Putting Evidence Into Practice Smoking Cessation

Putting evidence into practice: Smoking cessationKlara Brunnhuber K. Michael Cummings Sheila Feit Scott Sherman James Woodcock Summer 2007 Letterpart Ltd – Typeset in XML A Division: plm_FrontCover F Sequential 1 This report was commissioned by the United Health Foundation. The BMJ Publishing Group Limited (BMJPG) is a world leader in medical publishing. Its journals and online products address major specialties, lead the debate on health care, and deliver innovative knowledge and best practices to doctors, health professionals, researchers and patients, when and where they need it. The BMJPG publishes BMJ Clinical Evidence, an evidence-based compendium of therapies, which is an authoritative resource for informing treatment decisions and improving patient care. Funding This report was funded by the United Health Foundation. Disclaimer The information contained in this publication is intended for medical professionals. We rely on studies to confirm the accuracy of the information presented, and to describe generally accepted practices, and therefore we cannot warrant its accuracy. Readers should be aware that professionals in the field may have different opinions. Because of this fact and also because of regular advances in medical research, we strongly recommend that readers independently verify specified treatments and drugs, including manufacturers’ guidance. Ultimately, it is the readers’ responsibility to make their own professional judgements, so as to appropriately advise and treat their patients. Description of reference to a product or publication does not imply endorsement of that product or publication, unless it is owned by the BMJ Publishing Group Limited. To the fullest extent permitted by law, BMJ Publishing Group Limited and its authors and editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, product liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication. © BMJ Publishing Group Limited 2007 Letterpart Ltd – Typeset in XML A Division: plm_FrontCover F Sequential 2 Authors Klara Brunnhuber, MD Clinical Editor, BMJ Publishing Group Limited K. Michael Cummings, PhD, MPH (Public policy on smoking) Chair, Department of Health Behavior, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY Sheila Feit, MD Deputy Editor, Point of Care, BMJ Publishing Group Limited Scott Sherman, MD, MPH (Toolkit: 12-step guide to a primary care systems approach for smoking cessation) Associate Professor, Department of Medicine, NYU Medical Center, NY James Woodcock, MSc Product Development Editor, BMJ Publishing Group Limited Acknowledgments Dr Nicholas Gaudin (Head of Communications IARC, WHO, Lyon, France) for providing pre-publication access to Tobacco Control, Vol. 11: Reversal of Risk After Quitting Smoking Dr Beth Nash (Product Development Manager, BMJ Publishing Group Limited) for her help with planning and reviewing the paper Sam Martin (Information Specialist, BMJ Publishing Group Limited) and Alex McNeil (Information Specialist, BMJ Publishing Group Limited) for conducting literature searches and assisting with appraisal of studies Polly Brown (Freelance Scientific Editor, BMJ Publishing Group Limited) and Dr Karen Devries (PhD, London School of Hygiene and Tropical Medicine) for writing evidence summaries Tricia Lawrence (Copy Editor, BMJ Publishing Group Limited) for copyediting the paper Advisory board and peer review K. Michael Cummings, PhD, MPH Chair, Department of Health Behavior, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY Michael Fischer, MD, MS Associate Physician in the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital; Instructor in Medicine, Harvard Medical School, Boston, MA Nancy Rigotti, MD Associate Professor, Department of Medicine, Harvard Medical School; Associate Professor, Department of Health and Social Behavior, Harvard School of Public Health; Director, Tobacco Research and Treatment Unit, Massachusetts General Hospital, Boston, MA Scott Sherman MD, MPH Associate Professor, Department of Medicine, NYU Medical Center, NY Letterpart Ltd – Typeset in XML A Division: plm_Authors F Sequential 1 Additional peer reviewers Carolyn Dresler, MD, MPA Associate Professor of Health Policy and Management Department of Health Policy and Management, University of Arkansas for Medical Sciences, Fayetteville, AR Nancy Lee Clinical Pharmacist, University of California, UCLA Medical Center, Los Angeles, CA Maria Leon-Roux, MPH Tobacco and Cancer Team, Lifestyle, Environment and Cancer Group, IARC, WHO, Lyon, France Competing interests K. Michael Cummings, PhD, MPH has been paid by the Pfizer Corporation to give lectures to doctors about their new stop-smoking medication, Chantix. The Pfizer Corporation and GlaxoSmithKline have also supported continuing medical education (CME) programs for health care professionals that he has helped to organize. He is co-author of six articles that are referenced in this report. Carolyn Dresler, MD was the medical director for research and development for the Smoking Control Category (Nicotine replacement products) for GlaxoSmithKline Consumer Healthcare from June 1998 to June 2004. Maria Leon-Roux, MPH is one of the officers overseeing a comprehensive review referenced in this report. Nancy Rigotti, MD has consulted for the Pfizer Corporation and Sanofi-Aventis regarding smoking cessation treatments. The Tobacco Research and Treatment Center that she directs has received research grants from the Pfizer Corporation, Sanofi-Aventis, and Nabi Biopharmaceuticals to study smoking cessation treatments. She is co-author of four articles that are referenced in this report. Letterpart Ltd – Typeset in XML A Division: plm_Authors F Sequential 2 .............................13 Interventions for smoking cessation.................................................................................................................................15 Economic issues in smoking cessation ....................................................................38 Letterpart Ltd – Typeset in XML A Division: Contents-citi F Sequential 1 ..............................................................................................3 Health benefits of cessation...................................................................................2 Disease burden from smoking .........................................................................................................................................................4 Predictors of quitting and maintained cessation ............................................................................................................................................Contents Introduction...1 Demographics .................................................................................................................................................................................12 Public policy on smoking.....................................................................28 Appendix: Methodology ....................34 Toolkit: 12-step guide to a primary care systems approach for smoking cessation ...............................26 References .................................................... Letterpart Ltd – Typeset in XML A Division: Contents-citi F Sequential 2 . pancreas. patients can discuss difficult situations and how to handle them. bladder. mouth. the most effective way to eliminate smoking-related illness is to prevent people from starting use of tobacco. + Behavioral counseling addresses the habit. or pediatric visits) are opportunities to relay smoking cessation information. larynx.4 In the long run. and infant deaths related to maternal smoking. or lack motivation and confidence to quit. + Motivation to quit smoking is important..2. in order to tailor treatment to individual needs. discontinuing use is the best and surest option for reducing health risks. Although no method is proven to prevent relapse. such as cardiac disease and lung cancer. + Medications treat the addiction component of smoking. + Smoking can be thought of as a chronic illness.1. This paper will examine the disease burden related to smoking and the health benefits of quitting. hospitalization. It will present the evidence for interventions to help adults quit smoking. with exacerbations and remissions. cancer (e.5 Many need encouragement.2 Increasingly. At follow-up.3 Cigarette smoking remains the single most avoidable cause of death and disability in the United States. the dangers of secondhand smoke.g. so about 45 million American adults still smoke.2. lung. Drugs are available that increase the chance of a successful quit attempt. but it’s not enough..Most smokers want to quit.g. Encouraging smoking cessation is now recognized as an important part of medical care and public health. most attempts fail. acute respiratory illness. Trials have generally included behavioral support and most have excluded people with serious medical or psychiatric illnesses. patients can try to identify triggers and plan or rehearse responsive strategies. Smoking is both a habit and a coping strategy. + A systems approach may help to identify and treat smokers.2 Sequelae of smoking include cardiovascular and respiratory disease. but although some smokers succeed. Introduction © BMJ Publishing Group 2007 1 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 1 .1 But most attempts fail and new smokers are constantly recruited. kidneys). pregnancy. are also recognized by researchers and policy makers. assistance. Considering smoking status a vital sign can highlight its importance. and provide a practical toolkit for putting the evidence into everyday practice.6 A brief tobacco use assessment can help identify those people who are highly nicotine-dependent. cervix. esophagus. and guidance.7 Electronic tools may be a promising component of delivering smoking cessation interventions efficiently.3. Most people think they can quit on their own. For those who already smoke. [See Toolkit: 12-step guide to a primary care systems approach for smoking cessation] Office visits and any contact with the health care system (e. About 40% of smokers stop for at least a day in an attempt to quit each year. 645 in 2004) smoke. smoking is an important contributor to health disparities.9 2 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 2 .8 More men smoke than women (23% vs. compared to about 8. Overall. Figure 1.8 Smoking is more common among lower socioeconomic groups. Length of education is associated with lower smoking rates. smoking is most common among American Indians/Native Alaskans (33%) and least common among Asians/Pacific Islanders (11. population.S. Therefore. Changes in prevalence of smoking among adults in the United States8 The remainder of the population is about evenly split between former (21%) and current (21%) smokers.Demographics The prevalence of smoking has decreased by about 50% over the past 50 years to around one fifth of the U.S. Among people of different ancestries.8 Levels in all of these groups are above the U. About 21% of people at or above the poverty line ($9. ranging from 26% in people with less than 12 years of education to 10% in those with 16 years or more. The prevalence of smoking for both blacks and whites is 21%. Smoking rates are higher among young adults (aged 18 to 24) than older ones. Currently about 58% of Americans have never smoked. compared to 29% of those below the poverty line. 19%). government’s Healthy People 2010 goal: an adult smoking rate of less than 12%.8 About 22% to 24% of adults aged 18 to 64 are smokers. 