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Noncommunicable diseases (NCDs) place a huge burden on healthcare systems and society as a whole. Relatively early in the coronavirus disease 2019 (COVID-19) pandemic, clinicians became aware that in individuals infected with COVID-19, those with preexisting NCDs such as diabetes mellitus and cardiovascular disease (CVD) were at a greater risk of poor outcomes and mortality than those without. The importance of adherence to medications and lifestyle changes to control and prevent NCDs has been a major focus for many years, but with limited success – the proportion of patients adherent and persistent to their medications remains very low. There are many facets to adherence and persistence. Recent evidence suggests that a patient-centric approach is important, and ensuring that a patient is both motivated and empowered is critical to improving adherence/persistence. The COVID-19 pandemic has brought many changes to the way in which patients with NCDs are managed, with telemedicine and ehealth becoming more common. Changes have also occurred in the way in which patients can gain access to medications during the pandemic. The potential for these changes forms the basis of improving the management of patients with NCDs both during and after the pandemic. Over the coming months, a huge amount of work will be put into initiatives to promote adherence to COVID-19 vaccination programs. Those at highest risk of severe COVID-19, such as people aged 80 years and older, are likely to receive the vaccine first in some parts of world. Finally, social determinants of health are critical elements that can impact not just the likelihood of having an NCD or becoming infected with COVID-19, but also access to healthcare, and a patient’s adherence and persistence with their treatments.

A vast quantity of real-world data (RWD) are available to healthcare researchers. Such data come from diverse sources such as electronic health records, insurance claims and billing activity, product and disease registries, medical devices used in the home, and applications on mobile devices. The analysis of RWD produces real-world evidence (RWE), which is clinical evidence that provides information about usage and potential benefits or risks of a drug. This review defines and explains RWD, and it also details how regulatory authorities are using RWD and RWE. The main challenges in harnessing RWD include collating and analyzing numerous disparate types or categories of available information including both structured (eg, field entries) and unstructured (eg, doctor notes, discharge summaries, social media posts) data. Although the use of artificial intelligence to capture, amalgamate, standardize, and analyze RWD is still evolving, it has the potential to support the increased use of RWE to improve global health and healthcare.

Vaibhav B Katkade, Kafi N Sanders, Kelly H Zou Pfizer Inc, New York, NY, USA Abstract: Evidence from medication use in the real world setting can help to extrapolate and/or augment data obtained in randomized controlled trials and establishes a broad picture of a medication’s place in everyday clinical practice. By supplementing and complementing safety and efficacy data obtained in a narrowly defined (and often optimized) patient population in the clinical trial setting, real world evidence (RWE) may provide stakeholders with valuable information about the safety and effectiveness of a medication in large, heterogeneous populations. RWE is emerging as a credible information source; however, there is scope for enhancements to real world data (RWD) sources by understanding their complexities and applying the most appropriate analytical tools in order to extract relevant information. In addition to providing information for clinicians, RWE has the potential to meet the burden of evidence for regulatory considerations and may be used in approval of new indications for medications. Further understanding of RWD collection and analysis is needed if RWE is to achieve its full potential. Keywords: electronic health records, evidence-based medicine, real world data, real world evidence, randomized controlled trial

The Best Linear Unbiased Predictor (BLUP) in mixed models is a function of the variance components and they are estimated using maximum likelihood (ML) or restricted ML methods. Nonconvergence of BLUP would occur due to a drawback of the standard likelihood-based approaches. In such situations, ML and REML either do not provide any BLUPs or all become equal. To overcome this drawback, we provide a generalized estimate (GE) of BLUP that does not suffer from the problem of negative or zero variance components, and compare its performance against the ML and REML estimates of BLUP. Simulated and published data are used to compare BLUP.

Adherence with oral medication for overactive bladder syndrome is suboptimal. To improve adherence, the YourWay plan was developed to assist patients and health care providers in defining treatment expectations and facilitating communication.To evaluate medication adherence among patients with overactive bladder syndrome enrolled in the YourWay patient support plan, patient adoption of behavioral interventions, patient satisfaction with the plan, and physician experience with the plan.In this 13-week, single-arm, open-label, multicenter, noninterventional study, fesoterodine-naïve patients received a prescription for fesoterodine 4 or 8 mg and a packet including a 14-day fesoterodine sample, educational materials, and progress tracker. Patients registered for the YourWay plan, which included an educational resource kit, interactive voice-response calls, and optional online and mail support. The primary end point was the proportion of patients who filled a prescription for a ≥ 90-day supply of fesoterodine within 90 days of enrollment. Secondary end points were the proportion of patients who filled ≥ 1 prescription and ≥ 2 prescriptions (post hoc), patient evaluation of their experience and satisfaction with the YourWay plan, and differences between prescription fillers and nonfillers in plan adoption and assessment (post hoc). We surveyed an independent sample of physicians to assess their experience with YourWay.Of 500 study completers, 10.4% filled a prescription for a ≥ 90-day supply of fesoterodine. Of those filling a prescription, 26.2% filled ≥ 1 prescription and among those, 61.0% refilled their prescription at least once. Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers were more likely to take fesoterodine as directed, whereas adoption of behavioral recommendations or plan satisfaction did not differ between fillers and nonfillers. Most patients reported that the plan was informative and feasible to implement, and that they were satisfied with various aspects of the plan. Physicians also reported positive experiences.Most patients adopted YourWay components and viewed the plan positively, although adherence remained a challenge.

