Toward Better Data Dashboards for US Drug Value Assessments.

OBJECTIVES: To explore the use of data dashboards to convey information about a drug's value, and reduce the need to collapse dimensions of value to a single measure. METHODS: Review of the literature on US Drug Value Assessment Frameworks, and discussion of the value of data dashboards to improve the manner in which information on value is displayed. RESULTS: The incremental cost per quality-adjusted life-year ratio is a useful starting point for conversation about a drug's value, but it cannot reflect all of the elements of value about which different audiences care deeply. Data dashboards for drug value assessments can draw from other contexts. Decision makers should be presented with well-designed value dashboards containing various metrics, including conventional cost per quality-adjusted life-year ratios as well as measures of a drug's impact on clinical and patient-centric outcomes, and on budgetary and distributional consequences, to convey a drug's value along different dimensions. CONCLUSIONS: The advent of US drug value frameworks in health care has forced a concomitant effort to develop appropriate information displays. Researchers should formally test different formats and elements.

The methodological quality of 176,620 randomized controlled trials published between 1966 and 2018 reveals a positive trend but also an urgent need for improvement.

Many randomized controlled trials (RCTs) are biased and difficult to reproduce due to methodological flaws and poor reporting. There is increasing attention for responsible research practices and implementation of reporting guidelines, but whether these efforts have improved the methodological quality of RCTs (e.g., lower risk of bias) is unknown. We, therefore, mapped risk-of-bias trends over time in RCT publications in relation to journal and author characteristics. Meta-information of 176,620 RCTs published between 1966 and 2018 was extracted. The risk-of-bias probability (random sequence generation, allocation concealment, blinding of patients/personnel, and blinding of outcome assessment) was assessed using a risk-of-bias machine learning tool. This tool was simultaneously validated using 63,327 human risk-of-bias assessments obtained from 17,394 RCTs evaluated in the Cochrane Database of Systematic Reviews (CDSR). Moreover, RCT registration and CONSORT Statement reporting were assessed using automated searches. Publication characteristics included the number of authors, journal impact factor (JIF), and medical discipline. The annual number of published RCTs substantially increased over 4 decades, accompanied by increases in authors (5.2 to 7.8) and institutions (2.9 to 4.8). The risk of bias remained present in most RCTs but decreased over time for allocation concealment (63% to 51%), random sequence generation (57% to 36%), and blinding of outcome assessment (58% to 52%). Trial registration (37% to 47%) and the use of the CONSORT Statement (1% to 20%) also rapidly increased. In journals with a higher impact factor (>10), the risk of bias was consistently lower with higher levels of RCT registration and the use of the CONSORT Statement. Automated risk-of-bias predictions had accuracies above 70% for allocation concealment (70.7%), random sequence generation (72.1%), and blinding of patients/personnel (79.8%), but not for blinding of outcome assessment (62.7%). In conclusion, the likelihood of bias in RCTs has generally decreased over the last decades. This optimistic trend may be driven by increased knowledge augmented by mandatory trial registration and more stringent reporting guidelines and journal requirements. Nevertheless, relatively high probabilities of bias remain, particularly in journals with lower impact factors. This emphasizes that further improvement of RCT registration, conduct, and reporting is still urgently needed.

Decreasing trends in cholangiocarcinoma incidence and relative survival in Khon Kaen, Thailand: An updated, inclusive, population-based cancer registry analysis for 1989-2018.

