mortality was assessed as a primary or secondary end point. OUTCOMES MEASURED: The primary outcome was mortality. RESULTS: Statistically and clinically significant improvement, including a statistically significant reduction in mortality, has been noted in patients receiving therapy with either bisoprolol, carvedilol, or metoprolol. Pooled analysis revealed a statistically significant reduction in the risk of total mortality (odds ratio [OR]MH=0.66; 95% confidence interval [CI], 0.58-0.75) and sudden death (ORMH=0.61; 95% CI, 0.5-0.75) for patients receiving beta-blocker therapy. CONCLUSIONS: All patients with New York Heart Association class II and III heart failure should receive beta-blocker therapy with bisoprolol, carvedilol, or metoprolol. Additional clinical trials are ongoing and will provide further data on which patients receive the greatest benefit from therapy and which beta-blocker may be preferred.

Adrenergic beta-Antagonists↗

Small group learning in medical education: a second look at the Springer, Stanne, and Donovan meta-analysis.

All in all, the evidence is not convincing. Only four of the nine randomized studies used the conventional small-group learning paradigm and qualify as studies of small-group learning, which are relevant to medical education. The results of one of the four are impossible to interpret because of the involvement of the investigator in teaching and test construction. The three remaining studies showed no effect, a negative effect, and a positive effect, respectively. The nonrandomized studies failed to establish the comparability of the groups. The evidence does not support the authors' call for "more widespread implementation of small-group learning in undergraduate SMET". Small-group learning has not been shown to support the acquisition of content any better [or worse] than large-group learning. In medical education, small-groups are employed in large part to develop team work skills, communication skills, and peer- and self-assessment skills. But these outcomes are not addressed in this meta-analysis. More seriously, our rereading of these studies raises general concerns about meta-analysis in education, which have important implications for evidence-based medical education. The meta-analysis under discussion at first appeared to be just the kind needed to guide an evidence-based educational enterprise. However, a closer look revealed both what is lacking in the meta-analysis and some of the ways educational research and reporting need to be changed if anything like evidence-based education is ever to become a reality. At the least, study design must be clearly described. In addition, if the design is nonrandomized, the groups should be described in sufficient detail to allow a meaningful interpretation of the role of preexisting differences on the outcome measures. (This is why we limited our discussion here to the randomized studies.) Also, effect-size measures should be reported for all comparisons that bear on the impact of the intervention, including preexisting differences. Reporting significance is not enough. This shows only whether sampling error can be ruled out (with a low probability of error, p < .05) as a possible explanation of the connection between the intervention and the outcome. The effect can still be trivial and the comparisons confounded. In addition, descriptions of the actual educational interventions employed need to be more comprehensive and precise. For the most part, the papers would have been strengthened by providing more information for replicating the studies and for deciding which should be included in a given meta-analysis. Perhaps most seriously, our rereading of these studies makes us wonder about the possibility of meaningfully synthesizing the results of educational studies, given their idiosyncrasies and their many extraneous, uncontrolled factors. The conclusions from most educational studies, then--whether randomized or not--must be highly qualified, with explicit warnings about preexisting differences and other confounding factors that plausibly account for the study results. However, these narrative qualifications do nothing to adjust the effect-size measures, which are typically pooled or synthesized across studies--confounds and all. The idiosyncrasies of the studies seem to preclude a blanket qualification that can be applied conceptually across the collection of studies to arrive at a sound conclusion from the synthesis. In brief, the meta-analysis considered here does not support the application of small-group learning in medical education and it raises questions about meta-analysis in education with implications for evidence-based education.

Curriculum↗

Revascularization in patients with coronary artery disease, left ventricular dysfunction, and viability: a meta-analysis.

