Abstract Context The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) of the Food and Drug Administration (FDA) reviews safety and efficacy data for cardiovascular and renal drugs, ultimately making recommendations to the Commissioner of Food and Drugs for approval. The Open Public Hearing segment of these meetings allows for patients, advocates, healthcare professionals, clinical trialists, and members of the public to provide testimony, which often results in expressing their preference for, or against, drug approval. Prior to providing testimony, the public speakers are highly encouraged to disclose any financial conflicts of interest (FCOIs) with the sponsor or other groups. Given the potential influence of these speakers on drug approval recommendations, we investigated the industry associations disclosed by public speakers in the Open Public Hearing section of the CRDAC meetings. Previous studies, such as one done by Lurie et al. indicated that positive testimony is tied to a higher likelihood of drug approval, and because drug companies provide financial compensation for speakers to provide testimony in general, we wanted to determine the likelihood with which speakers who have an FCOI provided a positive testimony vs. those without any FCOI. Objectives The purpose is to evaluate whether public speakers with an FCOI are more likely to provide positive testimony regarding the drug in question during the CRDAC of the FDA between February 2009 and December 2019 through the use of publicly available transcripts. Methods Independent researchers investigated public transcripts and minutes of the CRDAC meetings with public speakers (n=20). We identified all speakers, along with characteristics such as an FCOI, and classified statements utilizing a pilot-tested Google form. The data collected were analyzed utilizing Stata. The speaker’s testimony was then compared with their FCOI. An ordered logistic regression was performed utilizing the speaker’s testimony regarding the drug as the dependent variable. Results Of the 88 speakers represented in our sample, 35 (35/88, 39.8%) disclosed an FCOI, most commonly regarding travel cost. Among speakers with an FCOI, 30 (30/35, 85.7%) spoke positively. Speakers with an FCOI were 4.96 times more likely to provide positive testimony (OR=4.96, 95% CI 1.67–14.78). Speakers with the disease were also more likely to provide positive testimony (OR=13.05, 95% CI 2.84–59.93). Conclusions Public speakers often play a role during meetings, and they may also have an FCOI, most commonly related to travel expenses. Our study shows that speakers with an FCOI are more likely to provide positive testimony. Stipulations, such as requiring disclosure of FCOI and randomizing the selection process of speakers, can help ensure the integrity of the drug approval process.

Background:Thus, the purpose of the present study was to (1) characterize common postoperative complications and (2) quantify the rates of revision in patients undergoing hemiarthroplasty to reverse total shoulder arthroplasty revisional surgery. We hypothesize that hardware loosenings will be the most common complication to occur in the sample, with the humeral component being the most common loosening.Methods:This systematic review adhered to PRISMA reporting guideline. For our inclusion criteria, we included any study that contained intraoperative and/or postoperative complication data, and revision rates on patients who had undergone revision reverse total shoulder arthroplasty due to a failed hemiarthroplasty. Complications include neurologic injury, deep surgical site infections, hardware loosening/prosthetic instability, and postoperative fractures (acromion, glenoid, and humeral fractures).Results:The study contained 22 studies that assessed complications from shoulders that had revision reverse total shoulder arthroplasty from a hemiarthroplasty, with a total sample of 925 shoulders. We found that the most common complication to occur was hardware loosenings (5.3%), and of the hardware loosenings, humeral loosenings (3.8%) were the most common. The revision rate was found to be 10.7%.Conclusion:This systematic review found that revision reverse total shoulder arthroplasty for failed hemiarthroplasty has a high overall complication and reintervention rates, specifically for hardware loosening and revision rates.

Objective In light of the current national mental health crisis, we use Google Trends, Twitter and data obtained from the National Suicide Prevention Lifeline to evaluate the effect of '1-800-273-8255' on public awareness for the National Suicide Prevention Lifeline. Design Cross-sectional analysis. Main outcome measures We extracted data from Google Trends and Twitter for terms related to suicide following the release of Logic's song, '1-800-273-8255'. We then used a forecasting autoregressive integrated moving algorithm model to determine the greater than expected search interest. Results Google searches for 'Suicide Hotline' increased 49% more than expected the day after Logic's song was released and sustained increase of queries resulted in an average relative search volume of 59.5%-9.1% higher than the mean forecasted value of 50.4% for the 28 days following the release. Tweets that engaged with the account '@800 273talk' on Twitter increased by 10 450% more than expected the day after the song was released and increased by a mean of 1497% greater than expected the week after the songs released. Conclusion Findings from our study suggest that the entertainment industry can play an important role in increasing awareness of hotline numbers. Logic's song provides an example of a positive influence on public health and provides support for further development and standards for proper awareness of suicide in the public view.