26% of young adult men and 22% of young adult women smoke.8% of people aged 65 or older.3%) and Hispanics (15%). The highest percentage of young adult smokers is in men with less than 12 years of education (40%). cervical). respiratory diseases and harmful effects on reproduction. many more people are harmed by tobacco use than is indicated by mortality statistics. followed by emphysema (24%). or placental abruption. Exposure to secondhand tobacco smoke is a significant health risk for nonsmokers.9 to 10. lung cancer. In 2000. abdominal aortic aneurysm + Respiratory disease: chronic obstructive pulmonary disease (COPD). Evidence is still being accumulated for other harms of smoking. pancreatic). placenta previa.6 (95% CI 6.000 deaths among women in the United States (see figures 2 and 3). Smoking also adversely impacts wound healing in patients who have undergone surgery. especially those with pre-existing respiratory and cardiac conditions. peptic ulcer disease.000 deaths among men and 243. such as cardiovascular disease. For former smokers. hematologic (myeloid leukemia) + Cardiovascular disease: atherosclerosis. chronic bronchitis was the most prevalent condition (49%). and previous heart attack (24%). However. According to the 2004 Surgeon General’s Report there is sufficient evidence that smoking causes the following conditions:10. kidney.5) million people in the United States had disease attributable to smoking. smoking was responsible for 269. emphysema (24%). and impaired lung growth during childhood and adolescence + Reproductive effects: decreased fertility in women. oral (laryngeal).11 + Cancers: lung. low bone density. Disease burden from smoking © BMJ Publishing Group 2007 3 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 3 . diminished health status In 2000. increased susceptibility to pneumonia. liver. the three most prevalent conditions were chronic bronchitis (26%). still birth. sudden infant death syndrome (SIDS) + Other: hip fractures. cataracts. cerebrovascular and coronary heart disease (CHD). miscarriage. Health care professionals should routinely question all their patients about exposure to secondhand smoke and advise their patients to adopt a smoke-free home and car policy. reduced lung function in infants. GU (bladder. GI (esophageal.Smoking is the biggest preventable cause of premature mortality in the United States and is a major factor in many diseases and adverse health events. low birth weight. stomach. complications of pregnancy such as premature rupture of the membranes. an estimated 8.13 For current smokers. for others there remains an elevated risk for many decades.Figures 2. all opportunities need to be taken. Although for some conditions the risk falls off quickly after quitting toward the level of a never smoker. lag times differ among conditions between smoking and development of disease. Although the largest potential benefits 4 © BMJ Publishing Group 2007 Health benefits of cessation Letterpart Ltd – Typeset in XML A Division: Text F Sequential 4 . However. and 3. This means that it is important to promote smoking cessation as early as possible among young smokers who have the greatest chance of avoiding adverse smoking-related events. As these populations are usually in good health and have limited contact with the medical community. Number of deaths attributable to smoking in men and women in 200012 Stopping smoking reduces the risk of many of the conditions associated with smoking. Individual risk often depends on previous duration and intensity of smoking and varies between those with and without pre-existing evidence of disease. Figure 4. The best evidence on benefits of cessation comes from a new systematic review by the International Agency for Research on Cancer (IARC). CHD: coronary heart disease are in young smokers.439 male British doctors. Timeline of health benefits after smoking cessation14 COPD: chronic obstructive pulmonary disease. These groups should also be encouraged to quit. There © BMJ Publishing Group 2007 5 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 5 . there are benefits from quitting even among elderly smokers and people with considerable comorbidities. Some of the longest term data has come from 50 years’ follow-up of 34.14 Mortality There is strong and consistent evidence from cohort and case control studies that sustained smoking cessation reduces mortality compared with ongoing smoking.15 This study found a difference in life expectancy of 10 years between continuing smokers and never smokers for men born between 1900 and 1930. 03). 9 years at age 40.17 The Lung Health Study in 10 clinical centers in the United States and Canada followed 5. Because of the high relative risk for lung cancer from smoking and the high disease burden.505 women and 25.14 It concluded that most of the increased risk is avoided by those who stop smoking before middle age. Lung cancer rates. However.113. 21 in women. the absolute annual risk of developing or dying from lung cancer does not decrease after stopping smoking. cessation is extremely beneficial for all age groups.4% vs. 10.S. and the earlier smokers quit.200 YLL in women.034 men over 26 years and collected smoking status at multiple time points. female smokers started later and smoked smaller amounts than men.4%).887 middle-aged volunteers with asymptomatic airway obstruction and compared an intensive smoking cessation intervention versus usual care. but that there is a smaller but still substantial gain among those who quit in middle or older age. According to the Centers for Disease Control and Prevention (CDC). overall mortality decreased among nonsmokers over the second half of the 20th century. However. A population-based cohort study in Norway followed 24. the impact of cessation is relatively easy to study. As Figure 5 shows. smoking-related lung cancer accounts for more than 10 times the number of years of potential life lost (YLL) in the United States compared with any other smoking-related cancer (based on data from 1997 to 2001: 1.were substantial benefits from cessation. Evidence from observational studies has been supplemented by recent evidence from a large randomized trial with long-term follow-up that found benefits from cessation even though only a minority of the population successfully quit. the closer will their chances of survival resemble that of never smokers.14 6 © BMJ Publishing Group 2007 Cancer risk Letterpart Ltd – Typeset in XML A Division: Text F Sequential 6 . 19. in part because of historically lower smoking levels. which may have produced a lower loss of life. Less good data exist for women. Table 1 summarizes a meta-analysis of U. this difference increasingly no longer applies. as a result of earlier and more intensive smoking. P = 0. and 10 years at age 30. However.600 YLL in men and 740. were similar in women and men. One systematic review found 34 studies with results in men. and 6 in both sexes. which had been adjusted for amount smoked and age started. resulting in an increased smoker to nonsmoker death rate ratio.38 per 1000 person-years. studies for the relative reduction in risk for quitters compared with persistent smokers.16 For women.10 Because of the time lag between cigarette smoke-related cell mutation. It found that all-cause mortality was significantly lower in the intervention group (8. this change was not observed among cigarette smokers. a difference in lung cancer risk between smokers and former smokers is not to be expected before around 2 years after quitting. and disease detection. 6 years at age 50. it found that mortality was approximately halved in smokers who stopped before the age of 40 compared with continuing smokers (risk of dying in middle age 9. but middle-aged women had lower cardiovascular mortality leading to less all-cause mortality from smoking. In the past. Lung cancer represents the biggest cause of smoking-related cancer mortality. In the study.83 per 1000 person-years vs. Gains in life expectancy were 3 years at age 60. Impact of smoking and smoking cessation on survival in men15 © BMJ Publishing Group 2007 7 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 7 .Figure 5. 42) 30–39 0. the risk remained elevated for at least 25 years after cessation. and an increased risk was probably maintained for at least 20 years + Evidence on adenocarcinoma was more limited with no clear reduction of risk on cessation.12) A systematic review found that smoking cessation was associated with a reduction in the risk of all the major histologic types of lung cancer.51) 0.000 YLL) + Good evidence of reduced risk for ex-smokers compared with current smokers for squamous cell esophageal cancer.13) 0. 20 © BMJ Publishing Group 2007 Cervical cancer 8 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 8 . Changes in relative risk (RR) for lung cancer after cessation between former and persistent smokers14 Years since cessation < 10 RR in men RR in women 0.15–0.08–0. other types of cancer are also causally linked to smoking. the relative risk returned rapidly to the level of never smokers. and the third among women (25.67–0.20 (95% CI 0.58–0.14 The risk is likely to remain elevated for at least 15 years after cessation.22) 0.200 YLL) and the fifth among women (19.19 It found that former smokers had significantly less than half (44%) of the risk of current smokers.04–0.10 (95% CI 0.14 after 10 years of cessation the risk among ex-smokers was still twice the risk of never smokers. Table 2. 14.903 veterans aged 30 years or older. and health benefits from cessation + Second biggest cause of years of life lost (YLL) through cancer from smoking among men (101.08–0. the risk for adenocarcinoma and large cell carcinoma fell off less rapidly than for small cell lung cancer and squamous cell carcinoma.18–0.14 Pancreatic cancer + Second biggest cause of smoking-related years of life lost from smoking among women (51.700 YLL) + Strong interaction between alcohol and smoking + The best evidence came from a study of 177.73 (95% CI 0.92) 10–19 0.13–0. + Following cessation.23 (95% CI 0.14 Oral cancer + Third biggest cause of years of life lost through cancer among men (63. A recent systematic review concluded that the risk remained elevated compared with never smokers up to 20 years after cessation. Cancer types other than lung cancer and their association with smoking Cancer type Esophageal cancer Disease burden from smoking.18 However.40) 20–29 0.92) 0. Urinary tract cancer + There is good evidence of reduced risk among former compared with persistent smokers.100 YLL).14 However.14 As described in Table 2.28 (95% CI 0.600 YLL) + There is good evidence of risk reduction following cessation.10 (95% CI 0.14 (95% CI 0. The subsequent review supported these findings.Table 1.78 (95% CI 0. additional risk factors. although an elevated risk remains compared with never smokers for at least 20 years. Coronary heart disease The evidence base for association of smoking with cerebrovascular disease is less good than for cardiovascular disease.14 In part this probably depends on past smoking habits.14 A systematic review found that smoking cessation decreased the RR for reinfarction or death by 36% among people with CHD.25 Three subsequent cohort studies confirmed the benefit from cessation in people with CHD. particularly in cancers that are not widely acknowledged as smoking-related. + Inconclusive evidence to assess the benefits of cessation for the risk of myeloid leukemia.14 Myeloid leukemia A recent study summarized the effects of smoking on cancer treatment efficacy in people with malignancies. and continuing to fall. It found that smoking was associated with pulmonary complications during and following surgery. although other studies found that RR was still 10% to 20% elevated 10 to 20 years after quitting. with light smokers (< 20 cigarettes/day) reaching the risk of never smokers within 5 years. + Helicobacter pylori infection and alcohol consumption are other important risk factors. it is clear from the IARC review that the RR decreases with cessation and may reach that of never smokers following 5 to 10 years of abstinence.23.21 It found that most oncology clinical trials did not collect data on smoking history and status. and overall healthier behavior by quitters.26–28 The IARC review found some studies showing that RR falls to that of never smokers 10 to 15 years after cessation. © BMJ Publishing Group 2007 9 Cerebrovascular disease Letterpart Ltd – Typeset in XML A Division: Text F Sequential 9 . reverse causation.14 As a result of possible confounding through misclassification of smoking status.10.22.Stomach cancer + Smoking has recently been found to be causally associated with stomach cancer. + Reduced relative risk compared with persistent smokers. smoking status was monitored in very few trials and infrequently reported or included as potential moderator of outcomes. whereas heavier smokers may never reach it. it is not possible to assess with the current body of evidence if any long-term residual risk remains. caution is warranted as the cohort studies measured smoking status only at enrollment. and increased complications from radiation therapy. However. It both reduces the ability of the blood to carry oxygen and causes progressive atherosclerosis with endothelial injury and thrombotic processes that may lead to acute infarction. poorer wound healing. Other studies have associated smoking cessation with increased survival times in breast cancer and non-small cell lung cancer. If collected.14 However. but insufficient evidence to assess whether the risk ever fell to that of never smokers. although there could still be some elevated risk.14 Laryngeal cancer + Rapid reduction in risk (about 60% at 10 to 15 years compared with persistent smokers).24 Cardiovascular risk Smoking operates at different stages in the development of coronary heart disease (CHD). after 50 years of observation. 