Ljubica (LJ) Ristovska

We examine the adoption of untested drugs and how physicians’ prescribing decisions respond to trials conducted in the pediatric population after initial market entry. While pediatric approval at market entry increases market share relative to no approval, physicians adopt drugs even in settings without corresponding FDA labeling information. Even though physicians use ex-post ineffective or unsafe drugs, the ex-post effective drugs comprise the majority of FDA-unapproved uses, indicating concordance between physician prescribing and FDA decisions. Subsequent FDA certification and decertification of pediatric uses of drugs have small impacts on prescription behavior due to high rates of off-label use and large delays between market entry and subsequent labeling changes.

Equally educated people are healthier if they live in more educated places. Every 10 percent point increase in an area’s share of adults with a college degree is associated with a decline in all-cause mortality by 7%, controlling for individual education, demographics, and area characteristics. Area human capital is also associated with lower disease prevalence and improvements in self-reported health. The association between area education and health increased greatly between 1990 and 2010. Spatial sorting does not drive these externalities; there is little evidence that sicker people move disproportionately into less educated areas. Differences in health-related amenities, ranging from hospital quality to pollution, explain no more than 17% of the area human capital spillovers on health. Over half of the correlation between area human capital and health is a result of the correlation between area human capital and smoking and obesity. More educated areas have stricter regulations regarding smoking and more negative beliefs about smoking. These have translated over time into a population that smokes noticeably less and that is less obese, leading to increasing divergence in health outcomes by area education.

Non-white individuals are 1.75 times more likely to get infected with COVID-19 and 1.54 times more likely to die of COVID-19 than white individuals. Using county-level data on COVID-19 cases by race, I find that average household size and public transportation use are statistically significantly correlated with case rates by race. Consequently, equalizing demographic, socio-economic, and environmental characteristics across racial groups, in particular average household size and percent elderly, is expected to reduce Black-white case rate differences by 66%, Hispanic-white case rate differences by 300%, and AIAN/NHPI-white case rate differences by 44.5%. Equalizing the strength of correlations between these characteristics and case rates across racial groups is expected to increase Black-white and AIAN/NHPI-white racial disparities but decrease Hispanic-white disparities due to the strong relationship between average household size and case rates among the Hispanic population.

Background: Data regarding the impact of symptomatic skeletal events (SSEs) on health economics and patient-reported outcomes in men with castration-resistant prostate cancer (CRPC) and bone metastases from a clinical setting are lacking. Hence, this study aimed to quantify the effects of SSEs on health-care resource utilization (HRU), health-related quality of life (HRQoL) and pain in men with CRPC metastasized to bone.

Methods: This cohort study included men with CRPC and bone metastasis treated at a tertiary center during December 1996–July 2015. SSEs, including pathological fracture, radiation to bone, spinal cord compression and bone surgery, as well as HRU were identified retrospectively through medical records and clinical database. A subset of surviving patients completed Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires. The incremental effect of SSEs on HRU was evaluated using multivariable generalized linear regression. Questionnaire scores were compared using effect sizes (ES); ES⩾0.33 indicated meaningful differences between SSE and non-SSE cohorts. Lower scores suggest lower HRQoL and pain.

Results: Of the 832 patients, 207 developed ⩾1 SSE (mean 1.5±0.8) during follow-up (median 2.1 years). Radiation to bone was the most common SSE (84.1%). SSE cohort had significantly higher emergency room (incidence rate ratio (IRR)=1.48; P=0.006), outpatient (IRR=1.17; P=0.005) and inpatient (IRR=1.74; P<0.001) visits. Of the 107 eligible survey patients, 103 (96.3%) responded. SSE cohort had lower mean FACT-P functional well-being (17.5 vs 19.8; P=0.158; ES=0.36), higher mean pain severity (2.5 vs 1.6; P=0.048; ES=0.47) and worst pain scores (3.6 vs 2.3; P=0.033; ES=0.50) compared with the non-SSE cohort, indicating meaningful differences between cohorts.

Conclusions: This study demonstrated high economic and HRQoL burden of SSEs. The findings underscore the need for better supportive and disease-modifying treatments for these patients.

Introduction: Little is known about functional limitations and health care resource utilization of people with cognitive impairment with no dementia (CIND).

Methods: Respondents with stable or progressive cognitive impairment (CI) after the first (index) indication of CIND in 2000–2010 were identified from the Health and Retirement Study (HRS). Respondents never exhibiting CI were identified as potential controls. Propensity score–based optimal matching was used to adjust for differences in demographics and history of stroke. Differences between cohorts were assessed accounting for HRS survey design.

Results: After matching, CIND respondents had more functional limitations (difficulty with ≥1 activities of daily living: 24% vs. 15%; ≥1 instrumental activities of daily living: 20% vs. 11%) and hospital stays (37% vs. 27%) than respondents with no CI (all P < .001). Seventy five percent of CIND respondents developed dementia in the observable follow-up (median time: ∼6 years).

