95 results on '"Clinical Trial Reporting"'
Search Results
2. Consistency of trial reporting between ClinicalTrials.gov and corresponding publications: one decade after FDAAA.
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Talebi, Ramtin, Redberg, Rita F., and Ross, Joseph S.
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CLINICAL trials monitoring , *CRIME & the press , *CLINICAL trial registries , *CLINICAL trials , *CROSS-sectional method - Abstract
The FDA Amendments Act (FDAAA) required that information for certain clinical trials, such as details about study design features and endpoints, as well as results, be publicly reported in ClinicalTrials.gov . We conducted a cross-sectional analysis of phase III trials with primary results published between January 1, 2016, and June 30, 2017, in high-impact journals and found 74% contained at least one discrepancy between results reported in ClinicalTrials.gov and the corresponding publication. Our findings underscore the necessity for monitoring of clinical trial information and result reporting between sources; a checklist may provide a systemized procedure for investigators and editors to monitor accurate reporting. [ABSTRACT FROM AUTHOR]
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- 2020
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3. Harmonized Outcome Measures for Use in Depression Patient Registries and Clinical Practice.
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Gliklich, Richard E., Leavy, Michelle B., Cosgrove, Lisa, Simon, Gregory E., Gaynes, Bradley N., Peterson, Lars E., Olin, Bryan, Cole, Collette, DePaulo Jr., J. Raymond, Wang, Philip, Crowe, Chris M., Cusin, Cristina, Nix, Mary, Berliner, Elise, Trivedi, Madhukar H., and DePaulo, J Raymond Jr
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MEDICAL registries , *MEDICAL quality control , *MENTAL depression , *PATIENT advocacy , *FERRANS & Powers Quality of Life Index , *ACQUISITION of data , *DISEASE incidence , *DISEASE management - Abstract
Major depressive disorder is a common mental health condition that affects an estimated 16.2 million adults and 3.1 million adolescents in the United States. Yet, a lack of uniformity remains in measurements and monitoring for depression both in clinical practice and in research settings. This project aimed to develop a minimum set of standardized outcome measures relevant to both patients and clinicians that can be collected in depression registries and clinical practice. Twenty-nine depression registries and related data collection efforts were identified and invited to submit outcome measures. Additional measures were identified through literature searches and reviews of quality measures. A multistakeholder panel representing clinicians; payers; government agencies; industry; and medical specialty, health care quality, and patient advocacy organizations categorized the 27 identified measures using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework. The panel identified 10 broadly relevant measures and harmonized definitions for these measures through in-person and virtual meetings. The harmonized measures represent a minimum set of outcomes that are relevant to clinicians and patients and appropriate for use in depression research and clinical practice. Routine and consistent collection of these measures in registries and other systems would support creation of a national research infrastructure to efficiently address new questions, improve patient management and outcomes, and facilitate care coordination. [ABSTRACT FROM AUTHOR]
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- 2020
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4. Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.
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Fink, Howard A., Linskens, Eric J., MacDonald, Roderick, Silverman, Pombie C., McCarten, J. Riley, Talley, Kristine M.C., Forte, Mary L., Desai, Priyanka J., Nelson, Victoria A., Miller, Margaret A., Hemmy, Laura S., Brasure, Michelle, Taylor, Brent C., Ng, Weiwen, Ouellette, Jeannine M., Sheets, Kerry M., Wilt, Timothy J., and Butler, Mary
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RESEARCH , *ALZHEIMER'S disease , *META-analysis , *RESEARCH methodology , *SYSTEMATIC reviews , *COGNITION , *EVALUATION research , *MEDICAL cooperation , *DIETARY supplements , *TREATMENT effectiveness , *COMPARATIVE studies , *DRUGS , *PHARMACODYNAMICS - Abstract
Background: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain.Purpose: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment.Data Sources: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.Study Selection: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD).Data Extraction: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy.Data Synthesis: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes.Limitation: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials.Conclusion: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes.Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897). [ABSTRACT FROM AUTHOR]- Published
- 2020
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5. Biomedical Research in Times of Emergency: Lessons From History.
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Doroshow, Deborah, Podolsky, Scott, and Barr, Justin
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MEDICAL research , *COVID-19 , *MUSTARD gas , *YELLOW fever , *WORLD War II , *HISTORY of epidemics , *HISTORY of medical research , *CORONAVIRUS disease treatment , *VIRAL pneumonia , *HISTORY , *MEDICAL emergencies - Abstract
Coronavirus disease 2019 (COVID-19) has sickened millions, killed hundreds of thousands, and utterly disrupted the daily lives of billions of people around the world. In an effort to ameliorate this devastation, the biomedical research complex has allocated billions of dollars and scientists have initiated hundreds of clinical trials in an expedited effort to understand, prevent, and treat this disease. National emergencies can stimulate significant investment of financial, physical, and intellectual resources that catalyze impressive scientific accomplishments, as evident with the Manhattan Project, penicillin, and the polio vaccines in the 20th century. However, pressurized research has also led to false promises, disastrous consequences, and breaches in ethics. Antiserum in the 1918 flu epidemic, contaminated yellow fever vaccines in World War II, and unethical human experimentation with mustard gas offer just a few cautionary exemplars. It is critical to continue biomedical research efforts to address this pandemic, and it is appropriate that they receive priority in both attention and funding. But history also demonstrates the importance of treating early results-such as those associated with hydroxychloroquine-with caution as we only begin to understand the biology, epidemiology, and potential target points of COVID-19. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Delays in completion and results reporting of clinical trials under the Paediatric Regulation in the European Union: A cohort study.
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Hwang, Thomas J., Tomasi, Paolo A., and Bourgeois, Florence T.
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CLINICAL trials , *PEDIATRICS , *COMMUNICATION in pediatrics , *MEDICAL care , *DRUG laws , *DRUG approval laws , *COMPARATIVE studies , *EXPERIMENTAL design , *INDUSTRIES , *MARKETING , *RESEARCH methodology , *MEDICAL cooperation , *PUBLISHING , *RESEARCH , *EVALUATION research , *STANDARDS - Abstract
Background: Few medicines have been approved for children, leading to rates of off-label prescribing reported to be as high as 90%. In 2007, the European Union adopted the Paediatric Regulation, which mandates that pharmaceutical companies conduct paediatric studies for all new medicines, unless granted a waiver. We aimed to evaluate the availability of paediatric trial results from studies required under the Paediatric Regulation for new medicines authorised in the EU.Methods and Findings: The European Medicines Agency (EMA) public database of paediatric investigation plans was searched for new medicines centrally authorised in the EU between 1 January 2010 and 31 December 2014 with at least 1 required paediatric study. For our study cohort of paediatric clinical trials required for these medicines, we used internal EMA databases and publicly available trial registries to determine changes to the planned completion date or study design, rates of trial completion, time to trial completion, and results reporting (peer-reviewed publication or posting on trial registry). Cox proportional hazards regression models were constructed to examine factors associated with study completion. A total of 326 paediatric clinical trials were required for 122 novel medicines authorised by the EMA between 2010 and 2014. In all, 76% (247/326) of paediatric studies were not planned to be completed until after the initial marketing authorisation. The planned completion dates for 50% (162/326) were further postponed by a median of 2.2 years. Overall, 38% (124/326) of paediatric studies were completed as of 30 November 2017. The rate of trial completion for paediatric studies planned to be completed after initial marketing authorisation was 23% (56/247), versus 86% (68/79) for trials planned to be completed before authorisation (adjusted hazard ratio 0.11; 95% CI 0.06-0.19). Among completed studies, the results were reported in a public registry or in the peer-reviewed literature for 85% (105/124) at a median of 1.1 years after study completion, and 60% (74/124) were published in a peer-reviewed journal. Limitations of this study include the potential lack of generalisability to medicines not authorised by the EMA and the possibility for more of these trials to be completed or published in the future.Conclusions: The completion of many paediatric studies required under the Paediatric Regulation has been delayed. Paediatric studies planned to be completed after marketing authorisation were associated with a lower likelihood of eventual completion, highlighting the need to examine the implementation of current policies in ensuring timely availability of important paediatric information. [ABSTRACT FROM AUTHOR]- Published
- 2018
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7. Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov.
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Cahan, Amos and Anand, Vibha
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RANDOMIZED controlled trials , *RANDOMIZATION (Statistics) , *MEDICAL research , *DATA analysis ,MENTAL health & society - Abstract
Background: ClinicalTrials.gov is valuable for aggregate-level analysis of trials. The recently published final rule aims to improve reporting of trial results. We aimed to assess variability in ClinicalTirals.gov records reporting participants’ baseline measures. Methods and findings: The September 2015 edition of the database for Aggregate Analysis of ClinicalTrials.gov (AACT), was used in this study. To date, AACT contains 186,941 trials of which 16,660 trials reporting baseline (participant) measures were analyzed. We also analyzed a subset of 13,818 Highly Likely Applicable Clinical Trials (HLACT), for which reporting of results is likely mandatory and compared a random sample of 30 trial records to their journal articles. We report counts for each mandatory baseline measure and variability reporting in their formats. The AACT dataset contains 8,161 baseline measures with 1206 unique measurement units. However, of these 6,940 (85%) variables appear only once in the dataset. Age and Gender are reported using many different formats (178 and 49 respectively). “Age” as the variable name is reported in 60 different formats. HLACT subset reports measures using 3,931 variables. The most frequent Age format (i.e. mean (years) ± sd) is found in only 45% of trials. Overall only 4 baseline measures (Region of Enrollment, Age, Number of Participants, and Gender) are reported by > 10% of trials. Discrepancies are found in both the types and formats of ClinicalTrials.gov records and their corresponding journal articles. On average, journal articles include twice the number of baseline measures (13.6±7.1 (sd) vs. 6.6±7.6) when compared to the ClinicalTrials.gov records that report any results. Conclusions: We found marked variability in baseline measures reporting. This is not addressed by the final rule. To support secondary use of ClinicalTrials.gov, a uniform format for baseline measures reporting is warranted. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Reporting bias in clinical trials: Progress toward transparency and next steps
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Mayookha, Mitra-Majumdar and Aaron S, Kesselheim
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Pharmacology ,Clinical Trials as Topic ,Drug Research and Development ,Medical Journals ,Statistics ,Drugs ,Antidepressants ,Research Assessment ,Research and Analysis Methods ,Bias ,Research Design ,Perspective ,Physical Sciences ,Medicine and Health Sciences ,General Medical Journals ,Humans ,Clinical Trials ,Clinical Trial Reporting ,Clinical Medicine ,Medical Humanities ,Phase II clinical investigation ,Mathematics ,Statistical Data - Abstract
Mayookha Mitra-Majumdar and Aaron Kesselheim reflect on steps taken to combat reporting bias in clinical trials over the last two decades.
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- 2022
9. ‘Spin’ in published biomedical literature: A methodological systematic review.
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Chiu, Kellia, Grundy, Quinn, and Bero, Lisa
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SPIN-spin interactions , *CLINICAL trials , *SCIENTIFIC observation , *META-analysis , *PROCTOLOGY - Abstract
In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. This systematic review aims to explore the nature and prevalence of spin in the biomedical literature. We searched MEDLINE, PreMEDLINE, Embase, Scopus, and hand searched reference lists for all reports that included the measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of reports and their included studies and all spin-related outcomes. Results were grouped inductively into themes by spin-related outcome and are presented as a narrative synthesis. We used meta-analyses to analyse the association of spin with industry sponsorship of research. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research. [ABSTRACT FROM AUTHOR]
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- 2017
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10. Effects of research complexity and competition on the incidence and growth of coauthorship in biomedicine.
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Brunson, Jason Cory, Wang, Xiaoyan, and Laubenbacher, Reinhard C.