0. After quitting. One RCT. found an increase in FEV1 in the first year following smoking cessation. and hydrogen cyanide.Smoking is the dominant risk factor for peripheral artery disease (PAD). such as formaldehyde.32. P < 0. the Lung Health Study. The reduction in RR is slower than for cerebrovascular and CHD. reverse causality may lead to underestimatation of the benefits of cessation. with lower cigarette dependency being associated with a greater chance of successful quitting.4 There is a prothrombotic effect with increased platelet stickiness.14 The strongest evidence for benefit is in people with mild COPD.11 for never smokers.14 Long-term studies suggested a substantial reduction in mortality compared with continuing smokers. found age-standardized mortality rates per 1000 man-years for COPD of 0.959 men and 26.56 for current smokers. with reduced patency in heavy smokers compared with moderate smokers.34 Reduced cigarette consumption Secondhand smoke is now a recognized carcinogen. containing over 50 harmful chemicals. A meta-analysis of 4 randomized controlled trials (RCTs) and 12 prospective studies included in a systematic review found that smoking increased graft failure 3.14 However. Recent long-term studies from Norway (24. which included people with mild to moderate COPD. benzene.5 years) found no evidence of reduced mortality in smokers who reduced smoking. breathing secondhand smoke has been found to be immediately detrimental to the cardiovascular system.64 for former smokers.00001) in people with PAD who were undergoing arterial reconstructive surgery in the lower extremities.30 Subsequently the rate of decline in sustained quitters was half that of continuing smokers.15 Given the long time lag between first symptoms and death from COPD.34–4. However.4 Concentrations of many harmful chemicals are higher in secondhand smoke than in that inhaled by smokers.732 people with a mean follow-up of 15. reduced cigarette consumption may be useful as a step toward cessation. The British doctors’ study. lung cancer. Chronic obstructive pulmonary disease Although there is good evidence of a dose response effect from smoking from studies of both intensity and duration. and cardiovascular disease. Difficulties studying the link between secondhand smoke and disease incidence include the need to examine large numbers of people for long time lengths.31 Limited evidence in people with severe COPD suggested also a large benefit.08. arsenic.29 It demonstrated a clear dose response relationship.09-fold (95% CI 2. vinyl chloride.251 women aged 20–49 years) and Denmark (19. ammonia. a lack of controlled study conditions and recall bias on the part of study participants. Peripheral artery disease The IARC review found that the general decline in lung function with age reverted to that of never smokers within 5 years of cessation. decreased 10 © BMJ Publishing Group 2007 Secondhand smoke Letterpart Ltd – Typeset in XML A Division: Text F Sequential 10 . with elevated risk observed even after 20 years. patency failure rates returned to the level of never smokers. there is evidence of a clearer and more rapid benefit in people with advanced PAD who quit smoking. with no difference in patency rates between autogenous and polyester grafts. the evidence on reduced smoking is less clear than the evidence for benefit from smoking cessation on mortality.33 However. and 1. acute respiratory infections. Maternal exposure during pregnancy is associated with a small decrease in birth weight and persistent adverse effects on lung function throughout childhood. or bars are at highest risk. Nonsmokers exposed to secondhand smoke at home or at work have about a 25% to 30% increased risk of heart disease and 20% to 30% increased risk of lung cancer. a few regions have introduced fines for smoking in cars with children. Infants and young children are considered especially vulnerable. Air cleaning systems leave behind small particles. millions of Americans continue to be exposed to secondhand smoke.4 Millions of indoor workers are still not covered by smoke-free workplace rules. Most of the included studies (20 of 25) found an increased lung cancer risk among never smokers exposed to workplace secondhand smoke. gender.37 © BMJ Publishing Group 2007 11 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 11 .4. Custody and foster arrangements may be affected by parental smoking. restaurants. Meta-analysis found that relative risk increased on average by 24%.coronary flow reserves. The Surgeon General has concluded that there is no safe level for secondhand smoke exposure. gender. ear problems. Secondhand smoke exposure varies by occupation. A final frontier is the restriction of smoking in cars and homes. Parental smoke is linked to ever having asthma.35 The analysis stratified studies depending on level of exposure and weighted evidence on several key issues including geographic location. including 60% of children aged 3 to 11 years. Mechanical ventilation or separation of smokers does not fully eliminate the risk. Pooled evidence has indicated a causal relationship between secondhand smoke and both lung cancer and CHD. with people in the highest workplace exposure categories being twice as likely to develop lung cancer compared with nonexposed people. and reduced heart rate variability.36. Heating and cooling systems may distribute smoke throughout a building. but exposure tends to be higher in lower socioeconomic groups. excluding studies that featured former smokers. and ethnicity. and exposure in children has been associated with increased risk for sudden infant death syndrome (SIDS). Despite declining smoking rates. and increased severity of asthma. some residential buildings are now smoke-free. A recent systematic review and meta-analysis looked specifically at workplace exposure to tobacco smoke. People who work in entertainment jobs. and level of exposure to other lung carcinogens such as coal heating fumes. and. Homes and vehicles also remain important places of exposure. 38.38 Table 3.39 However.There are two aspects to cessation: making a quit attempt and maintaining cessation.41 Gender as a predictor of success 12 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 12 . Two prospective studies (including over 13.39 Prior quit attempts38.39 Definition Low Heaviness of Smoking Index (variable of number of cigarettes smoked per day and time to first cigarette) or smoking less than daily Quit date set or strong desire to quit Longest time off smoking in the past ≥6 months Tried to quit during previous year Assessed by length of education or income No smoking within 2 weeks of attempt Increased quit attempts + Increased cessation success + Predictors of quitting and maintained cessation High motivation34. as assessed by length of time to first cigarette of the day and number of cigarettes smoked per day.40 + + + + No data Small effect + – + + The recent International Tobacco Control (ITC) Four Country Survey and the Community Intervention Trial for Smoking Cessation (COMMIT) trial found some evidence for higher successful cessation rates among men. Predictors of quit attempts and cessation success Predictive factor Low nicotine dependence34.000 smokers) found that nicotine dependence was the key predictor of cessation success.38.39 Longer prior attempt38.39 Higher socioeconomic status34 Initial success38.34.34. a systematic review did not show that the relative benefits of different smoking cessation interventions varied by sex.38. the potential impact of current and emerging treatments for tobacco use will depend not only on their efficacy.54 although a study of NRT and telephone counseling found no benefit. Interventions that have the greatest chance of reducing tobacco use in the population are those that reach the most smokers.48–50 Studies have found that rewardbased (quit and win) campaigns may increase quit rates. This means successful cessation can be more difficult as a result of greater exposure to cues for smoking.46. state to begin a comprehensive tobacco control program. Health care providers have an important role to play in creating practice environments that promote cessation treatment as part of routine care. and use of effective interventions include the promotion of a national quit line number on cigarette packs and the availability of more consumer-appealing cessation treatments.43 However.45 Medicare currently covers cessation counseling benefits. California was the first U. another recent trial found that giving away vouchers for nicotine replacement therapy (NRT) to smokers as part of a broader campaign increased quit rates.44 The main reason for this failure is the generally low utilization of these therapies. comprehensive advertising bans. Not much evidence is available to support the idea that therapies for treating tobacco use have dramatically influenced rates of smoking on a population level. and smoke-free policies. low-income smokers may have lower access to pharmacotherapy and other treatments that improve cessation.52 A meta-analysis of four studies found that such a policy helped an additional 2% (95% CI 0–5%) of smokers to quit. but misreporting cessation makes studying them difficult. Furthermore.51 Smoking is more widespread among lower socioeconomic groups and is a major contributor to health inequities. This is one of the reasons why past research has shown that the most potent demand-reducing influences on tobacco use have been interventions that impact all smokers repeatedly. which is in part the result of a need for health care workers to more aggressively assist their tobacco-using patients in quitting. though not over-the-counter (OTC) products such as nicotine patches and gum. and its prescription drug benefit (Part D) plan also covers smoking cessation treatments. A systematic review looked at the effect of reducing the cost of smoking cessation treatments for smokers. population-based studies have found that women with low educational levels were particularly responsive to media messages and were more sensitive to price increases than more educated women (elasticity near 1 for the period 1992 to 2002.56 Comprehensive tobacco control measures can prove effective across the population. implying that a 10% increase in price would reduce smoking by 10%).42 Fortunately.53 Similarly. and encourage those who do try to quit to use treatments that will increase their odds of staying quit. appeal.S. One large subsequent controlled study found that sending free nicotine replacement therapy to smokers who called a quit line substantially increased cessation. such as higher taxes on tobacco products. © BMJ Publishing Group 2007 13 Public policy on smoking Letterpart Ltd – Typeset in XML A Division: Text F Sequential 13 .55 Moreover.47 Other strategies that can increase the reach. pack warnings. but also the extent to which these treatments reach those who might benefit from them. with several new treatments in the pipeline.47 These hold great untapped potential to reduce overall adult smoking prevalence and growing disparities in tobacco use in the future.Efforts to increase smoking cessation at the population level involve interventions that convince smokers to make quit attempts. hard-hitting anti-tobacco education campaigns. effective treatments for tobacco use are available.46. 6% to 19. and spent considerably more than other states per head on tobacco control during the 1990s. The Institute supported local efforts. and indoor public places Enact comprehensive bans on tobacco advertising. increased funding and coordination of state activities.48 The study found that increased taxation accounted for most of the reduction. Food and Drug Administration (FDA).57 In New York. limitations on advertising. and educational levels.60 Table 4. increased cigarette taxes. across both sexes and among all age groups. In order to establish an environment conducive to reducing tobacco use. although out-of-state purchase of tobacco reduced the benefit. This resulted in higher rates of cessation among younger and to a lesser extent middle-aged smokers than in other states. but also advised giving regulatory authority to a federal agency such as the U. public transport.59 The first proposed step was to strengthen traditional tobacco control measures and the second to change the current regulatory landscape. the Institute of Medicine (part of the National Academy of Sciences) issued a report recommending a two-pronged approach to reducing tobacco use in the United States. and individual sellers + + + + + + 14 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 14 . increased provision of cessation services. because other interventions have not been implemented to the degree necessary to achieve major change.2% during 2002 and 2003. for example. The FCTC commits countries to implement a comprehensive range of policies (see table 4).S. decreased nicotine content of cigarettes. Suggested actions included stepped-up health warnings.4% by 2010. obligate the placement of rotating health warnings on tobacco packaging that cover at least 30% (but ideally 50% or more) of the principal display areas and include pictures or pictograms Regulate the testing and disclosure of the content and emissions of tobacco products Promote public awareness of tobacco control issues by ensuring broad access to effective comprehensive educational and public awareness programs on the health risks of tobacco and exposure to tobacco smoke Promote and implement effective programs aimed at promoting the cessation of tobacco use Combat smuggling. and education were credited with reducing the prevalence of smoking. restaurants. and public places would reduce the prevalence of smoking by 3. Key policy provisions of the Framework Convention on Tobacco Control (FCTC) + + + + + Increase tobacco taxes Protect citizens from exposure to tobacco smoke in workplaces. and sponsorship Regulate the packaging and labeling of tobacco products to prevent the use of misleading and deceptive terms such as light and mild Regulate the packaging and labeling of tobacco products to ensure appropriate product warnings are communicated to consumers. which is the first global health treaty negotiated under the auspices of the World Health Organization (WHO). which fell from 21.58 Projections predict that a total smoking ban in workplaces. over 140 countries have ratified the Framework Convention on Tobacco Control (FCTC). Simulation modeling found that the largest reductions in smoking prevalence in the United States between 1993 and 2003 have come from price increases. higher tobacco taxes. ethnicities. growers. In May 2007.including price increases and mass media campaigns. including a free nicotine patch program. including the placing of final destination markings on packs Implement legislation and programs to prohibit the sale of tobacco products to minors Implement policies to support economically viable alternative sources of income for tobacco workers. smoke-free legislation. and a national ban on indoor smoking. promotion. FDA-approved nonnicotine-based drug treatments include bupropion and varenicline.6.5.to 2-fold. Other effective drugs include nortriptyline or clonidine.62 Bupropion increases odds of smoking cessation 2-fold. inhaler. hunger.66 Two recent high-quality systematic reviews found all forms of NRT to be effective. anxiety. gum. or lozenge.61 Nicotine-based therapies are available as transdermal patch. found that NRT achieved an overall © BMJ Publishing Group 2007 15 Nicotine replacement Letterpart Ltd – Typeset in XML A Division: Text F Sequential 15 . impatience. although of high quality. difficulty concentrating.Interventions for smoking cessation Both nicotine. Comparison of FDA-approved drug therapies for smoking cessation Mechanism of action Efficacy compared with: placebo or control therapy NRT increases odds of smoking cessation 1.7-fold compared to bupropion**65 * NRT: nicotine replacement therapy ** All studies included in this systematic review. craving.62 The first review.65 Nicotine replacement therapy (NRT) reduces the withdrawal symptoms associated with smoking cessation.6.64 N/A NRT* bupropion varenicline Effectiveness of drug treatments NRT Reduces nicotine withdrawal symptoms NRT and bupropion seem equally efficacious 63 No RCTs Bupropion Antidepressant or independent neurologic effects64 Bupropion and NRT seem equally efficacious63 N/A Varenicline increases odds of smoking cessation about 1. such as anger. with follow-up of at least 6 months. nasal spray. or restlessness.62. received industry funding from the varenicline manufacturer Pfizer. but side effects may limit their use.and nonnicotine-based therapies can increase the chances of successful smoking cessation.7-fold compared to bupropion**65 N/A Varenicline Partial nicotine receptor agonist Varenicline increases odds of smoking cessation 3-fold**65 No RCTs Varenicline increases odds of smoking cessation about 1. Table 5. and the population included in the trial.68 Side effects of NRT include local irritation. although most trials of NRT have included some type of nonpharmacologic support. is generally used as the base product. the manifestation of which depends on route of administration. However. Relapse rates did not differ between NRT and control groups over time or depend upon length of initial NRT treatment or length of final follow-up.62 It found little good evidence that NRT was effective for people who smoke fewer than 10 to 15 cigarettes daily.62 As a result of concerns regarding the sympathomimetic effects of nicotine. In current clinical practice.abstinence rate of about 17% compared with 10% in the control groups. costs. with other shorter-acting forms used as add-ons. using only 6 to 12 months of results. with its long-acting effect because of stable nicotine blood levels. depending on the length of follow-up.3 years of follow-up. Another trial compared four different formats of NRT and found that women were more successful with inhaler compared with gum and men vice versa. whereas highly dependent obese people from a nonwhite background had higher cessation rates with the spray.6 Relative efficacy of NRT over and above placebo fell from 11% at 1 year to 7% at an average of 4.62 Patient preference. 16 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 16 . An additional cohort study found that nicotine patches were more effective in achieving long-term cessation (52 weeks) in smokers with moderate nicotine dependence compared with those with mild or high dependence. how cessation was assessed.40 The review found no evidence that one form of NRT is preferable or that additional counseling offered any benefit. as usually reported in reviews and guidelines.69 Higher doses of the patch (> 22 mg/day or > 15 mg/16 hours) may be slightly more efficacious than standard dosage. or side effects may be considerations when choosing NRT. but treatment beyond 8 to 12 weeks did not improve efficacy.6. NRT appears to be generally safe in patients with a history of stable cardiovascular disease.70 Higher doses may be useful for heavy smokers (≥ 30 cigarettes/day) or patients relapsing with withdrawal symptoms on standard dosage. The second review looked at a follow-up of more than 1 year after the start of treatment. there was considerable variation in control group abstinence rates.62 An additional trial looked at nicotine patches compared with nasal spray and found no significant difference in abstinence between the two treatments at 6 months. most studies have excluded people with unstable cardiac disease.62 However. the patch. NRT has an FDA Category D rating in pregnancy. it found that positive predictors for the patch were different compared with the nasal spray: low to moderate dependency smokers with white ancestry and a BMI less than 30 kg/m2 were more successful with the patch. also found increased 1-year success rates associated with a higher dose patch. The low relapse rates after the second year showed that NRT had a permanent effect on smoking cessation. One multicenter European trial. which looked at higher doses and longer durations of treatment. will result in overestimating the lifetime benefits and cost savings from NRT by about 30%.67 However. The first review observed that the main factor determining the effectiveness of NRT on quit rates was the level of nicotine dependence. 4 mg: $105 to $279 1 patch per day: + Generic 7.82 √ Throat irritation. Nicotine replacement therapy* Pre scription only Dose/Regime** Side effects Approximate cost of 30 days of treatment***71 9 to 24 doses per day: + Generic 2 mg: $54 to $144. 14 mg per day for 2 weeks.79 Over-thecounter Bad taste. jaw pain. 1 every 4–8 hours for weeks 10–12. dyspepsia. mouth irritation. 14 or 21 mg: $67. or 21 mg: $97. cough. gastrointestinal disturbances. 4 mg: $68 to $180 + Nongeneric 2 mg: $93 to $248. but at least 8 doses per day + Gradually reduce over weeks 9–14 + Maximum dose: 5 doses per hour or 40 doses per day72. 7 mg per day for 2 weeks72–74 Mouth irritation.76 Skin irritation62.83 6 to 16 cartridges per day: + Nongeneric: $148. dyspepsia62. some insurance plans cover the cost of smoking cessation treatments .00 to $395 Lozenge √ A Division: Text Nasal spray F Oral inhalator (for buccal absorption) Sequential 17 *in the United States ** dosing in this table is based on manufacturers’ recommendations 17 *** Prices should be used for comparative purposes only.81 9 to 20 lozenges per day: + Generic 2 mg: $150 to $334. maximum: 24 pieces per day72–75 + >10 cigarettes per day: 21 mg per day for 4–6 weeks.00 + 2 mg if < 25 cigarettes per day or + 4 mg if ≥ 25 cigarettes per day + 1 every 1–2 hours for 6 weeks. bad taste. 78 √ Nasal/sinus irritation.76. oral burning.79 + + + + One 10-mg cartridge delivers 4 mg nicotine 6 to 16 cartridges per day for weeks 1–12 Gradually reduce over next 6 to 12 weeks Maximum dose: 16 cartridges per day72.00 + Nongeneric 7. 14. hiccoughs. nocturnal use of patch may be associated with sleep disturbances: consider removal of patch at night 77 Gum √ © BMJ Publishing Group 2007 Patch √ Letterpart Ltd – Typeset in XML + 2 mg if smokes first cigarette > 30 minutes after waking up or + 4 mg if smokes first cigarette within 30 minutes after waking up + 1 every 1–2 hours for 6 weeks. 4 mg: $128 to $284 + Nongeneric 2 or 4 mg: $152 to $338 8 to 40 doses per day: + Nongeneric: $82 to $408 + One dose equals 2 sprays (1 per nostril) (0. orodental problems62. 1 every 2–4 hours for weeks 7–9. nausea. 7 mg per day for 2 weeks + ≤ 10 cigarettes/day: 14 mg per day for 6 weeks. 1 every 2–4 hours for weeks 7–9.Table 6. runny nose62. hiccups 76.5 mg per spray or 1 mg nicotine per dose) + 1 or 2 doses per hour for 6 to 8 weeks. 1 every 4–8 hours for weeks 10–12 + Maximum dose: 5 lozenges in 6 hours or 20 lozenges per day72. either alone 9.4-fold higher with combination than monotherapy.There is weak evidence that combination NRT may be more effective than single forms.2 Abstinence rates Significantly higher with combination early on. either alone 3% 7% 0.9% (spray) (at 6 months) 14% 0.1 Patch + inhaler vs. inhaler alone 19. abstinence rates were 1.3 Patch + inhaler vs.8 18 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 18 .1% (at 6 months) + 7.077 Patch + nasal spray vs. trend continued but no significant difference between groups at 1 year62 Significantly higher with combination at 1 year62 Trend continued but no significant difference between groups at 6 years85 No significant difference between groups at 6 months62 Significantly higher with combination at 12 weeks.84 Table 7.62 Overall. Possible benefits include sensory effects of multiple delivery systems.2 Patch + nasal spray vs. no therapy 15% 14% 0.8% (patch) + 6. patch alone Combination therapy 18% Monotherapy or no therapy 13% P value 0. trend continued but no significant difference between groups at 1 year62 No significant difference between groups at 1 year62 No significant difference between groups at 1 year62 Combination NRT Patch + gum vs.5% 0.002 16% (at 6 years) 9% (at 6 years) 0. but no significant difference between groups at 1 year62 Significantly higher with combination at 12 weeks. One-year abstinence rates with combined NRT delivery * Combination used Patch + gum vs. higher nicotine substitution. gum alone 24% 17% 0.2 Patch + inhaler vs. patch alone 27% 11% 0. or other factors. or setting in which NRT was given. Bupropion and nortriptyline appear to be about equally efficacious with NRT.93 Initial trials suggest that bupropion may be less efficacious than varenicline.94. Possible. a nicotine receptor antagonist. mechanisms of action include: + improving depressive symptoms precipitated by quitting smoking + substituting for possible antidepressant effects of nicotine + independent neurologic effect(s).62 One trial showed that NRT plus physician training improved quit rates over physician training alone.64 The opioid antagonist naltrexone is under investigation as an adjunct to treatment such as NRT and may attenuate smoking cessation-associated weight gain. As for many older drugs. intensity of other support. A recent trial has shown it to be effective and safe in people with acute cardiovascular disease. such as nicotine receptor antagonism. although so far all relevant high-quality trials have received industry funding from varenicline’s manufacturer. or clonidine.92 Extended therapy with bupropion to prevent relapse has not been found to be beneficial. to NRT may be superior to NRT alone. Bupropion has been shown to be effective in varied populations and settings. in people with and without depression. anxiolytics.