Comparative Pricing of Branded Tenofovir Alafenamide–Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate–Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 172, No 9

Background: Tenofovir alafenamide–emtricitabine (F/TAF) was recently approved as a noninferior and potentially safer option than tenofovir disoproxil fumarate–emtricitabine (F/TDF) for HIV preexposure prophylaxis (PrEP) in the United States. Objective: To estimate the greatest possible clinical benefits and economic savings attributable to the improved safety profile of F/TAF and the maximum price payers should be willing to pay for F/TAF over generic F/TDF. Design: Cost-effectiveness analysis. Data Sources: Published literature on F/TDF safety (in persons with and those without HIV) and the cost and quality-of-life effects of fractures and end-stage renal disease (ESRD). Target Population: Age-stratified U.S. men who have sex with men (MSM) using PrEP. Time Horizon: Five years. Perspective: Health care sector. Intervention: Preexposure prophylaxis with F/TAF versus F/TDF. Outcome Measures: Fractures averted, cases of ESRD averted, quality-adjusted life-years (QALYs) saved, costs, incremental cost-effectiveness ratios (ICERs), and maximum justifiable price for F/TAF compared with generic F/TDF. Results of Base-Case Analysis: Over a 5-year horizon, compared with F/TDF, F/TAF averted 2101 fractures and 25 cases of ESRD for the 123 610 MSM receiving PrEP, with an ICER of more than $7 million per QALY. At a 50% discount for generic F/TDF ($8300 per year) and a societal willingness to pay up to $100 000 per QALY, the maximum fair price for F/TAF was $8670 per year. Results of Sensitivity Analysis: Among persons older than 55 years, the ICER for F/TAF remained more than $3 million per QALY and the maximum permissible fair price for F/TAF was $8970 per year. Results were robust to alternative time horizons and PrEP-using population sizes. Limitation: Intermittent use and on-demand PrEP were not considered. Conclusion: In the presence of a generic F/TDF alternative, the improved safety of F/TAF is worth no more than an additional $370 per person per year. Primary Funding Source: National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, and Massachusetts General Hospital Executive Committee on Research.

Tenofovir Alafenamide for HIV Preexposure Prophylaxis: What Can We DISCOVER About Its True Value?

Dietary Assessment and Opportunities to Enhance Nutritional Epidemiology Evidence

Achieving Health Equity in Preventive Services: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Background: Disadvantaged populations in the United States experience disparities in the use of preventive health services. Purpose: To examine effects of barriers that create health disparities in 10 recommended preventive services for adults, and to evaluate the effectiveness of interventions to reduce them. Data Sources: English-language searches of Ovid MEDLINE, PsycINFO, SocINDEX, and the Veterans Affairs Health Services database (1 January 1996 to 5 July 2019); reference lists. Study Selection: Trials, observational studies with comparison groups, and systematic reviews of populations adversely affected by disparities that reported effects of barriers on use of any of the 10 selected preventive services or that reported the effectiveness of interventions to reduce disparities in use of a preventive service by improving intermediate or clinical outcomes. Data Extraction: Dual extraction and assessment of study quality, strength of evidence, and evidence applicability. Data Synthesis: No studies reported effects of provider-specific barriers on preventive service use. Eighteen studies reporting effects of patient barriers, such as insurance coverage or lack of a regular provider, on preventive service use had mixed and inconclusive findings. Studies of patient–provider interventions (n = 12), health information technologies (n = 11), and health system interventions (n = 88) indicated higher cancer screening rates with patient navigation; telephone calls, prompts, and other outreach methods; reminders involving lay health workers; patient education; risk assessment, counseling, and decision aids; screening checklists; community engagement; and provider training. Single studies showed that clinician-delivered and technology-assisted interventions improved rates of smoking cessation and weight loss, respectively. Limitation: Insufficient or low strength of evidence and applicability for most interventions except patient navigation, telephone calls and prompts, and reminders involving lay health workers. Conclusion: In populations adversely affected by disparities, patient navigation, telephone calls and prompts, and reminders involving lay health workers increase cancer screening. Primary Funding Source: National Institutes of Health Office of Disease Prevention through an interagency agreement with the Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109263)