BACKGROUND: Cholangiocarcinoma (CCA) is a leading cause of cancer death in northeastern Thailand. We reported on the incidence of CCA using only one method. In the current study, we used three different statistical methods to forecast future trends and estimate relative survival. METHODS: We reviewed the CCA cases diagnosed between 1989 and 2018 recorded in the population-based Khon Kaen Cancer Registry (KKCR). Annual percent change (APC) was calculated to quantify the incidence rate trends using Joinpoint regression. Age-period-cohort models (APC model) were used to examine the temporal trends of CCA by age, calendar year, and birth cohort. We projected the incidence of CCA up to 2028 using three independent approaches: the Joinpoint, Age-period-cohort, and Nordpred models. Survival assessments were based on relative survival (RS). RESULTS: The respective APC in males and females decreased significantly (-3.1%; 95%CI: -4.0 to -2.1 and -2.4%; 95%CI: -3.6 to -1.2). The APC model-AC-P for male CCA-decreased according to a birth-cohort. The CCA incidence for males born in 1998 was 0.09 times higher than for those born in 1966 (Incidence rate ratios, IRR = 0.09; 95%CI: 0.07 to 0.12). The relative incidence for female CCA similarly decreased according to a birth-cohort (IRR = 0.11; 95%CI: 0.07 to 0.17). The respective projection for the age-standardized rate for males and females for 2028 will be 7.6 per 100,000 (102 patients) and 3.6 per 100,000 (140 patients). The five-year RS for CCA was 10.9% (95%CI: 10.3 to 11.6). CONCLUSION: The incidence rate of CCA has decreased. The projection for 2028 is that the incidence will continue to decline. Nevertheless, the survival of patients with CCA remains poor.

Tobacco Use Is Associated with Readmission within 90 Days after Craniotomy.

OBJECTIVE: Tobacco use increases morbidity and mortality following craniotomy. Readmission is an important hospital metric of patient outcomes and has been used to inform reimbursement. This study aims to determine if tobacco use is associated with readmission within 90 days of hospital discharge among patients undergoing elective craniotomy. METHODS: The Nationwide Readmissions Database (NRD), a population-based, nationally representative database, was queried from 2010-2014. Patients undergoing craniotomy for benign or malignant tumors, vascular pathologies, and epilepsy were identified. Readmissions within 90 days of index hospitalization were characterized by admitting diagnoses. Tobacco use was defined by ICD-9 coding for active or prior use. Descriptive and multivariable regression analyses evaluated patient and hospital factors associated with readmission. RESULTS: The study population included 77,903 patients treated with craniotomy. Of these, 17,674 (22.6%) were readmitted within 90 days. The most common reasons for readmission were post-operative infection (5.8%), septicemia (4.2%), pulmonary embolism (3.9%), and pneumonia (2.9%). Tobacco use was associated with a 7% increased likelihood of 90-day readmission (OR 1.07, 95% CI 1.03-1.11, p = 0.0008) after accounting for other patient-, disease-, and hospital-level factors in multivariate analysis. CONCLUSIONS: Tobacco use was associated with increased 90-day readmission in patients undergoing craniotomy. Recognizing tobacco use as a modifiable risk factor of readmission presents an opportunity to identify susceptible patients.

Critical Steps in Data Management During a Crisis.

Data management is essential in a flow cytometry (FCM) shared resource laboratory (SRL) for the integrity of collected data and its long-term preservation, as described in the Cytometry publication from 2016, ISAC Flow Cytometry Shared Resource Laboratory (SRL) Best Practices (Barsky et al.: Cytometry Part A 89A(2016): 1017-1030). The SARS-CoV-2 pandemic introduced an array of challenges in the operation of SRLs. The subsequent laboratory shutdowns and access restrictions brought to the forefront well-established practices that withstood the impact of a sudden change in operations and illuminated areas that need improvement. The most significant challenges from a data management perspective were data access for remote analysis and workstation management. Notably, lessons learned from this challenge emphasize the importance of safeguarding collected data from loss in various emergencies such as fire or natural disasters where the physical hardware storing data could be directly affected. Here, we describe two data management systems that have been successful during the current emergency created by the pandemic, specifically remote access and automated data transfer. We will discuss other situations that could arise and lead to data loss or challenges in interpreting data. © 2020 International Society for Advancement of Cytometry.

Timely access to trial data in the context of a pandemic: the time is now.