*based on trials including 100 to 500 smokers. but symptoms rebound when bupropion is discontinued.63 There is also insufficient evidence about combining an antidepressant and NRT. a systematic review found the relative benefit of NRT to be mostly independent of length of therapy. One small trial found that bupropion was associated with higher smoking cessation rates at 6 months compared with nortriptyline or placebo when each was added to intensive counseling therapy.65 Since May 2006. nortriptyline has not been rated by its manufacturer but has received Pregnancy Category C listings.87–89 There is no good evidence about combining NRT with varenicline. Combining NRT with other drug treatments Although the absolute chances of quitting increase when NRT is used in conjunction with additional support. but direct comparisons are few. bupropion has an FDA Pregnancy Category C rating.64 Bupropion is a selective serotonin/norepinephrine uptake inhibitor (SSNRI) and nortriptyline is a tricyclic antidepressant (TCA). exceptions to 1-year time frame noted in table Two small studies suggest that adding mecamylamine.90 Adding NRT to nondrug therapy Monotherapy with either bupropion or nortriptyline approximately doubles the odds of smoking cessation at 6 months.91 It decreases depressive symptoms in highly nicotinedependent smokers.95 One cohort study of predictors of abstinence in people who were receiving long-term sustained release bupropion. and in combination with different types of behavioral support. but unproven.64 Nortriptyline has been studied in fewer trials than bupropion. found that older age and minimal early weight gain were © BMJ Publishing Group 2007 19 Antidepressants Letterpart Ltd – Typeset in XML A Division: Text F Sequential 19 .86 A benefit from adding antidepressants to NRT has not been shown. previous use of NRT.60.101 Varenicline increases smoking cessation approximately 3-fold at 1 year compared with placebo. then 150 mg twice daily + Continue treatment total 7–12 weeks107 + Total dosage in studies has generally been 75–100 mg daily for 6–12 weeks64 + Dry mouth. shorter previous quit attempts. lobeline.99.100.97 One cohort study looked at bupropion and nicotine patches in combination and concluded that positive predictive factors for continued abstinence at 1 year were:98 + Absent history of COPD + Having effectively quit after the first week of treatment + In people with COPD: lower value for mid-range forced expiratory flow (FEF 25–75) Antidepressants such as selective serotonin uptake inhibitors (SSRIs) or monoamine oxidase (MAO) inhibitors have not been shown to help smoking cessation.60 A systematic review found that compared with bupropion. Like varenicline. risk of arrhythmia64 Nortriptyline 20 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 20 .106 Table 8. Cytisine is the natural chemical from which varenicline was developed. is less well studied but may also aid smoking cessation.96 One randomized control trial found that risk factors for relapse in people treated with bupropion and counseling (in varying dosages and intensities) were younger age. which usually improves over time. high levels of nicotine dependence. urinary retention.109 + Seizure (1/1000 when used for smoking cessation)64 + Has not been linked to increased risk of suicide. but has a considerably lower price. it works as a nicotine partial receptor agonist.65 The main side effect has been nausea.positive predictive factors for long-term abstinence (52 weeks).7-fold at 1 year. sedation 108.64 but all antidepressants are labeled with a Black Box warning about possibly increased risk + Sedation.65. Nonnicotine drugs for smoking cessation FDAapproved for indication Bupropion SR √ Dose Side effects Nicotine partial receptor agonists + Set target quit date for during second week of treatment. Varenicline has been given an FDA Pregnancy Category C rating. + 150 mg daily x 3 days.104 Direct comparisons with NRT are lacking. although this result is based on studies that have received industry funding. constipation.103. varenicline increased the odds of smoking cessation approximately 1.102 It is not clear whether further lengthening the duration of therapy would be beneficial or whether varenicline may help prevent relapse.64. and self-reported depression. female sex.105 There have been no good quality trials about a third partial nicotine agonist. It is currently only available in Europe. which limit its use.01). Products include smokeless inhalers. However. headache60. they may bypass regulatory oversight and are not regulated by the FDA.26.5 mg once daily for 3 days then twice daily days 4–7 + Increase to 1 mg twice daily from day 8 through end of 12 weeks total therapy104 + Nausea. based on concern about psychiatric side effects. has been studied mostly in conjunction with behavioral counseling. buspirone improved smoking abstinence in high-anxiety smokers. a centrally acting antihypertensive agent.FDAapproved for indication Varenicline √ Dose Side effects + Set a target quit date for 1 week after starting treatment + 0.110 Hypertensive patients in particular are at risk for rebound hypertension upon abrupt cessation.104 Other drug therapies + Clonidine. + There have been no systematic reviews or good quality trials evaluating the efficacy of rimonabant (a CB1 cannabinoid receptor antagonist) for smoking cessation. OTC devices and aids for smoking cessation The purpose of current drug therapies for smoking cessation is to either replace nicotine from cigarettes with nicotine in safer forms or try to otherwise reduce © BMJ Publishing Group 2007 21 Under investigation: Nicotine conjugate vaccine Letterpart Ltd – Typeset in XML A Division: Text F Sequential 21 . sleep disturbances.113 Many smoking cessation devices or aids are sold OTC in the United States. the confidence intervals were compatible with both clinically significant benefit and possible negative effect (OR 1. We found no high-quality evidence that these products work. If not specifically marketed as a cessation tool. but only for the duration of therapy.112 In one trial. + Silver acetate gum. + There is no consistent evidence that anxiolytics aid smoking cessation. possibly because of reportedly poor compliance. or spray causes an unpleasant taste when combined with cigarettes. especially dry mouth and sedation.87 Adding naltrexone to NRT did not attenuate weight gain in smoking cessation.111 Limited data do not support a role for it. nicotine filtering devices. It is marketed in Europe. + Limited evidence from four trials identified by a systematic review found no significant long-term benefit for smoking cessation from the opioid antagonist naltrexone compared with placebo.80–2. but had side effects. and a water-soluble gel containing tobacco extracts. 95% CI 0. it increased smoking cessation approximately 2-fold. Based on limited data. lozenge.108 Tapering of dosing at the end of therapy is recommended to avoid withdrawal effects of clonidine. but in June 2007 the FDA refused approval for its use as a weight loss aid.69. in combination. and 6 months. 100. but the absolute benefit may be similar. + The effectiveness of rapid (aversive) smoking is unproven.withdrawal symptoms.and computer-based programs may offer some benefit. or 200 µg) intramuscularly or placebo at approximately 0. or along with drug therapies. or acupuncture increase cessation. + Self-help materials and brief advice both increase the chances of smoking cessation. Self-help materials and group behavioral counseling may not offer additional benefit when added to NRT. but because of the high number of contacts with health care professionals. particularly if the importance of follow-up is emphasized. self-help materials may not offer additional benefit when more intensive interventions are used.114 Vaccine is conjugated because ordinarily nicotine is a small. group. Nicotine conjugate vaccine is currently in Phase IIb trials in the United States but achieving adequate antibody response and duration of antibodies remain challenges in its development. 22 © BMJ Publishing Group 2007 Effectiveness of nondrug treatments for smoking cessation Letterpart Ltd – Typeset in XML A Division: Text F Sequential 22 . When provided with NRT. given the additional benefits. + It is not clear which interventions reduce relapse. In one small study. + Exercise reduces symptoms of withdrawal. individual counseling offers a lower relative benefit than on its own. Similarly. + Internet. delivery systems such as doctor counseling and/or quit lines with access to drug treatments are significantly more effective than nondrug treatments alone. A vaccine currently in development aims to induce nicotinespecific antibodies in order to prevent nicotine’s passage into the brain. + Providing telephone quit lines increases cessation. However. + Individual. but more research is needed to identify effective programs. Training health professionals may offer some benefit. and telephone counseling are effective at a patient level and are recommended for those willing to accept them. patients received either a nicotine conjugate vaccine given as one of 3 doses (50. The benefit per patient is low. 2. There is good evidence that combining brief practical advice to quit with pharmacotherapy increases success rates. + There is no good evidence that biomedical risk assessment. 1. self-help materials and brief advice both offer an important opportunity to promote cessation with potentially large population effects. Nonpharmacologic measures can be used singly. hypnotherapy. Although evidence for long-term cessation is less clear. nonimmunogenic molecule.115 Vaccine immunogenicity and 30-day abstinence rates were dose-related. it can be recommended. 121 Although the relative benefit appeared lower when used in conjunction with NRT.120 Individual counseling + One review found that individual counseling by nurses increased quit rates about 1.121 © BMJ Publishing Group 2007 23 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 23 . + However. Most studies have been conducted in a primary care setting. Brief advice + Any interaction with a health care professional is an opportunity to provide brief advice.7-fold (absolute increase of about 2. and nurses. + In one review. + Self-help materials are an easy intervention. + Individual counseling by physicians seems to be most effective. whether tailored or not. whereas there was no evidence of benefit in other hospitalized smokers.117 + The absolute benefit in trials of brief advice is lower than in trials involving highly motivated people.117 Brief advice may be given by a physician or nurse. + One subsequent trial found that individual counseling (primarily in person but allowing phone counseling) was more effective than advice and minimal support for abstinence at 6 months. followed by multidisciplinary teams.5%) compared with no advice (or usual care). Nurse counseling offered a larger relative benefit for inpatients with cardiovascular disease and when offered as part of cardiac rehabilitation. defined as > 20 minutes. there was no evidence that self-help materials would be of benefit when added to NRT or face-to-face contact.5-fold compared with no intervention (absolute difference about 2%). Nondrug treatments for smoking cessation Intervention Evidence Clinical implications Self-help materials + In one review.122 + Another subsequent RCT found 5-fold higher cessation after 6 and 12 months with motivational interviewing than with brief advice.5-fold. although the evidence was not conclusive. + Forty smokers would need to be given intensive rather than minimal advice to produce one extra quitter after 6 to 12 months. self-help materials.Table 9. + One recent subsequent UK trial found no significant difference between basic and weekly support added to NRT. increased long-term abstinence about 1.123 Smoking cessation counselor + Most trials were conducted with inpatients. dentists. + The review found no evidence that intensive counseling was more effective than shorter sessions.116 Tailored materials might be more effective than standard materials. the absolute benefit appeared to be similar in trials with and without NRT. The review did not report on harms. and should be readily available in the office and offered to all smokers. + There is possibly a small benefit to follow-up visits. but the evidence was not conclusive. or a self-help manual) over minimal advice. + The review did not look at potential harms from physician counseling.119 + One review found that individual