L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms: Secondary Analysis of a Randomized Trial: Annals of Internal Medicine: Vol 172, No 11

Background: L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit. Objective: To determine whether L-thyroxine improves hypothyroid symptoms and tiredness among older adults with SCH and greater symptom burden. Design: Secondary analysis of the randomized, placebo-controlled trial TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial). (ClinicalTrials.gov: NCT01660126) Setting: Switzerland, Ireland, the Netherlands, and Scotland. Participants: 638 persons aged 65 years or older with persistent SCH (thyroid-stimulating hormone level of 4.60 to 19.9 mIU/L for >3 months and normal free thyroxine level) and complete outcome data. Intervention: L-thyroxine or matching placebo with mock dose titration. Measurements: 1-year change in Hypothyroid Symptoms and Tiredness scores (range, 0 to 100; higher scores indicate more symptoms) on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire among participants with high symptom burden (baseline Hypothyroid Symptoms score >30 or Tiredness score >40) versus lower symptom burden. Results: 132 participants had Hypothyroid Symptoms scores greater than 30, and 133 had Tiredness scores greater than 40. Among the group with high symptom burden, the Hypothyroid Symptoms score improved similarly between those receiving L-thyroxine (mean within-group change, −12.3 [95% CI, −16.6 to −8.0]) and those receiving placebo (mean within-group change, −10.4 [CI, −15.3 to −5.4]) at 1 year; the adjusted between-group difference was −2.0 (CI, −5.5 to 1.5; P = 0.27). Improvements in Tiredness scores were also similar between those receiving L-thyroxine (mean within-group change, −8.9 [CI, −14.5 to −3.3]) and those receiving placebo (mean within-group change, −10.9 [CI, −16.0 to −5.8]); the adjusted between-group difference was 0.0 (CI, −4.1 to 4.0; P = 0.99). There was no evidence that baseline Hypothyroid Symptoms score or Tiredness score modified the effects of L-thyroxine versus placebo (P for interaction = 0.20 and 0.82, respectively). Limitation: Post hoc analysis, small sample size, and examination of only patients with 1-year outcome data. Conclusion: In older adults with SCH and high symptom burden at baseline, L-thyroxine did not improve hypothyroid symptoms or tiredness compared with placebo. Primary Funding Source: European Union FP7.

National Institutes of Health Pathways to Prevention Workshop: Achieving Health Equity in Preventive Services

Expert groups, including the U.S. Preventive Services Task Force (USPSTF), recommend a range of clinical preventive services for persons at average risk for disease. Use of these services often is substantially lower among racial and ethnic minority groups, rural residents, and persons of lower socioeconomic status. On 19 and 20 June 2019, the National Institutes of Health (NIH) convened the Pathways to Prevention Workshop: Achieving Health Equity in Preventive Services to assess the available evidence on disparities in the use of 10 USPSTF-recommended clinical preventive services for cancer, heart disease, and diabetes. The workshop was cosponsored by the NIH Office of Disease Prevention; National Institute on Minority Health and Health Disparities; National Cancer Institute; National Heart, Lung, and Blood Institute; and National Institute of Diabetes and Digestive and Kidney Diseases. A multidisciplinary working group developed the agenda, and an Evidence-based Practice Center prepared the evidence report. During the workshop, invited experts considered the evidence, with discussion among attendees. After weighing evidence from the review, presentations, and public comments, an independent panel prepared a draft report that was posted for public comment. This final report summarizes the panel's findings, identifying current gaps in knowledge. The panel made 26 recommendations for new research and methods development to improve implementation of proven services to reduce disparities in preventable conditions.

