The LEGACy study: a European and Latin American consortium to identify risk factors and molecular phenotypes in gastric cancer to improve prevention strategies and personalized clinical decision making globally.

BACKGROUND: Gastric Cancer (GC) is the fourth most deadly cancer worldwide. Enhanced understanding of its key epidemiological and molecular drivers is urgently needed to lower the incidence and improve outcomes. Furthermore, tumor biology in European (EU) and Latin American (LATAM) countries is understudied. The LEGACy study is a Horizon 2020 funded multi-institutional research approach to 1) detail the epidemiological features including risk factors of GC in current time and 2) develop cost-effective methods to identify and integrate biological biomarkers needed to guide diagnostic and therapeutic approaches with the aim of filling the knowledge gap on GC in these areas. METHODS: This observational study has three parts that are conducted in parallel during 2019-2023 across recruiting centers from four EU and four LATAM countries: Part 1) A case-control study (800 cases and 800 controls) using questionnaires on candidate risk factors for GC, which will be correlated with clinical, demographic and epidemiological parameters. Part 2) A case-control tissue sampling study (400 cases and 400 controls) using proteome, genome, microbiome and immune analyses to characterize advanced (stage III and IV) GC. Patients in this part of the study will be followed over time to observe clinical outcomes. The first half of samples will be used as training cohort to identify the most relevant risk factors and biomarkers, which will be selected to propose cost-effective diagnostic and predictive methods that will be validated with the second half of samples. Part 3) An educational study, as part of our prevention strategy (subjects recruited from the general public) to test and disseminate knowledge on GC risk factors and symptoms by a questionnaire and informative video. Patients could be recruited for more than one of the three LEGACy studies. DISCUSSION: The LEGACy study aims to generate novel, in-depth knowledge on the tumor biological characteristics through integrating epidemiological, multi-omics and clinical data from GC patients at an EU-LATAM partnership. During the study, cost-effective panels with potential use in clinical decision making will be developed and validated. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: Part 1: NCT03957031 . Part 2: NCT04015466 . Part 3: NCT04019808 .

Global Patterns and Prevalence of Dual and Poly-Tobacco Use: A Systematic Review.

INTRODUCTION: Improving understanding of the epidemiology of dual and poly-tobacco product use is essential for tobacco control policy and practice. The present study aimed to systematically review existing epidemiologic evidence on current dual and poly-tobacco use among adults globally. METHODS: We systematically searched online databases for studies published up to June 30, 2020. We included quantitative studies with measures of nationally representative prevalence of current dual or poly-tobacco use among adults. Prevalence estimates for each country were extracted manually and stratified by WHO regions and World Bank income classifications. RESULTS: Twenty studies with nationally representative prevalence data on current dual or poly-tobacco use in the adult population across 48 countries were included. Definitions of dual and poly-tobacco use varied widely. Prevalence of dual and poly-tobacco use was higher in low- and lower-middle-income countries compared to other higher-income countries. Current dual use of smoked and smokeless tobacco products among males ranged from 0.2% in Ukraine (2010) and Mexico (2009) to 17.9% in Nepal (2011). Poly-tobacco use among males ranged from 0.8% in Mexico (2009) and 0.9% in Argentina (2010) to 11.4% in the United Kingdom and 11.9% in Denmark in 2012. Dual tobacco use was generally higher in South-East Asia; poly-tobacco use was prevalent in Europe as well as in South-East Asia. CONCLUSIONS: This is the first systematic review of the prevalence estimates of dual and poly-tobacco use among adults globally. The results of the current study could significantly help health policy makers to implement effective tobacco control policies. IMPLICATIONS: This study demonstrates that dual/poly-tobacco use is common in many countries of the world, and highlights the need for in-depth exploration of this field in future studies, especially in high prevalence regions such as South-East Asian and European countries. In light of this, the global tobacco control community and health authorities should also agree upon a consistent operational definition of dual and poly-tobacco use to propel research and improve surveillance of dual/poly-use in health surveys for better communication and understanding of these phenomena.

Compliance of e-cigarette refill liquids with regulations on labelling, packaging and technical design characteristics in nine European member states.

