Patient preferences for chronic lymphocytic leukemia treatments: a discrete-choice experiment.

Aim: Patient preferences for the features of targeted chronic lymphocytic leukemia (CLL) therapies may differ. Materials & methods: A discrete-choice experiment (DCE) survey was administered to 229 respondents recruited through the CLL Society. Results: Respondents placed most importance on increasing the chance of progression-free survival (PFS) at 2 years from 70 to 90% and confirming results with measurable residual disease (MRD) testing instead of routine testing. Respondents also preferred daily oral administration over intravenous infusion every 4 weeks, fixed-duration treatments over treat-to-progression treatments and treatments with lower side effect risks. Reducing risk of tumor lysis syndrome was least important relative to changes in other attributes. Conclusion: The combination of improving PFS combined with confirming results using MRD testing was more important than changes in all other study attributes included in the DCE. Results from this study can help inform shared decision-making when selecting therapies for CLL.

Several targeted treatments are available for people with chronic lymphocytic leukemia (CLL). These treatments target specific proteins present in CLL cancer cells. They differ in how long they keep cancer from progressing, how the results are measured and the side effects they cause. Some targeted CLL treatments are taken as a daily pill, and others are given by intravenous infusion. Some targeted treatments are given for a fixed amount of time, and others are given until CLL progresses. We surveyed 229 US patients with CLL to understand what features they most value in a targeted CLL treatment. Survey participants were recruited through the CLL Society, a nonprofit organization devoted to education, support, advocacy and research for the CLL community. Survey results indicated that participants placed the most importance on increasing the chance that the cancer would not progress after 2 years from 70 to 90% and confirming results with measurable residual disease testing (which can detect minute levels of leukemia cells) instead of routine testing. Participants also preferred taking a pill every day over receiving an intravenous infusion every 4 weeks and preferred treatments given for a fixed amount of time over treatments given until CLL progresses. Participants preferred treatments with lower chances of tumor lysis syndrome (a potentially organ-damaging condition that may result following treatment), irregular heartbeat and fatigue. It is important for doctors to understand the treatment features that matter to people living with CLL so that they can work with patients individually to choose the right treatment.

Real-World Health Care Resource Use and Costs Among Patients With Chronic Lymphocytic Leukemia Treated With Venetoclax-Based and Bruton Tyrosine Kinase Inhibitor-Based Regimens in the Second-Line Setting.

PURPOSE: Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. METHODS: This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi. Baseline characteristics were balanced using stabilized inverse probability of treatment weights. Mean monthly cost difference (MMCD) between cohorts for all-cause and CLL-specific per patient per month (PPPM) costs was estimated. Rates of PPPM-HRU were compared between cohorts using rate ratios (RRs). RESULTS: Of 280 patients, median age 75.5 years, 64.6% and 35.4% received BTKi- versus venetoclax-based regimens, respectively. Most BTKi-treated patients received monotherapy (88.4%), whereas 62.3% of venetoclax-treated patients received combination therapy with anti-CD20 agents. The median duration of 2L therapy was 11.6 and 11.0 months for BTKi versus venetoclax cohorts, respectively. All-cause total costs were lower for venetoclax versus BTKi (MMCD [SE], $-2,497.64 [$1,006.77] in US dollars (USD); P = .01), driven by lower medication costs offsetting medical costs; trends were similar for CLL-specific estimates. Outpatient HRU was higher for venetoclax versus BTKi (RR all-cause: 1.22 versus CLL-specific: 1.64). CONCLUSION: Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.

Real-world adherence and discontinuation among Medicare beneficiaries initiating venetoclax vs. BTKis in relapsed/refractory chronic lymphocytic leukemia.

The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton's tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015-2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12 months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p < .001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p < .001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults.

Treatment Discontinuation Patterns for Patients With Chronic Lymphocytic Leukemia in Real-World Settings: Results From a Multi-Center International Study.

