Systematic reviews address a specific clinical question by unbiasedly assessing and analyzing the pertinent literature. Citation screening is a time-consuming and critical step in systematic reviews. ...Typically, reviewers must evaluate thousands of citations to identify articles eligible for a given review. We explore the application of machine learning techniques to semi-automate citation screening, thereby reducing the reviewers' workload.
We present a novel online classification strategy for citation screening to automatically discriminate "relevant" from "irrelevant" citations. We use an ensemble of Support Vector Machines (SVMs) built over different feature-spaces (e.g., abstract and title text), and trained interactively by the reviewer(s). Semi-automating the citation screening process is difficult because any such strategy must identify all citations eligible for the systematic review. This requirement is made harder still due to class imbalance; there are far fewer "relevant" than "irrelevant" citations for any given systematic review. To address these challenges we employ a custom active-learning strategy developed specifically for imbalanced datasets. Further, we introduce a novel undersampling technique. We provide experimental results over three real-world systematic review datasets, and demonstrate that our algorithm is able to reduce the number of citations that must be screened manually by nearly half in two of these, and by around 40% in the third, without excluding any of the citations eligible for the systematic review.
We have developed a semi-automated citation screening algorithm for systematic reviews that has the potential to substantially reduce the number of citations reviewers have to manually screen, without compromising the quality and comprehensiveness of the review.
Studies suggest that vitamin D supplementation may reduce cancer and fracture risks.
To examine the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of ...cancer and fractures in adults.
English-language studies identified from MEDLINE and the Cochrane Central Register of Controlled Trials through July 2011.
Randomized, controlled trials (RCTs), prospective cohort studies, and nested case-control studies reporting incidence of or death from cancer and fracture outcomes.
Multiple reviewers extracted details about participant characteristics, including baseline vitamin D status and use of supplements; details of statistical analyses, including adjustments for confounding; and methodological quality. Differences were resolved by consensus.
19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed. Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-OHD) concentrations might be associated with increased risk for cancer. Mixed-effects dose-response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose-response relationships for prostate and breast cancer. Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 CI, 0.78 to 0.99) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 CI, 0.57 to 0.89) versus community-dwelling (relative risk, 0.89 CI, 0.76 to 1.04). One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones.
Most trial participants were older (aged≥65 years) postmenopausal women. Observational studies were heterogeneous and were limited by potential confounders.
Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects may be smaller among community-dwelling older adults than among institutionalized elderly persons. Appropriate dose and dosing regimens, however, require further study. Evidence is not sufficiently robust to draw conclusions regarding the benefits or harms of vitamin D supplementation for the prevention of cancer.
Agency for Healthcare Research and Quality.
Meta-analysis is increasingly used as a key source of evidence synthesis to inform clinical practice. The theory and statistical foundations of meta-analysis continually evolve, providing solutions ...to many new and challenging problems. In practice, most meta-analyses are performed in general statistical packages or dedicated meta-analysis programs.
Herein, we introduce Meta-Analyst, a novel, powerful, intuitive, and free meta-analysis program for the meta-analysis of a variety of problems. Meta-Analyst is implemented in C# atop of the Microsoft .NET framework, and features a graphical user interface. The software performs several meta-analysis and meta-regression models for binary and continuous outcomes, as well as analyses for diagnostic and prognostic test studies in the frequentist and Bayesian frameworks. Moreover, Meta-Analyst includes a flexible tool to edit and customize generated meta-analysis graphs (e.g., forest plots) and provides output in many formats (images, Adobe PDF, Microsoft Word-ready RTF). The software architecture employed allows for rapid changes to be made to either the Graphical User Interface (GUI) or to the analytic modules.We verified the numerical precision of Meta-Analyst by comparing its output with that from standard meta-analysis routines in Stata over a large database of 11,803 meta-analyses of binary outcome data, and 6,881 meta-analyses of continuous outcome data from the Cochrane Library of Systematic Reviews. Results from analyses of diagnostic and prognostic test studies have been verified in a limited number of meta-analyses versus MetaDisc and MetaTest. Bayesian statistical analyses use the OpenBUGS calculation engine (and are thus as accurate as the standalone OpenBUGS software).
We have developed and validated a new program for conducting meta-analyses that combines the advantages of existing software for this task.
Background Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk. Study ...Design Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level. Setting & Population Patients with anemia of CKD irrespective of dialysis status. Selection Criteria for Studies We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for the treatment of anemia in adults with CKD, with a minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis. Predictors ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels. Outcomes All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression, or transfusion requirement. Results 31 trials (12,956 patients) met the criteria. All-cause mortality was associated with higher (per epoetin alfa–equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio IRR, 1.42; 95% CI, 1.10-1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02-1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 1.41; 95% CI, 1.08-1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction, but not statistically significant. Higher total-study-period mean ESA dose also was associated with increased rate of hypertension, stroke, and thrombotic events, including dialysis vascular access–related thrombotic events. Limitations Use of study-level aggregated data; use of epoetin alfa–equivalent doses; lack of adjustment for confounders. Conclusions In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin level.
Abstract Objective This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the ...Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. Study Design and Setting We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. Results We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. Conclusion Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency.
Summary
Multiple randomized controlled trials, each comparing a subset of competing interventions, can be synthesized by means of a network meta‐analysis to estimate relative treatment effects ...between all interventions in the evidence base. Here we focus on estimating relative treatment effects for time‐to‐event outcomes. Cancer treatment effectiveness is frequently quantified by analyzing overall survival (OS) and progression‐free survival (PFS). We introduce a method for the joint network meta‐analysis of PFS and OS that is based on a time‐inhomogeneous tri‐state (stable, progression, and death) Markov model where time‐varying transition rates and relative treatment effects are modeled with parametric survival functions or fractional polynomials. The data needed to run these analyses can be extracted directly from published survival curves. We demonstrate use by applying the methodology to a network of trials for the treatment of non‐small‐cell lung cancer. The proposed approach allows the joint synthesis of OS and PFS, relaxes the proportional hazards assumption, extends to a network of more than two treatments, and simplifies the parameterization of decision and cost‐effectiveness analyses.
