Deprescribing interventions in older adults: An overview of systematic reviews.

OBJECTIVE: The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for deprescribing interventions in older adults. METHODS: 11 databases were searched from 1st January 2005 to 16th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). RESULTS: We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment. CONCLUSION: Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178860.

Estimating the Allocation of the Economic Value Generated by Utilization of All-Oral Direct-Acting Antivirals for Hepatitis C in the United States, 2015 to 2019.

OBJECTIVES: Between 2013 to 2019, several all-oral direct-acting antivirals (DAAs) were launched with the potential to cure patients with hepatitis C virus (HCV). They generated economic value in terms of the health gains for patients and cost-savings for the US healthcare system. We estimated the share of this value allocated to 4 manufacturers vs society. METHODS: For 2015 to 2019, we estimated the incremental impact of DAAs on HCV health outcomes and costs. We used the Center for Disease Analysis Foundation Polaris Observatory database to estimate utilization. Per-patient projections of lifetime quality-adjusted life-years (QALYs) gained and medical costs avoided were based on a standard 9-state HCV disease-progression model for DAA treatment vs alternatives. Annual QALY gains were valued at $114 000 per QALY. Outcomes and costs were discounted at 3%. Estimated revenues were based on reported sales. RESULTS: An estimated 1 080 000 patients received DAAs: 81.5% would not have received the pre-DAA standard of care. On average, these patients were projected to gain 4.4 QALYs and save $104 400 in lifetime healthcare costs, generating $531.8 billion in value. Those who would have received treatment gained 1.7 QALYs and saved $41 500 in lifetime costs, generating $47.4 billion in economic value. As treatment costs fell nearly 75%, the 4 manufacturers reported $37.4 billion from DAA sales-an allocation of 6.5% of the total value. CONCLUSIONS: The significant majority (∼90%) of the economic value of curing HCV with DAAs were health benefits to patients and net cost-savings to society. DAA manufacturers received a minority share (6.5%) of the aggregate economic value generated.

Geographic disparity in the distribution of cancer clinical trials in the United States and the associated factors.

BACKGROUND: Little is known regarding the geographic disparity in the distribution of phase 1-3 clinical trials of new cancer treatments in the US and the associated factors. OBJECTIVE: To examine county-level variation in the number of phase 1-3 cancer clinical trials and the associations between county characteristics and having phase 1-3 cancer clinical trials. METHODS: We identified phase 1-3 cancer clinical trials started in the US between January 2008 and December 2022 from the Aggregate Analysis of ClinicalTrials.gov database. We analyzed the distribution of phase 1-3 cancer clinical trials at the county level. Using a mixed-effects regression with states as random intercepts, we estimated the associations between a county's median age, median household income, percentage of population from racial and ethnic minority groups, proportion of population aged 25 years or older with an educational attainment of bachelor's degree or higher, rurality, cancer incidence rate, and number of medical oncologists per population with having any phase 1-3 cancer clinical trial in a county. RESULTS: After excluding trials that were suspended, terminated, and withdrawn, a total of 14,977 phase 1-3 cancer clinical trials started in the United States between January 2008 and December 2022 were included in the primary analysis. Only 1,333 out of 3,143 counties (42.4%) had 1 or more trial during this period. Counties that were rural, with lower median household income, a less educated population, fewer medical oncologists per population, and lower cancer incidence rates demonstrated a significantly lower likelihood of having phase 1-3 cancer clinical trials. CONCLUSIONS: Our study revealed substantial geographic disparities in the distribution of phase 1-3 cancer clinical trials. Limited trial availability in low-income, low-education, low-oncologist, and rural areas can be a significant barrier to patient participation, potentially hindering adoption and worsening outcomes in disadvantaged populations.

How Much Does the US Public Value Equity in Health? A Systematic Review.

OBJECTIVES: This systematic review aims to summarize and qualitatively assess published evaluations on the US public's preferences for health equity and their willingness to trade-off efficiency for equity. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension guidelines, we searched MEDLINE and Embase for relevant peer-reviewed publications on this topic before February 2021. We included English-language articles that solicited US preferences regarding efficiency-equity trade-offs and prioritizing healthcare resources based on socioeconomic status, race, disability, or burden of disease. Quantitative and qualitative data captured were decided a priori and iteratively adapted as themes emerged. RESULTS: Fourteen studies were found over a 25-year span. Only 4 focused on resource allocation across social groups. Three distinct notions of fairness were studied: equal distribution of resources, priority to the worse-off, and equal health achieved. We found modest support for equal distribution of resources and willingness to sacrifice efficiency for equity in the United States. Prioritizing the underserved was relatively less studied and received less support and was more preferred when resources were scarce, when allocating resources between social groups, or when participants were informed about the fundamental origins of health inequities. Equal health was the least studied, but received nontrivial support. CONCLUSIONS: The existing literature evaluating the US public's understanding and preferences toward equity was severely limited by the lack of rigorous quantitative studies and heterogeneous attribute selection and fairness definitions. High-quality studies that clearly define fairness, focus on social groups, and apply rigorous methods to quantify equity preferences are needed to integrate the public's value on equity into healthcare decisions.