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AUTHORSHIP collaboration , *REGRESSION analysis , *MULTILEVEL models , *CLINICAL medicine , *CLINICAL trials - Abstract
Background: Investigations into the factors behind coauthorship growth in biomedical research have mostly focused on specific disciplines or journals, and have rarely controlled for factors in combination or considered changes in their effects over time. Observers often attribute the growth to the increasing complexity or competition (or both) of research practices, but few attempts have been made to parse the contributions of these two likely causes. Objectives: We aimed to assess the effects of complexity and competition on the incidence and growth of coauthorship, using a sample of the biomedical literature spanning multiple journals and disciplines. Methods: Article-level bibliographic data from PubMed were combined with publicly available bibliometric data from Web of Science and SCImago over the years 1999–2007. We selected four predictors of coauthorship were selected, two (study type, topical scope of the study) associated with complexity and two (financial support for the project, popularity of the publishing journal) associated with competition. A negative binomial regression model was used to estimate the effects of each predictor on coauthorship incidence and growth. A second, mixed-effect model included the journal as a random effect. Results: Coauthorship increased at about one author per article per decade. Clinical trials, supported research, and research of broader scope produced articles with more authors, while review articles credited fewer; and more popular journals published higher-authorship articles. Incidence and growth rates varied widely across journals and were themselves uncorrelated. Most effects remained statistically discernible after controlling for the publishing journal. The effects of complexity-associated factors held constant or diminished over time, while competition-related effects strengthened. These trends were similar in size but not discernible from subject-specific subdata. Conclusions: Coauthorship incidence rates are multifactorial and vary with factors associated with both complexity and competition. Coauthorship growth is likewise multifactorial and increasingly associated with research competition. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Reporting of cross-over clinical trials of analgesic treatments for chronic pain: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review and recommendations.
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Gewandter, Jennifer S., McDermott, Michael P., McKeown, Andrew, Kim Hoang, Iwan, Katarzyna, Kralovic, Sarah, Rothstein, Daniel, Gilron, Ian, Katz, Nathaniel P., Raja, Srinivasa N., Senn, Stephen, Smith, Shannon M., Turk, Dennis C., Dworkin, Robert H., and Hoang, Kim
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CLINICAL trials , *ANALGESICS , *META-analysis , *INFORMATION theory , *CROSSOVER trials , *ANIMAL experimentation , *CHRONIC pain , *DATABASES , *RESEARCH funding , *TRANSLATIONS , *SYSTEMATIC reviews - Abstract
Cross-over trials are typically more efficient than parallel group trials in that the sample size required to yield a desired power is substantially smaller. It is important, however, to consider some issues specific to cross-over trials when designing and reporting them, and when evaluating the published results of such trials. This systematic review evaluated the quality of reporting and its evolution over time in articles of cross-over clinical trials of pharmacologic treatments for chronic pain published between 1993 and 2013. Seventy-six (61%) articles reported a within-subject primary analysis, or if no primary analysis was identified, reported at least 1 within-subject analysis, which is required to achieve the gain in power associated with the cross-over design. For 39 (31%) articles, it was unclear whether analyses conducted were within-subject or between-group. Only 36 (29%) articles reported a method to accommodate missing data (eg, last observation carried forward, n = 29), and of those, just 14 included subjects in the analysis who provided data from only 1 period. Of the articles that identified a within-subject primary analysis, 21 (51%) provided sufficient information for the results to be included in a meta-analysis (ie, estimates of the within-subject treatment effect and variability). These results and others presented in this article demonstrate deficiencies in reporting of cross-over trials for analgesic treatments. Clearer reporting in future trials could improve readers' ability to critically evaluate the results, use these data in meta-analyses, and plan future trials. Recommendations for proper reporting of cross-over trials that apply to any condition are provided. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring
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BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, imp, SCOPUS: re.j, info:eu-repo/semantics/published
- Published
- 2021
13. Outcome Reporting Bias in Government-Sponsored Policy Evaluations: A Qualitative Content Analysis of 13 Studies.
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Vaganay, Arnaud
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POLICY sciences , *ANALYTICAL chemistry , *PHARMACOLOGY , *RESEARCH & development , *CLINICAL trials - Abstract
The reporting of evaluation outcomes can be a point of contention between evaluators and policy-makers when a given reform fails to fulfil its promises. Whereas evaluators are required to report outcomes in full, policy-makers have a vested interest in framing these outcomes in a positive light–especially when they previously expressed a commitment to the reform. The current evidence base is limited to a survey of policy evaluators, a study on reporting bias in education research and several studies investigating the influence of industry sponsorship on the reporting of clinical trials. The objective of this study was twofold. Firstly, it aimed to assess the risk of outcome reporting bias (ORB or ‘spin’) in pilot evaluation reports, using seven indicators developed by clinicians. Secondly, it sought to examine how the government’s commitment to a given reform may affect the level of ORB found in the corresponding evaluation report. To answer these questions, 13 evaluation reports were content-analysed, all of which found a non-significant effect of the intervention on its stated primary outcome. These reports were systematically selected from a dataset of 233 pilot and experimental evaluations spanning three policy areas and 13 years of government-commissioned research in the UK. The results show that the risk of ORB is real. Indeed, all studies reviewed here resorted to at least one of the presentational strategies associated with a risk of spin. This study also found a small, negative association between the seniority of the reform’s champion and the risk of ORB in the evaluation of that reform. The publication of protocols and the use of reporting guidelines are recommended. [ABSTRACT FROM AUTHOR]
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- 2016
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14. How Much Participant Outcome Data Is Missing from Sight: Findings from a Cohort of Trials Submitted to a German Research Ethics Committee.
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Kirkham, Jamie J., Dwan, Kerry M., Blümle, Anette, von Elm, Erik, and Williamson, Paula R.
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RANDOMIZED controlled trials , *RESEARCH ethics , *MISSING data (Statistics) , *PUBLICATION bias , *MEDICAL publishing - Abstract
Background: Study publication bias and outcome reporting bias have been recognised as two threats to the validity of systematic reviews. The purpose of this research was to estimate the proportion of missing participant outcome data from randomised controlled trials (RCTs) due to lack of publication of whole studies and due to outcome data missing within study publications. Methods and Findings: Data were extracted from protocols of clinical research projects submitted to the research ethics committee of the University of Freiburg (Germany) between 2000 and 2002 and associated fully published articles. The total amount of published and unpublished outcome data from all trial participants was calculated for each trial and the overall proportion of missing data from both unpublished and published trials computed. Full and partially reported outcome data was also taken into consideration. The impact of funding source on missingness was also considered at the trial level. From 308 parallel group trials in the study cohort, 167 were published and 141 were unpublished. Overall, 260,563 participants contributed to a total of 2,618,116 participant outcome data across all trials. About half (47%) of the participant outcome data from the 308 trials was reported in full but at least 81% were partially reported. Of the 19% of participant data that were missing, 4% was attributable to missing data from published trials and 15% from unpublished trials. Commercially funded trials had a higher probability of publication (relative risk 1.20, 95% confidence interval 0.86, 1.67; p = 0.27) but were less likely to fully report all outcomes than non-commercially funded trials (relative risk 0.64, 95% confidence interval 0.30, 1.38; p = 0.26). Conclusions: Missing participant outcome data from both published and unpublished trials is frequent. Clinical trial registration including outcome information not only identifies that clinical trials exist but the systematic examination and monitoring of trial information within a registry can help detect selective reporting of entire studies and of outcome data within studies and possibly prevent it. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Sharing Individual Participant Data (IPD) within the Context of the Trial Reporting System (TRS).
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Zarin, Deborah A. and Tse, Tony
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INFORMATION sharing , *NEWSPAPER court reporting , *CLINICAL trial registries , *REPORTERS & reporting , *INFORMATION resources management , *DATABASES , *CLINICAL trials , *COMMUNICATION , *INDUSTRIES , *RESEARCH funding , *STANDARDS - Abstract
Deborah Zarin and Tony Tse of ClinicalTrials.Gov consider how sharing individual participant data can and cannot help improve the reporting of clinical trials. [ABSTRACT FROM AUTHOR]
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- 2016
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16. The Immunologic Effects of Mesalamine in Treated HIV-Infected Individuals with Incomplete CD4+ T Cell Recovery: A Randomized Crossover Trial.
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Somsouk, Ma, Dunham, Richard M., Cohen, Michelle, Albright, Rebecca, Abdel-Mohsen, Mohamed, Liegler, Teri, Lifson, Jeffrey, Piatak, Michael, Gorelick, Robert, Huang, Yong, Wu, Yuaner, Hsue, Priscilla Y., Martin, Jeffrey N., Deeks, Steven G., McCune, Joseph M., and Hunt, Peter W.
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MESALAMINE , *HIV-positive persons , *RANDOMIZED controlled trials , *CD4 antigen , *ULCERATIVE colitis , *T cells - Abstract
The anti-inflammatory agent, mesalamine (5-aminosalicylic acid) has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT), has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm3 and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART) to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P = 0.38 and P = 0.63, respectively), or in the CD4+ T cell count at week 12 (P = 0.83). The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P = 0.86, P = 0.84, respectively). During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]
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- 2014
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17. Multi-Reader Multi-Case Studies Using the Area under the Receiver Operator Characteristic Curve as a Measure of Diagnostic Accuracy: Systematic Review with a Focus on Quality of Data Reporting.
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Dendumrongsup, Thaworn, Plumb, Andrew A., Halligan, Steve, Fanshawe, Thomas R., Altman, Douglas G., and Mallett, Susan
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RECEIVER operating characteristic curves , *MEDICAL radiology , *DIAGNOSTIC imaging , *MEDICAL informatics , *SYSTEMATIC reviews , *IMAGE analysis - Abstract
Introduction: We examined the design, analysis and reporting in multi-reader multi-case (MRMC) research studies using the area under the receiver-operating curve (ROC AUC) as a measure of diagnostic performance. Methods: We performed a systematic literature review from 2005 to 2013 inclusive to identify a minimum 50 studies. Articles of diagnostic test accuracy in humans were identified via their citation of key methodological articles dealing with MRMC ROC AUC. Two researchers in consensus then extracted information from primary articles relating to study characteristics and design, methods for reporting study outcomes, model fitting, model assumptions, presentation of results, and interpretation of findings. Results were summarized and presented with a descriptive analysis. Results: Sixty-four full papers were retrieved from 475 identified citations and ultimately 49 articles describing 51 studies were reviewed and extracted. Radiological imaging was the index test in all. Most studies focused on lesion detection vs. characterization and used less than 10 readers. Only 6 (12%) studies trained readers in advance to use the confidence scale used to build the ROC curve. Overall, description of confidence scores, the ROC curve and its analysis was often incomplete. For example, 21 (41%) studies presented no ROC curve and only 3 (6%) described the distribution of confidence scores. Of 30 studies presenting curves, only 4 (13%) presented the data points underlying the curve, thereby allowing assessment of extrapolation. The mean change in AUC was 0.05 (−0.05 to 0.28). Non-significant change in AUC was attributed to underpowering rather than the diagnostic test failing to improve diagnostic accuracy. Conclusions: Data reporting in MRMC studies using ROC AUC as an outcome measure is frequently incomplete, hampering understanding of methods and the reliability of results and study conclusions. Authors using this analysis should be encouraged to provide a full description of their methods and results. [ABSTRACT FROM AUTHOR]
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- 2014
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18. LDL-Migration Index (LDL-MI), an Indicator of Small Dense Low-Density Lipoprotein (sdLDL), Is Higher in Non-Alcoholic Steatohepatitis than in Non-Alcoholic Fatty Liver: A Multicenter Cross-Sectional Study.
