Triangulating Abuse Liability Assessment for Flavoured Cigar Products Using Physiological, Behavioural Economic and Subjective Assessments: A Within-subjects Clinical Laboratory Protocol

Introduction In the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability. Methods and analyses Participants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18–25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models

Feasibility and Quality Validation of a Mobile Application for Enhancing Adherence to Opioids in Sickle Cell Disease

Prescription opioid nonadherence, specifically opioid misuse, has contributed to the opioid epidemic and opioid-related mortality in the US. Popular methods to measure and control opioid adherence have limitations, but mobile health, specifically smartphone applications, offers a potentially useful technology for this purpose. We developed, tested, and validated the OpPill application using the Mobile Applications Rating Scale (MARS), a validated tool for assessing the quality of mobile health apps. The MARS contains four scales (range of each scale = 0–4) that rate Engagement, Functionality, Aesthetics, and Information Quality. It also assesses subjective quality, relevance, and overall application impact. Our application was built to be a mobile monitoring and reporting system intended to enhance opioid adherence by collecting data and providing systematic feedback on pain and opioid use. Patients (n = 28) all had one of various SCD genotypes, were ages 19 to 59 years (mean 36.56), 53.6% were female, and 39.3% had completed some college. Patients rated the OpPill application highly on all four scales: Engagement, 3.93 ± 0.73; Functionality, 4.54 ± 0.66; Aesthetics, 3.92 ± 0.81; Information, 3.91 ± 0.87. The majority of patients found the application to be relevant for their care. A total of 96% reported the information within the app was complete, while 4% estimated the information to be minimal or overwhelming. Patients (91.7%) overwhelmingly reported that the quality of information as it pertained to SCD patients was relevant; only 8.3% found the application to be poorly relevant to SCD. Similarly, patients (91.7%) overwhelmingly rated both the application’s performance and ease of use positively. The large majority of participants (85.7%) found the application to be interesting to use, while 74% found it entertaining. All users found the application’s navigation to be logical and accurate with consistent and intuitive gestural design. We conclude that the OpPill application, specifically targeted to monitor opioid use and pain and opioid behavior in patients with Chronic Non-Cancer Pain, was feasible and rated by SCD patients as easy-to-use using a validated rating tool

Real-world effectiveness of voxelotor for treating sickle cell disease in the US: a large claims data analysis

Sickle cell disease (SCD) is a genetic disease that impacts patients' quality of life, healthcare costs, and life expectancy. Elevated sickle hemoglobin (HbS), which readily polymerizes, causes red blood cell sickling, leading to chronic hemolytic anemia and complications often requiring hospitalization and transfusions. In 2019, voxelotor, which inhibits HbS polymerization, was approved for SCD treatment. This study uses real-world evidence to assess voxelotor's effectiveness in SCD patients in typical clinical practice from 2019 to 2021 using a national medical claims database (N = 3128). After initiating voxelotor, 60.8% of patients with available hemoglobin (Hb) laboratory data (n = 74) showed a Hb increase >1 g/dL. Mean transfusion rate per patient-year dropped 52% in patients with ≥1 transfusion before treatment (n = 190). In patients with ≥1 of the corresponding events (n = 1065), decreases were observed in mean vaso-occlusive crisis (VOC) frequency (-23%); mean VOC-related hospitalizations and length of stay (LOS) time (-34% and -30%, respectively); mean all-cause hospitalization and LOS time (-37% and -23%, respectively); outpatient visits (-10%); iron chelation use (-46%); and prescribed opioids (-13%). These data align with randomized controlled trial results showing voxelotor improvements and support that voxelotor may lower transfusion and VOC rates in clinical practice

Real-World Experience of Voxelotor for the Management of Complications in Sickle Cell Disease

