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Biomedical subjects

Alex J Sutton

Publications and source records attributed to Alex J Sutton.

17 recordsLinked to original sources
PubMed2006

Collaborative care for depression: a cumulative meta-analysis and review of longer-term outcomes.

BACKGROUND: Depression is common in primary care but is suboptimally managed. Collaborative care, that is, structured care involving a greater role of nonmedical specialists to augment primary care, has emerged as a potentially effective candidate intervention to improve quality of primary care and patient outcomes. METHODS: To quantify the short-term and longer-term effectiveness of collaborative care compared with standard care and to understand mechanisms of action by exploring between-study heterogeneity, we conducted a systematic review of randomized controlled trials that compared collaborative care with usual primary care in patients with depression. We searched MEDLINE (from the beginning of 1966), EMBASE (from the beginning of 1980), CINAHL (from the beginning of 1980), PsycINFO (from the beginning of 1980), the Cochrane Library (from the beginning of 1966), and DARE (Database of Abstracts of Reviews of Effectiveness) (from the beginning of 1985) databases from study inception to February 6, 2006. RESULTS: We found 37 randomized studies including 12 355 patients with depression receiving primary care. Random effects meta-analysis showed that depression outcomes were improved at 6 months (standardized mean difference, 0.25; 95% confidence interval, 0.18-0.32), and evidence of longer-term benefit was found for up to 5 years (standardized mean difference, 0.15; 95% confidence interval, 0.001-0.31). When exploring determinants of effectiveness, effect size was directly related to medication compliance and to the professional background and method of supervision of case managers. The addition of brief psychotherapy did not substantially improve outcome, nor did increased numbers of sessions. Cumulative meta-analysis showed that sufficient evidence had emerged by 2000 to demonstrate the statistically significant benefit of collaborative care. CONCLUSIONS: Collaborative care is more effective than standard care in improving depression outcomes in the short and longer terms. Future research needs to address the implementation of collaborative care, particularly in settings other than the United States.

Confidence Intervals↗
PubMed2006

Conducting a critical interpretive synthesis of the literature on access to healthcare by vulnerable groups.

BACKGROUND: Conventional systematic review techniques have limitations when the aim of a review is to construct a critical analysis of a complex body of literature. This article offers a reflexive account of an attempt to conduct an interpretive review of the literature on access to healthcare by vulnerable groups in the UK METHODS: This project involved the development and use of the method of Critical Interpretive Synthesis (CIS). This approach is sensitised to the processes of conventional systematic review methodology and draws on recent advances in methods for interpretive synthesis. RESULTS: Many analyses of equity of access have rested on measures of utilisation of health services, but these are problematic both methodologically and conceptually. A more useful means of understanding access is offered by the synthetic construct of candidacy. Candidacy describes how people's eligibility for healthcare is determined between themselves and health services. It is a continually negotiated property of individuals, subject to multiple influences arising both from people and their social contexts and from macro-level influences on allocation of resources and configuration of services. Health services are continually constituting and seeking to define the appropriate objects of medical attention and intervention, while at the same time people are engaged in constituting and defining what they understand to be the appropriate objects of medical attention and intervention. Access represents a dynamic interplay between these simultaneous, iterative and mutually reinforcing processes. By attending to how vulnerabilities arise in relation to candidacy, the phenomenon of access can be better understood, and more appropriate recommendations made for policy, practice and future research. DISCUSSION: By innovating with existing methods for interpretive synthesis, it was possible to produce not only new methods for conducting what we have termed critical interpretive synthesis, but also a new theoretical conceptualisation of access to healthcare. This theoretical account of access is distinct from models already extant in the literature, and is the result of combining diverse constructs and evidence into a coherent whole. Both the method and the model should be evaluated in other contexts.

Health Services Accessibility↗
PubMed2006

Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.

CONTEXT: Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies. OBJECTIVE: To assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy. DATA SOURCES: A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies. STUDY SELECTION: We included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo. DATA EXTRACTION: Data on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors. DATA SYNTHESIS: We calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF-treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months. CONCLUSIONS: There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.

Adalimumab↗
PubMed2006

Comparison of two methods to detect publication bias in meta-analysis.