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Imajo, Kento, Hyogo, Hideyuki, Yoneda, Masato, Honda, Yasushi, Kessoku, Takaomi, Tomeno, Wataru, Ogawa, Yuji, Taguri, Masataka, Mawatari, Hironori, Nozaki, Yuichi, Fujita, Koji, Kirikoshi, Hiroyuki, Saito, Satoru, Sumida, Yoshio, Ono, Masafumi, Wada, Koichiro, Nakajima, Atsushi, and Eguchi, Yuichiro
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FATTY liver , *LOW density lipoproteins , *CARDIOVASCULAR diseases , *CROSS-sectional method , *ATHEROSCLEROTIC plaque , *CLINICAL trials , *DISEASE risk factors - Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risks of atherosclerotic diseases, including cardiovascular disease. However, the difference in risk between patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) has not yet been determined. Accumulating evidence has shown that high amounts of small dense low-density lipoprotein (sdLDL) are closely associated with atherosclerotic diseases. This study investigated differences in risk factors for atherosclerotic diseases, especially LDL-migration index (LDL-MI), an indicator of sdLDL, between patients with NAFL and NASH. Methods: LDL-MI was analyzed in a primary cohort of 156 patients with NAFLD, including 53 with NAFL and 103 with NASH, and a validation cohort of 69 patients with NAFLD, including 25 with NAFL and 44 with NASH. Results: In the primary cohort, NASH was associated with elevated LDL-MI (p = 0.039). Multiple regression analysis showed that NASH and the non-use of lipid lowering medications were independently correlated with higher LDL-MI in all patients with NAFLD. Among patients not on lipid lowering medications, those with NASH had significantly higher LDL-MI than those with NAFL (p = 0.001). These findings were confirmed in a validation cohort, in that LDL-MI was significantly higher in patients with NASH than with NAFL (p = 0.043). Conclusion: This study is the first to show that LDL-MI, an indicator of sdLDL, was higher in patients with NASH than with NAFL, suggesting that the risk of atherosclerotic diseases may be higher in NASH than NAFL. Patients with NASH should be followed closely, especially for the progression of liver pathology and atherosclerotic diseases. Trial Registration: [ABSTRACT FROM AUTHOR]
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- 2014
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19. Using ROC Curves to Choose Minimally Important Change Thresholds when Sensitivity and Specificity Are Valued Equally: The Forgotten Lesson of Pythagoras. Theoretical Considerations and an Example Application of Change in Health Status.
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Froud, Robert and Abel, Gary
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RECEIVER operating characteristic curves , *PYTHAGOREAN theorem , *HEALTH outcome assessment , *CHRONIC diseases , *PSYCHOMETRICS , *CLINICAL trials - Abstract
Background: Receiver Operator Characteristic (ROC) curves are being used to identify Minimally Important Change (MIC) thresholds on scales that measure a change in health status. In quasi-continuous patient reported outcome measures, such as those that measure changes in chronic diseases with variable clinical trajectories, sensitivity and specificity are often valued equally. Notwithstanding methodologists agreeing that these should be valued equally, different approaches have been taken to estimating MIC thresholds using ROC curves. Aims and objectives: We aimed to compare the different approaches used with a new approach, exploring the extent to which the methods choose different thresholds, and considering the effect of differences on conclusions in responder analyses. Methods: Using graphical methods, hypothetical data, and data from a large randomised controlled trial of manual therapy for low back pain, we compared two existing approaches with a new approach that is based on the addition of the sums of squares of 1-sensitivity and 1-specificity. Results: There can be divergence in the thresholds chosen by different estimators. The cut-point selected by different estimators is dependent on the relationship between the cut-points in ROC space and the different contours described by the estimators. In particular, asymmetry and the number of possible cut-points affects threshold selection. Conclusion: Choice of MIC estimator is important. Different methods for choosing cut-points can lead to materially different MIC thresholds and thus affect results of responder analyses and trial conclusions. An estimator based on the smallest sum of squares of 1-sensitivity and 1-specificity is preferable when sensitivity and specificity are valued equally. Unlike other methods currently in use, the cut-point chosen by the sum of squares method always and efficiently chooses the cut-point closest to the top-left corner of ROC space, regardless of the shape of the ROC curve. [ABSTRACT FROM AUTHOR]
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- 2014
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20. Elevated Pulse Pressure is Associated with Hemolysis, Proteinuria and Chronic Kidney Disease in Sickle Cell Disease.
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Novelli, Enrico M., Hildesheim, Mariana, Rosano, Caterina, Vanderpool, Rebecca, Simon, Marc, Kato, Gregory J., and Gladwin, Mark T.
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SICKLE cell anemia , *HEMOLYSIS & hemolysins , *PROTEINURIA , *CHRONIC kidney failure , *DISEASE prevalence , *HYPERTENSION - Abstract
A seeming paradox of sickle cell disease is that patients do not suffer from a high prevalence of systemic hypertension in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, some patients do develop systolic hypertension and increased pulse pressure, an increasingly recognized major cardiovascular risk factor in other populations. Hence, we hypothesized that pulse pressure, unlike other blood pressure parameters, is independently associated with markers of hemolytic anemia and cardiovascular risk in sickle cell disease. We analyzed the correlates of pulse pressure in patients (n = 661) enrolled in a multicenter international sickle cell trial. Markers of hemolysis were analyzed as independent variables and as a previously validated hemolytic index that includes multiple variables. We found that pulse pressure, not systolic, diastolic or mean arterial pressure, independently correlated with high reticulocyte count (beta = 2.37, p = 0.02) and high hemolytic index (beta = 1.53, p = 0.002) in patients with homozygous sickle cell disease in two multiple linear regression models which include the markers of hemolysis as independent variables or the hemolytic index, respectively. Pulse pressure was also independently associated with elevated serum creatinine (beta = 3.21, p = 0.02), and with proteinuria (beta = 2.52, p = 0.04). These results from the largest sickle cell disease cohort to date since the Cooperative Study of Sickle Cell Disease show that pulse pressure is independently associated with hemolysis, proteinuria and chronic kidney disease. We propose that high pulse pressure may be a risk factor for clinical complications of vascular dysfunction in sickle cell disease. Longitudinal and mechanistic studies should be conducted to confirm these hypotheses. [ABSTRACT FROM AUTHOR]
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- 2014
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21. The Definition of Placebo in the Informed Consent Forms of Clinical Trials.
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Hernández, Astrid, Baños, Josep-E., Llop, Cristina, and Farré, Magí
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PLACEBOS , *INFORMED consent (Medical law) , *CLINICAL trials , *PATIENTS , *MEDICAL ethics - Abstract
Aim: Lack of knowledge concerning the nature of placebo and why it is necessary may influence the participation of patients in clinical trials. The objective of the present study is to review how placebo is described in written information for participants in clinical trials to be evaluated by a Human Research Ethics Committee. Methods: All research protocols submitted for evaluation in a Spanish hospital during 2007–2013 were reviewed. The main characteristics of the studies using a placebo were collected. Three authors read each of them to determine how the term “placebo” was explained and if there was any comment on its efficacy and safety. Results: Two thousand seven-hundred and forty research protocols were evaluated, of which three hundred and fifty-nine used a placebo. Pharmaceutical companies sponsored most placebo-controlled clinical trials (91.9%), and phase III studies were the commonest (59.9%). Oncology (15.0%), cardiology (14.2%), and neurology (13.1%) made the greatest contributions. A review of the informed consent forms showed that placebo was described in a similar manner in most studies: the explanation was limited to between four and eight words. Very few gave information about the risks of its use or adverse reactions from its administration. None of the studies provided details about the placebo effect. And 23 lacked any information about placebo at all. Conclusions: Explanations about placebo in informed consent forms is often scarce, and information about the placebo effect and associated risks are absent. This situation may influence a full understanding of placebo by participants in clinical trials and might reduce their informed decision to participate. [ABSTRACT FROM AUTHOR]
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- 2014
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22. Methodological Reporting of Randomized Trials in Five Leading Chinese Nursing Journals.
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Shi, Chunhu, Tian, Jinhui, Ren, Dan, Wei, Hongli, Zhang, Lihuan, Wang, Quan, and Yang, Kehu
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NURSING care facilities , *RANDOMIZED controlled trials , *HEALTH outcome assessment , *CLINICAL medicine , *REGRESSION analysis - Abstract
Background: Randomized controlled trials (RCTs) are not always well reported, especially in terms of their methodological descriptions. This study aimed to investigate the adherence of methodological reporting complying with CONSORT and explore associated trial level variables in the Chinese nursing care field. Methods: In June 2012, we identified RCTs published in five leading Chinese nursing journals and included trials with details of randomized methods. The quality of methodological reporting was measured through the methods section of the CONSORT checklist and the overall CONSORT methodological items score was calculated and expressed as a percentage. Meanwhile, we hypothesized that some general and methodological characteristics were associated with reporting quality and conducted a regression with these data to explore the correlation. The descriptive and regression statistics were calculated via SPSS 13.0. Results: In total, 680 RCTs were included. The overall CONSORT methodological items score was 6.34±0.97 (Mean ± SD). No RCT reported descriptions and changes in “trial design,” changes in “outcomes” and “implementation,” or descriptions of the similarity of interventions for “blinding.” Poor reporting was found in detailing the “settings of participants” (13.1%), “type of randomization sequence generation” (1.8%), calculation methods of “sample size” (0.4%), explanation of any interim analyses and stopping guidelines for “sample size” (0.3%), “allocation concealment mechanism” (0.3%), additional analyses in “statistical methods” (2.1%), and targeted subjects and methods of “blinding” (5.9%). More than 50% of trials described randomization sequence generation, the eligibility criteria of “participants,” “interventions,” and definitions of the “outcomes” and “statistical methods.” The regression analysis found that publication year and ITT analysis were weakly associated with CONSORT score. Conclusions: The completeness of methodological reporting of RCTs in the Chinese nursing care field is poor, especially with regard to the reporting of trial design, changes in outcomes, sample size calculation, allocation concealment, blinding, and statistical methods. [ABSTRACT FROM AUTHOR]
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- 2014
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23. Prospective Randomized Trial of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid for Prevention of Radiation-Induced Liver Toxicity.
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Seidensticker, Max, Seidensticker, Ricarda, Damm, Robert, Mohnike, Konrad, Pech, Maciej, Sangro, Bruno, Hass, Peter, Wust, Peter, Kropf, Siegfried, Gademann, Günther, and Ricke, Jens
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ENOXAPARIN , *PENTOXIFYLLINE , *URSODEOXYCHOLIC acid , *HEPATOTOXICOLOGY , *LIVER cancer , *CANCER radiotherapy , *RANDOMIZED controlled trials - Abstract
Background/Aim: Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI). Methods and Materials: Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data. Results: Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up. Conclusions: The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1–8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI. Trial Registration: EU clinical trials register ClinicalTrials.gov [ABSTRACT FROM AUTHOR]
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- 2014
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24. A Pilot RCT of Psychodynamic Group Art Therapy for Patients in Acute Psychotic Episodes: Feasibility, Impact on Symptoms and Mentalising Capacity.
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Montag, Christiane, Haase, Laura, Seidel, Dorothea, Bayerl, Martin, Gallinat, Jürgen, Herrmann, Uwe, and Dannecker, Karin
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PSYCHOSES , *PSYCHIATRIC treatment , *PSYCHODYNAMIC psychotherapy , *ART therapy , *SCHIZOPHRENIA treatment , *MENTAL depression , *EMOTIONS - Abstract
: This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]
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- 2014
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25. A Comparative Study on the Efficacy of Solifenacin Succinate in Patients with Urinary Frequency with or without Urgency.
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Han, Ji-Yeon, Lee, Kyu-Sung, Park, Won Hee, Park, Choal Hee, Lee, Jeong Gu, Lee, Jeong Zoo, Kim, Duk Yoon, Na, Yong Gil, Kwon, Dong Deuk, and Choo, Myung-Soo
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URINATION disorders , *MUSCARINIC antagonists , *DRUG efficacy , *OVERACTIVE bladder , *COMPARATIVE studies , *CLINICAL trials , *THERAPEUTICS - Abstract
Objectives: Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency. Materials and Methods: This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire. Results: Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115; with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of −2.49±0.35 (mean ± standard error) and −2.63±0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was −1.14, which is smaller than the −0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well. Conclusions: It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]
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- 2014
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26. Cytoplasmic and/or Nuclear Expression of β-Catenin Correlate with Poor Prognosis and Unfavorable Clinicopathological Factors in Hepatocellular Carcinoma: A Meta-Analysis.
