Pharmacogenetic testing in primary care could bolster depression treatment: A value proposition.

Pharmacogenetic testing could reduce the time to identify a safe and effective medication for depression; however, it is underutilized in practice. Major depression constitutes the most common mental disorder in the US, and while antidepressant therapy can help, the current trial -and error approach can require patients to endure multiple medication trials before finding one that is effective. Tailoring the fit of pharmacogenetic testing with prescribers' needs across a variety of settings could help to establish a generalizable value proposition to improve likelihood of adoption. We conducted a study to explore the value proposition for health systems using pharmacogenetic testing for mental health medications through prescribers' real-world experiences using implementation science concepts and systematic interviews with prescribers and administrators from four health care systems. To identify a value proposition, we organized the themes according to the Triple Aim framework, a leading framework for health care policy which asserts that high-value care should focus on three key metrics: (1) better health care quality and (2) population-level outcomes with (3) reduced per capita costs. Primary care providers whom we interviewed said that they value pharmacogenetic testing because it would provide more information about medications that they can prescribe, expanding their ability to identify medications that best-fit patients and reducing their reliance on referrals to specialists; they said that this capacity would help meet patients' needs for access to mental health care through primary care. At the same time, prescribers expressed differing views about how pharmacogenetic testing can help with quality of care and whether their views about out-of-pocket cost would prevent them from offering it. Thus, implementation should focus on integrating pharmacogenetic testing into primary care and using strategies to support prescribers' interactions with patients.

Sticking to the script: Breast cancer patients' decision making regarding oral endocrine therapy.

OBJECTIVES: We sought to understand why some women with early-stage breast cancer decide to forgo or discontinue endocrine therapy (ET), and to identify factors that might lead to greater acceptance of, and long-term adherence to, this treatment. METHODS: We conducted in-depth interviews with N = 53 stage I-III HR+ women who were either non-initiators of ET, initiators who discontinued or initiators who continued with variable daily patterns of adherence. An inductive content analysis was performed to explore the decision-making process of women prescribed ET. RESULTS: Qualitative analyses revealed 55 themes that drove complex decision making. The initiators generally trusted their physicians and did little research before starting the medication. Non-initiators were more suspicious of the medical system, believing that ET presented more risks than benefits. Most discontinuers stopped ET because of side effects. Both non-initiators and discontinuers indicated that push-back from their physicians could have changed their decision. Stories and social support were important in decision making. CONCLUSIONS: Although ET can significantly reduce the risk of breast cancer recurrence, substantial barriers prevent many women from initiating or continuing it. PRACTICE IMPLICATIONS: Physicians have powerful influence over patients' decisions to initiate ET and can be important levers for motivating patients to persist.

Chemotherapy safe handling practices in Ethiopia: A comprehensive multi-center evaluation.

INTRODUCTION: The increasing incidence of cancer and capacity for cancer care in Ethiopia has led to an upsurge in chemotherapy use in the country; however, studies indicate that there is a gap in the safe handling of chemotherapy by healthcare workers. There exists a need to understand if such unsafe practices occur in Ethiopia and, if so, which areas along the chemotherapy life cycle need the most improvement. METHODS: This study utilized a multi-method design through an online survey administered to health care professionals and evaluative site visits of eight cancer units in Addis Ababa, Ethiopia to understand the current conditions of chemotherapy handling. In addition, a survey was conducted among Ethiopian health care professionals from across the country. RESULTS: Fifty-five percent of survey participants disagreed or strongly disagreed that there are systems in place to identify, prevent, and address chemotherapy hazards in their workplace, and 71% of respondents denied having an active and effective health and safety committee and/or worker health and safety representative where they work. At evaluative site visits, only 30% of health care workers met the minimum guidelines for proper hand hygiene, and 20% of health care workers used adequate Personal Protective Equipment according to guidelines across the chemotherapy lifecycle. CONCLUSIONS: Results of this study indicate an urgent need for implementation of evidence-based interventions to improve chemotherapy handling in Ethiopia so that all patients and health care workers are protected from the hazardous toxicities of these drugs.

