Use of pembrolizumab among older adults with cancer in the United States, before and after FDA approval of its tumor-agnostic indication.

INTRODUCTION: Pembrolizumab, an anticancer immunotherapy agent, has received multiple approvals since its first approval by the U.S. Food and Drug Administration (FDA) in 2014. Limited data exist on its real-world use and shifts post tumor-agnostic approval in 2017 for the treatment of patients with any microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) solid tumors. This study analyzes pembrolizumab's pre and post-tumor-agnostic approval use among older U.S. adults, revealing its evolving role in oncology practice. METHODS: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare data (2014-2019), we examined the cancer sites of pembrolizumab recipients before and after tumor-agnostic approval. Cancer sites were classified based on the timing of site-specific approvals (before/after tumor-agnostic approval) or no site-specific approval, and inclusion in MSI-H/dMMR clinical trials. RESULTS: The total number of pembrolizumab recipients increased from 4221 in the pre-agnostic period to 20 479 in the post-agnostic period. Pembrolizumab was used for a broad range of cancer types, including cancers that had no FDA-approved site-specific indications at the time of use (25.8% in pre- and 24.6% in post-agnostic periods). The proportion of pembrolizumab recipients receiving pembrolizumab for cancers with site-specific approvals before tumor-agnostic approval decreased from 77.3% to 70.8%. The proportion of pembrolizumab recipients receiving pembrolizumab for cancers that gained site-specific approvals following tumor-agnostic approval almost doubled (6.8% to 13.0%). The proportion of pembrolizumab recipients with cancers included in MSI-H/dMMR trials also doubled (12.3% to 25.5%) following tumor-agnostic approval. CONCLUSIONS: Pembrolizumab use has expanded over time among older adults with cancer, extending beyond those with FDA-approved site-specific indications.

Association of individual low-income status and area deprivation with mortality in multiple myeloma.

INTRODUCTION: Lower individual-level socioeconomic status (SES) and area-level SES have each been associated with poor survival outcomes among patients with multiple myeloma (MM). A body of literature suggests that individual-level SES may be differentially associated with mortality depending on area-level SES, and vice versa. This study assessed the effect of the cross-level interaction between individual low-income status and area deprivation on mortality among patients with MM. MATERIALS AND METHODS: This retrospective cohort study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2006-2016). Individuals were defined as having low income if they were dually eligible for Medicare and Medicaid and/or if they received the Low-Income Subsidy. The county-level Social Deprivation Index (SDI) was linked to individual-level SEER-Medicare data and categorized into quintiles, from the least deprived (Quintile 1) to the most deprived (Quintile 5). Adjusted hazard ratios (HRs) for the associations between low-income status, area deprivation, and all-cause mortality were estimated from a mixed-effects Cox proportional-hazards (PH) model. RESULTS: The mortality hazard was higher for individuals with low income than individuals without low income in all quintiles of area deprivation, with the exception of Quintile 5 (Quintile 1: HR 1.53 [95% confidence interval [CI]: 1.32-1.77]; Quintile 2: HR 1.17 [95%CI: 1.01-1.36]; Quintile 3: HR 1.34 [95%CI: 1.18-1.53]; Quintile 4: HR 1.33 [95%CI: 1.17-1.52]; Quintile 5: HR 1.09 [95%CI: 0.96-1.23]). Among individuals without low income, individuals residing in the most deprived area had a higher mortality hazard than individuals residing in the least deprived area (HR: 1.22 [95%CI: 1.03-1.45]). In contrast, among individuals with low income, residing in a more deprived area, Quintile 2, was associated with a lower hazard of death than residing in the least deprived area, Quintile 1 (HR: 0.82 [95%CI: 0.67-0.99]), and there was no statistically significant difference between Quintile 1 and Quintiles 3, 4, and 5. DISCUSSION: In this analysis, there was a statistically significant cross-level interaction between individual low-income status and area deprivation on mortality. More research is needed to fully understand the mechanism behind these associations, but the findings show that patients and their health should be considered in the context of where they live.

Similar values, different expectations: How do patients and providers view 'health' and perceive the healthcare experience?

