Christopher H Schmid

School of Public Health- Brown University · Biostatistics and Center for Evidence Based Medicine

Background Despite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in...

An N-of-1 trial is a multiple crossover trial conducted in a single individual to provide evidence to directly inform personalized treatment decisions. Advancements in wearable devices greatly improved the feasibility of adopting these trials to identify optimal individual treatment plans, particularly when treatments differ among individuals and r...

Introduction: Recurring outbreaks of cholera coupled with lack of laboratory diagnostic capacity in low resource settings fuels clinicians’ reliance on clinical case definitions and highlights the importance of accurate diagnostic guidelines. While “rice-water” stool color is the hallmark predictor of cholera, few have examined the diagnostic accur...

Objective: We propose the origami plot, which maintains the original functionality of a radar chart and avoids potential misuse of its connected regions, with newly added features to better assist multi-criteria decision-making. Study design and setting: Built upon a radar chart, the origami plot adds additional auxiliary axes and points such th...

[This corrects the article DOI: 10.1371/journal.pntd.0009266.].

Media Summary Data science is commonly construed as the process of extracting or mining knowledge from ‘big data’ obtained from a large group of individuals, for insights that can be used to shape clinical, corporate, or public policies. This article introduces a complementary construction: personalized data science (Per-DS), the scientific investi...

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...

Objectives: Evidence about Specific Carbohydrate Diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD to a modified SCD (MSCD) and comparing each to the participant's baseline, usual diet (UD). Methods: Across 19 sites, we recruited patients 7-18 years with IBD a...

Introduction: Black and Hispanic individuals in the US experience more socioeconomic adversities that are associated with disparities in tobacco use and cessation than White individuals. This study examined if racial/ethnic differences in smoking abstinence were mediated by socioeconomic (SES) adversities. Methods: Data from 7,101 established sm...

Background Antimicrobial resistance (AMR) is a global public health threat and is increasingly prevalent among enteric pathogens in low- and middle-income countries (LMICs). However, the burden of multidrug-resistant organisms (MDROs) in older children, adults, and elderly patients with acute diarrhea in LMICs is poorly understood. This study’s aim...

Background Episodes of acute diarrhea lead to dehydration, and existing care algorithms base treatment around categorical estimates for fluid resuscitation. This study aims to develop models for the percentage dehydration (fluid deficit) in individuals with acute diarrhea, to better target treatment and avoid the potential sequelae of over or under...

Importance Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown....

In 2016, diarrheal disease was the eighth leading cause of mortality globally accounting for over 1.6 million deaths with the majority of deaths in adults and children over 5 years. This study aims to investigate the clinical, sociodemographic, and environmental risk factors associated with common bacterial acute diarrhea among adults and children...

N-of-1 trials, single participant trials in which multiple treatments are sequentially randomized over the study period, can give direct estimates of individual-specific treatment effects. Combining n-of-1 trials gives extra information for estimating the population average treatment effect compared with randomized controlled trials and increases p...

Clinicians and patients often try a treatment for an initial period to inform longer‐term therapeutic decisions. A more rigorous approach involves N‐of‐1 trials. In these single‐patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double‐blinded, random sequence o...

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 availability of mobile clinical decision-support (CDS) tools has grown substantially with the increased prevalence of smartphone devices and applications (apps). Though healthcare providers express interest in integrating mobile health (mHealth) technologies into their clinical settings, concerns raised include perceived disagreement...

Background: The availability of mobile clinical decision support (CDS) tools has grown substantially with the increased prevalence of smartphone devices and apps. Although health care providers express interest in integrating mobile health (mHealth) technologies into their clinical settings, concerns have been raised, including perceived disagreem...

Objective Accurately assessing dehydration severity is a critical step in reducing mortality from diarrhea, but is complicated by cholera and undernutrition. This study seeks to assess the accuracy of two clinical diagnostic models for dehydration among patients over five years with cholera and undernutrition and compare their respective performanc...

Diarrheal disease accounts for more than one million deaths annually in patients over 5 years of age. Although most patients can be managed with oral rehydration solution, patients with severe dehydration require resuscitation with intravenous fluids. Scoring systems to assess dehydration have been empirically derived and validated in children unde...

Objective : To examine pain treatment preferences before and after participation in an N-of-1 trial. Study Design and Setting : In this observational study nested within a randomized trial, we examined chronic pain patients’ preferences before and after treatment in relation to N-of-1 trial results; assessed the influence of different schemes for...

Introduction E-cigarette (e-cig) use is widespread and may play an important role in facilitating smoking reduction. Racial/ethnic minorities are less likely than Whites to use e-cigs and suffer disproportionate tobacco-related disease, making them a priority for harm reduction. This paper explores factors associated with smoking reduction among Af...

The pooled estimate of the average effect is of primary interest when fitting the random‐effects model for meta‐analysis. However estimates of study specific effects, for example those displayed on forest plots, are also often of interest. In this tutorial, we present the case, with the accompanying statistical theory, for estimating the true study...

Diarrheal diseases lead to an estimated 1.3 million deaths each year, with the majority of those deaths occurring in patients over five years of age. As the severity of diarrheal disease can vary widely, accurately assessing dehydration status remains the most critical step in acute diarrhea management. The objective of this study is to empirically...

Systematic reviews and meta-analyses synthesize results from well-conducted studies to optimize healthcare decision-making. Network meta-analysis (NMA) is particularly useful for improving precision, drawing new comparisons and ranking multiple interventions. However, recommendations can be misled if published results are a selective sample of what...

Objectives Few studies have evaluated determinants of multidrug resistant (MDR) Vibrio cholerae O1 in older children and adults. This study’s aim was to characterize the prevalence of MDR V. cholerae O1 and associated risk factors among patients over five years in Bangladesh. Methods Stool culture and antimicrobial susceptibility testing were perf...

The normal‐normal hierarchical model (NNHM) constitutes a simple and widely used framework for meta‐analysis. In the common case of only few studies contributing to the meta‐analysis, standard approaches to inference tend to perform poorly, and Bayesian meta‐analysis has been suggested as a potential solution. The Bayesian approach, however, requir...

The growing number of available treatment options have led to urgent needs for reliable answers when choosing the best course of treatment for a patient. As it is often infeasible to compare a large number of treatments in a single randomized controlled trial, multivariate network meta-analyses (NMAs) are used to synthesize evidence from existing t...

Importance Fourth-generation nicotine salt pod system (NSPS) electronic cigarettes (e-cigarettes) are the leading class of e-cigarettes. They contain high nicotine concentrations, which may facilitate switching among smokers, but could also lead to increased exposure to nicotine and biomarkers of potential harm. African American and Latinx smokers...

We describe methods for assessing heterogeneity of treatment effects over pre-specified subgroups in observational studies, using outcome model-based (g-formula), inverse probability weighting, doubly robust, and matching estimators of subgroup-specific potential outcome means, conditional average treatment effects, and measures of heterogeneity of...

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...

Background: Most randomized controlled trials (RCTs) and meta-analyses of RCTs examine effect modification (also called a subgroup effect or interaction), in which the effect of an intervention varies by another variable (e.g., age or disease severity). Assessing the credibility of an apparent effect modification presents challenges; therefore, we...

The normal-normal hierarchical model (NNHM) constitutes a simple and widely used framework for meta-analysis. In the common case of only few studies contributing to the meta-analysis, standard approaches to inference tend to perform poorly, and Bayesian meta-analysis has been suggested as a potential solution. The Bayesian approach, however, requir...

Although group-level evidence supports the use of behavioral interventions to enhance cognitive and emotional well-being, different interventions may be more acceptable or effective for different people. N-of-1 trials are single-patient crossover trials designed to estimate treatment effectiveness in a single patient. We designed a mobile health (m...

Endovascular interventions are commonly utilized for treatment of femoropopliteal peripheral artery disease. The relative efficacy of these interventions remains unclear. A Bayesian network meta-analysis was performed comparing 5 endovascular treatment modalities: balloon angioplasty (BA), bare metal stent (BMS), covered stent (CS), drug coated bal...

Background Whether revascularization should be performed as multivessel intervention at the time of index procedure (MV‐index), staged procedure (MV‐staged), or culprit only intervention (COI) in patients with multivessel disease (MVD) presenting with acute coronary syndrome (ACS) is unclear. We performed a systematic review and network meta‐analys...

Randomised clinical trials are the preferred method for establishing average intervention effects for groups. Using key methodological elements of these trials, n-of-1 trials provide rigorous evidence of intervention effects for individuals. N-of-1 trials are particularly useful for situations where randomised clinical trials are not always feasibl...

Background: During systematic reviews, "data abstraction" refers to the process of collecting data from reports of studies. The data abstractors' level of experience may affect the accuracy of data abstracted. Using data from a randomized crossover trial in which different data abstraction approaches were compared, we examined the association betw...

Objectives: We propose a one-shot, privacy-preserving distributed algorithm to perform logistic regression (ODAL) across multiple clinical sites. Materials and methods: ODAL effectively utilizes the information from the local site (where the patient-level data are accessible) and incorporates the first-order (ODAL1) and second-order (ODAL2) grad...

Objectives Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment (“N-of-1 trial”) on analgesic prescribing in patients...

Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted d...

Objectives: Data Abstraction Assistant (DAA) is a software for linking items abstracted into a data collection form for a systematic review to their locations in a study report. We conducted a randomized cross-over trial that compared DAA-facilitated single-data abstraction plus verification ("DAA verification"), single data abstraction plus verif...

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...

In Reply Many of the questions raised by Chapple and Blackston and by McDonald and colleagues about our recent Original Investigation¹ are addressed in Pocock and Stone’s recent review on what to do when the primary outcome fails.² Certainly, a trial in which the primary outcome falls short of statistical significance can be distressing to investig...

We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the single-case reporting guideline in behavioural intervent...

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 (...

Introduction During systematic reviews, data abstraction is labor‐ and time‐intensive and error‐prone. Existing data abstraction systems do not track specific locations and contexts of abstracted information. To address this limitation, we developed a software application, the Data Abstraction Assistant (DAA), and surveyed early users about their e...

Importance Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of treatments directed at various conditions, including chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may limit uptake in research and practice. Objectives To determine whether patients randomized to participate in a...

Objectives To determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration. Design Prospective, randomized, 52 week, single blind comparative effectiveness trial. Setting Urban...

Supplementary information: web tables 1-6

Background: N-of-1 (individual comparison) trials are a promising approach for comparing the effectiveness of 2 or more treatments for individual patients; yet, few studies have qualitatively examined how patients use and make sense of their own patient-generated health data (PGHD) in the context of N-of-1 trials. Objective: The objective of our...

Inspection and analysis of funnel plots cannot reliably identify publication and reporting bias, the non-publication of results that are not statistically significant. Instead, researchers should thoroughly and systematically search available information sources such as databases, registries and unpublished reports. Even then, it is not possible to...

A number of publications have discussed approaches to training the scientific workforce in comparative effectiveness research (CER) and patient-centered outcomes research (PCOR). To meet this need, funders have offered resources for developing educational materials and establishing training programs. To extend these efforts into specific researcher...

Background N-of-1 trials are multiple cross-over trials done in individual participants, generating individual treatment effect information. While reporting guidelines for the CONSORT Extension for N-of-1 trials (CENT) and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) already exist, there is no standardized recomme...

Background Fibromyalgia is a complex disorder with strong psychological and pain components. Tai Chi is an integrated mind-body approach that enhances both physical and mental health and has great potential to treat fibromyalgia (1–2). Objectives We aimed to investigate whether Tai Chi is more effective with longer lasting effects than aerobic exe...

Background Acute diarrhea remains both common and deadly in children worldwide. Proper treatment depends on accurately assessing dehydration status. Current World Health Organization (WHO) guidelines include an algorithm for classifying children as having no, some, or severe dehydration, which has never been properly validated. The Dehydration: Ass...

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...

Background Data abstraction, a critical systematic review step, is time-consuming and prone to errors. Current standards for approaches to data abstraction rest on a weak evidence base. We developed the Data Abstraction Assistant (DAA), a novel software application designed to facilitate the abstraction process by allowing users to (1) view study a...

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...

Healthcare practitioners are increasingly using search functionality embedded in Electronic Medical Record (EMR) software to search for relevant evidence summaries at point of care. We introduce a learning to rank approach that exploits information carried in EMR data and UpToDate user accounts to (significantly) improve ranking results, compared t...

Background: Dehydration due to diarrhoea is a leading cause of child death worldwide, yet no clinical tools for assessing dehydration have been validated in resource-limited settings. The Dehydration: Assessing Kids Accurately (DHAKA) score was derived for assessing dehydration in children with diarrhoea in a low-income country setting. In this stu...

We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural intervent...

Meta-analysis of diagnostic test accuracy often involves mixture of case–control and cohort studies. The existing bivariate random-effects models, which jointly model bivariate accuracy indices (e.g., sensitivity and specificity), do not differentiate cohort studies from case–control studies and thus do not utilize the prevalence information contai...

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder affecting 5 % of children worldwide. A prevalent problem for children with ADHD is initial insomnia. The gold standard treatment to manage ADHD symptoms is stimulant medications, which may exacerbate the severity of existing initial insomnia. Currently, n...

We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural intervent...