INTRODUCTION: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings. MATERIALS AND METHODS: Using deidentified electronic medical records from the CLL Collaborative Study of Real-World Evidence, premature treatment discontinuation was assessed among FCR, BR, BTKi-based, and BCL-2-based regimen cohorts. RESULTS: Of 1364 1L patients (initiated in 1997-2021), 190/13.9% received FCR (23.7% discontinued prematurely); 255/18.7% received BR (34.5% discontinued prematurely); 473/34.7% received BTKi-based regimens, of whom 28.1% discontinued prematurely; and 43/3.2% received venetoclax-based regimens, of whom 16.3% discontinued prematurely (venetoclax monotherapy: 7/0.5%, of whom 42.9% discontinued; VG/VR: 36/2.6%, of whom 11.1% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 25/13.2%; BR: 36/14.1%; BTKi-based regimens: 75/15.9%) and disease progression (venetoclax-based: 3/7.0%). Of 626 2L patients, 20/3.2% received FCR (50.0% discontinued); 62/9.9% received BR (35.5% discontinued); 303/48.4% received BTKi-based regimens, of whom 38.0% discontinued; and 73/11.7% received venetoclax-based regimens, of whom 30.1% discontinued (venetoclax monotherapy: 27/4.3%, of whom 29.6% discontinued; VG/VR: 43/6.9%, of whom 27.9% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 6/30.0%; BR: 11/17.7%; BTKi-based regimens: 60/19.8%; venetoclax-based: 6/8.2%). CONCLUSION: The findings of this study highlight the continued need for tolerable therapies in CLL, with finite therapy offering a better tolerated option for patients who are newly diagnosed or relapsed/refractory to prior treatments.

A Probabilistic Cost-Effectiveness Analysis of Venetoclax and Obinutuzumab as a First-Line Therapy in Chronic Lymphocytic Leukemia in Canada.

BACKGROUND: Venetoclax is a first-in-class targeted therapy option that is an inducer of apoptosis in chronic lymphocytic leukemia (CLL) cells. The open-label phase III CLL14 clinical trial showed that venetoclax combined with obinutuzumab (VEN+O) is superior to obinutuzumab combined with chlorambucil in newly diagnosed patients with CLL. The aim of this study was to assess the health economic value of VEN+O for the frontline treatment of CLL in Canada from a publicly funded healthcare system perspective. METHODS: A partitioned survival analyses model was developed including three health states: progression free, progressed, and death. A cycle length of 28 days and a time horizon of 10 years was assumed. VEN+O treatment for a fixed duration of 12 months was compared to obinutuzumab combined with chlorambucil, fludarabine plus cyclophosphamide plus rituximab, bendamustine plus rituximab, chlorambucil plus rituximab, ibrutinib, and acalabrutinib. The population in the model included both unfit and overall frontline CLL patients, two subgroups were also assessed (patients with del17p/TP53 mutations and patients without del17p/TP53 mutations). Survival data extrapolated from the CLL14 trial were used to populate the model. Uncertainty was assessed via one-way sensitivity analyses, probabilistic analyses, and scenario analyses. RESULTS: Based on the probabilistic analyses, unfit frontline CLL patients receiving VEN+O were estimated to incur costs of Canadian dollars ($) 217,727 [confidence interval (CI) $170,725, $300,761] (del17p/TP53: $209,102 [CI $159,698, $386,190], non-del17p/TP53: $217,732 [CI $171,232, $299,063]) and accrue 4.96 [CI 4.04, 5.82] quality-adjusted life-years (del17p/TP53: 3.11 [CI 2.00, 4.20], non-del17p/TP53: 5.04 [CI 4.05, 5.92]). Obinutuzumab combined with chlorambucil, bendamustine plus rituximab, chlorambucil plus rituximab, and ibrutinib accrued lower quality-adjusted life-years and higher costs and as such, VEN+O was the dominant treatment option. The full incremental analysis showed that acalabrutinib was more expensive and more efficacious compared with VEN+O with an incremental-cost-effectiveness-ratio of $2,139,180/quality-adjusted life-year versus VEN+O and not a cost-effective option in Canada. Probabilistic analyses show that at a willingness to pay of $50,000/quality-adjusted life-year gained, VEN+O has the greatest probability of being cost effective. CONCLUSIONS: VEN+O is a cost-effective treatment option for unfit frontline CLL patients and provides value for money to healthcare payers.

