Immunolab: Combining targeted real-world data with advanced analytics to generate evidence at scale in immunology.

Real-world evidence (RWE) has traditionally been used by regulatory or payer authorities to inform disease burden, background risk, or conduct post-launch pharmacovigilance, but in recent years RWE has been increasingly used to inform regulatory decision-making. However, RWE data sources remain fragmented, and datasets are disparate and often collected inconsistently. To this end, we have constructed an RWE-generation platform, Immunolab, to facilitate data-driven insights, hypothesis generation and research in immunological diseases driven by type 2 inflammation.

Characterizing real world safety profile of oral Janus kinase inhibitors among adult atopic dermatitis patients: evidence transporting from the rheumatoid arthritis population.

Objective: To address potential safety concerns of Janus Kinase Inhibitors (JAK-Is), we characterized their safety profile in the atopic dermatitis (AD) patient population.

Methods: In this retrospective observational study, we used propensity score-based methods and a Poisson modeling framework to estimate the incidence of health outcomes of interest (HOI) for the AD patient. To that end, two mutually exclusive cohorts were created using a real world data resource: a rheumatoid arthritis (RA) cohort, where we directly quantify the safety risk of JAK-Is on HOIs, and an AD cohort, that comprises the target population of interest and to whom we transport the results obtained from the RA cohort.

Bridging the Gap Between RCTs and RWE Through Endpoint Selection.

This commentary is authored by several industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of Industry Leaders who have come together as non-competitive partners to understand and respond to RWD/E challenges and opportunities with a single expert voice. Here, the forum discusses the value in bridging the industry disconnect between RTCs and RWE, with a view to promoting the use of RWE in the RCT environment. RCT endpoints are explored along several axes including their clinical relevance and their measure of direct patient benefit, and then compared with their real-world counterparts to identify suitable paths, or gaps, for assimilating RWE endpoints into the RCT environment.

Designing, Conducting, Monitoring, and Analyzing Data from Pragmatic Randomized Clinical Trials: Proceedings from a Multi-stakeholder Think Tank Meeting.

In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to inform clinical or policy decisions by assessing the real-world effectiveness of an intervention. There is general agreement among experts that the use of existing healthcare and patient-generated data holds promise for making randomized trials more efficient, less costly, and more generalizable.

Strengthening pharma's contract with society: the value of trusted partnerships between pharma and healthcare facilitated by real-world data.

This White Paper is authored by 11 industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of industry leaders who come together as noncompetitive partners to understand and respond to internal or external RWD/E challenges and opportunities with a single expert voice. Herein we aim to clarify the rules of engagement between pharma and healthcare in order to establish trust-based partnerships, which will unlock unique value for society, including the medical community and the ultimate beneficiary, the patient.

Epidemiology and health outcomes associated with hyperkalemia in a primary care setting in England.

Background: Real-world incidence, clinical consequences, and healthcare resource utilization (HRU) of hyperkalemia (HK) remain poorly characterized, particularly in patients with specific comorbidities.

Methods: Data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases were analyzed to determine incidence of an index HK event, subsequent clinical outcomes, and HRU in the English population. Factors associated with index HK in a primary care setting were also identified for those with an index HK event during the study period (2009-2013) and matched controls.

Comparison of Methods to Generalize Randomized Clinical Trial Results Without Individual-Level Data for the Target Population.

Our study explored the application of methods to generalize randomized controlled trial results to a target population without individual-level data. We compared 4 methods using aggregate data for the target population to generalize results from the international trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), to a target population of trial-eligible patients in the UK Clinical Practice Research Datalink (CPRD). The gold-standard method used individual data from both the trial and CPRD to predict probabilities of being sampled in the trial and to reweight trial participants to reflect CPRD patient characteristics.

Burden of cardio-renal-metabolic conditions in adults with type 2 diabetes within the Diabetes Collaborative Registry.

We examined the prevalence of cardio-renal-metabolic (CaReMe) conditions and their combinations among 530 747 adults with type 2 diabetes in a USA-based outpatient registry of 271 primary care, cardiology and endocrinology offices. We evaluated the following CaReMe conditions: hypertension, hyperlipidaemia, coronary artery disease (CAD), chronic kidney disease (CKD), cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and gout or hyperuricaemia; prevalence estimates were adjusted based on the distribution of diabetes by age in the US population in 2015. We found that it was uncommon for patients to have isolated type 2 diabetes without other CaReMe conditions, with only 6.

Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

Statins are indicated in patients with elevated levels of high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on results of the multicountry trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using data from the UK Clinical Practice Research Datalink (CPRD), 2001-2014. We multiply imputed missing baseline characteristics for the CPRD population and selected the trial-eligible participants as the target population based on observed and imputed values.

Laxative utilization over time in chronic pain patients with opioid-induced constipation.

Aim: To determine laxative utilization over time among chronic noncancer pain patients with opioid-induced constipation (OIC).

Setting: A prospective longitudinal study conducted in the USA, Canada, Germany and UK.

Methods: Patients on daily opioid therapy for treatment of chronic noncancer pain with OIC were recruited from clinics to complete a survey at Baseline and weeks 2, 4, 6, 8, 12, 16, 20 and 24.

Opioid-Induced Constipation among a Convenience Sample of Patients with Cancer Pain.

Background: Little is known regarding the burden of opioid-induced constipation (OIC) among patients who suffer from cancer-related pain.

Methods: A prospective longitudinal study was conducted among cancer patients in the United Kingdom (UK), Canada, and Germany, which included medical record data abstraction, Internet-based patient surveys, and physician surveys. Patients on daily opioid therapy (≥30 mg for ≥4 weeks) for treatment of cancer pain with self-reported OIC were recruited.