OBJECTIVE: To evaluate electronic cigarette (e-cigarette) product compliance with European regulations (Tobacco Products Directive (TPD), Implementing Decisions), with a focus on labelling/packaging practices and technical design/safety features. METHODS: Before the implementation of the TPD, in early 2016, we randomly selected e-cigarette refill liquids from the five top-selling companies in France, Poland, Germany, Netherlands, UK, Spain, Romania, Hungary and Greece. Identical products were purchased after the implementation of the TPD (early 2018) and assessment of compliance was performed on self-matched samples (n=107) using a prospective cohort design. Compliance with the Classification, Labelling and Packaging (CLP) regulations was also evaluated. RESULTS: Following the implementation of the TPD, improvements were noted with regards to the existence of text-only warnings (32.7% pre vs 86.0% post, p<0.001), child-resistant fastenings (93.3% pre vs 100.0% post, p=0.016), tamper-proof vials (58.9% pre vs 86.9%, post p<0.001) and maximum refill volume ≤10 mL in vials (86.9% pre vs 94.4% post, p=0.008). Lower compliance was noted with regards to the inclusion of a leaflet (26.2% pre vs 53.3% post, p<0.001), refilling instructions (28.0% pre vs 51.4% post, p<0.001) and health warnings on the box, vial or leaflet (32.7% pre vs 86.0%, p<0.001). Overall, 86.0% of products had a warning label in the post-TPD phase in comparison to 32.7% of products before the implementation of the TPD (p<0.001). Compliance with the CLP regulations, also increased in the post TPD follow-up phase. CONCLUSIONS: This is the first study to evaluate the level of implementation of the e-cigarette regulations in nine EU member states. Our results indicate that refill liquids had substantial but not full compliance in most of the characteristics evaluated. Further effort is needed to ensure complete compliance.

Changes in electronic cigarette use and label awareness among smokers before and after the European Tobacco Products Directive implementation in six European countries: findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: Article 20 of the European Tobacco Product Directive (TPD), which went into effect in May 2016, regulates electronic cigarettes (e-cigarettes) in the European Union (EU). The aim of this study was to evaluate changes in e-cigarette use, design attributes of the products used and awareness of e-cigarette labelling and packaging among smokers from six EU Member States (MS) before and after TPD implementation. METHODS: Data come from Wave 1 (2016, pre-TPD) and Wave 2 (2018, post-TPD) of the ITC Six European Country Survey among a sample of smokers and recent quitters who use e-cigarettes from six EU MS. Weighted logistic generalized estimating equations regression models were estimated to test the change in binary outcomes between Waves 1 and 2 using SAS-callable SUDAAN. RESULTS: In 2018, current daily/weekly e-cigarette use among adult smokers was just over 2%, but this varied from the highest in Greece (4%) to lowest in Poland (1.2%). From Waves 1 to 2, there was a significant increase in respondents reporting noticing and reading health and product safety information on leaflets inside e-cigarette packaging (8.39-11.62%, P < 0.001). There were no significant changes between waves of respondents reporting noticing or reading warning labels on e-cigarette packages/vials. CONCLUSIONS: e-cigarette use among smokers in these six EU countries is low. Although reported noticing and reading leaflets included in the packaging of e-cigarettes increased significantly from before to after the TPD, there was no significant change in reported noticing and reading of warning labels. Findings indicate the importance of continued monitoring of TPD provisions around e-cigarettes.

Transitions in product use during the implementation of the European Tobacco Products Directive: cohort study findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: The emergence of new types of tobacco and tobacco-related products on the European Union (EU) market has precipitated the possibility for both poly-tobacco use and transitions between products. In the EU, the regulatory environment has shifted with the implementation of the European Tobacco Products Directive (TPD) in May 2016, which may influence consumer transitions between products. METHODS: The aim of this paper was to examine trends and transitions in tobacco products from 2016 to 2018 -before and after implementation of the TPD in the EU. Data come from Wave 1 (pre-TPD) and Wave 2 (post-TPD) of the EUREST-PLUS ITC Six European Country Survey, a cohort study of adults who at the time of recruitment were smokers from six EU countries- Germany, Greece, Hungary, Poland, Romania, and Spain. D (N = 3195). Bivariate and logistic regression analyses of weighted data was conducted using SAS-callable SUDAAN. RESULTS: Overall, among those who smoked factory-made cigarettes (FM) only at Wave 1, 4.3% switched to roll-your-own tobacco (RYO) only. Among RYO only users at Wave 1, 17.0% switched to FM only, however compared to all other countries, respondents from Hungary had the highest percentage of FM only users at Wave 1 switch to RYO only at Wave 2 (18.0%). CONCLUSIONS: The most prominent transition overall was from smoking RYO exclusively at Wave 1 to smoking FM tobacco exclusively at Wave 2, however this varied across countries. As the tobacco control regulatory environment of the EU develops, it is important to continue to monitor transitions between types of products, as well as trends in cessation.