BACKGROUND: The effects of viability status and treatment allocation on long-term mortality in patients with left ventricular dysfunction and coronary artery disease have not been determined. Several observational studies with significant limitations have addressed this issue, and a recent meta-analysis has attempted to combine these results to increase statistical power. However, the analysis did not test for an interaction between viability status and treatment type, and included extraneous studies. We provide an alternate meta-analysis of this primary literature, utilizing interaction statistical methodology on relevant data and factoring in multiple limitations. METHODS: We examined papers from this prior meta-analysis examining viable and nonviable patients undergoing surgical or medical therapy. We determined an interaction odds ratio for each study and used an empirical Bayes random-effects model to obtain a combined interaction odds ratio that was tested for statistical significance. We compared our results against an interaction odds ratio we estimated from the primary studies included in the previous meta-analysis. RESULTS: Nine relevant studies with 1244 patients and 172 events were identified that utilized all 4 treatment/viability subsets. The interaction odds ratio was 2.76 (P =.0176, 95% CI 1.19-6.38), 2.5 times lower than our estimated interaction odds ratio of 7.27 for the prior meta-analysis. CONCLUSIONS: We found a markedly reduced but statistically significant interaction between viability status and treatment allocation. However, numerous limitations in the primary studies and the application of meta-analysis along with significant improvements in medical therapies render a randomized controlled trial necessary to reach a definitive conclusion to this critical question.

Coronary Artery Disease↗

Recurrent events in meta-analysis of multiple clinical trials.

AIM: To study the efficacy and safety of drug or therapy with recurrent events in meta-analysis of multiple clinical trials. METHODS: A nonparametric approach is proposed to estimate the rates of recurrent events for meta-analysis of trials. The method was used in meta-analysis of angiotensin-converting enzyme (ACE) inhibitor clinical trials to analyze the relative rates and the excess rates between ACE inhibitor and placebo treatment groups for endpoints of hospitalizations for CHF, hospitalizations for CHF or cardiac death, and hospitalizations for CHF or any death, respectively. RESULTS: The estimates of those three endpoints were 69%, 74%, and 76% (P < 0.01). Compared with placebo, ACE inhibitor reduced 30 cases of hospitalizations for CHF per 1000 person-years, or 40 cardiac deaths or hospitalizations for CHF per 1000 person-years (P < 0.01). CONCLUSION: The method was a simple and efficient approach to conduct meta-analysis of clinical trials with recurrent events.

Angiotensin-Converting Enzyme Inhibitors↗

Acupuncture for back pain: a meta-analysis of randomized controlled trials.

BACKGROUND: Acupuncture is commonly used to treat back pain, but there is no published meta-analysis of trials of its effectiveness for this condition. OBJECTIVE: To perform a meta-analysis of trials of acupuncture for the treatment of back pain. METHODS: A systematic literature search was conducted to retrieve all randomized controlled trials of any form of acupuncture for any type of back pain in humans. The adequacy of the acupuncture treatment was assessed by consulting 6 experienced acupuncturists. The main outcome measure for the meta-analysis was numbers of patients whose symptoms were improved at the end of treatment. RESULTS: Twelve studies were included, of which 9 presented data suitable for meta-analysis. The odds ratio of improvement with acupuncture compared with control intervention was 2.30 (95% confidence interval, 1.28-4.13). For sham-controlled, evaluator-blinded studies, the odds ratio was 1.37 (95% confidence interval, 0.84-2.25). CONCLUSION: Acupuncture was shown to be superior to various control interventions, although there is insufficient evidence to state whether it is superior to placebo.

Acupuncture Therapy↗

Methods of meta-analysis: an analysis.

PURPOSE OF REVIEW: To understand the principles of systematic reviewing and meta-analysis, using recent examples from the medical literature to highlight some of these points. RECENT FINDINGS: The word 'meta-analysis' is an intimidating one, and its associated jargon makes it seem incomprehensible. Actually, it is only a mathematical maneuver to add up data in a systematic review; it might be better called 'meta-addition'. The systematic review is a process of using the best available evidence to answer a particular clinical question. Data combination (usually done with meta-analysis) increases the power to see small differences and makes a more precise estimate of a treatment effect. Its major drawback is heterogeneity (the proverbial problem of adding apples and oranges). Systematic reviews have been used by medical societies to create position statements. Such statements have suggested that parenteral nutrition is far less efficacious than previously believed. Systematic reviews in some areas of nutritional support have clarified type II errors. Problems exist, however, in a number of the published meta-analyses of aspects of this therapy. SUMMARY: Especially in an era of resource restraint, we need to become more skilled at interpreting evidence from clinical research.

