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Outputs from living evidence syntheses projects have been used widely during the pandemic by guideline developers to form evidence‐based recommendations. However, the needs of different stakeholders cannot be accommodated by solely providing pre‐defined non amendable numerical summaries. Stakeholders also need to understand the data and perform their own exploratory analyses. This requires resources, time, statistical expertise, software knowledge as well as relevant clinical expertise to avoid spurious conclusions. To assist them, we created the metaCOVID application which, based on automation processes, facilitates the fast exploration of the data and the conduct of sub‐analyses tailored to end‐users needs. metaCOVID has been created in R and is freely available as an R‐Shiny application. Based on the COVID‐NMA platform (https://covid-nma.com/) the application conducts living meta‐analyses of randomized controlled trials related to COVID‐19 treatments and vaccines for several outcomes. Several options are available for subgroup and sensitivity analyses. The results are presented in downloadable forest plots. We illustrate metaCOVID through three examples involving well‐known treatments and vaccines for COVID‐19. The application is freely available from https://covid-nma.com/metacovid/. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our work is to describe the level of evidence supporting therapeutic recommendations in United States pancreatic adenocarcinoma guidelines, and its evolution over time. We recorded the level of evidence for each therapeutic recommendation extracted from the American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. In both United States guidelines, less than 9% of therapeutic recommendations are supported by a high level of evidence. In the National Comprehensive Cancer Network guidelines, there was no significant increase in high level of evidence recommendations over time. However, guidelines authors can only deal with the available evidence to develop recommendations while highlighting the strengths and weaknesses of included studies. There is a need for a more collaborative effort in pancreatic adenocarcinoma treatment to tackle important therapeutic questions and challenge the current framework of evidence. Cancer guidelines are ideally based on high levels of evidence (LOE). We aim to evaluate the LOE supporting recommendations in United States (US) guidelines on pancreatic adenocarcinoma (PDAC) treatment and its evolution over time. We searched for current guidelines from the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) and their prior publicly available versions on societies' websites and/or MEDLINE. We recorded the LOE and class of recommendation (opinion of the writing panel) for each recommendation. We defined high LOE as: a "high" quality of evidence from the GRADE methodology (ASCO) and "Category 1" (NCCN). Our main outcome was the proportion of PDAC recommendations supported by high LOE. Proportions of high LOE recommendations were 5% (2/40) and 8% (12/153) in current ASCO and NCCN guidelines, respectively. Less than 10% of class I recommendations were based on high LOE. For NCCN guidelines, the proportion of high LOE recommendations did not improve over time and only three recommendations increased their LOE. We identified a small percentage of high LOE recommendations for PDAC treatment in US guidelines. However, guidelines authors can only deal with the available evidence. The current framework of evidence should be challenged with consideration of observational evidence. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Our aim was to evaluate the availability of results of interventional studies studying CRC. We searched the ClinicalTrials.gov registry for all interventional studies on CRC management in adults completed or terminated between 01/01/2013 and 01/01/2020. To identify results, we searched for results posted on the ClinicalTrials.gov registry and/or published in a full-text article. Our primary outcome was the proportion of CRC interventional studies with available results (i.e. posted on the ClinicalTrials.gov registry and/or published in a full-text article). Secondary outcomes were 1) median time between primary completion and earliest date of results availability, 2) the cumulative percentage of interventional studies with results available over time 3) the cumulative percentage of interventional studies with results posted on the ClinicalTrials.gov registry over time and 4) the percentage of results available in open access. We identified 763 eligible interventional studies in ClinicalTrials.gov, which included 679 198 patients. Of these, 286 (37%) trials, including 270 845 (40%) patients, did not have any results available. Median time for results availability was 32.6 months (IQ 16.1-unreached). The cumulative percentage of interventional studies with available results was 17% at 12 months, 39% at 24 months and 55% at 36 months. Results were more likely available for trials that were randomized, completed, had one trial site in the United States, and with mixed funding. The cumulative percentage of interventional studies with results posted on ClinicalTrials.gov was 2% at 12 months. Results were available in open access for 420 (420/477 = 88%) trials. Our results highlight an important waste in research for interventional studies studying CRC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is currently one of the most frequently diagnosed cancers. Our aim was to evaluate transparency and selective reporting in interventional trials studying CRC.Methods: First, we assessed indicators of transparency with completeness of reporting, according to the CONSORT statement, and data sharing. We evaluated a selection of reporting items for a sample of randomized controlled trials (RCTs) studying CRC with published full-text articles between 2021-03-22 and 2018-03-22. Selected items were issued from the previously published CONSORT based peer-review tool (COBPeer tool). Then, we evaluated selective reporting through retrospective registration and primary outcome(s) switching between registration and publication. Finally, we determined if primary outcome(s) switching favored significant outcomes.Results: We evaluated 101 RCTs with published full-text articles between 2021-03-22 and 2018-03-22. Five trials (5%) reported all selected CONSORT items completely. Seventy-four (73%), 53 (52%) and 13 (13%) trials reported the primary outcome(s), the allocation concealment process and harms completely. Twenty-five (25%) trials were willing to share data. In our sample, 49 (49%) trials were retrospectively registered and 23 (23%) trials had primary outcome(s) switching. The influence of primary outcome(s) switching could be evaluated in 16 (16/23 = 70%) trials, with 6 (6/16 = 38%) trials showing a discrepancy that favored statistically significant results.Conclusions: Our results highlight a lack of transparency as well as frequent selective reporting in interventional trials studying CRC. [ABSTRACT FROM AUTHOR]

Objectives. To assess the effects of the Nutri-Score label (relative to the Reference Intakes label or no label) on the nutritional quality of students' food purchases. Methods. A 3-arm randomized controlled trial was conducted in France in 2017; 2907 participants were randomized into 1 of the 3 study arms (Nutri-Score, Reference Intakes, no label) and invited to purchase groceries from an experimental Web-based supermarket. The main outcome was the overall nutritional quality of purchases, measured according to a modified version of the Food Standards Agency Nutrient Profiling System (FSAm-NPS/HCSP) score. Results. The mean (±SD) FSAm-NPS/HCSP score was lower in the Nutri-Score group (2.02 ±3.56) than in the Reference Intakes group (2.69 ±3.44), reflecting higher nutritional quality; however, there was no significant difference between the Nutri-Score and no-label (2.45 ±3.28) groups or between the Reference Intakes and no-label groups. Shopping cart content was lower in calories and saturated fatty acids and higher in fruits and vegetables in the Nutri-Score arm than in the other arms. Conclusions. The Nutri-Score label appeared to improve the nutritional composition of students' food purchases relative to the Reference Intakes label or no label. [ABSTRACT FROM AUTHOR]

The authors propose an "evidence ecosystem" for COVID-19–related studies that minimizes multiple low-quality reviews and helps connect evidence generation, synthesis, and decision making. [ABSTRACT FROM AUTHOR]

