Too Much Dentistry.

This Viewpoint explores whether all dental procedures are clinically necessary given their expense and the disparate access to treatment among some socioeconomic and racial and ethnic groups.

High certainty evidence is stable and trustworthy, whereas evidence of moderate or lower certainty may be equally prone to being unstable.

OBJECTIVES: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available. METHODS: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance. RESULTS: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations). CONCLUSION: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated.

Defining success in adult obesity management: A systematic review and framework synthesis of clinical practice guidelines.

Obesity is a chronic and complex disease affecting millions of people worldwide. Currently, there is no standard definition of success for the management of obesity. We set out to complete a synthesis of clinical practice guidelines for obesity management for adult populations, aiming to provide both a quantitative descriptive and qualitative analysis of definitions of success in clinical practice guidelines. An electronic search retrieved 4477 references. Sixteen clinical practice guidelines were included after screening and full-text review. We coded definitions of success 147 times across the included guidelines. No standard or explicit definition of success was identified in the guidelines but rather success was implicitly defined. We developed three themes describing how success was defined in the clinical practice guidelines: Knowledge-based decision making; management of expectations; and the perception of control. The review reinforced that success is an inherently subjective and complex concept. Defining success is limited by existing studies that focus on weight loss and would benefit from additional research on different outcomes. Equally, the relationship between people living with obesity and their clinicians should be further explored to understand how defining success is controlled, discussed and framed in a clinical setting.

Clinical trials of pharmacological interventions for SARS-CoV-2 published in leading medical journals report adherence but not how it was assessed.

AIMS: Adherence to pharmacological interventions in clinical trials is crucial for accurate identification of beneficial and adverse outcomes. The ways in which adherence to interventions should be reported in trial publications are described in the Template for Intervention Description and Replication (TIDieR), a 12-item extension of the Consolidated Standards of Reporting Trials reporting guidelines. The objective of this study was to assess compliance with TIDieR Items 11 and 12 of randomized controlled trials (RCTs) of interventions in SARS-CoV-2 infection published in 5 selected journals during 2021. METHODS: We assessed pharmacological interventions for SARS-CoV-2 infection reported in RCTs published in 2021 in the Annals of Internal Medicine, The BMJ, JAMA, The Lancet and The New England Journal for Medicine for compliance with TIDieR items addressing intervention adherence (Items 11 and 12). We calculated proportional adherence for pharmacological and comparator interventions where available. RESULTS: We found 75 eligible RCTs. Twenty-eight (37%) reported results of SARS-CoV-2 vaccinations. Compliance with Items 11 and 12 could be assessed in 71 of these 75. Of the 71 RCTs, 37 (52%) reported how adherence was assessed (Item 11), and 70 reported adherence rates (Item 12). Only 1 of the 71 RCTs (1.4%, 0-7.6%) fully complied with TIDieR Items 11 and 12. CONCLUSION: Half of RCTs of SARS-CoV-2 pharmacological interventions published in leading medical journals in 2021 complied with reporting of how adherence assessments were made and almost none complied with both TIDieR Items 11 and 12. The implications for interpretation, application and replication of findings based on these publications warrant consideration.

Insights into the quantification and reporting of model-related uncertainty across different disciplines.

Quantifying uncertainty associated with our models is the only way we can express how much we know about any phenomenon. Incomplete consideration of model-based uncertainties can lead to overstated conclusions with real-world impacts in diverse spheres, including conservation, epidemiology, climate science, and policy. Despite these potentially damaging consequences, we still know little about how different fields quantify and report uncertainty. We introduce the "sources of uncertainty" framework, using it to conduct a systematic audit of model-related uncertainty quantification from seven scientific fields, spanning the biological, physical, and political sciences. Our interdisciplinary audit shows no field fully considers all possible sources of uncertainty, but each has its own best practices alongside shared outstanding challenges. We make ten easy-to-implement recommendations to improve the consistency, completeness, and clarity of reporting on model-related uncertainty. These recommendations serve as a guide to best practices across scientific fields and expand our toolbox for high-quality research.

Changing patterns in reporting and sharing of review data in systematic reviews with meta-analysis of the effects of interventions: cross sectional meta-research study.