An evaluation of the cost-effectiveness of population genetic screening for familial hypercholesterolemia in US patients.

BACKGROUND AND AIMS: Familial hypercholesterolemia is an underdiagnosed genetic metabolic condition limiting the clearance of low-density lipoprotein cholesterol and increasing lifetime risk of cardiovascular disease. Population genetic screening in unselected individuals could quickly identify cases of familial hypercholesterolemia and enable early prevention, but the economic impact of widespread screening on patients has not been studied. METHODS: We assessed the cost-effectiveness of population genetic screening for familial hypercholesterolemia in 20 and 35-year-old adults in the United States from the perspective of patients. We developed a decision tree Markov hybrid model to examine diagnoses, cardiovascular disease, cardiac events, quality of life, and costs under population genetic screening compared to family-based cascade testing. RESULTS: While population genetic screening increased diagnoses and reduced incidence of cardiovascular disease, population genetic screening was not cost-effective compared to cascade testing at current levels of willingness to pay. Lower genetic testing costs, combined screening with other genetic conditions, and support to maintain lipid-lowering therapy use over time could improve the cost-effectiveness of population genetic screening. CONCLUSIONS: Future research is needed to examine how cost-sharing strategies may affect the cost-effectiveness of screening to patients and how families and providers experience the clinical and economic outcomes of population screening.

Challenges and opportunities for Lynch syndrome cascade testing in the United States.

Lynch syndrome is an underdiagnosed genetic condition that increases lifetime colorectal, endometrial, and other cancer risk. Cascade testing in relatives is recommended to increase diagnoses and enable access to cancer prevention services, yet uptake is limited due to documented multi-level barriers. Individual barriers such as feelings of fear, guilt, and anxiety and limited knowledge about Lynch syndrome as well as interpersonal barriers including complex family dynamics and language barriers limit family communication about Lynch syndrome and prevent uptake of genetic screening for relatives. Organizational and environmental barriers including a shortage of genetics professionals, high costs, and fears of discrimination also reduce cascade testing. These multi-level barriers may disproportionately impact underserved populations in the United States, such as individuals with lower incomes, limited English-speaking proficiency, lower educational attainment, and inadequate access to health systems. Multi-level facilitators of cascade testing include interpersonal support from family members, peers, and healthcare providers, educational resources, and motivation to improve family health. Taken together, these barriers and facilitators demonstrate a need for interventions and strategies that address multi-level factors to increase cascade testing in families with Lynch syndrome and other hereditary cancer conditions. We provide an example of a cascade testing intervention that has been developed for use in individuals diagnosed with Lynch syndrome and discuss the variety of current approaches to addressing these multi-level barriers.

Measuring Costs of Cardiovascular Disease Prevention for Patients with Familial Hypercholesterolemia in Administrative Claims Data.

INTRODUCTION: Familial hypercholesterolemia is a common genetic condition that significantly increases an individual's risk of cardiovascular events such as heart attack, stroke, and cardiac death and is a candidate for population-wide screening programs. Economic analyses of strategies to identify and treat familial hypercholesterolemia are limited by a lack of real-world cost estimates for screening services and medications for reducing cardiovascular risk in this population. METHODS: We estimated the cost of lipid panel testing in patients with hyperlipidemia and the cost of statins, ezetimibe, and PCKS9 inhibitors in patients with familial hypercholesterolemia from a commercial claims database and report costs and charges per panel and prescription by days' supply. RESULTS: The mean cost for a 90-day supply for statins was $183.33, 2.3 times the mean cost for a 30-day supply at $79.35. PCSK9 inhibitors generated the highest mean costs among medications used by patients with familial hypercholesterolemia. CONCLUSIONS: Lipid testing and lipid-lowering medications for cardiovascular disease prevention generate substantial real-world costs which can be used to improve cost-effectiveness models of familial hypercholesterolemia screening and care management.

Key considerations for developing an equitable faculty teaching workload.

