Publications by authors named "Penny F Whiting"

19 Publications

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Agreement was moderate between data-based and opinion-based assessments of biases affecting randomized trials within meta-analyses.

J Clin Epidemiol 2020 09 13;125:16-25. Epub 2020 May 13.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; NIHR Applied Research Collaboration (ARC) West, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

Background And Objective: Randomized trials included in meta-analyses are often affected by bias caused by methodological flaws or limitations, but the degree of bias is unknown. Two proposed methods adjust the trial results for bias using empirical evidence from published meta-epidemiological studies or expert opinion.

Methods: We investigated agreement between data-based and opinion-based approaches to assessing bias in each of four domains: sequence generation, allocation concealment, blinding, and incomplete outcome data. From each sampled meta-analysis, a pair of trials with the highest and lowest empirical model-based bias estimates was selected. Independent assessors were asked which trial within each pair was judged more biased on the basis of detailed trial design summaries.

Results: Assessors judged trials to be equally biased in 68% of pairs evaluated. When assessors judged one trial as more biased, the proportion of judgments agreeing with the model-based ranking was highest for allocation concealment (79%) and blinding (79%) and lower for sequence generation (59%) and incomplete outcome data (56%).

Conclusion: Most trial pairs found to be discrepant empirically were judged to be equally biased by assessors. We found moderate agreement between opinion and data-based evidence in pairs where assessors ranked one trial as more biased.
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http://dx.doi.org/10.1016/j.jclinepi.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482431PMC
September 2020

Interpreting a covid-19 test result.

BMJ 2020 May 12;369:m1808. Epub 2020 May 12.

Sentara Healthcare and Eastern Virginia Medical School, Norfolk, VA, USA.

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http://dx.doi.org/10.1136/bmj.m1808DOI Listing
May 2020

PROBAST: A Tool to Assess Risk of Bias and Applicability of Prediction Model Studies: Explanation and Elaboration.

Ann Intern Med 2019 01;170(1):W1-W33

Institute of Applied Health Research, National Institute for Health Research Birmingham Biomedical Research Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.M.).

Prediction models in health care use predictors to estimate for an individual the probability that a condition or disease is already present (diagnostic model) or will occur in the future (prognostic model). Publications on prediction models have become more common in recent years, and competing prediction models frequently exist for the same outcome or target population. Health care providers, guideline developers, and policymakers are often unsure which model to use or recommend, and in which persons or settings. Hence, systematic reviews of these studies are increasingly demanded, required, and performed. A key part of a systematic review of prediction models is examination of risk of bias and applicability to the intended population and setting. To help reviewers with this process, the authors developed PROBAST (Prediction model Risk Of Bias ASsessment Tool) for studies developing, validating, or updating (for example, extending) prediction models, both diagnostic and prognostic. PROBAST was developed through a consensus process involving a group of experts in the field. It includes 20 signaling questions across 4 domains (participants, predictors, outcome, and analysis). This explanation and elaboration document describes the rationale for including each domain and signaling question and guides researchers, reviewers, readers, and guideline developers in how to use them to assess risk of bias and applicability concerns. All concepts are illustrated with published examples across different topics. The latest version of the PROBAST checklist, accompanying documents, and filled-in examples can be downloaded from www.probast.org.
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http://dx.doi.org/10.7326/M18-1377DOI Listing
January 2019

PROBAST: A Tool to Assess the Risk of Bias and Applicability of Prediction Model Studies.

Ann Intern Med 2019 01;170(1):51-58

Institute of Applied Health Research, National Institute for Health Research Birmingham Biomedical Research Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom (S.M.).