Cost-effectiveness of a 12-month fixed-duration venetoclax treatment in combination with obinutuzumab in first-line, unfit chronic lymphocytic leukemia in the United States.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a significant health and economic burden in the United States. Treatments include chemoimmunotherapy, such as obinutuzumab (G) plus chlorambucil (Clb) or bendamustine plus rituximab (BR), and chemotherapy-free regimens incorporating oral targeted therapies such as ibrutinib (Ibr), acalabrutinib (Acala), or venetoclax (Ven). Most chemotherapy-free regimens require continuous treatment to progression, while Ven plus G (VenG) is given for a fixed duration of 12 months, based on the CLL14 trial that led to its approval. Fixed-duration VenG has the potential for cost savings compared with treat-to-progression chemotherapy-free regimens. OBJECTIVE: To evaluate the cost-effectiveness of 12 months fixed-duration VenG in first-line treatment of unfit patients with CLL from a US health care payer perspective compared with GClb, BR, Ibr, Ibr + G, Ibr + R, Acala, and Acala + G. METHODS: A partitioned survival model was developed with 3 health states: progression-free survival (PFS), postprogression survival, and dead. The patient population, as based on the CLL14 trial, comprised previously untreated unfit patients with CLL (mean age 71.1 years, 33.1% female). The distribution of patients in each health state over time was estimated using extrapolated PFS and overall survival (OS) curves for VenG and GClb, based on CLL14 data 2 or more years after treatment cessation. PFS and OS for the other comparators were estimated using hazard ratios vs VenG, based on a network metaanalysis. Adverse events, utility values, and costs were obtained from published literature. The model estimated life-years gained, quality-adjusted life-years (QALYs) gained, and costs. The time horizon was 20 years, with a cycle time of 28 days. Outcomes and costs were discounted at 3.0% per year, and costs were estimated from a US health care payer perspective. One-way and probabilistic sensitivity analyses were conducted. RESULTS: In this cross-trial analysis of unfit CLL patients, in the base case, VenG had lower projected total costs than all comparators investigated. VenG also had larger projected health benefits (more QALYs gained) than GClb, BR, Ibr, and Ibr + R. VenG was therefore more effective and less costly than these comparators (dominant). Ibr + G, Acala, and Acala + G showed higher QALYs gained vs VenG (0.022, 0.672, and 0.961, respectively), and substantially higher projected costs vs VenG ($1,488,400, $1,579,737, and $1,656,154, respectively). Thus, Ibr + G, Acala, and Acala + G would cost more than $1,000,000 per QALY gained vs VenG. At the commonly used willingness-to-pay threshold of $150,000 per QALY gained, Ibr + G, Acala, and Acala + G were not cost-effective compared with VenG. CONCLUSIONS: Fixed-duration VenG for 12 months is a cost-effective first-line treatment option for unfit CLL patients compared with other available options and provides value for money to US health care payers at a threshold of $150,000 per QALY gained. Future studies with longer trial follow-up and more mature survival data may help to confirm longer-term cost benefits of VenG. DISCLOSURES: Genentech Inc. and AbbVie provided financial support for this study. Genentech Inc., AbbVie, and Pharmerit - An OPEN Health Company participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. Venetoclax is being developed in a collaboration between Genentech Inc. and AbbVie. Ravelo and Shapouri are employed by Genentech Inc. and have ownership interests. Manzoor and Sail are employed by AbbVie and have ownership interests. Chatterjee, van de Wetering, and Qendri, employees of Pharmerit - An OPEN Health Company, received consultancy fees from AbbVie. Davids has received consultancy fees from AbbVie, AstraZeneca, Eli Lilly, Genentech Inc., Janssen, MEI Pharma, Novartis, Pharmacyclics, and Verastem; research funding from Ascentage Pharma, Genentech Inc., MEI Pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, and Verastem; and has served on board of directors or advisory committees for AbbVie, Adaptive Biotechnologies, AstraZeneca, BeiGene, Eli Lilly, Genentech Inc., Janssen, Pharmacyclics, TG Therapeutics, and Verastem. This study was presented as a poster at ASH 61st Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

Budget Impact of 12-Month Fixed Treatment Duration Venetoclax in Combination with Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia Patients in the United States.

