A Benefit-Risk Conceptual Framework for Biologic Use During Pregnancy: A Mini-Review.

Recent reports related to in utero exposure of marketed immunosuppressive biologics led to clinical recommendations to delay live vaccinations for infants due to the concern of reduced vaccine effectiveness and/or increased risk of vaccine-related disease. These delays can increase the risk of children contracting vaccine preventable diseases, yet the alternative cessation of biologics during pregnancy may result in increased autoimmune disease activity for the pregnant person, raising complex benefit-risk (B-R) considerations and trade-offs. Our goal is to develop a conceptual framework for B-R assessment based on the key benefits and risks pregnant people would consider for themselves and their children when continuing (vs. discontinuing) a biologic during pregnancy. The proposed framework defines the decision contexts, key domains and attributes for potential benefits, and risks of biologic use during pregnancy, informed by a literature review of indications for biologics and refined with key clinical stakeholders. The framework includes both the pregnant person taking the biologic and the infant potentially exposed to the biologic in utero, with potential benefit and risk domains and attributes for each participant. To advance this conceptual framework, there are considerations of potential biases and uncertainty of available data that will be imperative to address when quantifying the B-R framework. For these reasons, we recommend the formation of a consortium to ensure development of a robust, validated framework that can be adopted in the healthcare setting.

Preferences for Treatments for Major Depressive Disorder: Formative Qualitative Research Using the Patient Experience.

OBJECTIVES: The goals of this formative research are to elicit attributes of treatment and desired outcomes that are important to individuals with major depressive disorder (MDD), to develop a stated preference instrument, and to pre-test the instrument. METHODS: A three-phase survey study design elicited the patient's journey with MDD to design and pre-test the discrete choice experiment (DCE) instrument. Participants were 20 adults aged ≥ 18 with MDD who did not also have bipolar disorder or post-partum depression. We engaged patient advocates and a multi-disciplinary stakeholder advisory group to select and refine attributes for inclusion in a DCE instrument. The DCE was incorporated into a survey that also collected depression treatment and management and sociodemographic characteristics. The DCE was pre-tested with ten adults with MDD. RESULTS: Six attributes were included in the DCE: mode of treatment (medicine only, psychotherapy only, all modalities including brain stimulation), time to treatment effect (6, 9, 12 weeks), days of hopefulness (2, 4, 6 days/week), effect on productivity (40%, 60%, 90% increase), relations with others (strained, improved, no impact), and out-of-pocket costs ($30, $60, $90/month). The DCE test led to the refinement of mode of treatment (medicine, medicine and psychotherapy, and all modalities); time to treatment effect (4, 6, 9 weeks); monthly out-of-pocket costs ($30, $90, $270). CONCLUSIONS: MDD treatment preferences revealed trade-offs among mode of treatment, time to treatment effect, functional outcomes, and cost. The findings demonstrate the potential for meaningfully incorporating the patient experience in preference measures.

Community Adversity and Utilization of Psychotropic Medications Among Children in Foster Care.

The objective of this study was to examine the association between community adversity and psychotropic use among children in foster care in one US state. This study uses a cross-sectional design integrated foster care and Medicaid administrative data with data from Kids Count, the US Census, and the Area Health Resource File. There were 4,334 children ages 5-18 in foster care in 2014. We used K-means cluster analysis grouped state counties using indicators of school performance, juvenile justice involvement, and food insecurity. Chi-square tests assessed significance between psychotropic medication and community adversity cluster. A generalized linear mixed model assessed the relationship between psychotropic use and community adversity cluster, accounting for individual-level and cluster-level factors. Children in foster care living in high adversity communities were significantly less likely to use psychotropic medication (p < .0001). Future research can investigate the specific community factor influencing judicious use of psychotropic medication and the impact on children outcomes.

Utilization of Screening Mammograms in the Medicare Population Before and After the Affordable Care Act Implementation.

Objective: This study examined screening mammograms in women aged 65 to 74 years and 75+ years before and after the Affordable Care Act (ACA) implementation. Method: This repeated cross-sectional study of community-dwelling women age 65+ years without a history of breast cancer or mastectomy utilized the Medicare Current Beneficiary Survey and Medicare fee-for-service claims data from 2001 to 2013. We used covariate-adjusted logistic regression with generalized estimating equations, stratified by age group. Results: The adjusted odds of screening mammograms in women aged 65-74 (n = 742) and 75+ years (n = 681) were lower in 2013 (odds ratio [OR]: 0.75, 95% confidence interval [CI]: [0.67, 0.83]; OR: 0.67, 95% CI: [0.60, 0.75], respectively) than the odds of screening mammograms in 2001. Discussion: Annual screening mammograms decreased in women aged 65 to 74 years and 75+ years, despite increased access from the ACA implementation. Future research as to why women are no longer receiving screening mammograms, such as changes in physician specialty guidelines, is warranted.

Factors associated with use of disease modifying agents for rheumatoid arthritis in the National Hospital and Ambulatory Medical Care Survey.

OBJECTIVE: We examined the treatment patterns among adults with rheumatoid arthritis (RA) and identified factors influencing access to traditional and biological disease modifying antirheumatic drugs (DMARDs). METHODS: We analyzed visits recorded in the National Ambulatory Medical Care Survey from 2005 to 2014 with a RA diagnosis. The primary outcome was DMARD use (traditional and/or biological). We included prescriptions of all RA-related treatments such as traditional and biological DMARDs, glucocorticoids, gold preparations, immunosuppressants, and non-steroidal anti-inflammatory drugs. Covariates in the logistic regression models included age, gender, race/ethnicity, type of health care coverage, provider type, geographic region, and number of comorbidities. RESULTS: Among 1405 visits with a RA diagnosis, 60.4% (n = 807) were prescribed DMARDs and 23.8% (n = 334) biological DMARDs. In fully adjusted models, females have 1.57 times higher odds of any DMARD use (95% confidence interval (CI): 1.02-2.46). Also, Medicare beneficiaries as compared to privately insured have 2.31 times higher odds of receiving any DMARDs (95% CI: 1.40-3.82), while visits with specialist vs. general physician are 2.38 times more associated with any DMARD use (95% CI: 1.37-4.14). For biological DMARDs, Medicare beneficiaries were at 2.58 times higher odds (95% CI: 1.42-4.70) than privately insured, while visits with specialist are at 3.37 times higher odds than general physician (95% CI: 1.40-8.23). CONCLUSION: Visits with a specialist and Medicare beneficiaries were significantly associated with any DMARD or biological DMARD use. Additionally, contrary to prior evidence, race/ethnicity was not associated with any DMARD or biological DMARD use, which may indicate reduction in disparity of treatment access.

The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies.