Graphical presentation of diagnostic information

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.

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee

BACKGROUND: Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. METHODS: We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. RESULTS: 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. CONCLUSIONS: In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Multidimensional preventive home visit programs for community-dwelling older adults: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Multidimensional preventive home visit programs aim at maintaining health and autonomy of older adults and preventing disability and subsequent nursing home admission, but results of randomized controlled trials (RCTs) have been inconsistent. Our objective was to systematically review RCTs examining the effect of home visit programs on mortality, nursing home admissions, and functional status decline. METHODS: Data sources were MEDLINE, EMBASE, Cochrane CENTRAL database, and references. Studies were reviewed to identify RCTs that compared outcome data of older participants in preventive home visit programs with control group outcome data. Publications reporting 21 trials were included. Data on study population, intervention characteristics, outcomes, and trial quality were double-extracted. We conducted random effects meta-analyses. RESULTS: Pooled effects estimates revealed statistically nonsignificant favorable, and heterogeneous effects on mortality (odds ratio [OR] 0.92, 95% confidence interval [CI], 0.80-1.05), functional status decline (OR 0.89, 95% CI, 0.77-1.03), and nursing home admission (OR 0.86, 95% CI, 0.68-1.10). A beneficial effect on mortality was seen in younger study populations (OR 0.74, 95% CI, 0.58-0.94) but not in older populations (OR 1.14, 95% CI, 0.90-1.43). Functional decline was reduced in programs including a clinical examination in the initial assessment (OR 0.64, 95% CI, 0.48-0.87) but not in other trials (OR 1.00, 95% CI, 0.88-1.14). There was no single factor explaining the heterogenous effects of trials on nursing home admissions. CONCLUSION: Multidimensional preventive home visits have the potential to reduce disability burden among older adults when based on multidimensional assessment with clinical examination. Effects on nursing home admissions are heterogeneous and likely depend on multiple factors including population factors, program characteristics, and health care setting.

Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study

OBJECTIVE: To examine whether the association of inadequate or unclear allocation concealment and lack of blinding with biased estimates of intervention effects varies with the nature of the intervention or outcome. DESIGN: Combined analysis of data from three meta-epidemiological studies based on collections of meta-analyses. DATA SOURCES: 146 meta-analyses including 1346 trials examining a wide range of interventions and outcomes. MAIN OUTCOME MEASURES: Ratios of odds ratios quantifying the degree of bias associated with inadequate or unclear allocation concealment, and lack of blinding, for trials with different types of intervention and outcome. A ratio of odds ratios <1 implies that inadequately concealed or non-blinded trials exaggerate intervention effect estimates. RESULTS: In trials with subjective outcomes effect estimates were exaggerated when there was inadequate or unclear allocation concealment (ratio of odds ratios 0.69 (95% CI 0.59 to 0.82)) or lack of blinding (0.75 (0.61 to 0.93)). In contrast, there was little evidence of bias in trials with objective outcomes: ratios of odds ratios 0.91 (0.80 to 1.03) for inadequate or unclear allocation concealment and 1.01 (0.92 to 1.10) for lack of blinding. There was little evidence for a difference between trials of drug and non-drug interventions. Except for trials with all cause mortality as the outcome, the magnitude of bias varied between meta-analyses. CONCLUSIONS: The average bias associated with defects in the conduct of randomised trials varies with the type of outcome. Systematic reviewers should routinely assess the risk of bias in the results of trials, and should report meta-analyses restricted to trials at low risk of bias either as the primary analysis or in conjunction with less restrictive analyses.

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

An empirical comparison of methods for meta-analysis of diagnostic accuracy showed hierarchical models are necessary

OBJECTIVE: Meta-analysis of studies of the accuracy of diagnostic tests currently uses a variety of methods. Statistically rigorous hierarchical models require expertise and sophisticated software. We assessed whether any of the simpler methods can in practice give adequately accurate and reliable results. STUDY DESIGN AND SETTING: We reviewed six methods for meta-analysis of diagnostic accuracy: four simple commonly used methods (simple pooling, separate random-effects meta-analyses of sensitivity and specificity, separate meta-analyses of positive and negative likelihood ratios, and the Littenberg-Moses summary receiver operating characteristic [ROC] curve) and two more statistically rigorous approaches using hierarchical models (bivariate random-effects meta-analysis and hierarchical summary ROC curve analysis). We applied the methods to data from a sample of eight systematic reviews chosen to illustrate a variety of patterns of results. RESULTS: In each meta-analysis, there was substantial heterogeneity between the results of different studies. Simple pooling of results gave misleading summary estimates of sensitivity and specificity in some meta-analyses, and the Littenberg-Moses method produced summary ROC curves that diverged from those produced by more rigorous methods in some situations. CONCLUSION: The closely related hierarchical summary ROC curve or bivariate models should be used as the standard method for meta-analysis of diagnostic accuracy.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between January 2000 and December 2005. SETTING: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. STUDY PARTICIPANTS: A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). RESULTS: Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Evidence-based diagnosis

Making an accurate diagnosis is essential to ensure that a patient receives appropriate treatment and correct information regarding their prognosis. Characteristics of diagnostic tests are quantified in test accuracy studies, but many such studies have methodological flaws. The HSRC evidence-based diagnosis programme has focused on methods for systematic reviews of test accuracy studies, and the wider context in which tests are ordered and interpreted. We carried out a range of projects relating to literature searching, quality assessment, meta-analysis, presentation of results, and interactions between doctors and patients during the diagnostic process. We have shown that systematic reviews of test accuracy studies should search a range of databases and that current diagnostic filters do not have sufficient accuracy to be used in test accuracy reviews. Summary quality scores should not be used in test accuracy reviews; the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews (QUADAS) tool for assessing test accuracy studies is acceptable for quality assessment. We have shown that the hierarchical summary receiver operating characteristic (HSROC) and bivariate models for meta-analysis of test accuracy are statistically equivalent in many circumstances, and have developed an add-on module for the statistical software package Stata that enables these statistically rigorous models to be fitted by those without expert statistical knowledge. Three areas that would benefit from further research are literature searching, synthesis of results from individual patient data and presentation of results.