ObjectiveEvidence-based decision making is crucial in reducing the health and economic burdens imposed by tonsillar-related pathologies. Clinical practice guidelines are used to guide these decisions; however, uptake of recommendations in these guidelines is low. Systematic reviews are the highest level of evidence used to influence guideline recommendations; therefore, improving the reporting and methodological quality of systematic reviews related to tonsillar-related pathologies may improve guideline uptake and patient care.MethodsWe used PubMed to search for all clinical practice guidelines related to tonsillar-related pathologies from 2010 to 2020. Included guidelines were then searched for all systematic reviews and meta-analyses. Study characteristics were extracted from each cited systematic review/meta-analysis before being evaluated using the PRISMA (Preferred Reporting Instrument for Systematic Reviews and Meta-Analyses) and AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews 2) instruments. We then compared systematic reviews conducted by a Cochrane systematic review group with non-Cochrane systematic reviews.ResultsSeven clinical practice guidelines were included in our study and within these guidelines 98 SRs/MAs were cited, 80 of which were unique and included. Systematic reviews composed 9.1% (98/1082) of all guideline citations. Guideline PRISMA scores ranged from 0.47 to 0.83 with a mean score of 0.71 (n = 80) and guideline AMSTAR-2 scores ranged from 0.52 to 0.83 with a mean of 0.56 (7.29/13) and 0.75 (11.94/16) (n = 80). Cochrane systematic reviews displayed greater PRISMA (0.88 vs. 0.64: p < 0.001) and AMSTAR-2 (0.90 vs. 0.57; p < 0.001) scores compared to the non-Cochrane studies. We found PRISMA and AMSTAR-2 scores were positively correlated across guidelines (r = 0.93).ConclusionWide variation exists in adherence to PRISMA and AMSTAR-2 guidelines among systematic reviews cited in clinical practice guidelines for tonsillar-related pathologies. Prior registration and adequate risk of bias assessment are two areas where improvements may be needed. Given the importance of guideline uptake, careful considerations to improve the methodological and reporting quality of evidence supporting tonsillar-related pathology recommendations are necessary.

IntroductionComplete reporting of systematic reviews of interventions is essential to the interpretation of research findings and the reproducibility of research results. The Template for Intervention Description and Replication (TIDieR) checklist—and the version specific to systematic reviews (TIDieR-SR)—was created to provide authors and researchers an evidence-based guide for reporting trial and systematic review interventions. In this study, we apply TIDieR-SR to Cochrane systematic reviews of surgical interventions.MethodsWe searched the Cochrane Database for relevant systematic reviews. Two investigators applied inclusion/exclusion criteria to all titles/abstracts and full texts. These same investigators extracted all data in duplicate while masked to the other’s data. The primary outcome was adherence to TIDieR-SR items.ResultsTwo hundred and thirty-eight systematic reviews were included. Overall, included SRs adhered to a median of 6 (IQR 5–7) out of eight TIDieR-SR items. The item with the lowest adherence was item 7 (share intervention materials, 1/238 (0.4%).DiscussionOur results are encouraging, but the generalisability of our findings is compromised by the inclusion of only Cochrane systematic reviews. Future reporting of intervention materials is likely to improve the application of effective surgical interventions in the clinical practice.

CONTEXT:The misrepresentation and distortion of research findings, known as "spin," has been shown to affect clinical decision making. Spin has been found in randomized controlled trials (RCTs) published in various fields of medicine.OBJECTIVE:To evaluate the abstracts of RCTs found in the cardiology literature for spin.METHODS:The authors searched PubMed using a specific string of keywords to identify previously published articles documenting RCTs of cardiovascular treatments in humans. To be included, a cardiology trial had to randomize humans to an intervention, statistically compare 2 or more groups, and have a nonsignificant primary endpoint. Records were excluded if they did not meet these criteria. Data extraction was double-blinded and done using a pilot-tested Google Form. Items extracted from each trial included the title, journal, funding source, comparator arm, primary endpoint, statistical analysis of the primary endpoint, secondary endpoints, statistical analysis of secondary endpoints, and trial registration number (if reported). The 2 authors who screened records for inclusion were then asked whether spin was present in the abstract of the randomized trial. Spin in the title, abstract results, abstract conclusions, and selection of reported endpoints were considered.RESULTS:Of the 651 PubMed citations retrieved by our search string, 194 RCTs with a clearly defined primary endpoint were identified. Of these 194 RCTs, 66 trials contained nonsignificant primary endpoints and were evaluated for spin. Of these trials, spin was identified in 18 of the 66 abstracts (27.3%).CONCLUSIONS:Spin was present in our sample of cardiology RCTs. Spin may influence clinical decision making by creating false impressions of the true validity of a drug or intervention.