Clinical Trials as Topic↗

Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study.

UNLABELLED: With the rise of molecular and genetic epidemiology, molecular association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved. INTRODUCTION: With the rise of molecular and genetic epidemiology, molecular association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the association of vitamin D receptor (VDR) gene polymorphisms and BMD/osteoporosis and highlights methodological issues. MATERIALS AND METHODS: Studies published from 1994 to 2001 were identified through Medline using PubMed software. The reference lists of the articles retrieved were also reviewed. Where eligible papers had insufficient information, we contacted authors by mail (up to three mailings) for additional information. Any observational study, which tested the association between VDR BsmI genotypes and either BMD or osteoporosis at the femoral neck or spine in adult women, was included in the review. Data were extracted independently by two reviewers (AT and JA) using a standardized data extraction form. RESULTS: The B allele was significantly associated with BMD at the spine; it seemed to follow a recessive model, with the BB genotype having lower BMD than Bb/bb genotypes at baseline, which led to greater bone mineral loss over time. Highlighted methodological lessons included the need to check Hardy-Weinberg equilibrium and the importance of exploring heterogeneity, pooling data in a manner that is sensitive to genetic models, and avoiding multiple comparisons. CONCLUSION: With the proliferation of molecular association studies, there will be an increased need to quantify the magnitude of the risk associated with genetic polymorphisms. This will likely entail meta-analytic methods, and this meta-analysis highlights some of the methodological issues that will need to be resolved.

Adult↗

[Value of the Cochrane Collaboration: the point of view of meta-analysis practitioner].

To-date, most of the meta-analyses performed are exclusively based on published data; however, some are based on individual patient data of published and unpublished trials. This last method is the reference method, but it is time-consuming and costly. The quality of meta-analyses is varied and could partly explain the criticisms this method is subject to. The Cochrane Collaboration could help in the following fields: promotion of registries of trials and meta-analyses, methodological research on meta-analysis, improvement of trial search, trial data storage and pertinence of information in published trials, improvement of meta-analysis quality, and dissemination of results. The interventions of the Cochrane Collaboration could thus improve the quality and the time performance of meta-analyses, reducing expenses and enabling the widespread dissemination of regularly updated results.

France↗

Assessing the potential for bias in meta-analysis due to selective reporting of subgroup analyses within studies.

Subgroup analysis is frequently used to investigate heterogeneity in meta-analysis. Subgroup data are not always available, and researchers should record what data were available for each trial. If data were not available, and it is known that the subgroup data were collected, the potential for selective reporting should be considered. Bias due to selective publishing of reports is widely recognized in meta-analysis. In contrast, selective reporting within studies is little discussed but potentially important. We explored this problem by evaluating the effect of potential bias in subgroup analysis due to within-study selective reporting with an existing meta-analysis. The review addressed malaria chemoprophylaxis in pregnancy. The conclusion in the original review, that benefit is limited to primigravidae, was based on subgroup analysis using the three trials out of five which reported on subgroups. We developed a method of sensitivity analysis that imputes data for the missing subgroups to assess the robustness of the results and the conclusions drawn. In this particular example, our analysis indicates that the estimate of effect reported in the review is most likely to overestimate the true effect and the conclusion that benefit is limited to primigravidae may be false.

Bias↗

The role of meta-analysis in the regulatory process for foods, drugs, and devices.

Synthesis of research findings has a long-standing tradition in science. While synthesis is currently required in the US food and drug regulatory process, formal meta-analysis may substitute for a pivotal study or broaden the generalizability of drug efficacy through a preplanned meta-analysis. Preplanned meta-analysis of individual trials with deliberately introduced heterogeneity may maximize the generalizability of results from randomized trials. Combining observational data may help to support an alternative claim or to quantify adverse events. In this setting, methods to address potentially greater sources of bias are required. Overall, meta-analysis adds evidence through the synthesis study findings and permits examination of how treatment effects vary across of subgroups, such as age and sex, and across study settings.

Drug Approval↗

The risks of death and of severe nonfatal reactions with high- vs low-osmolality contrast media: a meta-analysis.