Publication in peer-reviewed journals is an essential step in the scientific process. However, publication is not simply the reporting of facts arising from a straightforward analysis thereof. Authors have broad latitude when writing their reports and may be tempted to consciously or unconsciously "spin" their study findings. Spin has been defined as a specific intentional or unintentional reporting that fails to faithfully reflect the nature and range of findings and that could affect the impression the results produce in readers. This article, based on a literature review, reports the various practices of spin from misreporting by "beautification" of methods to misreporting by misinterpreting the results. It provides data on the prevalence of some forms of spin in specific fields and the possible effects of some types of spin on readers' interpretation and research dissemination. We also discuss why researchers would spin their reports and possible ways to avoid it. [ABSTRACT FROM AUTHOR]

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists. Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports. [ABSTRACT FROM AUTHOR]

Background: Active discopathy is associated with a specific phenotype of chronic low back pain (LBP). Local inflammation has a role in active discopathy–associated symptoms. Objective: To assess the efficacy of a single glucocorticoid intradiscal injection (GC IDI) in patients with chronic LBP with active discopathy. Design: Prospective, parallel-group, double-blind, randomized, controlled study. (ClinicalTrials.gov: NCT00804531) Setting: 3 tertiary care centers in France. Patients: 135 patients with chronic LBP with active discopathy on magnetic resonance imaging (MRI). Intervention: A single GC IDI (25 mg prednisolone acetate) during discography (n = 67) or discography alone (n = 68). Measurements: The primary outcome was the percentage of patients with LBP intensity less than 40 on an 11-point numerical rating scale (0 [no pain] to 100 [maximum pain] in 10-point increments) in the previous 48 hours at 1 month after the intervention. The main secondary outcomes were LBP intensity and persistent active discopathy on MRI at 12 months and spine-specific limitations in activities, health-related quality of life, anxiety and depression, employment status, and use of analgesics and nonsteroidal anti-inflammatory drugs at 1 and 12 months. Results: All randomly assigned patients were included in the primary efficacy analysis. At 1 month after the intervention, the percentage of responders (LBP intensity <40) was higher in the GC IDI group (36 of 65 [55.4%]) than the control group (21 of 63 [33.3%]) (absolute risk difference, 22.1 percentage points [95% CI, 5.5 to 38.7 percentage points]; P = 0.009). The groups did not differ in LBP intensity at 12 months and in most secondary outcomes at 1 and 12 months. Limitation: Tertiary care setting. Conclusion: In chronic LBP associated with active discopathy, a single GC IDI reduces LBP at 1 month but not at 12 months. [ABSTRACT FROM AUTHOR]

Trials has 10 years of experience in providing open access publication of protocols for randomised controlled trials. In this editorial, the senior editors and editors-in-chief of Trials discuss editorial issues regarding managing trial protocol submissions, including the content and format of the protocol, timing of submission, approaches to tracking protocol amendments, and the purpose of peer reviewing a protocol submission. With the clarification and guidance provided, we hope we can make the process of publishing trial protocols more efficient and useful to trial investigators and readers. [ABSTRACT FROM AUTHOR]

Background: The CONSORT Statement is an evidence-informed guideline for reporting randomised controlled trials. A number of extensions have been developed that specify additional information to report for more complex trials. The aim of this study was to evaluate the impact of using a simple web-based tool (WebCONSORT, which incorporates a number of different CONSORT extensions) on the completeness of reporting of randomised trials published in biomedical publications. Methods: We conducted a parallel group randomised trial. Journals which endorsed the CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not actively implement it (i.e. require authors to submit a completed CONSORT checklist) were invited to participate. Authors of randomised trials were requested by the editor to use the web-based tool at the manuscript revision stage. Authors registering to use the tool were randomised (centralised computer generated) to WebCONSORT or control. In the WebCONSORT group, they had access to a tool allowing them to combine the different CONSORT extensions relevant to their trial and generate a customised checklist and flow diagram that they must submit to the editor. In the control group, authors had only access to a CONSORT flow diagram generator. Authors, journal editors, and outcome assessors were blinded to the allocation. The primary outcome was the proportion of CONSORT items (main and extensions) reported in each article post revision. Results: A total of 46 journals actively recruited authors into the trial (25 March 2013 to 22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166; control n = 158), of which 197 were reports of randomised trials (n=94; n = 103). Over a third (39%; n = 127) of registered manuscripts were excluded from the analysis, mainly because the reported study was not a randomised trial. Of those included in the analysis, the most common CONSORT extensions selected were non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n=10; n=9). In a quarter of manuscripts, authors either wrongly selected an extension or failed to select the right extension when registering their manuscript on the WebCONSORT study site. Overall, there was no important difference in the overall mean score between WebCONSORT (mean score 0.51) and control (0.47) in the proportion of CONSORT and CONSORT extension items reported pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10). Conclusions: This study failed to show a beneficial effect of a customised web-based CONSORT checklist to help authors prepare more complete trial reports. However, the exclusion of a large number of inappropriately registered manuscripts meant we had less precision than anticipated to detect a difference. Better education is needed, earlier in the publication process, for both authors and journal editorial staff on when and how to implement CONSORT and, in particular, CONSORT-related extensions. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of a computer-assisted Screening, Brief Intervention, and Referral to Treatment (SBIRT) on daily consumption of alcohol by patients with hazardous drinking disorder detected after systematic screening during their admission to an emergency department (ED).Design: Two-arm, parallel group, multicentre, randomized controlled trial with a centralised computer-generated randomization procedure.Setting: Four EDs in university hospitals located in the Paris area in France.Participants: Patients admitted in the ED for any reason, with hazardous drinking disorder detected after systematic screening (i.e., Alcohol Use Disorder Identification Test score ≥5 for women and 8 for men OR self-reported alcohol consumption by week ≥7 drinks for women and 14 for men).Interventions: The experimental intervention was computer-assisted SBIRT and the comparator was a placebo-controlled intervention (i.e., a computer-assisted education program on nutrition). Interventions were administered in the ED and followed by phone reinforcements at 1 and 3 months.Main Outcome Measure: The primary outcome was the mean number of alcohol drinks per day in the previous week, at 12 months. Results From May 2005 to February 2011, 286 patients were randomized to the computer-assisted SBIRT and 286 to the comparator intervention. The two groups did not differ in the primary outcome, with an adjusted mean difference of 0.12 (95% confidence interval, -0.88 to 1.11).Conclusions: There was no additional benefit of the computer-assisted alcohol SBIRT as compared with the computer-assisted education program on nutrition among patients with hazardous drinking disorder detected by systematic screening during their admission to an ED. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial). Design: Multicenter, two-arm, parallel-group, open-label randomized controlled trial. Setting: 11 university hospital ambulatory surgery units in Paris, France. Participants: Patients scheduled for ambulatory surgery and able to be reached by telephone. Intervention: A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone. Main Outcome Measures: Rate of cancellation on the day of surgery or the day before. Results: The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state. Conclusions: A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Incomplete reporting is a frequent waste in research. Our aim was to evaluate the impact of a writing aid tool (WAT) based on the CONSORT statement and its extension for non-pharmacologic treatments on the completeness of reporting of randomized controlled trials (RCTs).Methods: We performed a 'split-manuscript' RCT with blinded outcome assessment. Participants were masters and doctoral students in public health. They were asked to write, over a 4-hour period, the methods section of a manuscript based on a real RCT protocol, with a different protocol provided to each participant. Methods sections were divided into six different domains: 'trial design', 'randomization', 'blinding', 'participants', 'interventions', and 'outcomes'. Participants had to draft all six domains with access to the WAT for a random three of six domains. The random sequence was computer-generated and concealed. For each domain, the WAT comprised reminders of the corresponding CONSORT item(s), bullet points detailing all the key elements to be reported, and examples of good reporting. The control intervention consisted of no reminders. The primary outcome was the mean global score for completeness of reporting (scale 0-10) for all domains written with or without the WAT.Results: Forty-one participants wrote 41 different manuscripts of RCT methods sections, corresponding to 246 domains (six for each of the 41 protocols). All domains were analyzed. For the primary outcome, the mean (SD) global score for completeness of reporting was higher with than without use of the WAT: 7.1 (1.2) versus 5.0 (1.6), with a mean (95 % CI) difference 2.1 (1.5-2.7; P <0.01). Completeness of reporting was significantly higher with the WAT for all domains except for blinding and outcomes.Conclusion: Use of the WAT could improve the completeness of manuscripts reporting the results of RCTs.Trial Registration: Clinicaltrials.gov ( http://clinicaltrials.gov NCT02127567 , registration date first received April 29, 2014). [ABSTRACT FROM AUTHOR]