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Chen, Jiang, Liu, Jinghua, Jin, Renan, Shen, Jiliang, Liang, Yuelong, Ma, Rui, Lin, Hui, Liang, Xiao, Yu, Hong, and Cai, Xiujun
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GENE expression , *CELL membranes , *CATENINS , *LIVER cancer , *CONFIDENCE intervals , *META-analysis - Abstract
Background: The β-catenin is an important effector in WNT/β-catenin signaling pathway, which exerts a crucial role in the development and progression of hepatocellular carcinoma (HCC). Some researchers have suggested that the overexpression of β-catenin in cytoplasm and/or nucleus was closely correlated to metastasis, poor differentiation and malignant phenotype of HCC while some other researchers hold opposite point. So far, no consensus was obtained on the prognostic and clinicopathological significance of cytoplasmic/nuclear β-catenin overexpression for HCCs. Methods: Systematic strategies were applied to search eligible studies in all available databases. Subgroup analyses, sensitivity analyses and multivariate analysis were performed. In this meta-analysis, we utilized either fixed- or random-effects model to calculate the pooled odds ratios (OR) and its 95% confidence intervals (CI). Results: A total of 22 studies containing 2334 cases were enrolled in this meta-analysis. Pooled data suggested that accumulation of β-catenin in cytoplasm and/or nucleus significantly correlated with poor 1-, 3- and 5-year OS and RFS. Moreover, nuclear accumulation combined with cytoplasmic accumulation of β-catenin tended to be associated with dismal metastasis and vascular invasion while cytoplasmic or nuclear expression alone showed no significant effect. Besides, no significant association was observed between cytoplasmic and/or nuclear β-catenin expression and poor differentiation grade, advanced TNM stage, liver cirrhosis, tumor size, tumor encapsulation, AFP and etiologies. Additional subgroup analysis by origin suggested that the prognostic value and clinicopathological significance of cytoplasmic and/or nuclear β-catenin expression was more validated in Asian population. Multivariate analyses of factors showed that cytoplasmic and/or nuclear β-catenin expression, as well as TNM stage, metastasis and tumor size, was an independent risk factors for OS and RFS. Conclusions: Cytoplasmic and/or nuclear accumulation of β-catenin, as an independent prognostic factor, significantly associated with poor prognosis and deeper invasion of HCC, and could serve as a valuable prognostic predictor for HCC. [ABSTRACT FROM AUTHOR]
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- 2014
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27. A Machine Learning Approach to Identify Clinical Trials Involving Nanodrugs and Nanodevices from ClinicalTrials.gov.
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de la Iglesia, Diana, García-Remesal, Miguel, Anguita, Alberto, Muñoz-Mármol, Miguel, Kulikowski, Casimir, and Maojo, Víctor
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CLINICAL trials , *NANOTECHNOLOGY , *MACHINE learning , *BIOLOGICAL products , *ARTIFICIAL intelligence , *NANOSTRUCTURED materials - Abstract
Background: Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs—even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. Methods: We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. Results and Conclusions: The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is essential to discover any precedents for nanotoxicity events or advantages for targeted drug therapy. [ABSTRACT FROM AUTHOR]
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- 2014
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28. A Capsaicin (8%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial.
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Bischoff, Joakim M., Ringsted, Thomas K., Petersen, Marian, Sommer, Claudia, Üçeyler, Nurcan, and Werner, Mads U.
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CAPSAICIN , *POSTOPERATIVE pain treatment , *RANDOMIZED controlled trials , *EVIDENCE-based medicine , *PLACEBOS , *PAIN management - Abstract
Background: Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods: Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0–10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results: The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95% CI]: 5.0 [0.09 to 9.9]; P = 0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [−0.1 to 3.9] and 0.6 [−1.2 to 2.5] fibers/mm, respectively (P = 0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions: The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application. Trial Registration: Clinicaltrialsregister.eu ClinicalTrials.gov [ABSTRACT FROM AUTHOR]
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- 2014
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29. Role of Editorial and Peer Review Processes in Publication Bias: Analysis of Drug Trials Submitted to Eight Medical Journals.
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van Lent, Marlies, Overbeke, John, and Out, Henk Jan
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CLINICAL drug trials , *PROFESSIONAL peer review , *MEDICAL periodicals , *CLINICAL medicine , *RANDOMIZED controlled trials - Abstract
Background: Publication bias is generally ascribed to authors and sponsors failing to submit studies with negative results, but may also occur after submission. We evaluated whether submitted manuscripts on randomized controlled trials (RCTs) with drugs are more likely to be accepted if they report positive results. Methods: Manuscripts submitted from January 2010 through April 2012 to one general medical journal (BMJ) and seven specialty journals (Annals of the Rheumatic Diseases, British Journal of Ophthalmology, Gut, Heart, Thorax, Diabetologia, and Journal of Hepatology) were included, if at least one study arm assessed the efficacy or safety of a drug and a statistical test was used to evaluate treatment effects. Publication status was retrospectively retrieved from submission systems or provided by journals. Sponsorship and trial results were extracted from manuscripts and classified according to predefined criteria. Main outcome measure was acceptance for publication. Results: Of 15,972 manuscripts submitted, 472 (3.0%) were drug RCTs, of which 98 (20.8%) were published. Among submitted drug RCTs, 287 (60.8%) had positive and 185 (39.2%) negative results. Of these, 60 (20.9%) and 38 (20.5%), respectively, were published. Manuscripts on non-industry trials (n = 213) reported positive results in 138 (64.8%) manuscripts, compared to 71 (47.7%) on industry-supported trials (n = 149), and 78 (70.9%) on industry-sponsored trials (n = 110). Twenty-seven (12.7%) non-industry trials were published, compared to 27 (18.1%) industry-supported and 44 (40.0%) industry-sponsored trials. After adjustment for other trial characteristics, manuscripts reporting positive results were not more likely to be published (OR, 1.00; 95% CI, 0.61 to 1.66). Submission to specialty journals, sample size, multicentre status, journal impact factor, and corresponding authors from Europe or US were significantly associated with publication. Conclusions: For the selected journals, there was no tendency to preferably publish manuscripts on drug RCTs that reported positive results, suggesting that publication bias may occur mainly prior to submission. [ABSTRACT FROM AUTHOR]
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- 2014
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30. Intervention Strategies for Improving Patient Adherence to Follow-Up in the Era of Mobile Information Technology: A Systematic Review and Meta-Analysis.
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Lin, Haotian and Wu, Xiaohang
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PATIENT compliance , *CHRONIC diseases , *FOLLOW-up studies (Medicine) , *INFORMATION technology , *MOBILE communication systems , *SYSTEMATIC reviews , *RANDOMIZED controlled trials - Abstract
Background: Patient adherence to follow-up plays a key role in the medical surveillance of chronic diseases and affects the implementation of clinical research by influencing cost and validity. We previously reported a randomized controlled trial (RCT) on short message service (SMS) reminders, which significantly improved follow-up adherence in pediatric cataract treatment. Methods: RCTs published in English that reported the impact of SMS or telephone reminders on increasing or decreasing the follow-up rate (FUR) were selected from Medline, EMBASE, PubMed, and the Cochrane Library through February 2014. The impacts of SMS and telephone reminders on the FUR of patients were systematically evaluated by meta-analysis and bias was assessed. Results: We identified 13 RCTs reporting on 3276 patients with and 3402 patients without SMS reminders and 8 RCTs reporting on 2666 patients with and 3439 patients without telephone reminders. For the SMS reminders, the majority of the studies (>50%) were at low risk of bias, considering adequate sequence generation, allocation concealment, blinding, evaluation of incomplete outcome data, and lack of selective reporting. For the studies on the telephone reminders, only the evaluation of incomplete outcome data accounted for more than 50% of studies being at low risk of bias. The pooled odds ratio (OR) for the improvement of follow-up adherence in the SMS group compared with the control group was 1.76 (95% CI [1.37, 2.26]; P<0.01), and the pooled OR for the improvement of follow-up adherence in the telephone group compared with the control group was 2.09 (95% CI [1.85, 2.36]; P<0.01); both sets showed no evidence of publication bias. Conclusions: SMS and telephone reminders could both significantly improve the FUR. Telephone reminders were more effective but had a higher risk of bias than SMS reminders. [ABSTRACT FROM AUTHOR]
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- 2014
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31. How Frequently Do the Results from Completed US Clinical Trials Enter the Public Domain? - A Statistical Analysis of the ClinicalTrials.gov Database.
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Saito, Hiroki and Gill, Christopher J.
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CLINICAL trials , *PUBLIC domain , *MEDICAL databases , *QUANTITATIVE research , *KAPLAN-Meier estimator , *PUBLISHING - Abstract
Background: Achieving transparency in clinical trials, through either publishing results in a journal or posting results to the ClinicalTrials.gov (CTG) web site, is an essential public health good. However, it remains unknown what proportion of completed studies achieve public disclosure of results (PDOR), or what factors explain these differences. Methods: We analyzed data from 400 randomly selected studies within the CTG database that had been listed as ‘completed’ and had at least four years in which to disclose results. Using Kaplan-Meier curves, we calculated times from completion to PDOR (defined as publishing the primary outcomes in a journal and/or posting results to CTG), and identified explanatory variables predicting these outcomes using Cox proportional hazards models. Findings: Among the 400 clinical trials, 118 (29.5%) failed to achieve PDOR within four years of completion. The median day from study completion to PDOR among 282 studies (70.5%) that achieved PDOR was 602 days (mean 647 days, SD 454 days). Studies were less likely to achieve PDOR if at earlier stages (phase 2 vs. phase 3/4, adjusted HR 0.60, 95% CI 0.47–0.78), if they only included adult subjects (adjusted HR 0.61, 95% CI 0.45–0.83), involved randomization (adjusted HR 0.62, 95% CI 0.46–0.83), or had smaller sample sizes (≤50 subjects vs. >50, adjusted HR 0.60, 95% CI 0.44–0.83). Industry-funded studies were significantly less likely to be published than non-industry or blended studies (adjusted HR 0.49, 95% CI 0.36–0.66). Conclusions: A significant proportion of completed studies did not achieve PDOR within the four years of follow-up, particularly smaller studies at earlier stages of development with industry funding. This constitutes reporting bias and threatens the validity of the clinical research literature in the US. [ABSTRACT FROM AUTHOR]
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- 2014
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32. Primed to comply: Individual participant data sharing statements on ClinicalTrials.gov
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Bhagyashree Sonwane, Sarah A. White, Barbara E. Bierer, and Emily E. Statham
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Medical Journals ,Commit ,01 natural sciences ,Geographical locations ,0302 clinical medicine ,Medicine and Health Sciences ,030212 general & internal medicine ,Statistical Data ,Clinical Trials as Topic ,Multidisciplinary ,Pharmaceutics ,Statistics ,Journalism, Medical ,Outreach ,Chemistry ,ICMJE recommendations ,Physical Sciences ,Medicine ,Clinical Trial Reporting ,Psychology ,Editorial Policies ,Research Article ,Chemical Elements ,medicine.medical_specialty ,Drug Research and Development ,Science ,education ,MEDLINE ,Disclosure ,Research and Analysis Methods ,03 medical and health sciences ,Drug Therapy ,medicine ,Humans ,Clinical Trials ,0101 mathematics ,Drug Regulation ,Pharmacology ,Health Care Policy ,Information Dissemination ,Individual participant data ,010102 general mathematics ,Manuscripts, Medical as Topic ,bacterial infections and mycoses ,Medical Writing ,United States ,Data sharing ,Clinical trial ,Comprehension ,Health Care ,Family medicine ,North America ,Clinical Medicine ,People and places ,Medical Humanities ,Mathematics - Abstract
In June 2017, the International Committee of Medical Journal Editors (ICMJE) announced a requirement that authors reporting the results of clinical trials to journals that follow ICMJE recommendations must include an individual participant data (IPD) sharing statement with manuscripts submitted after 01 July 2018. Additionally, all new clinical trials for which enrollment began on or after 01 January 2019 must include a data sharing statement in the trial's publicly posted registration. This study sought to understand whether IPD sharing statements of clinical trials first registered on ClinicalTrials.gov before 01 January 2019 reflected comprehension of the expectations and a willingness to share. To establish baseline characteristics for the prevalence and quality of IPD sharing statements, we examined IPD sharing statements among 2,040 clinical trials first posted on ClinicalTrials.gov between 01 January 2018 and 06 June 2018. Two independent coders further analyzed the quality of the IPD sharing statements of trials whose registration records indicated the intent to share IPD. The vast majority of trials included in this study did not indicate an intent to share IPD (n = 1,928; 94.5%). Among the trials that did commit to sharing IPD (n = 112, 5.5%), significant variability existed in the content and structure of IPD sharing statements. The results of this study suggest that successful compliance with the IPD sharing statement requirements of the ICMJE will require further clarification, enhanced education, and outreach to investigators.
