TY - JOUR
T1 - Heated tobacco products for smoking cessation and reducing smoking prevalence
AU - Tattan-Birch, Harry
AU - Hartmann-Boyce, Jamie
AU - Kock, Loren
AU - Simonavicius, Erikas
AU - Brose, Leonie
AU - Jackson, Sarah
AU - Shahab, Lion
AU - Brown, Jamie
N1 - Funding Information:
Quote: "K.M.C. has been a consultant and received grant funding from Pfizer, Inc. in the past five years. K.M.C. has also been a paid expert witness in litigation against the cigarette industry. D.T.S. does not accept money from any entity with a financial interest in promoting any tobacco or nicotine product, nor from any organization that promotes an abstinence-only position on nicotine and tobacco products".
Funding Information:
Tobacco industry funded: quote: "The study was supported by British American Tobacco (Investments) Limited".
Funding Information:
No funding from the tobacco industry: quote: "This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors".
Funding Information:
• remove studies that are funded by (or authors have received funding from) the tobacco industry;
Funding Information:
Quote: "EM, DS and RP are full-time employee of the University of Catania, Italy. PC, MC and RE are fixed-term researcher at University of Catania, Italy. MM is fixed-term researcher at Centro per la Prevenzione e Cura del Tabagismo, University of Catania. BB is full-time employee of ARNAS Garibaldi, Catania, Italy. AP is full-time employee of Casa di Cura Musumeci-Gecas, Gravina di Cata-nia, Italy. UP is full-time employee of Ospedale “San Vincenzo" – Taormina, Italy. In relation to his work in the area of tobacco control, RP has received lecture fees and research funding from Pfizer and GlaxoSmithKline, manufacturers of stop smoking medications. He has also received sup-
Funding Information:
Tobacco industry funded: quote: "This research is supported by an Investigator-Initiated Study award by Philip Morris Products SA (PMI.IIS.2016.006). The study protocol was written by EM who was also the principal investigator of the study. Philip Morris Products SA had no role in the design of the study protocol and will not have any role during its execution, analysis, data interpretation or writing of the manuscript".
Funding Information:
We gratefully acknowledge peer review by K Michael Cummings, PhD, MPH, Medical University of South Carolina, USA and Sophie Braznell, Tobacco Control Research Group, Department for Health, University of Bath, Bath, UK, and consumer review by Sandra Wilcox. We would like to thank authors of included studies for assisting with our search for reports not found in databases. We would also like to thank the following organisations who provided salary or studentship support to the authors of this review: Public Health England, National Institute for Health Research Maudsley Biomedical Research Centre, UK Prevention Research Partnership, and Cancer Research UK. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of these organisations.
Funding Information:
ES has a PhD studentship funded by the National Institute for Health Research Maudsley Biomedical Research Centre. This is not deemed to be a conflict of interest.
Funding Information:
HTB holds a studentship funded by Public Health England. This is not deemed to be a conflict of interest.
Funding Information:
Tobacco industry funded: quote: "The study was funded by Philip Morris Products S.A.".
Funding Information:
LK: salary is funded by the UK Prevention Research Partnership, an initiative funded by UK Research and Innovation Councils, the Department of Health and Social Care (England), and the UK devolved administrations and leading health research charities. This is not deemed to be a conflict of interest.
Funding Information:
No funding from the tobacco industry: quote: "K.M.C. and G.J.N. receive funding support from grants from the US National Cancer Institute (P01 CA200512, P30 CA138313)".
Funding Information:
Tobacco industry funded: quote: "The work reported in all eight parts of this supplement was funded by PMI R&D".
Publisher Copyright:
Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.