Residence near power lines and mortality from neurodegenerative diseases: longitudinal study of the Swiss population

The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000-2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220-380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220-380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.

What do case-control studies estimate? Survey of methods and assumptions in published case-control research

To evaluate strategies used to select cases and controls and how reported odds ratios are interpreted, the authors examined 150 case-control studies published in leading general medicine, epidemiology, and clinical specialist journals from 2001 to 2007. Most of the studies (125/150; 83%) were based on incident cases; among these, the source population was mostly dynamic (102/125; 82%). A minority (23/125; 18%) sampled from a fixed cohort. Among studies with incident cases, 105 (84%) could interpret the odds ratio as a rate ratio. Fifty-seven (46% of 125) required the source population to be stable for such interpretation, while the remaining 48 (38% of 125) did not need any assumptions because of matching on time or concurrent sampling. Another 17 (14% of 125) studies with incident cases could interpret the odds ratio as a risk ratio, with 16 of them requiring the rare disease assumption for this interpretation. The rare disease assumption was discussed in 4 studies but was not relevant to any of them. No investigators mentioned the need for a stable population. The authors conclude that in current case-control research, a stable exposure distribution is much more frequently needed to interpret odds ratios than the rare disease assumption. At present, investigators conducting case-control studies rarely discuss what their odds ratios estimate.

Promotion of health in older people: a randomised controlled trial of health risk appraisal in British general practice

BACKGROUND: there is inadequate evidence to support currently formulated NHS strategies to achieve health promotion and preventative care in older people through broad-based screening and assessment in primary care. The most extensively evaluated delivery instrument for this purpose is Health Risk Appraisal (HRA). This article describes a trial using HRA to evaluate the effect on health behaviour and preventative-care uptake in older people in NHS primary care. METHODS: a randomised controlled trial was undertaken in three London primary care group practices. Functionally independent community-dwelling patients older than 65 years (n = 2,503) received a self-administered Health Risk Appraisal for Older Persons (HRA-O) questionnaire leading to computer-generated individualised written feedback to participants and general practitioners (GPs), integrated into practice information-technology (IT) systems. All primary care staff received training in preventative health in older people. The main outcome measures were self-reported health behaviour and preventative care uptake at 1-year follow-up. RESULTS: of 2,503 individuals randomised, 2,006 respondents (80.1%) (intervention, n = 940, control n = 1,066) were available for analysis. Intervention group respondents reported slightly higher pneumococcal vaccination uptake and equivocal improvement in physical activity levels compared with controls. No significant differences were observed for any other categories of health behaviour or preventative care measures at 1-year follow-up. CONCLUSIONS: HRA-O implemented in this way resulted in minimal improvement of health behaviour or uptake of preventative care measures in older people. Supplementary reinforcement involving contact by health professionals with patients over and above routine clinical encounters may be a prerequisite to the effectiveness of IT-based delivery systems for health promotion in older people.

[The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies]

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies.

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

BACKGROUND: Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields. METHODS: We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 muT-years), and less or little exposed shunting yard engineers (42.1 muT-years), train attendants (13.3 muT-years) and station masters (5.7 muT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models. RESULTS: For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants. Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 10 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 muT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction. CONCLUSION: This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.

Statistical analysis of personal radiofrequency electromagnetic field measurements with nondetects

Exposimeters are increasingly applied in bioelectromagnetic research to determine personal radiofrequency electromagnetic field (RF-EMF) exposure. The main advantages of exposimeter measurements are their convenient handling for study participants and the large amount of personal exposure data, which can be obtained for several RF-EMF sources. However, the large proportion of measurements below the detection limit is a challenge for data analysis. With the robust ROS (regression on order statistics) method, summary statistics can be calculated by fitting an assumed distribution to the observed data. We used a preliminary sample of 109 weekly exposimeter measurements from the QUALIFEX study to compare summary statistics computed by robust ROS with a naïve approach, where values below the detection limit were replaced by the value of the detection limit. For the total RF-EMF exposure, differences between the naïve approach and the robust ROS were moderate for the 90th percentile and the arithmetic mean. However, exposure contributions from minor RF-EMF sources were considerably overestimated with the naïve approach. This results in an underestimation of the exposure range in the population, which may bias the evaluation of potential exposure-response associations. We conclude from our analyses that summary statistics of exposimeter data calculated by robust ROS are more reliable and more informative than estimates based on a naïve approach. Nevertheless, estimates of source-specific medians or even lower percentiles depend on the assumed data distribution and should be considered with caution.

[The Strengthening the Reporting of Observational Studies in Epidemiology [STROBE] statement: guidelines for reporting observational studies]

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a che-cklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies.