Robert W Platt

McGill University | McGill · Department of Epidemiology, Biostatistics and Occupational Health

Subgroup analyses are common in epidemiologic and clinical research. Unfortunately, restriction to subgroup members to test for heterogeneity can yield imprecise effect estimates. If the true effect differs between members and non-members due to different distributions of other measured effect measure modifiers (EMMs), leveraging data from non-memb...

Cox models with time‐dependent coefficients and covariates are widely used in survival analysis. In high‐dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time‐dependent Cox models lack flexibility in enforcing specific sparsity patterns (ie, covariate structures). We propose a flex...

Aim: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin am...

Objective There is a lack of evidence on the optimal target blood pressure (BP) for patients with hypertension at low cardiovascular risk. Our population-based study aimed to determine whether following an intensive target BP control plan is associated with a decreased risk of major adverse cardiovascular events (MACE) compared with following a sta...

(Abstracted from Am J Obstet Gynecol 2023;229:545.e1–545.e11 Severe maternal morbidity (SMM) is a composite outcome that encompasses life-threatening maternal complications and eclampsia around the time of delivery and up to 42 days after birth. It is associated with a higher incidence of cardiovascular disease and all-cause mortality long-term, be...

External validity is an important part of epidemiologic research. To validly estimate effects in specific external target populations using a chosen effect measure (i.e., "transport"), some methods require that one account for all effect measure modifiers [EMMs]. However, little is known about how including other variables that are not EMMs (i.e.,...

Importance Severe maternal morbidity (SMM) can have long-term health consequences for the affected mother. The association between SMM and future maternal mental health conditions has not been well studied. Objective To assess the association between SMM in the first recorded birth and the risk of hospitalization or emergency department (ED) visit...

Importance Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized. Objectives To assess whether concomitant use of SSRIs...

Distributed network studies and multisite studies assess drug safety and effectiveness in diverse populations by pooling information. Targeting groups of clinical or policy interest (including specific sites or site combinations) and applying weights based on effect measure modifiers (EMMs) prior to pooling estimates within multisite studies may in...

Purpose: To describe the prescribing trends of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2 RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019. Methods: We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all chil...

Background: Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these valsartan products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the US, C...

IntroductionAdministrative health records (AHRs) are used to conduct population-based post-market drug safety and comparative effectiveness studies to inform healthcare decision making. However, the cost of data extraction, and the challenges associated with privacy and securing approvals can make it challenging for researchers to conduct methodolo...

The objective of this review is to examine the application of target trial emulation in perinatal pharmacoepidemiology research. Given that randomized clinical trials—the gold standard for causal inference—are often not feasible or ethical for studying medication safety during pregnancy, alternative methodologies are critically needed. This paper d...

Introduction The dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas. Research design and methods Using the United Kingdom Clinica...

Background While the benefits of levothyroxine are well‐established for overt hypothyroidism, they are unclear for subclinical hypothyroidism (SCH) among pregnant women. Objective To estimate the effect of initiation of levothyroxine on pregnancy loss among women with SCH with an emulated target trial using observational data. Methods We emulated...

Aims The objective of this study was to determine whether the use of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) is associated with an increased risk of melanoma and nonmelanoma skin cancer, separately, compared with the use of sulfonylureas among patients with type 2 diabetes. Materials and Methods Using the United Kingdom Clinical Prac...

Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase statistical precision. Here...

Objective To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy. Design Population based, retrospective cohort study. Setting Ontario, Canada, from 20 December...

Background: Five-alpha reductase inhibitors (5αRIs) are used to treat benign prostatic hyperplasia (BPH). However, the cardiovascular effects of 5αRIs remain poorly understood. The study objective was to compare the rate of hospitalization for heart failure among men with BPH prescribed 5αRIs to that of men with BPH not prescribed BPH medications....