Clinical prediction models combine multiple predictors to estimate risk for the presence of a particular condition (diagnostic models) or the occurrence of a certain event in the future (prognostic models). PROBAST (Prediction model Risk Of Bias ASsessment Tool), a tool for assessing the risk of bias (ROB) and applicability of diagnostic and prognostic prediction model studies, was developed by a steering group that considered existing ROB tools and reporting guidelines. The tool was informed by a Delphi procedure involving 38 experts and was refined through piloting. PROBAST is organized into the following 4 domains: participants, predictors, outcome, and analysis. These domains contain a total of 20 signaling questions to facilitate structured judgment of ROB, which was defined to occur when shortcomings in study design, conduct, or analysis lead to systematically distorted estimates of model predictive performance. PROBAST enables a focused and transparent approach to assessing the ROB and applicability of studies that develop, validate, or update prediction models for individualized predictions. Although PROBAST was designed for systematic reviews, it can be used more generally in critical appraisal of prediction model studies. Potential users include organizations supporting decision making, researchers and clinicians who are interested in evidence-based medicine or involved in guideline development, journal editors, and manuscript reviewers.
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http://dx.doi.org/10.7326/M18-1376DOI Listing
January 2019

Quality of family relationships and outcomes of dementia: a systematic review.

BMJ Open 2018 01 21;8(1):e015538. Epub 2018 Jan 21.

Bristol Medical School, University of Bristol, Bristol, UK.

Objectives: To evaluate the association between the quality of relationship between a person with dementia and their family carer and outcomes for the person with dementia.

Design: Systematic review.

Eligibility Criteria: Cohort studies of people with clinically diagnosed dementia and their main carers. Exposures of interest were any elements of relationship quality, for example, attachment style, expressed emotion and coping style. Our primary outcome was institutionalisation, and secondary outcomes were hospitalisation, death, quality of life and behavioural and psychiatric symptoms of dementia ('challenging behaviour').

Data Sources: MEDLINE, Embase, Web of Science, PsycInfo, the Cochrane Library and Opengrey were searched from inception to May 2017.

Study Appraisal And Synthesis Methods: The Newcastle-Ottawa Scale was used to assess risk of bias. A narrative synthesis of results was performed due to differences between studies.

Results: Twenty studies were included. None of the studies controlled for all prespecified confounding factors (age, gender, socioeconomic status and severity of dementia). Reporting of results was inadequate with many studies simply reporting whether associations were 'statistically significant' without providing effect size estimates or CIs. There was a suggestion of an association between relationship factors and global challenging behaviour. All studies evaluating global challenging behaviour provided statistical evidence of an association (most P values below 0.02). There was no consistent evidence for an association for any other outcome assessed.

Conclusions: There is currently no strong or consistent evidence on the effects of relationship factors on institutionalisation, hospitalisation, death or quality of life for people with dementia. There was a suggestion of an association between relationship factors and challenging behaviour, although the evidence for this was weak. To improve our ability to support those with dementia and their families, further robust studies are needed.

Prospero Registration Number: CRD42015020518.
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http://dx.doi.org/10.1136/bmjopen-2016-015538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780722PMC
January 2018

Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

BJU Int 2016 08 13;118(2):193-204. Epub 2016 May 13.

School of Social and Community Medicine, University of Bristol, Bristol, UK.

To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.
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http://dx.doi.org/10.1111/bju.13499DOI Listing
August 2016

How well do health professionals interpret diagnostic information? A systematic review.

BMJ Open 2015 Jul 28;5(7):e008155. Epub 2015 Jul 28.

School of Social and Community Medicine, University of Bristol, Bristol, UK.

Objective: To evaluate whether clinicians differ in how they evaluate and interpret diagnostic test information.

Design: Systematic review.

Data Sources: MEDLINE, EMBASE and PsycINFO from inception to September 2013; bibliographies of retrieved studies, experts and citation search of key included studies.

Eligibility Criteria For Selecting Studies: Primary studies that provided information on the accuracy of any diagnostic test (eg, sensitivity, specificity, likelihood ratios) to health professionals and that reported outcomes relating to their understanding of information on or implications of test accuracy.

