What Can Current Biomarker Data Tell Us About the Risks of Lung Cancer Posed by Heated Tobacco Products?

INTRODUCTION: Heated tobacco products (HTPs) are marketed as less harmful alternatives to cigarettes, but the lung cancer risk of HTPs is unknown. In the absence of epidemiological data, assessing the risks of HTPs relies on biomarker data from clinical trials. This study examined existing biomarker data to determine what it tells us about the lung cancer risk posed by HTPs. AIMS AND METHODS: We identified all biomarkers of exposure and potential harm measured in HTP trials and evaluated their appropriateness based on ideal characteristics for measuring lung cancer risk and tobacco use. The effects of HTPs on the most appropriate biomarkers within cigarette smokers switched to HTPs and compared to continued cigarette smoking or cessation were synthesized. RESULTS: Sixteen out of eighty-two biomarkers (7 exposure and 9 potential harm) measured in HTP trials have been associated with tobacco use and lung cancer, dose-dependently correlated with smoking, modifiable upon cessation, measured within an appropriate timeframe, and had results published. Three of the exposure biomarkers significantly improved in smokers who switched to HTPs and were not significantly different from cessation. The remaining 13 biomarkers did not improve-in some instances worsening upon switching to HTPs-or were inconsistently affected across studies. There were no appropriate data to estimate the lung cancer risk of HTPs in non-smokers. CONCLUSIONS: The appropriateness of existing biomarker data in assessing lung cancer risk of HTPs, both relative to cigarettes and their absolute risk, is limited. Furthermore, findings on the most appropriate biomarkers were conflicting across studies and largely showed no improvement following a switch to HTPs. IMPLICATIONS: Biomarker data are fundamental to assessing the reduced risk potential of HTPs. Our evaluation suggests much of the existing biomarker data on HTPs is inappropriate for determining the risk of lung cancer posed by HTPs. In particular, there is a paucity of data on the absolute lung cancer risk of HTPs, which could be obtained from comparisons to smokers who quit and never smokers exposed to or using HTPs. There is an urgent need for further exploration of the lung cancer risks posed by HTPs, via clinical trials and, in the long-term, confirmation of these risks via epidemiological studies. However, careful consideration should be given to biomarker selection and study design to ensure both are appropriate and will provide valuable data.

"Keep it a secret": leaked documents suggest Philip Morris International, and its Japanese affiliate, continue to exploit science for profit.

INTRODUCTION: The tobacco industry has a long history of manipulating science to conceal the harms of its products. As part of its proclaimed transformation, the world's largest tobacco company, Philip Morris International (PMI), states it conducts "transparent science". This paper uses recently leaked documents from PMI and its Japanese affiliate, Philip Morris Japan (PMJ), to examine its contemporary scientific practices. METHODS: 23 documents dating 2012 through 2020 available from Truth Tobacco Industry Documents Library were examined using Forster's hermeneutic approach to analysing corporate documentation. Thematic analysis using the Science for Profit Model was conducted to assess whether PMI/PMJ employed known corporate strategies to influence science in their interests. RESULTS: PMJ contracted a third-party external research organisation, CMIC, to covertly fund a study on smoking cessation conducted by Kyoto University academics. No public record of PMJ's funding or involvement in this study was found. PMJ paid life sciences consultancy, FTI-Innovations, ¥3,000,000 (approx. £20,000) a month between 2014 and 2019 to undertake extensive science-adjacent work, including building relationships with key scientific opinion leaders and using academic events to promote PMI's science, products and messaging. FTI-Innovation's work was hidden internally and externally. These activities resemble known strategies to influence the conduct, publication and reach of science, and conceal scientific activities. CONCLUSIONS: The documents reveal PMI/PMJ's recent activities mirror past practices to manipulate science, undermining PMI's proclaimed transformation. Tobacco industry scientific practices remain a threat to public health, highlighting the urgent need for reform to protect science from the tobacco industry's vested interests.Implications: Japan is a key market for PMI, being a launch market for IQOS and having the highest heated tobacco product use globally. Our findings, in conjunction with other recent evidence, challenge PMI's assertion that it is a source of credible science and cast doubt on the quality and ethical defensibility of its research, especially its studies conducted in Japan. This, in turn, brings into question the true public health impacts of its products. There is urgent need to reform the way tobacco-related science is funded and conducted. Implementation of models through which research can be funded using the industry's profits while minimising its influence should be explored.

Corporate communication of the relative health risks of IQOS through a webchat service.

BACKGROUND: Communication of the relative health risks of IQOS can attract potential consumers, aiding its commercial success. However, health-related claims need to be used cautiously to avoid inaccuracies and attracting non-smokers. We used the live webchat service on the IQOS website to identify information and claims on the relative risks of IQOS made directly to potential consumers in different countries. METHODS: The study was promoted through authors' networks and conducted between 1 August and 30 November 2020. Participants collected webchat conversation responses to three queries regarding the safety of IQOS relative to cigarettes and e-cigarettes using step-by-step guidance and a predesigned form. Responses were analysed to identify health-related claims and information provided. RESULTS: 70 webchat attempts were recorded across 27 countries, 54 of which (in 22 countries) were successful webchat conversations. In 48 of these, one or more claims were used to indicate IQOS is safer than cigarettes, such as IQOS is smoke free, emits less harmful substances or reduces harm. Four conversations contained statements indicating IQOS is safer than e-cigarettes. Some statements provided were contradictory. Participant age was consistently requested on accessing the website, but tobacco/nicotine use was not. Other information provided included referral to the 2020 US Food and Drug Administration Modified Risk Tobacco Product decision, IQOS or Philip Morris International web pages and claims that IQOS is not risk free nor a cessation device. CONCLUSIONS: A variety of claims and information on the relative safety of IQOS were used in webchat communications. Response variation highlights that clearer regulation is needed to appropriately control corporate communications via live webchat services.

Critical appraisal of interventional clinical trials assessing heated tobacco products: a systematic review.

OBJECTIVE: To critically assess the methodological characteristics and quality of interventional clinical trials investigating the effects of heated tobacco products (HTPs). DATA SOURCES: Web of Science (Core collection and MEDLINE), Scopus, MedRxiv, ClinicalTrials.gov and ICTRP trial databases and transnational HTP manufacturer online publication libraries were searched for clinical trials on HTPs published between January 2010 and April 2022. STUDY SELECTION: Interventional clinical trials of any design, in which at least one group of adult participants used a currently marketed HTP, were selected by two reviewers with good or very good agreement. DATA EXTRACTION: Data relating to trial characteristics and effects of intervention on primary outcomes were extracted using a predesigned form. Risk of bias was assessed using Cochrane's Risk of Bias tool v1. DATA SYNTHESIS: 40 trials were included, 29 of which were tobacco industry affiliated. Methodological characteristics, such as registration, design, setting, comparator interventions, participants, outcomes and analyses, varied between trials, though there were few significant differences between industry-affiliated and independent trials. Of the 40 trials, 33 were judged to be at high risk of bias and 6 at unclear risk of bias. Trial findings were not significantly associated with either affiliation or risk of bias. CONCLUSIONS: The conduct and reporting of HTP interventional clinical trials were poor in many respects and limited to investigating effects of short-term exposure. These trials fall short of what is needed to determine whether HTPs are beneficial to public health, meaning they may not be a sound basis for tobacco control policy decisions.