To assess the impact of access restrictions on varenicline utilization.Employer-sponsored health plans contributing to the MarketScan Commercial Claims and Encounters Database were categorized according to 2009 varenicline access restrictions: no coverage; prior authorization; smoking cessation program requirement; no restrictions. The cohort comprised all adults continuously enrolled in plans during 2009. Each restriction cohort was compared with the no restrictions cohort using descriptive analyses. Data were assessed using logistic regression; demographic and clinical characteristics were covariates.In this study (no coverage, n = 454,419; prior authorization, n = 171,530; smoking cessation program, n = 108,181; no restrictions, n = 607,389), compared with the no restrictions cohort, the odds of treatment were 71% lower (odds ratio: 0.29; 95% CI: 0.26, 0.31) in the smoking cessation program cohort (p0.001) and 80% lower (odds ratio: 0.20; 95% CI: 0.19, 0.22) in the prior authorization cohort (p0.001).Access restrictions were associated with significantly lower odds for varenicline utilization.

To address the gap in knowledge about the impact of chronic obstructive pulmonary disease (COPD) on older working adults, this study examined quality of life, worker productivity, and healthcare resource utilization among employed adults aged 65 and older with and without COPD. Among 2009 National Health and Wellness Survey (a cross-sectional, internet-based survey representative of the US adult population) respondents, employed adults aged 65 years and older, with COPD (n = 297) and without COPD (n = 3061), were included in analyses. Impact of self-reported COPD diagnosis on mean quality of life (using health utilities and mental, MCS, and physical, PCS, component summary scores from SF-12v2), work productivity and activity impairment (using the WPAI questionnaire), and resource use were examined. Adjusting for demographic and health characteristics such as co-morbidities (weighted to project to the US population) in regression models (linear, negative binomial, or logistic, as appropriate given the outcome measure), older workers with COPD reported significantly lower MCS (52.1 vs. 53.4, p < .05), PCS (40.3 vs. 47.2, p < .05), and health utilities (0.72 vs. 0.79, p < .05) than those without COPD, and significantly greater percentages of impairment while at work (presenteeism) (12.6% vs. 8.7%, p < .0001), overall work impairment (absenteeism and presenteeism combined) (19.3% vs. 10.0%, p < .05), and impairment in daily activities (23.9% vs. 13.7%, p < .05). There were no significant differences in absenteeism or healthcare use. Quality of life and work productivity suffered among employed adults aged 65 years and older with COPD, emphasizing the need for disease management in this population.

We develop semiparametric and parametric transformation models for estimation and comparison of ROC curves derived from measurements from two diagnostic tests on the same subjects. We assume the existence of transformed measurement scales, one for each test, on which the paired measurements have bivariate normal distributions. The resulting pair of ROC curves are estimated by maximum likelihood algorithms, using joint rank data in the semiparametric model with unspecified transformations and using Box-Cox transformations in the parametric transformation case. Several hypothesis tests for comparing the two ROC curves, or characteristics of them, are developed. Two clinical examples are presented and simulation results are provided.

We consider a semiparametric and a parametric transformation-to-normality model for bivariate data. After an unstructured or structured monotone transformation of the measurement scales, the measurements are assumed to have a bivariate normal distribution with correlation coefficient „ , here termed the 'transformation correlation coefficient'. Under the semiparametric model with unstructured transformation, the principle of invariance leads to basing inference on the marginal ranks. The resulting rank-based likelihood function of „ is maximized via a Monte Carlo procedure. Under the parametric model, we consider Box-Cox type transformations and maximize the likelihood of „ along with the nuisance parameters. Efficiencies of competing methods are reported, both theoretically and by simulations. The methods are illustrated on a real-data example.