Results: We included 24 studies. 6 assessed ability to define accuracy metrics: health professionals were less likely to identify the correct definition of likelihood ratios than of sensitivity and specificity. -25 studies assessed Bayesian reasoning. Most assessed the influence of a positive test result on the probability of disease: they generally found health professionals' estimation of post-test probability to be poor, with a tendency to overestimation. 3 studies found that approaches based on likelihood ratios resulted in more accurate estimates of post-test probability than approaches based on estimates of sensitivity and specificity alone, while 3 found less accurate estimates. 5 studies found that presenting natural frequencies rather than probabilities improved post-test probability estimation and speed of calculations.

Conclusions: Commonly used measures of test accuracy are poorly understood by health professionals. Reporting test accuracy using natural frequencies and visual aids may facilitate improved understanding and better estimation of the post-test probability of disease.
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http://dx.doi.org/10.1136/bmjopen-2015-008155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521525PMC
July 2015

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

JAMA 2015 Jun 23-30;313(24):2456-73

Kleijnen Systematic Reviews Ltd, Escrick, York, United Kingdom10School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, the Netherlands.

Importance: Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.

Objective: To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.

Data Sources: Twenty-eight databases from inception to April 2015.

Study Selection: Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.

Data Extraction And Synthesis: Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis.

Main Outcomes And Measures: Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.

Results: A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.

Conclusions And Relevance: There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
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http://dx.doi.org/10.1001/jama.2015.6358DOI Listing
July 2015

Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials.

Clin Infect Dis 2014 Feb 13;58(4):470-80. Epub 2013 Dec 13.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine.

Background: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood.

Methods: We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression.

Results: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25).

Conclusions: Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.
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http://dx.doi.org/10.1093/cid/cit790DOI Listing
February 2014

A systematic review classifies sources of bias and variation in diagnostic test accuracy studies.

J Clin Epidemiol 2013 Oct 17;66(10):1093-104. Epub 2013 Aug 17.

Kleijnen Systematic Reviews Ltd, Unit 6, Escrick Business Park, Riccall Road, Escrick, York YO19 6FD, United Kingdom.

Objective: To classify the sources of bias and variation and to provide an updated summary of the evidence of the effects of each source of bias and variation.

Study Design And Setting: We conducted a systematic review of studies of any design with the main objective of addressing bias or variation in the results of diagnostic accuracy studies. We searched MEDLINE, EMBASE, BIOSIS, the Cochrane Methodology Register, and Database of Abstracts of Reviews of Effects (DARE) from 2001 to October 2011. Citation searches based on three key papers were conducted, and studies from our previous review (search to 2001) were eligible. One reviewer extracted data on the study design, objective, sources of bias and/or variation, and results. A second reviewer checked the extraction.

Results: We summarized the number of studies providing evidence of an effect arising from each source of bias and variation on the estimates of sensitivity, specificity, and overall accuracy.

Conclusions: We found consistent evidence for the effects of case-control design, observer variability, availability of clinical information, reference standard, partial and differential verification bias, demographic features, and disease prevalence and severity. Effects were generally stronger for sensitivity than for specificity. Evidence for other sources of bias and variation was limited.
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http://dx.doi.org/10.1016/j.jclinepi.2013.05.014DOI Listing
October 2013

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

Ann Intern Med 2011 Oct;155(8):529-36

University of Bristol, United Kingdom.

In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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http://dx.doi.org/10.7326/0003-4819-155-8-201110180-00009DOI Listing
October 2011

Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis.

Ann Intern Med 2010 Apr;152(7):456-64; W155-66

Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, United Kingdom.

Background: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis.

Purpose: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease.

Data Sources: 10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies.

Study Selection: Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 x 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria).

Data Extraction: One reviewer abstracted data on patient characteristics, ACPA details, and 2 x 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions.

Data Synthesis: 151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case-control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone.

Limitations: Most studies used a diagnostic case-control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed.

Conclusion: Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.
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http://dx.doi.org/10.7326/0003-4819-152-7-201004060-00010DOI Listing
April 2010

Graphical presentation of diagnostic information.