INTRODUCTION: No one can argue on the importance of health in one's life. However, the value of health in the context of other priorities for individuals is not always as clear. Further, patients' experience with the healthcare system is rarely contrasted with the service providers' expectations. The aim of this paper is to examine and compare patients' and providers' own definitions of health and their perceptions of the healthcare delivery experience from the lens of residents and providers in West Baltimore, Maryland. METHODS: This was a qualitative study with semi-structured focus groups (15 sessions) and individual in-depth interviews (21 interviews) with 94 participants. Two independent coders thematically analysed the transcripts. RESULTS: Patients identified five areas where health systems can help them stay healthy or become healthier: affordability and costs of care; accessibility; clinician/patient communication; addressing social determinants; and stigma and trust. Providers acknowledged that the healthcare experience is not always perfect. While the medical team focuses on conversations that enhance medical care, patients are expecting providers to touch on subjects beyond medical care. CONCLUSIONS: Patients and providers need to consider that although they have a common value towards health, there is still a gap in what users expect and what providers can offer. To further align those expectations, there is a need for increasing involvement of patient in care administration and improving dialogue between the parties about these differences. PATIENT OR PUBLIC CONTRIBUTION: A Stakeholder Advisory Board (SAB)-comprised of a patient, two community leaders, a physician and two healthcare administrators-was instrumental in codeveloping the study material (e.g., interview guides), engaging patients in the research process, identifying participants and codeveloping dissemination material. Two SAB members-Gail Graham, a patient consultant/professor, and Marcia Cort, a physician-are coauthors.

Comparative effectiveness and safety of pharmaceuticals assessed in observational studies compared with randomized controlled trials.

BACKGROUND: There have been ongoing efforts to understand when and how data from observational studies can be applied to clinical and regulatory decision making. The objective of this review was to assess the comparability of relative treatment effects of pharmaceuticals from observational studies and randomized controlled trials (RCTs). METHODS: We searched PubMed and Embase for systematic literature reviews published between January 1, 1990, and January 31, 2020, that reported relative treatment effects of pharmaceuticals from both observational studies and RCTs. We extracted pooled relative effect estimates from observational studies and RCTs for each outcome, intervention-comparator, or indication assessed in the reviews. We calculated the ratio of the relative effect estimate from observational studies over that from RCTs, along with the corresponding 95% confidence interval (CI) for each pair of pooled RCT and observational study estimates, and we evaluated the consistency in relative treatment effects. RESULTS: Thirty systematic reviews across 7 therapeutic areas were identified from the literature. We analyzed 74 pairs of pooled relative effect estimates from RCTs and observational studies from 29 reviews. There was no statistically significant difference (based on the 95% CI) in relative effect estimates between RCTs and observational studies in 79.7% of pairs. There was an extreme difference (ratio < 0.7 or > 1.43) in 43.2% of pairs, and, in 17.6% of pairs, there was a significant difference and the estimates pointed in opposite directions. CONCLUSIONS: Overall, our review shows that while there is no significant difference in the relative risk ratios between the majority of RCTs and observational studies compared, there is significant variation in about 20% of comparisons. The source of this variation should be the subject of further inquiry to elucidate how much of the variation is due to differences in patient populations versus biased estimates arising from issues with study design or analytical/statistical methods.

Are Communities Willing to Transition Into Learning Health Care Communities? A Community-Based Participatory Evaluation of Stakeholders' Receptivity.

This article aims to determine receptivity for advancing the Learning Healthcare System (LHS) model to a novel evidence-based health care delivery framework-Learning Health Care Community (LHCC)-in Baltimore, as a model for a national initiative. Using community-based participatory, qualitative approach, we conducted 16 in-depth interviews and 15 focus groups with 94 participants. Two independent coders thematically analyzed the transcripts. Participants included community members (38%), health care professionals (29%), patients (26%), and other stakeholders (7%). The majority considered LHCC to be a viable model for improving the health care experience, outlining certain parameters for success such as the inclusion of home visits, presentation of research evidence, and incorporation of social determinants and patients' input. Lessons learned and challenges discussed by participants can help health systems and communities explore the LHCC aspiration to align health care delivery with an engaged, empowered, and informed community.

Prioritization and Refinement of Patient-Informed Value Elements as Attributes for Chronic Obstructive Pulmonary Disease Treatment Preferences.