Background Systematic reporting of funding sources is recommended in the CONSORT Statement for abstracts. However, no specific recommendation is related to the reporting of conflicts of interest (CoI). The objective was to compare physicians' confidence in the conclusions of abstracts of randomized controlled trials of pharmaceutical treatment indexed in PubMed. Methods We planned a three-arm parallel-group randomized trial. French general practitioners (GPs) were invited to participate and were blinded to the study's aim. We used a representative sample of 75 abstracts of pharmaceutical industry-funded randomized controlled trials published in 2010 and indexed in PubMed. Each abstract was standardized and reported in three formats: 1) no mention of the funding source or CoI; 2) reporting the funding source only; and 3) reporting the funding source and CoI. GPs were randomized according to a computerized randomization on a secure Internet system at a 1:1:1 ratio to assess one abstract among the three formats. The primary outcome was GPs' confidence in the abstract conclusions (0, not at all, to 10, completely confident). The study was planned to detect a large difference with an effect size of 0.5. Results Between October 2012 and June 2013, among 605 GPs contacted, 354 were randomized, 118 for each type of abstract. The mean difference (95% confidence interval) in GPs' confidence in abstract findings was 0.2 (-0.6; 1.0) (P = 0.84) for abstracts reporting the funding source only versus no funding source or CoI; -0.4 (-1.3; 0.4) (P = 0.39) for abstracts reporting the funding source and CoI versus no funding source and CoI; and -0.6 (-1.5; 0.2) (P = 0.15) for abstracts reporting the funding source and CoI versus the funding source only. Conclusions We found no evidence of a large impact of trial report abstracts mentioning funding sources or CoI on GPs' confidence in the conclusions of the abstracts. Trial Registration ClinicalTrials.gov identifier: NCT01679873 [ABSTRACT FROM AUTHOR]

Background: Previous studies indicate that in published reports, trial results can be distorted by the use of "spin" (specific reporting strategies, intentional or unintentional, emphasizing the beneficial effect of the experimental treatment). We aimed to (1) evaluate the presence of "spin" in press releases and associated media coverage; and (2) evaluate whether findings of randomized controlled trials (RCTs) based on press releases and media coverage are misinterpreted. Methods and Findings: We systematically searched for all press releases indexed in the EurekAlert! database between December 2009 and March 2010. Of the 498 press releases retrieved and screened, we included press releases for all twoarm, parallel-group RCTs (n = 70). We obtained a copy of the scientific article to which the press release related and we systematically searched for related news items using Lexis Nexis. "Spin," defined as specific reporting strategies (intentional or unintentional) emphasizing the beneficial effect of the experimental treatment, was identified in 28 (40%) scientific article abstract conclusions and in 33 (47%) press releases. From bivariate and multivariable analysis assessing the journal type, funding source, sample size, type of treatment (drug or other), results of the primary outcomes (all nonstatistically significant versus other), author of the press release, and the presence of "spin" in the abstract conclusion, the only factor associated, with "spin" in the press release was "spin" in the article abstract conclusions (relative risk [RR] 5.6, [95% CI 2.8-11.1], p<0.001). Findings of RCTs based on press releases were overestimated for 19 (27%) reports. News items were identified for 41 RCTs; 21 (51%) were reported with "spin," mainly the same type of "spin" as those identified in the press release and article abstract conclusion. Findings of RCTs based on the news item was overestimated for ten (24%) reports. Conclusion: "Spin" was identified in about half of press releases and media coverage. In multivariable analysis, the main factor associated with "spin" in press releases was the presence of "spin" in the article abstract conclusion. [ABSTRACT FROM AUTHOR]

Background: With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs) evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life). Methods: On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1) patient- important outcomes such as clinical events, functional status, pain, or quality of life or 2) surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge. Principal Findings: We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patientimportant outcomes represented 54% (178 of 333) of all primary outcomes and 46% (286 of 623) of all secondary outcomes. Overall, 69% of trials (104 of 150) used at least one patient-important outcome as a primary outcome and 66% (99 of 150) as a secondary outcome. Finally, for 31% of trials (46 of 150), primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61) of primary outcomes, as compared with 54% (32 of 59) in malignant neoplasm and 18% (4 of 22) in diabetes mellitus trials. In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months). Conclusions: There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs. [ABSTRACT FROM AUTHOR]

Context: We aimed to develop a new tool for assessing and depicting the applicability of the results of surgical randomized controlled trials (RCTs) from the trial investigators' perspective. Methods: We identified all items related to applicability by a systematic methodological review, and then a sample of surgeons used these items in a web-based survey to evaluate the applicability of their own trial results. For each applicability item, participants had to indicate on a numerical scale that was simplified as a three-item scale: 1) items essential to consider, 2) items requiring attention, and 3) items inconsequential to the applicability of the results of their own RCT to clinical practice. For the final tool, we selected only items that were rated as being essential or requiring attention for at least 25% of the trials evaluated. We propose a specific process to construct the tool and to depict applicability in a graph. We identified all investigators of published and registered ongoing RCTs assessing surgery and invited them to participate in the web-based survey. Results: 148 surgeons assessed applicability for their own trial and participated in the process of item selection. The final tool contains 22 items (4 dedicated to patients, 5 to centers, 5 to surgeons and 8 to the intervention). We proposed a straightforward process of constructing the graphical tool: 1) a multidisciplinary team of investigators or other care providers participating in the trial could independently assess each item, 2) a consensus method could be used, and 3) the investigators could depict their assessment of the applicability of the trial results in 4 graphs related to patients, centers, surgeons and the intervention. Conclusions: This investigator-reported assessment tool could help readers define under what conditions they could reasonably apply the results of a surgical RCT to their clinical practice. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications-pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions. Methods and Findings: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based ''on-treatment'' population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. Conclusions: Elderly patients are poorly represented in RCTs of drugs they are likely to receive. [ABSTRACT FROM AUTHOR]

