Enamel Caries Detection and Diagnosis:An Analysis of Systematic Reviews

Detection and diagnosis of caries-typically undertaken through a visual-tactile examination, often with supporting radiographic investigations-is commonly regarded as being broadly effective at detecting caries that has progressed into dentine and reached a threshold where restoration is necessary. With earlier detection comes an opportunity to stabilize disease or even remineralize the tooth surface, maximizing retention of tooth tissue and preventing a lifelong cycle of restoration. We undertook a formal comparative analysis of the diagnostic accuracy of different technologies to detect and inform the diagnosis of early caries using published Cochrane systematic reviews. Forming the basis of our comparative analysis were 5 Cochrane diagnostic test accuracy systematic reviews evaluating fluorescence, visual or visual-tactile classification systems, imaging, transillumination and optical coherence tomography, and electrical conductance or impedance technologies. Acceptable reference standards included histology, operative exploration, or enhanced visual assessment (with or without tooth separation) as appropriate. We conducted 2 analyses based on study design: a fully within-study, within-person analysis and a network meta-analysis based on direct and indirect comparisons. Nineteen studies provided data for the fully within-person analysis and 64 studies for the network meta-analysis. Of the 5 technologies evaluated, the greatest pairwise differences were observed in summary sensitivity points for imaging and all other technologies, but summary specificity points were broadly similar. For both analyses, the wide 95% prediction intervals indicated the uncertainty of future diagnostic accuracy across all technologies. The certainty of evidence was low, downgraded for study limitations, inconsistency, and indirectness. Summary estimates of diagnostic accuracy for most technologies indicate that the degree of certitude with which a decision is made regarding the presence or absence of disease may be enhanced with the use of such devices. However, given the broad prediction intervals, it is challenging to predict their accuracy in any future "real world" context

Minimal important changes in standard deviation units are highly variable and no universally applicable value can be determined

[Objectives] This study aims to describe the distribution of anchor-based minimal important change (MIC) estimates in standard deviation (SD) units and examine if the robustness of such estimates depends on the specific SD used or on the methodological credibility of the anchor-based estimates. [Design and Setting] We included all anchor-based MIC estimates from studies published in MEDLINE and relevant literature databases upto October 2018. Each MIC was converted to SD units using baseline, endpoint, and change from baseline SDs. We performed a descriptive analysis of MICs in SD units and checked how the distribution would change if MICs with low methodological credibility were excluded from the analysis. [Results] We included 1, 009 MIC estimates from 182 studies. The medians and interquartile ranges of MICs in SD units were 0.43 (0.25 to 0.69), 0.42 (0.22 to 0.70), and 0.51 (0.28 to 0.78) for baseline, endpoint, and change SD units, respectively. Some MICs were extremely large or small. The distribution did not change significantly after excluding MICs estimated by less credible methods. [Conclusions] The size of the universally applicable MIC in SD units could not be determined. Anchor-based MICs in SD units were widely distributed, with more than half in the range of 0.2 to 0.8

Enamel Caries Detection and Diagnosis: An Analysis of Systematic Reviews

Detection and diagnosis of caries-typically undertaken through a visual-tactile examination, often with supporting radiographic investigations-is commonly regarded as being broadly effective at detecting caries that has progressed into dentine and reached a threshold where restoration is necessary. With earlier detection comes an opportunity to stabilize disease or even remineralize the tooth surface, maximizing retention of tooth tissue and preventing a lifelong cycle of restoration. We undertook a formal comparative analysis of the diagnostic accuracy of different technologies to detect and inform the diagnosis of early caries using published Cochrane systematic reviews. Forming the basis of our comparative analysis were 5 Cochrane diagnostic test accuracy systematic reviews evaluating fluorescence, visual or visual-tactile classification systems, imaging, transillumination and optical coherence tomography, and electrical conductance or impedance technologies. Acceptable reference standards included histology, operative exploration, or enhanced visual assessment (with or without tooth separation) as appropriate. We conducted 2 analyses based on study design: a fully within-study, within-person analysis and a network meta-analysis based on direct and indirect comparisons. Nineteen studies provided data for the fully within-person analysis and 64 studies for the network meta-analysis. Of the 5 technologies evaluated, the greatest pairwise differences were observed in summary sensitivity points for imaging and all other technologies, but summary specificity points were broadly similar. For both analyses, the wide 95% prediction intervals indicated the uncertainty of future diagnostic accuracy across all technologies. The certainty of evidence was low, downgraded for study limitations, inconsistency, and indirectness. Summary estimates of diagnostic accuracy for most technologies indicate that the degree of certitude with which a decision is made regarding the presence or absence of disease may be enhanced with the use of such devices. However, given the broad prediction intervals, it is challenging to predict their accuracy in any future "real world" context

