Thomas Trikalinos

Brown University · Center for Evidence-Based Medicine

Study objectives: Systematic review of long-term health outcomes of continuous positive airway pressure (CPAP) use in adults with obstructive sleep apnea. Methods: We updated prior systematic reviews with searches in multiple databases through January 3, 2023. We included randomized controlled trials (RCTs) and adjusted nonrandomized comparative...

Objective To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). Methods PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no...

Background We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism. Methods Ten models are being independently developed as part of the Canc...

Background: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable...

Medical systematic reviews are crucial for informing clinical decision making and healthcare policy. But producing such reviews is onerous and time-consuming. Thus, high-quality evidence synopses are not available for many questions and may be outdated even when they are available. Large language models (LLMs) are now capable of generating long-for...

Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear. Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes. Data sources: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022. Study selection: Eligible tr...

Background Disparities in the health and economic burden of gonorrhoea have not been systematically quantified. We estimated population-level health losses and costs associated with gonococcal infection and sequelae in the United States. Methods We used probability-tree models to capture gonorrhoea sequelae and to estimate attributable disease bur...

We provide a quantitative and qualitative analysis of self-repetition in the output of neural summarizers. We measure self-repetition as the number of n-grams of length four or longer that appear in multiple outputs of the same system. We analyze the behavior of three popular architectures (BART, T5 and Pegasus), fine-tuned on five datasets. In a r...

Objective To describe and pilot a novel method for continuously identifying newly published trials relevant to a systematic review, enabled by combining artificial intelligence (AI) with human expertise. Study Design and Setting We used RobotReviewer LIVE to keep a review of Covid-19 vaccination trials updated from February–August 2021. We compare...

Background Increasing awareness of the emotional impact of an Intensive Care Unit (ICU) hospitalization on patients and their families has led to a rise in studies seeking to mitigate Post Intensive Care Syndrome (PICS) for both groups. In efforts to decrease symptoms of anxiety and depression, ICUs have implemented a variety of programs to reduce...

Objectives Multivariate meta-analysis allows the joint synthesis of multiple outcomes accounting for their correlation. This enables borrowing of strength ( BoS ) across outcomes, which may lead to greater efficiency and even different conclusions compared to separate univariate meta-analyses. However, multivariate meta-analysis is complex to apply...

Objective: Systematic reviews form the basis of evidence-based medicine but are expensive and time-consuming to produce. To address this burden, we have developed a literature identification system (Pythia) that combines the query formulation and citation screening steps. Study design: Pythia incorporates a set of natural-language questions with...

Traditionally, literature identification for systematic reviews has relied on a two-step process: first, searching databases to identify potentially relevant citations, and then manually screening those citations. A number of tools have been developed to streamline and semi-automate this process, including tools to generate terms; to visualize and...

Objectives Multivariate meta-analysis allows the joint synthesis of multiple outcomes accounting for their correlation. This enables borrowing of strength (BoS) across outcomes, which may lead to greater efficiency and even different conclusions compared to separate univariate meta-analyses. However, multivariate meta-analysis is complex to apply,...

Background: The typical approach to literature identification involves two discrete and successive steps: (i) formulating a search strategy (i.e., a set of Boolean queries) and (ii) manually identifying the relevant citations in the corpus returned by the query. We have developed a literature identification system (Pythia) that combines the query f...

Purpose: Bayesian calibration is generally superior to standard direct-search algorithms in that it estimates the full joint posterior distribution of the calibrated parameters. However, there are many barriers to using Bayesian calibration in health decision sciences stemming from the need to program complex models in probabilistic programming lan...

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. Often there is an interest in estimating the relative treatment effects regarding time-to-event outcomes. Cancer trea...

Context: Adolescents with problematic substance use (SU) are at risk for far-reaching adverse outcomes. Objective: Synthesize the evidence regarding the effects of brief behavioral interventions for adolescents (12-20 years) with problematic SU. Data sources: We conducted literature searches in Medline, the Cochrane Central Register of Control...

An emulator is a fast‐to‐evaluate statistical approximation of a detailed mathematical model (simulator). When used in lieu of simulators, emulators can expedite tasks that require many repeated evaluations, such as sensitivity analyses, policy optimization, model calibration, and value‐of‐information analyses. Emulators are developed using the out...

One key question in the ongoing COVID-19 pandemic is understanding the impact of government interventions, and when society can return to normal. To this end, we develop DELPHI, a novel epidemiological model that captures the effect of under-detection and government intervention. We applied DELPHI across 167 geographical areas since early April, an...

Effect size can differ as a function of the elapsed time since treatment or as a function of other key covariates, such as sex or age. In evidence synthesis, a better understanding of the precise conditions under which treatment does work or does not work well has been highly valued. With increasingly accessible individual patient or participant da...