Awareness and correlates of noticing changes to cigarette packaging design after implementation of the European Tobacco Products Directive: findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: The European Tobacco Products Directive (TPD), which went into effect in May 2016, regulates packaging design and labelling of cigarettes and roll-your-own (RYO) tobacco. The aim of the current study was to examine whether smokers and recent quitters in six European Union (EU) countries (Germany, Greece, Hungary, Poland, Romania and Spain) reported noticing TPD-related changes to packaging, and correlates of noticing these changes. METHODS: Cross-sectional data from the Wave 2 of the ITC 6 European Country Survey in 2018 after implementation of the TPD. Bivariate analyses included adult smokers (n = 5597) and recent quitters (n = 412). Adjusted logistic regression analyses were restricted to the subset of current smokers (n = 5597) and conducted using SAS-callable SUDAAN. RESULTS: Over half of smokers (58.2%) and 30% of quitters noticed at least one of five types of TPD-related pack changes. Over one-quarter of all respondents noticed changes to health warnings (30.0%), standardized openings (27.7%), minimum pack unit size (27.9%), and the removal of tar, nicotine and carbon monoxide information (26.7%) on packaging. Cross-country differences were observed across all measures, with noticing all pack changes markedly lower in Spain than the other countries. Correlates of noticing specific pack changes included sociodemographic characteristics, smoking behaviours and related to packaging. CONCLUSIONS: This is one of the first cross-country studies to examine the extent to which TPD changes to cigarette and RYO tobacco packaging are being noticed by smokers and recent quitters. Findings indicate that the majority of smokers noticed at least one type of pack change, but this varied across countries and sub-populations.

Quitting behaviours and cessation methods used in eight European Countries in 2018: findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: We examined quit attempts, use of cessation assistance, quitting beliefs and intentions among smokers who participated in the 2018 International Tobacco Control (ITC) Europe Surveys in eight European Union Member States (England, Germany, Greece, Hungary, the Netherlands, Poland, Romania and Spain). METHODS: Cross-sectional data from 11 543 smokers were collected from Wave 2 of the ITC Six European Country (6E) Survey (Germany, Greece, Hungary, Poland, Romania and Spain-2018), the ITC Netherlands Survey (the Netherlands-late 2017) and the Four Countries Smoking and Vaping (4CV1) Survey (England-2018). Logistic regression was used to examine associations between smokers' characteristics and recent quit attempts. RESULTS: Quit attempts in the past 12 months were more frequently reported by respondents in the Netherlands (33.0%) and England (29.3%) and least frequently in Hungary (11.5%), Greece (14.7%), Poland (16.7%) and Germany (16.7%). With the exception of England (35.9%), the majority (56-84%) of recent quit attempts was unaided. Making a quit attempt was associated with younger age, higher education and income, having a smoking-related illness and living in England. In all countries, the majority of continuing smokers did not intend to quit in the next 6 months, had moderate to high levels of nicotine dependence and perceived quitting to be difficult. CONCLUSIONS: Apart from England and the Netherlands, smokers made few quit attempts in the past year and had low intentions to quit in the near future. The use of cessation assistance was sub-optimal. There is a need to examine approaches to supporting quitting among the significant proportion of tobacco users in Europe and increase the use of cessation support as part of quit attempts.