BACKGROUND AND OBJECTIVE: Formative research studies can inform stated-preference instrument development to quantify the importance of various attributes of healthcare treatments. The objective of this study was to elicit from patients with chronic obstructive pulmonary disease the prioritization of an established set of patient-informed value elements. METHODS: Using an iterative mixed-methods study design, we engaged individuals living with chronic obstructive pulmonary disease in Phase 1 value element elicitation and Phase 2 language refinement. Study participants were recruited from March to July 2019. Four guided activities, administered in an online instrument, elicited individual preferences for 40 disease-agnostic value elements that were aligned with treatment, outcomes, or care process. Responses from the guided activities were summarized and then presented to a patient advocate and additional patient participants for further refinement of the value elements and the phrasing. RESULTS: Twenty-three participants, 18 male and five female, mean age of 66 years (standard deviation = 7) were enrolled in Phase 1. Participant responses informed the selection of eight elements as the key candidates for the Phase 2 language refinement: Side Effects, New Therapeutic Option, Available Treatment, Appropriateness of Care, Predictable Healthcare Needs, Physical Activities: Endurance and Symptom Control, and Explanation of Treatment. With feedback from a patient advocate and additional patient participants, elements were refined, rephrased, or modified and this list was narrowed to six value elements (Side Effects, New Therapeutic Option, Willingness to Pay, Physical Activities, Explanation of Treatment, and Access to Care) to serve as attributes in a conceptual framework for a future quantitative stated-preference instrument. CONCLUSIONS: This patient-engaged formative work identified patients with chronic obstructive pulmonary disease key attributes of value-based decision making that underpin benefit-risk trade-offs between physical endurance, treatment side effects, care access, and cost. This study illustrates an iterative process for eliciting and refining a comprehensive list of value elements, resulting in a subgroup of elements important to a specific patient population.

The Economic Burden of Comorbid Obstructive Sleep Apnea Among Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on patients and the health care system. The presence of comorbid obstructive sleep apnea (OSA) has been shown to increase the risk of morbidity and mortality in patients with COPD. There is limited information available on the incremental economic burden of comorbid OSA among patients with COPD. OBJECTIVE: To estimate the incremental health care resource utilization (HCRU) and direct medical costs associated with having comorbid OSA among individuals with COPD in a nationally representative commercially insured population in the United States. METHODS: We identified individuals with a diagnosis of COPD between January 2008 and December 2014, with and without OSA, from the IQVIA PharMetrics Plus database. The index date was defined as the first claim with a diagnosis of COPD. All baseline characteristics were measured in the 12-month pre-index period, and all outcomes were measured in the 12-month post-index period. The odds of experiencing one or more hospitalizations and emergency room (ER) visits were compared between individuals with and without comorbid OSA using logistic regression models. Twelve-month total, physician office visit, and other outpatient costs were compared between individuals with and without OSA using generalized linear models. To account for a high proportion of zero costs, 2-part models were fit to examine inpatient, ER visit, and pharmacy costs. Average marginal costs were estimated to compare the costs of individuals with and without OSA. All costs represented direct medical costs from the health plan perspective. RESULTS: Following application of inclusion and exclusion criteria, the study sample included 85,940 individuals with COPD alone and 7,942 individuals with COPD and OSA. The odds of experiencing a hospitalization and an ER visit were significantly higher in the COPD-OSA cohort than in the COPD-only cohort (hospitalization OR = 1.45, 95% CI = 13531.38-1.53; ER visit OR = 1.24, 95% CI = 1.18-1.30). The average difference in total cost between individuals with and without comorbid OSA was $8,144 (95% CI = $7,295-$8,993). The average difference in costs for physician office visits and other outpatient services was $392 (95% CI = $351-$433) and $2,831 (95% CI = $2,463-$3,200), respectively. Among individuals with a non-zero, strictly positive inpatient cost, the average difference in inpatient costs was $2,792 (95% CI = $1,354-$4,230). Similarly, among individuals with strictly positive pharmacy and ER costs, the average difference in costs between individuals with and without comorbid OSA was $1,772 (95% CI = $1,590-$1,953) and $144 (95% CI = $101-$188), respectively. CONCLUSIONS: Total medical cost and costs for inpatient, ER, pharmacy, physician office visit, and other outpatient services were higher among COPD patients with comorbid OSA compared to patients without. The economic burden of comorbid OSA among patients with COPD in the commercially insured U.S. population is substantial. DISCLOSURES: No outside funding supported this study. Onukwugha reports grants from Bayer Healthcare Pharmaceuticals and Pfizer, unrelated to this work. Slejko reports grants from PhRMA, the PhRMA Foundation, Novartis Pharmaceuticals, and Takeda Pharmaceuticals, along with a teaching honorarium from Pfizer, unrelated to this work. Hong has nothing to disclose.

Stakeholder-Engaged Derivation of Patient-Informed Value Elements.