PURPOSE: Faculty teaching workload has become a focus for many academic institutions given the increasing amount of faculty burnout and need for equitable distribution of effort. Many gaps exist in faculty workload guidance which contribute to decreased faculty productivity, lack of appropriate recognition, faculty burnout, and subsequently, retention of faculty. A task force was created to develop teaching workload guidance and to outline minimum teaching expectations at our school of pharmacy. DESCRIPTION: This manuscript highlights the need for clarity around the definition of roles of the contemporary educator and considerations when developing guidance around teaching workload expectations using the "What? So What? Now What?" reflection framework. ANALYSIS/INTERPRETATION: Teaching workload guidance first starts with establishing a definition of the contemporary roles of the educator. Challenges, considerations, and eight next steps are outlined that are critical to address before equitable teaching workload guidance is established. CONCLUSIONS: Teaching workload guidance should include transparency, clarity, credit, norms, context, and accountability. Additionally, solutions created to address the gaps in workload policies should be data driven. IMPLICATIONS: The current traditional system of evaluating faculty workload has many gaps due to forces driving change in pharmacy education. Roles of the pharmacy educator should be valued and recognized across all mission centric learning programs.

Defining contemporary roles of the pharmacy educator: The essential first step in developing equitable faculty teaching workload.

INTRODUCTION: Faculty workload policy has gained increased attention recently given the growing amount of faculty burnout leading to decreased productivity, worsened faculty morale, and impaired retention. Faculty are one of the most valuable resources of an academic institution; thus, it is essential that a clear picture of the "jobs to be done" are defined and valued. PERSPECTIVE: The approach of a task force charged with developing a teaching workload policy is described. Through this work, it was recognized that essential roles of the contemporary pharmacy educator have not been defined, resulting in workload policies that might only value and recognize "traditional" educator roles. This led the task force to evaluate the forces driving change in education and to identify the roles of faculty as educators. The stepwise approach used to define nine essential roles of contemporary pharmacy educators is described. IMPLICATIONS: Roles of the educator have become more complex, and traditional definitions of these roles do not recognize and value the multifaceted nature of the job to be done. Consideration of contemporary definitions of educator roles is a critical first step for developing workload policies. The new definition of educator roles will allow the academic institution to have more clarity around total teaching effort and recognize the value faculty provide the institution. We believe this is the essential first step for the Academy when developing teaching workload policies that are fair and equitable, while also understanding the overall faculty needs for executing their educational enterprise.

Patient Perspectives of Barriers and Facilitators for the Uptake of Pharmacogenomic Testing in Veterans Affairs' Pharmacogenomic Testing for the Veterans (PHASER) Program.

We applied implementation science frameworks to identify barriers and facilitators to veterans' acceptance of pharmacogenomic testing (PGx), which was made available as a part of clinical care at 25 VA medical centers. We conducted 30 min interviews with veterans who accepted (n = 14), declined (n = 9), or were contemplating (n = 8) PGx testing. Six team members coded one transcript from each participant group to develop the codebook and finalize definitions. Three team members coded the remaining 28 transcripts and met regularly with the larger team to reach a consensus. The coders generated a matrix of implementation constructs by testing status to identify the similarities and differences between accepters, decliners, and contemplators. All groups understood the PGx testing procedures and possible benefits. In the decision-making, accepters prioritized the potential health benefits of PGx testing, such as reducing side effects or the number of medications. In contrast, decliners prioritized the possibilities of data breach or the negative impact on healthcare insurance or Veterans Affairs benefits. Contemplators desired to speak to a provider to learn more before making a decision. Efforts to improve the clarity of data security and the impact on benefits may improve veterans' abilities to make more informed decisions about whether to undergo PGx testing.

Genetic Testing and Other Healthcare Use by Black and White Individuals in a Genomic Sequencing Study.