Estimates of the risks associated with the use of radiologic contrast agents frequently are based on a subjective review of some of the numerous articles that have been published on the subject. We have chosen instead to synthesize the existing evidence in an objective, quantitative way by statistically combining the data from individual studies through meta-analysis. Although meta-analysis is subject to whatever biases may exist in the underlying data, and may inappropriately pool data from studies with significant differences, the estimates draw proportionately from each original study and, in addition, gain considerable precision owing to the increased amounts of data considered. Using this technique, we analyzed the data from all available original reports appearing since 1980. Crude rates derived from all reports were used to estimate risks with high-osmolality media. Weighted rate differences based on comparative studies only were used in the estimation of the reductions in risk obtainable with low-osmolality media. The risk of death with high-osmolality media was 0.9 per 100,000 uses (95% confidence interval, 0.3-2.6 per 100,000). The difference in risk produced by using low-osmolality media was 0 (95% confidence interval, -1.1 to 1.1 per 100,000). The risk of severe reactions associated with high-osmolality media was 157 per 100,000 uses (95% confidence interval, 144-172 per 100,000). The reduction in risk that can be obtained by the use of low-osmolality media was estimated to be 126 per 100,000 (95% confidence interval, 110-142 per 100,000). This meta-analysis shows that the risk of death is very low with either type of contrast material and that there is no difference between them. Severe nonfatal reactions with high-osmolality media, although more frequent, are still rare; approximately 80% of them can be prevented by using low-osmolality media.

Contrast Media↗

Surgical treatment of endometriosis-associated infertility: meta-analysis compared with survival analysis.

OBJECTIVE: Our purpose was to evaluate the role of surgery in the treatment of endometriosis associated with infertility. STUDY DESIGN: We used a prospective cohort analysis of pregnancy rates and variables affecting pregnancy rates for surgical, medical, and no treatment. Our studies were combined with those reported by Hughes et al. (Fertil Steril 1993; 59:963-70), and the meta-analysis was expanded to include additional comparisons. Treatment was performed by a single surgeon in a referral reproductive endocrinology and surgery private practice. Results from 579 women with endometriosis and infertility in our study and the meta-analysis of 25 studies by Hughes et al. were examined. Interventions consisted of no treatment, medical treatment, or surgical treatment by laparoscopy or laparotomy. The main outcome measure was pregnancy rates. RESULTS: For minimal and mild disease, no treatment, laparoscopy, and laparotomy had equivalent 3-year estimated cumulative life-table pregnancy rates (67% +/- 12%, 68% +/- 4%, and 74% +/- 8%, respectively) that were higher than medical treatment pregnancy rates (Breslow p = 0.003). For moderate and severe disease, all but 11 patients were treated surgically. The 3-year estimated cumulative life-table pregnancy rates were 62% + 6% [corrected] for 120 laparoscopy cases and 44% + 6% [corrected] for 102 laparotomy cases (Breslow p = 0.054). For endometriomas, 48 laparoscopy patients had a 3-year estimated cumulative life-table pregnancy rate of 52% +/- 9% and 52 laparotomy patients had a 3-year estimated cumulative life-table pregnancy rate of 46% +/- 9% (Breslow p = 0.48). For 28 patients with complete cul-de-sac obliteration, the 3-year estimated cumulative life-table pregnancy rates were 30% +/- 14% after laparoscopy and 24% +/- 12% after laparotomy (Breslow p = 0.084). Comparison of our results with the expanded meta-analysis revealed deficiencies in the design of meta-analysis studies and the impact of our using life-table pregnancy rates controlled for factors influencing outcome (survival analysis with fixed covariates) rather than the simple pregnancy rates used in the meta-analysis. Benefits of sophisticated statistical techniques, including propensity scores, to adjust for noncomparability of groups in prospective cohort studies were identified. CONCLUSION: Both our study and the meta-analysis show that either no treatment or surgery is superior to medical treatment for minimal and mild endometriosis associated with infertility. For moderate and severe disease, surgery is usually used. In these patients experienced surgeons utilizing good clinical judgment can achieve results at operative laparoscopy at least equivalent to those at laparotomy, even in cases involving endometriomas and complete cul-de-sac obliteration. Prospective randomized trials should be performed to confirm these findings.

Cohort Studies↗