OBJECTIVES: This study aimed to assess the total cost of care (TCC) and budget impact of introducing 12-month fixed duration venetoclax + obinutuzumab (VEN+G) as first-line treatment for chronic lymphocytic leukemia (CLL) from the perspective of a US health plan with 1,000,000 (1M) members. METHODS: The 3-year model included the following comparators: fludarabine + cyclophosphamide + rituximab (FCR), bendamustine + rituximab (BR), obinutuzumab + chlorambucil (GClb), ibrutinib (Ibr), and Ibr+Rituximab/obinutuzumab [Ibr+R/Ibr+G]). TCC included US-specific costs associated with treatment (i.e., drug, administration, and wastage), adverse events, routine care, and monitoring. Dosing and safety data were drawn from clinical trials and US package inserts. Budget impact outcomes were presented on an absolute and per-member per-month (PMPM) basis. Sensitivity analyses explored uncertainty in influential parameters, including scenarios testing the duration of treat-to-progression agents. RESULTS: Over the 3-year time horizon, introducing VEN+G in a 1M-member health plan resulted in total cost savings of $1,550,663 (PMPM - $0.04), compared to a scenario without VEN+G. The fixed 12-month duration of VEN+G contributed to this cost saving by reducing cumulative treatment costs compared with Ibr-based regimens. By year 3, the cumulative difference in TCC of VEN+G compared with Ibr, Ibr+G, and Ibr+R amounted to - $300,942, - $367,001, and - $369,784, respectively. Extensive sensitivity analyses supported the base case findings. CONCLUSIONS: Introducing VEN+G among first-line CLL treatments to a US health plan resulted in cost savings compared to a plan with chemoimmunotherapies and Ibr-based therapies only. Economic benefits of VEN+G, a novel agent with fixed treatment duration, coupled with proven clinical benefits should help inform formulary adoption decisions and treatment recommendations.

Facilitators and Barriers to the Adoption of Pharmacogenetic Testing in an Inner-City Population.

OBJECTIVES: To examine the knowledge, attitudes, and interest of an inner-city population toward pharmacogenetic testing, with the primary objective of identifying facilitators and barriers toward pharmacogenetic testing; and secondary objectives of determining predictors of patient interest in pharmacogenetic testing and how much patients would pay for the test. METHODS: Patients were recruited from an Antithrombosis Clinic from March to April 2014. A cross-sectional 19-question survey was administered in person to determine patients' knowledge and awareness of pharmacogenetic testing and collect demographic information. After explaining pharmacogenetics, patients ranked their interest toward the test and answered open-ended questions that elicited facilitators and barriers toward pharmacogenetic testing and elucidated how much patients would pay for testing. RESULTS: A total of 120 patients (mean age 55.0 ± 14.0 years, 39.2% male, 69.2% African American) were surveyed. Facilitators included providing further information about pharmacogenetic testing; elaborating on benefits of testing to predict treatment efficacy; patients' trust in their providers to make correct genotype-guided prescribing decisions; and insurance coverage and test affordability. Barriers to testing included concerns about the negative consequences associated with test results; burden of the testing process; perceived lack of utility among elderly and those whose medications were working; privacy issues; and concerns regarding insurance coverage and test affordability. Women had 4.2 times higher adjusted odds of being interested in pharmacogenetic testing. Almost half (44.4%) of the patients with high interest in the test were willing to pay $20 or more, whereas 76.2% of patients with low interest wanted testing at no cost. CONCLUSION: This study identified facilitators, such as providing additional pharmacogenetic test information, and barriers, such as perceived negative impact of the results and test utility, as issues to address when engaging an urban, largely minority population in pharmacogenetic testing. Female sex was a predictor of interest toward pharmacogenetic testing. These facilitators and barriers should be taken into consideration as pharmacogenetic testing gains widespread utility among inner-city populations.

High number of newly initiated direct oral anticoagulant users switch to alternate anticoagulant therapy.