Transitions from and to roll-your-own tobacco, perceptions and health beliefs among smokers: findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: The prevalence of roll-your-own tobacco (RYO) in Europe has been increasing. The aim of this study was to investigate transitions between factory-made (FM) cigarettes and RYO in a longitudinal sample of European smokers, and their perceptions of relative harmfulness and knowledge of health effects. METHODS: We used data collected from the EUREST-PLUS ITC 6 European Country (6E) Surveys in 2016 (n = 6011 smokers) and in 2018 (n = 6027) in Germany, Greece, Hungary, Poland, Romania and Spain. A total of 3195 cohort respondents were interviewed in both years. Use of RYO and FM, knowledge of health effects of smoking as well as perceptions about RYO were assessed. We used logistic regression models to explore sociodemographic correlates of transitions from one product to the other, of perceptions and knowledge related to smoking health effects. RESULTS: Approximately 7.4% of exclusive FM smokers transitioned to RYO and 29.5% of exclusive RYO smokers transitioned to FM cigarettes from 2016 to 2018. RYO use in 2018 was more frequent among smokers of low education and income, but none of these factors were associated with transitions. Most RYO smokers perceived RYO as cheaper than FM and 21.7% of them considered RYO to be less harmful than FM. Knowledge of the health effects of smoking was not associated with type of product smoked. CONCLUSIONS: RYO is popular among European smokers; its lower cost seems to be a major factor for RYO users; reasons for transitions to and from RYO are less clear and need to be further investigated.

Cost, prevalence and correlates of cigarillo use in 28 European countries in 2017.

OBJECTIVES: Although manufactured cigarettes remain the most popular tobacco product worldwide, the use of other products, including little cigar and cigarillo, has been rising in recent years; however, there is a paucity of data on the correlates of current and ever use of cigarillos in Europe. The aim of this study was to explore the extent and determinants of cigarillo use, as well as to describe the cost and affordability of cigarillos across the EU, in light of the current regulatory framework at a European level. METHODS: We performed a secondary analysis of data collected across 28 European Union (EU) Member States through wave 87.1 of the Eurobarometer survey, conducted in March 2017 (N = 27,901). A multilevel logistic regression model was fitted to assess the association of current and ever cigarillo use with the above socio-demographic factors. We also analysed Euromonitor International data on cigarillo prices in 2017 from 24 EU Member States. RESULTS: Across the EU, 0.46% (95% CI: 0.33-0.63) of those aged ≥ 15 years reported at least weekly current use of cigarillos in 2017, which corresponds to 1,966,516 (95% CI: 1,426,554-2,709,563) people. Finland recorded the highest prevalence (20.51%) of ever cigarillo use in Europe while Ireland had the lowest (1.15%). Male sex, living in urban area and being over 55 years old compared to 15-24 year olds were associated with greater odds of ever cigarillo use. Median cigarillo prices varied widely, ranging from 3.60 Euros in Portugal to 20.40 Euros in Bulgaria per 20 sticks. CONCLUSIONS: The use of cigarillos in Europe is associated with several socio-demographic factors such as gender, age and living area. Policy makers of EU countries, especially now under the regulatory framework of the EU Tobacco Products Directive, should work together to enforce more restrictive rules for cigarillos.

Composition and chemical health hazards of the most common electronic cigarette liquids in nine European countries.

BACKGROUND: The aim of the present study was to identify the composition and reported chemical health hazards of the most common electronic cigarette liquids (e-liquids) in nine European Union (EU) Member States (MS) prior to adoption of the Tobacco Product Directive (TPD). MATERIALS AND METHODS: Within the Horizon2020, EUREST-PLUS study, 122 of the most commonly sold e-liquids in 9 EU MS were randomly selected and purchased. A quantitative and qualitative chemical analysis was performed using a previously validated based gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry method. The most commonly detected compounds were then divided according to the Danger Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Warning GHS codes. RESULTS: Within our qualitative analysis, 171 different compounds were detected. Discrepancies in measured versus reported nicotine concentration were identified. Forty-one (85.4%) of the most commonly detected compounds were registered with Warning GHS codes, 11 with Danger GHS codes and 9 with both codes. Of the total number of the detected compounds, 293 were attributable to fruits flavor, followed by tobacco flavor (204), nonalcoholic drinks (n = 64), desserts-sweets (n = 50), menthol - mint (n = 42) and alcohol (n = 39). Menthol which is classified as a strong irritant to skin and eye was the most frequently detected compound. CONCLUSION: A large plethora of compounds with varying warning codes was identified in e-cigarette samples. The systematic monitoring and chemical evaluation of e-liquids are warranted, so as to ensure consumer protection.