OBJECTIVE: Clinical trial data sharing has the potential to accelerate scientific progress, answer new lines of scientific inquiry, support reproducibility and prevent redundancy. Vivli, a non-profit organisation, operates a global platform for sharing of individual participant-level trial data and associated documents. Sharing of these data collected from each trial participant enables combining of these data to drive new scientific insights or assess reproducibility-not possible with the aggregate or summary data tables historically made available. We report on our initial experience including key metrics, lessons learned and how we see our role in the data sharing ecosystem. We also describe how Vivli is addressing the needs of the COVID-19 challenge through a new dedicated portal that provides a direct search function for COVID-19 studies, availability for fast-tracked request review and data sharing. DATA SUMMARY: The Vivli platform was established in 2018 and has partnered with 28 diverse members from industry, academic institutions, government platforms and non-profit foundations. Currently, 5400 trials representing 3.6 million participants are shared on the platform. From July 2018 to September 2020, Vivli received 201 requests. To date, 106 of 201 requests received approval, 5 have been declined, 27 withdrew and 27 are in the revision stage. CONCLUSIONS: The pandemic has only magnified the necessity for data sharing. If most data are shared and in a manner that allows interoperability, then we have hope of moving towards a cohesive scientific understanding more quickly not only for COVID-19 but also for all diseases. Conversely, if only isolated pockets of data are shared then society loses the opportunity to close vital gaps in our understanding of this rapidly evolving epidemic. This current challenge serves to highlight the value of data sharing platforms-critical enablers that help researchers build on prior knowledge.

Open access publishers: The new players.

The essential role of journals as registries of scientific activity in all areas of knowledge justifies concern about their ownership and type of access. The purpose of this research is to analyze the main characteristics of publishers with journals that have received the DOAJ Seal. The specific objectives are a) to identify publishers and journals registered with the DOAJ Seal; b) to characterize those publishers; and c) to analyze their article processing fees. The research method involved the use of the DOAJ database, the Seal option and the following indicators: publisher, title, country, number of articles, knowledge area, article processing charges in USD, time for publication in weeks, and year of indexing in DOAJ. The results reveal a fast-rising oligopoly, dominated by Springer with 35% of the titles and PLOS with more than 20% of the articles. We've identified three models of expansion: a) a few titles with hundreds of articles; b) a high number of titles with a mix of big and small journals; and c) a high number of titles with medium-size journals. We identify a high number of titles without APCs (27%) in all areas while medicine was found to be the most expensive area. Commercial publishers clearly exercise control over the scope of journals and the creation of new titles, according to the interests of their companies, which are not necessarily the same as those of the scientific community or of society in general.

Osteoporosis-related Vertebral Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Own the Bone Database.

STUDY DESIGN: Retrospective cohort study of the Own the Bone database which is a fracture liaison service designed to improve recognition and treatment of osteoporosis. OBJECTIVE: To use the Own the Bone (OTB) database to 1) examine the specific demographics of patients presenting with a low-energy clinical vertebral fracture (VFX) and 2) compare demographic and fracture-specific risk factors between patients with clinical VFX versus patients with nonvertebral low-energy fracture (NVFX). SUMMARY OF BACKGROUND DATA: Large database studies have described risk factors for developing VFX. It is well described that a history of previous VFX portends an increased risk of future VFX. Few studies have reported cohorts from a fracture liaison service such as the OTB initiative. METHODS: 35,039 unique cases of fragility fracture occurred between 2009 and 2016 and were included in analysis. VFX accounted for 3395 (9.9%) of the presenting fractures at OTB enrollment. The demographics, lifestyle factors, medication use, and fracture-specific data for patients in the OTB registry with vertebral fractures were summarized and then statistically compared to those with nonvertebral fragility fractures. RESULTS: The majority of VFX patients were Caucasian, postmenopausal women (74.4%). There was an increased likelihood of presenting with a vertebral fracture in patients who sustained a previous VFX after the age of 50, while patients who sustained a prior nonvertebral fracture (NVFX) were more likely to present with a subsequent NVFX. After controlling for patients with a history of fracture after the age of 50, VFX patients (vs. NVFX) were more likely to be age 70-79, class 1 obesity, with a history of taking anti-osteoporotic prescription medications. CONCLUSIONS: Multiple factors were associated with a significantly increased risk of VFX compared with NVFX. Understanding the risk factors unique to fragility VFX is a critical component for targeting "at-risk" patients and preventing future osteoporosis-related fractures and their consequences. LEVEL OF EVIDENCE: 4.