PY - 2022/1/6
Y1 - 2022/1/6
N2 - BACKGROUND: Heated tobacco products (HTPs) are designed to heat tobacco to a high enough temperature to release aerosol, without burning it or producing smoke. They differ from e-cigarettes because they heat tobacco leaf/sheet rather than a liquid. Companies who make HTPs claim they produce fewer harmful chemicals than conventional cigarettes. Some people report stopping smoking cigarettes entirely by switching to using HTPs, so clinicians need to know whether they are effective for this purpose and relatively safe. Also, to regulate HTPs appropriately, policymakers should understand their impact on health and on cigarette smoking prevalence.OBJECTIVES: To evaluate the effectiveness and safety of HTPs for smoking cessation and the impact of HTPs on smoking prevalence. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, CENTRAL, MEDLINE, and six other databases for relevant records to January 2021, together with reference-checking and contact with study authors and relevant groups.SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people who smoked cigarettes were randomised to switch to exclusive HTP use or a control condition. Eligible outcomes were smoking cessation, adverse events, and selected biomarkers. RCTs conducted in clinic or in an ambulatory setting were deemed eligible when assessing safety, including those randomising participants to exclusively use HTPs, smoke cigarettes, or attempt abstinence from all tobacco. Time-series studies were also eligible for inclusion if they examined the population-level impact of heated tobacco on smoking prevalence or cigarette sales as an indirect measure.DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking at the longest follow-up point available, adverse events, serious adverse events, and changes in smoking prevalence or cigarette sales. Other outcomes included biomarkers of harm and exposure to toxicants/carcinogens (e.g. NNAL and carboxyhaemoglobin (COHb)). We used a random-effects Mantel-Haenszel model to calculate risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes. For continuous outcomes, we calculated mean differences on the log-transformed scale (LMD) with 95% CIs. We pooled data across studies using meta-analysis where possible.MAIN RESULTS: We included 13 completed studies, of which 11 were RCTs assessing safety (2666 participants) and two were time-series studies. We judged eight RCTs to be at unclear risk of bias and three at high risk. All RCTs were funded by tobacco companies. Median length of follow-up was 13 weeks. No studies reported smoking cessation outcomes. There was insufficient evidence for a difference in risk of adverse events between smokers randomised to switch to heated tobacco or continue smoking cigarettes, limited by imprecision and risk of bias (RR 1.03, 95% CI 0.92 to 1.15; I2 = 0%; 6 studies, 1713 participants). There was insufficient evidence to determine whether risk of serious adverse events differed between groups due to very serious imprecision and risk of bias (RR 0.79, 95% CI 0.33 to 1.94; I2 = 0%; 4 studies, 1472 participants). There was moderate-certainty evidence for lower NNAL and COHb at follow-up in heated tobacco than cigarette smoking groups, limited by risk of bias (NNAL: LMD -0.81, 95% CI -1.07 to -0.55; I2 = 92%; 10 studies, 1959 participants; COHb: LMD -0.74, 95% CI -0.92 to -0.52; I2 = 96%; 9 studies, 1807 participants). Evidence for additional biomarkers of exposure are reported in the main body of the review. There was insufficient evidence for a difference in risk of adverse events in smokers randomised to switch to heated tobacco or attempt abstinence from all tobacco, limited by risk of bias and imprecision (RR 1.12, 95% CI 0.86 to 1.46; I2 = 0%; 2 studies, 237 participants). Five studies reported that no serious adverse events occurred in either group (533 participants). There was moderate-certainty evidence, limited by risk of bias, that urine concentrations of NNAL at follow-up were higher in the heated tobacco use compared with abstinence group (LMD 0.50, 95% CI 0.34 to 0.66; I2 = 0%; 5 studies, 382 participants). In addition, there was very low-certainty evidence, limited by risk of bias, inconsistency, and imprecision, for higher COHb in the heated tobacco use compared with abstinence group for intention-to-treat analyses (LMD 0.69, 95% CI 0.07 to 1.31; 3 studies, 212 participants), but lower COHb in per-protocol analyses (LMD -0.32, 95% CI -1.04 to 0.39; 2 studies, 170 participants). Evidence concerning additional biomarkers is reported in the main body of the review. Data from two time-series studies showed that the rate of decline in cigarette sales accelerated following the introduction of heated tobacco to market in Japan. This evidence was of very low-certainty as there was risk of bias, including possible confounding, and cigarette sales are an indirect measure of smoking prevalence.AUTHORS' CONCLUSIONS: No studies reported on cigarette smoking cessation, so the effectiveness of heated tobacco for this purpose remains uncertain. There was insufficient evidence for differences in risk of adverse or serious adverse events between people randomised to switch to heated tobacco, smoke cigarettes, or attempt tobacco abstinence in the short-term. There was moderate-certainty evidence that heated tobacco users have lower exposure to toxicants/carcinogens than cigarette smokers and very low- to moderate-certainty evidence of higher exposure than those attempting abstinence from all tobacco. Independently funded research on the effectiveness and safety of HTPs is needed. The rate of decline in cigarette sales accelerated after the introduction of heated tobacco to market in Japan but, as data were observational, it is possible other factors caused these changes. Moreover, falls in cigarette sales may not translate to declining smoking prevalence, and changes in Japan may not generalise elsewhere. To clarify the impact of rising heated tobacco use on smoking prevalence, there is a need for time-series studies that examine this association.
