Number of trials to assess human eyeblink classical conditioning.

Eyeblink classical conditioning ( EBCC) is a useful paradigm for studying the neurobiology of learning and memory. EBCC shows large age effects and has been shown to be sensitive to Alzheimer-like neuropathology. The EBCC data of 241 participants, including young, middle-aged, and elderly normal adults, adults with Down's syndrome, and patients with probable Alzheimer's disease, were analyzed to identify a minimum number of trials for reliable assessment. Results indicate that EBCC performance can be as reliably assessed in 63 trials as in 90 trials. Using fewer conditioning trials reduces administration time, making EBCC more practical for both research and potential diagnostic purposes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Incorporation of sequential trials into a fixed effects meta-analysis

The technique of meta-analysis provides a systematic and quantitative approach to the summary of results from a collection of similar randomized studies. Comprehensive methodology exists for analysis when all trials are of a fixed sample size design, but this is based on assumptions which are no longer valid when incorporating sequentially designed studies. In this paper the effect of incorporating one or more sequential trials into a meta-analysis otherwise consisting of fixed sample size trials is investigated. The results from simulation studies of a variety of plausible scenarios are presented. The aim is to quantify the extent to which bias is introduced. It was found that when incorporating two alternative sequential designs, the triangular test and the O'Brien and Fleming procedure, the results of a conventional meta-analysis remain accurate.     

Meta-analysis of multiple outcomes by regression with random effects

Earlier work showed how to perform fixed-effects meta-analysis of studies or trials when each provides results on more than one outcome per patient and these multiple outcomes are correlated. That fixed-effects generalized-least-squares approach analyzes the multiple outcomes jointly within a single model, and it can include covariates, such as duration of therapy or quality of trial, that may explain observed heterogeneity of results among the trials. Sometimes the covariates explain all the heterogeneity, and the fixed-effects regression model is appropriate. However, unexplained heterogeneity may often remain, even after taking into account known or suspected covariates. Because fixed-effects models do not make allowance for this remaining unexplained heterogeneity, the potential exists for bias in estimated coefficients, standard errors and p-values. We propose two random-effects approaches for the regression meta-analysis of multiple correlated outcomes. We compare their use with fixed-effects models and with separate-outcomes models in a meta-analysis of periodontal clinical trials. A simulation study shows the advantages of the random-effects approach. These methods also facilitate meta-analysis of trials that compare more than two treatments.     

Consensus standards for the process of cancer care: a modified expert panel method applied to head and neck cancer. South and West Expert Tumour Panel for Head and Neck Cancer

There are many pressures to improve the standard of care delivered to cancer patients, including the reforms subsequent to the Calman-Hine report. The establishment of standards is a prerequisite for audit, benchmarking and certification of cancer centres and units. Randomized trials of head and neck cancer are uncommon, and other forms of evidence often conflicting. In the south and west of England, a multidisciplinary expert panel consensus method has been applied to the development of standards. A panel representative of specialties involved in the process of care at all three levels, plus social medicine and lay members, was constructed. A model for the process of care was developed consisting of activity areas. For each activity, a near exhaustive list of tasks and standards was established. A three-iteration method with statistical group response was then used to refine the standards. The same method was also applied to the production of a minimum data set for registration, recording and audit. The resulting standards will be regularly reviewed. We have developed a model of the care process, and an expert panel methodology that is applicable to a wide range of problems in clinical oncology.     

Borrowing strength from external trials in a meta-analysis

There exists a variety of situations in which a random effects meta-analysis might be undertaken using a small number of clinical trials. A problem associated with small meta-analyses is estimating the heterogeneity between trials. To overcome this problem, information from other related studies may be incorporated into the meta-analysis. A Bayesian approach to this problem is presented using data from previous meta-analyses in the same therapeutic area to formulate a prior distribution for the heterogeneity. The treatment difference parameters are given non-informative priors. Further, related trials which compare one or other of the treatments of interest with a common third treatment are included in the model to improve inference on both the heterogeneity and the treatment difference. Two approaches to estimating relative efficacy are considered, namely a general parametric approach and a method explicit to binary data. The methodology is illustrated using data from 26 clinical trials which investigate the prevention of cirrhosis using beta-blockers and sclerotherapy. Both sources of external information lead to more precise posterior distributions for all parameters, in particular that representing heterogeneity.     

Limitations of the dodo bird verdict and the role of clinical trials in psychotherapy research: Comment on Wampold et al. (1997).