Benchmarks of Duration and Magnitude of Opioid Consumption After Common Spinal Procedures: A Database Analysis of 47,823 Patients.

STUDY DESIGN: A retrospective cohort study performed in a nationwide insurance claims database. OBJECTIVE: This study aimed to examine duration and magnitude of postoperative opioid prescriptions following common spinal procedures. SUMMARY OF BACKGROUND DATA: Postoperative opioid prescription practices vary widely among providers and procedures and standards of care are not well-established. Previous work does not adequately quantify both duration and magnitude of opioid prescription. METHODS: Forty seven thousand eight hundred twenty three patients with record of any of four common spinal procedures in a nationwide insurance claims database were stratified by preoperative opioid use into three categories: "opioid naive," "sporadic user," or "chronic user," defined as 0, 1, or 2+ prescriptions filled in the 6 months preceding surgery. Those with record of subsequent surgery or readmission were excluded. Duration of opioid use was defined as the time between the index surgery and the last record of filling an opioid prescription. Magnitude of opioid use was defined as milligram morphine equivalents (MME) filled by 30 days post-op, converted to 5 mg oxycodone pills for interpretation. RESULTS: Opioid naive patients were less likely than chronic opioid users to fill any opioid prescription after surgery (63-68% naive vs. 91-95% chronic, P < 0.001), and when they did, their prescriptions were smaller in magnitude (76-91 pills naive vs. 127-152 pills chronic). One year after surgery, 15% to 18% of opioid naive and 50% to 64% of chronic opioid users continued filling prescriptions. CONCLUSION: Opioid naive patients use less postoperative opioids, and for a shorter period of time, than chronic users. This study serves as a normative benchmark for examining postoperative opioid use, which can assist providers in identifying patients with opioid dependence. Importantly, this work calls out the high risk of opioid exposure, as 15% to 18% of opioid naive patients continued filling opioid prescriptions 1 year after surgery. LEVEL OF EVIDENCE: 3.

From enhanced collaborations to space advancements: technologies to bring libraries (and librarians) full circle and into the future.

Since the Journal of the Medical Library Association (JMLA) Virtual Projects section was first announced in 2012, the virtual projects featured in the JMLA have expanded or improved library spaces, services, collaborations, connections, and future directions. Virtual projects selected by the JMLA Virtual Projects Section Advisory Committee have been both practical and responsive to library and patron needs and illustrate ways that librarians are leading their communities and services in new directions. Virtual projects highlighted in this year's section demonstrate innovative adaptations of technology into the modern medical library that strengthen collaborative commitments and clinical and research partnerships. They also illustrate how technologies support the idea of "library as place" by providing spaces for users to explore new technologies, as well as tools for space and service planning. This year's virtual projects fully embrace changes in learning, research patterns, technologies, and the role of the health sciences librarian and the library.

Early warnings and repayment plans: novel trial management methods for monitoring and managing data return rates in a multi-centre phase III randomised controlled trial with paper Case Report Forms.