Cox models with time-dependent coefficients and covariates are widely used in survival analysis. In high-dimensional settings, sparse regularization techniques are employed for variable selection, but existing methods for time-dependent Cox models lack flexibility in enforcing specific sparsity patterns (i.e., covariate structures). We propose a fl...

Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas to increase their risk of hypoglycemia. Our population-based study assessed whether intra-class pharmacologic heterogeneity among sulfonylureas (long- versus short-acting) and DPP-4i (peptidomimetic versus non-peptidomimetic) modifies this interaction. We conducted a cohort stud...

Real-world data sources offer opportunities to compare the effectiveness of treatments in practical clinical settings. However, relevant outcomes are often recorded selectively and collected at irregular measurement times. It is therefore common to convert the available visits to a standardized schedule with equally spaced visits. Although more adv...

Background: Severe maternal morbidity is a composite indicator of maternal health and obstetrical care. Little is known about the risk of recurrent severe maternal morbidity in a subsequent delivery. Objective: To estimate the risk of recurrent severe maternal morbidity in the next delivery after a complicated first delivery. Study design: We...

Introduction In the COVID-19 pandemic, healthcare workers (HCWs) were at high risk of infection due to their exposure to COVID infections. HCWs were the backbone of our healthcare response to this pandemic; every HCW withdrawn or lost due to infection had a substantial impact on our capacity to deliver care. Primary prevention was a key approach to...

Aim: To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes. Methods: Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who ini...

Both inadequate and excessive maternal weight gain are correlated with preterm delivery in singleton pregnancies, yet this relationship has not been adequately studied in twins. We investigated the relationship between time-varying maternal weight gain and gestational age at delivery in twin pregnancies and compared to that in singletons delivered...

Background: Among people who inject drugs, frequent injecting and experiencing withdrawal are associated with facilitating others' first injections. As these factors may reflect an underlying substance use disorder, we investigated whether first-line oral opioid agonist treatment (OAT; methadone or buprenorphine/naloxone) reduces the likelihood th...

Statistical approaches to adaptive treatment strategies (ATS) can be used to mimic the sequential decision-making inherently found in clinical practice. To illustrate the use of a statistical ATS approach, we emulated a target trial of different blood pressure (BP) control plans for the prevention of cardiovascular events among individuals with hyp...

Objectives To examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled. Design Retrospective cohort study. Setting USA, Canadian administrative healthcare data, Danish National Prescription Regis...

Aims: The contemporary prescription patterns of antidiabetic drugs following guideline changes recommending metformin as first-line gestational diabetes (GDM) pharmacotherapy is underexplored. We aimed to examined use of metformin and insulin during pregnancy among women with GDM over 20 years in the United Kingdom. Methods: We conducted a popul...

Background: The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. Objective: To determine whether HCTZ is associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs). Methods: Two new-user, active comparator cohorts were...

The inherent correlation between the total amount of weight gained in pregnancy and the duration of pregnancy creates major methodological challenges in the study of pregnancy weight gain. In this issue (Am J Epidemiol. 2023;XXX(XX):XXXX-XXXX), Richards et al. examine the extent to which different measures of pregnancy weight gain (including covari...

OBJECTIVE The hypoglycemic potential of β-blockers among users of sulfonylureas, drugs that strongly increase the risk of this potentially fatal adverse effect, is not well understood. Our population-based cohort study assessed the potential association between concomitant use of sulfonylureas and β-blockers versus use of sulfonylureas alone and th...

Background The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. Methods In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vit...

Objective To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014. Methods We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchew...

Real‐world evidence (RWE) used for regulatory, payer, and clinical decision‐making requires principled epidemiology in design and analysis, applying methods to minimize confounding given the lack of randomization. One technique to deal with potential confounding is propensity score (PS) analysis, which allows for the adjustment for measured pre‐exp...

Anticoagulants are a potential treatment for the thrombotic complications resulting from COVID-19. We aimed to determine the association between anticoagulant use and adverse outcomes among hospitalized patients with COVID-19. We used data from the COVID-19 International Collaborative Research Project in South Korea from January to June 2020. We de...