Background: The registration of clinical trials has been promoted to prevent publication bias and increase research transparency. Despite general agreement about the minimum amount of information needed for trial registration, we lack clear guidance on descriptions of non-pharmacologic interventions in trial registries. We aimed to evaluate the quality of registry descriptions of non-pharmacologic interventions assessed in ongoing randomized controlled trials (RCTs) of patient education. Methods: On 6 May 2009, we searched for all ongoing RCTs registered in the 10 trial registries accessible through the World Health Organization International Clinical Trials Registry Platform. We included trials evaluating an educational intervention (that is, designed to teach or train patients about their own health) and dedicated to participants, their family members or home caregivers. We used a standardized data extraction form to collect data related to the description of the experimental intervention, the centers, and the caregivers. Results: We selected 268 of 642 potentially eligible studies and appraised a random sample of 150 records. All selected trials were registered in 4 registers, mainly ClinicalTrials.gov (61%). The median [interquartile range] target sample size was 205 [100 to 400] patients. The comparator was mainly usual care (47%) or active treatment (47%). A minority of records (17%, 95% CI 11 to 23%) reported an overall adequate description of the intervention (that is, description that reported the content, mode of delivery, number, frequency, duration of sessions and overall duration of the intervention). Further, for most reports (59%), important information about the content of the intervention was missing. The description of the mode of delivery of the intervention was reported for 52% of studies, the number of sessions for 74%, the frequency of sessions for 58%, the duration of each session for 45% and the overall duration for 63%. Information about the caregivers was missing for 70% of trials. Most trials (73% )took place in the United States or United Kingdom, 64% involved only one centre, and participating centers were mainly tertiary-care, academic or university hospitals (51%). Conclusions: Educational interventions assessed in ongoing RCTs of educational interventions are poorly described in trial registries. The lack of adequate description raises doubts about the ability of trial registration to help patients and researchers know about the treatment evaluated in trials of education. [ABSTRACT FROM AUTHOR]

Background: A recent study suggested that results of single-center trials are frequently contradicted when similar trials are performed in multicenter settings. Purpose: To perform a meta-epidemiologic study to evaluate whether estimates of treatment effect differ between single-center and multicenter randomized, controlled trials (RCTs). Data Sources: MEDLINE was searched via PubMed for metaanalyses of RCTs with binary outcomes that were publishedbetween August 2008 and January 2009 and in the first 6 months of 2010 in the 10 leading journals of each medical specialty. One issue of the Cochrane Database of Systematic Reviews was also searched. Study Selection: All individual RCTs included in the meta-analyses were selected. Data Extraction: Data were extracted and their quality was assessed by use of the risk of bias tool of the Cochrane Collaboration. Data Synthesis: The primary outcome was the ratio of odds ratios (ROR), used to quantify the difference in estimated intervention effect between single-center and multicenter RCTs. An ROR less than 1 would indicate larger estimates of the intervention effect in single-center trials. Sensitivity analyses were performed with adjustment for sample size, risk of bias within RCTs, and variance of the log odds ratio to take publication bias into account. Forty-eightmeta-analyses were selected, including 421 RCTs (223 were singlecenter and 198 were multicenter). Single-center RCTs showed a larger intervention effect than did multicenter RCTs (combined ROR, 0.73 [95% CI, 0.64 to 0.83]), with low heterogeneity across individual meta-analyses (I2 = 12.0%; P = 0.24). Adjustment for sample size yielded consistent results (ROR, 0.85 [CI, 0.74 to 0.97]), as did adjustment for risk of bias within RCTs, such asallocation concealment (ROR, 0.76 [CI, 0.67 to 0.86]), and variance of log odds ratio (ROR, 0.83 [CI, 0.72 to 0.96]). Limitation: Despite sensitivity analyses, meta-confounding cannot be fully excluded. Conclusion: Single-center RCTs showed larger treatment effects than did multicenter RCTs, a finding that was consistent in all sensitivity analyses. These results suggest that this item should be considered when the results of RCTs and meta-analyses are interpreted. [ABSTRACT FROM AUTHOR]

Purpose: To identify the views of patients and care providers regarding the management of knee osteoarthritis (OA) and to reveal potential obstacles to improving health care strategies. Methods: We performed a qualitative study based on semi-structured interviews of a stratified sample of 81 patients (59 women) and 29 practitioners (8 women, 11 general practitioners [GPs], 6 rheumatologists, 4 orthopedic surgeons, and 8 [4 GPs] delivering alternative medicine). Results: Two main domains of patient views were identified: one about the patient-physician relationship and the other about treatments. Patients feel that their complaints are not taken seriously. They also feel that practitioners act as technicians, paying more attention to the knee than to the individual, and they consider that not enough time is spent on information and counseling. They have negative perceptions of drugs and a feeling of medical uncertainty about OA, which leads to less compliance with treatment and a switch to alternative medicine. Patients believe that knee OA is an inevitable illness associated with age, that not much can be done to modify its evolution, that treatments are of little help, and that practitioners have not much to propose. They express unrealistic fears about the impact of knee OA on daily and social life. Practitioners' views differ from those of patients. Physicians emphasize the difficulty in elaborating treatment strategies and the need for a tool to help in treatment choice. Conclusions: This qualitative study suggests several ways to improve the patient-practitioner relationship and the efficacy of treatment strategies, by increasing their acceptability and compliance. Providing adapted and formalized information to patients, adopting more global assessment and therapeutic approaches, and dealing more accurately with patients' paradoxal representation of drug therapy are main factors of improvement that should be addressed. [ABSTRACT FROM AUTHOR]

Background: The challenge for evidence-based healthcare is to reduce mortality and the burden of diseases. This study aimed to compare where research is conducted to where research is needed for 2 public health priorities: tobacco consumption and HIV infection. Methods: We identified randomized controlled trials (RCTs) included in Cochrane systematic reviews published between 1997 and 2007 and registered ongoing RCTs identified in January 2009 through the World Health Organization's International Clinical Trials Registry Platform (WHO-ICTRP) evaluating interventions aimed at reducing or stopping tobacco use and treating or preventing HIV infection. We used the WHO and World Bank reports to classify the countries by income level, as well as map the global burden of disease and mortality attributable to tobacco use and HIV infection to the countries where the trials performed. Results: We evaluated 740 RCTs included in systematic reviews and 346 ongoing RCTs. For tobacco use, 4% of RCTs included in systematic reviews and 2% of ongoing trials were performed in low- and middle-income countries, even though these countries represented 70% of the mortality related to tobacco use. For HIV infection, 31% of RCTs included in systematic reviews and 33% of ongoing trials were performed in low- and middle-income countries, even though these countries represented 99% of the mortality related to HIV infection. Conclusions: Our results highlight an important underrepresentation of low- and middle-income countries in currently available evidence (RCTs included in systematic reviews) and awaiting evidence (registered ongoing RCTs) for reducing or stopping tobacco use and treating or preventing HIV infection. [ABSTRACT FROM AUTHOR]

The article discusses a study which identified the nature and frequency of distorted presentation in published reports of randomized controlled trials (RCTs) with statistically nonsignificant results for primary outcomes. The researchers analyzed data from MEDLINE through PubMed using the Cochrane Highly Sensitive Search Strategy to determine RCTs published in December 2006. It was concluded by the researchers that the reporting and interpretation of findings was inconsistent with the results in the representative sample of RCTs.