Background and Aims Selective outcome reporting occurs when trialists pre-specify primary and secondary outcomes during trial planning but alter the definitions in the published report. Here, we investigate selective outcome reporting in published addiction randomized controlled trials (RCTs) and evaluate whether particular funding sources are associated with an increased likelihood of selective outcome reporting. Design We conducted a cross-sectional study of published addiction clinical trials. A PubMed search was performed to identify RCTs in addiction journals from 2013 to 2017. Included studies used a randomized design to address one of the following topics: (1) drug, alcohol and tobacco addiction prevention, (2) stabilization following excessive use of a substance, (3) relapse prevention or (4) recovery maintenance. Setting Single-center, medical research institution. Participants Our sample included 162 RCTs that were prospectively registered with a clearly defined primary outcome. Measurement We extracted the following items from addiction RCTs: journal, funding source, trial registry number (if included), sample size, dates of subject enrollment, whether primary and secondary outcomes were denoted, all published outcomes, P-value for all outcomes and whether authors mentioned any deviations from the trial protocol as it related to RCT outcomes. Findings In total, 47 of 162 RCTs (29.0%) had at least one major discrepancy between the trial registry and published RCT. Overall, these 47 RCTs included 54 major discrepancies. The most common major discrepancy was demotion of a primary registered outcome (19/54, 35.2%). The majority of RCTs (132/162, 81.5%) were funded from public sources. Additionally, 166 RCTs were excluded from our sample because registration could not be confirmed. Conclusions There is evidence suggestive of selective outcome reporting in addiction randomized controlled trials (RCTs). The most common major discrepancies pertained to the primary outcome.

Vasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients.What is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response?We performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation.Of 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 μg/kg/min vs +0.04 μg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients.In postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality.

Objectives/Hypothesis Spin-the practice of adding or omitting information intentionally or unintentionally to make the results of a study more favorable-may influence clinical decision making, especially when present in study abstracts. Here, we quantify and characterize the presence of spin in the abstracts of systematic reviews regarding tonsillectomy. Methods This study is an analysis of systematic review abstracts. Searches were conducted on September 23, 2019 on PubMed and Embase using the advanced search feature to retrieve systematic reviews regarding tonsillectomies. The nine most severe forms of spin were then evaluated. Spin was classified by two investigators in parallel, with each blinded to the classifications of the other. Study characteristics were also recorded in duplicate. Consensus meetings between investigators were held to resolve disagreements. Results In the 85 included systematic reviews, at least one form of spin was present in 44.7% (38/85) of abstracts. Journals with higher impact factors were less likely to contain spin in the abstracts of systematic reviews (point biserial correlation coefficient of -0.30). No statistically significant associations were found between the presence of spin and intervention type (P= .56) or adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P= .08); however, there was a significant association between spin and funding source (P= .03). Conclusions Spin was common in the abstracts of our sample of tonsillectomy systematic reviews. Researchers, clinicians, and peer reviewers could benefit from learning to recognize spin in medical literature. Further research is needed into the effects of spin on clinical decision making. Level of Evidence NALaryngoscope, 2020