INTRODUCTION: Early adopters play a critical role in the diffusion of medical innovations by spreading awareness, increasing acceptability, and driving demand. Understanding the role of race in the context of other characteristics of potential early adopters can shed light on disparities seen in the early implementation of genomic medicine. We aimed to understand the association between self-identified race and individual experience with genetic testing outside of the research context. METHODS: We assessed factors associated with the odds of having ever received genetic testing prior to enrollment in a genomic sequencing study among 674 self-identified white and 407 self-identified African, African American, or Afro-Caribbean ("Black") individuals. RESULTS: Controlling for individual determinants of healthcare use (demographics, personality traits, knowledge and attitudes, and health status), identifying as Black was associated with lower odds of prior genetic testing (OR = 0.43, 95% CI [0.27-0.68], p < 0.001). In contrast, self-identified race was not associated with the use of non-genetic clinical screening tests (e.g., echocardiogram, colonoscopy). Black and white individuals were similar on self-reported personality traits tied to early adoption but differed by sociodemographic and resource facilitators of early adoption. CONCLUSION: Persistent racial disparities among early adopters may represent especially-entrenched disparities in access to and knowledge of genomic technologies in clinical settings.

Extending an Antiracism Lens to the Implementation of Precision Public Health Interventions.

Precision public health holds promise to improve disease prevention and health promotion strategies, allowing the right intervention to be delivered to the right population at the right time. Growing concerns underscore the potential for precision-based approaches to exacerbate health disparities by relying on biased data inputs and recapitulating existing access inequities. To achieve its full potential, precision public health must focus on addressing social and structural drivers of health and prominently incorporate equity-related concerns, particularly with respect to race and ethnicity. In this article, we discuss how an antiracism lens could be applied to reduce health disparities and health inequities through equity-informed research, implementation, and evaluation of precision public health interventions. (Am J Public Health. 2023;113(11):1210-1218. https://doi.org/10.2105/AJPH.2023.307386).

Factors Associated With Receipt of Molecular Testing and its Impact on Time to Initial Systemic Therapy in Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: Despite recommendations for molecular testing irrespective of patient characteristics, differences exist in receipt of molecular testing for oncogenic drivers amongst metastatic non-small cell lung cancer (mNSCLC) patients. Exploration into these differences and their effects on treatment is needed to identify opportunities for improvement. PATIENTS AND METHODS: We conducted a retrospective cohort study of adult patients diagnosed with mNSCLC between 2011 and 2018 using PCORnet's Rapid Cycle Research Project dataset (n = 3600). Log-binomial, Cox proportional hazards (PH), and time-varying Cox regression models were used to ascertain whether molecular testing was received, and time from diagnosis to molecular testing and/or initial systemic treatment in the context of patient age, sex, race/ethnicity, and multiple comorbidities status. RESULTS: The majority of patients in this cohort were ≤ 65 years of age (median [25th, 75th]: 64 [57, 71]), male (54.3%), non-Hispanic white individuals (81.6%), with > 2 comorbidities in addition to mNSCLC (54.1%). About half the cohort received molecular testing (49.9%). Patients who received molecular testing had a 59% higher probability of initial systemic treatment than patients who were yet to receive testing. Multiple comorbidity status was positively associated with receipt of molecular testing (RR, 1.27; 95% CI 1.08, 1.49). CONCLUSION: Receipt of molecular testing in academic centers was associated with earlier initiation of systemic treatment. This finding underscores the need to increase molecular testing rates amongst mNSCLC patients during a clinically relevant period. Further studies to validate these findings in community centers are warranted.

Scoping Review to Inform the Future Development of a Measure for Team-Based Care in Oncology.

PURPOSE: Team-based care is the delivery of health services to an individual by at least two health care providers working collaboratively to achieve optimal care. Participants on the National Cancer Institute and the ASCO Teams in the Cancer Care Delivery Project have defined 13 key principles to serve as the foundation for a successful team; however, it is unclear whether there exist measures of these key principles. METHODS: A scoping literature search was conducted for each key principle on PubMed and Embase to identify existing measures for key principles. Articles of interest were exported to a citation manager, Sciwheel, cataloged by the key principle. Existing measures were extracted via a two-stage screening process, with an abstract review followed by a full-text review. RESULTS: Fifteen unique measures were identified, with items extrapolated for 12 of the 13 key principles. Measures were not exclusive and could represent more than one key principle. The number of measures varied per principle from zero to five, with Team Composition and Diversity yielding no existing measure. CONCLUSION: The long-term goal is to compile and edit these measures, to create a comprehensive measure to be used in various team-based oncology care settings, and to address areas for improvement, ultimately optimizing patient care.