Background: The purpose of the study was to evaluate systematic reviews of research into two public health priorities, tobacco consumption and HIV infection, in terms of the reporting of data related to the applicability of trial results (i.e., whether the results of a trial can be reasonably applied or generalized to a definable group of patients in a particular setting in routine practice, also called external validity or generalisability). Methods: All systematic reviews of interventions aimed at reducing or stopping tobacco use and treating or preventing HIV infection published in the Cochrane database of systematic reviews and in journals indexed in MEDLINE between January 1997 and December 2007 were selected. We used a standardized data abstraction form to extract data related to applicability in terms of the context of the trial, (country, centres, settings), participants (recruitment, inclusion and exclusion criteria, baseline characteristics of participants such as age, sex, ethnicity, coexisting diseases or co-morbidities, and socioeconomic status), treatment (duration, intensity/dose of treatment, timing and delivery format), and the outcomes assessment from selected reviews. Results: A total of 98 systematic reviews were selected (57 Cochrane reviews and 41 non-Cochrane reviews); 49 evaluated interventions aimed at reducing or stopping tobacco use and 49 treating or preventing HIV infection. The setting of the individual studies was reported in 45 (46%) of the systematic reviews, the number of centres in 21 (21%), and the country where the trial took place in 62 (63%). Inclusion and exclusion criteria of the included studies were reported in 16 (16%) and 13 (13%) of the reviews, respectively. Baseline characteristics of participants in the included studies were described in 59 (60%) of the reviews. These characteristics concerned age in about half of the reviews, sex in 46 (47%), and ethnicity in 9 (9%). Applicability of results was discussed in 13 (13%) of the systematic reviews. The reporting was better in systematic reviews by the Cochrane Collaboration than by non-Cochrane groups. Conclusions: Our study highlighted the lack of consideration of applicability of results in systematic reviews of research into 2 public health priorities: tobacco consumption and HIV infection. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the reporting of safety results in randomized controlled trials (RCTs). It notes that a review of reports published in six medical journals is made. Methods include searching the MEDLINE database for published reports from January 1, 2006 to January 1, 2007 wherein data were extracted through standardized form. The study found important heterogeneity and variability in the reports for harm-related results of RCTs.

The article discusses a study which compared the registered and published primary outcome of randomized controlled trials (RCT). Study authors reviewed MEDLINE via PubMed to search for RCT reports in cardiology, rheumatology and gastroenterology that were indexed in 2008 in 10 general medical and specialty journals. They found that 45.5 percent of the trials were adequately registered, while 27.6 percent published reports lack trial registration. They also noted that 31 percent of trials with adequate registration showed some discrepancies between the outcomes registered and outcomes published. Study authors concluded that selective outcome reporting is prevalent in RCT.

Abstract: Objectives: Adjudication committees (ACs) are recommended in randomized controlled trials (RCTs) to standardize the assessment of events. We aimed to assess the reporting and functioning of ACs (synonyms: clinical event committees, endpoint committees) in clinical trials. Study Design and Setting: We searched five high-impact-factor medical journals for reports of RCTs with clinical event endpoints published between January 1, 2004 and December 31, 2005. Results: ACs were reported in 33.4% of the 314 reports of RCTs. ACs were reported in 29.6% of trials with low risk of misclassification (i.e., “hard” main outcome), in 47.5% of trials with medium risk of misclassification (i.e., subjective main outcome and intervention delivered in a blinded fashion) and in 31% of trials with high risk of misclassification (i.e., subjective main outcome without intervention delivered in a blinded fashion). Selected cases to be adjudicated consisted largely of events identified by site investigators (93.3%). Data provided to the AC were reported for 47.4% of ACs. Conclusion: Reporting of ACs is not fitted to the risk of biased misclassification. Important aspects of the functioning of ACs are insufficiently reported or raise methodological issues. We propose some recommendations for planning and reporting ACs in clinical trials. [Copyright &y& Elsevier]

The article presents a study which examined data reporting related to external validity from randomized controlled trials (RCTs) assessing pharmacologic and nonpharmacologic treatment for hip and knee osteoarthritis (OA). Discussions of the methods used as well as the results of the said study are offered. The study found that there is low reporting of data related to external validity in reports of RCTs assessing pharmacologic and nonpharmacologic treatments for hip and knee OA.

Background: The aim of this study was to assess the reporting of harm in randomized controlled trials evaluating stents for percutaneous coronary intervention. Methods: The study design was a methodological systematic review of randomized controlled trials. The data sources were MEDLINE and the Cochrane Central Register of Controlled Trials. All reports of randomized controlled trials assessing stent treatment for coronary disease published between January 1, 2003, and September 30, 2008 were selected. A standardized abstraction form was used to extract data. Results: 132 articles were analyzed. Major cardiac adverse events (death, cardiac death, myocardial infarction or stroke) were reported as primary or secondary outcomes in 107 reports (81%). However, 19% of the articles contained no data on cardiac events. The mode of data collection of adverse events was given in 29 reports (22%) and a definition of expected adverse events was provided in 47 (36%). The length of follow-up was reported in 95 reports (72%). Assessment of adverse events by an adjudication committee was described in 46 reports (35%), and adverse events were described as being followed up for 6 months in 24% of reports (n = 32), between 7 to 12 months in 42% (n = 55) and for more than 1 year in 4% (n = 5). In 115 reports (87%), numerical data on the nature of the adverse events were reported per treatment arm. Procedural complications were described in 30 articles (23%). The causality of adverse events was reported in only 4 articles. Conclusion: Several harm-related data were not adequately accounted for in articles of randomized controlled trials assessing stents for percutaneous coronary intervention. Trials Registration: Trials manuscript: 5534201182098351 (T80802P) [ABSTRACT FROM AUTHOR]

Background: Knee arthroplasty is increasing exponentially due to the aging of the population and to the broadening of indications. We aimed to compare physical disability and its evolution over two years in people with knee arthroplasty to that in the general population. A secondary objective was to compare the level of disabilities of people with knee to people with hip arthroplasty. Methodology/Principal Findings: 16,945 people representative of the French population were selected in 1999 from the French census and interviewed about their level of disability. This sample included 815 people with lower limb arthroplasty. In 2001, 608 of them were re-interviewed, among whom 134 had knee arthroplasty. Among the other participants reinterviewed, we identified 68 who had undergone knee arthroplasty and 145 hip arthroplasty within the last two years (recent arthroplasty). People with knee arthroplasty reported significantly greater difficulties than the general population with bending forward (odds ratio [OR] = 4.7; 95% confidence interval [CI]: 1.7, 12.6), walking more than 500 meters (OR = 6.0; 95% CI: 1.5, 24.7) and carrying 5 kg kilograms for 10 meters (OR = 4.6; 95% CI: 1.3, 16.4). However, the two years evolution in disability was similar to that in the general population for most activities. The level of mobility was similar between people with recent knee arthroplasty and those with recent hip arthroplasty. Nevertheless, people with recent knee arthroplasty reported a lower level of disability than the other group for washing and bending forward (OR = 0.3; 95% CI: 0.1, 0.6 and OR = 0.4; 95% CI: 0.1, 0.9, respectively). Conclusions/Significance: People with knee arthroplasty reported a higher risk of disability than the general population for common activities of daily living but a similar evolution. There was no relevant difference between recent knee and hip arthroplasties for mobility. [ABSTRACT FROM AUTHOR]