- Published
- 2020
33. Reporting quality and spin in abstracts of randomized clinical trials of periodontal therapy and cardiovascular disease outcomes
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John C. Gunsolley, Khadijeh Al-Abedalla, Helen Swede, Julie Wagner, Effie Ioannidou, and Murad Shaqman
- Subjects
medicine.medical_specialty ,Blinding ,Randomization ,Drug Research and Development ,Science ,Oral Medicine ,MEDLINE ,Dental and Oral Procedures ,Surgical and Invasive Medical Procedures ,Cardiovascular Medicine ,Research and Analysis Methods ,Biochemistry ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Cohen's kappa ,Randomized controlled trial ,Oral Diseases ,law ,Medicine and Health Sciences ,Medicine ,Clinical Trials ,030212 general & internal medicine ,Periodontitis ,Periodontal Diseases ,Pharmacology ,Multidisciplinary ,business.industry ,Consolidated Standards of Reporting Trials ,Biology and Life Sciences ,030206 dentistry ,Research Assessment ,Lipids ,Randomized Controlled Trials ,Cholesterol ,Data extraction ,Cardiovascular Diseases ,Bibliometrics ,Cohort ,Citation Analysis ,Physical therapy ,Clinical Trial Reporting ,Clinical Medicine ,business ,Research Article - Abstract
ObjectivePoor reporting in randomized clinical trial (RCT) abstracts reduces quality and misinforms readers. Spin, a biased presentation of findings, could frequently mislead clinicians to accept a clinical intervention despite non-significant primary outcome. Therefore, good reporting practices and absence of spin enhances research quality. We aim to assess the reporting quality and spin in abstracts of RCTs evaluating the effect of periodontal therapy on cardiovascular (CVD) outcomes.MethodsPubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and 17 trial registration platforms were searched. Cohort, non-randomized, non-English studies, and pediatric studies were excluded. RCT abstracts were reviewed by 2 authors using the CONSORT for abstracts and spin checklists for data extraction. Cohen's Kappa statistic was used to assess inter-rater agreement. Data on the selected RCT publication metrics were collected. Descriptive analysis was performed with non-parametric methods. Correlation analysis between quality, spin and bibliometric parameters was conducted.Results24 RCTs were selected for CONSORT analysis and 14 fulfilled the criteria for spin analysis. Several important RCT elements per CONSORT were neglected in the abstract including description of the study population (100%), explicitly stated primary outcome (87%), methods of randomization and blinding (100%), trial registration (87%). No RCT examined true outcomes (CVD events). A significant fraction of the abstracts appeared with at least one form of spin in the results and conclusions (86%) and claimed some treatment benefit in spite of non-significant primary outcome (64%). High-quality reporting had a significant positive correlation with reporting of trial registration (p = 0.04) and funding (p = 0.009). Spinning showed marginal negative correlation with reporting quality (p = 0.059).ConclusionPoor adherence to the CONSORT guidelines and high levels of data spin were found in abstracts of RCTs exploring the effects of periodontal therapy on CVD outcomes. Our findings indicate that journal editors and reviewers should consider strict adherence to proper reporting guidelines to improve reporting quality and reduce waste.
- Published
- 2019
34. Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring
- Author
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Dario Trapani, Jan Bogaerts, Martine Piccart, Barbara Kiesewetter, Christoph C. Zielinski, Ruth Wester, N. Tarazona, Urania Dafni, Giuseppe Curigliano, Carlos Gomez-Roca, T. Amaral, Felipe Roitberg, G. Zarkavelis, Bishal Gyawali, Antonio Passaro, Sjoukje F. Oosting, Antonio Calles, Nathan I. Cherny, Panagiota Zygoura, Georgios Pentheroudakis, E.G.E. de Vries, Jorge Barriuso, Josep Tabernero, Institut Català de la Salut, [Gyawali B] Department of Oncology, Queen’s University, Kingston, Ontario, Canada. Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada. Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada. [de Vries EGE] Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [Dafni U] Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens. Frontier Science Foundation-Hellas, Athens, Greece. [Amaral T] Skin Cancer Center, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany. [Barriuso J] The Christie NHS Foundation Trust and Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. [Bogaerts J] European Organisation for Research and Treatment of Cancer, Brussels, Belgium. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, IO-Quiron, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Data Analysis ,técnicas de investigación::métodos::diseño de la investigación [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Cancer Research ,bias ,media_common.quotation_subject ,clinical trial reporting ,ESMO-MCBS ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Review ,Medical Oncology ,clinical trial implementation ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,neoplasias [ENFERMEDADES] ,profesiones sanitarias::medicina::medicina interna::oncología médica [DISCIPLINAS Y OCUPACIONES] ,Neoplasms ,clinical trial analysis ,Investigative Techniques::Methods::Research Design [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Agency (sociology) ,Humans ,Quality (business) ,Health Occupations::Medicine::Internal Medicine::Medical Oncology [DISCIPLINES AND OCCUPATIONS] ,health care economics and organizations ,media_common ,Actuarial science ,Manchester Cancer Research Centre ,Càncer - Tractament ,ResearchInstitutes_Networks_Beacons/mcrc ,Clinical study design ,Health technology ,Généralités ,Publication bias ,clinical trial design ,Assaigs clínics - Disseny ,Neoplasms [DISEASES] ,Clinical trial ,Critical appraisal ,Oncology ,Research Design ,Scale (social sciences) ,Psychology - Abstract
BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment. METHODS: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment. RESULTS: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data. CONCLUSION: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS., SCOPUS: re.j, info:eu-repo/semantics/published
- Published
- 2021
35. Sharing Clinical Trial Data: A Proposal from the International Committee of Medical Journal Editors.
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Taichman, Darren B., Backus, Joyce, Baethge, Christopher, Bauchner, Howard, de Leeuw, Peter W., Drazen, Jeffrey M., Fletcher, John, Frizelle, Frank A., Groves, Trish, Haileamlak, Abraham, James, Astrid, Laine, Christine, Peiperl, Larry, Pinborg, Anja, Sahni, Peush, and Wu, Sinan
- Subjects
- *
INFORMATION sharing , *PATIENTS , *ANONYMITY , *CLINICAL trials , *COMMUNICATION , *INTERNATIONAL relations , *PUBLISHING - Abstract
In a joint publication across 14 member journals, the International Committee of Medical Journal Editors (ICMJE) proposes to require sharing of deidentified individual patient data underlying published clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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36. Delays in completion and results reporting of clinical trials under the Paediatric Regulation in the European Union: A cohort study
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Thomas J Hwang, Florence T. Bourgeois, and Paolo Tomasi
- Subjects
Research design ,medicine.medical_specialty ,Drug Research and Development ,Drug Industry ,MEDLINE ,Social Sciences ,lcsh:Medicine ,Research and Analysis Methods ,Pediatrics ,Geographical locations ,03 medical and health sciences ,0302 clinical medicine ,Sociology ,030225 pediatrics ,medicine ,Medicine and Health Sciences ,media_common.cataloged_instance ,Humans ,Clinical Trials ,030212 general & internal medicine ,European Union ,European union ,Child ,Drug Approval ,media_common ,Drug Regulation ,Marketing ,Pharmacology ,Publishing ,Clinical Trials as Topic ,Hazard ratio ,lcsh:R ,Drugs ,General Medicine ,Research Assessment ,Waiver ,Communications ,Clinical trial ,Europe ,Research Design ,Family medicine ,Cohort ,Drug and Narcotic Control ,Clinical Trial Reporting ,People and places ,Clinical Medicine ,Cohort study ,Research Article - Abstract
Background Few medicines have been approved for children, leading to rates of off-label prescribing reported to be as high as 90%. In 2007, the European Union adopted the Paediatric Regulation, which mandates that pharmaceutical companies conduct paediatric studies for all new medicines, unless granted a waiver. We aimed to evaluate the availability of paediatric trial results from studies required under the Paediatric Regulation for new medicines authorised in the EU. Methods and findings The European Medicines Agency (EMA) public database of paediatric investigation plans was searched for new medicines centrally authorised in the EU between 1 January 2010 and 31 December 2014 with at least 1 required paediatric study. For our study cohort of paediatric clinical trials required for these medicines, we used internal EMA databases and publicly available trial registries to determine changes to the planned completion date or study design, rates of trial completion, time to trial completion, and results reporting (peer-reviewed publication or posting on trial registry). Cox proportional hazards regression models were constructed to examine factors associated with study completion. A total of 326 paediatric clinical trials were required for 122 novel medicines authorised by the EMA between 2010 and 2014. In all, 76% (247/326) of paediatric studies were not planned to be completed until after the initial marketing authorisation. The planned completion dates for 50% (162/326) were further postponed by a median of 2.2 years. Overall, 38% (124/326) of paediatric studies were completed as of 30 November 2017. The rate of trial completion for paediatric studies planned to be completed after initial marketing authorisation was 23% (56/247), versus 86% (68/79) for trials planned to be completed before authorisation (adjusted hazard ratio 0.11; 95% CI 0.06–0.19). Among completed studies, the results were reported in a public registry or in the peer-reviewed literature for 85% (105/124) at a median of 1.1 years after study completion, and 60% (74/124) were published in a peer-reviewed journal. Limitations of this study include the potential lack of generalisability to medicines not authorised by the EMA and the possibility for more of these trials to be completed or published in the future. Conclusions The completion of many paediatric studies required under the Paediatric Regulation has been delayed. Paediatric studies planned to be completed after marketing authorisation were associated with a lower likelihood of eventual completion, highlighting the need to examine the implementation of current policies in ensuring timely availability of important paediatric information., Since 2007, the European Union has mandated that newly authorized medicines for adults are tested in pediatric trials. In this study, Florence Bourgeois and colleagues evaluate the success of this regulation in terms of planned, completed and reported pediatric trials., Author summary Why was this study done? Most new medicines are developed and tested in adults, and clinicians often need to treat paediatric patients with products lacking paediatric safety, efficacy, or dosing information. To increase the number of medicines that are appropriately studied in children, the European Union adopted the Paediatric Regulation in 2007, requiring pharmaceutical companies to study new medicines in children. Ten years since its implementation, there has been limited assessment of the availability of paediatric trial information resulting from studies required under the regulation. What did the researchers do and find? For all new medicines centrally authorised in the EU between 2010 and 2014, we identified those with paediatric trial requirements under the Paediatric Regulation. A total of 326 paediatric clinical trials were required for 122 medicines and comprised our study cohort. After a median follow-up of roughly 7 years, 38% of paediatric trials had been completed, and 17% of medicines had all paediatric requirements fulfilled. Most paediatric studies (76%) were not planned to be completed until after marketing authorisation. In addition, delays occurred due to changes in the planned completion date, with 50% of studies extending the completion date at the request of pharmaceutical companies. Overall, trials planned to be completed after marketing authorisation were associated with an 89% lower likelihood of completion compared to trials with planned completion before marketing authorisation. The results for 85% of completed studies were published or publicly reported in a trial registry, at a median of 1.1 years after the completion date. What do these findings mean? Many paediatric studies required under the Paediatric Regulation have not been completed due to delays. Among paediatric trials that were completed, trial results were disseminated in a timely fashion for a majority of the studies. Our findings highlight the need to examine the implementation of current policies—including requirements around the timing of trial completion—to ensure timely availability of important paediatric information for new medicines.