Context: Robust methodology and ethical reporting are paramount for quality scientific research, but recently, that quality in addiction research has been questioned. Avenues to improve such research quality include adherence to reporting guidelines and proper usage of clinical trial registries. Reporting guidelines and clinical trial registries have been shown to lead researchers to more ethical and transparent methodology. Objectives: To investigate the reporting guideline and clinical trial registration policies of addiction research journals and identify areas of improvement. Methods: We used Google Scholar Metrics' h-5 index to identify the top 20 addiction research journals. We then examined the instructions for authors from each journal to identify whether they required, recommended, or made no mention of trial registration and reporting guidelines, including the Consolidated Standards of Reporting Trials (CONSORT), Meta-Analysis of Observational Studies in Epidemiology (MOOSE), Quality of Reporting of Meta-analyses (QUOROM), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Standards for Reporting Diagnostic Accuracy Studies (STARD), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), Animal Research: Reporting of In Vivo Experiments (ARRIVE), Case Reports (CARE), Consolidated Health Economic Evaluation Reporting Standards (CHEERS), Standards for Reporting Qualitative Research (SRQR), Standards for Quality Improvement Reporting Excellence (SQUIRE), Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), Consolidated Criteria for Reporting Qualitative Research (COREQ), Transparent Reporting of a Multivariate Prediction Model for Individual Prognosis or Diagnosis (TRIPOD), Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the International Committee of Medical Journal Editors (ICMJE) guidelines. We performed the same analysis regarding requirements for clinical trial registration. Results: Of the 20 journals included in this study, 10 journals (50%) did not require adherence to any reporting guidelines. Trial registration followed a similar trend; 15 journals (75%) did not mention any form of trial or systematic review registration, and ClinicalTrials.gov was only recommended by only 1 journal (5%). Conclusions: Among top addiction medicine journals, required adherence to reporting guidelines and clinical trial registry policies remains substandard. A step toward fulfilling the National Institute on Drug Abuses' call for improvement in transparency and reproducibility within addiction research should include all journals adopting a strict reporting guideline and clinical trial registry adherence policy.

This cross-sectional study uses Google Trends and cleidocranial dysplasia–related foundation website data to investigate the association of television portrayals of cleidocranial dysplasia with public interest and awareness of the disorder.

Abstract Background Clinical practice guidelines (CPGs) can positively affect the quality of patient care offered by physicians because they decrease variability in clinical practice and may help reduce unnecessary testing, promoting a more responsible use of resources. Building on existing framework for reporting guideline development, including the work of the Enhancing the Quality and Transparency of Health Research Network, the Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group created a 2016 checklist of 35 items considered essential for high-quality reporting of CPGs. Objectives To evaluate how many previously published CPGs in orthopedic surgery met the RIGHT criteria and assess how improvements can be made in future orthopedic CPGs based on any found deficiencies. Methods All 18 CPGs published before January 1, 2018, by the American Academy of Orthopedic Surgeons (AAOS) are publicly available on orthoguidelines.org. Two authors downloaded each file and both of those authors independently scored each CPG using piloted abstraction RIGHT checklist forms. Results Of the 35 RIGHT criteria outlined in 22 checklist items, 23 (65.7%) were met across all AAOS guidelines, 6 (17.1%) were not met by any of the AAOS guidelines, and 6 (17.2%) were met by some of the AAOS guidelines. Conclusion Overall, the AAOS guidelines addressed many important recommendations within the RIGHT checklist. Assessing adherence to the RIGHT checklist can help ensure that future guidelines are more effectively communicated, hopefully assisting end users in efficient implementation and increasing the level of evidence-based patient care.

Introduction Robust, clearly reported clinical practice guidelines (CPGs) are essential for evidence-based clinical practice. The Reporting Items for practice Guidelines in HealThcare (RIGHT) Statement and Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument were published to improve the methodological and reporting quality in healthcare CPGs. Methods We applied the RIGHT Statement checklist and AGREE-II instrument to 48 National Comprehensive Cancer Network (NCCN) guidelines. Our primary objective was to assess the adherence to RIGHT and AGREE-II items. Since neither RIGHT nor AGREE-II can judge the clinical usefulness of a guideline, our study is designed to only focus on the methodological and reporting quality of each guideline. Results The NCCN guidelines demonstrated notable strengths and weaknesses. For example, RIGHT Statement items 19 (conflicts of interest), 7b (description of subgroups) and 13a (clear, precise recommendations) were fully reported in all guidelines. However, the guidelines inconsistently incorporated patient values and preferences and cost. Regarding the AGREE-II instrument, the NCCN guidelines scored highly on the domains 4 (clear, precise recommendations) and 6 (handling of conflicts of interest), but lowest on domain 2 (inclusion of all relevant stakeholders). Conclusions In this investigation, we found that NCCN CPGs demonstrate key strengths and weaknesses with respect to the reporting of key items essential to CPGs. We recommend the continued use of NCCN guidelines and improvements to weaknesses in reporting and methods. Doing so serves to improve the evidence delivered to healthcare providers, thus potentially improving patient care.