Background: More people with rare diseases likely receive disease education and emotional and practical support from peer-led support groups than any other way. Most rare-disease support groups are delivered outside of the health care system by untrained leaders. Potential benefits may not be achieved and harms, such as dissemination of inaccurate...

OBJECTIVE To determine whether sodium–glucose cotransporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk of early bladder cancer events. RESEARCH DESIGN AND METHODS We conducted a multisite, population-based, new-user, ac...

Introduction: Whether the reduction in brain amyloid beta (Aβ) plaque alone may substantially slow cognitive and functional decline in patients with dementia or mild cognitive impairment due to Alzheimer's disease (AD) remains debated. Methods: An instrumental variable meta-analysis was performed to infer the effect of change in positron emissio...

Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase the statistical precision. H...

Background: Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressants, are associated with a modestly increased risk of major bleeding. However, in patients treated with both SSRIs and oral anticoagulants (OACs) the risk of major bleeding may be substantial. Objective: To assess the risk of major bleeding associated wi...

In biomedical studies, survival data with a cure fraction (the proportion of subjects cured of disease) are commonly encountered. The mixture cure and bounded cumulative hazard models are two main types of cure fraction models when analyzing survival data with long-term survivors. In this article, in the framework of the Cox proportional hazards mi...

Gestational diabetes mellitus (GDM) increases the risk of early-onset type 2 diabetes, which further exacerbates the risk of developing diabetic complications such as kidney, circulatory, and neurological complications. Yet, existing models have solely focused on the prediction of type 2 diabetes, and not of its complications, which are arguably th...

Predictor identification is important in medical research as it can help clinicians to have a better understanding of disease epidemiology and identify patients at higher risk of an outcome. Variable selection is often used to reduce the dimensionality of a prediction model. When conducting variable selection, it is often beneficial to take selecti...

Objective: Evidence suggests that beta-blockers increase the risk of hypoglycemia. However, their effects among users of sulfonylureas, drugs that also cause hypoglycemia, are not well understood. Thus, our study assessed the potential association between concomitant use of sulfonylureas and beta-blockers and the risk of severe hypoglycemia. Desi...

Aims: To compare the risk of cardiovascular outcomes with long-acting insulin analogues versus Neutral Protamine Hagedorn (NPH) insulin among patients with type 2 diabetes. Materials and methods: We conducted a population-based retrospective cohort study, using the United Kingdom Clinical Practice Research Datalink Aurum, linked with hospitaliza...

Background: Time-related biases, such as immortal time and time-window bias, frequently occur in pharmacoepidemiologic research. However, the prevalence of these biases in perinatal pharmacoepidemiology is not well understood. Objective: To describe the frequency of time-related biases in observational studies of medications commonly used during...

Background With many disease-modifying therapies currently approved for the management of multiple sclerosis, there is a growing need to evaluate the comparative effectiveness and safety of those therapies from real-world data sources. Propensity score methods have recently gained popularity in multiple sclerosis research to generate real-world evi...

Objective To update a recently published analysis exploring the causal association between positron emission tomography (PET)-measured change in brain β-amyloid plaque and cognitive decline in patients with Alzheimer’s disease (AD) enrolled in randomized clinical trials (RCTs). Design Updated instrumental variable meta-analysis. Setting Sixteen R...

Aims: Studies using contemporary cohorts are needed to assess the association between type 2 diabetes and cancer. Methods: Using the United Kingdom Clinical Practice Research Datalink, we matched patients with type 2 diabetes between 1988 to 2019 to patients without type 2 diabetes. Poisson regression models were fit to estimate incidence rate r...

Many studies seek to evaluate the effects of potentially harmful pregnancy exposures during specific gestational periods. We consider an observational pregnancy cohort where pregnant individuals can initiate medication usage or become exposed to a drug at various times during their pregnancy. An important statistical challenge involves how to defin...