counseling by a trained smoking cessation counselor providing one or more face-to-face sessions outside of usual care increased cessation about 1. more visits. + There appeared to be a small advantage of intensive advice (longer.5-fold. + Brief advice is an easy intervention and has the potential to have a large population impact. brief advice increased the odds of quitting approximately 1.118 NRT use in the trials varied considerably. Exercise Biomedical risk assessment + Evidence is limited about biomedical risk assessment (e. + The number of calls. + Among visitors to a smoking cessation website.132 Complementary interventions + There is no evidence that hypnotherapy.130 + Exercise reduces post-smoking cessation weight-gain.124 Similar results were found for telephone counseling not initiated by calls to help lines.128 + The evidence is not conclusive on how group programs compare with individual counseling. + More research is needed to evaluate the efficacy of biomedical risk assessment. + A single session of exercise seems to temporarily reduce cigarette craving. laser therapy. + The review suggested that adding group behavior therapy to NRT provided no additional benefit.135 24 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 24 .Intervention Evidence Clinical implications Telephone counseling + One recent systematic review found that smokers who received additional call back counseling after phoning a quit line were about 1.126 Group behavior therapy + Patient acceptance of group therapy may vary. group programs were about twice as effective as self-help programs or no intervention. or electrostimulation help quit rates.125 Telephone quit lines Internet + More research is needed about which patients benefit.4-fold more likely to quit (absolute difference about 3%).130 + One trial identified by the systematic review suggested that adding exercise to NRT may be of benefit. + There was a small benefit from adding telephone counseling to NRT.134. and duration varied considerably between different quit lines. The study suggested that increasing the number of calls increased the benefit. light smokers benefited the most from telephone counseling initiated by health care personnel and added to other minimal interventions. spirometry). + One review found limited evidence that providing a telephone hotline helped 1 in 50 extra smokers to quit. how to add internet to other interventions and use of the internet in sophisticated or interactive ways.131 + Even with weak evidence of effectiveness of increased smoking cessation. which include information on health risks and coping strategies. exercise offers a wide range of other benefits. + Cost effectiveness compared with individual counseling is not clear. alone or added to a smoking cessation program.g.126 It is not yet clear how well more recent interactive computer systems work. male.133 acupuncture.128 + Evidence is lacking about specific psychological methods aside from usual support. may be more effective than a shorter program with more information on nicotine replacement therapy and nicotine dependence127 + In one review.129 but a systematic review found only weak evidence that exercise improved quit rates.124 + In early studies. + A meta-analysis suggested that younger. + These measures cannot be recommended for smoking cessation on the basis of current evidence. mailing computer-generated feedback reports was associated with improved quit rates. + Studies have been small and heterogeneous. acupressure. counseling letters and email reminders based on psychological and addiction theory.. their content. but the control groups included behavioral components that may have affected the results. exhaled carbon monoxide. 117 + In one review. reminder letters) and teamwork increased rates and effectiveness of counseling and increased quit rates. flow charts.136 Aversive smoking + There is sufficient indication of promise to warrant further evaluation of this technique.Intervention Nondrug treatments for relapse prevention Evidence + There is no evidence that skills training (e. It is not clear if this improves quit rates.62..g.138 Interventions aimed at health professionals + Training health professionals on a group basis and offering prompts may increase the chance of smoking cessation interventions being offered to patients.90 The trial with the most promising result emphasized follow-up more than other trials and physicians were paid for follow-up visits.g.137 + The studies in one review mostly included only brief or written interventions. prompts increased how often smoking cessation interventions were offered.136 + The available evidence does not allow determination of the effectiveness of rapid (aversive) smoking.138 Clinical implications + Many patients relapse. questionnaires. avoidance of triggers) or other specific interventions prevent relapse136.139 [See Toolkit: 12-step guide to a primary care systems approach for smoking cessation] © BMJ Publishing Group 2007 25 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 25 . so a benefit from more intensive face-to-face contact can not be excluded. chart stickers. Another review found limited evidence that tools (e. checklists.. thus effective strategies are greatly needed. the cost per year of life saved with nicotine treatments and bupropion across different age groups fell substantially below the generally accepted thresholds for cost effectiveness in the United States. This has not supported informed decision making. Results based on these measures provide a key input into cost-effectiveness analyses. whereas NRT plus counseling cost $8794. with a cost of $0 per year of life saved.S. the health provider or society. It found that counseling or self help (with smokers choosing between them) cost $2340 per year of life saved. These interventions do not have large effects and the extra investment in intensive interventions can achieve additional benefit and offer a superior return compared with many interventions that are routinely paid for in other fields.The massive toll of smoking measured in morbidity and mortality is reflected in a large economic burden on society. assessing cost effectiveness can be difficult because of variations in study populations and their motivation to quit. The health industry benefits from reduced expenditure attributable to both primary and secondhand smoke. A review looking at U. Cost effectiveness of smoking cessation can be analyzed from the perspective of the individual. For those populations without pre-existing disease. dollars) and found that standardizing the measures used in studies often increased the cost-effectiveness ratios substantially.5 billion in health care costs alone. as well as extrapolation of relapse rates and baseline cessation rates. this has been estimated for 1998 at $75. the outcome measures in clinical studies of cessation are varied and sometimes difficult to assess. Although the least intensive interventions may offer the best cost effectiveness ratio. Furthermore. This makes calculations particularly sensitive to how future costs and benefits are discounted. Beyond this. Studies have approached these issues in different ways and are not always clear about their perspective and which costs they have included. reduced cost of cleaning up after smokers. In the United States. However. The individual saves through reduced expenditure on cigarettes. their low cost and the extremely large potential gains do not mean they should be selected in preference to more intensive interventions. which makes it hard to reach and interpret definitive conclusions. smoking interventions still remained clearly cost effective. lower private health care costs.141 Despite this.S. the benefits may be measurable only decades down the line. and fewer smoking-related fires.142 Economic issues in smoking cessation 26 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 26 . there are costs in terms of lost productivity estimated at $81. The review identified a self-help manual written for a specific subgroup of pregnant women as the most cost-effective intervention.140 Smoking cessation can reduce some of this burden and studies have consistently found that effective interventions for smoking cessation are cost effective. whereas society profits from increased productivity.9 billion as the annual average between 1995 and 1999. cost effectiveness from a third-party payer perspective found that in 2003. and increased income. A systematic review of cost-effectiveness studies of smoking cessation recalculated the cost effectiveness from a societal perspective (using Dutch price levels but in U. 142 Cost per year of life saved by age group ($) Age group (years) 20– 34 35– 49 50– 64 Nicotine replacement Gum Men 5976 5008 6637 Women 10.816 7882 8354 Men 2284 1914 2537 Women 4112 2997 3176 Bupropion © BMJ Publishing Group 2007 27 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 27 .758 7840 8309 Men 3661 3068 4066 Patch Women 6591 4803 5090 Men 6230 5221 6920 Spray Women 11.Table 10. Cost per life year saved for different drug therapies by age in the United States in 2003.217 8174 8663 Men 6008 5035 6673 Inhaler Women 10. S. Cigarette Smoking—Attributable Morbidity— United States. Accessed on: July 8. Cancer Epidemiol Biomarkers Prev 2005. Mortality from smoking in developed countries 1950– 2000. Boreham J. 26. Accessed on: July 8.ahrq.gov/ tobacco/data_statistics/MMWR/2006/ mm5542_highlights. Morbid Mort Wkly Rep MMWR 2003. 2007. Levy D. Centers for Disease Control and Prevention. 21.gov/nccdphp/publications/ factsheets/Prevention/tobacco. Peto R. International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans. 2007. Vollset SE.cdc. et al.cdc. 2007.ctsu.. 2004 Surgeon General’s Report: The Health Consequences of Smoking. Rothenbacher D. 2007. et al. Cochrane Controlled Trial Register. 11. Hamed H. Doll R. Smoking and prognosis in women with breast cancer. Chichester. 25.ahrq.60(2):190–193. Scientific and Technical Proceedings. Smoking cessation before diagnosis and survival in early stage non-small cell lung cancer patients.uk/~tobacco/C2450. Khuder SA. Romano E. In: The Cochrane Library. 12. Mortality in relation to smoking: 50 years’ observations on male British doctors.htm. Targeting Tobacco Use: The Nation’s Leading Cause of Death. MD. Fentiman IS. Available at: http://www. 2005. Sun B. Centers for Disease Control and Prevention.S. Accessed on: July 8. et al.cdc. Tobacco Control Reversal of Risk After Quitting Smoking. 6. Smoking and deaths between 40 and 70 years of age in women and men. Critchley J. Int J Cancer 2006. Science Citation Index. Aubry Z. Available at: http://www.2005. 2007. et al. Treating Tobacco Use and Dependence—A Systems Approach. 2007. Accessed on: July 8. 2. Dissertation Abstracts BIDS ISI Index. Smoking. Available at: http://monographs. November 2000. 23. Twardella D. Liu G. veterans: a 26-year follow-up. 2007. 2002. BMJ 2004.gov/clinic/ tobacco/systems. Nicotine replacement therapy for long-term smoking cessation: a meta-analysis. Etter J-F. Chest 2001. primary source MEDLINE. PsychLit. Lung Cancer 2005. The relationship of smoking cessation to sociodemographic characteristics. Hrubec Z. Mumford E.53:375–380. Ann Intern Med 2006. 19. 2007. 18. Appleby P.142:233–239. 2006 Surgeon General’s Report: The Health Consequences of Involuntary Exposure to Tobacco Smoke.47:165–172. reference lists of retrieved articles and contact with experts.htm.ac. Smoking and tobacco use. CINAHL. Centers for Disease Control and Prevention.52(35):842–844. Anthonisen N.118:1481–1495. Centers for Disease Control and Prevention. Sutherland I. Volume 11.5year mortality: a randomized clinical trial. 2007. Nicotine Tob Res 2005. Gjessing HK. et al. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13. Accessed on: July 8.gov/nccdphp/publications/aag/ osh. and tobacco control policies. Tobacco Smoke and Involuntary Smoking. Accessed on: July 8. Healthy people 2010 leading health indicators. EMBASE.gov/clinic/ 3rduspstf/behavior/behtab1. Lopez AD. 14. 2007. Accessed on: July 8. Duration of smoking abstinence as a predictor for nonsmall-cell lung cancer survival in women. Centers for Disease Control and Prevention. Williams E. 9. Available at: http://www.gov/mmwr/preview/mmwrhtml/ mm5235a4. U. Managed Care Organizations. 10. 