Real-world evidence focusing on medication switching patterns amongst direct oral anticoagulant (DOACs) has not been well studied. The objective of this study is to evaluate patterns of prescription switching in non-valvular atrial fibrillation (NVAF) patients initiated on a DOAC and previously naïve to anticoagulation (AC) therapy. Data was obtained from Truven Health MarketScan® Commercial and Medicare Supplemental database (2009-2013). AC naïve (those without prior anticoagulant use) NVAF patients initiated on a DOAC, with 6 months of continuous health plan enrollment before and after treatment initiation and maintained on continuous therapy for a minimum of 6 months were included. Of 34,022 AC naïve NVAF patients initiating a DOAC, 6613 (19.4%) patients switched from an index DOAC prescription to an alternate anticoagulant and 27,409 (80.6%) remained on the DOAC [age: 68.5 ± 11.7 vs. 67.1 ± 12.7 years, p < 0.001; males: 3781 (57.2%) vs. 17,160 (62.6%), p < 0.001]. Amongst those that switched medication, 3196 (48.3%) did so within the first 6 months of therapy. Overall, 2945 (44.5%) patients switched to warfarin, 2912 (44.0%) switched to another DOAC and 756 (11.4%) switched to an injectable anticoagulant. The highest proportion of patients switched from dabigatran to warfarin (N = 2320; 42.5%) or rivaroxaban (N = 2252; 41.3%). The median time to switch from the index DOAC to another DOAC was 309.5 days versus 118.0 days (p < 0.001) to switch to warfarin. In NVAF patients newly initiated on DOAC therapy, one in five patients switch to an alternate anticoagulant and one of every two patients do so within the first 6 months of therapy. Switching from an initial DOAC prescription to traditional anticoagulants occurs as frequently as switching to an alternate DOAC.

Quality of Pharmacist-Managed Anticoagulation Therapy in Long-Term Ambulatory Settings: A Systematic Review.

OBJECTIVE: To perform a systematic review to evaluate the quality of warfarin anticoagulation control in outpatient pharmacist-managed anticoagulation services (PMAS) compared with routine medical care (RMC). DATA SOURCES: MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, and Cochrane CENTRAL, from inception to May 2017. Search terms employed: ("pharmacist-managed" OR "pharmacist-provided" OR "pharmacist-led" OR "pharmacist-directed") AND ("anticoagulation services" OR "anticoagulation clinic" OR "anticoagulation management" OR "anticoagulant care") AND ("quality of care" OR "outcomes" OR "bleeding" OR "thromboembolism" OR "mortality" OR "hospitalization" OR "length of stay" OR "emergency department visit" OR "cost" OR "patient satisfaction"). STUDY SELECTION AND DATA EXTRACTION: Criteria used to identify selected articles: English language; original studies (comments, letters, reviews, systematic reviews, meta-analyses, editorials were excluded); warfarin use; outpatient setting; comparison group present; time in therapeutic range (TTR) included as a measure of quality of anticoagulant control; study design was not a case report. DATA SYNTHESIS: Of 177 articles identified, 25 met inclusion criteria. Quality of anticoagulation control was better in the PMAS group compared with RMC in majority of the studies (N = 23 of 25, 92.0%). Clinical outcomes were also favorable in the PMAS group as evidenced by lower or equal risk of major bleeding (N = 10 of 12, 83.3%) or thromboembolic events (N = 9 of 10, 90.0%), and lower rates of hospitalization or emergency department visits (N = 9 of 9, 100%). When reported, PMAS have also resulted in cost-savings in all (N=6 of 6, 100%) of studies. CONCLUSIONS: Compared with routine care, pharmacist-managed outpatient-based anticoagulation services attained better quality of anticoagulation control, lower bleeding and thromboembolic events, and resulted in lower health care utilization.

Real-World Adherence and Persistence with Direct Oral Anticoagulants in Adults with Atrial Fibrillation.

BACKGROUND: Evidence of adherence and persistence patterns in anticoagulation (AC) therapy comparing treatment-naïve and non-naïve patients is lacking. The objective of this study was to evaluate patterns of medication adherence and persistence in a real-world setting among AC-naïve and AC-experienced patients with atrial fibrillation (AF) who were treated with direct oral anticoagulants (DOACs). METHODS: AF patients newly initiating a DOAC with a minimum of 6 months of continuous health plan enrollment pre and postindex date (first DOAC prescription) were identified from the Truven Health MarketScan Commercial and Medicare Supplemental databases (2009-2013). DOAC adherence (proportion of days covered [PDC]), persistence, and predictors of adherence were assessed at 6 and 12 months postindex. RESULTS: Of 66,090 AF patients included, 46.6% (n=30,826) were AC naïve and 53.4% (n=35,264) were AC experienced (age: 66.9 ± 12.7 vs 70.4 ± 11.4 yrs, p<0.001; male: n=19,132 [62.1%] vs n=21,691 [61.5%], p=0.14, respectively). A majority of patients received dabigatran as their index DOAC (n=49,210; 74.5%). The mean PDC in AC-naïve versus AC-experienced patients at 6 and 12 months of follow-up was 72.3% versus 83.3% (p<0.001) and 63.7% versus 79.9% (p<0.001), respectively. Persistence with DOAC therapy in AC-naïve and AC-experienced patients at 6 and 12 months ranged from 59.3% and 76.3% (p<0.0001) to 31.6% and 50.2% (p<0.0001), respectively. Predictors of higher DOAC adherence were older age and higher number of concomitant medications. Predictors of lower adherence were higher number of comorbidities and AC-naïve user status. CONCLUSION: Medication adherence and persistence with DOACs declined over time and both were suboptimal and lower (at 6 and 12 mo postindex) in AC-naïve compared to AC-experienced patients. These findings can help target future strategies or interventions for patient education and long-term AC management especially in those patients naïve to DOAC therapy. Future investigation should examine potential reasons for differences in DOAC adherence and persistence between AC-experienced versus AC-naïve patients and the implications for patient outcomes.