OBJECTIVES: To examine changes in completeness of reporting and frequency of sharing data, analytical code, and other review materials in systematic reviews over time; and factors associated with these changes. DESIGN: Cross sectional meta-research study. POPULATION: Random sample of 300 systematic reviews with meta-analysis of aggregate data on the effects of a health, social, behavioural, or educational intervention. Reviews were indexed in PubMed, Science Citation Index, Social Sciences Citation Index, Scopus, and Education Collection in November 2020. MAIN OUTCOME MEASURES: The extent of complete reporting and the frequency of sharing review materials in the systematic reviews indexed in 2020 were compared with 110 systematic reviews indexed in February 2014. Associations between completeness of reporting and various factors (eg, self-reported use of reporting guidelines, journal policies on data sharing) were examined by calculating risk ratios and 95% confidence intervals. RESULTS: Several items were reported suboptimally among 300 systematic reviews from 2020, such as a registration record for the review (n=113; 38%), a full search strategy for at least one database (n=214; 71%), methods used to assess risk of bias (n=185; 62%), methods used to prepare data for meta-analysis (n=101; 34%), and source of funding for the review (n=215; 72%). Only a few items not already reported at a high frequency in 2014 were reported more frequently in 2020. No evidence indicated that reviews using a reporting guideline were more completely reported than reviews not using a guideline. Reviews published in 2020 in journals that mandated either data sharing or inclusion of data availability statements were more likely to share their review materials (eg, data, code files) than reviews in journals without such mandates (16/87 (18%) v 4/213 (2%)). CONCLUSION: Incomplete reporting of several recommended items for systematic reviews persists, even in reviews that claim to have followed a reporting guideline. Journal policies on data sharing might encourage sharing of review materials.

Open science and conflict of interest policies of medical and health sciences journals before and during the COVID-19 pandemic: A repeat cross-sectional study: Open science policies of medical journals.

Objectives: To audit the transparent and open science standards of health and medical sciences journal policies and explore the impact of the COVID-19 pandemic. Design: Repeat cross-sectional study. Setting: 19 journals listed in Google Scholar's Top Publications for health and medical sciences. Participants: Blood, Cell, Circulation, European Heart Journal, Gastroenterology, Journal of Clinical Oncology, Journal of the American College of Cardiology, Nature Genetics, Nature Medicine, Nature Neuroscience, Neuron, PLoS ONE, Proceedings of the National Academy of Sciences, Science Translational Medicine, The British Medical Journal, The Journal of the American Medical Association, The Lancet, The Lancet Oncology, and The New England Journal of Medicine. Main outcome measures: We used the Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) to evaluate journals standards. Results: TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2-12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4-12) in May 2021, but overall, scores were very low at both time points. Journal policies scored highest for their adherence to data transparency and scored lowest for preregistration of study protocols and analysis plans and the submission of replication studies. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n = 16) and during (95%; n = 18) the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has highlighted the importance of practising open science. However, requirements for open science practices in audited policies were overall low, which may impede progress in health and medical research. As key stakeholders in disseminating research, journals should promote a research culture of greater transparency and more robust open science practices.

Physical activity for treatment of irritable bowel syndrome.

