Estimating the Public Health Impact from Introducing Tobacco-Free Nicotine Pouches Into the US

2021 ◽  
Author(s):  
Peter N Lee ◽  
John S Fry ◽  
Tryggve Ljung
Keyword(s):  
Smoking Status ◽  
Health Impact ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Initiation Rate ◽  
Individual Parameter ◽  
Product Use ◽  
The Us ◽  
Current Product

Abstract BackgroundFor smokers not intending to quit, switching to a reduced-risk nicotine product should be healthier than continuing smoking. We estimate the health impact, over the period 2000-2050, of introducing into the US the nicotine pouch ZYN. ZYN’s toxicant profile and method of use is like that for Swedish snus, a product with known health effects much less than smoking. MethodsOur modelling approach is similar to others developed for estimating potential effects of new tobacco products. It starts with a simulated cohort of 100,000 individuals in the year 2000 subdivided by age, sex, and smoking status (including years since quitting). They are followed annually accounting for births, net immigrations, deaths and product use changes, with follow-up carried out in the Base Case (ZYN not introduced) and Modified Case (ZYN introduced). Using informed assumptions about initiation, quitting and switching rates, distributions of the population over time are then constructed for each Case, which are used to estimate product-related mortality based on assumptions about the relative risk according to product use. ResultsWhereas in both Base and Modified Cases, the prevalence of any current product use is predicted to decline from about 22% to 10% during follow-up, in the Modified Case about 25% of current users use ZYN by 2050, about a quarter being dual users and the rest ZYN-only users. Over the 50 years, deaths at ages 35-84 from product use among the 100,000 are estimated as 249 less in the Modified than the Base Case, equivalent to about 700,000 less deaths in the whole US. Sensitivity analyses varying individual parameter values confirm the benefits of switching to ZYN, which increase as either the switching rate to ZYN increases or the initiation rate of ZYN relative to smoking increases. Even assuming the reduction in excess mortality risk using ZYN use is 20% of that from smoking rather than the 3.5% assumed in the main analyses, the reduction in product-related deaths would still be 213, or about 600,000 in the US. ConclusionsAlthough such model-based estimates are subject to uncertainties, the results suggest that introducing ZYN could substantially reduce smoking-attributable deaths.

scholarly journals Modeling the Population Health Impact of ENDS in the U.S.

2021 ◽  
Vol 45 (3) ◽  
pp. 588-610
Author(s):  
Rasmus Wissmann ◽  
Changhua Zhan ◽  
Kenneth D'Amica ◽  
Shivaani Prakash ◽  
Yingying Xu
Keyword(s):  
Population Health ◽  
Health Benefit ◽  
Population Level ◽  
Health Impact ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Premature Deaths ◽  
Key Population ◽  
The Us ◽  
Health Model

Objectives: Our objective was to improve understanding of the population health impact of electronic nicotine delivery systems (ENDS) availability in the US via computational modeling. Methods: We present an agent-based population health model (PHM) that simulates annual smoking, ENDS use, and associated mortality for individual agents representing the US population, both adults and youth, between 2000 and 2100. Model transitions were derived from key population surveys and a large longitudinal study of JUUL purchasers. The mortality impact of ENDS is modeled as excess risk relative to smoking. Outcomes are compared between a cigarettes-only Base Case and a Modified Case where ENDS are introduced in 2010. Model validation demonstrates that the PHM simulates population-level behavior and outcomes realistically. Results: The availability of ENDS in the US is projected to reduce smoking and prevent 2.5 million premature deaths by 2100 in the Modified Case. Sensitivity analyses show that a significant population health benefit occurs under all plausible scenarios. Conclusions: Our results suggest the availability of ENDS is likely to result in a significant health benefit to the US population as a whole, after accounting for both beneficial and harmful uses.

scholarly journals Correlates of tobacco product initiation among youth and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)

2020 ◽  
Vol 29 (Suppl 3) ◽  
pp. s191-s202 ◽  
Author(s):  
Karin A Kasza ◽  
Kathryn C Edwards ◽  
Zhiqun Tang ◽  
Cassandra A Stanton ◽  
Eva Sharma ◽  
...  
Keyword(s):  
Older Adults ◽  
Tobacco Product ◽  
Health Study ◽  
Product Use ◽  
Frequent Use ◽  
The Us ◽  
The Usa ◽  
Nationally Representative ◽  
Tobacco Initiation