Processes and perceptions of chemotherapy supply chain in Ethiopia: A mixed-method study.

BACKGROUND: The impact and downstream effects of the chemotherapy supply chain in Ethiopia are not well understood. The purpose of this study was to identify perceived gaps in supply chain and characterize their impact on patient care. METHODS: A concurrent mixed-method study was conducted at a large academic cancer center in Ethiopia. In-depth interviews (IDIs) and surveys were completed in collaboration with external stakeholders with knowledge about chemotherapy supply chain in Ethiopia. Thematic coding was used for qualitative analysis of IDI and descriptive statistics were used to summarize quantitative survey data. RESULTS: Six stakeholders participated in the IDIs and seven completed surveys. IDIs revealed that most chemotherapeutic agents are purchased by the Ethiopian Pharmaceutical Supply Agency (EPSA) and are distributed to cancer treatment centers. A free-market purchasing option also exists, but for chemotherapy obtained outside of government-subsidized channels, the potential for substandard or falsified chemotherapy was a concern. Participants expressed confidence that the correct treatment was administered to patients, but viewpoints on reliability and consistency of medication supply were variable. Quantitative data from the survey showed that participants were not confident that medications are prepared safely and correctly. Improper storage and manipulation of high-risk medications remain a significant risk to staff. CONCLUSIONS: This study provides insight from a healthcare staff perspective on how gaps in the chemotherapy supply chain process impact patient care in a low-income country. Inventory management, disruptions in supply chain, and product integrity were perceived as the largest gaps in the current chemotherapy supply chain structure.

Development and initial testing of a multi-stakeholder intervention for Lynch syndrome cascade screening: an intervention mapping approach.

BACKGROUND: Lynch syndrome is an underdiagnosed hereditary condition carrying an increased lifetime risk for colorectal and endometrial cancer and affecting nearly 1 million people in the United States. Cascade screening, systematic screening through family members of affected patients, could improve identification of Lynch syndrome, but this strategy is underused due to multi-level barriers including low knowledge about Lynch syndrome, low access to genetics services, and challenging family dynamics. METHODS: We used intervention mapping, a 6-step methodology to create stakeholder-driven interventions that meet the needs of a target population, to develop an intervention to improve cascade screening for Lynch syndrome. The intervention development process was guided by input from key stakeholders in Lynch syndrome care and patients. We conducted usability testing on the intervention with Lynch syndrome patients using qualitative semi-structured interviewing and rapid qualitative analysis. RESULTS: We developed a workbook intervention named Let's Talk that addresses gaps in knowledge, skills, self-efficacy, outcome expectancy and other perceived barriers to cascade screening for Lynch syndrome. Let's Talk contained educational content, goal setting activities, communication planning prompts and supplemental resources for patients to plan family communication. Evidence-based methods used in the workbook included information chunking, guided practice, goal setting and gain-framing. We conducted usability testing focused on the complexity and relative advantage of the intervention through 45-min virtual interviews with 10 adult patients with Lynch syndrome recruited from a national advocacy organization in the United States. Usability testing results suggested the intervention was acceptable in terms of complexity and relative advantage to other available resources, but additional information for communication with young or distant family members and a web-based platform could enhance the intervention's usability. CONCLUSIONS: Intervention mapping provided a framework for intervention development that addressed the unique needs of Lynch syndrome patients in overcoming barriers to cascade screening. Future work is needed to transform Let's Talk into a web-based tool and evaluate the effectiveness of the intervention in clinical practice with patients and genetic counselors. Intervention mapping can be useful to researchers as an evidence-based technique to develop stakeholder-centered interventions for addressing the needs of other unique populations.