Study objective: Randomized controlled trials govern evidence-based clinical practice, and it is therefore critical that their results be robust. We aim to investigate the fragility of randomized controlled trials in emergency medicine by determining how often significance would be nullified with small changes in outcomes using the fragility index. Methods: We conducted a methodological systematic review of randomized controlled trials in emergency medicine published in the top 10 general medicine journals and the top 10 emergency medicine journals. Inclusion criteria required that trials be emergency medicine studies structured with a 2-arm or 2-by-2 factorial design and report at least 1 statistically significant dichotomous outcome. Results: A total of 180 trials met inclusion criteria. The median fragility index across all trials in emergency medicine was 4 (interquartile range [IQR] 2 to 10) and the median sample size was 140 (IQR 69.5 to 286). For trials from general medicine journals (n = 32), the median fragility index was 9 (IQR 4 to 16.5) and the median sample size was 415.5 (IQR 219.5 to 901); for trials from emergency medicine journals (n = 148), the median fragility index was 4 (IQR 1 to 9) and the median sample size was 119 (IQR 60 to 227.25). One third of all trials (62/180) had a loss to follow-up that was greater than or equal to the fragility index. There was a modest correlation between fragility index and total number of events (r = 0.36; 95% confidence interval [CI] 0.23 to 0.48) and a weak correlation between fragility index and total sample size (r = 0.26; 95% CI 0.12 to 0.39). There was no correlation between fragility index and either P value (r = -0.14; 95% CI -0.28 to -0.006) or Science Citation Index (r = 0.07; 95% CI -0.08 to 0.22). Conclusion: The statistical significance of the results of randomized controlled trials in emergency medicine was often contingent on a small number of events. Until frequentist interpretation of clinical trials is replaced with Bayesian analysis, the fragility index may have utility as a tool to aid clinicians in assessing the robustness of randomized controlled trials in emergency medicine when considered in conjunction with the fragility quotient and other reported metrics.

ObjectiveSpin, the misrepresentation and distortion of research findings, has been shown to affect clinical decision making. Spin has been found in randomized controlled trials (RCTs) published in various fields of medicine, but no study has tested for the presence of spin in otolaryngology RCTs. The purpose of this study is to evaluate the abstracts of RCTs found in the otolaryngology literature for spin.MethodsIn this cross‐sectional analysis, we analyzed the abstracts of RCTs for spin using a pilot‐tested form. Double data extraction was performed by two blinded authors, and discrepancies were resolved using mutual discussion.ResultsOut of the 534 PubMed citations retrieved by our search string, 162 parallel‐group RCTs with clearly defined primary and secondary endpoints were identified. Further analysis identified 47 trials with nonsignificant primary outcomes, which were then evaluated for spin. Spin was identified in 33 of the 47 (70%) abstracts. Spin was found in the results sections of 25 (53%) of the included abstracts and was found in the conclusion section of 27 (57%) of the abstracts. Spin was not present in the titles of any of the included studies.ConclusionSpin was common in our sample of otolaryngology RCTs. Spin may potentially create false impressions about the true validity of a drug or intervention. Further research needs to test for potential clinical implications of spin in the otolaryngology literature.Level of EvidenceNALaryngoscope, 129:2036–2040, 2019

Wieruszewski, Patrick1; Davison, Danielle2; Cooper, Craig3; Butler, Simona4; Clark, Angela4; Tendler, Rachel5; Kashani, Kianoush1; Wittwer, Erica1; Barreto, Erin1 Author Information