B. E. Wampold et al.'s (1997) meta-analysis provides a useful and methodologically sophisticated summary of the results of comparative psychotherapy outcome research. Despite its strengths, some limitations of the meta-analysis that may have biased the results against finding differences between treatments are pointed out in this article. In addition, the types of treatments and patient populations to which the results can be generalized are clarified through an analysis of the studies contained within the meta-analysis. The importance of exceptions to the Dodo bird verdict is emphasized. Disagreements with Wampold et al. on the implications of the their meta-analysis for research and practice, in particular the role of clinical trials in psychotherapy research and the need for identifying treatments that are "empirically supported," are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An empirical assessment of meta-analytic practice.

In the three decades after the publication of the first meta-analyses in the behavioral sciences, hundreds of articles and a number of technical guides have emerged concerning meta-analytic practice and reporting standards. The purpose of the present study is to review the practice and reporting standards of a random sample of published meta-analyses (n = 100) in psychology and related disciplines in the decade from 1994 through 2004. We focus on practice and reporting at each stage of the meta-analytic process and explore differences between psychological subdisciplines. These findings suggest that the practice of meta-analysis in the last decade has not yet converged on a set of common standards, though some expert recommendations are beginning to be heeded. Authors should be attentive to proper procedure and reporting in light of the numerous threats to the validity of a meta-analysis. Ironically, even though meta-analysts often struggle with incomplete or inconsistent reporting in primary research they are themselves not entirely consistent in reporting their methods and results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multiple-outcome meta-analysis of clinical trials

When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.     

Reliability of variables in the kinematic analysis of spring hurdles

The purpose of this study was to investigate the reliability of kinematic variables in spring hurdles and to find out how many trials are needed to achieve reliable data. Seven British National level athletes in sprint hurdles were videotaped and all eight trials of each athlete were digitized from two camera views to produce three dimensional coordinates. The reliability of 28 kinematic variables across eight trials ranged from 0.54 to 1.00 for females and from 0.00 to 0.99 for males. The number of trials needed to reach a certain reliability level was evaluated using Spearman-Brown prophecy formula, and in the worst case (horizontal velocity lost for males) 78 trials would be needed to reach 0.90 reliability. The results showed reasonably high reliability, and the values for the female trials were generally higher than the male trials. The relative height of the hurdles enforces a more demanding clearance for males that can lead to increased variation within the subjects and thus lowered reliability. Subsequently, the results indicate that often more than one trial is needed to provide accurate quantitative results of the technique.     

The relative benefits of meta-analysis conducted with individual participant data versus aggregated data.

The authors describe the relative benefits of conducting meta-analyses with (a) individual participant data (IPD) gathered from the constituent studies and (b) aggregated data (AD), or the group-level statistics (in particular, effect sizes) that appear in reports of a study’s results. Given that both IPD and AD are equally available, meta-analysis of IPD is superior to meta-analysis of AD. IPD meta-analysis permits synthesists to perform subgroup analyses not conducted by the original collectors of the data, to check the data and analyses in the original studies, to add new information to the data sets, and to use different statistical methods. However, the cost of IPD meta-analysis and the lack of available IPD data sets suggest that the best strategy currently available is to use both approaches in a complementary fashion such that the first step in conducting an IPD meta-analysis would be to conduct an AD meta-analysis. Regardless of whether a meta-analysis is conducted with IPD or AD, synthesists must remain vigilant in how they interpret their results. They must avoid ecological fallacies, Simpson’s paradox, and interpretation of synthesis-generated evidence as supporting causal inferences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coronary heart disease and Type A behaviors: Update on and alternative to the Booth-Kewley and Friedman (1987) quantitative review.

This article reports a meta-analysis of the association of Type A behaviors and coronary heart disease (CHD). It differs from a previous meta-analysis reported in Booth-Kewley and Friedman (1987): it uses different decision rules and updates that analysis by using the most recently published papers fron ongoing investigations and by including published reports from four new prospective investigations. The results of the present meta-analysis show that Type A behavior across all measures and prospective study designs is not a reliable predictor of CHD incidence, when the number of independent studies and number of participants in those studies are weighted. However, Type A-CHD associations are significant in population-based studies. It is suggested that Type A may be an important influence on the precipitating factors accounting for initial CHD events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Meta-analyses of studies of the diagnostic accuracy of laboratory tests: a review of the concepts and methods