OBJECTIVES: Our objective was to identify patient-informed value elements that can be used to make value assessment more patient centered. METHODS: Mixed methods were used iteratively to collect and integrate qualitative and quantitative data in a four-stage process: identification (stage 1), prioritization (stage 2), refinement (stage 3), and synthesis (stage 4). Qualitative methods involved one-on-one discussions with 14 patient stakeholders from diverse medical communities representing mental health, osteoporosis, blindness, lupus, eczema, oncology, chronic obstructive pulmonary disease, and hypercholesterolemia. Stakeholders completed guided activities to prioritize elements important to patient healthcare decision making. Responses were summarized descriptively as frequencies and proportions. RESULTS: Stakeholders identified 94 value elements in stage 1. Of these, 42 elements remained following the stage 2 prioritization and the stage 3 refinement. During the stage 4 synthesis, the 42 patient-informed value elements comprised the principal set of value elements that were organized by 11 categories: tolerability, disease burden, forecasting, accessibility of care/treatment, healthcare service delivery, cost incurred on the patient, cost incurred on the family, personal well-being, stigma, social well-being, and personal values. The categories fell under five domains: short- and long-term effects of treatment, treatment access, cost, life impact, and social impact. CONCLUSIONS: In total, 75% of the value elements in the conceptual model were patient derived and distinct from the elements used in existing value frameworks. Recommendations for tailoring, quantifying, and applying the patient-informed value elements in distinct patient communities are provided. This provides a foundation from which future research may test patient-informed value elements in existing value frameworks and economic evaluations.

Patient-Reported Outcomes in Orphan Drug Labels Approved by the US Food and Drug Administration.

OBJECTIVES: In recent years, there has been increasing recognition of the need to assess treatment benefit from the patient's perspective. The extent of patient-reported outcome (PRO) data included in labeling for rare disease treatment is largely unknown. The objective of this study was to review trends over time for PRO-based labeling granted by the US Food and Drug Administration (FDA) for orphan drugs. STUDY DESIGN: Review of FDA package inserts. METHODS: Products included in this analysis were all new molecular entities (NMEs) and biologic license applications (BLAs) with orphan designations approved by the FDA from 2002 through 2017. For identified products, package inserts were reviewed to determine the number and type of PRO claim(s) granted, endpoint status, and PRO measure named. Two trends were analyzed: (1) over all years 2002 to 2017 and (2) 2002 to 2017 stratified into 3 periods (before draft FDA PRO guidance [2006], between draft and final guidance release, and after final guidance [2009] release. RESULTS: A total of 156 NMEs and BLAs with orphan designations were approved between 2002 and 2017. Of these, 13 products (8.3%) had PRO-based labeling, and 7 of 13 were symptom-related. The percent of orphan drugs approved with PRO-based labeling between 2002 and 2005, 2006 and 2008, and 2009 and 2017 was 0, 10.5, and 9.9, respectively. CONCLUSIONS: In FDA-approved labeling for orphan therapies, PRO measures used as primary and secondary endpoints increased after draft FDA PRO guidance release but remained relatively low thereafter. It is important to understand barriers to PRO measure use to ensure that treatments capture perspectives of patients with rare diseases.

Medication errors in community pharmacies: The need for commitment, transparency, and research.

Medication errors place a serious medical and economic burden on the United States (U.S.) healthcare system. Since 1975, government health agencies and non-profit organizations in the U.S., such as the Agency for Healthcare Research and Quality (AHRQ), the Institute of Medicine (IOM), and the Joint Commission, have undertaken initiatives intended to reduce medication errors, and there has been noteworthy progress in inpatient settings. However, there have been fewer advances in settings outside the hospital such as community pharmacies, where 4 billion prescriptions were dispensed to patients in 2017. There are limited information and research on community pharmacies' involvement in reducing and preventing medication errors. Most published studies on medication errors in community pharmacy settings are cross-sectional in design and often limited by geography, such that each study describes a single geographic region, i.e., one or a few practices in a single city or state within the U.S. An attempt to gain additional insight on how medication errors are managed was met with the inability of many pharmacy corporations to provide meaningful information. In order to reduce medication errors, improvement strategies such as transparency and bi-directional communication between pharmacists and patients are needed. Pharmacists are required by law to counsel patients, and research has shown that counseling can assist with detecting medication errors. Community pharmacies play a significant role in the U.S. healthcare system, but their efforts to reduce medication errors are not well known. By improving transparency in quality assurance processes and promoting patient engagement to improve patient safety, community pharmacies have the potential to play a more active role in reducing medication errors and safeguarding patients from harm.

Querying stakeholders to inform comparative effectiveness research.

Despite the growing recognition of the value of stakeholder engagement in research, there is limited guidance on effectively eliciting stakeholder views during the comparative effectiveness research (CER) process. This article outlines the potential role of each stakeholder (patient, provider, policymaker and payer) throughout the CER process and provides examples of practical questions that researchers can ask the four primary stakeholder groups at each step of the CER process. This guide aims to assist in the development of meaningful stakeholder-researcher shared decision-making to incorporate stakeholder views in the design, conduct and dissemination of patient-centered CER.