BMC Med Res Methodol 2008 Apr 11;8:20. Epub 2008 Apr 11.

Department of Social Medicine, Canynge Hall, Whiteladies Road, Bristol, BS8 2PR, UK.

Background: Graphical displays of results allow researchers to summarise and communicate the key findings of their study. Diagnostic information should be presented in an easily interpretable way, which conveys both test characteristics (diagnostic accuracy) and the potential for use in clinical practice (predictive value).

Methods: We discuss the types of graphical display commonly encountered in primary diagnostic accuracy studies and systematic reviews of such studies, and systematically review the use of graphical displays in recent diagnostic primary studies and systematic reviews.

Results: We identified 57 primary studies and 49 systematic reviews. Fifty-six percent of primary studies and 53% of systematic reviews used graphical displays to present results. Dot-plot or box-and- whisker plots were the most commonly used graph in primary studies and were included in 22 (39%) studies. ROC plots were the most common type of plot included in systematic reviews and were included in 22 (45%) reviews. One primary study and five systematic reviews included a probability-modifying plot.

Conclusion: Graphical displays are currently underused in primary diagnostic accuracy studies and systematic reviews of such studies. Diagnostic accuracy studies need to include multiple types of graphic in order to provide both a detailed overview of the results (diagnostic accuracy) and to communicate information that can be used to inform clinical practice (predictive value). Work is required to improve graphical displays, to better communicate the utility of a test in clinical practice and the implications of test results for individual patients.
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http://dx.doi.org/10.1186/1471-2288-8-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394529PMC
April 2008

Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies.

BMC Med Res Methodol 2006 Mar 6;6. Epub 2006 Mar 6.

MRC Health Services Research Collaboration, Department of Social Medicine, Canynge Hall, Whiteladies Road, Bristol, UK.

Background: A quality assessment tool for diagnostic accuracy studies, named QUADAS, has recently been developed. Although QUADAS has been used in several systematic reviews, it has not been formally validated. The objective was to evaluate the validity and usefulness of QUADAS.

Methods: Three reviewers independently rated the quality of 30 studies using QUADAS. We assessed the proportion of agreements between each reviewer and the final consensus rating. This was done for all QUADAS items combined and for each individual item. Twenty reviewers who had used QUADAS in their reviews completed a short structured questionnaire on their experience of QUADAS.

Results: Over all items, the agreements between each reviewer and the final consensus rating were 91%, 90% and 85%. The results for individual QUADAS items varied between 50% and 100% with a median value of 90%. Items related to uninterpretable test results and withdrawals led to the most disagreements. The feedback on the content of the tool was generally positive with only small numbers of reviewers reporting problems with coverage, ease of use, clarity of instructions and validity.

Conclusion: Major modifications to the content of QUADAS itself are not necessary. The evaluation highlighted particular difficulties in scoring the items on uninterpretable results and withdrawals. Revised guidelines for scoring these items are proposed. It is essential that reviewers tailor guidelines for scoring items to their review, and ensure that all reviewers are clear on how to score studies. Reviewers should consider whether all QUADAS items are relevant to their review, and whether additional quality items should be assessed as part of their review.
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http://dx.doi.org/10.1186/1471-2288-6-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421422PMC
March 2006

How does study quality affect the results of a diagnostic meta-analysis?

BMC Med Res Methodol 2005 Jun 8;5:20. Epub 2005 Jun 8.

Centre for Reviews and Dissemination, University of York, UK.

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies.

Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns.

Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations.

Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited.
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http://dx.doi.org/10.1186/1471-2288-5-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180444PMC
June 2005

Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.

BMC Pediatr 2005 Mar 15;5(1). Epub 2005 Mar 15.

Centre for Reviews and Dissemination, University of York, England.

Background: Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications.

Methods: We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age.

Results: 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation.

Conclusion: There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.
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http://dx.doi.org/10.1186/1471-2431-5-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079875PMC
March 2005