OBJECTIVE: To provide practicing pathologists and other laboratory professionals with the necessary background for reading and evaluating published reports of meta-analyses of studies of the diagnostic accuracy of laboratory tests. STUDY SELECTION: English language literature, 1980 to present, pertaining to the rationale, objectives, and interpretation of meta-analyses of randomized controlled trials, and meta-analyses of studies of the diagnostic accuracy of laboratory tests. CONCLUSIONS: Meta-analysis has several applications in the investigation of the diagnostic accuracy of laboratory tests. It can improve the quality of future primary studies by drawing attention to the methodologic deficiencies of existing reports; it can identify reasons for the variation in the results of those reports; and it can generate valid summary estimates of the diagnostic accuracy of laboratory tests based on all completed investigations, providing that the available primary studies are of high scientific validity. Several statistical techniques for integrating data from reports on diagnostic test accuracy have either been developed or are under development, but meta-analysis is often limited by the poor quality of the primary studies and the effect of publication bias. Meta-analysis can evolve into a reliable tool for assessing the accuracy of laboratory tests if both investigators and editors strive to improve the quality of the primary studies and to reduce the extent of publication bias in this area of the literature.     

Human quality control in naval air training.

"In training programs, whether these be military… or civilian… quality control requirements exist… . This paper describes an important instance of the application of psychological research methods to human quality control over a total training program… . Human quality control… should start with identification of graduates who have been unsuccessful on the job and work backwards to the determination of those minimum standards which will prevent the selection and/or graduation of potential failures… . minimum standards already installed and under investigation should reduce the number of unsatisfactory men reaching the fleet by about 50%." The study of minimum training standards is a continuing one. The procedures for translating criterion data into an effective quality control program are summarized in 5 steps. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adjuvant chemotherapy of breast cancer

Numerous randomized trials have been conducted in an attempt to demonstrate the role of adjuvant chemotherapy in localized operable breast cancer. A major meta-analysis has demonstrated its effectiveness in certain indications. These trials show that only long-term combination chemotherapy has an undeniable efficacy. The reference protocol is the classical CMF combining cyclophosphamid, methotrexate and 5 fluoro-uracil. Efficacy is clear for patients under 50 years of age. After this age, tamoxifen is effective. There does not appear to be any benefit from prolonging chemotherapy over 6 months. The meta-analysis has not however answered all the questions raised by adjuvant chemotherapy. Should chemotherapy be used in N-forms? What is the effect of treatment in patients over 65? What is the optimal treatment duration? Is there a dose-efficacy relationship? What is the relative effect of chemotherapy versus radiotherapy? Does perioperative chemotherapy add any benefit? What should be the relative roles of hormone therapy and chemotherapy? Is castration as effective as chemotherapy before menopause and tamoxifen after menopause? Currently, only partial answers to these questions have been obtained and many remaining problems will only be solved by the results of controlled trials currently under way.     

From the lab to the clinic: Effectiveness of cognitive-behavioral treatments for anxiety disorders.

A controversy exists over whether results of randomized controlled trials of psychological treatment methods generalize to routine clinical practice. To examine the generalizability of cognitive-behavioral interventions for anxiety disorders, a meta-analysis of 11 effectiveness studies was conducted. Only studies that closely approximated real-world clinical practice were included in the present meta-analysis (e.g., studies were conducted in a nonuniversity setting, practitioners had regular caseloads, clients were not excluded if they had comorbid conditions). Cognitive-behavioral interventions were associated with significant improvement in anxiety symptoms at the end of treatment (dw = 1.35) and again at follow-up (dw = 1.14). On the basis of these results, it seems that cognitive-behavioral interventions for anxiety disorders generalize to real-world clinical practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis

BACKGROUND: Infection remains a serious complication after permanent pacemaker implantation. Antibiotic prophylaxis is frequently prescribed at the time of insertion to reduce its incidence, although results of well-designed, controlled studies are lacking. METHODS AND RESULTS: We performed a meta-analysis of all available randomized trials to evaluate the effectiveness of antibiotic prophylaxis to reduce infection rates after permanent pacemaker implantation. Reports of trials were identified through a Medline, Embase, Current Contents, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, open or blind trials; (2) patients assigned to a systemic antibiotic group or a control group; (3) end point events related to any infection after pacemaker implantation: wound infection, septicemia, pocket abscess, purulent secretion, right infective endocarditis, inflammatory signs, a positive culture, septic pulmonary embolism, or repeat operation for an infective complication. Seven trials met the inclusion criteria. They included 2023 patients with established permanent pacemaker implantation (new implants or replacements). The incidence of end point events in control groups ranged from 0% to 12%. The meta-analysis suggested a consistent protective effect of antibiotic pretreatment (P=.0046; common odds ratio: 0.256, 95% confidence interval: 0.10 to 0.656). CONCLUSIONS: Results of the present meta-analysis suggest that systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications after permanent pacemaker implantation. They support the use of prophylactic antibiotics at the time of pacemaker insertion to prevent short-term pocket infection, skin erosion or septicemia.     