ObjectiveTo report on demographic and tobacco product use correlates of tobacco product initiation (cigarettes, electronic nicotine delivery systems (ENDS), cigars, hookah and smokeless tobacco) among the US population.DesignData were from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth (aged 12–17 years) and adults (aged 18+ years). Never users of at least one type of tobacco product at Wave 1 (W1, 2013/14) or Wave 2 (W2, 2014/15) were included (n=12 987 youth; n=25 116 adults). Generalised estimating equations were used to evaluate the association between demographic and tobacco product use characteristics at baseline, and tobacco product initiation at follow-up (ever, past 30 day (P30D), frequent (use on 20 or more of thepast 30 days)) over two 1-year periods (W1–W2 and W2–Wave 3).ResultsYouth aged 15–17 years were more likely than youth aged 12–14 years and adults aged 18–24 years were more likely than older adults to initiate P30D tobacco use across products; non-heterosexuals were more likely than heterosexuals to initiate P30D cigarette and ENDS use. Older adults were more likely than young adults, and males were more likely than females, to be frequent users of ENDS on initiation. Ever use of another tobacco product predicted P30D initiation of each tobacco product.DiscussionOther tobacco product use and age predict P30D tobacco initiation across products whereas associations with other demographic characteristics vary by product. Continued contemporary evaluation of initiation rates within the changing tobacco product marketplace is important.

scholarly journals Title: “Using data on snus use in Sweden to compare different modelling approaches to estimate the population health impact of introducing a smoke-free tobacco product”

2019 ◽  
Author(s):  
Smilja Djurdjevic ◽  
Laszlo Pecze ◽  
Rolf Weitkunat ◽  
Frank Luedicke ◽  
John Fry ◽  
...  
Keyword(s):  
Smoking Prevalence ◽  
Transition Probabilities ◽  
Health Impact ◽  
European Countries ◽  
Sensitivity Analyses ◽  
Mortality Data ◽  
Published Data ◽  
Advantages And Disadvantages ◽  
Prevalence Estimates

Abstract Background We have developed an approach for modelling the health impact of introducing new smoke-free tobacco products. We wished to compare its estimates with those of alternative approaches, when applied to snus, used in Sweden for many years.Methods Modelling was restricted to men aged 30-79 years for 1980-2009 and to four smoking-related diseases. Mortality data were extracted for Sweden and other European countries. Published data provided Swedish prevalence estimates for combinations of never/former/current smoking and snus use, and smoking prevalence estimates for other European countries. Approach 1 compares mortality in Sweden and in other countries with a smoking prevalence similar to Sweden’s prevalence of combined smoking/snus use. Approaches 2 and 3 compare mortality in Sweden with hypothetical mortality had snus users smoked. Approach 3 uses our health impact model, individuals starting with the tobacco prevalence of Sweden in 1980. Tobacco histories during 30-year follow-up were then estimated using transition probabilities, with risk derived using a negative exponential model. Approach 2 uses annual tobacco prevalence estimates coupled with estimates of relative risk of current and former smokers regardless of history. The main applications of Approaches 2 and 3 assume that only smoking affects mortality, though sensitivity analyses using Approach 3 allow for risk to vary in snus users and dual users.Results Using Approach 2, estimated mortality increases in Sweden in 1980-2009 had snus not been introduced were: lung cancer 8,786; COPD 1,781; IHD 10,409; stroke 1,720. The main Approach 3 estimates were similar (7,931; 1,969; 12,501; 1,901). They decreased as risk in snus users and dual users increased. Approach 1 estimates differed wildly (77,762; 32,538; 77,438; 76,946), remaining very different following correction for differences between Sweden and the comparison countries in non-smoking-related disease mortality.Conclusions Approach 1 is unreliable, accounting inadequately for non-tobacco factors affecting mortality. Approaches 2 and 3 provide reasonably similar approximate estimates of the mortality increase had snus not been available, but have differing advantages and disadvantages. Only Approach 3 considers tobacco history, but develops histories using tobacco transition probabilities, which is possibly less reliable than using estimated tobacco prevalences at each follow-up year.

scholarly journals A Computational Model for Assessing the Population Health Impact of Introducing a Modified Risk Claim on an Existing Smokeless Tobacco Product

2019 ◽  
Vol 16 (7) ◽  
pp. 1264 ◽  
Author(s):  
Raheema Muhammad-Kah ◽  
Yezdi Pithawalla ◽  
Edward Boone ◽  
Lai Wei ◽  
Michael Jones ◽  
...  
Keyword(s):  
Smokeless Tobacco ◽  
Computational Models ◽  
Transition Probabilities ◽  
Health Impact ◽  
Tobacco Product ◽  
Sensitivity Analyses ◽  
Relative Risk Ratio ◽  
Base Case ◽  
Net Benefit ◽  
Premature Deaths