Smoking cessation delivery by general practitioners in Crete, Greece.

Background: Tobacco dependence treatment in clinical settings is of prime public health importance, especially in Greece, a country experiencing one of the highest rates of tobacco use in Europe. Methods: Our study aimed to examine the characteristics of tobacco users and document rates of tobacco treatment delivery in general practice settings in Crete, Greece. A cross-sectional sample of patients (n = 2, 261) was screened for current tobacco use in 25 general practices in Crete, Greece in 2015/16. Current tobacco users completed a survey following their clinic appointment that collected information on patient characteristics and rates at which the primary care physician delivered tobacco treatment using the evidence-based 4 A's (Ask, Advise, Assist, Arrange) model during their medical appointment and over the previous 12-month period. Multi-level modeling was used to analyze data and examine predictors of 4 A's delivery. Results: Tobacco use prevalence was 38% among all patients screened. A total of 840 tobacco users completed the study survey [mean age 48.0 (SD 14.5) years, 57.6% male]. Approximately, half of the tobacco users reported their general practitioner 'asked' about their tobacco use and 'advised' them to quit smoking. Receiving 'assistance' with quitting (15.7%) and 'arranging' follow-up support (<3%) was infrequent. Patient education, presence of smoking-related illness, a positive screen for anxiety or depression and the type of medical appointment were associated with 4 A's delivery. Conclusion: Given the fundamental importance of addressing tobacco treatment, increasing the rates of 4 A's treatment in primary care settings in Greece is an important target for improving patient care.

Relationship of secondhand smoke exposure with sociodemographic factors and smoke-free legislation in the European Union.

BACKGROUND: To explore whether exposure to secondhand smoke (SHS) among non-smokers in the European Union (EU) showed any association with sociodemographic factors and/or the extent of national tobacco control policies. METHODS: A secondary analysis was performed on data from 26 751 individuals ≥15 years old from 27 EU member states (EU MS), collected during the 2012 Special Eurobarometer survey (wave 77.1). Respondents were asked whether they had been exposed to SHS in eating or drinking establishments during the past 6 months, and/or in their workplace. Data on smoke-free policies were extracted from the European Tobacco Control Status Report and the European Tobacco Control Scale (TCS) in 2013. RESULTS: In total, 29.0% of non-smoking participants reported being exposed to SHS in indoor areas. Males (vs. females) as well as individuals with difficulties to pay bills (vs. those with no difficulties), had significantly greater odds of being exposed to SHS in bars, restaurants and workplaces. For every unit increase of a country's score on the Smoke-free Component of the TCS (indicating greater adherence to smoke-free legislations) the odds ratio of reporting exposure to SHS was 0.82 in bars, 0.85 in restaurants and 0.94 in workplaces. CONCLUSIONS: Differences in exposure to SHS clearly exist between and within EU MS, despite the fact that they all have signed the Framework Convention on Tobacco Control, with the burden found to disproportionally affect younger people and individuals with financial difficulties. Moreover, enforcement of smoke-free legislation was inversely associated with SHS exposure, highlighting the importance of enforcing comprehensive smoking bans.

Disposable e-cigarette use and associated factors in US middle and high school students, 2021-2022.