Abstract Background: Sickle cell disease (SCD) is an inherited systemic disorder characterized by chronic hemolytic anemia and recurrent vaso-occlusion, which can lead to acute and chronic complications, disability, and early mortality. Patients with SCD are hospitalized frequently and most commonly for vaso-occlusive crises (VOCs). Furthermore, most will require a blood transfusion for prevention or acute management of complications, with >90% of adults receiving ≥1 transfusion in their lifetime. Voxelotor (Oxbryta ®) tablets are indicated for treatment of SCD in adults and adolescents aged ≥12 years. Emerging evidence shows that voxelotor, an oral, once-daily sickle hemoglobin-polymerization inhibitor, may improve the clinical symptoms of SCD and reduce VOC rates as well as the need for transfusions. This study sought to assess the real-world impact of voxelotor treatment on the rates and management of SCD-related complications. Methods: Medical and pharmacy claims data for patients aged ≥12 years with SCD who initiated voxelotor therapy between November 2019 and March 2021 were procured from the Symphony Health claims database. Patients with ≥1 year's data before the index date (date of the first voxelotor claim for each patient) were included in the analyses. Baseline demographic and clinical characteristics were summarized using descriptive and inferential statistics. Annualized rates per patient-year (PPY) for transfusions, VOCs, VOC-related and all-cause hospitalizations, before and after voxelotor initiation were compared. Hemoglobin (Hb) responses were evaluated for a subset of patients for whom Hb lab data were available (≥1 Hb value recorded 30 days before initiating voxelotor and ≥1 Hb value recorded after the index date). Results: As of March 2021, a total of 2695 eligible patients from the Symphony Health claims database were included in the analysis (mean age: 34.6 years; 60% female); 915 patients (34%) had ≥1 VOC in the 3 months before initiating voxelotor. Among the subset of patients with pre- and post-voxelotor Hb measurements (n=63), mean (95% CI) Hb was 7.9 (7.5-8.2) g/dL at baseline, and final Hb was 8.9 (8.4-9.4) g/dL after voxelotor initiation. Most patients (38/63; 60.3%) achieved a Hb increase of >1 g/dL at any time point during follow-up. In 357 patients who received ≥1 transfusion in the year before voxelotor initiation, the mean (95% CI) transfusion rate decreased by 43%, from 3.2 (2.8-3.7) to 1.8 (1.4-2.3) PPY (P<0.001) (Table). In 40 patients receiving chronic transfusions (≥8), the mean (95% CI) transfusion rate decreased by 34%, from 9.8 (8.3-11.4) to 6.5 (4.4-8.5) PPY (P=0.007). Among patients who had ≥1 VOC in the 3 months before initiating voxelotor, the mean (95% CI) annualized VOC rate decreased by 22%, from 10.9 (10.4-11.5) to 8.5 (7.8-9.3) (P<0.001); and the mean (95% CI) rate of VOC-related hospitalizations decreased by 32%, from 7.3 (6.9-7.7) to 5.0 (4.4-5.6) (P<0.001). In 636 patients who were previously hospitalized in the 3 months before voxelotor initiation, the mean (95% CI) all-cause hospitalization rate reduced by 36%, from 7.5 (7.1-7.9) to 4.8 (4.3-5.3) (P<0.001) after treatment. Limitations of this analysis include the possibility of secular trend biases or general regression to the mean. Conclusions: In real-world practice, voxelotor increased Hb by ≥1 g/dL, consistent with the HOPE trial. Data suggest statistically significant reductions in transfusions, VOCs, all-cause and VOC-related hospitalizations after voxelotor use. This real-world evidence provides additional support for the use of voxelotor in the treatment of hemolytic anemia and the management of its associated complications. Figure 1 Figure 1. Disclosures Shah: Novartis: Research Funding, Speakers Bureau; Emmaus: Consultancy; Alexion: Speakers Bureau; GLG: Consultancy; GBT: Consultancy, Research Funding, Speakers Bureau; Guidepoint Global: Consultancy; Bluebird Bio: Consultancy; CSL Behring: Consultancy. Lipato: Global Blood Therapeutics: Speakers Bureau. Alvarez: Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; GBT: Membership on an entity's Board of Directors or advisory committees. Delea: Global Blood Therapeutics: Research Funding; Amgen: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Merck: Research Funding; Policy Analysis Inc.: Current Employment; AbbVie: Research Funding; Novartis: Research Funding; Regeneron: Research Funding; Sanofi: Research Funding. Lonshteyn: Policy Analysis Inc. (PAI): Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Weycker: Policy Analysis Inc. (PAI): Current Employment, Current equity holder in publicly-traded company; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Nguyen: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Beaubrun: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Agodoa: Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company