Computational models are valuable tools for predicting the population effects prior to Food and Drug Administration (FDA) authorization of a modified risk claim on a tobacco product. We have developed and validated a population model using best modeling practices. Our model consists of a Markov compartmental model based on cohorts starting at a defined age and followed up to a specific age accounting for 29 tobacco-use states based on a cohort members transition pathway. The Markov model is coupled with statistical mortality models and excess relative risk ratio estimates to determine survival probabilities from use of smokeless tobacco. Our model estimates the difference in premature deaths prevented by comparing Base Case (“world-as-is”) and Modified Case (the most likely outcome given that a modified risk claim is authorized) scenarios. Nationally representative transition probabilities were used for the Base Case. Probabilities of key transitions for the Modified Case were estimated based on a behavioral intentions study in users and nonusers. Our model predicts an estimated 93,000 premature deaths would be avoided over a 60-year period upon authorization of a modified risk claim. Our sensitivity analyses using various reasonable ranges of input parameters do not indicate any scenario under which the net benefit could be offset entirely.

scholarly journals Using data on snus use in Sweden to compare different modelling approaches to estimate the population health impact of introducing a smoke-free tobacco product

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Smilja Djurdjevic ◽  
Laszlo Pecze ◽  
Rolf Weitkunat ◽  
Frank Luedicke ◽  
John Fry ◽  
...  
Keyword(s):  
Smoking Prevalence ◽  
Transition Probabilities ◽  
Health Impact ◽  
European Countries ◽  
Sensitivity Analyses ◽  
Mortality Data ◽  
Published Data ◽  
Advantages And Disadvantages ◽  
Prevalence Estimates

Abstract Background We have developed an approach for modelling the health impact of introducing new smoke-free tobacco products. We wished to compare its estimates with those of alternative approaches, when applied to snus, used in Sweden for many years. Methods Modelling was restricted to men aged 30–79 years for 1980–2009 and to four smoking-related diseases. Mortality data were extracted for Sweden and other European countries. Published data provided Swedish prevalence estimates for combinations of never/former/current smoking and snus use, and smoking prevalence estimates for other European countries. Approach 1 compares mortality in Sweden and in other countries with a smoking prevalence similar to Sweden’s prevalence of combined smoking/snus use. Approaches 2 and 3 compare mortality in Sweden with hypothetical mortality had snus users smoked. Approach 3 uses our health impact model, individuals starting with the tobacco prevalence of Sweden in 1980. Tobacco histories during 30-year follow-up were then estimated using transition probabilities, with risk derived using a negative exponential model. Approach 2 uses annual tobacco prevalence estimates coupled with estimates of relative risk of current and former smokers regardless of history. The main applications of Approaches 2 and 3 assume that only smoking affects mortality, though sensitivity analyses using Approach 3 allow for risk to vary in snus users and dual users. Results Using Approach 2, estimated mortality increases in Sweden in 1980–2009 had snus not been introduced were: lung cancer 8786; COPD 1781; IHD 10,409; stroke 1720. The main Approach 3 estimates were similar (7931, 1969; 12,501; 1901). They decreased as risk in snus users and dual users increased. Approach 1 estimates differed wildly (77,762, 32,538; 77,438; 76,946), remaining very different following correction for differences between Sweden and the comparison countries in non-smoking-related disease mortality. Conclusions Approach 1 is unreliable, accounting inadequately for non-tobacco factors affecting mortality. Approaches 2 and 3 provide reasonably similar approximate estimates of the mortality increase had snus not been available, but have differing advantages and disadvantages. Only Approach 3 considers tobacco history, but develops histories using tobacco transition probabilities, which is possibly less reliable than using estimated tobacco prevalences at each follow-up year.

scholarly journals Transitions in Smoking among Adults Newly Purchasing the JUUL System

2021 ◽  
Vol 45 (3) ◽  
pp. 546-562
Author(s):  
Shivaani Prakash ◽  
Yingying Xu ◽  
Nicholas I. Goldenson ◽  
Rasmus Wissmann ◽  
Robyn Gougelet ◽  
...  
Keyword(s):  
Smoking Prevalence ◽  
Smoking Status ◽  
Health Impact ◽  
Adult Age ◽  
Sample Composition ◽  
Former Smokers ◽  
Never Smokers ◽  
One Year ◽  
First Time