Drug-Alcohol Interactions in Older U.S. Adults.

OBJECTIVES: To characterize the extent and nature of drug-alcohol interactions in older U.S. adults. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: Nationally representative population-based sample of community-dwelling older adults (N = 2,975). MEASUREMENTS: Regular drinkers were defined as respondents who consumed alcohol at least weekly. Medication use was defined as the use of a prescription or nonprescription medication or dietary supplement at least daily or weekly. Micromedex was used to determine drug interactions with alcohol and their corresponding severity. RESULTS: One thousand one hundred six (41%) of the participants consumed alcohol regularly, and 567 (20%) were at-risk for a drug-alcohol interaction because they were regular drinkers and concurrently using alcohol-interacting medications. More than 90% of these interactions were of moderate or major severity. Antidepressants and analgesics were the most commonly used alcohol-interacting medications in regular drinkers. Older adult men with multiple chronic conditions had the highest prevalence of potential drug-alcohol interactions. CONCLUSION: The potential for drug-alcohol interactions in the older U.S. adult population may have important clinical implications. Efforts to better understand and prevent the use of alcohol-interacting medications by regular drinkers, particularly heavy drinkers, are warranted in this population.

Comparative effectiveness of patient-centered strategies to improve FDA medication guides.

BACKGROUND: Med Guides are the only Food and Drug Administration-regulated source of written patient information distributed with prescriptions drugs. Despite their potential value, studies have found them to have limited utility. OBJECTIVE: To evaluate the effectiveness of patient-centered strategies for the design of Med Guides to improve comprehension. DESIGN: A cross-sectional, randomized trial. SETTING: Two primary care clinics in Chicago, Illinois; one based in a public university hospital and the other within a private academic medical center. PATIENTS: A total of 1003 adults aged 18-85 years. INTERVENTION: The format and layout of content from 3 typical Med Guides (by reading difficulty, length, exposure) were modified several ways to promote information accessibility. Working with patients, the 3 most preferred versions were evaluated. The first used 2 columns to organize content (Column), a second mimicked over-the-counter "Drug Facts" labeling (Drug Facts), and the third followed health literacy best practices using a simple table format (Health Literacy prototype). MEASURES: Tailored comprehension assessment of content from 3 representative Med Guides. RESULTS: Comprehension was significantly greater for all 3 prototypes compared with the current standard (all P<0.001). The Health Literacy prototype consistently demonstrated the highest comprehension scores, and in multivariable analyses, outperformed both the Drug Facts [ß=-4.43, 95% confidence interval (CI), -6.21 to -2.66] and Column (ß=-4.04, 95% CI, -5.82 to -2.26) prototypes. Both older age (older than 60 y: ß=-10.54, 95% CI, -15.12 to -5.96), low and marginal literacy skills were independently associated with poorer comprehension (low: ß=-31.92, 95% CI, -35.72 to -28.12; marginal: ß=-12.91, 95% CI, -16.01 to -9.82). CONCLUSIONS: The application of evidence-based practices to the redesign of Med Guides significantly improved patient comprehension. Although some age and literacy disparities were reduced with the Health Literacy format in particular, both older age and low literacy remained independently associated with poorer comprehension. More aggressive strategies will likely be needed to gain assurances that all patients are informed about their prescribed medications. TRIAL REGISTRATION: Clinical Trials.Gov #NCT01731405.