Tests for disease often produce a continuous measure, such as the concentration of some biomarker in a blood sample. In clinical practice, a threshold C is selected such that results, say, greater than C are declared positive and those less than C negative. Measures of test accuracy such as sensitivity and specificity depend crucially on C, and the...

Systematic reviews are used by a diverse range of users to address an ever-expanding set of questions and needs. It is unlikely that a single static report will efficiently satisfy the different needs of diverse users. Methods: An open-source Web-based interactive report presentation of a systematic review was developed to allow users to generate...

Systematic reviews routinely characterize the trustworthiness of individual studies 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. Mechanistic risk o...

Importance Computed tomographic (CT) scanning is the standard for the rapid diagnosis of intracranial injury, but it is costly and exposes patients to ionizing radiation. The Pediatric Emergency Care Applied Research Network (PECARN) rules for identifying children with minor head trauma who are at very low risk of clinically important traumatic bra...

Objective Assessing risks of bias in randomized controlled trials (RCTs) is an important but laborious task when conducting systematic reviews. RobotReviewer (RR), an open-source machine learning (ML) system, semi-automates bias assessments. We conducted a user study of RobotReviewer, evaluating time saved and usability of the tool. Materials and...

Objective: To evaluate diagnostic tests, analysts use meta-analyses to provide inputs to parameters in decision models. Choosing parameter estimands from meta-analyses requires understanding the meta-analytic and decision-making contexts. Study design and setting: We expand on an analysis comparing positron emission tomography (PET), PET with co...

Background Urinary incontinence (UI) is a common malady in women. Numerous nonsurgical treatments are available, each associated with risk of adverse events (AEs). Methods We systematically reviewed nonsurgical interventions for urgency, stress, or mixed UI in women, focusing on AEs. We searched MEDLINE®, Cochrane Central Trials Registry, Cochrane...

Objective: Summarize the psychometric properties of functional, ambulatory, and quality of life instruments among adult lower limb amputees, highlighting evidence deemed generalizable to the United States Medicare population. Data sources: Six databases and existing systematic reviews through October 30, 2017. Searches included terms for lower l...

Background: Urinary incontinence (UI), a common malady in women, most often is classified as stress, urgency, or mixed. Purpose: To compare the effectiveness of pharmacologic and nonpharmacologic interventions to improve or cure stress, urgency, or mixed UI in nonpregnant women. Data sources: MEDLINE, Cochrane Central Register of Controlled Tr...

Background. Leveraging cumulative network meta-analysis (NMA) and value of information (VOI) analysis, this article aims to understand the evolving value of medical research and to identify gaps in the evidence for future research. Methods. As an illustration, we identified 31 randomized controlled trials (RCT) from 1980 to 2013 that examined a n...

An emulator is a fast-to-evaluate statistical approximation of a detailed mathematical model (simulator). When used in lieu of simulators, emulators can expedite tasks that require many repeated evaluations, such as model calibration and value-of-information analyses. Emulators are developed using the output of simulators at specific input values (...

Objectives: In 2016, the Second Panel on Cost-effectiveness in Health and Medicine updated the seminal work of the original panel from 2 decades earlier. The Second Panel had an opportunity to reflect on the evolution of cost-effectiveness analysis (CEA) and to provide guidance for the next generation of practitioners and consumers. In this articl...

Background: Most interventions for basal cell carcinoma (BCC) have not been compared in head-to-head randomized trials. Purpose: To evaluate the comparative effectiveness and safety of treatments of primary BCC in adults. Data sources: English-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Sy...

Importance The prevalence of obesity in patients older than 65 years is increasing. A substantial number of beneficiaries covered by Medicare meet eligibility criteria for bariatric procedures. Objective To assess the comparative effectiveness and safety of bariatric procedures in the Medicare-eligible population. Evidence Review This systematic...

Background: To systematically review evidence on the feasibility and efficacy of real-time electronic notifications about patients at high risk of emergency department (ED) recidivism. Methods: Eight electronic databases were searched for empirical studies of real-time ED-based electronic tools, identifying adult patients at high risk of frequen...

Background: We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. Method: We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review's last literature search, screened the records using the...

Important decisions related to human health, such as screening strategies for cancer, need to be made without a satisfactory understanding of the underlying biological and other processes. Rather, they are often informed by mathematical models that approximate reality. Often multiple models have been made to study the same phenomenon, which may lea...

Background: While in its early years the HIV epidemic affected primarily the male and the young, nowadays, the population living with HIV/AIDS is approximately 24% women, and its age composition has shifted towards older ages. Many of the older women who live with HIV/AIDS also live with the medical and social conditions that accompany aging. This...

Importance Testing for and treating latent tuberculosis infection (LTBI) is among the main strategies to achieve TB elimination in the United States. The best approach to testing among non-US born residents, particularly those with comorbid conditions, is uncertain. Objective To estimate health outcomes, costs, and cost-effectiveness of LTBI testi...