Background: The conduct of randomized, controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports. Objective: To develop an extension of the CONSORT (Consolidated Standards of Reporting Trials) Statement for trials of nonpharmacologic treatments. Design: A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses randomized trials of nonpharmacologic treatments. To prepare for the meeting, a survey was conducted to identify the specific issues for discussion. Setting: Consensus meeting in Paris, France. Participants: A total of 33 experts attended the meeting. The experts were methodologists (n = 17); surgeons (n = 6); editors (n = 5); and clinicians involved in rehabilitation (n = 1), psychotherapy (n = 2), education (n = 1), and implantable devices (n = 1). Measurements: Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments. During a 3-day consensus meeting, all items were discussed and additional methodological issues related to nonpharmacologic research were identified. Results: The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials: item 1 (title and abstract), item 3 participants), item 4 (interventions), item 7 (sample size), item 8 (randomization), item 11 (blinding), item 12 (statistical methods), item 13 (participant flow), item 15 (baseline data), item 20 (discussion: interpretation), and item 21 (generalizability). In addition, the meeting participants added 1 item related to implementation of the intervention. Limitation: Evidence was not always available to support the inclusion of each checklist item. Conclusion: The methods and processes used to develop this extension could be used for other reporting guidelines. The use of this extension to the CONSORT Statement should improve the quality of reporting randomized, controlled trials assessing nonpharmacologic treatments. [ABSTRACT FROM AUTHOR]

Adequate reporting of randomized, controlled trials (RCTs) is necessary to allow accurate critical appraisal of the validity and applicability of the results. The CONSORT (Consolidated Standards of Reporting Trials) Statement, a 22-item checklist and flow diagram, is intended to address this problem by improving the reporting of RCTs. However, some specific issues that apply to trials of nonpharmacologic treatments (for example, surgery, technical interventions, devices, rehabilitation, psychotherapy, and behavioral intervention) are not specifically addressed in the CONSORT Statement. Furthermore, considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement. Therefore, the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments. A consensus meeting of 33 experts was organized in Paris, France, in February 2006, to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments. The participants extended 11 items from the CONSORT Statement, added 1 item, and developed a modified flow diagram. To allow adequate understanding and implementation of the CONSORT extension, the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting. This extension, in conjunction with the main CONSORT Statement and other CONSORT extensions, should help to improve the reporting of RCTs performed in this field. [ABSTRACT FROM AUTHOR]

Background: The aim of this trial was to compare the effectiveness of two generations of progressive lenses for presbyopia. Methods: A multicenter cross-over randomized controlled trial performed in a primary care setting (5 optical dispensaries) was planned. Two categories of progressive lenses were compared: 1) a new-generation lens (i.e., VARILUX PANAMIC ORMA CRIZAL), which is expensive but a supposed improvement in comfort, and 2) an older-generation lens (i.e., VARILUX CONFORT ORMA CRIZAL), which is less expensive and is considered the reference lens. Patients were randomized to wear one generation of progressive lens for 4 weeks, then cross over to wear the other lens for 4 weeks, without knowing the sequence of lenses. Inclusion criteria were 1) age 43-60 years; 2) outpatients already wearing progressive lenses and referred to an optician ophthalmologist for optical correction prescription within the last 6 months; 3) receiving a correction of ≤3 dioptres in cases of associated myopia, hyperopia or astigmatism; 4) understanding and speaking French and able to answer a questionnaire; and 5) giving written consent to participate in the study. The primary outcome was patient preference for one progressive lens at week 8. Secondary outcomes were subjective measures of bifocal visual performance, including a) near visual acuity, b) visual field, c) kinetic visual skills, d) visual adaptability, e) visual comfort, and f) rapidity of adaptation. Results: 127 patients were randomized to one of the lens groups. Two patients withdrew prematurely; 98.4% and 97.6% patients who wore the new versus older lenses, respectively, wore their progressive lenses every day during the 4-week period 1 and period 2. The number of participants in each of 5 centres varied from 16 (12.6%) to 35 (27.6%). 57.9% patients preferred the new-generation lenses, 36.5% the older-generation lenses, and 5.6% had no preference (p = 0.01). The two groups did not differ in any of the measures of bifocal visual performance except near visual acuity. Conclusion: Patients with presbyopia had slightly higher preference for the new-generation than older-generation lens, with no difference in lens groups for most of the visual outcomes assessed. Trial Registration: ClinicalTrials.gov NCT00635115 [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (-5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. [ABSTRACT FROM AUTHOR]

Background Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on ‘creative’ (nonstandard) methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. Methods and Findings We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs) assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment), or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography), or adjudications of clinical events. Conclusions This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials. [ABSTRACT FROM AUTHOR]

Background Blinding is a cornerstone of therapeutic evaluation because lack of blinding can bias treatment effect estimates. An inventory of the blinding methods would help trialists conduct high-quality clinical trials and readers appraise the quality of results of published trials. We aimed to systematically classify and describe methods to establish and maintain blinding of patients and health care providers and methods to obtain blinding of outcome assessors in randomized controlled trials of pharmacologic treatments. Methods and Findings We undertook a systematic review of all reports of randomized controlled trials assessing pharmacologic treatments with blinding published in 2004 in high impact-factor journals from Medline and the Cochrane Methodology Register. We used a standardized data collection form to extract data. The blinding methods were classified according to whether they primarily (1) established blinding of patients or health care providers, (2) maintained the blinding of patients or health care providers, and (3) obtained blinding of assessors of the main outcomes. We identified 819 articles, with 472 (58%) describing the method of blinding. Methods to establish blinding of patients and/or health care providers concerned mainly treatments provided in identical form, specific methods to mask some characteristics of the treatments (e.g., added flavor or opaque coverage), or use of double dummy procedures or simulation of an injection. Methods to avoid unblinding of patients and/or health care providers involved use of active placebo, centralized assessment of side effects, patients informed only in part about the potential side effects of each treatment, centralized adapted dosage, or provision of sham results of complementary investigations. The methods reported for blinding outcome assessors mainly relied on a centralized assessment of complementary investigations, clinical examination (i.e., use of video, audiotape, or photography), or adjudication of clinical events. Conclusions This review classifies blinding methods and provides a detailed description of methods that could help trialists overcome some barriers to blinding in clinical trials and readers interpret the quality of pharmalogic trials. [ABSTRACT FROM AUTHOR]