Objectives: In this study, we prospectively assessed changes in smoking a year after US adults' first-time purchase of a JUUL Starter Kit (JSK). Methods: Descriptive analyses assessed transitions in smoking status at 12 months among adult (age ≥21) JSK purchasers providing baseline and 12-month follow-up data (N = 27,164 [49.0% of baseline]), stratified by baseline smoking status. Baseline regular use of other ENDS was also considered. Results: Purchasers included baseline past 30-day smokers (65.2%), former smokers (12.0%), and never smokers (9.7%); over 90% were ever-smokers. One year later, the majority (58%) of those smoking at baseline reported no longer smoking. Former smokers or never smokers who were smoking at 12 months represented less than 2% of respondents. Former and current smokers who were regularly using other ENDS at baseline were less likely to report smoking at 12 months. Conclusions: Past 30-day smoking prevalence in a large longitudinal study of first-time JSK purchasers fell by more than half over 12 months. Analyzing the sample composition at purchase and transitions within subgroups defined by smoking status allows for a detailed understanding to help inform assessments of the population health impact of ENDS.

scholarly journals Estimating the reduction in US mortality if cigarettes were largely replaced by e-cigarettes

2021 ◽  
Author(s):  
Peter N. Lee ◽  
John S. Fry ◽  
Stanley Gilliland ◽  
Preston Campbell ◽  
Andrew R. Joyce
Keyword(s):  
Effective Dose ◽  
Sensitivity Analyses ◽  
Prior Work ◽  
Additional Insight ◽  
Initiation Rate ◽  
Life Years ◽  
Pessimistic Scenario ◽  
Life Years Lost ◽  
Age Range

Abstract Background Recent estimates indicated substantially replacing cigarettes by e-cigarettes would, during 2016–2100, reduce US deaths and life-years lost (millions) by 6.6 and 86.7 (Optimistic Scenario) and 1.6 and 20.8 (Pessimistic). To provide additional insight we use alternative modelling based on a shorter period (1991–2040), four main smoking-associated diseases, deaths aged 30–79 years, and a full product history. We consider variations in: assumed effective dose of e-cigarettes versus cigarettes (F); their relative quitting rate (Q); proportions smoking after 10 years (X); and initiation rate (I) of vaping, relative to smoking. Methods We set F = 0.05, X = 5%, Q = 1.0 and I = 1.0 (Main Scenario) and F = 0.4, X = 10%, Q = 0.5 and I = 1.5 (Pessimistic Scenario). Sensitivity Analyses varied Main Scenario parameters singly; F from 0 to 0.4, X 0.01% to 15%, and Q and I 0.5 to 1.5. To allow comparison with prior work, individuals cannot be dual users, re-initiate, or switch except from cigarettes to e-cigarettes. Results Main Scenario reductions were 2.52 and 26.23 million deaths and life-years lost; Pessimistic Scenario reductions were 0.76 and 8.31 million. These were less than previously, due to the more limited age-range and follow-up, and restriction to four diseases. Reductions in deaths (millions) varied most for X, from 3.22 (X = 0.01%) to 1.31 (X = 15%), and F, 2.74 (F = 0) to 1.35 (F = 0.4). Varying Q or I had little effect. Conclusions Substantial reductions in deaths and life-years lost were observed even under pessimistic assumptions. Estimates varied most for X and F. These findings supplement literature indicating e-cigarettes can importantly impact health challenges from smoking.

scholarly journals Using data on snus use in Sweden to compare different modelling approaches to estimate the population health impact of introducing a smoke-free tobacco product

2019 ◽  
Author(s):  
Peter Lee ◽  
Smilja Djurdjevic ◽  
Laszlo Pecze ◽  
Rolf Weitkunat ◽  
Frank Luedicke ◽  
...  
Keyword(s):  
Smoking Prevalence ◽  
Transition Probabilities ◽  
Health Impact ◽  
European Countries ◽  
Sensitivity Analyses ◽  
Mortality Data ◽  
Published Data ◽  
Advantages And Disadvantages ◽  
Prevalence Estimates