Minimally important difference estimates and methods: A protocol

Introduction: Patient-reported outcomes (PROs) are often the outcomes of greatest importance to patients. The minimally important difference (MID) provides a measure of the smallest change in the PRO that patients perceive as important. An anchor-based approach is the most appropriate method for MID determination. No study or database currently exists that provides all anchor-based MIDs associated with PRO instruments; nor are there any accepted standards for appraising the credibility of MID estimates. Our objectives are to complete a systematic survey of the literature to collect and characterise published anchor-based MIDs associated with PRO instruments used in evaluating the effects of interventions on chronic medical and psychiatric conditions and to assess their credibility. Methods and analysis: We will search MEDLINE, EMBASE and PsycINFO (1989 to present) to identify studies addressing methods to estimate anchor-based MIDs of target PRO instruments or reporting empirical ascertainment of anchor-based MIDs. Teams of two reviewers will screen titles and abstracts, review full texts of citations, and extract relevant data. On the basis of findings from studies addressing methods to estimate anchor-based MIDs, we will summarise the available methods and develop an instrument addressing the credibility of empirically ascertained MIDs. We will evaluate the credibility of all studies reporting on the empirical ascertainment of anchorbased MIDs using the credibility instrument, and assess the instrument's inter-rater reliability. We will separately present reports for adult and paediatric populations. Ethics and dissemination: No research ethics approval was required as we will be using aggregate data from published studies. Our work will summarise anchor-based methods available to establish MIDs, provide an instrument to assess the credibility of available MIDs, determine the reliability of that instrument, and provide a comprehensive compendium of published anchor-based MIDs associated with PRO instruments which will help improve the interpretability of outcome effects in systematic reviews and practice guidelines

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

BACKGROUND: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. METHODS AND FINDINGS: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. CONCLUSIONS: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES: To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials

Authors seldom report the most patient-important outcomes and absolute effect measures in systematic review abstracts

Objectives: Explicit reporting of absolute measures is important to ensure treatment effects are correctly interpreted. We examined the extent to which authors report absolute effects for patient-important outcomes in abstracts of systematic review (SR). Study Design and Setting: We searched OVID MEDLINE and Cochrane Database of Systematic Reviews to identify eligible SRs published in the year 2010. Citations were stratified into Cochrane and non-Cochrane reviews, with repeated random sampling in a 1:1 ratio. Paired reviewers screened articles and recorded abstract characteristics, including reporting of effect measures for the most patient-important outcomes of benefit and harm. Results: We included 96 Cochrane and 94 non-Cochrane reviews. About 117 (77.5%) relative measures were reported in abstracts for outcomes of benefit, whereas only 34 (22.5%) absolute measures were reported. Similarly, for outcomes of harm, 41 (87.2%) relative measures were provided in abstracts, compared with only 6 (12.8%) absolute measures. Eighteen (9.5%) abstracts reported both absolute and relative measures for outcomes of benefit, whereas only two (1.1%) abstracts reported both measures for outcomes of harm. Results were similar between Cochrane and non-Cochrane reviews. Conclusion: SR abstracts seldom report measures of absolute effect. Journal editors should insist that authors report both relative and absolute effects for patient-important outcomes. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Systematic reviews experience major limitations in reporting absolute effects

Objectives: Expressing treatment effects in relative terms yields larger numbers than expressions in absolute terms, affecting the judgment of the clinicians and patients regarding the treatment options. It is uncertain how authors of systematic reviews (SRs) absolute effect estimates are reported in. We therefore undertook a systematic survey to identify and describe the reporting and methods for calculating absolute effect estimates in SRs. Study Design and Setting: Two reviewers independently screened title, abstract, and full text and extracted data from a sample of Cochrane and non-Cochrane SRs. We used regression analyses to examine the association between study characteristics and the reporting of absolute estimates for the most patient-important outcome. Results: We included 202 SRs (98 Cochrane and 104 non-Cochrane), most of which (92.1%) included standard meta-analyses including relative estimates of effect. Of the 202 SRs, 73 (36.1%) reported absolute effect estimates for the most patient-important outcome. SRs with statistically significant effects were more likely to report absolute estimates (odds ratio, 2.26; 95% confidence interval: 1.08, 4.74). The most commonly reported absolute estimates were: for each intervention, risk of adverse outcomes expressed as a percentage (41.1%); number needed to treat (26.0%); and risk for each intervention expressed as natural units or natural frequencies (24.7%). In 12.3% of the SRs that reported absolute effect estimates for both benefit and harm outcomes, harm outcomes were reported exclusively as absolute estimates. Exclusively reporting of beneficial outcomes as absolute estimates occurred in 6.8% of the SRs. Conclusions: Most SRs do not report absolute effects. Those that do often report them inadequately, thus requiring users of SRs to generate their own estimates of absolute effects. For any apparently effective or harmful intervention, SR authors should report both absolute and relative estimates to optimize the interpretation of their findings. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

How to design high quality acupuncture trials—a consensus informed by evidence

An international panel including patients, clinicians, researchers, acupuncture and surgery trialists, statisticians, and experts in clinical epidemiology and methodology have developed new guidance for randomised controlled trials in acupuncture. It addresses the most prevalent and critical concerns of current acupuncture trials and will help funding agencies, trial registers, and journal editors to evaluate the relevance, importance, and quality of submitted trial proposals and completed trial

Premature Discontinuation of Pediatric Randomized Controlled Trials : A Retrospective Cohort Study

Objectives To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs. Study design A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists. Results We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants). Conclusion Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.Peer reviewe