INTRODUCTION: Disposable e-cigarettes are the predominant type of vaping product used by adolescents and pose a significant public health concern. Identifying factors contributing to this growing trend is essential to curbing the vaping epidemic among youths. This study aims to investigate the growing prevalence and correlates of disposable e-cigarette use among US students. METHODS: Data from 48437 US middle and high school students from the 2021 and 2022 National Youth Tobacco Survey (NYTS) were analyzed using logistic and ordinal regression models to evaluate disposable e-cigarette use and frequency of use (low, medium, and high) with demographic and psychosocial factors. Weighted prevalence of current e-cigarette use with 95% CIs by device types in 2021 and 2022, were calculated. Odds ratios (ORs) of correlations of disposable e-cigarette use and frequency of use with demographic and psychosocial factors were analyzed. RESULTS: Disposable e-cigarette use increased from 3.9% (95% CI: 3.3-4.7) in 2021 to 5.1% (95% CI: 4.2-6.1) in 2022, and was associated with being female (OR=1.57; 95% CI: 1.29-1.91 vs male), high schoolers (OR=5.14; 95% CI: 3.96-6.67 vs middle schoolers), having low harm perceptions of e-cigarettes (OR=7.75; 95% CI: 5.58-10.75 vs lot of harm), and high exposure to marketing (OR=1.57; 95% CI: 1.05-2.35 vs low exposure). Identifying as LGBTQ (OR=1.41; 95% CI: 1.00-2.00 vs straight), having low academic performance (OR=2.16; 95% CI: 1.15-4.07, D vs A grades), and having psychological distress (OR=2.01; 95% CI: 1.64-2.47, severe vs none) were also linked to increased frequency of use. CONCLUSIONS: This study underscores increasing disposable e-cigarette use among US students, noting existing disparities. It identifies high-risk adolescent subgroups vulnerable to disposable e-cigarette use. These findings emphasize the urgency of targeted prevention and stricter regulations on disposable e-cigarettes to combat nicotine addiction among youths.

Changes in tobacco industry advertising around high schools in Greece following an outdoor advertising ban: a follow-up study.

BACKGROUND: As tobacco advertising bans are enacted in accordance with the Framework Convention on Tobacco Control, it is essential to assess enforcement and how the industry may circumvent such measures. OBJECTIVE DESIGN: During this longitudinal study, we compared the characteristics of points-of-sale (POS) advertising within 300 m of all high schools in Heraklion, Greece before (n=101 POS and 44 billboards in 2007) and after (n=106 POS in 2011) an outdoor advertising ban was implemented in 2009. Cigarette advertisements in all retailers near all high schools were assessed. RESULTS: Following the ban, tobacco industry billboards around schools were eradicated (from 44 to 0). The proportion of POS that had external advertisements dropped from 98% to 66% (p<0.001), more so in regulated convenience stores (from 97% to 35%, p<0.001) than in kiosks (98% to 92%, p=0.192), which were exempt from the ban. The proportion of convenience stores that had advertisements on the door (79.5% to 20.4%, p<0.001), ads that could be seen from the street (92.3% to 22.4%, p<0.001) or illuminated exterior ads (46.2% to 10.2%, p<0.001) was also significantly reduced. Overall, the average number of exterior advertisements per POS fell from 7.4 to 3.9 (p<0.05). This reduction was noted in regulated convenience stores (4.8±3.0 vs 0.9±2.1, p<0.001) and in unregulated kiosks (9.0±6.7 vs 6.5±4.5, p=0.019). CONCLUSIONS: The outdoor advertising restriction in Greece has led to a reduced number of tobacco advertisements per POS, and the eradication of billboard advertising. Nevertheless, there is a need to regulate kiosks, which were identified as a key vector for tobacco advertising, and to increase compliance among regulated convenience stores.

How can patient preferences be used and communicated in the regulatory evaluation of medicinal products? Findings and recommendations from IMI PREFER and call to action.

Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products. This paper aims to summarize findings and recommendations from IMI PREFER regarding i) PPS applications in regulatory evaluation, ii) when and how to consult with regulators on PPS, iii) how to reflect PPS in regulatory communication and iv) barriers and open questions for PPS in regulatory decision-making. Methods: PREFER performed six literature reviews, 143 interviews and eight focus group discussions with regulators, patient representatives, industry representatives, Health Technology Assessment bodies, payers, academics, and clincians between October 2016 and May 2022. Results: i) With respect to PPS applications, prior to the conduct of clinical trials of medicinal products, PPS could inform regulators' understanding of patients' unmet needs and relevant endpoints during horizon scanning activities and scientific advice. During the evaluation of a marketing authorization application, PPS could inform: a) the assessment of whether a product meets an unmet need, b) whether patient-relevant clinical trial endpoints and outcomes were studied, c) the understanding of patient-relevant effect sizes and acceptable trade-offs, and d) the identification of key (un-)favorable effects and uncertainties. ii) With respect to consulting with regulators on PPS, PPS researchers should ideally have early discussions with regulators (e.g., during scientific advice) on the PPS design and research questions. iii) Regarding external PPS communication, PPS could be reflected in the assessment report and product information (e.g., the European Public Assessment Report and the Summary of Product Characteristics). iv) Barriers relevant to the use of PPS in regulatory evaluation include a lack of PPS use cases and demonstrated impact on regulatory decision-making, and need for (financial) incentives, guidance and quality criteria for implementing PPS results in regulatory decision-making. Open questions concerning regulatory PPS use include: a) should a product independent broad approach to the design of PPS be taken and/or a product-specific one, b) who should optimally be financing, designing, conducting, and coordinating PPS, c) when (within and/or outside clinical trials) to perform PPS, and d) how can PPS use best be operationalized in regulatory decisions. Conclusion: PPS have high potential to inform regulators on key unmet needs, endpoints, benefits, and risks that matter most to patients and their acceptable trade-offs. Regulatory guidelines, templates and checklists, together with incentives are needed to foster structural and transparent PPS submission and evaluation in regulatory decision-making. More PPS case studies should be conducted and submitted for regulatory assessment to enable regulatory discussion and increase regulators' experience with PPS implementation and communication in regulatory evaluations.