Medical and Non-medical Costs of Sickle Cell Disease and Treatments from a US Perspective: A Systematic Review and Landscape Analysis.

BACKGROUND: Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making. OBJECTIVE: We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs. METHODS: We searched MEDLINE and EMBASE (2008-2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle-Ottawa Scale, and costs were adjusted to 2019 US$. RESULTS: Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals (cost difference range: $6636-$63,436 annually). The highest medical cost component for SCD patients was inpatient ($11,978-$59,851 annually), followed by outpatient and then pharmacy. No studies characterized the cost burden throughout the lifetime disease trajectory of an SCD individual, and no studies captured caregiver or productivity costs. CONCLUSION: Our results reveal an incomplete characterization of medical and non-medical costs within SCD. A deeper understanding of the medical and non-medical cost burden requires completion of additional studies that capture the burden across the patient's lifetime, in addition to expression of the impact of existing and emergent health technologies on disease trajectory.

Interventions to Reduce Fall-Risk-Increasing Drug Use to Prevent Falls: A Narrative Review of Randomized Trials.

BACKGROUND: Falls and fall-related injuries are of growing concern among older adults. Use of fall-risk-increasing drugs (FRIDs) is a potentially modifiable risk factor. This narrative review describes randomized controlled trials that focused on interventions to reduce FRID use and examined fall-related outcomes (e.g., falls, fractures, risk of injury) as the primary outcome. METHODS: A comprehensive literature search was conducted to identify eligible studies. Two reviewers screened titles and abstracts and then performed a full-text review of relevant articles. Each study is summarized, and a discussion of strengths and limitations is provided. RESULTS: 7 of 22 trials were included in this narrative review. Two studies used a computerized decision support intervention, three used a health professional-led (pharmacist or geriatrician) intervention, and two were direct medication withdrawal interventions. Three studies showed a reduction in fall-related outcomes (two identified fall injuries using claims data; one used an injury risk prediction score). Of these, only one reported FRID reduction. Of four studies that did not find a reduction in falls, one study reported a significant reduction in FRIDs, two found no reduction, and one did not report on this outcome. Most interventions consisted of a one-time FRID assessment, and most targeted either providers or patients (not both). CONCLUSION: Most interventions did not reduce FRID use or change fall-related outcomes. Future studies should test "multi-pronged" intervention strategies that simultaneously target both patients and their providers and include more than a single intervention interaction to reduce this modifiable fall risk factor.

Expenditure, Utilization, and Cost of Specialty Drugs for Multiple Sclerosis in the US Medicaid Population, 2008-2018.

BACKGROUND: Multiple sclerosis (MS) is a rare, long-standing, and disabling disease that affects the central nervous system and causes several clinical manifestations. As a result, this disease is associated with a high societal economic burden. OBJECTIVE: To analyze the trends in drug expenditure, utilization, and cost of specialty drugs for the treatment of patients with MS in the US Medicaid program. METHODS: In this retrospective drug utilization research analysis, we obtained prescription data and reimbursement of disease-modifying therapies for MS from the Centers for Medicare & Medicaid Services Medicaid State Drug Utilization Data between January 2008 and December 2018. The specialty drugs considered in our analysis included dimethyl fumarate, fingolimod, teriflunomide, cladribine, siponimod, alemtuzumab, natalizumab, ocrelizumab, daclizumab, glatiramer acetate, peginterferon beta-1a, interferon beta-1a, and interferon beta-1b. The annual trends of the number of prescriptions, reimbursement expenditures, and costs were calculated. The average reimbursement per prescription was calculated as an estimate of the drug cost. RESULTS: The annual MS drug utilization increased from 85,209 prescriptions in 2008 to 223,604 in 2016, and then decreased to 194,877 in 2018. The annual reimbursement surged by 633% in the 10-year study period between 2008 and 2018, from almost $172 million in 2008 to more than $1.4 billion in 2017, and then to approximately $1.26 billion in 2018. The cost per prescription increased over time for most MS brand-name drugs (eg, from $2033 in 2008 to $5114 in 2018 for natalizumab, and from $19,138 in 2016 to $23,588 in 2018 for alemtuzumab). In 2008, self-injectable drugs dominated the market. In recent years, a shift has occurred in the utilization and reimbursement of MS drugs, with oral medications becoming predominant. CONCLUSION: The study findings indicate intermarket and interbrand competition among the MS specialty drugs. The growing utilization and spending trends for specialty MS medications are significant and sizable in the US Medicaid programs. Medicaid cost-containment strategy is warranted to control the economic burden of state budgets across the country.