Abstract Background We have developed an approach for modelling the health impact of introducing new smoke-free tobacco products. We wished to compare its estimates with those of alternative approaches, when applied to snus, used in Sweden for many years. Methods Modelling was restricted to men aged 30-79 years for 1980-2009 and to four smoking-related diseases. Mortality data were extracted for Sweden and other European countries. Published data provided Swedish prevalence estimates for combinations of never/former/current smoking and snus use, and smoking prevalence estimates for other European countries. Approach 1 compares mortality in Sweden and in other countries with a smoking prevalence similar to Sweden’s prevalence of combined smoking/snus use. Approaches 2 and 3 compare mortality in Sweden with hypothetical mortality had snus users smoked. Approach 3 uses our health impact model, individuals starting with the tobacco prevalence of Sweden in 1980. Tobacco histories during 30-year follow-up were then estimated using transition probabilities, with risk derived using a negative exponential model. Approach 2 uses annual tobacco prevalence estimates coupled with estimates of relative risk of current and former smokers regardless of history. The main applications of Approaches 2 and 3 assume that only smoking affects mortality, though sensitivity analyses using Approach 3 allow for risk to vary in snus users and dual users. Results Using Approach 2, estimated mortality increases in Sweden in 1980-2009 had snus not been introduced were: lung cancer 8,786; COPD 1,781; IHD 10,409; stroke 1,720. The main Approach 3 estimates were similar (7,931; 1,969; 12,501; 1,901). They decreased as risk in snus users and dual users increased. Approach 1 estimates differed wildly (77,762; 32,538; 77,438; 76,946), remaining very different following correction for differences between Sweden and the comparison countries in non-smoking-related disease mortality. Conclusions Approach 1 is unreliable, accounting inadequately for non-tobacco factors affecting mortality. Approaches 2 and 3 provide reasonably similar approximate estimates of the mortality increase had snus not been available, but have differing advantages and disadvantages. Only Approach 3 considers tobacco history, but develops histories using tobacco transition probabilities, which is possibly less reliable than using estimated tobacco prevalences at each follow-up year.

Patterns of E-Cigarette Use Among Youth and Young Adults: Review of the Impact of E-Cigarettes on Cigarette Smoking

2018 ◽  
Vol 21 (10) ◽  
pp. 1320-1330 ◽  
Author(s):  
Allison Glasser ◽  
Haneen Abudayyeh ◽  
Jennifer Cantrell ◽  
Raymond Niaura
Keyword(s):  
Young Adults ◽  
Cigarette Smoking ◽  
Smoking Status ◽  
Small Sample ◽  
Future Research ◽  
Cigarette Use ◽  
Product Use ◽  
Youth And Young Adults ◽  
The Impact

Abstract There is concern that e-cigarette use among youth and young adults (YAs) may lead to future cigarette or other combustible tobacco product use. A synthesis of the literature on this topic is needed because existing longitudinal studies are limited in number and not consistent in their conclusions. We conducted a search in PubMed through December 31, 2017 for peer-reviewed studies related to e-cigarette patterns of use. Of 588 relevant studies, 26 had a youth or YA sample, were longitudinal in design, and assessed e-cigarette use at baseline and cigarette smoking at follow-up. Most studies followed a sample over time and compared cigarette smoking at follow-up between baseline e-cigarette users and nonusers. Other studies examined the difference at follow-up in cigarette smoking status among smokers according to e-cigarette use at baseline. Results suggest that, among never smokers, e-cigarette use is associated with the future (6 months to 2.5 years) cigarette trial; however, firm conclusions cannot be drawn because of limitations including small sample size, measurement of experimental use (ie, ever use, past 30-day use) rather than established use, and inadequate controls for potentially confounding variables. Conclusions also cannot be drawn from studies examining the impact of e-cigarette use among smokers due to the limited number of studies and additional limitations. A comprehensive understanding of this literature is needed to inform policy makers and consumers for evidence-based decision-making and to guide future research on e-cigarette use among youth and young adults. Implications The present article provides a review of the impact of e-cigarette use on subsequent cigarette smoking among youth and YAs. Studies presented here suggest that e-cigarette use among nonsmokers is associated with subsequent cigarette smoking, but study designs are subject to numerous limitations. Future research should focus on addressing the characteristics that put youth and YAs at the risk of using either product and how appeal and accessibility of these products are related to product use in order to inform future policy-making.