The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.
To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.
PubMed, ...Embase, and ClinicalTrials.gov from database inception through 9 December 2022.
Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.
The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.
Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 95% CI, 0.75 to 0.96) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 CI, 0.16 to 0.36), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 CI, 1.16 to 1.46). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 CI, 0.69 to 1.99; hypercalcemia: 2.34 CI, 0.83 to 6.66; hypercalciuria: 1.65 CI, 0.83 to 3.28; death: 0.85 CI, 0.31 to 2.36).
Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.
In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.
None. (PROSPERO: CRD42020163522).
Summary Background Over the past 20 years, percutaneous transluminal balloon coronary angioplasty (PTCA), bare-metal stents (BMS), and drug-eluting stents (DES) succeeded each other as catheter-based ...treatments for coronary artery disease. We undertook a systematic overview of randomised trials comparing these interventions with each other and with medical therapy in patients with non-acute coronary artery disease. Methods We searched Medline for trials contrasting at least two of the four interventions (PTCA, BMS, DES, and medical therapy). Eligible outcomes were death, myocardial infarction, coronary artery bypass grafting, target lesion or vessel revascularisation, and any revascularisation. Random effects meta-analyses summarised head-to-head (direct) comparisons, and network meta-analyses integrated direct and indirect evidence. Findings 61 eligible trials (25 388 patients) investigated four of six possible comparisons between the four interventions; no trials directly compared DES with medical therapy or PTCA. In all direct or indirect comparisons, succeeding advancements in percutaneous coronary intervention did not produce detectable improvements in deaths or myocardial infarction. The risk ratio (RR) for indirect comparisons between DES and medical therapy was 0·96 (95% CI 0·60–1·52) for death and 1·15 (0·73–1·82) for myocardial infarction. By contrast, we recorded sequential significant reductions in target lesion or vessel revascularisation with BMS compared with PTCA (RR 0·68 0–60·0·77) and with DES compared with BMS (0·44 0·35–0·56). The RR for the indirect comparison between DES and PTCA for target lesion or vessel revascularisation was 0·30 (0·17–0·51). Interpretation Sequential innovations in the catheter-based treatment of non-acute coronary artery disease showed no evidence of an effect on death or myocardial infarction when compared with medical therapy. These results lend support to present recommendations to optimise medical therapy as an initial management strategy in patients with this disease. Funding US National Institutes of Health.
Abstract
The trustworthiness of individual studies is routinely characterized in systemic reviews by evaluating risk of bias, often by mechanistically applying standardized algorithms. However, such ...instruments prioritize the repeatability of the process over a more thoughtful and informative but necessarily somewhat more subjective approach. In mechanistic risk of bias assessments, the focus is on determining whether specific biases are present, but these assessments do not provide insights into the direction, magnitude, and relative importance of individual biases. In such assessments, all potential biases are naively treated as equally important threats to validity and equally important across all research topics, potentially leading to inappropriate conclusions about the overall strength of the available evidence. Instead, risk of bias assessments be should focused on identifying a few of the most likely influential sources of bias, based on methodologic and subject matter expertise, classifying each specific study on the basis of on how effectively it has addressed each potential bias, and determining whether results differ across studies in relation to susceptibility to each hypothesized source of bias. This approach provides insight into the potential impact of each specific bias, identifies a subset of studies likely to best approximate the causal effect, and suggests design features needed to improve future research.
IMPORTANCE: Since publication of the report by the Panel on Cost-Effectiveness in Health and Medicine in 1996, researchers have advanced the methods of cost-effectiveness analysis, and policy makers ...have experimented with its application. The need to deliver health care efficiently and the importance of using analytic techniques to understand the clinical and economic consequences of strategies to improve health have increased in recent years. OBJECTIVE: To review the state of the field and provide recommendations to improve the quality of cost-effectiveness analyses. The intended audiences include researchers, government policy makers, public health officials, health care administrators, payers, businesses, clinicians, patients, and consumers. DESIGN: In 2012, the Second Panel on Cost-Effectiveness in Health and Medicine was formed and included 2 co-chairs, 13 members, and 3 additional members of a leadership group. These members were selected on the basis of their experience in the field to provide broad expertise in the design, conduct, and use of cost-effectiveness analyses. Over the next 3.5 years, the panel developed recommendations by consensus. These recommendations were then reviewed by invited external reviewers and through a public posting process. FINDINGS: The concept of a “reference case” and a set of standard methodological practices that all cost-effectiveness analyses should follow to improve quality and comparability are recommended. All cost-effectiveness analyses should report 2 reference case analyses: one based on a health care sector perspective and another based on a societal perspective. The use of an “impact inventory,” which is a structured table that contains consequences (both inside and outside the formal health care sector), intended to clarify the scope and boundaries of the 2 reference case analyses is also recommended. This special communication reviews these recommendations and others concerning the estimation of the consequences of interventions, the valuation of health outcomes, and the reporting of cost-effectiveness analyses. CONCLUSIONS AND RELEVANCE: The Second Panel reviewed the current status of the field of cost-effectiveness analysis and developed a new set of recommendations. Major changes include the recommendation to perform analyses from 2 reference case perspectives and to provide an impact inventory to clarify included consequences.