BACKGROUND: Current recommendations for people with irritable bowel syndrome (IBS) to partake in physical activity are based on low-level evidence, do not incorporate evidence from all available randomised controlled trials (RCTs) and provide little information regarding potential adverse effects. OBJECTIVES: To assess the benefits and harms of physical activity interventions in adults diagnosed with irritable bowel syndrome and to explore possible effect moderators including type, setting and nature of physical activity interventions. SEARCH METHODS: We searched nine electronic databases including CENTRAL, MEDLINE and Embase to 5 November 2021. We handsearched reference lists and sought unpublished studies through trial registries. SELECTION CRITERIA: We included RCTs involving adults (aged 18 years or older) diagnosed with IBS and conducted in any setting comparing a physical activity intervention with no intervention, usual care or wait-list control group or another physical activity intervention group and assessing a validated measure of symptoms, quality of life or bowel movement. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence. We pooled studies that evaluated similar outcomes using a random-effects meta-analysis, and synthesised data from other studies narratively. MAIN RESULTS: We included 11 RCTs with data for 622 participants. Most (10/11) were set in high- or middle- to high-income countries, with five involving supervised physical activity, three unsupervised activity and three a mix of supervised and unsupervised activity. No trial was at low risk of bias. Four trials specified a minimally important difference for at least one assessed outcome measure. Data for 10 trials were obtained from published journal articles, with data for one obtained from an unpublished Masters degree thesis. Irritable bowel syndrome symptoms Six RCTs assessed the effectiveness of a physical activity intervention compared with usual care on global symptoms of IBS. Meta-analysis of five studies showed an observed improvement in reported symptoms following physical activity (standardised mean difference (SMD) -0.93, 95% confidence interval (CI) -1.44 to -0.42; 185 participants). We rated the certainty of evidence for this outcome as very low due to unclear and high risk of bias, inconsistency and imprecision from sparse data. This means physical activity may improve IBS symptoms but the evidence is very uncertain. The results of the remaining study supported the meta-analysis but were at unclear risk of bias and sample size was small. Two studies assessed the effectiveness of a yoga intervention compared with a walking intervention on global IBS symptoms. Meta-analysis of these two studies found no conclusive evidence of an effect of yoga compared with walking on IBS symptoms (SMD -1.16, 95% CI -3.93 to 1.62; 124 participants). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of yoga interventions compared with walking interventions on IBS symptoms. Two studies assessed the effectiveness of a physical activity intervention (yoga) compared with medication. One reported no observed difference in global IBS symptoms, though CIs were wide, suggesting uncertainty in the observed estimates and risk of bias was high (MD -1.20, 95% CI -2.65 to 0.25; 21 participants). We excluded IBS symptom data for the remaining study as it used a non-validated method. One study compared a yoga intervention with a dietary intervention and reported an observed improvement in symptoms with both interventions but neither intervention was superior to the other. Quality of life Five RCTs assessed the impact of physical activity on self-reported quality of life compared with usual care. Meta-analysis of data from four studies found no improvement in quality of life following a physical activity intervention (SMD 1.17, 95% CI -0.30 to 2.64; 134 participants; very low certainty due to risk of bias, inconsistency and imprecision). We rated the certainty of evidence as very low, meaning the evidence is very uncertain about the effect of physical activity interventions on quality-of-life outcomes in people with IBS. One study assessed the impact on quality of life of a yoga intervention compared with walking and observed an improvement in the yoga group (MD 53.45, 95% CI 38.85 to 68.05; 97 participants ).  One study reported no observed difference in quality of life between a yoga and a dietary intervention. Abdominal pain Two trials assessed the impact of physical activity compared with usual care on reported abdominal pain. Meta-analysis found no improvement in abdominal pain with physical activity compared with usual care (SMD 0.01, 95% CI -0.48 to 0.50; 64 participants). We rated the certainty of the evidence as very low due to risk of bias and imprecision, meaning the evidence is very uncertain about the effect of physical activity interventions on abdominal pain in people with IBS. One study assessing the impact of a yoga intervention compared with walking advice reported no observed differences between groups on abdominal pain. One study comparing a yoga intervention with a dietary intervention found neither intervention had a more beneficial impact than the other and both interventions did not conclusively reduce abdominal pain. There was insufficient evidence to adequately assess adverse effects associated with physical activity due to a lack of reporting in trials. One study reported a musculoskeletal injury in a yoga intervention group but this did not result in withdrawal from the study. AUTHORS' CONCLUSIONS: Findings from a small body of evidence suggest that physical activity comprising of yoga, treadmill exercise or support to increase physical activity may improve symptoms but not quality of life or abdominal pain in people diagnosed with IBS but we have little confidence in these conclusions due to the very low certainty of evidence. The numbers of reported adverse events were low and the certainty of these findings was very low for all comparisons, so no conclusions can be drawn. Discussions with patients considering physical activity as part of symptom management should address the uncertainty in the evidence to ensure fully informed decisions. If deemed sufficiently important to patients and healthcare providers, higher quality research is needed to enable more certain conclusions.

High quality (certainty) evidence changes less often than low-quality evidence, but the magnitude of effect size does not systematically differ between studies with low versus high-quality evidence.