Quality-Adjusted Time without Symptoms of Disease and Toxicity (Q-TWiST) Analysis of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed High-Risk/Secondary Acute Myeloid Leukemia (AML)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 55-56
Author(s):  
Jorge E. Cortes ◽  
Tara Lin ◽  
Geoffrey L Uy ◽  
Robert J. Ryan ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Newly Diagnosed ◽  
Case Scenario ◽  
Base Case Scenario ◽  
Grade 3 ◽  
Intent To Treat

Introduction: CPX-351 (Vyxeos®; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has been approved by the US FDA and the EMA for the treatment of adults with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes. The primary analysis of the pivotal phase 3 study (NCT01696084) that formed the basis for these approvals evaluated patients aged 60 to 75 years with newly diagnosed high-risk/secondary AML and found that, with a median follow-up of 20.7 months, CPX-351 significantly improved median overall survival (OS) versus conventional 7+3, with a comparable safety profile. Final 5-year follow-up results recently reported demonstrated that the OS benefit was maintained. To evaluate both quality and quantity of life, we conducted a Q-TWiST analysis of the phase 3 study to compare survival between patients receiving CPX-351 versus 7+3. Methods: Q-TWiST is used to evaluate outcomes in oncology trials by measuring how much of the survival improvement time is spent with toxicities, how much after disease progression or relapse, and how much is valuable time (ie, Time Without Symptoms of Disease and Toxicity [TWiST]). For this analysis, the OS for each patient from the 5-year follow-up analysis was partitioned into 3 health states: TOX (time before response plus any additional time with a grade 3 or 4 toxicity), TWiST (time without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Q-TWiST gain was assessed as the mean time spent in each state weighted by its respective quality of life, represented by health utility (U; scale of 0.0 [indicates death] to 1.0 [indicates "perfect" health]). Q-TWiST gain was calculated as follows: Q-TWiST = (UTWiST × TWiST) + (UTOX × TOX) + (UREL × REL). The base case scenario used the intent-to-treat population, any grade 3 or 4 toxicities, TOX and REL utility weights of 0.5, and a TWiST utility weight of 1.0. Sensitivity analyses were performed for all treated patients (CPX-351: n = 153; 7+3: n = 151) and the intent-to-treat population, any and treatment-related grade 3 or 4 toxicities, and TOX and REL utility weights of 0, 0.5, and 1.0. A variation of the base case scenario was also performed for the subset of patients who achieved complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CR+CRi; CPX-351: n = 73; 7+3: n = 52). When comparing across populations or studies, reporting relative Q-TWiST gains is an effective measure for evaluating clinical benefit (ie, Q-TWiST gains compared to a control; Solem CT, et al. Expert Rev Pharm Out 2018). A relative Q-TWiST gain of 15% or greater is considered a clinically important difference (CID) in oncology studies (Revicki DA, et al. Qual Life Res 2006). The relative Q-TWiST gain was calculated using the following equation: Q-TWiST difference ÷ mean OS of control arm × 100. Results: In total, 309 patients were randomized to CPX-351 (n = 153) or 7+3 (n = 156). In the base case scenario, the means difference (95% CI) for CPX-351 versus 7+3 was 183 days (60, 306) for the TWiST state, 7 days (−63, 78) for the TOX state, and 22 days (5, 38) for the REL states. The resulting means difference (95% CI) for Q-TWiST gain was 197 days (76, 319) for CPX-351 versus 7+3, and the relative Q-TWiST gain was 53.6%. Among patients who achieved CR or CRi, the means difference (95% CI) for Q-TWiST gain was 248 days (−1, 496) for CPX-351 versus 7+3, and the relative Q-TWiST gain was 39.8%. Both relative Q-TWiST gains were considerably above the standard CID of 15% for oncology. Across the various sensitivity analyses, the relative Q-TWiST gains for CPX-351 versus 7+3 varied from 48.0% to 57.6%, remaining all well above the standard CID threshold (Table). Conclusions: Results of this post hoc analysis suggest the survival benefit with CPX-351 for patients with high-risk/secondary AML are mostly from valuable time (TWiST), thus supporting the clinical benefit for patients. The relative Q-TWiST gains were well above what is considered CID (15%) in the cancer literature and were maintained across various sensitivity analyses, supporting the robustness of the benefit. In the absence of direct measures of quality of life, these results can be used together with the antileukemia effect when considering treatment options for this patient population. Disclosures Cortes: Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Telios: Research Funding; Astellas: Research Funding; Amphivena Therapeutics: Research Funding; Arog: Research Funding; BiolineRx: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Merus: Research Funding; Immunogen: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Lin:Aptevo: Research Funding; Abbvie: Research Funding; Gilead Sciences: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Ono Pharmaceutical: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Prescient Therapeutics: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding. Uy:Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

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