This review examines the conduct and reporting of observational studies using propensity score-based methods to compare coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy for patients with coronary artery disease. A systematic selection process identified 48 studies: 20 CABG vs. PCI; 21 bare-metal s...

Systematic reviews are increasingly used to inform health care decisions, but are expensive to produce. We explore the use of crowdsourcing (distributing tasks to untrained workers via the web) to reduce the cost of screening citations. We used Amazon Mechanical Turk as our platform and 4 previously conducted systematic reviews as examples. For eac...

Context: Tympanostomy tube placement is the most common ambulatory surgery performed on children in the United States. Objectives: The goal of this study was to synthesize evidence for the effectiveness of tympanostomy tubes in children with chronic otitis media with effusion and recurrent acute otitis media. Data sources: Searches were conduc...

Context: Children with tympanostomy tubes often develop ear discharge. Objective: Synthesize evidence about the need for water precautions (ear plugs or swimming avoidance) and effectiveness of topical versus oral antibiotic treatment of otorrhea in children with tympanostomy tubes. Data sources: Searches in Medline, the Cochrane Central Trial...

Objective: To compare statistical methods for meta-analysis of sensitivity and specificity of medical tests (e.g., diagnostic or screening tests). Study design and setting: We constructed a database of PubMed-indexed meta-analyses of test performance from which 2×2 tables for each included study could be extracted. We re-analyzed the data using...

Introduction: Structural models are mathematical representations of the salient aspects of a phenomenon or process. Models of even moderate complexity are “run” using computer-based numerical analysis and simulation. In medicine, such models are used for inference, prediction, or to inform clinical and policy decision-making; thus, model assessment...

Essentials Despite trial data, guidelines have not endorsed direct oral Xa inhibitors above other options. We provide profiles of venous thromboembolism and hemorrhage risk for 12 options. Direct oral Xa inhibitors had a favorable profile compared with low-molecular-weight heparin. Other options did not have favorable profiles compared with low-mol...

Meta‐analysis and meta‐regression are statistical methods for synthesizing and modelling the results of different studies, and are critical research synthesis tools in ecology and evolutionary biology (E&E). However, many E&E researchers carry out meta‐analyses using software that is limited in its statistical functionality and is not easily updata...

Models and simulations are valuable tools for addressing the uncertainty, tradeoffs, and heterogeneous preferences that complicate research questions in health technology assessment. This article presents recommendations for the conduct and reporting of modeling and simulation studies based on a systematic review of published recommendation stateme...

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 cl...

Background: The effect and association of omega-3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes. Objectives: Evaluate the effect of n-3 FA on clinical and selecte...

Oral mechanical bowel preparation is often used before elective colorectal surgery to reduce postoperative complications. The purpose of this study was to synthesize the evidence on the comparative effectiveness and safety of oral mechanical bowel preparation versus no preparation or enema. We searched MEDLINE, the Cochrane Central Register of Cont...

Searching multiple sources when conducting systematic reviews is considered good practice. We aimed to investigate the impact of using sources beyond PubMed in systematic reviews of therapeutic interventions. We randomly selected 50 Cochrane reviews that searched the PubMed (or MEDLINE) and EMBASE databases and included a meta-analysis of ≥10 studi...

In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between st...

: Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potential...

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting...

The reliable identification of patients with abdominal pain who need surgical intervention for acute appendicitis can improve clinical outcomes and reduce resource use. The test performance and impact on outcomes of alternative diagnostic strategies are unclear. We searched PubMed(R), Embase(R), the Cochrane Central Register of Controlled Trials, a...

Existing methods for meta-analysis of diagnostic test accuracy focus primarily on a single index test. We propose models for the joint meta-analysis of studies comparing multiple index tests on the same participants in paired designs. These models respect the grouping of data by studies, account for the within-study correlation between the tests' t...

Purpose: The U.S. Agency for Healthcare Research and Quality (AHRQ) solicited the development of guidance for decision and simulation modeling in the context of systematic reviews. Method: We updated and expanded existing systematic reviews of recommendations for the conduct and reporting of decision and simulation modeling with input from a mult...

There are heterogeneous approaches to cranial irradiation therapy (CRT) for T-lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of studies that specified a radiation strategy and reported survival for pediatric T-ALL. Our analysis included 62 publications reporting 78 treatment groups (patient n=5844). The average event...

Background To improve quality of care and patient outcomes, health system decision-makers need to identify and implement effective interventions. An increasing number of systematic reviews document the effects of quality improvement programs to assist decision-makers in developing new initiatives. However, limitations in the reporting of primary st...