A receiver operating characteristic (ROC) curve is a plot of two survival functions, derived separately from the diseased and healthy samples. A special feature is that the ROC curve is invariant to any monotone transformation of the measurement scale. We propose and analyse semiparametric and parametric transformation models for this two-sample problem. Following an unspecified or specified monotone transformation, we assume that the healthy and diseased measurements have two normal distributions with different means and variances. Maximum likelihood algorithms for estimating ROC curve parameters are developed. The proposed methods are illustrated on the marker CA125 in the diagnosis of gastric cancer.

Margaret K Pasquale,1 Yihua Xu,1 Christine L Baker,2 Kelly H Zou,3 John G Teeter,4 Andrew M Renda,5 Cralen C Davis,1 Theodore C Lee,6 Joel Bobula2 1Comprehensive Health Insights, Inc., Humana Inc., Louisville, KY, 2Outcomes and Evidence, Global Health & Value, Pfizer Inc., 3Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, Pfizer Inc., New York, NY, 4Global Medical Development, Global Innovative Pharma Business, Pfizer Inc., Groton, CT, 5Retail Strategy& Execution, Humana Inc., Louisville,KY, 6Global Medical Affairs, Global Innovative Pharma Business, Pfizer Inc., New York, NY, USA Background: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs.Methods: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis­eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs.Results: Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P0.10).Conclusion: The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history. Keywords: Global initiative for chronic Obstructive Lung Disease, COPD symptomatology, exacerbations, exacerbation-related cost, survey data

Christine L Baker,1 Kelly H Zou,1 Jun Su21Pfizer Inc., New York, NY, USA; 2Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USABackground: Treatment of stable chronic obstructive pulmonary disease (COPD) with long-acting bronchodilator (LABD) medications is recommended by the 2014 Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines. The primary objective of this study was to examine LABD prescription fills after a COPD-related hospitalization.Methods: This retrospective observational study used claims from Truven Health MarketScan® Commercial and Medicare Supplemental databases. Patients (age ≥40, commercial; age ≥65, Medicare supplemental) had a first hospitalization with a primary COPD diagnosis between April 1, 2009 and June 30, 2011 (index hospitalization) and were continuously enrolled for 1 year before and 9 months after hospitalization. Patients were categorized according to pre-index and/or post-index pharmacy claims.Results: A total of 27,738 patients had an index hospitalization and met inclusion/exclusion criteria. Of those, 19,783 patients had COPD as a primary or secondary diagnosis during the year before index hospitalization and were included in the analysis. Approximately one quarter of the patients (26.32%) did not fill a prescription for an LABD or short-acting bronchodilator both 90 days before and 90 days after hospitalization. During the 90-day pre-index period, 40.57% of patients filled an LABD (with or without a short-acting bronchodilator) prescription. Over half of the patients (56.88%) filled an LABD prescription at some point during the 180-day post-index period, but, of those, a significantly greater proportion of patients filled an LABD prescription in the 1- to 90-day post-index period than in the 91- to 180-day post-index period (51.27% versus 43.66%; P

Marco daCosta DiBonaventura1, Ryne Paulose-Ram2, Jun Su3, Margaret McDonald2, Kelly H Zou2, Jan-Samuel Wagner1, Hemal Shah31Health Sciences Practice, Kantar Health, New York, NY, USA; 2Pfizer, Inc, New York, NY, USA; 3Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USAObjective: To examine quality of life, work productivity, and health care resource use among employed adults ages 40–64 years with chronic obstructive pulmonary disease (COPD) in the United States.Methods: Data from the 2009 National Health and Wellness Survey were used. All employed adults ages 40–64 years with or without a self-reported diagnosis of COPD were included in the study. Impact on quality of life (using the mental and physical component summary scores and health utilities from the Short Form-12v2), work productivity and activity impairment (using the Work Productivity and Activity Impairment questionnaire), and resource use were analyzed using regression modeling.Results: There were 1112 employed adults with COPD versus 18,912 employed adults without COPD. After adjusting for demographics and patient characteristics, adults with COPD reported significantly lower mean levels of mental component summary (46.8 vs 48.5), physical component summary (45.6 vs 49.2), and health utilities (0.71 vs 0.75) than adults without COPD. Workers with COPD reported significantly greater presenteeism (18.9% vs 14.3%), overall work impairment (20.5% vs 16.3%), and impairment in daily activities (23.5% vs 17.9%) than adults without COPD. Employed adults with COPD also reported more mean emergency room visits (0.21 vs 0.12) and more mean hospitalizations (0.10 vs 0.06) in the previous 6 months than employed adults without COPD. All of the above differences were significant at two-sided P < 0.05.Conclusion: After adjusting for various confounders, employed adults with COPD reported significantly lower quality of life and work productivity, and increased health care resource utilization than employed adults without COPD. These results highlight the substantial impact and burden of COPD in the United States workforce.Keywords: chronic obstructive pulmonary disease, quality of life, work productivity, activities of daily living, health care resource use