AB - BACKGROUND: Heated tobacco products (HTPs) are designed to heat tobacco to a high enough temperature to release aerosol, without burning it or producing smoke. They differ from e-cigarettes because they heat tobacco leaf/sheet rather than a liquid. Companies who make HTPs claim they produce fewer harmful chemicals than conventional cigarettes. Some people report stopping smoking cigarettes entirely by switching to using HTPs, so clinicians need to know whether they are effective for this purpose and relatively safe. Also, to regulate HTPs appropriately, policymakers should understand their impact on health and on cigarette smoking prevalence.OBJECTIVES: To evaluate the effectiveness and safety of HTPs for smoking cessation and the impact of HTPs on smoking prevalence. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, CENTRAL, MEDLINE, and six other databases for relevant records to January 2021, together with reference-checking and contact with study authors and relevant groups.SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people who smoked cigarettes were randomised to switch to exclusive HTP use or a control condition. Eligible outcomes were smoking cessation, adverse events, and selected biomarkers. RCTs conducted in clinic or in an ambulatory setting were deemed eligible when assessing safety, including those randomising participants to exclusively use HTPs, smoke cigarettes, or attempt abstinence from all tobacco. Time-series studies were also eligible for inclusion if they examined the population-level impact of heated tobacco on smoking prevalence or cigarette sales as an indirect measure.DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking at the longest follow-up point available, adverse events, serious adverse events, and changes in smoking prevalence or cigarette sales. Other outcomes included biomarkers of harm and exposure to toxicants/carcinogens (e.g. NNAL and carboxyhaemoglobin (COHb)). We used a random-effects Mantel-Haenszel model to calculate risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes. For continuous outcomes, we calculated mean differences on the log-transformed scale (LMD) with 95% CIs. We pooled data across studies using meta-analysis where possible.MAIN RESULTS: We included 13 completed studies, of which 11 were RCTs assessing safety (2666 participants) and two were time-series studies. We judged eight RCTs to be at unclear risk of bias and three at high risk. All RCTs were funded by tobacco companies. Median length of follow-up was 13 weeks. No studies reported smoking cessation outcomes. There was insufficient evidence for a difference in risk of adverse events between smokers randomised to switch to heated tobacco or continue smoking cigarettes, limited by imprecision and risk of bias (RR 1.03, 95% CI 0.92 to 1.15; I2 = 0%; 6 studies, 1713 participants). There was insufficient evidence to determine whether risk of serious adverse events differed between groups due to very serious imprecision and risk of bias (RR 0.79, 95% CI 0.33 to 1.94; I2 = 0%; 4 studies, 1472 participants). There was moderate-certainty evidence for lower NNAL and COHb at follow-up in heated tobacco than cigarette smoking groups, limited by risk of bias (NNAL: LMD -0.81, 95% CI -1.07 to -0.55; I2 = 92%; 10 studies, 1959 participants; COHb: LMD -0.74, 95% CI -0.92 to -0.52; I2 = 96%; 9 studies, 1807 participants). Evidence for additional biomarkers of exposure are reported in the main body of the review. There was insufficient evidence for a difference in risk of adverse events in smokers randomised to switch to heated tobacco or attempt abstinence from all tobacco, limited by risk of bias and imprecision (RR 1.12, 95% CI 0.86 to 1.46; I2 = 0%; 2 studies, 237 participants). Five studies reported that no serious adverse events occurred in either group (533 participants). There was moderate-certainty evidence, limited by risk of bias, that urine concentrations of NNAL at follow-up were higher in the heated tobacco use compared with abstinence group (LMD 0.50, 95% CI 0.34 to 0.66; I2 = 0%; 5 studies, 382 participants). In addition, there was very low-certainty evidence, limited by risk of bias, inconsistency, and imprecision, for higher COHb in the heated tobacco use compared with abstinence group for intention-to-treat analyses (LMD 0.69, 95% CI 0.07 to 1.31; 3 studies, 212 participants), but lower COHb in per-protocol analyses (LMD -0.32, 95% CI -1.04 to 0.39; 2 studies, 170 participants). Evidence concerning additional biomarkers is reported in the main body of the review. Data from two time-series studies showed that the rate of decline in cigarette sales accelerated following the introduction of heated tobacco to market in Japan. This evidence was of very low-certainty as there was risk of bias, including possible confounding, and cigarette sales are an indirect measure of smoking prevalence.AUTHORS' CONCLUSIONS: No studies reported on cigarette smoking cessation, so the effectiveness of heated tobacco for this purpose remains uncertain. There was insufficient evidence for differences in risk of adverse or serious adverse events between people randomised to switch to heated tobacco, smoke cigarettes, or attempt tobacco abstinence in the short-term. There was moderate-certainty evidence that heated tobacco users have lower exposure to toxicants/carcinogens than cigarette smokers and very low- to moderate-certainty evidence of higher exposure than those attempting abstinence from all tobacco. Independently funded research on the effectiveness and safety of HTPs is needed. The rate of decline in cigarette sales accelerated after the introduction of heated tobacco to market in Japan but, as data were observational, it is possible other factors caused these changes. Moreover, falls in cigarette sales may not translate to declining smoking prevalence, and changes in Japan may not generalise elsewhere. To clarify the impact of rising heated tobacco use on smoking prevalence, there is a need for time-series studies that examine this association.
UR - http://www.scopus.com/inward/record.url?scp=85122302603&partnerID=8YFLogxK
U2 - 10.1002/14651858.CD013790.pub2
DO - 10.1002/14651858.CD013790.pub2
M3 - Article
C2 - 34988969
SN - 1469-493X
VL - 2022
SP - CD013790
JO - The Cochrane database of systematic reviews
JF - The Cochrane database of systematic reviews
IS - 1
M1 - CD013790
ER -