Meta-analysis of day treatment and contingency-management dismantling research: Birmingham Homeless Cocaine Studies (1990-2006).

Four successive randomized clinical trials studying contingency management (CM), involving various treatment arms of drug-abstinent housing and work therapy and day treatment (DT) with a behavioral component, were compared on common drug abstinence outcomes at 2 treatment completion points (2 and 6 months). The clinical trials were conducted from 1990 to 2006 in Birmingham, Alabama, with a total of 644 homeless persons with primary crack cocaine addiction. The meta-analysis utilized the weighted least squares approach to integrate data encompassing 9 different treatment arms to assess the effects of CM and DT (neither, DT only, CM only, and CM = DT) on a common estimate of prevalence of drug abstinence. Taken together, the results show much stronger benefits from CM = DT and from CM only than for DT alone. Throughout all of the Birmingham Homeless Cocaine Studies, the CM = DT consistently produced higher abstinence prevalence than did no CM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of cumulative meta-analysis in the design, monitoring, and final analysis of a clinical trial: a case study

From 1983 to 1987, the Department of Veterans Affairs (DVA) Cooperative Studies Program (CSP) conducted a multicenter clinical trial (CSP #207) to determine whether four different antiplatelet regimens compared to placebo could prevent the occlusion of grafts following coronary artery bypass surgery. The study showed that all of the active regimens tended to be better than placebo and that the three regimens containing aspirin were statistically significantly better. A cumulative meta-analysis of 12 trials performed shortly before the end of CSP #207 raised the issue as to whether the meta-analysis, if done earlier, would have changed the conduct of the trial. At the start of the planning period, one trail of size n = 37 had been published with a nonsignificant odds ratio (OR) of 0.74 (95% CI: 0.18, 3.12). At the time that CSP # 207 was approved by the DVA Cooperative Studies Evaluation Committee, two trials had been published (cumulative n = 150, OR = 0.44, 95% CI 0.19, 0.99). At the time patient intake started, five trials showed cumulative n = 769, OR = 0.42, 95% CI = 0.26, 0.68. Although the first 6-month CSP #207 progress report showed no treatment effect, by the time of the 12-month review by the Data Monitoring Board (DMB) a trend was developing in favor of active treatment. If the results of the meta-analysis had been available to the DMB at that time, conceivably the Board would have recommended stopping the placebo arm because of a convincing treatment effect based on the totality of the evidence. Cumulative meta-analysis could be useful as an adjunct in the planning, conduct, and final analysis of a clinical trial. It could also be used as one piece of evidence in the monitoring of the ongoing phase of a trial.     

Efficacy of estrogen therapy in urinary incontinence. A meta-analytic study

OBJECTIVE: To analyze by meta-analysis the results of randomized controlled clinical trials on the efficacy of estrogen treatment in menopausal patients with urinary incontinence. STUDY DESIGN: Meta-analysis. MATERIALS AND METHODS: Randomized controlled clinical trials, published from January 1965 to December 1996, on estrogen therapy in patients with urinary incontinence, were selected. They included: trials with placebo vs estrogen therapy, studies on menopausal patients with confirmed diagnosis of urinary incontinence based on clinical and/or urodynamic tests, studies with sufficient statistical informations on the results obtained and with information about subjective and objective outcome. RESULTS: Out of 72 articles reviewed, 7 were selected and only 4 were considered on the basis of the requested criteria. Subjective outcome was statistically different in patients treated with estrogen therapy compared with patients treated with placebo. Objective clinical and urodynamic outcome was not statistically different in the two types of treatment (estrogen vs placebo treatment). CONCLUSIONS: There were few published randomized controlled studies on estrogen therapy in patients with urinary incontinence in medical literature. Different results between subjective and objective outcome showed by meta-analysis, could be explained either by an estrogen induced unperceivable improvement not registered by clinical and instrumental parameters or by insufficient systems used to collect subjective data. Therefore, it is suggested that, for future research, randomized controlled clinical trials on topical or transcutaneous systemic estrogen treatment with a more than 6 months follow-up will be carry out.     

Implications of direct and indirect range restriction for meta-analysis methods and findings.

Range restriction in most data sets is indirect, but the meta-analysis methods used to date have applied the correction for direct range restriction to data in which range restriction is indirect. The authors show that this results in substantial undercorrections for the effects of range restriction, and they present meta-analysis methods for making accurate corrections when range restriction is indirect. Applying these methods to a well-known large-sample empirical database, the authors estimate that previous meta-analyses have underestimated the correlation between general mental ability and job performance by about 25%, indicating that this is potentially an important methodological issue in meta-analysis in general. (PsycINFO Database Record (c) 2010 APA, all rights reserved)