RATIONALE, AIMS, AND OBJECTIVES: It is generally believed that evidence from low quality of evidence generate inaccurate estimates about treatment effects more often than evidence from high (certainty) quality evidence (CoE). As a result, we would expect that (a) estimates of effects of health interventions initially based on high CoE change less frequently than the effects estimated by lower CoE (b) the estimates of magnitude of effect size differ between high and low CoE. Empirical assessment of these foundational principles of evidence-based medicine has been lacking. METHODS: We reviewed the Cochrane Database of Systematic Reviews from January 2016 through May 2021 for pairs of original and updated reviews for change in CoE assessments based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We assessed the difference in effect sizes between the original versus updated reviews as a function of change in CoE, which we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies in which CoE changed from very low/low (VL/L) to moderate/high (M/H) versus M/H to VL/L. Heterogeneity and inconsistency were assessed using the tau and I2 statistic. We also assessed the change in precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute deviation in estimates of treatment effects (aROR). RESULTS: Four hundred and nineteen pairs of reviews were included of which 414 (207 × 2) informed the CoE appraisal and 384 (192 × 2) the assessment of effect size. We found that CoE originally appraised as VL/L had 2.1 [95% confidence interval (CI): 1.19-4.12; p = 0.0091] times higher odds to be changed in the future studies than M/H CoE. However, the effect size was not different (p = 1) when CoE changed from VL/L → M/H [ROR = 1.02 (95% CI: 0.74-1.39)] compared with M/H → VL/L (ROR = 1.02 [95% CI: 0.44-2.37]). Similar overlap in aROR between the VL/L → M/H versus M/H → VL/L subgroups was observed [median (IQR): 1.12 (1.07-1.57) vs. 1.21 (1.12-2.43)]. We observed large inconsistency across ROR estimates (I2 = 99%). There was larger imprecision in treatment effects when CoE changed from VL/L → M/H (seR = 1.46) than when it changed from M/H → VL/L (seR = 0.72). CONCLUSIONS: We found that low-quality evidence changes more often than high CoE. However, the effect size did not systematically differ between the studies with low versus high CoE. The finding that the effect size did not differ between low and high CoE indicate urgent need to refine current EBM critical appraisal methods.

Adherence in leading medical journals to the CONSORT 2010 statement for reporting of binary outcomes in randomised controlled trials: cross-sectional analysis.

Clinicians and lay people tend to overestimate the effectiveness of a treatment when only the relative effect is presented, particularly if the relative effect is large, but the absolute effect is small. In recognition of this problem, item 17b of The Consolidated Standards of Reporting Trials (CONSORT) 2010 statement stipulates authors present both absolute and relative effects for binary outcomes in randomised controlled trials (RCTs). Adherence to item 17b and the effect of differing levels of CONSORT endorsement by journals on adherence is not well known. We assessed the extent to which item 17b is adhered to in 258 RCTs published in five leading medical journals (Annals of Internal Medicine, BMJ, JAMA, The Lancet and The New England Journal of Medicine) between January and December 2019 that all endorsed the CONSORT statement to varying degrees. Only 53 of 258 (20.5%; 95% CI 15.8% to 26.0%) included studies adhered fully to item 17b. Proportional adherence was higher in journals that endorsed the statement more strictly (BMJ and JAMA, 47.4% [34.0% to 61.0%]) compared with journals less strict in their endorsement (NEJM and Ann Intern Med, 12.2% [7.0% to 19.3%]; The Lancet, 14.1% [7.3% to 23.8%]). Journals that only recommend author adherence to CONSORT had a greater proportion of studies reporting only relative effects in the main results section (62.6%) and abstract (64.2%) compared with journals that require authors to submit a completed checklist (24.6% and 29.8%, respectively). The majority of RCTs (79.5%) with binary primary outcomes published in five leading medical journals during 2019 do not report both absolute and relative effect estimates as per item 17b of the CONSORT guideline despite its universal endorsement. Differences in adherence were observed between journals that endorsed the CONSORT statement to differing extents.

Incidence of Sudden Cardiac Arrest and Death in Young Athletes and Military Members: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the quality of the evidence on the incidence of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in athletes and military members and estimate the annual incidence of SCA and SCD. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, BIOSIS, Scopus, SPORTDiscus, PEDro, and ClinicalTrials.gov from inception to dates between February 21 and July 29, 2019. STUDY SELECTION: Studies in which the incidence of SCA, SCD, or both in athletes or military members aged <40 years was reported were eligible for inclusion. We identified 40 studies for inclusion. DATA EXTRACTION: Risk of bias (ROB) was assessed using a validated, customized tool for prevalence studies. Twelve had a low ROB, while the remaining 28 had a moderate or high ROB. Data were extracted for narrative review and meta-analysis. DATA SYNTHESIS: Random-effects meta-analysis was performed in studies judged to have a low ROB in 2 categories: (1) 5 studies of regional- or national-level data, including athletes at all levels and both sexes, demonstrated 130 SCD events with a total of 11 272 560 athlete-years, showing a cumulative incidence rate of 0.98 (95% CI = 0.62, 1.53) per 100 000 athlete-years and high heterogeneity (I2 = 78%) and (2) 3 studies of competitive athletes aged 14 to 25 years were combined for a total of 183 events and 17 798 758 athlete-years, showing an incidence rate of 1.91 (95% CI = 0.71, 5.14) per 100 000 athlete-years and high heterogeneity (I2 = 97%). The remaining low-ROB studies involved military members and were not synthesized. CONCLUSIONS: The worldwide incidence of SCD is rare. Low-ROB studies indicated the incidence was <2 per 100 000 athlete-years. Overall, the quality of the available evidence was low, but high-quality individual studies inform the question of incidence levels. PROSPERO REGISTRATION: CRD42019125560.

