Equity issues rarely addressed in the development of COVID-19 formal recommendations and good practice statements: a cross-sectional study.

BACKGROUND AND OBJECTIVE: To identify COVID-19 actionable statements (e.g., recommendations) focused on specific disadvantaged populations in the living map of COVID-19 recommendations (eCOVIDRecMap) and describe how health equity was assessed in the development of the formal recommendations. METHODS: We employed the place of residence, race or ethnicity or culture, occupation, gender or sex, religion, education, socio-economic status, and social capital-Plus framework to identify statements focused on specific disadvantaged populations. We assessed health equity considerations in the evidence to decision frameworks (EtD) of formal recommendations for certainty of evidence and impact on health equity criteria according to the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We identified 16% (124/758) formal recommendations and 24% (186/819) good practice statements (GPS) that were focused on specific disadvantaged populations. Formal recommendations (40%, 50/124) and GPS (25%, 47/186) most frequently focused on children. Seventy-six percent (94/124) of the recommendations were accompanied with EtDs. Over half (55%, 52/94) of those considered indirectness of the evidence for disadvantaged populations. Considerations in impact on health equity criterion most frequently involved implementation of the recommendation for disadvantaged populations (17%, 16/94). CONCLUSION: Equity issues were rarely explicitly considered in the development COVID-19 formal recommendations focused on specific disadvantaged populations. Guidance is needed to support the consideration of health equity in guideline development during health emergencies.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

The 2018 Global Point Prevalence Survey of antimicrobial consumption and resistance in 47 Canadian hospitals: a cross-sectional survey.

BACKGROUND: Patient-level surveillance of antimicrobial use (AMU) in Canadian hospitals empowers the reduction of inappropriate AMU and was piloted in 2017 among 14 hospitals in Canada. We aimed to describe AMU on the basis of patient-level data in Canadian hospitals in 2018 in terms of antimicrobial prescribing prevalence and proportions, antimicrobial indications, and agent selection in medical, surgical and intensive care wards. METHODS: Canadian adult, pediatric and neonatal hospitals were invited to participate in the standardized web-based cross-sectional Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) conducted in 2018. An identified site administrator assigned all wards admitting inpatients to specific surveyors. A physician, pharmacist or nurse with infectious disease training performed the survey. The primary outcomes were point prevalence rates for AMU over the study period regarding prescriptions, indications and agent selection in medical, surgical and intensive care wards. The secondary outcomes were AMU for resistant organisms and practice appropriateness evaluated on the basis of quality indicators. Antimicrobial consumption is presented in terms of prevalence and proportions. RESULTS: Forty-seven of 118 (39.8%) hospitals participated in the survey; 9 hospitals were primary care centres, 15 were secondary care centres and 23 were tertiary or specialized care centres. Of 13 272 patients included, 33.5% (n = 4447) received a total of 6525 antimicrobials. Overall, 74.1% (4832/6525) of antimicrobials were for therapeutic use, 12.6% (n = 825) were for medical prophylaxis, 8.9% (n = 578) were for surgical prophylaxis, 2.2% (n = 143) were for other use and 2.3% (n = 147) were for unidentified reasons. A diagnosis or indication was documented in the patient's file at the initiation for 87.3% (n = 5699) of antimicrobials; 62.9% (n = 4106) of antimicrobials had a stop or review date; and 72.0% (n = 4697) of prescriptions were guided by local guidelines. INTERPRETATION: Overall, three-quarters of AMU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.

GRADE Guidelines 30: the GRADE approach to assessing the certainty of modeled evidence-An overview in the context of health decision-making.