CONTEXT: Egger's regression test is often used to help detect publication bias in meta-analyses. However, the performance of this test and the usual funnel plot have been challenged particularly when the summary estimate is the natural log of the odds ratio (lnOR). OBJECTIVE: To compare the performance of Egger's regression test with a regression test based on sample size (a modification of Macaskill's test) with lnOR as the summary estimate. DESIGN: Simulation of meta-analyses under a number of scenarios in the presence and absence of publication bias and between-study heterogeneity. MAIN OUTCOME MEASURES: Type I error rates (the proportion of false-positive results) for each regression test and their power to detect publication bias when it is present (the proportion of true-positive results). RESULTS: Type I error rates for Egger's regression test are higher than those for the alternative regression test. The alternative regression test has the appropriate type I error rates regardless of the size of the underlying OR, the number of primary studies in the meta-analysis, and the level of between-study heterogeneity. The alternative regression test has comparable power to Egger's regression test to detect publication bias under conditions of low between-study heterogeneity. CONCLUSION: Because of appropriate type I error rates and reduction in the correlation between the lnOR and its variance, the alternative regression test can be used in place of Egger's regression test when the summary estimates are lnORs.

Meta-Analysis as Topic↗
PubMed2006

A systematic review of systematic reviews and meta-analyses of animal experiments with guidelines for reporting.

To maximize the findings of animal experiments to inform likely health effects in humans, a thorough review and evaluation of the animal evidence is required. Systematic reviews and, where appropriate, meta-analyses have great potential in facilitating such an evaluation, making efficient use of the animal evidence while minimizing possible sources of bias. The extent to which systematic review and meta-analysis methods have been applied to evaluate animal experiments to inform human health is unknown. Using systematic review methods, we examine the extent and quality of systematic reviews and meta-analyses of in vivo animal experiments carried out to inform human health. We identified 103 articles meeting the inclusion criteria: 57 reported a systematic review, 29 a systematic review and a meta-analysis, and 17 reported a meta-analysis only. The use of these methods to evaluate animal evidence has increased over time. Although the reporting of systematic reviews is of adequate quality, the reporting of meta-analyses is poor. The inadequate reporting of meta-analyses observed here leads to questions on whether the most appropriate methods were used to maximize the use of the animal evidence to inform policy or decision-making. We recommend that guidelines proposed here be used to help improve the reporting of systematic reviews and meta-analyses of animal experiments. Further consideration of the use and methodological quality and reporting of such studies is needed.

Animal Experimentation↗
PubMed2005

How vague is vague? A simulation study of the impact of the use of vague prior distributions in MCMC using WinBUGS.

There has been a recent growth in the use of Bayesian methods in medical research. The main reasons for this are the development of computer intensive simulation based methods such as Markov chain Monte Carlo (MCMC), increases in computing power and the introduction of powerful software such as WinBUGS. This has enabled increasingly complex models to be fitted. The ability to fit these complex models has led to MCMC methods being used as a convenient tool by frequentists, who may have no desire to be fully Bayesian. Often researchers want 'the data to dominate' when there is no prior information and thus attempt to use vague prior distributions. However, with small amounts of data the use of vague priors can be problematic. The results are potentially sensitive to the choice of prior distribution. In general there are fewer problems with location parameters. The main problem is with scale parameters. With scale parameters, not only does one have to decide the distributional form of the prior distribution, but also whether to put the prior distribution on the variance, standard deviation or precision. We have conducted a simulation study comparing the effects of 13 different prior distributions for the scale parameter on simulated random effects meta-analysis data. We varied the number of studies (5, 10 and 30) and compared three different between-study variances to give nine different simulation scenarios. One thousand data sets were generated for each scenario and each data set was analysed using the 13 different prior distributions. The frequentist properties of bias and coverage were investigated for the between-study variance and the effect size. The choice of prior distribution was crucial when there were just five studies. There was a large variation in the estimates of the between-study variance for the 13 different prior distributions. With a large number of studies the choice of prior distribution was less important. The effect size estimated was not biased, but the precision with which it was estimated varied with the choice of prior distribution leading to varying coverage intervals and, potentially, to different statistical inferences. Again there was less of a problem with a larger number of studies. There is a particular problem if the between-study variance is close to the boundary at zero, as MCMC results tend to produce upwardly biased estimates of the between-study variance, particularly if inferences are based on the posterior mean. The choice of 'vague' prior distribution can lead to a marked variation in results, particularly in small studies. Sensitivity to the choice of prior distribution should always be assessed.