Abstract: Background and Objective: To develop a checklist of items measuring the quality of reports of randomized clinical trials (RCTs) assessing nonpharmacological treatments (NPTs). Study Design and Setting: The Delphi consensus method was used to select and reduce the number of items in the checklist. A total of 154 individuals were invited to participate: epidemiologists and statisticians involved in the field of methodology of RCTs (n = 55), members of the Cochrane Collaboration (n = 41), and clinicians involved in planning NPT clinical trials (n = 58). Participants ranked on a 10-point Likert scale whether an item should be included in the checklist. Results: Fifty-five experts (36%) participated in the survey. They were experienced in systematic reviews (68% were involved in the Cochrane Collaboration) and in planning RCTs (76%). Three rounds of the Delphi method were conducted to achieve consensus. The final checklist contains 10 items and 5 subitems, with items related to the standardization of the intervention, care provider influence, and additional measures to minimize the potential bias from lack of blinding of participants, care providers, and outcome assessors. Conclusions: This tool can be used to critically appraise the medical literature, design NPT studies, and assess the quality of trial reports included in systematic reviews. [Copyright &y& Elsevier]

Abstract: Background and Objective: To determine methods to assess the success of blinding in randomized controlled trials (RCTs). Methods: We searched MEDLINE, the Cochrane Controlled Trials Register, and the Cochrane Method Register and performed a manual search to target studies that attempt to assess blinding and describe the methods used in those studies. Results: A total of 90 reports were selected. Reports assessed the success of blinding participants (n = 58), care providers (n = 36), and outcome assessors (n = 15). Of the 58 reports assessing the success of blinding participants, 54 (93%) reported asking participants to guess their treatment assignment. There was no consistency in timing of assessment (e.g., once at the end of the trial, 57%, or several times during the trial, 26%) or modalities of answering (e.g., “do not know” answers, 43%, or participants forced to guess, 31%). A statistical analysis was performed in 57% of reports. The statistical analysis mainly compared the proportion of correct guesses to those produced by chance (32%) or checked for a relation between participants'' guesses and treatment assignment (23%). Conclusions: Methods of assessing the success of blinding, analysis and reporting the results were inconsistent and questionable. [Copyright &y& Elsevier]

Background: Reports of clinical trials usually emphasize benefits and give less attention to harms. Purpose: To compare the reporting of harm in trials of pharmacologic and nonpharmacologic treatment. Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials. Study Selection: Reports of randomized, controlled trials assessing treatment of rheumatic disease that were published between January 1999 and January 2005. Data Extraction: A standardized abstraction form was used to extract data. Data Synthesis: 193 articles were analyzed. After adjustment for medical area, sample size, funding source, and multicenter trials, data on harm were more often described in pharmacologic treatment reports than in non pharmacologic treatment reports in reporting adverse events (odds ratio, 5.2 [95% CI, 2.1 to 12.9]), reporting withdrawals due to adverse events (odds ratio, 4.6 [CI, 2.0 to 10.9]), reporting severity (odds ratio, 3.7 [CI, 1.5 to 9.1]), and allocating space for describing harm (odds ratio, 1.6 [CI, 1.2 to 2.3]). Limitations: Extrapolating results to trials in areas other than rheumatic disease is questionable. Conclusions: The lack of reporting harm in trials assessing nonpharmacologic treatment in rheumatic disease is an important barrier to evaluating the benefit-harm balance of nonpharmacologic treatments. [ABSTRACT FROM AUTHOR]

Objective: To compare the feasibility of blinding and the perceived risk of unblinding in trials evaluating pharmacologic (PT) and nonpharmacologic treatments (NPT) of hip or knee osteoarthritis.Study design and setting: Two independent reviewers assessed the feasibility of blinding patients, care providers, and outcome assessors, the perceived risk of unblinding, and whether blinding was reported in 110 reports of randomized controlled trials (RCTs) evaluating PT and NPT in patients with hip or knee osteoarthritis.Results: Blinding was considered to be possible less often in NPT trials than in PT trials for patients (42 vs. 96%; P < .001), care providers (12 vs. 96%; P < .001), and outcome assessors (34 vs. 98%; P < .001). When blinding was judged feasible, the perceived risk of unblinding was more often considered moderate or important in NPT than PT trials for patients (35 vs. 14%, P = .02) and outcome assessors (44 vs. 10%, P = .0004). When blinding was judged feasible, it was reported less often in NPT reports than in PT reports for patients (46 vs. 98%, P < .001), care providers (43 vs. 83%, P = .03), and outcome assessors (72 vs. 98%, P = .0006).Conclusion: Blinding appears to be more difficult to achieve and unblinding may occur more often in NPT than PT trials. [Copyright &y& Elsevier]

Context: Randomized controlled trials have been developed essentially in the context of pharmacological treatments (ie, oral drugs; intra-articular injection; and topical, intramuscular, and intravenous treatments), but assessment of the effectiveness of nonpharmacological treatments (ie, surgery, arthroscopy, joint lavage, rehabilitation, acupuncture, and education) presents specific issues.Objectives: To compare the quality of articles of nonpharmacological and pharmacological treatments of hip and knee osteoarthritis and to identify specific methodological issues related to assessment of nonpharmacological treatments.Design and Setting: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for articles of randomized controlled trials published between January 1, 1992, and February 28, 2002, in 28 general medical and specialty journals with high impact factors and assessing nonpharmacological and pharmacological treatments in patients with hip or knee osteoarthritis.Main Outcome Measures: The quality of the methods reported in the selected articles was assessed by 2 independent reviewers using the Jadad scale, the Delphi list, and guidelines found in the Users' Guides to the Medical Literature. Investigators also used a checklist of items developed by the authors to analyze study characteristics.Results: A total of 110 articles were included in the analysis; 50 (45.5%) assessed nonpharmacological treatments and 60 (54.5%) assessed pharmacological treatments. Reports of nonpharmacological treatments had a lower global quality score than did reports of pharmacological treatments as measured by the Jadad scale (mean [SD] score, 1.4 [1.3] vs 3.0 [1.3]) and the Delphi list (mean [SD] score, 5.2 [1.5] vs 7.5 [1.1]). Lack of reporting adequate random sequence generation and intention-to-treat analyses were found in both nonpharmacological and pharmacological articles. Nonpharmacological treatments were less often compared with a placebo than were pharmacological treatments (28.0% of articles vs 71.7%). Compared with pharmacological articles, nonpharmacological articles less often described blinding of patients (26.0% vs 96.7%), care providers (6.0% vs 81.7%), and outcome assessors (68.0% vs 98.3%). Care providers' skill levels could influence treatment effect in 84.0% of nonpharmacological articles vs 23.3% of pharmacological articles.Conclusions: In this analysis of reports of hip and knee osteoarthritis therapy, nonpharmacological articles scored lower than pharmacological articles in terms of quality. Assessments of nonpharmacological treatments must take into consideration additional methodological issues. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Methodological limitations affect a significant number of oncology and haematology trials, raising concerns about the applicability of their results. For example, a suboptimal control arm or limited access to best care upon progression may skew the trial results toward a benefit in the experimental arm. Beyond the fact that such limitations do not prevent drugs reaching the market, other assessment tools, such as those developed by professional societies—ESMO‐MCBS and ASCO Value Framework—do not integrate these important shortcomings.We propose creating a novel framework with the scope of assessing registration cancer clinical trials in haematology and oncology (randomized or single arm)—that is trials leading to a marketing authorization. The main steps of the methods are (1) assembling a scientific board; (2) defining the scope, goal and methods through pre‐specified, pre‐registered and protocolized methodology; (3) preregistration of the protocol; (4) conducting a scoping review of limitations and biases affecting oncology trials and assessing existing scores or methods; (5) developing a list of features to be included and assessed within the framework; (6) assessing each feature through a questionnaire sent to highly cited haematologists and oncologists involved in clinical trials; and (7) finalizing the first version of framework.Not applicable.Our proposal emerged in response to the lack of consideration for key limitations in current trial assessments. The goal is to create a framework specifically designed to assess single trials leading to marketing authorization in the field of oncology and haematogy. [ABSTRACT FROM AUTHOR]