Satisfaction with Therapy Among Patients with Chronic Noncancer Pain with Opioid-Induced Constipation.

Background: Greater satisfaction with medication is associated with better adherence; however, specific to opioid-induced constipation (OIC), data on the relationship between medication satisfaction and efficacy are lacking.

Objective: To understand satisfaction with therapy among patients with chronic noncancer pain and OIC.

Methods: A prospective longitudinal study was conducted in the United States, Canada, Germany, and the United Kingdom using web-based patient surveys.

The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports.

Background: Opioid-induced constipation (OIC), a common side effect of opioid treatment for chronic pain, affects patient health-related quality of life (HRQL) and may prompt some patients to lower the dose or alter adherence to their opioid medication, compromising pain relief. Although health care providers (HCPs) are aware of the potential for OIC, patients may not inform their HCPs of their OIC symptoms, and HCPs may not initiate conversation regarding OIC if their patients' pain is controlled. Patients often try to address OIC symptoms on their own by using natural approaches or over-the-counter options.

Treatment patterns, healthcare utilization, and costs of chronic opioid treatment for non-cancer pain in the United States.

Objectives: To evaluate treatment patterns, healthcare resource utilization, and costs among patients within a large managed care population chronically using opioids for non-cancer pain.

Study Design: Retrospective cohort study.

Methods: Patients aged ≥18 years with ≥1 prescription initiating opioids between January 1, 2007, and December 31, 2011, who also had 12 months of continuous pre-index health plan enrollment, were identified.

Opioid-Induced Constipation Among Patients with Chronic Noncancer Pain in the United States, Canada, Germany, and the United Kingdom: Laxative Use, Response, and Symptom Burden Over Time.

Purpose: Estimate rate of laxative inadequate response (LIR) over time among patients with chronic noncancer pain with opioid-induced constipation (OIC).

Methods: A prospective longitudinal study was conducted in United States, Canada, Germany, and United Kingdom. Patients on opioid therapy for ≥4 weeks for chronic noncancer pain and OIC completed an Internet-based survey at Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24.

A description of clinical characteristics and treatment patterns observed within prescribed opioid users in Germany and the UK.

Aims: To describe a cohort of new opioid users (adult noncancer patients) in terms of clinical characteristics and treatment patterns in the UK and Germany.

Material & Methods: Data used were extracted from electronic medical records databases (UK: Clinical Practice Research Database-Hospital Episode Statistics; Germany: IMS Disease Analyzer) covering the 2008-2012 period.

Results: Most eligible patients were treated with opioids for less than 6 months (UK: 78.

The role of prediction modeling in propensity score estimation: an evaluation of logistic regression, bCART, and the covariate-balancing propensity score.

The covariate-balancing propensity score (CBPS) extends logistic regression to simultaneously optimize covariate balance and treatment prediction. Although the CBPS has been shown to perform well in certain settings, its performance has not been evaluated in settings specific to pharmacoepidemiology and large database research. In this study, we use both simulations and empirical data to compare the performance of the CBPS with logistic regression and boosted classification and regression trees.

Description of cardiovascular event rates in patients initiating chronic opioid therapy for noncancer pain in observational cohort studies in the US, UK, and Germany.

Introduction: Previous observational studies in the US suggest that opioid analgesic use increases the risk of cardiovascular (CV) events. The current study provides additional background event rates for five prespecified CV outcomes of interest in patients from three countries.

Methods: Three observational cohort studies were conducted in patients from the US (N = 17,604), the UK (N = 9,823), and Germany (N = 9,412).

Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review.

Background: The characteristics of patients who suffer from noncancer pain and opioid-induced constipation are not well understood.

Methods: Cross-sectional patient survey and chart review data from the baseline assessment of an ongoing longitudinal study in the USA, Canada, Germany, and the UK were evaluated via descriptive statistics. Participants had confirmation of daily opioid therapy ≥30 mg for ≥4 weeks and self-reported opioid-induced constipation.

Variable selection for propensity score models when estimating treatment effects on multiple outcomes: a simulation study.

Purpose: It is often preferable to simplify the estimation of treatment effects on multiple outcomes by using a single propensity score (PS) model. Variable selection in PS models impacts the efficiency and validity of treatment effects. However, the impact of different variable selection strategies on the estimated treatment effects in settings involving multiple outcomes is not well understood.

Guidelines for good database selection and use in pharmacoepidemiology research.

The use of healthcare databases in research provides advantages such as increased speed, lower costs and limitation of some biases. However, database research has its own challenges as studies must be performed within the limitations of resources, which often are the product of complex healthcare systems. The primary purpose of this document is to assist in the selection and use of data resources in pharmacoepidemiology, highlighting potential limitations and recommending tested procedures.

Transition to managed care impacts health care service utilization by children insured by Medicaid.

Purpose. To evaluate the impact of transition to managed care from fee for service on asthma service utilization among Maryland Medicaid insured children. Methods.

Looking beyond urban/rural differences: emergency department utilization by asthmatic children.

Asthma causes pediatric morbidity throughout the US with substantial regional variability. Emergency department (ED) utilization data were studied to determine if geographic variability of pediatric asthma cases exists within a state. Records for non-neonatal Maryland children less than 18 years of age seen and discharged from Maryland EDs from April 1997 through March 2001 were analyzed.

Risk areas for pediatric acute care: asthma differs from upper and lower respiratory illness.

Objective: To determine if emergency department utilization for pediatric respiratory illness varies across small geographic jurisdictions within a large urban city.

Design: A retrospective analysis of Maryland Health Services Cost Review Commission Emergency Department discharge data.

Setting/patients: All non-neonatal, Baltimore City residents <18 years old with valid diagnoses admitted and discharged from emergency departments (ED) in the state of Maryland from April 1, 1997 to December 31, 2000 (n=245,339).