Anti-Bacterial Agents↗
PubMed2005

Meta-analysis: The value of clinical assessment in the diagnosis of deep venous thrombosis.

BACKGROUND: Clinical assessment of suspected deep venous thrombosis (DVT) should be based on systematically evaluated evidence. PURPOSE: To determine whether clinical findings, risk scores, and physicians' empirical judgments affect the likelihood of detecting DVT on definitive testing. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, ACP Journal Club, and citation lists (1966 to January 2005). STUDY SELECTION: Cohort studies published in English, French, Spanish, or Italian that compared clinical assessment with a reference standard. DATA EXTRACTION: The authors extracted standardized data, including setting, exclusions, population characteristics, reference standard, and results, and assessed quality against validated criteria. DATA SYNTHESIS: The authors combined data by using random-effects meta-analysis and, if appropriate, used meta-regression to identify covariates that predicted diagnostic accuracy. Only malignancy (likelihood ratio [LR], 2.71), previous DVT (LR, 2.25), recent immobilization (LR, 1.98), difference in calf diameter (LR, 1.80), and recent surgery (LR, 1.76) were useful for ruling in DVT, while only absence of calf swelling (LR, 0.67) or difference in calf diameter (LR, 0.57) was useful for ruling out DVT. The Wells clinical score was more valuable than the individual characteristics; it stratified patients into groups with high (LR, 5.2), intermediate, and low (LR, 0.25) probability of DVT. The Wells score seemed able to stratify patients by risk only for proximal DVT, and it performed better in cohorts that were younger or excluded patients with previous thromboembolism. LIMITATIONS: Pooled estimates were subject to substantial heterogeneity. This may limit extrapolation between observers and settings. Only published studies were included, so findings may be subject to publication bias. CONCLUSION: Individual clinical features are of limited value in diagnosing DVT. Overall assessment of clinical probability by using the Wells score is more useful.

Humans↗
PubMed2005

The use of systematic reviews when designing studies.

BACKGROUND: The importance of systematic reviews in identifying gaps in the evidence base and providing a quantitative basis for informing new research initiatives is widely acknowledged, but little is known about what actually happens in practice. Our objective was to assess the use made of results of reviews in the designing of new studies. METHODS: Of all Cochrane reviews published in 1996, those updated in 2002 or 2003 were identified. Authors of trials added in the updates were contacted and asked if use had been made of the 1996 Cochrane or other reviews in designing their study. RESULTS: Of 32 authors of studies newly included in 33 Cochrane reviews which met our inclusion criteria, 24 (75%) responded. Eleven (46%) respondents were aware of the relevant Cochrane review at the time they designed their study. In eight (33%) cases the design of the new study had been influenced by a review; in two (8%) this was the relevant Cochrane review. CONCLUSIONS: Cautious interpretation of these results is necessary, but it is apparent that the proportion of study investigators using Cochrane or other systematic reviews in designing their new studies was very limited. Inclusion of encouragement in publication or application guidelines to consider and cite review results is desirable.

Clinical Trials as Topic↗
PubMed2004

Finding qualitative research: an evaluation of search strategies.

BACKGROUND: Qualitative research makes an important contribution to our understanding of health and healthcare. However, qualitative evidence can be difficult to search for and identify, and the effectiveness of different types of search strategies is unknown. METHODS: Three search strategies for qualitative research in the example area of support for breast-feeding were evaluated using six electronic bibliographic databases. The strategies were based on using thesaurus terms, free-text terms and broad-based terms. These strategies were combined with recognised search terms for support for breast-feeding previously used in a Cochrane review. For each strategy, we evaluated the recall (potentially relevant records found) and precision (actually relevant records found). RESULTS: A total yield of 7420 potentially relevant records was retrieved by the three strategies combined. Of these, 262 were judged relevant. Using one strategy alone would miss relevant records. The broad-based strategy had the highest recall and the thesaurus strategy the highest precision. Precision was generally poor: 96% of records initially identified as potentially relevant were deemed irrelevant. Searching for qualitative research involves trade-offs between recall and precision. CONCLUSIONS: These findings confirm that strategies that attempt to maximise the number of potentially relevant records found are likely to result in a large number of false positives. The findings also suggest that a range of search terms is required to optimise searching for qualitative evidence. This underlines the problems of current methods for indexing qualitative research in bibliographic databases and indicates where improvements need to be made.