In the statistical literature, a number of methods have been proposed to ensure valid inference about marginal effects of variables on a longitudinal outcome in settings with irregular monitoring times. However, the potential biases due to covariate-driven monitoring times and confounding have rarely been considered simultaneously, and never in a s...

Background: Although gestational diabetes might be more common in twin versus singleton pregnancies, reasons for this are unclear. We evaluated the extent to which the relationship is explained by higher mid-pregnancy weight gain within normal weight and overweight pre-pregnancy body mass index (BMI) strata. Methods: We analyzed serial weights a...

Introduction: Although long-acting insulin analogs (glargine, detemir, and degludec) and neutral protamine Hagedorn (NPH) insulin show similar efficacy for glycemic control among patients with type 2 diabetes, their comparative effectiveness in reducing cardiovascular events is unclear. Objective: To compare the risk of major adverse cardiovascula...

Introduction: Although long-acting insulin analogs (glargine, detemir, and degludec) and neutral protamine Hagedorn (NPH) insulin show similar efficacy for glycemic control among patients with type 2 diabetes, their comparative effectiveness in reducing cardiovascular events is unclear. Objective: To compare the risk of major adverse cardiovascular...

Purpose To describe the prescribing trends of 17 therapeutic drug categories and the specific drug classes of systemic antibiotics, analgesics, and antidepressants in children and adolescents in the United Kingdom between 1998 and 2018. Methods A population-based retrospective cohort study including children and adolescents aged 0 to 18 years. Ove...

Variable selection is commonly used to arrive at a parsimonious model when relating an outcome to high-dimensional covariates. Oftentimes a selection rule that prescribes the permissible variable combinations in the final model is desirable due to the inherent structural constraints among the candidate variables. Penalized regression methods can in...

The accelerated failure time model is an alternative to the Cox proportional hazards model in survival analysis. However, conclusions regarding the associations of prognostic factors with event times are valid only if the underlying modeling assumptions are met. In contrast to several flexible methods for relaxing the proportional hazards and linea...

Background Several antihypertensive drugs are available for the primary prevention of cardiovascular disease (CVD). However, existing evidence on prescription patterns was primarily generated among patients at high CVD risk with short-term follow-up, and failed to capture impacts of time and patient characteristics. Our objective was therefore to d...

Our study aimed to describe levothyroxine prescription patterns and trends over time among pregnant women with subclinical hypothyroidism (SCH) in the United Kingdom. We used data from the Clinical Practice Research Datalink linked to its Pregnancy Register and the Hospital Episode Statistics database from 1998 to 2017. The study population include...

In the statistical literature, a number of methods have been proposed to ensure valid inference about marginal effects of variables on a longitudinal outcome in settings with irregular monitoring times. However, the potential biases due to covariate‐driven monitoring times and confounding have rarely been considered simultaneously, and never in a s...

In studying the marginal effect of antidepressants on body mass index using electronic health records data, we face several challenges. Patients' characteristics can affect the exposure (confounding) as well as the timing of routine visits (measurement process), and those characteristics may be altered following a visit which can create dependencie...

Objective To establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using healthcare databases from four European countries and six provinces in Canada. Methods A retrospective cohort study was performed according to a similar protocol. First-users of VKAs or D...

Aims: To describe changes in the utilization of basal insulins (glargine, detemir, degludec, neutral protamine Hagedorn [NPH]) among individuals with type 2 diabetes between 2003 and 2018 in the United Kingdom (UK). Materials and methods: Using the UK Clinical Practice Research Datalink (CPRD) Aurum, we created three study cohorts of individuals...

Purpose: Researchers are interested in studying longitudinal patterns of gestational weight gain, yet this requires daily/weekly weights, and maternal weight is measured only during prenatal visits. We evaluated the relative accuracy and precision of methods for estimating maternal weight between prenatal visits among twin and singleton pregnancie...