The beta distribution is a basic distribution serving several purposes. It is used to model data, and also, as a more flexible version of the uniform distribution, it serves as a prior distribution for a binomial probability. The bivariate beta distribution plays a similar role for two probabilities that have a bivariate binomial distribution. We p...

We consider the task of grouping doctors with respect to communication patterns exhibited in outpatient visits. We propose a novel approach toward this end in which we model speech act transitions in conversations via a log-linear model incorporating physician specific components. We train this model over transcripts of outpatient visits annotated...

Online physician reviews are a massive and potentially rich source of information capturing patient sentiment regarding healthcare. We analyze a corpus comprising nearly 60 000 such reviews with a state-of-the-art probabilistic model of text. We describe a probabilistic generative model that captures latent sentiment across aspects of care (eg, int...

We develop a Bayesian multinomial network meta-analysis model for unordered (nominal) categorical outcomes that allows for partially observed data in which exact event counts may not be known for each category. This model properly accounts for correlations of counts in mutually exclusive categories and enables proper comparison and ranking of treat...

The aim of evidence-based medicine (EBM) is to inform clinical practice in the light of all available evidence. Systematic review, in which one rigorously synthesizes all of the published literature relevant to a precisely formulated clinical question, is the foundation of EBM. Creating such syntheses involves identifying, extracting and combining...

Treatment effects for multiple outcomes can be meta-analyzed separately or jointly, but no systematic empirical comparison of the two approaches exists. From the Cochrane Library of Systematic Reviews, we identified 45 reviews, including 1473 trials and 258,675 patients, that contained two or three univariate meta-analyses of categorical outcomes f...

Despite the great realized or potential value of network meta-analysis of randomized controlled trial evidence to inform health care decision making, many decision makers might not be familiar with these techniques. The Task Force developed a consensus-based 26-item questionnaire to help decision makers assess the relevance and credibility of indir...

To minimize bias, clinical practice guidelines (CPG) for managing patients with multiple conditions should be informed by well-planned syntheses of the totality of the relevant evidence by means of systematic reviews and meta-analyses. However, deficiencies along the entire evidentiary pathway hinder the development of evidence-based CPGs. Publishe...

Background: When meta-analysing studies examining the diagnostic/predictive accuracy of classifications based on a continuous test, each study may provide results for one or more thresholds, which can vary across studies. Researchers typically meta-analyse each threshold independently. We consider a multivariate meta-analysis to synthesise results...

Many health decisions about screening and treatment for cancers involve uncertainty or tradeoffs between the expected benefits and harms. Patient decision aids have been developed to help health care consumers and their providers identify the available alternatives and choose the one that aligns with their values. It is unclear whether the effectiv...

Core needle biopsy and open surgical biopsy are the most frequently used procedures for diagnosis of suspicious breast lesions. An AHRQ evidence report on the comparative effectiveness and adverse events of breast biopsy methods was completed in 2009. The availability of additional studies and the uncertainties surrounding newer biopsy techniques p...

Annotated patient-provider encounters can provide important insights into clinical communication, ultimately suggesting how it might be improved to effect better health outcomes. But annotating outpatient transcripts with Roter or General Medical Interaction Analysis System (GMIAS) codes is expensive, limiting the scope of such analyses. We propose...

Google Translate offers free Web-based translation, but it is unknown whether its translation accuracy is sufficient to use in systematic reviews to mitigate concerns about language bias. We compared data extraction from non-English language studies with extraction from translations by Google Translate of 10 studies in each of five languages (Chine...

We performed a survey of meta-analyses of test performance to describe the evolution in their methods and reporting. Studies were identified through MEDLINE (1966-2009), reference lists, and relevant reviews. We extracted information on clinical topics, literature review methods, quality assessment, and statistical analyses. We reviewed 760 publica...

The Center for Evidence-Based Medicine in the Brown School of Public Health develops computational tools to help analyze the vast amounts of data generated by medical research. By conducting meta-analyses and systemic reviews of published literature, Center researchers can tease out which treatments are most effective and efficient, helping to guid...

The objective of this study is to empirically compare alternative meta‐analytic methods for combining dose‐response data from epidemiological studies. We identified meta‐analyses of epidemiological studies that analyzed the association between a single nutrient and a dichotomous outcome. For each topic, we performed meta‐analyses of odds ratios wit...

Preferential loss of heterozygosity at the rs1042522 locus of the tumor protein 53 gene (TP53) (Arg72Pro) is observed in several tumors. Genetic association studies in oncology often use tumor tissue rather than unaffected tissue for genotyping; in such cases, loss of heterozygosity at the TP53 locus could lead to differential misclassification and...

Systematic reviews are being increasingly used to inform all levels of healthcare, from bedside decisions to policy-making. Since they are designed to minimize bias and subjectivity, they are a preferred option to assess the comparative effectiveness and safety of healthcare interventions. However, producing systematic reviews and keeping them up-t...