We commend the work by Brown et al1Brown J. Lane A. Cooper C. et al.The results of randomized controlled trials in emergency medicine are frequently fragile.Ann Emerg Med. 2019; 73: 565-576Google Scholar that, using the fragility index and fragility quotient, assesses the fragility of randomized controlled trials in the emergency medicine literature. Although they provide a good overview of the limitations of the 2 metrics, we would like to further question the utility of fragility measures. In their critique of fragility measures, Carter et al2Carter R.E. McKie P.M. Storlie C.B. The fragility index: a P-value in sheep’s clothing?.Eur Heart J. 2017; 38: 346-348Google Scholar suggested that fragility index is a “P-value in sheep’s clothing.” In their article, they demonstrated the strong relationship between P values, fragility index, and sample size. The results of their study were based on 60,000 simulated clinical trials using a combination of 10 sample sizes (100 to 1,000), with relative risks of 1.0, 0.67, and 0.33 for intervention versus control.2Carter R.E. McKie P.M. Storlie C.B. The fragility index: a P-value in sheep’s clothing?.Eur Heart J. 2017; 38: 346-348Google Scholar They showed that P values decrease as sample size increases when the effect size is nonzero; the inverse relationship is observed when fragility index and sample size are compared. Stated another way, if the effect size is held constant and the sample size increases, the fragility index likewise increases.2Carter R.E. McKie P.M. Storlie C.B. The fragility index: a P-value in sheep’s clothing?.Eur Heart J. 2017; 38: 346-348Google Scholar In their study, Brown et al noted that the overall sample size for included trials was a median of 140 (interquartile range 69.5 to 286), with the overall fragility index for primary outcomes of the 74 included studies equal to 5 (interquartile range 2 to 11.75) and a fragility quotient of 0.039 (interquartile range 0.015 to 0.081). The small median sample size in randomized controlled trials in this study could be one reason for the low fragility index, as mentioned above. Furthermore, as Carter et al2Carter R.E. McKie P.M. Storlie C.B. The fragility index: a P-value in sheep’s clothing?.Eur Heart J. 2017; 38: 346-348Google Scholar observed, randomized controlled trials “are designed to balance the sample size with expected efficacy. In doing so, the [fragility index] is also minimized and results will necessarily hinge on fewer events. This is unavoidable, particularly in the context of clinical equipoise and finite resources.” Although certainly fragility quotient (fragility index normalized to study size) addresses some of these concerns, relative measures of fragility have not proven to be a reliable indicator of study quality, as the authors suggested (for example, the Collaborative Study Group captopril study, which established the use of angiotensin-converting enzyme inhibitors for the prevention of worsening diabetic nephropathy).3Lewis E.J. Hunsicker L.G. Bain R.P. et al.The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. Collaborative Study Group.N Engl J Med. 1993; 329: 1456-1462Google Scholar The primary endpoint of Collaborative Study Group was a doubling of the baseline serum creatinine concentration. Using the methods of Brown et al, we calculated the fragility index of Collaborative Study Group’s primary endpoint to be 4, with a fragility quotient of 0.009, or 1 event per 100 patients. Or consider the West of Scotland Coronary Prevention trial, the first major study to demonstrate the efficacy of statins in the primary prevention of nonfatal myocardial infarction or death from coronary artery disease in men with hypercholesterolemia.4Shepherd J. et al.Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med. 1995; 333: 1301-1308Google Scholar The fragility index of this study was 34, with a fragility quotient of 0.005. The fragility index and fragility quotient of these studies suggest these trials are quite fragile, yet have proved clinically meaningful in daily practice. Despite the more recent use of the fragility index and fragility quotient in the literature, we recommend caution in relation to their use until research establishes their utility in clinical context. Until then, their clinical utility for randomized controlled trials remains uninterpretable. The Results of Randomized Controlled Trials in Emergency Medicine Are Frequently FragileAnnals of Emergency MedicineVol. 73Issue 6PreviewRandomized controlled trials govern evidence-based clinical practice, and it is therefore critical that their results be robust. We aim to investigate the fragility of randomized controlled trials in emergency medicine by determining how often significance would be nullified with small changes in outcomes using the fragility index. Full-Text PDF In reply:Annals of Emergency MedicineVol. 73Issue 6PreviewWe thank Niforatos et al for their contribution to the discussion in regard to the limitations of the fragility index and fragility quotient. In their letter, they expand on some of the limitations to the application of the fragility index and fragility quotient discussed in our original work and ultimately question their utility. Although they highlight some important considerations, we believe that the measures have clinical utility. Here, we explore further some key points about their application and provide insight into how clinicians might use these tools. Full-Text PDF