The Impact of a Sweetened Beverage Tax on Beverage Volume Sold in Cook County, Illinois, and Its Border Area

Background: Sugar-sweetened beverage (SSB) consumption is linked to adverse health outcomes. Objective: To evaluate the impact of the 2017 Cook County, Illinois, Sweetened Beverage Tax (SBT) on the volume of taxed and untaxed beverages sold in Cook County and its 2-mile border area. Design: Pre–post intervention–comparison site difference-in-differences study. Setting: Cook County, Illinois, and St. Louis City and County, Missouri, 2016 to 2017. Participants: Universal product code–level store scanner data from supermarkets and grocery, convenience, drug, mass merchandise, and dollar stores. Measurements: Beverage volume sold of taxed and untaxed beverages, across product categories and sizes. Results: Volume sold of taxed beverages decreased by 27% (ratio of incidence rate ratios [RIRR], 0.73 [95% CI, 0.70 to 0.75]) on average in Cook County relative to St. Louis during the 4 months that the SBT was in effect (compared with the same 4-month pretax period), with a net decrease of 21% after increases in volume sold in its border area (cross-border shopping) were taken into account. The magnitude of the decrease in volume sold across types of taxed beverages was heterogeneous: −32% (RIRR, 0.68 [CI, 0.65 to 0.72]) for soda versus −11% (RIRR, 0.89 [CI, 0.82 to 0.97]) for energy drinks, −37% (RIRR, 0.63 [CI, 0.59 to 0.66]) for artificially sweetened beverages versus −25% (RIRR, 0.75 [CI, 0.72 to 0.79]) for SSBs, and −29% (RIRR, 0.71 [CI, 0.68 to 0.74]) for family-size versus −19% (RIRR, 0.81 [CI, 0.79 to 0.84]) for individual-size beverages. There was no significant change in volume sold of untaxed beverages in Cook County or its border area. Limitation: Data source did not allow for evaluation by store type or distance of outlets from the border. Conclusion: The Cook County SBT led to a substantial reduction in the volume sold of taxed beverages in Cook County. Part of this effect was offset by cross-border shopping. Cross-border shopping was limited to tax avoidance and did not extend to untaxed beverages. Primary Funding Source: Bloomberg Philanthropies.

Effects of Interleukin-1β Inhibition on Incident Anemia: Exploratory Analyses From a Randomized Trial: Annals of Internal Medicine: Vol 172, No 8

Background: Inflammatory cytokines, such as interleukin (IL)-1β, alter iron homeostasis and erythropoiesis, resulting in anemia, but whether inhibition of IL-1β can reverse these effects is unclear. Objective: To determine whether IL-1β inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among those with prevalent anemia. Design: Exploratory analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01327846) Setting: Many clinical sites in 39 countries. Participants: 8683 CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) participants without anemia at trial entry and 1303 with prevalent anemia at trial entry. Intervention: Random assignment to receive placebo or canakinumab (50, 150, or 300 mg) subcutaneously once every 3 months. Measurements: Primary outcome was incident anemia (hemoglobin level <130 g/L in men or <120 g/L in women). Results: Anemia incidence increased with rising baseline levels of high-sensitivity C-reactive protein (hsCRP), and both hsCRP and IL-6 decreased among participants receiving canakinumab compared with the placebo group. During a median follow-up of 3.7 years, participants without baseline anemia who received canakinumab at any dosage had significantly less incident anemia than those who received placebo (hazard ratio, 0.84 [95% CI, 0.77 to 0.93]; P < 0.001). Compared with placebo, the greatest benefits of IL-1β inhibition on incident anemia were observed among participants with the most robust anti-inflammatory response, an effect corroborated in formal mediation analyses. Among those with baseline anemia, canakinumab increased mean hemoglobin levels by 11.3 g/L (P < 0.001) compared with placebo after 2 years of treatment. Canakinumab increased the risk for infection and was associated with mild cases of thrombocytopenia and neutropenia, none of which was grade 3 or higher. Limitation: CANTOS was not designed to assess the cause of anemia in individual trial participants. Conclusion: These exploratory analyses of randomized trial data provide proof of principle that inflammation inhibition, at least through the IL-1β/IL-6 signaling pathway, reduces the incidence of anemia and improves hemoglobin levels in patients with anemia. Primary Funding Source: Novartis Pharmaceuticals.

Comparative Modeling to Inform Health Policy Decisions: A Step Forward

Meat Consumption and Health: Food for Thought