OBJECTIVES: The objective of the study is to present the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) conceptual approach to the assessment of certainty of evidence from modeling studies (i.e., certainty associated with model outputs). STUDY DESIGN AND SETTING: Expert consultations and an international multidisciplinary workshop informed development of a conceptual approach to assessing the certainty of evidence from models within the context of systematic reviews, health technology assessments, and health care decisions. The discussions also clarified selected concepts and terminology used in the GRADE approach and by the modeling community. Feedback from experts in a broad range of modeling and health care disciplines addressed the content validity of the approach. RESULTS: Workshop participants agreed that the domains determining the certainty of evidence previously identified in the GRADE approach (risk of bias, indirectness, inconsistency, imprecision, reporting bias, magnitude of an effect, dose-response relation, and the direction of residual confounding) also apply when assessing the certainty of evidence from models. The assessment depends on the nature of model inputs and the model itself and on whether one is evaluating evidence from a single model or multiple models. We propose a framework for selecting the best available evidence from models: 1) developing de novo, a model specific to the situation of interest, 2) identifying an existing model, the outputs of which provide the highest certainty evidence for the situation of interest, either "off-the-shelf" or after adaptation, and 3) using outputs from multiple models. We also present a summary of preferred terminology to facilitate communication among modeling and health care disciplines. CONCLUSION: This conceptual GRADE approach provides a framework for using evidence from models in health decision-making and the assessment of certainty of evidence from a model or models. The GRADE Working Group and the modeling community are currently developing the detailed methods and related guidance for assessing specific domains determining the certainty of evidence from models across health care-related disciplines (e.g., therapeutic decision-making, toxicology, environmental health, and health economics).

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

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

Routine Surveillance Versus Independent Assessment by an Outcome Adjudication Committee in Assessing Patients for Sternal Surgical Site Infections After Cardiac Surgery.

Based on a cohort of 966 patients, routine surveillance data were not sufficiently accurate for use in clinical trials investigating surgical site infections. Surveillance data can only be used if adequate 90-day follow-up is provided and if cases identified by surveillance are independently reviewed by a blinded outcome adjudication committee.

Prevalence, characteristics, and publication of discontinued randomized trials.

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

Modern Management of Community-Acquired Pneumonia: Is It Cost-Effective and are Outcomes Acceptable?

Community-acquired pneumonia (CAP) is the most important cause of death from infectious diseases in the developed world and is associated with a high economic burden. Researchers have therefore sought ways to improve CAP outcomes while reducing costs. In this review, we highlight the current evidence supporting modern approaches to CAP management, including the use of severity indices to safely increase the proportion of patients treated at home, the use of procalcitonin to decrease antibiotic use, early intravenous to oral switch of antibiotic therapy, streamlining antimicrobials, and approaches to shorten antibiotic treatment duration. Although promising evidence exists for these modern strategies, there is still a considerable lack of high-quality evidence proving noninferiority of clinical outcomes and cost-effectiveness.

Outcomes of early switching from intravenous to oral antibiotics on medical wards.

OBJECTIVES: To evaluate outcomes following implementation of a checklist with criteria for switching from intravenous (iv) to oral antibiotics on unselected patients on two general medical wards. METHODS: During a 12 month intervention study, a printed checklist of criteria for switching on the third day of iv treatment was placed in the medical charts. The decision to switch was left to the discretion of the attending physician. Outcome parameters of a 4 month control phase before intervention were compared with the equivalent 4 month period during the intervention phase to control for seasonal confounding (before-after study; April to July of 2006 and 2007, respectively): 250 episodes (215 patients) during the intervention period were compared with the control group of 176 episodes (162 patients). The main outcome measure was the duration of iv therapy. Additionally, safety, adherence to the checklist, reasons against switching patients and antibiotic cost were analysed during the whole year of the intervention (n = 698 episodes). RESULTS: In 38% (246/646) of episodes of continued iv antibiotic therapy, patients met all criteria for switching to oral antibiotics on the third day, and 151/246 (61.4%) were switched. The number of days of iv antibiotic treatment were reduced by 19% (95% confidence interval 9%-29%, P = 0.001; 6.0-5.0 days in median) with no increase in complications. The main reasons against switching were persisting fever (41%, n = 187) and absence of clinical improvement (41%, n = 185). CONCLUSIONS: On general medical wards, a checklist with bedside criteria for switching to oral antibiotics can shorten the duration of iv therapy without any negative effect on treatment outcome. The criteria were successfully applied to all patients on the wards, independently of the indication (empirical or directed treatment), the type of (presumed) infection, the underlying disease or the group of antibiotics being used.