Breast Feeding↗
PubMed2004

Benefits and harms associated with hormone replacement therapy: clinical decision analysis.

OBJECTIVE: To evaluate harms and benefits associated with use of combined hormone replacement therapy (HRT) for five years in women with different baseline risks for breast cancer. DESIGN: Probabilistic clinical decision analysis. SETTING: Hypothetical population of white UK women aged 50 years with different baseline risks for breast cancer. MAIN OUTCOME MEASURE: Gain or loss in quality adjusted life years (QALYs). RESULTS: Women free of menopausal symptoms showed a net harm from HRT use, which increased for increasing baseline risk of breast cancer. Those with a baseline risk of 1.2% would expect a loss in QALYs of 0.4 months (- 0.03 QALYs, 95% credibility interval - 0.05 to - 0.01). The main analysis showed HRT to be on average beneficial in women with symptoms, with benefit decreasing with increasing baseline risk of breast cancer. The results were sensitive to the assumed value of quality of life with menopausal symptoms, therefore a contour plot was developed to show the probability of net harm for a range of different values and baseline risks. CONCLUSIONS: HRT for primary prevention of chronic diseases in women without menopausal symptoms is unjustified. Perceived quality of life in women with symptoms should be taken into account when deciding on HRT. Thus, a decision analysis tailored to an individual woman is more appropriate in clinical practice than a population based approach.

Aged↗
PubMed2004

A systematic review of molecular and biological tumor markers in neuroblastoma.

PURPOSE: The aim of this study was to conduct a systematic review, and where possible meta-analyses, of molecular and biological tumor markers described in neuroblastoma, and to establish an evidence-based perspective on their clinical value for the screening, diagnosis, prognosis, and monitoring of patients. EXPERIMENTAL DESIGN: A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. RESULTS: A total of 428 papers studying the use of 195 different tumor markers in neuroblastoma were identified. Small sample sizes, poor statistical reporting, large heterogeneity across studies (e.g., in cutoff levels), and publication bias limited meta-analysis to the area of prognosis only; MYCN, chromosome 1p, DNA index, vanillylmandelic acid:homovanillic acid ratio, CD44, Trk-A, neuron-specific enolase, lactate dehydrogenase, ferritin, and multidrug resistance were all identified as potentially important prognostic tools. CONCLUSIONS: This systematic review forms a knowledge base of the tumor markers studied thus far in neuroblastoma, and has identified some of the most important prognostic markers, which should be considered in future research and treatment strategies. Importantly, the review has also highlighted some general problems across primary tumor marker studies, in particular poor and heterogeneous reporting. These need to be addressed to allow better clinical interpretation and enable more appropriate evidence-based reviews in the future. In particular, collaboration of cancer research groups is needed to enable bigger sample sizes, standardize methods of analysis and reporting, and facilitate the pooling of individual patient data.

Biomarkers, Tumor↗
PubMed2004

Comprehensive decision analytical modelling in economic evaluation: a Bayesian approach.

Decision analytical models are widely used in economic evaluation of health care interventions with the objective of generating valuable information to assist health policy decision-makers to allocate scarce health care resources efficiently. The whole decision modelling process can be summarised in four stages: (i) a systematic review of the relevant data (including meta-analyses), (ii) estimation of all inputs into the model (including effectiveness, transition probabilities and costs), (iii) sensitivity analysis for data and model specifications, and (iv) evaluation of the model. The aim of this paper is to demonstrate how the individual components of decision modelling, outlined above, may be addressed simultaneously in one coherent Bayesian model (sometimes known as a comprehensive decision analytical model) and evaluated using Markov Chain Monte Carlo simulation implemented in the specialist software WinBUGS. To illustrate the method described, it is applied to two illustrative examples: (1) The prophylactic use of neurominidase inhibitors for the prevention of influenza. (2) The use of taxanes for the second-line treatment of advanced breast cancer. The advantages of integrating the four stages outlined into one comprehensive decision analytical model, compared to the conventional 'two-stage' approach, are discussed.