BACKGROUND:Statistical analysis of systematic reviews allows the results of previous studies to be combined and synthesized to assess the overall health effect of the intervention in question. Systematic reviews can also be used to guide the creation of clinical practice guidelines and are considered to have a high level of evidence. Thus, it is important that their methodological quality is of the highest standard. Publication bias presents 2 problems: (1) studies with significant results may be overrepresented in systematic reviews and meta-analyses ("false positives") and (2) studies without significant results may not be included in systematic reviews and meta-analyses ("false negatives") because each study, on its own, was underpowered, meaning that some treatment options that may have clinical benefit will not be adopted. METHODS:We performed a study to evaluate the techniques used by authors to report and evaluate publication bias in the top 10 orthopaedic journals as well as 3 orthopaedic-related Cochrane groups. Two authors independently screened the titles and abstracts to identify systematic reviews and meta-analyses. We assessed publication bias in the systematic reviews that did not assess publication bias themselves. RESULTS:Our final sample included 694 systematic reviews or meta-analyses that met our inclusion criteria. Our review included 502 studies (72%) that focused on clinical outcomes, with the majority of the remaining studies focused on predictive and prognostic accuracy (20%) or diagnostic accuracy (5%). Publication bias was discussed in 295 (42.5%) of the included studies and was assessed in 135 (19.5%). Of the studies that assessed publication bias, 31.9% demonstrated evidence of publication bias. Only 43% and 22% of studies that involved use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines discussed and assessed publication bias, respectively. CONCLUSIONS:Publication bias is infrequently discussed and assessed in the high-impact orthopaedic literature. Furthermore, nearly one-third of the studies that assessed for publication bias demonstrated evidence of publication bias. In addition to these shortcomings, fewer than half of these studies involved use of the PRISMA guidelines and yet only one-fourth of the studies assessed for publication bias. CLINICAL RELEVANCE:By understanding the degree to which publication bias is discussed and presented in high-impact orthopaedic literature, changes can be made by journals and researchers alike to improve the overall quality of research produced and reported.

IMPORTANCE:The ability of clinical practice guidelines to improve patient outcomes depends on the quality of evidence that they are built upon. Research into tonsillectomy in children is lacking, and the gaps in evidence were identified by guideline authors. OBJECTIVE:The objective of this study is to evaluate the extent that new research is addressing the gaps identified in the AAO-HNS Tonsillectomy in Children Guideline. DESIGN:For each recommendation in the AAO-HNS guideline Tonsillectomy In Children, we created PICO (Participants, Intervention, Comparator, Outcome) questions and search strings. PubMed was searched to locate studies undertaken after the final literature search performed by the AAO-HNS work group. These studies were then extracted and analyzed. SETTING:This study is relevant to all invested in focusing otolaryngological research on questions which currently lack strong evidence. PARTICIPANTS:Trials in tonsillectomy that started after the development of the AAO-HNS clinical practice guidelines. MAIN OUTCOME MEASURES:The main outcome measures of this study is the extent to which tonsillectomy research is addressing the evidence gaps listed in the clinical practice guideline. RESULTS:Of the 2519 studies included in our sample, 276 (11%) were relevant to the 18 recommendations made within the Tonsillectomy in Pediatric Patients clinical practice guideline. All but one of the recommendations was met by at least one study. CONCLUSIONS:and Relevance: Our findings indicate that knowledge gaps within the guideline at publication may have since been addressed and a guideline update may thus be warranted. LEVEL OF EVIDENCE:NA.

PURPOSE:An estimated 85% of research is of limited value or wasted because the wrong research questions are addressed. We sought to identify research gaps using American Academy of Orthopaedic Surgeon (AAOS) clinical practice guidelines Treatment of Osteoarthritis of the Knee and Surgical Management of Osteoarthritis of the Knee. Using these recommendations, we conducted searches of ClinicalTrials.gov to discover the extent to which new and ongoing research addresses areas of deficiency.METHODS:For each recommendation in the AAOS guidelines, we created participants, intervention, comparator, outcomes questions, and search strings using a systematic process. Searches were then conducted of ClinicalTrials.gov to locate relevant studies.RESULTS:Our searches of ClinicalTrials.gov returned 945 studies for surgical and 1416 for non-surgical management of osteoarthritis. Of the 945 studies returned using our search string for surgical trials, 186 (20%) were relevant to 30 (79%) of the 38 recommendations made within the surgical management guideline. Of the 1416 studies returned using our search for non-surgical trials, 360 (25%) were relevant to 16 (89%) of the 18 recommendations made within the conservative management guideline.CONCLUSIONS:The development of clinical practice guidelines is a unique opportunity to simultaneously redefine day-to-day decision-making and provide a critical analysis of the status of the literature. Upon our search of the literature since the guidelines introduction, we have found that some inconclusive areas have received more attention than others. Our results should guide researchers towards conducting research on the topics most in need and, by doing so, strengthen the clinical practice guideline recommendations.