- Published
- 2018
37. Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring.
- Author
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Gyawali B, de Vries EGE, Dafni U, Amaral T, Barriuso J, Bogaerts J, Calles A, Curigliano G, Gomez-Roca C, Kiesewetter B, Oosting S, Passaro A, Pentheroudakis G, Piccart M, Roitberg F, Tabernero J, Tarazona N, Trapani D, Wester R, Zarkavelis G, Zielinski C, Zygoura P, and Cherny NI
- Subjects
- Bias, Humans, Medical Oncology, Research Design, Data Analysis, Neoplasms drug therapy
- Abstract
Background: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment., Methods: As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment., Results: Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data., Conclusion: Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS., Competing Interests: Disclosure TA personal fees and travel grants from Bristol-Myers Squibb (BMS), personal fees, grants and travel grants from Novartis, personal fees from Pierre Fabre, grants from Neracare, Sanofi, and SkylineDx, personal fees from CeCaVa outside the submitted work; JBa reports grants, personal fees, and nonfinancial support from Ipsen; personal fees and nonfinancial support from Pfizer, Novartis; nonfinancial support from AAA, Nanostring, Roche; grants and personal fees from Servier; and personal fees from Nutricia outside the submitted work; JBo is a statistician on the SAG-O (scientific advice committee oncology) for EMA, and scientific director of EORTC Headquarters. EORTC carries out clinical trials with many (most) pharma and some biotechs either with financial or material support, or with the company as the sponsor (intent to register new indication); he is co-responsible for the management of EORTC. AC has received honoraria/consulting fees from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche/Genentech, Eli Lilly and Company, Takeda, Novartis, Merck Sharp & Dohme (MSD), and BMS; GC scientific advisory board for BMS, Roche, Novartis, Lilly, Pfizer, Seagen, AstraZeneca, Daichii Sankyo, and Veracyte; UD Tumour Agnostic Evidence Generation Working Group Member, Roche; BG reports receiving consulting fees from Vivio Health. CG-R BMS (institutional research and travel grants, speaker’s honoraria), Roche/Genentech (institutional research and travel grants, speaker’s honoraria), Pierre Fabre (travel and educational grants, speaker’s honoraria); MSD (travel grants); Eisai (speaker’s honoraria); Foundation Medicine (research grant, speaker’s honoraria); BK Honoraria for lectures from Ipsen, Novartis and MSD; SO research grants from Celldex and Novartis to the institution; AP received honoraria for consulting, advisory role or lectures from AstraZeneca, Agilent/Dako, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, MSD, Pfizer and Roche Genentech; GP received institutional financial support for advisory board/consultancy from Roche, Amgen, Merck, MSD, BMS, and institutional support for clinical trials or contracted research from Amgen, Roche, AstraZeneca, Pfizer, Merck, BMS, MSD, Novartis, Lilly; MP consulting or advisory role: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche, Genentech, Crescendo Biologics, Periphagen, Huya Bioscience, Debiopharm Group, Odante Therapeutics; Consulting or Advisory Role: G1 Therapeutics, Menarini, Seattle Genetics, Camel-IDS, Immunomedics, Oncolytics, Radius Health; Research Funding: AstraZeneca (Inst), Lilly (Inst), MSD (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Genentech (Inst), Radius Health (Inst), Synthon (Inst), Servier (Inst); Other Relationship: Radius Health; JT personal financial interest in the form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech, Inc., HalioDX SAS, Ikena Oncology, IQVIA, Imedex, Lilly, MSD, Menarini, Merck Serono, Mirati, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc. Institutional financial interest in the form of financial support for clinical trials or contracted research for Amgen Inc., Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., Janssen-Cilag SA, MSD, Novartis Farmacéutica SA, Taiho Pharma USA Inc., Pharma Mar, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK; EGEdV declares: institutional financial support for advisory board/consultancy from Sanofi, Daiichi, Sankyo, NSABP, Pfizer and Merck, and institutional support for clinical trials or contracted research from Amgen, Genentech, Roche, AstraZeneca, Synthon, Nordic Nanovector, G1 Therapeutics, Bayer, Chugai Pharma, CytomX Therapeutics, Servier and Radius Health; CZ consultancies and speaker’s honoraria: Roche, Novartis, BMS, MSD, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Shire, Eli Lilly, Athenex. Institution (Central European Cooperative Oncology Group): BMS, MSD, Pfizer, AstraZeneca, Servier, Eli Lilly; GZ received speaker’s honoraria from Amgen and Ipsen. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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38. Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov
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Vibha Anand and Amos Cahan
- Subjects
Male ,Physiology ,Epidemiology ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Body Mass Index ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Ethnicities ,030212 general & internal medicine ,lcsh:Science ,Clinical Trials as Topic ,Multidisciplinary ,Physiological Parameters ,Physical Sciences ,Female ,Clinical Trial Reporting ,Research Article ,Statistical Distributions ,medicine.medical_specialty ,Drug Research and Development ,MEDLINE ,Research and Analysis Methods ,Ethnic Epidemiology ,Age and gender ,03 medical and health sciences ,Humans ,Statistical dispersion ,Clinical Trials ,Baseline (configuration management) ,Scientific Publishing ,Pharmacology ,Internet ,Health Care Policy ,business.industry ,lcsh:R ,Body Weight ,Health Care Policy Reports ,Biology and Life Sciences ,Probability Theory ,Statistical Dispersion ,United States ,Clinical trial ,Health Care ,Aggregate analysis ,People and Places ,Physical therapy ,lcsh:Q ,Population Groupings ,Scientific publishing ,Clinical Medicine ,business ,Body mass index ,Mathematics - Abstract
Background ClinicalTrials.gov is valuable for aggregate-level analysis of trials. The recently published final rule aims to improve reporting of trial results. We aimed to assess variability in ClinicalTirals.gov records reporting participants’ baseline measures. Methods and findings The September 2015 edition of the database for Aggregate Analysis of ClinicalTrials.gov (AACT), was used in this study. To date, AACT contains 186,941 trials of which 16,660 trials reporting baseline (participant) measures were analyzed. We also analyzed a subset of 13,818 Highly Likely Applicable Clinical Trials (HLACT), for which reporting of results is likely mandatory and compared a random sample of 30 trial records to their journal articles. We report counts for each mandatory baseline measure and variability reporting in their formats. The AACT dataset contains 8,161 baseline measures with 1206 unique measurement units. However, of these 6,940 (85%) variables appear only once in the dataset. Age and Gender are reported using many different formats (178 and 49 respectively). “Age” as the variable name is reported in 60 different formats. HLACT subset reports measures using 3,931 variables. The most frequent Age format (i.e. mean (years) ± sd) is found in only 45% of trials. Overall only 4 baseline measures (Region of Enrollment, Age, Number of Participants, and Gender) are reported by > 10% of trials. Discrepancies are found in both the types and formats of ClinicalTrials.gov records and their corresponding journal articles. On average, journal articles include twice the number of baseline measures (13.6±7.1 (sd) vs. 6.6±7.6) when compared to the ClinicalTrials.gov records that report any results. Conclusions We found marked variability in baseline measures reporting. This is not addressed by the final rule. To support secondary use of ClinicalTrials.gov, a uniform format for baseline measures reporting is warranted.
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- 2016
39. Multi-reader multi-case studies using the area under the receiver operator characteristic curve as a measure of diagnostic accuracy: systematic review with a focus on quality of data reporting
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Thaworn Dendumrongsup, Andrew A Plumb, Steve Halligan, Thomas R Fanshawe, Douglas G Altman, and Susan Mallett
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Research Validity ,Systematic Reviews ,Imaging Techniques ,Clinical Research Design ,Diagnostic Tests, Routine ,Research Quality Assessment ,lcsh:R ,lcsh:Medicine ,Reproducibility of Results ,Image Analysis ,Research Assessment ,Research and Analysis Methods ,Sensitivity and Specificity ,Mathematical and Statistical Techniques ,ROC Curve ,Research Design ,Humans ,lcsh:Q ,Clinical Trials ,Clinical Trial Reporting ,Non-Randomized Controlled Trials ,Statistical Methods ,lcsh:Science ,Research Article - Abstract
Introduction We examined the design, analysis and reporting in multi-reader multi-case (MRMC) research studies using the area under the receiver-operating curve (ROC AUC) as a measure of diagnostic performance. Methods We performed a systematic literature review from 2005 to 2013 inclusive to identify a minimum 50 studies. Articles of diagnostic test accuracy in humans were identified via their citation of key methodological articles dealing with MRMC ROC AUC. Two researchers in consensus then extracted information from primary articles relating to study characteristics and design, methods for reporting study outcomes, model fitting, model assumptions, presentation of results, and interpretation of findings. Results were summarized and presented with a descriptive analysis. Results Sixty-four full papers were retrieved from 475 identified citations and ultimately 49 articles describing 51 studies were reviewed and extracted. Radiological imaging was the index test in all. Most studies focused on lesion detection vs. characterization and used less than 10 readers. Only 6 (12%) studies trained readers in advance to use the confidence scale used to build the ROC curve. Overall, description of confidence scores, the ROC curve and its analysis was often incomplete. For example, 21 (41%) studies presented no ROC curve and only 3 (6%) described the distribution of confidence scores. Of 30 studies presenting curves, only 4 (13%) presented the data points underlying the curve, thereby allowing assessment of extrapolation. The mean change in AUC was 0.05 (−0.05 to 0.28). Non-significant change in AUC was attributed to underpowering rather than the diagnostic test failing to improve diagnostic accuracy. Conclusions Data reporting in MRMC studies using ROC AUC as an outcome measure is frequently incomplete, hampering understanding of methods and the reliability of results and study conclusions. Authors using this analysis should be encouraged to provide a full description of their methods and results.
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- 2016
40. Sharing Individual Participant Data (IPD) within the Context of the Trial Reporting System (TRS)
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Tony Tse and Deborah A. Zarin
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Databases, Factual ,animal diseases ,Applied psychology ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Diagnostic Radiology ,Families ,0302 clinical medicine ,Medicine and Health Sciences ,030212 general & internal medicine ,Children ,Tomography ,Clinical Trials as Topic ,Depression ,Radiology and Imaging ,food and beverages ,General Medicine ,Research Assessment ,Reproducibility ,Systematic review ,Research Design ,Engineering and Technology ,Clinical Trial Reporting ,medicine.medical_specialty ,Drug Research and Development ,Drug Industry ,Essay ,Clinical Research Design ,Imaging Techniques ,Information Dissemination ,Context (language use) ,Neuroimaging ,Digital Imaging ,Research and Analysis Methods ,03 medical and health sciences ,Diagnostic Medicine ,Mental Health and Psychiatry ,medicine ,Humans ,Medical physics ,Clinical Trials ,Drug industry ,Pharmacology ,business.industry ,Mood Disorders ,Individual participant data ,lcsh:R ,fungi ,Biology and Life Sciences ,nervous system diseases ,Clinical trial ,Age Groups ,People and Places ,Population Groupings ,Adverse Events ,Scientific publishing ,Clinical Medicine ,business ,Safety Studies ,Reporting system ,Positron Emission Tomography ,Neuroscience - Abstract
Deborah Zarin and Tony Tse of ClinicalTrials.Gov consider how sharing individual participant data can and cannot help improve the reporting of clinical trials.