Screening Electrocardiogram in Young Athletes and Military Members: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the effect of electrocardiogram (ECG) screening on the prevention of sudden cardiac arrest and death in young athletes and military members. DATA SOURCES: MEDLINE, Embase, CENTRAL, Web of Science, BIOSIS, Scopus, SPORTDiscus, PEDro, and ClinicalTrials.gov were searched from inception to dates between February 21 and July 29, 2019. STUDY SELECTION: Randomized and nonrandomized controlled trials in which preparticipation examination including ECG was the primary intervention used to screen athletes or military members aged ≤40 years. Acceptable control groups were those receiving no screening, usual care, or preparticipation examination without ECG. Three published studies and 1 conference abstract were identified for inclusion. DATA EXTRACTION: In all 4 studies, risk of bias was assessed using the Cochrane risk-of-bias tool and was found to be generally high. Two studies had data extracted for random effects meta-analysis, and the remaining study and conference abstract were included in the narrative review. The overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. DATA SYNTHESIS: We included 4 nonrandomized studies (11 689 172 participants), of which all had a high risk of bias. Pooled data from 2 studies (n = 3 869 274; very low-quality evidence) showed an inconclusive 42% relative decrease in risk of sudden cardiac death (relative risk = 0.58; 95% CI = 0.23, 1.45), equating to an absolute risk reduction of 0.0016%. The findings were consistent with a potential 77% relative decreased risk to a 45% relative increased risk in participants screened using ECG. Heterogeneity was found to be high, as measured using I2 statistic (71%). Data from the remaining study and abstract were similarly inconclusive. CONCLUSIONS: Existing evidence for the effect of ECG screening is inconclusive and of very low quality. In our meta-analysis, we observed that screening ECG may result in a considerable benefit or harm to participants. Higher-quality studies are needed to reduce this uncertainty.

Adherence to conflicts of interest policy in Cochrane reviews where authors are also editorial board members: A cross-sectional analysis.

Cochrane devolves most editorial governance of the Cochrane Database of Systematic Reviews (CDSR), including title prioritization, protocol registration, peer-review, editorial oversight and subsequent review deposition, to specific Cochrane Review Group (CRG) editorial boards. Current Cochrane policy stipulates authors of reviews who are also members of the supporting CRG declare this non-financial conflict of interest and confirm no involvement in the review editorial process. The aim of this cross-sectional analysis was to assess adherence to Cochrane's editorial conflict of interest policy. All 260 published Cochrane reviews (CR) in issues 1 to 6 from 2019 of the CDSR were reviewed. A total of 133 (51.2%, 133/260) of CRs had at least one author that was also listed as an editor in the CRG. Of these, only five (3.8%, 5/133) appropriately declared the conflict according to Cochrane policy. In 6.5% (17/133) CRs, the contact author had a leading editorial position within the CRG and in only four of 17 was this declared according to Cochrane policy. No CR with the contact author who also had a leading editorial position described methods to prevent any potential issues related to this scenario during the editorial process in accordance with Cochrane policy. We propose a specific form to improve the transparency and reliability of editorial conflict of interest reporting in CRs. The suggested form can be adapted to other contexts.

Much ado about something: a response to "COVID-19: underpowered randomised trials, or no randomised trials?"

Non-pharmaceutical interventions (NPI) for infectious diseases such as COVID-19 are particularly challenging given the complexities of what is both practical and ethical to randomize. We are often faced with the difficult decision between having weak trials or not having a trial at all. In a recent article, Dr. Atle Fretheim argues that statistically underpowered studies are still valuable, particularly in conjunction with other similar studies in meta-analysis in the context of the DANMASK-19 trial, asking "Surely, some trial evidence must be better than no trial evidence?" However, informative trials are not always feasible, and feasible trials are not always informative. In some cases, even a well-conducted but weakly designed and/or underpowered trial such as DANMASK-19 may be uninformative or worse, both individually and in a body of literature. Meta-analysis, for example, can only resolve issues of statistical power if there is a reasonable expectation of compatible well-designed trials. Uninformative designs may also invite misinformation. Here, we make the case that-when considering informativeness, ethics, and opportunity costs in addition to statistical power-"nothing" is often the better choice.