Real-World Effectiveness of Voxelotor for Treating Sickle Cell Disease in the US

Background: Until late 2019, few treatments had been approved by the FDA for treating sickle cell disease (SCD). Voxelotor (Oxbryta®) is a sickle hemoglobin-polymerization inhibitor approved by the FDA in November 2019 for treatment of SCD in adults and adolescents aged ≥12 years under an accelerated approval based on results of the pivotal HOPE study. In HOPE, voxelotor increased average hemoglobin (Hb) by 1.1 g/dL from baseline in patients with 1-10 vaso-occlusive crises (VOCs) in the previous year and a Hb level between 5.5 and 10.5 g/dL who were not transfusion dependent. Of the participants on voxelotor 1500 mg, 51% had a Hb response >1.0 g/dL at week 24 (Vichinsky et al, NEJM 2019). This study sought to assess the real-world effectiveness of voxelotor based on data during the first 6 months post FDA approval. Methods: Data on medical and pharmacy claims for patients who were aged ≥12 years and receiving voxelotor from December 2019 to May 2020 were obtained from the Symphony Health claims dataset. For each patient, the date of the first voxelotor claim was defined as the "index date." Patients with at least 1 year's data prior to the index date were included in the analyses. Patients' demographic and clinical characteristics were summarized descriptively. Standardized annualized rates of transfusions and VOCs per patient per year (PPPY) prior to and after voxelotor initiation were compared. A subset of patients in the Symphony Health claims dataset had Hb lab data available. Patients with at least 1 Hb result within 30 days prior to the index date and at least 1 Hb result after the index date were included for Hb analyses. For these patients, change in Hb and the percentage of patients achieving a >1 g/dL increase in Hb were summarized. Confidence intervals and P values for changes in outcomes were based on bootstrapping. Results: As of May 31, 2020, 1275 patients from the Symphony Health claims datasets were identified who received voxelotor (40% male, mean age 35.7 years). In the year prior to voxelotor initiation, 715 (56.1%) of these patients received hydroxyurea, 121 (9.5%) received L-glutamine, 166 (13.0%) received at least 1 transfusion, 17 (1.3%) were on chronic transfusion (≥8 transfusions per year), and 681 (53.4%) had 1 or more VOCs. Mean (SD) follow-up was 64.9 (40.7) days. Among 1275 patients, 175 and 52 patients had at least 1 Hb level measurement during the 1 year prior to and after voxelotor initiation, respectively. Among the subset of patients with their Hb level tested within 30 days prior to the index date and at least 1 Hb level after index date (n=22), the baseline average Hb level was 8.0 g/dL (SD 1.4, median 7.9 g/dL, range 5.0-11.8 g/dL). Mean increase in Hb from baseline was 1.1-1.3 g/dL (Table 1) depending on the approach used to calculate Hb levels after voxelotor initiation; 55% (95% CI 32%-77%) of patients achieved a Hb increase >1 g/dL after voxelotor initiation. Among all 1275 patients, mean (SD) overall transfusion rates declined from 0.45 (1.67) PPPY pre-index to 0.31 (1.88) post-index, a change of -0.14 PPPY (P=0.005). Among 169 patients who received at least 1 transfusion in the year prior to initiation of voxelotor, the transfusion rate dropped from 3.39 (3.34) to 1.75 (4.30) PPPY, a change of -1.64 PPPY (P<0.001). Among 17 patients receiving chronic transfusions, the transfusion rate dropped from 11.29 (3.12) to 6.74 (7.37) PPPY, a change of -4.56 PPPY (P=0.013) (Table 2). After voxelotor initiation, the annualized rates of VOC were numerically reduced from 3.86 (6.69) to 3.64 (8.54) (P=0.248). To address the potential bias from the relatively short follow-up duration, similar results of transfusion and VOC rates were observed among patients with at least 30 days of follow-up or when only events within 3 months prior to index date were considered. Conclusions: Based on the first 6 months' data after the approval of voxelotor in the US, in real-world practice, voxelotor increases Hb by at least 1 g/dL, consistent with the HOPE randomized controlled trial results. Evidence suggests that transfusion rates decreased after voxelotor initiation. A favorable downward trend in VOC rates was also observed. This real-world evidence provides additional support for the use of this novel therapy in the treatment of hemolytic anemia and its associated complications in the SCD population. Further evaluation with a larger sample size and longer follow-up will help to confirm these findings. Disclosures Zaidi: Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria; Cyclerion: Consultancy, Honoraria; Imara: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; Emmaus Life Sciences: Consultancy, Honoraria. Alvarez:Novartis: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees. Lonshteyn:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Weycker:Policy Analysis Inc.: Current Employment, Current equity holder in publicly-traded company; Novartis: Research Funding; Global Blood Therapeutics: Research Funding. Pham:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Delea:Global Blood Therapeutics: Research Funding; Novartis: Research Funding; Policy Analysis Inc.: Current Employment, Current equity holder in private company. Agodoa:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Cong:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Alexion: Speakers Bureau; Bluebird Bio: Consultancy

Lessons Learned from Building a Pediatric-to-Adult Sickle Cell Transition Program.

OBJECTIVE:More effective transitions and transfers of young people with sickle cell disease (SCD) into the adult healthcare setting is a focus of both primary care and specialty care medical organizations. Effective transition and transfer requires six core elements: establishing a policy, tracking progress, administering transition readiness assessments, planning for adult care, transferring to adult care, and integrating into an adult practice. We developed a program using these six core elements. The objective of our report was to assess the development and implementation of this program. METHODS:We used the six core elements to develop and implement a program at Virginia Commonwealth University for children and adolescents with SCD to transition to adult health care. RESULTS:We assessed individuals' differences by age and grade, their independent living skills, their feelings about moving to adult care; tallied and analyzed several assessment scales; and assessed transfer success and patient retention. CONCLUSIONS:The principles and lessons we learned in developing and implementing this program over 5 years, accompanied by caring, flexible, and dedicated care team members, often can overcome even severe barriers to care transitions