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- 2016
41. Using ROC curves to choose minimally important change thresholds when sensitivity and specificity are valued equally : the forgotten lesson of Pythagoras : theoretical considerations and an example application of change in health status
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Robert J. Froud and Gary A. Abel
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Questionnaires ,Psychometrics ,Epidemiology ,lcsh:Medicine ,Research and Analysis Methods ,Bioinformatics ,Measure (mathematics) ,Statistics ,Medicine and Health Sciences ,Psychology ,Medicine ,Clinical Trials ,Sensitivity (control systems) ,lcsh:Science ,Divergence (statistics) ,QA ,Selection (genetic algorithm) ,Survey Research ,Multidisciplinary ,Receiver operating characteristic ,business.industry ,lcsh:R ,Explained sum of squares ,Biology and Life Sciences ,Estimator ,Research Assessment ,Variable (computer science) ,Research Design ,Research Reporting Guidelines ,Clinical Trial Reporting ,lcsh:Q ,Clinical Medicine ,business ,Research Article - Abstract
Background\ud \ud Receiver Operator Characteristic (ROC) curves are being used to identify Minimally Important Change (MIC) thresholds on scales that measure a change in health status. In quasi-continuous patient reported outcome measures, such as those that measure changes in chronic diseases with variable clinical trajectories, sensitivity and specificity are often valued equally. Notwithstanding methodologists agreeing that these should be valued equally, different approaches have been taken to estimating MIC thresholds using ROC curves.\ud \ud Aims and objectives\ud \ud We aimed to compare the different approaches used with a new approach, exploring the extent to which the methods choose different thresholds, and considering the effect of differences on conclusions in responder analyses.\ud \ud Methods\ud \ud Using graphical methods, hypothetical data, and data from a large randomised controlled trial of manual therapy for low back pain, we compared two existing approaches with a new approach that is based on the addition of the sums of squares of 1-sensitivity and 1-specificity.\ud \ud Results\ud \ud There can be divergence in the thresholds chosen by different estimators. The cut-point selected by different estimators is dependent on the relationship between the cut-points in ROC space and the different contours described by the estimators. In particular, asymmetry and the number of possible cut-points affects threshold selection.\ud \ud Conclusion\ud Choice of MIC estimator is important. Different methods for choosing cut-points can lead to materially different MIC thresholds and thus affect results of responder analyses and trial conclusions. An estimator based on the smallest sum of squares of 1-sensitivity and 1-specificity is preferable when sensitivity and specificity are valued equally. Unlike other methods currently in use, the cut-point chosen by the sum of squares method always and efficiently chooses the cut-point closest to the top-left corner of ROC space, regardless of the shape of the ROC curve.
- Published
- 2014
42. A Comparative Study on the Efficacy of Solifenacin Succinate in Patients with Urinary Frequency with or without Urgency
- Author
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Choal Hee Park, Won Hee Park, Myung Soo Choo, Jeong Zoo Lee, Dong Deuk Kwon, Kyu-Sung Lee, Yong Gil Na, Ji Yeon Han, Jeong Gu Lee, and Duk Yoon Kim
- Subjects
Solifenacin Succinate ,Male ,Quinuclidines ,Conservative management ,lcsh:Medicine ,urologic and male genital diseases ,Tetrahydroisoquinolines ,Medicine and Health Sciences ,lcsh:Science ,media_common ,Aged, 80 and over ,Multidisciplinary ,Cognitive Neurology ,Clinical Pharmacology ,Bladder and Ureteric Disorders ,Middle Aged ,female genital diseases and pregnancy complications ,Treatment Outcome ,Overactive bladder ,Neurology ,Clinical Trial Reporting ,Female ,Anatomy ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Urinary system ,media_common.quotation_subject ,Bladder ,Cognitive Neuroscience ,Urology ,Muscarinic Antagonists ,Research and Analysis Methods ,Urination ,medicine ,Humans ,In patient ,Clinical Trials ,Adverse effect ,Aged ,Pharmacology ,Solifenacin ,business.industry ,Urinary Bladder, Overactive ,lcsh:R ,Biology and Life Sciences ,Renal System ,medicine.disease ,lcsh:Q ,Clinical Medicine ,business ,Neuroscience - Abstract
Objectives Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency. Materials and Methods This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire. Results Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115; with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of −2.49±0.35 (mean ± standard error) and −2.63±0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was −1.14, which is smaller than the −0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well. Conclusions It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency. Trial Registration ClinicalTrials.gov NCT00979472
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- 2014
43. Cytoplasmic and/or Nuclear Expression of β-Catenin Correlate with Poor Prognosis and Unfavorable Clinicopathological Factors in Hepatocellular Carcinoma: A Meta-Analysis
- Author
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Hong Yu, Jiang Chen, Xiao Liang, Yuelong Liang, Hui Lin, Jiliang Shen, Jinghua Liu, Rui Ma, Renan Jin, and Xiujun Cai
- Subjects
Oncology ,Liver Cirrhosis ,Cytoplasm ,lcsh:Medicine ,Gene Expression ,Metastasis ,Medicine and Health Sciences ,Odds Ratio ,lcsh:Science ,beta Catenin ,Multidisciplinary ,Effector ,Liver Diseases ,Liver Neoplasms ,Wnt signaling pathway ,Gene Therapy ,Tumor Burden ,Hepatocellular carcinoma ,Cluster Trials ,Clinical Trial Reporting ,alpha-Fetoproteins ,Signal transduction ,Research Article ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Gastroenterology and Hepatology ,Biology ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Clinical Trials ,Molecular Biology Techniques ,Molecular Biology ,Neoplasm Staging ,Clinical Genetics ,Cell Nucleus ,lcsh:R ,Biology and Life Sciences ,Hepatocellular Carcinoma ,HCCS ,medicine.disease ,digestive system diseases ,Catenin ,Cancer research ,lcsh:Q ,Non-Randomized Controlled Trials ,Clinical Medicine ,Neoplasm Grading ,Neoplasm Recurrence, Local - Abstract
BACKGROUND: The β-catenin is an important effector in WNT/β-catenin signaling pathway, which exerts a crucial role in the development and progression of hepatocellular carcinoma (HCC). Some researchers have suggested that the overexpression of β-catenin in cytoplasm and/or nucleus was closely correlated to metastasis, poor differentiation and malignant phenotype of HCC while some other researchers hold opposite point. So far, no consensus was obtained on the prognostic and clinicopathological significance of cytoplasmic/nuclear β-catenin overexpression for HCCs. METHODS: Systematic strategies were applied to search eligible studies in all available databases. Subgroup analyses, sensitivity analyses and multivariate analysis were performed. In this meta-analysis, we utilized either fixed- or random-effects model to calculate the pooled odds ratios (OR) and its 95% confidence intervals (CI). RESULTS: A total of 22 studies containing 2334 cases were enrolled in this meta-analysis. Pooled data suggested that accumulation of β-catenin in cytoplasm and/or nucleus significantly correlated with poor 1-, 3- and 5-year OS and RFS. Moreover, nuclear accumulation combined with cytoplasmic accumulation of β-catenin tended to be associated with dismal metastasis and vascular invasion while cytoplasmic or nuclear expression alone showed no significant effect. Besides, no significant association was observed between cytoplasmic and/or nuclear β-catenin expression and poor differentiation grade, advanced TNM stage, liver cirrhosis, tumor size, tumor encapsulation, AFP and etiologies. Additional subgroup analysis by origin suggested that the prognostic value and clinicopathological significance of cytoplasmic and/or nuclear β-catenin expression was more validated in Asian population. Multivariate analyses of factors showed that cytoplasmic and/or nuclear β-catenin expression, as well as TNM stage, metastasis and tumor size, was an independent risk factors for OS and RFS. CONCLUSIONS: Cytoplasmic and/or nuclear accumulation of β-catenin, as an independent prognostic factor, significantly associated with poor prognosis and deeper invasion of HCC, and could serve as a valuable prognostic predictor for HCC.
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- 2014
44. A Pilot RCT of Psychodynamic Group Art Therapy for Patients in Acute Psychotic Episodes: Feasibility, Impact on Symptoms and Mentalising Capacity
- Author
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Dorothea Seidel, Uwe Herrmann, Christiane Montag, Jürgen Gallinat, Martin Bayerl, Laura Haase, and Karin Dannecker
- Subjects
Social Cognition ,Male ,Global Assessment of Functioning ,lcsh:Medicine ,Pilot Projects ,law.invention ,Behavioral Neuroscience ,Quality of life ,Randomized controlled trial ,law ,Medicine and Health Sciences ,lcsh:Science ,Depression (differential diagnoses) ,Multidisciplinary ,Cognitive Neurology ,Standard treatment ,Middle Aged ,Treatment Outcome ,Schizophrenia ,Psychotherapy, Group ,Clinical Trial Reporting ,Female ,Psychotherapy, Psychodynamic ,Psychosocial ,Research Article ,Adult ,medicine.medical_specialty ,Consciousness ,Art therapy ,Cognitive Neuroscience ,Self-Consciousness ,Neuropsychology ,Mental Health and Psychiatry ,medicine ,Humans ,Clinical Trials ,Psychiatry ,Neuropsychological Testing ,business.industry ,lcsh:R ,Cognitive Psychology ,Biology and Life Sciences ,Psychoses ,Art Therapy ,medicine.disease ,Randomized Controlled Trials ,Psychotherapy ,100 Philosophie und Psychologie::150 Psychologie ,Psychotic Disorders ,Physical therapy ,Quality of Life ,Cognitive Science ,lcsh:Q ,Clinical Medicine ,business ,Mental Health Therapies ,Neuroscience ,Follow-Up Studies - Abstract
This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function. Trial Registration ClinicalTrials.gov NCT01622166
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- 2014
45. A Capsaicin (8%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial
- Author
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Mads U. Werner, Thomas K. Ringsted, Claudia Sommer, Nurcan Üçeyler, Joakim M. Bischoff, and Marian Petersen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transdermal patch ,Placebo-controlled study ,lcsh:Medicine ,Pain ,Transdermal Patch ,Hernia, Inguinal ,Placebo ,Cutaneous patch ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Risk Factors ,Statistical significance ,Surveys and Questionnaires ,Medicine and Health Sciences ,Medicine ,Pain Management ,Humans ,Clinical Trials ,ddc:610 ,lcsh:Science ,Neuropathic Pain ,Aged ,Pain Measurement ,Skin ,Analgesics ,Multidisciplinary ,business.industry ,lcsh:R ,Middle Aged ,Randomized Controlled Trials ,Surgery ,chemistry ,Capsaicin ,Anesthesia ,Neuropathic pain ,lcsh:Q ,Clinical Trial Reporting ,Female ,Clinical Medicine ,business ,Research Article - Abstract
Background Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0–10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P
- Published
- 2014
46. ‘Spin’ in published biomedical literature: A methodological systematic review
- Author
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Lisa Bero, Kellia Chiu, and Quinn Grundy
- Subjects
Biomedical Research ,Cancer Treatment ,Social Sciences ,Scientific literature ,law.invention ,Governments ,Mathematical and Statistical Techniques ,0302 clinical medicine ,Randomized controlled trial ,law ,Medicine and Health Sciences ,Psychology ,030212 general & internal medicine ,Biology (General) ,Language ,General Neuroscience ,Research Assessment ,Surgical Oncology ,Systematic review ,Oncology ,Research Design ,Meta-analysis ,Physical Sciences ,Meta-Research Article ,Observational Studies ,Propaganda ,Clinical Trial Reporting ,General Agricultural and Biological Sciences ,Statistics (Mathematics) ,Prejudice ,Clinical psychology ,Clinical Oncology ,Drug Research and Development ,Systematic Reviews ,QH301-705.5 ,Political Science ,MEDLINE ,Scopus ,Biology ,Research and Analysis Methods ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Public Relations ,Clinical Trials ,Statistical Methods ,Pharmacology ,Publishing ,General Immunology and Microbiology ,Conflict of Interest ,Cognitive Psychology ,Biology and Life Sciences ,Randomized Controlled Trials ,Clinical trial ,Cognitive Science ,Observational study ,Clinical Medicine ,Mathematics ,030217 neurology & neurosurgery ,Meta-Analysis ,Neuroscience - Abstract
In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. This systematic review aims to explore the nature and prevalence of spin in the biomedical literature. We searched MEDLINE, PreMEDLINE, Embase, Scopus, and hand searched reference lists for all reports that included the measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of reports and their included studies and all spin-related outcomes. Results were grouped inductively into themes by spin-related outcome and are presented as a narrative synthesis. We used meta-analyses to analyse the association of spin with industry sponsorship of research. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research., Author summary In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. We conducted a systematic review to explore the nature and prevalence of spin in the biomedical literature. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research.