Discussion: Even before dementia onset, CI is associated with increased likelihood of functional limitations and greater health care resource use.

Background: It is not known if there is a differential impact on Alzheimer’s disease (AD) diagnosis and outcomes if/when patients are diagnosed with cognitive decline by specialists versus non-specialists. This study examined the cost trajectories of Medicare beneficiaries initially diagnosed by specialists compared to similar patients who received their diagnosis in primary care settings.

Methods: Patients with ≥2 claims for AD were selected from de-identified administrative claims data for US Medicare beneficiaries (5 % random sample). The earliest observed diagnosis of cognitive decline served as the index date. Patients were required to have continuous Medicare coverage for ≥12 months pre-index (baseline) and ≥12 months following the first AD diagnosis, allowing for up to 3 years from index to AD diagnosis. Time from index date to AD diagnosis was compared between those diagnosed by specialists (i.e., neurologist, psychiatrist, or geriatrician) versus non-specialists using Kaplan-Meier analyses with log-rank tests. Patient demographics, Charlson Comorbidity Index (CCI) during baseline, and annual all-cause medical costs (reimbursed by Medicare) in baseline and follow-up periods were compared across propensity-score matched cohorts.

Results: Patients first diagnosed with cognitive decline by specialists (n = 2593) were younger (78.8 versus 80.8 years old), more likely to be male (40 % versus 34 %), and had higher CCI scores and higher medical costs at baseline than those diagnosed by non-specialists (n = 13,961). However, patients diagnosed by specialists had a significantly shorter time to AD diagnosis, both before and after matching (mean [after matching]: 3.5 versus 4.6 months, p < 0.0001). In addition, patients diagnosed by specialists had significantly lower average total all-cause medical costs in the first 12 months after their index date, a finding that persisted after matching ($19,824 versus $25,863, p < 0.0001). Total per-patient annual medical costs were similar for the two groups starting in the second year post-index.

Conclusions: Before and after matching, patients diagnosed by a specialist had a shorter time to AD diagnosis and incurred lower costs in the year following the initial cognitive decline diagnosis. Differences in costs converged during subsequent years. This suggests that seeking care from specialists may yield more timely diagnosis, appropriate care and reduced costs among those with cognitive decline.

Objective: To assess the real-world medical services utilization and associated costs of Medicare patients with diabetic foot ulcers (DFUs) treated with Apligraf (bioengineered living cellular construct (BLCC)) or Dermagraft (human fibroblast-derived dermal substitute (HFDS)) compared with those receiving conventional care (CC).

Methods: DFU patients were selected from Medicare de-identified administrative claims using ICD-9-CM codes. The analysis followed an ‘intent-to-treat’ design, with cohorts assigned based on use of (1) BLCC, (2) HFDS, or (3) CC (i.e., ≥1 claim for a DFU-related treatment procedure or podiatrist visit and no evidence of skin substitute use) for treatment of DFU in 2006–2012. Propensity score models were used to separately match BLCC and HFDS patients to CC patients with similar baseline demographics, wound severity, and physician experience measures. Medical resource use, lower-limb amputation rates, and total healthcare costs (2012 USD; from payer perspective) during the 18 months following treatment initiation were compared among the resulting matched samples.

Results: Data for 502 matched BLCC-CC patient pairs and 222 matched HFDS-CC patient pairs were analyzed. Increased costs associated with outpatient service utilization relative to matched CC patients were offset by lower amputation rates (−27.6% BLCC, −22.2% HFDS), fewer days hospitalized (−33.3% BLCC, −42.4% HFDS), and fewer emergency department visits (−32.3% BLCC, −25.7% HFDS) among BLCC/HFDS patients. Consequently, BLCC and HFDS patients had per-patient average healthcare costs during the 18-month follow-up period that were lower than their respective matched CC counterparts (−$5253 BLCC, −$6991 HFDS).

Limitations: Findings relied on accuracy of diagnosis and procedure codes contained in the claims data, and did not account for outcomes and costs beyond 18 months after treatment initiation.

Conclusion: These findings suggest that use of BLCC and HFDS for treatment of DFU may lower overall medical costs through reduced utilization of costly healthcare services.

Pediatric studies of drugs and devices are warranted because of the heterogeneous physiological and psychological development and response to treatment between adults and children. However, most clinical studies are conducted in adults, which implies that many drugs and devices are used in the pediatric population without being adequately tested for efficacy and safety. Many regulatory agencies have imposed regulations and legislations aimed at filling this gap and incentivizing or requiring sponsors to conduct pediatric studies. This paper discusses several important definitions related to pediatric labeling and drug development, outlines the regulatory framework in the US and EU regarding pediatric studies, and presents several data sources suitable for study of pediatric labeling and pediatric studies.