Epidemiologists sometimes use external sources of variation to explore highly-confounded exposure-outcome relationships or exposures that cannot be randomized. These exogenous sources of variation, or natural experiments, are sometimes proposed as instrumental variables to examine the effects of a given exposure(s) on a given outcome(s). Previous e...

Background: In perinatal epidemiology, the development of risk prediction models is complicated by parity; how repeat pregnancies influence the predictive accuracy of models that include obstetrical history is unclear. Methods: To assess the influence of repeat pregnancies on the association between predictors and the outcomes, as well as the in...

COVID-19 vaccines are now being deployed as essential tools in the public health response to the global SARS-CoV-2 pandemic. Pregnant individuals are a unique subgroup of the population with distinctive considerations regarding risk and benefit that extend beyond themselves to their fetus/newborn. As a complement to traditional pharmacovigilance an...

Context: The efficacy and safety of metformin for obesity in children and adolescents remains unclear. Objective: To assess the efficacy and safety of metformin via systematic review. Data sources: Data sources included PubMed, Embase, the Cochrane Library, Scopus, and ClincalTrials.gov (inception to November 2019). Study selection: We selec...

Background: A previous large randomized trial indicated that preconception-initiated low-dose aspirin (LDA) therapy did not have a positive effect on pregnancy outcomes. However, this trial was subject to nonadherence, which was not taken into account by the intention-to-treat approach. Objective: To estimate per protocol effects of preconceptio...

Purpose: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have been associated with an increased risk of genitourinary tract infections. Through similar biological mechanisms, they may also increase the risk of community-acquired pneumonia. Our objective was to compare the rate of hospitalization for community-acquired pneumonia (HCAP) with SGL...

Objective: To compare medication persistence of tofacitinib with persistence of injectable biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA). Methods: We performed a retrospective new-user cohort study of patients with RA in the IBM MarketScan Research Databases. New users of tofacitinib or bDMARD...

Introduction Ectopic pregnancy occurs in 1% to 2% of the all recognized pregnancies, yet half of women who have an ectopic pregnancy do not have any known risk factors. A potential but unstudied risk factor for ectopic pregnancy is benzodiazepine use, which could affect muscle contraction in the fallopian tube. Objectives and Approach We compared...

Background Propensity score (PS) analyses are increasingly used in multiple sclerosis (MS) research, largely owing to the greater availability of large observational cohorts and registry databases. Objective To evaluate the use and quality of reporting of PS methods in the recent MS literature. Methods We searched the PubMed database for articles...

Background: Observational healthcare data can be used for drug safety and effectiveness research. The use of inverse probability of treatment weights (IPW) reduces measured confounding under the assumption of accurate measurement of the outcome variable; however, many datasets suffer from systematic outcome misclassification. Methods: We introdu...

The accelerated failure time (AFT) model has been suggested as an alternative to the Cox proportional hazards model. However, a parametric AFT model requires the specification of an appropriate distribution for the event time, which is often difficult to identify in real‐life studies and may limit applications. A semiparametric AFT model was develo...

Deriving valid confidence intervals for complex estimators is a challenging task in practice. Estimators of dynamic weighted survival modeling (DWSurv), a method to estimate an optimal dynamic treatment regime of censored outcomes, are asymptotically normal and consistent for their target parameters when at least a subset of the nuisance models is...

In this tutorial, we focus on the problem of how to define and estimate treatment effects when some patients develop a contraindication and are thus ineligible to receive a treatment of interest during follow‐up. We first describe the concept of positivity, which is the requirement that all subjects in an analysis be eligible for all treatments of...

Precision medicine is an approach to health care in which treatment decisions are tailored to patient-level information. Statistical methods for the estimation of dynamic treatment regimes (DTRs) allow to uncover a sequence of personalized treatment rules for patients with chronic diseases. Of particular interest is the identification of an optimal...