Balancing benefits and risks in lung cancer therapies: patient preferences for lung cancer treatment alternatives.

Background: In the treatment of Non-Small Cell Lung Cancer (NSCLC) the combination of Immuno- Oncotherapy (IO) and chemotherapy (CT) has been found to be superior to IO or CT alone for patients' survival. Patients and clinicians are confronted with a preference sensitive choice between a more aggressive treatment with a greater negative effect on quality of life versus alternatives that are less effective but have fewer side effects. Objectives: The aims of this study were to: (a) quantify patients' preferences for relevant attributes related to Immuno-Oncotherapy treatment alternatives, and (b) evaluate the maximum acceptable risk (MAR)/Minimum acceptable benefit (MAB) that patients would accept for treatment alternatives. Methods: An online preference survey using discrete-choice experiment (DCE) was completed by NSCLC patients from two hospitals in Italy and Belgium. The survey asked patients' preferences for five patient- relevant treatment attributes. The DCE was developed using a Bayesian D-efficient design. DCE analyses were performed using mixed logit models. Information regarding patient demographics, health literacy, locus of control, and quality of life was also collected. Results: 307 patients (158 Italian, 149 Belgian), stage I to IV, completed the survey. Patients preferred treatments with a higher 5-year survival chance as the most important attribute over all the other attributes. Preference heterogeneity for the attribute weights depended on health literacy, patients' age and locus of control. Patients were willing to accept a substantially increased risks of developing side effects in exchange for the slightest increase (1%) in the chance of surviving at least 5 years from the diagnosis of cancer. Similarly, patients were willing to accept a switch in the mode of administration or complete loss of hair to obtain an increase in survival. Conclusion: In this study, the proportion of respondents who systematically preferred survival over all other treatment attributes was particularly high. Age, objective health literacy and locus of control accounted for heterogeneity in patients' preferences. Evidence on how NSCLC patients trade between survival and other NSCLC attributes can support regulators and other stakeholders on assessing clinical trial evidence and protocols, based on patients' conditions and socio-demographic parameters.

Geriatric assessment for older people with cancer: policy recommendations.

Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole.

How well do European patients understand cancer-associated thrombosis? A patient survey.

Ongoing concerns regarding the morbidity and mortality from cancer-associated thrombosis led the European Cancer Patient Coalition (ECPC), the voice of cancer patients across Europe, to create a pan-European cancer-associated awareness patient survey to assess cancer-associated thrombosis (CAT) knowledge among a large population of patients with cancer. The ECPC survey represents the largest of its kind among patients/caregivers with CAT. It identified significant gaps in patient awareness and knowledge of CAT as well as a need for educational CAT-related discussions and interventions between healthcare professionals and patients with cancer and their caregivers. The aim of this paper is to highlight these gaps and to provide awareness of what/when information should be shared with patients/caregivers. Notably, the importance of providing information on how to reduce their risk of CAT, the role of anticoagulant prophylaxis and treatment (short- and long-term) including possible side-effects, and finally how to identify CAT symptoms early. Here we outline what type of information should be provided, as well as when and how to best discuss CAT with our oncology patients and their caregivers along the cancer care continuum, to reduce the risk of CAT and associated complications with a goal of improving patient outcomes.