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- 2017
47. Effects of research complexity and competition on the incidence and growth of coauthorship in biomedicine
- Author
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Reinhard Laubenbacher, Xiaoyan Wang, and Jason Cory Brunson
- Subjects
Biomedical Research ,Economics ,Social Sciences ,lcsh:Medicine ,Bioinformatics ,0302 clinical medicine ,Citation analysis ,Medicine and Health Sciences ,030212 general & internal medicine ,lcsh:Science ,Data Management ,Multidisciplinary ,05 social sciences ,Health services research ,Research Assessment ,Random effects model ,Controlled Vocabularies ,Research Design ,Regression Analysis ,Clinical Trial Reporting ,Health Services Research ,Periodicals as Topic ,050904 information & library sciences ,Research Article ,PubMed ,Computer and Information Sciences ,Drug Research and Development ,Science Policy ,Research Grants ,Sample (statistics) ,Biology ,Bibliometrics ,Research and Analysis Methods ,Research Funding ,Competition (economics) ,03 medical and health sciences ,Humans ,Clinical Trials ,Biomedicine ,Publishing ,Pharmacology ,Actuarial science ,business.industry ,lcsh:R ,Popularity ,Authorship ,Health Care ,lcsh:Q ,Clinical Medicine ,0509 other social sciences ,business ,Finance - Abstract
Background Investigations into the factors behind coauthorship growth in biomedical research have mostly focused on specific disciplines or journals, and have rarely controlled for factors in combination or considered changes in their effects over time. Observers often attribute the growth to the increasing complexity or competition (or both) of research practices, but few attempts have been made to parse the contributions of these two likely causes. Objectives We aimed to assess the effects of complexity and competition on the incidence and growth of coauthorship, using a sample of the biomedical literature spanning multiple journals and disciplines. Methods Article-level bibliographic data from PubMed were combined with publicly available bibliometric data from Web of Science and SCImago over the years 1999–2007. We selected four predictors of coauthorship were selected, two (study type, topical scope of the study) associated with complexity and two (financial support for the project, popularity of the publishing journal) associated with competition. A negative binomial regression model was used to estimate the effects of each predictor on coauthorship incidence and growth. A second, mixed-effect model included the journal as a random effect. Results Coauthorship increased at about one author per article per decade. Clinical trials, supported research, and research of broader scope produced articles with more authors, while review articles credited fewer; and more popular journals published higher-authorship articles. Incidence and growth rates varied widely across journals and were themselves uncorrelated. Most effects remained statistically discernible after controlling for the publishing journal. The effects of complexity-associated factors held constant or diminished over time, while competition-related effects strengthened. These trends were similar in size but not discernible from subject-specific subdata. Conclusions Coauthorship incidence rates are multifactorial and vary with factors associated with both complexity and competition. Coauthorship growth is likewise multifactorial and increasingly associated with research competition.
- Published
- 2017
48. Intervention Strategies for Improving Patient Adherence to Follow-Up in the Era of Mobile Information Technology: A Systematic Review and Meta-Analysis
- Author
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Xiaohang Wu and Haotian Lin
- Subjects
medicine.medical_specialty ,Medical surveillance ,Research Validity ,Short Message Service ,Systematic Reviews ,Research Quality Assessment ,education ,MEDLINE ,lcsh:Medicine ,Research and Analysis Methods ,Health informatics ,law.invention ,Randomized controlled trial ,law ,medicine ,Medicine and Health Sciences ,Humans ,Clinical Trials ,Intensive care medicine ,lcsh:Science ,Randomized Controlled Trials as Topic ,Multidisciplinary ,Research Monitoring ,business.industry ,Information Dissemination ,lcsh:R ,Health services research ,Research Assessment ,Systematic review ,Meta-analysis ,Patient Compliance ,lcsh:Q ,Clinical Trial Reporting ,Clinical Medicine ,business ,psychological phenomena and processes ,Cell Phone ,Medical Informatics ,Research Article - Abstract
Background Patient adherence to follow-up plays a key role in the medical surveillance of chronic diseases and affects the implementation of clinical research by influencing cost and validity. We previously reported a randomized controlled trial (RCT) on short message service (SMS) reminders, which significantly improved follow-up adherence in pediatric cataract treatment. Methods RCTs published in English that reported the impact of SMS or telephone reminders on increasing or decreasing the follow-up rate (FUR) were selected from Medline, EMBASE, PubMed, and the Cochrane Library through February 2014. The impacts of SMS and telephone reminders on the FUR of patients were systematically evaluated by meta-analysis and bias was assessed. Results We identified 13 RCTs reporting on 3276 patients with and 3402 patients without SMS reminders and 8 RCTs reporting on 2666 patients with and 3439 patients without telephone reminders. For the SMS reminders, the majority of the studies (>50%) were at low risk of bias, considering adequate sequence generation, allocation concealment, blinding, evaluation of incomplete outcome data, and lack of selective reporting. For the studies on the telephone reminders, only the evaluation of incomplete outcome data accounted for more than 50% of studies being at low risk of bias. The pooled odds ratio (OR) for the improvement of follow-up adherence in the SMS group compared with the control group was 1.76 (95% CI [1.37, 2.26]; P
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- 2014
49. LDL-migration index (LDL-MI), an indicator of small dense low-density lipoprotein (sdLDL), is higher in non-alcoholic steatohepatitis than in non-alcoholic fatty liver: a multicenter cross-sectional study
- Author
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Yoshio Sumida, Yuji Ogawa, Yuichiro Eguchi, Yasushi Honda, Atsushi Nakajima, Koichiro Wada, Hiroyuki Kirikoshi, Koji Fujita, Takaomi Kessoku, Satoru Saito, Masataka Taguri, Yuichi Nozaki, Hideyuki Hyogo, Masafumi Ono, Kento Imajo, Masato Yoneda, Hironori Mawatari, and Wataru Tomeno
- Subjects
Male ,Pathology ,Atorvastatin ,Nutritional Disorders ,lcsh:Medicine ,Gastroenterology ,chemistry.chemical_compound ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Medicine and Health Sciences ,Medicine ,lcsh:Science ,Multidisciplinary ,Anticholesteremic Agents ,Fatty liver ,Middle Aged ,Lipoproteins, LDL ,Low-density lipoprotein ,Female ,Clinical Trial Reporting ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Cardiology ,Gastroenterology and Hepatology ,Research and Analysis Methods ,digestive system ,Ezetimibe ,Internal medicine ,Humans ,Pyrroles ,Clinical Trials ,Nutrition ,business.industry ,Cholesterol ,lcsh:R ,nutritional and metabolic diseases ,Biology and Life Sciences ,medicine.disease ,Atherosclerosis ,digestive system diseases ,Health Care ,Cross-Sectional Studies ,chemistry ,Heptanoic Acids ,Metabolic Disorders ,Azetidines ,lcsh:Q ,Multi-Center Trials ,Steatohepatitis ,Clinical Medicine ,business ,Dyslipidemia ,Lipoprotein - Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risks of atherosclerotic diseases, including cardiovascular disease. However, the difference in risk between patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) has not yet been determined. Accumulating evidence has shown that high amounts of small dense low-density lipoprotein (sdLDL) are closely associated with atherosclerotic diseases. This study investigated differences in risk factors for atherosclerotic diseases, especially LDL-migration index (LDL-MI), an indicator of sdLDL, between patients with NAFL and NASH. METHODS: LDL-MI was analyzed in a primary cohort of 156 patients with NAFLD, including 53 with NAFL and 103 with NASH, and a validation cohort of 69 patients with NAFLD, including 25 with NAFL and 44 with NASH. RESULTS: In the primary cohort, NASH was associated with elevated LDL-MI (p = 0.039). Multiple regression analysis showed that NASH and the non-use of lipid lowering medications were independently correlated with higher LDL-MI in all patients with NAFLD. Among patients not on lipid lowering medications, those with NASH had significantly higher LDL-MI than those with NAFL (p = 0.001). These findings were confirmed in a validation cohort, in that LDL-MI was significantly higher in patients with NASH than with NAFL (p = 0.043). CONCLUSION: This study is the first to show that LDL-MI, an indicator of sdLDL, was higher in patients with NASH than with NAFL, suggesting that the risk of atherosclerotic diseases may be higher in NASH than NAFL. Patients with NASH should be followed closely, especially for the progression of liver pathology and atherosclerotic diseases. TRIAL REGISTRATION: UMIN000009614.
- Published
- 2014
50. Methodological reporting of randomized trials in five leading Chinese nursing journals
- Author
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Chunhu Shi, Hongli Wei, Lihuan Zhang, Kehu Yang, Jinhui Tian, Quan Wang, and Dan Ren
- Subjects
Research design ,Research Report ,Blinding ,Psychological intervention ,lcsh:Medicine ,Guidelines as Topic ,Nursing ,law.invention ,Nursing care ,Nursing Science ,Randomized controlled trial ,law ,Interim ,Medicine and Health Sciences ,Medicine ,Humans ,Clinical Trials ,lcsh:Science ,Randomized Controlled Trials as Topic ,Multidisciplinary ,business.industry ,lcsh:R ,Checklist ,Health Care ,Sample size determination ,Research Design ,lcsh:Q ,Clinical Trial Reporting ,Guideline Adherence ,Clinical Medicine ,Periodicals as Topic ,business ,Research Article - Abstract
BackgroundRandomized controlled trials (RCTs) are not always well reported, especially in terms of their methodological descriptions. This study aimed to investigate the adherence of methodological reporting complying with CONSORT and explore associated trial level variables in the Chinese nursing care field.MethodsIn June 2012, we identified RCTs published in five leading Chinese nursing journals and included trials with details of randomized methods. The quality of methodological reporting was measured through the methods section of the CONSORT checklist and the overall CONSORT methodological items score was calculated and expressed as a percentage. Meanwhile, we hypothesized that some general and methodological characteristics were associated with reporting quality and conducted a regression with these data to explore the correlation. The descriptive and regression statistics were calculated via SPSS 13.0.ResultsIn total, 680 RCTs were included. The overall CONSORT methodological items score was 6.34±0.97 (Mean ± SD). No RCT reported descriptions and changes in “trial design,” changes in “outcomes” and “implementation,” or descriptions of the similarity of interventions for “blinding.” Poor reporting was found in detailing the “settings of participants” (13.1%), “type of randomization sequence generation” (1.8%), calculation methods of “sample size” (0.4%), explanation of any interim analyses and stopping guidelines for “sample size” (0.3%), “allocation concealment mechanism” (0.3%), additional analyses in “statistical methods” (2.1%), and targeted subjects and methods of “blinding” (5.9%). More than 50% of trials described randomization sequence generation, the eligibility criteria of “participants,” “interventions,” and definitions of the “outcomes” and “statistical methods.” The regression analysis found that publication year and ITT analysis were weakly associated with CONSORT score.ConclusionsThe completeness of methodological reporting of RCTs in the Chinese nursing care field is poor, especially with regard to the reporting of trial design, changes in outcomes, sample size calculation, allocation concealment, blinding, and statistical methods.
- Published
- 2014
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