BACKGROUND: Monitoring and managing data returns in multi-centre randomised controlled trials is an important aspect of trial management. Maintaining consistently high data return rates has various benefits for trials, including enhancing oversight, improving reliability of central monitoring techniques and helping prepare for database lock and trial analyses. Despite this, there is little evidence to support best practice, and current standard methods may not be optimal. METHODS: We report novel methods from the Trial of Imaging and Schedule in Seminoma Testis (TRISST), a UK-based, multi-centre, phase III trial using paper Case Report Forms to collect data over a 6-year follow-up period for 669 patients. Using an automated database report which summarises the data return rate overall and per centre, we developed a Microsoft Excel-based tool to allow observation of per-centre trends in data return rate over time. The tool allowed us to distinguish between forms that can and cannot be completed retrospectively, to inform understanding of issues at individual centres. We reviewed these statistics at regular trials unit team meetings. We notified centres whose data return rate appeared to be falling, even if they had not yet crossed the pre-defined acceptability threshold of an 80% data return rate. We developed a set method for agreeing targets for gradual improvement with centres having persistent data return problems. We formalised a detailed escalation policy to manage centres who failed to meet agreed targets. We conducted a post-hoc, descriptive analysis of the effectiveness of the new processes. RESULTS: The new processes were used from April 2015 to September 2016. By May 2016, data return rates were higher than they had been at any time previously, and there were no centres with return rates below 80%, which had never been the case before. In total, 10 centres out of 35 were contacted regarding falling data return rates. Six out of these 10 showed improved rates within 6-8 weeks, and the remainder within 4 months. CONCLUSIONS: Our results constitute preliminary effectiveness evidence for novel methods in monitoring and managing data return rates in randomised controlled trials. We encourage other researchers to work on generating better evidence-based methods in this area, whether through more robust evaluation of our methods or of others.

Impact of Patient's Global Assessment on Achieving Remission in Patients With Rheumatoid Arthritis: A Multinational Study Using the METEOR Database.

OBJECTIVE: There is an ongoing debate about excluding patient's global assessment (PtGA) from composite and Boolean-based definitions of rheumatoid arthritis (RA) remission. This study aimed at determining the influence of PtGA on RA disease states, exploring differences across countries, and understanding the association between PtGA, measures of disease impact (symptoms), and markers of disease activity (inflammation). METHODS: Cross-sectional data from the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology international database were used. We calculated the proportion of patients failing American College of Rheumatology/European League Against Rheumatism Boolean-based remission (4-variable remission) solely due to PtGA (PtGA-near-remission) in the overall sample and in the most representative countries (i.e., those with >3,000 patients in the database). Multivariable linear regression models were used to identify the main determinants of PtGA, grouped in predominantly inflammatory impact factors (28 tender joint counts, 28 swollen joint counts, and C-reactive protein level) and disease impact factors (pain and function). RESULTS: This study included 27,768 patients. Excluding PtGA from the Boolean-based definition (3-variable remission) increased the remission rate from 5.8% to 15.8%. The rate of PtGA-near-remission varied considerably between countries, from 1.7% in India to 17.9% in Portugal. One-third of the patients in PtGA-near-remission group scored PtGA >4 of 10. Pain and function were the main correlates of PtGA, with inflammation-related variables contributing less to the model (R2 = 0.57). CONCLUSION: PtGA is moderately related to joint inflammation overall, but only weakly so in low levels of disease activity. A considerable proportion of patients otherwise in biologic remission still perceive high PtGA, putting them at risk of excessive immunosuppressive treatment.

LncRNADisease 2.0: an updated database of long non-coding RNA-associated diseases.

Mounting evidence suggested that dysfunction of long non-coding RNAs (lncRNAs) is involved in a wide variety of diseases. A knowledgebase with systematic collection and curation of lncRNA-disease associations is critically important for further examining their underlying molecular mechanisms. In 2013, we presented the first release of LncRNADisease, representing a database for collection of experimental supported lncRNA-disease associations. Here, we describe an update of the database. The new developments in LncRNADisease 2.0 include (i) an over 40-fold lncRNA-disease association enhancement compared with the previous version; (ii) providing the transcriptional regulatory relationships among lncRNA, mRNA and miRNA; (iii) providing a confidence score for each lncRNA-disease association; (iv) integrating experimentally supported circular RNA disease associations. LncRNADisease 2.0 documents more than 200 000 lncRNA-disease associations. We expect that this database will continue to serve as a valuable source for potential clinical application related to lncRNAs. LncRNADisease 2.0 is freely available at http://www.rnanut.net/lncrnadisease/.