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↗
PubMed2004

Transurethral electrovaporization vs transurethral resection for symptomatic prostatic obstruction: a meta-analysis.

OBJECTIVE: To compare the effectiveness and safety of transurethral electrovaporization (TUEVP) and transurethral resection of the prostate (TURP) for symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH). METHODS: Publications comparing TUEVP and TURP were identified systematically using Medline, the Cochrane Controlled Trial Register and other database search engines. From a total of 25 randomized controlled trials, 20 studies met the predefined inclusion criteria and were subjected to a formal meta-analysis. Primary endpoints were symptom scores and peak urinary flow rates. Secondary endpoints included transfusion requirements, operative time, duration of catheterization, incidence of adverse events, hospital stay, re-operation rates and sexual dysfunction. RESULTS: After 1 year of follow-up there was no significant difference between TUEVP and TURP in urinary symptom scores and peak urinary flow rates. There was heterogeneity at baseline for both primary outcome measures. TUEVP was associated with significantly lower transfusion requirements, a shorter catheterization time, and a shorter length of stay. TURP was associated with a lower risk of urinary retention afterward and re-operation than was TUEVP. CONCLUSION: This formal meta-analysis suggests that both TUEVP and TURP in patients with symptomatic bladder outlet obstruction provide comparable improvements in maximum urinary flow rates and symptom scores. While comparative analysis is limited by the methodological shortcomings of the underlying studies and the short follow-up, both TURP and TUEVP may offer distinct advantages in terms of secondary outcomes. A future, well-designed, multicentre randomized clinical trial with extended follow-up may be needed to better define the role of vaporization techniques in treating patients with symptomatic BPH.

Electrocoagulation↗
PubMed2002

Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy.

BACKGROUND: Despite the great possibility of publication bias in studies of diagnostic test research, empirical studies about publication bias have mainly focused on studies of treatment effect. METHODS: A sample of 28 meta-analyses of diagnostic accuracy was selected from the Database of Abstracts of Reviews of Effectiveness (DARE). Methods used to deal with publication and related biases in these meta-analyses were examined. Asymmetry of funnel plot of estimated test accuracy against corresponding precision for each meta-analysis was assessed by three statistical methods: rank correlation method, regression analysis, and Trim and Fill method. RESULTS: In reviews of diagnostic accuracy, there was a general lack of consideration of appropriate literature searching to minimize publication bias, and the impact of possible publication bias has not been systematically assessed. The results of the three different statistical methods consistently showed that in a large proportion of the 28 meta-analyses evaluated, the smaller studies were associated with a greater diagnostic accuracy. Exploratory analyses found that the fewer the literature databases searched, the greater the funnel plot asymmetry in meta-analyses. Funnel plot asymmetry tended to be greater in meta-analyses that included smaller number of primary studies. Our data revealed no consistent relationship between funnel plot asymmetry and language restriction in reviews. CONCLUSIONS: Further research is required to explain why smaller studies tended to report greater test accuracy in a large proportion of meta-analyses of diagnostic tests. In systematic reviews of diagnostic studies, literature search should be sufficiently comprehensive and possible impact of publication bias should be assessed.

Diagnostic Techniques and Procedures↗
PubMedDate not supplied

Use of Bayesian Markov Chain Monte Carlo methods to model cost-of-illness data.

It is well known that the modeling of cost data is often problematic due to the distribution of such data. Commonly observed problems include 1) a strongly right-skewed data distribution and 2) a significant percentage of zero-cost observations. This article demonstrates how a hurdle model can be implemented from a Bayesian perspective by means of Markov Chain Monte Carlo simulation methods using the freely available software WinBUGS. Assessment of model fit is addressed through the implementation of two cross-validation methods. The relative merits of this Bayesian approach compared to the classical equivalent are discussed in detail. To illustrate the methods described, patient-specific non-health-care resource-use data from a prospective longitudinal study and the Norfolk Arthritis Register (NOAR) are utilized for 218 individuals with early inflammatory polyarthritis (IP). The NOAR database also includes information on various patient-level covariates.

Arthritis↗