Comprehensive systematic reviews require many hours of manual review by researchers. This study retrospectively investigates the use of GPT-3.5 Turbo to screen titles and abstracts as a second reviewer or to prescreen citations for human review. The authors describe the process of prompt development as well as the performance of GPT-3.5 Turbo in terms of citations missed and the added number of citations for reconciliation for 5 different already completed reviews. Background: Systematic reviews are performed manually despite the exponential growth of scientific literature. Objective: To investigate the sensitivity and specificity of GPT-3.5 Turbo, from OpenAI, as a single reviewer, for title and abstract screening in systematic reviews. Design: Diagnostic test accuracy study. Setting: Unannotated bibliographic databases from 5 systematic reviews representing 22 665 citations. Participants: None. Measurements: A generic prompt framework to instruct GPT to perform title and abstract screening was designed. The output of the model was compared with decisions from authors under 2 rules. The first rule balanced sensitivity and specificity, for example, to act as a second reviewer. The second rule optimized sensitivity, for example, to reduce the number of citations to be manually screened. Results: Under the balanced rule, sensitivities ranged from 81.1% to 96.5% and specificities ranged from 25.8% to 80.4%. Across all reviews, GPT identified 7 of 708 citations (1%) missed by humans that should have been included after full-text screening at the cost of 10 279 of 22 665 false-positive recommendations (45.3%) that would require reconciliation during the screening process. Under the sensitive rule, sensitivities ranged from 94.6% to 99.8% and specificities ranged from 2.2% to 46.6%. Limiting manual screening to citations not ruled out by GPT could reduce the number of citations to screen from 127 of 6334 (2%) to 1851 of 4077 (45.4%), at the cost of missing from 0 to 1 of 26 citations (3.8%) at the full-text level. Limitations: Time needed to fine-tune prompt. Retrospective nature of the study, convenient sample of 5 systematic reviews, and GPT performance sensitive to prompt development and time. Conclusion: The GPT-3.5 Turbo model may be used as a second reviewer for title and abstract screening, at the cost of additional work to reconcile added false positives. It also showed potential to reduce the number of citations before screening by humans, at the cost of missing some citations at the full-text level. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Background: The increasing use of preprints to disseminate evidence on the effect of interventions for the coronavirus disease 2019 (COVID-19) can lead to multiple evidence sources for a single study, which may differ in the reported evidence. We aim to describe the proportion of evidence on the effect of interventions for COVID-19 from preprints and journal articles and map changes in evidence between and within different sources reporting on the same study.Methods: Meta-research study. We screened the Cochrane living systematic review and network meta-analysis (COVID-NMA) database to identify all preprints and journal articles on all studies assessing interventions for COVID-19 published up to 15 August 2020. We compared all evidence sources (i.e., preprint and associated journal article) and the first and latest versions of preprints for each study to identify changes in two evidence components: study results (e.g., numeric change in hazard ratio, odds ratio, event rate, or change in p value > or < 0.05 in any outcome) and abstract conclusions (classified as positive, negative or neutral regarding the intervention effect, and as reporting uncertainty in the findings or not). Changes in study results were further classified as important changes if they (1) represented a change in any effect estimate by ≥ 10% and/or (2) led to a change in the p value crossing the threshold of 0.05.Results: We identified 556 studies. In total, 338 (61%) had been reported in a preprint: 66 (20%) of these had an associated journal article (median time to publication 76 days [interquartile range (IQR) 55-106]) and 91 (27%) had > 1 preprint version. A total of 139 studies (25% of the overall sample) were reported in multiple evidence sources or versions of the same source: for 63 (45%), there was a change in at least one evidence component between or within sources (42 [30%] had a change in study results, and in 29 [21%] the change was classified as important; 33 [24%] had a change in the abstract conclusion). For studies with both a preprint and an article, a median of 29% (IQR 14-50) of total citations were attributed to the preprint instead of the article.Conclusions: Results on the effect of interventions for COVID-19 are often reported in multiple evidence sources or source versions for a single study. Evidence is not stable between and within evidence sources. Real-time linkage of all sources per study could help to keep systematic reviews up-to-date. [ABSTRACT FROM AUTHOR]

Background: This study examined the synthesis methods used in meta-analyses pooling data from observational studies (OSs) and randomised controlled trials (RCTs) from various medical disciplines. Methods: We searched Medline via PubMed to identify reports of systematic reviews of interventions, including and pooling data from RCTs and OSs published in 110 high-impact factor general and specialised journals between 2015 and 2019. Screening and data extraction were performed in duplicate. To describe the synthesis methods used in the meta-analyses, we considered the first meta-analysis presented in each article. Results: Overall, 132 reports were identified with a median number of included studies of 14 [9–26]. The median number of OSs was 6.5 [3–12] and that of RCTs was 3 [1–6]. The effect estimates recorded from OSs (i.e., adjusted or unadjusted) were not specified in 82% (n = 108) of the meta-analyses. An inverse-variance common-effect model was used in 2% (n = 3) of the meta-analyses, a random-effects model was used in 55% (n = 73), and both models were used in 40% (n = 53). A Poisson regression model was used in 1 meta-analysis, and 2 meta-analyses did not report the model they used. The mean total weight of OSs in the studied meta-analyses was 57.3% (standard deviation, ± 30.3%). Only 44 (33%) meta-analyses reported results stratified by study design. Of them, the results between OSs and RCTs had a consistent direction of effect in 70% (n = 31). Study design was explored as a potential source of heterogeneity in 79% of the meta-analyses, and confounding factors were investigated in only 10% (n = 13). Publication bias was assessed in 70% (n = 92) of the meta-analyses. Tau-square was reported in 32 meta-analyses with a median of 0.07 [0–0.30]. Conclusion: The inclusion of OSs in a meta-analysis on interventions could provide useful information. However, considerations of several methodological and conceptual aspects of OSs, that are required to avoid misleading findings, were often absent or insufficiently reported in our sample. [ABSTRACT FROM AUTHOR]