24.htm.59:1051–1054. for the Lung Health Study Research Group The effects of a smoking cessation intervention on 14. Agency for Healthcare Research and Quality. Available at: http://www. Int J Cancer 1995. Lung Cancer 2006.htm. Accessed on: July 9. Available at: http://www. Peto R.14(10):2287– 2293. and Purchasers. Beral V.328(7455):1519. Centers for Disease Control and Prevention. Int J Clin Pract 2005. Blot WJ.541 women with carcinoma of the cervix and 23. Preventing Tobacco Use. Zhou W. 20.120:1577–1583.gov/tobacco/data_statistics/sgr/ sgr_2004/index. Morb Mortal Weekly Rep MMWR 2006.pdf. Available at: http:// www. Accessed on: July 8.cdc. Ann Intern Med. 15.htm.144:381–389.pdf. Tob Control 2006. Available at: http://www. UK National Research Register. smoking intensity. Tobacco Use Among Adults—United States. Smoking cessation for the secondary prevention of coronary heart disease (Cochrane Review).017 women without carcinoma of the cervix from 23 epidemiological studies. International Agency for Research on Cancer (IARC) Handbooks of Cancer Prevention.ox. Accessed on: July 8. 2000. Gritz ER. 5. 2007. Berrington D. Available at: http://www. Mutgi AB. Stapleton JA.cdc. 2007.7(3):387–396. Centers for Disease Control and Prevention. A Guide for Health Care Administrators. 3. Available at: http:// www. 2004. Insurers.cdc. 8. 22. At a Glance 2006.gov/tobacco/data_statistics/ tables/adult/table_2. Agency for Healthcare Research and Quality. 83.15:280–85. 2005.htm. Tverdal A. 16. Search date: 2003. McLaughlin JK. 7. UK: John Wiley & Sons Ltd. 4.gov/tobacco/data_statistics/sgr/ sgr_2006/. Accessed on: July 9. Heist RS. Public Health Service. the missing drug interaction in clinical trials: ignoring the obvious. Capewell S. Skeans M.iarc. Boreham J.cdc.References 1. et al. Effect of smoking cessation on major histologic types of lung cancer. 2007. 17. Available at: http:// www. 2006. et al. Allen DS. The underestimated impact of smoking and smoking cessation on the risk of secondary cardiovascular disease events in patients with 28 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 28 . Rockville. Wise R.htm. Hahmann H. 2003.htm.55(42).fr/ENG/Monographs/ vol83/volume83. Smoking and cancer mortality among U. Issue 4. 13. 156(11):994–1001. Br J Gen Pract 1996. Croyle R. Smoking and lung function of Lung Health Study participants after 11 years. Liu SY. Teijink JA. American Lung Association. Am J Health Promotion 2007.lungusa.cms. 48. et al. Am J Public Health 2005.32:202–209.2(2):63–74. 40.94:205– 210. 30. et al. et al. Text and graphic warnings on cigarette packs. et al. Connett JE. 33. Mostashari F. and the Multicenter Automatic Defibrillator Implantation Trial-II Investigators. Hyland A. Belluck P. Zhu S. Mumford E. Health consequences of reduced daily cigarette consumption. The Lung Health Study. 49. 46. Cummings KM. Issue 2. The California © BMJ Publishing Group 2007 29 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 29 . Bauer JE.166(5):675–679. Bartelink ML. Halpin H.47:887– 889. Maine city bans smoking in cars with children. McMenamin S. Am J Respir Crit Care Med 2002. Holst C. Sasco AJ.69:7–12. et al. et al. Smoking cessation: overview. primary source the Tobacco Addiction Review Group tirals register. D. Predictors of cessation in a cohort of current and former smokers followed over 13 years. et al. et al. Healthcare financing systems for increasing the use of tobacco dependence treatment (Cochrane Review) In: The Cochrane Library. Cummings KM. Am J Prev Med 2006. Curr Oncol Rep 2006. Impact of smoking cessation aids among recent quitters. MEDLINE. Hey K. Impact of the new EU health warnings on the Dutch quit line. Mahoney M. 2007. Which smokers are helped to give up smoking using transdermal nicotine patches? Results from a randomized. 53. January 19.6(Suppl 3):S363–S369.11:381–382. behavioural. Feldman HR.. and mortality: a 16-year follow-up of 19. Issue 2. MEDLINE. 37. J Vasc Surg 2005. Evidence for smoking cessation: implications for gender-specific strategies. Lancet 2005. Carlin-Menter SM. 2006. Rideout J.7:262–267. Godtfredsen NS. reference lists of relevant reviews and identified studies.30:217–224. Tob Control 2006. Am J Respir Crit Care Med 2000. Hyland A. Accessed on: July 8. Smoking and the patency of lower extremity bypass grafts: a meta-analysis. the Cochrane Central Register of Controlled trials (CENTRAL). Anthonisen NR. et al. Kerker BD. EMBASE. 54. Hammond D. et al. Li Q. Fiore M. double-blind.17:931–936. smoking cessation. 47. Murray RP. 39. 45. Am J Public Health 2004. 2002–2003. Giving away free nicotine medications and a cigarette substitute (Better Quit) to promote calls to a quitline.15(3):iii83–94. stable coronary heart disease: prospective cohort study.asp. Kinjo K.43:54– 65. 2007. 36. Severens JL. Biener L. Compton C. Preventing 3 43. Hyland A. Pierce JP. Am J Epidemiol 2002. Messer K. Tob Control 2005. Tob Control 2006. Miller N. Connett JE. primary source the Tobacco Addiction Review Group trials register. Waller LA. 41. Simons C. Tob Control 1998. Sakata Y. Available at: http://slati. 2007. Zeeman G. Jones L. UK: John Wiley & Sons Ltd. New York Times. UK: John Wiley & Sons Ltd. McNitt S. Current and emerging treatment approaches for tobacco dependence. Search date: 2003. Cigarette smoking and the risk of supraventricular and ventricular tachyarrhythmias in high-risk cardiac patients with implantable cardioverter defibrillators. Wakefield. 2007:2. 50. 29. Nicotine Tob Res 2004. et al. Ann Rev Public Health 2005. 44. Stayner L. Yudkin PL. 56. placebo-controlled trial. and health determinants of successful smoking cessation: a longitudinal study of Danish adults.org/default. Levy. et al. 51. et al.14:166–171. Psychosocial. Impact of UK policy initiative on use of medicines to aid smoking cessation. EMBASE. 31. Gitchell A. 28.46:145–148.hhs. Centers for Medicare and Medicaid Services. 42. Search date: 2004.95:1016–1023. 2007. State Legislated Actions on Tobacco Issues (SLATI). DiMarino ME. 52. West R. Lung cancer risk and workplace exposure to environmental tobacco smoke. Reimer RL. Available at: www. J Epidemiol Community Health 2006.26:583–599. Frieden TR. Kaper J. et al. and contact with experts. Bena J. Wagena EJ.8:475–483.365:1849–1854. Adult tobacco use levels after intensive tobacco control measures: New York City. Curry S.12:60–67. Borland R. Scanlon PD. Worldviews on Evidence-Based Nursing 2005. The impact of nicotine replacement therapy on smoking behavior. Li Q. Moss AJ.42:67–74.15:472–480. Smoking cessation and lung function in mild-tomoderate chronic obstructive pulmonary disease.60(Suppl II):ii20–ii26. 34.27. The costs and effectiveness of different benefit designs for treating tobacco dependence: results from a randomized trial. 55.97(3):545–551. Smoking reduction. Effectiveness of a large-scale distribution programme of free nicotine patches: a prospective evaluation. Circ J 2005. Sato H. et al. Willigendael EM. et al. Prescott E. Chichester. Impact of smoking status on long-term mortality in patients with acute myocardial infarction.161:381–390. Frieden TR. Tob Control 2002. J Public Health Manag Pract 2006. Celestino PB. Am J Public Health 2007. 32. Tobacco control policies and smoking in a population of low education women.732 men and women from The Copenhagen Centre for Prospective Population Studies. Willemsen MC. Levin RF. CINAHL and PsychINFO. Osler M. Bjartveit K. Quit and win contests for smoking cessation (Cochrane Review) In: The Cochrane Library. J Am Coll Cardiol 2006. et al. 1992–2002. 38. et al. Goldenberg I. Accessed on: July 9. million premature deaths and helping 5 million smokers quit: a national action plan for tobacco cessation. Bauer JE. Individuallevel predictors of cessation behaviours among participants in the International Tobacco Control (ITC) Four Country Survey. Inquiry 2006. Perera R. 35. Fong GT. Tverdal A. 57. et al. Borland R. Chichester. Lancaster T.gov/SmokingCessation. Prescott E. et al. Singleton JK. J Cardiovasc Electrophysiol 2006. Sood A. UK: John Wiley & Sons Ltd.html. et al. WHO. A brief review of pharmacotherapies for smoking cessation. Available at: http://www. Available at: http:// 164. journals. Hays JT. 64. March 25.co. 60. Wallace RB. Marsh H. 30 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 30 . Accessed on: July 9.asp?CID=2038&DID=7028&DOC=FILE. UK: John Wiley & Sons Ltd. Stratton K. Rukstalis M. 2007. eds. Washington. Stead L. 2007:487–508. Board on Population Health and Public Health Practice. Accessed on: July 8. Individual differences in preferences for and responses to four nicotine replacement products. and Consequences. Cohen SJ. Eur Resp J 1999. and contact with experts. Dimoulas P. Tob Control 2007. Ending the Tobacco Problem: A Blueprint for the Nation. Ebbert JO. Ann Intern Med 2004. Stratton K. 77. Med Lett 2006. Available at: http:// books. 59. 67. Antidepressants for smoking cessation (Cochrane Review) In: The Cochrane Library. Product Information. 2007.com.109.who. 71. FDA approves nicotine nasal spray. Hughes JR. Barriers. Lerman C. et al. 68.edu/books/0309103827/html/ index. Available at: http://www. Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. 2003. reference lists of previous trials and overviews.nap. DC: The National Academies Press.58. Issue 3.fcgi?rid=hstat2. A replication and extension. Accessed on: July 9. 2007:487–508. GlaxoSmithKline. Psychopharmacology (Berl) 2001. Available at: http://www. West R. Stead LF.com. 2005. American Society of Health-System Pharmacists. open-label study. and Consequences.nicotrol. 2007. Lancaster T. reference lists of identified studies. 76. 2007. MEDLINE. Accessed on July 9. Higher dosage nicotine patches increase oneyear smoking cessation rates: Results from the European CEASE trial. Ending the Tobacco Problem: A Blueprint for the Nation. Wu P. 2007. Stead LF. NRT pricing information available at: www. recent reviews of nonnicotine pharmacotherapy and abstracts from the meetings of the Society for Research on Nicotine and Tobacco. World Health Organization. 65.uk). Nicotrol NS.nicorette. product information.edu/ openbook. et al.2:249–256.16:85–90.drugstore. et al. Wilson K.php?record_id=11795&page=487. Nilsson F. handsearching of specialist 66. Accessed on: July 9. 2007. PsycLIT/PsycINFO. EMBASE. 2007. MEDLINE.commitlozenge. product information. 70. Search date: 2006.nicodermcq. conference proceedings.nlm. Geneva.glaxowellcome. product information. Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12-week.com. Jae H. eds. Search date: 2006. Accessed on: July 8. Paoletti P. 2007. randomized. Treating Tobacco Use and Dependence (revised 2000): Clinical Practice Guideline 18. 80. Minnix JA. Tonnesen P. BMC Public Health 2006. Nicotine receptor partial agonists for smoking cessation (Cochrane Review) In: The Cochrane Library.ashp. et al. Gust SW.27(10):1571–1587.140(6):426– 433.gov/books/ bv.13:238–246. Accessed on: July 9. 72. EMBASE. Habitrol.4:583–589. Treating tobacco dependence: review of the best and latest treatment options. MEDLINE. 2007.html. primary source Tobacco Addiction Group’s specialised register. Wallace RB. J Thorac Oncol 2007.nih.6:300. DC: The National Academies Press. Symptoms of tobacco withdrawal. Tobacco Control Program’s effect on adult smokers: (1) Smoking Cessation. Gustavsson G. Arch Gen Psychiatry 1991. Skoog K. MEDLINE Express. Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial. 2007. Pfizer. Accessed on: May 25. 79. Accessed on: June 15. Novartis Consumer Health.nap. primary source the Tobacco Addiction Review Group trials register. Dresler CM. primary source the Cochrane Central Register of Controlled Trials (CENTRAL). et al. Agency for Health Care Policy and Research (AHCPR) Supported Clinical Practice Guidelines.48:66–68. Robinson JD. 2007. GlaxoSmithKline. Levy D. Chichester. 75.210/product. UK: John Wiley & Sons Ltd. Available at: http:// www.153(2):225–230. Available at http:// www. et al. Committee on Reducing Tobacco Use: Strategies. Varenicline (Chantix) for tobacco dependence. GlaxoSmithKline. et al. 2006. The role of public policies in reducing smoking prevalence: results from the SimSmoke Tobacco Policy Simulation Model. 2007. Science Citation Index. Lancaster T. CINAHL PsycINFO and Web of Science. Bailey WC.7644. Washington. Fiore MC. Nicotine replacement therapy for smoking cessation (Cochrane Review) In: The Cochrane Library. 63. Bonnie RJ. Accessed on: July 8. 69.com/. Kaufmann V. Hajek P. EMBASE. product information. 74. Lancaster T. Available at: http://www. Nicoderm CQ. 61.70. Issue 1. Accessed on: May 25.48:52–59.com.chapter. et al. Board on Population Health and Public Health Practice. 78. Barriers. 2007. Available at: http:// www. Chichester.org/s_ashp/ bin. 2004. J Nat Comp Cancer Net 2006. Clin Ther 2005. 62. Cahill K. 73. 81. Chichester. Commit Lozenges. In: Committee on Reducing Tobacco Use: Strategies. Available at: http:// www. Nicorette Gum. Tobacco cessation pharmacologic product guide: FDA approved medications.PDF. Lam CY. Framework Convention on Tobacco Control. Issue 1. contact with experts and the GlaxoSmithKline Clinical Trials Register (http:ctr. Bonnie RJ. 2007.ncbi. Search date: 2004. Hughes JR.int/tobacco/ framework/download/en/. et al. Silagy C. CNS Drugs 2001. Thomson PDR 2007. PsycLIT. Tonnesen P.18:362–366. BMJ 1999. Sussenbach-Vaz E. 95. Said S. Prescribing information.gov/bbs/ topics/ANSWERS/ANS00720. Arch Intern Med 2006. Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Sampablo I. et al. www. Am J Med 2006. Haggstram FM. efficacy and tolerability. et al. 98. NJ. Gudmundsson LJ. Mitta W. Bupropion for pharmacologic relapse: predictors of outcome.gov. 4th edition. David S. Rigotti NA. A preliminary placebo-controlled trial of selegiline hydrochloride for smoking cessation. 1997. Montvale. et al. Montvale.15(6):453–467.119. Bupropion for smokers hospitalized for acute cardiovascular disease. 100. Addict Behav 2002. primary source the Tobacco Addiction Review Group trials register.27(4):493–507. Available at: http://www.html. Available at: http:// www. Lancaster T. Australian categorisation of drugs: Central nervous system. et al. Berlin I.318:285–289. Mayer FS. Freeman RK. UK: John Wiley & Sons Ltd. et al. Predictive factors in smoking cessation with combined therapy with bupropion and nicotine patches. vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Arch Intern Med 2006. 2007. primary source the Tobacco Addiction Review Group trials register. Issue 3. UK: John Wiley & Sons Ltd. Lores L. Accessed on July 9. Nicotine Tob Res 2003. Wolter TD. MEDLINE and reference lists of relevant reviews. 1996. Termine A. Chichester.296:64–71. Search date: 2006. Kupersmith A. Chichester. Chatkin JM. Lobeline for smoking cessation (Cochrane Review) In: The Cochrane Library. Frishman WH. 109.82. 90. Regan S. MEDLINE. Jack LM. Drugs in Pregnancy and Lactation. 101. 107. Jorenby DE. Fowler G. 84. Curry S. Stead LF. 83. April 2003.166:667–674. Fant RV. 108. dependent smokers. Clin Pharmacol Ther 1995. Etter J-F. handsearches of specialist journals. Swan GE. et al.61:2517–2521. 103. an alpha4beta2 nicotinic acetylcholine receptor partial agonist. Psychol Addict Behav 2004. 2006. May 2007. JAMA. Stead LF. Efficacy of varenicline. et al. et al. Chichester. UK: John Wiley & Sons Ltd. 94.com and email newsgroup of the Society for Research on Nicotine and Tobacco. 97.1080–1087. Combination nicotine replacement therapy for smoking cessation: rationale. EMBASE and PsycLit. MEDLINE. UK: John Wiley & Sons Ltd. 110.59(2):171–176. King A. Issue 2.com/products/assets/us_zyban. © BMJ Publishing Group 2007 31 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 31 . Accessed on July 9. Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. 87. Lancaster T. Biberman R.fda. conference proceedings. Katzir I.19(3):205–209. et al. 93. Zyban. Bupropion SR and counseling for smoking cessation in actual practice: predictors of outcome. Addiction 2003. Clonidine for smoking cessation (Cochrane Review) In: The Cochrane Library. 92.gov/ohrms/DOCKETS/ dailys/03/May03/052303/03P-0196-cp00001vol1. et al. Spreux-Varoquaux O. A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation. 2000.tga. et al. reference lists of previous trials and overviews. 91.53:136–143. primary source the Tobacco Addiction Review Group trials register. 99.au/docs/html/mip/ medicine. Lerman C. reference lists of relevant reviews and meta-analyses. Cooney JL. et al. Yaffe SJ. JAMA 2006. Issue 4. Available at: http://www. Training health professionals in smoking cessation (Cochrane Review) In: The Cochrane Library. Search date: 2004. Chichester. Citizen’s petition for switching Nicotrol Inhaler from Rx to OTC. Prescribing medicines in pregnancy. Mecamylamine (a nicotine antagonist) for smoking cessation (Cochrane Review) In: The Cochrane Library. Niaura R. Accessed on: July 9. 2007. Silagy C. Nicotine Tob Res 2006. et al. 2006. Search date: 2006. 86. Hurt RD. 2007.fda. Nicotrol inhaler. Neumann R. 2005. Issue 3. Effect of bupropion on depression symptoms in a smoking cessation clinical trial. Cytisine for smoking cessation: a literature review and a meta-analysis. primary source the Tobacco Addiction Review Group trials register. Coll-Klein F.controlled-trials. Chichester. 89. Pulmonary Pharmacol Ther 2006. Rigotti N.296(1):56–63.58:444–452. 2004.pdf. 104. [erratum appears in JAMA. Rigotti NA. 2007. O’Malley SS. sustained-release bupropion and placebo for smoking cessation: preliminary results. Issue 3.166:1553–1559.com/. Monaldi Arch Chest Dis 2003. De Wit H. et al.pdf. Collins BN. product information.gsk. GlaxoSmithKline. Lancaster T. Stead LF. Briggs GG. Williams & Wilkins.htm#cns. 88. Riley RC. George TP. Baltimore. Krishnan-Sarin S. Fagerstrom KO. Accessed on: June 15. UK: John Wiley & Sons Ltd. Gourlay SG. A controlled trial of nortriptyline.nicotrol. et al. Thorndike AN. Search date: 2006.] Tonstad S. 106. Available at http:// us. 2007. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. Biol Psychiatry 2003. Accessed on: July 9. et al. Hughes JR. 7th ed. Zyban.296(11):1355. 1999. 85. Pfizer. Vessicchio JC. 96. Stead LF.8:671–682. Chantix. Search date: not reported. A reversible monoamine oxidase: a inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy. Olafsdottir I. Hajek P. NJ. 1998. and contact with experts. Hays JT. 2005. Benowitz NL.5:911–921. Sweeney CT. et al. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Opioid antagonists for smoking cessation (Cochrane Review) In: The Cochrane Library. Available at: http://www. primary source the Tobacco Addiction Review Group trials register and MEDLINE. 2006. Thomson PDR 2007.98:1403–1407. 102. 105.61:1644–1650. MD: Lippincott. Blondal T. Stead LF. Chichester. Issue 2. 116. Can exercise minimise weight gain in women after smoking cessation? Am J Public Health 1996. Stead LF. Physician advice for smoking cessation (Cochrane Review) In: The Cochrane Library. PsycINFO.25:91–101. Chichester. Meta-analysis of the efficacy of tobacco counseling by health care providers. Search date: 2004. 2005. primary source the Tobacco Addiction Review Group trials register. Telephone counseling for smoking cessation (Cochrane Review) In: The Cochrane Library. et al. Curr Opin Mol Ther 2006. Lancaster T. Chichester. Perera R. reference lists of relevant studies. Seay S. Wright JA. 124. SPORTDiscus and CINAHL. Brown K. Williams GC. Nursing interventions for smoking cessation (Cochrane Review) In: The Cochrane Library. 2005. reference lists. Chichester. Taylor AH. Rotnitzky AG. UK: John Wiley & Sons Ltd. meta-analyses and US guidelines (AHCPR and AHRQ). 129. 131. 2005. Saunders C. Kawachi I. primary source the Tobacco Addiction Review Group trials register. 1997. Issue 3. 2006. conference abstracts. The acute effects of exercise on cigarette cravings. Issue 4. UK: John Wiley & Sons Ltd. conference proceedings and reference lists of relevant trials and overviews. et al.8:11–16. Stead.13:2012–2022. 132. Issue 3. Burnand B. 117. Issue 1. Lancaster T. conference proceedings and reference lists of relevant trials and overviews Hughes JR. A randomised controlled trial of weekly versus basic smoking cessation support in primary care. Issue 1. reviews and abstracts from the meetings of the Society for Research on Nicotine and Tobacco. Search date: 2004.86:999–1004. and additional searches on key authors. UK: John Wiley & Sons Ltd. A review of computer and Internet-based interventions for smoking behavior. Cardiology In Review 2006. Health Ed Res 2006. Search date: 2006. Bize R. 2004. and reference lists of relevant trials and overviews. Sharp D. 113.and low-anxiety smokers. EMBASE. Cancer Epidemiol Biomarkers Prev 2004. the Cochrane Controlled Trials Register (CENTRAL). Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. Hatsukami DK. et al. LF. Addiction 2007. EMBASE. withdrawal symptoms. 120.79:396]. Lancaster T. A placebo-controlled evaluation of the effects of buspirone on smoking cessation: differences between high.56:768–774. primary source the Tobacco Addiction Review Group trials register and other studies cited in previous reviews. J Clin Psychopharmacol 1995. Cinciripini PM. Lapitzky L. the Cumulative Index to Nursing and Allied Health Literature (CINAHL). Testing a self-determination theory intervention for motivating tobacco cessation: supporting autonomy and competence in a clinical trial. EMBASE. reference lists of relevant reviews. 2004. Jorenby D. et al. UK: John Wiley & Sons Ltd. Search date: 2004. Issue 2. 123. primary source the Tobacco Addiction Review Group trials register. et al. UK: John Wiley & Sons Ltd. handsearching of specialist journals. Comparing the efficacy of two Internet-based. UK: John Wiley & Sons Ltd. PsycLIT. A randomised controlled trial of motivational interviewing for smoking cessation.21:416–427. 112.15:182–191. 121. conference proceedings. T. Search date: 2004. Search date: 2003. Biomedical 32 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 32 . 122. Silver acetate for smoking cessation (Cochrane Review) In: The Cochrane Library. Exercise interventions for smoking cessation (Cochrane Review) In: The Cochrane Library. PsycINFO and US Public Health Service Clinical Practice Guidelines. 126. primary source the Tobacco Addiction Review Group trials register. Troisi RJ. Chichester. handsearching of specialist journals. Health Psychol 2006. MEDLINE. Gorin SS. Search date: 2006. Search date: 2005. Lancaster. Issue 4. Br J Gen Pract 2006. handsearching of specialist journals. Maurer P. Stead LF. Walters ST. J Med Internet Res 2005. Ussher M. 125. computer-tailored smoking cessation programs: a randomized trial.7:e2. 130. 127. MEDLINE. Mueller Y. Bachmann MF. Individual behavioral counseling for smoking cessation (Cochrane Review) In: The Cochrane Library. Pan W. Stead LF. Stead LF. Issue 3. Nicotine and non-nicotine smoking cessation pharmacotherapies. Self-help interventions for smoking cessation (Cochrane Review) In: The Cochrane Library. Anxiolytics for smoking cessation (Cochrane Review) In: The Cochrane Library.78:456–467 [erratum in Clin Pharmacol Ther 2006. primary source the Tobacco Addiction Review Group trials register. Lancaster T. 114. 2005. PUBMED and references of relevant reviews and metaanalyses. Rice VH. Faulkner G. Lancaster T. MEDLINE. Ussher MH. affect and smoking behavior: a systematic review. Dissertation Abstracts. 128. MEDLINE and EMBASE. UK: John Wiley & Sons Ltd. primary source the Tobacco Addiction Review Group trials register. Lancaster T. Therapeutic vaccines for nicotine dependence. Search date: 2003. Escolano C. Clin Pharmacol Ther 2005. primary source the Tobacco Addiction Review Group trials register. Aveyard P. MEDLINE. primary source the Tobacco Addiction Review Group trials register. et al. Soria R. Stead LF. Proactive telephone counseling as an adjunct to minimal intervention for smoking cessation: a meta-analysis.31(2):264–277. 119.111. Stead LF. Chichester. Chichester. UK: John Wiley & Sons Ltd. Thorax Published Online First: 4 May 2007. McGregor HA. EMBASE and PsycLit.14:57–73.102(4):534–543. et al. Shegog R. 115. 2000. 118. Etter J-F. Addict Behav 2006. Rennard S. UK: John Wiley & Sons Ltd. Chichester. Legido A. Heck JE. Chichester. Group behavior therapy programs for smoking cessation (Cochrane Review) In: The Cochrane Library. the Cochrane Central Register of Controlled Trials (CENTRAL). PsycINFO. MEDLINE. 2005. handsearching of Behaviour Research and Therapy. Resch KL. the Cochrane Central Register of Controlled Trials (CENTRAL). Stead LF. PsycINFO. Costeffectiveness of pharmacotherapies for nicotine dependence in primary care settings: a multinational comparison. Psychol Bull 1992 Jan. MEDLINE. 142. Search date: 2005. West R. Velicer WF. Rossi JS. The validity of self-reported smoking: a review and meta-analysis. Tob Control 2006. UK: John Wiley & Sons Ltd. Arch Int Med 2006. Chichester. Journal of Consulting and Clinical Psychology. et al. Aversive smoking for smoking cessation (Cochrane Review) In: The Cochrane Library. UK: John Wiley & Sons Ltd. Am J Pub Health 1987. risk assessment as an aid for smoking cessation (Cochrane Review) In: The Cochrane Library. 137.25:437–448. et al. Chichester. Acupuncture and related interventions for smoking cessation (Cochrane Review) In: The Cochrane Library. PsycINFO. et al. Hajek P.84(7):1086–93. A meta-analysis of acupuncture techniques for smoking cessation. and Economic Costs: United States. et al. UK: John Wiley & Sons Ltd. Tunstall-Pedoe H. 2006. primary source the Tobacco Addiction Review Group trials register. 2005. Am J Public Health 1994 Jul. Journal of Behavioural Medicine. CISCOM and the Medical Acupuncture Research Foundation Acubriefs website. Systematic review of economic evaluations of smoking cessation: standardizing the cost-effectiveness. Hajek P. Annual Smoking—Attributable Mortality. 138. Issue 4. Gemson DH.133. Science Citation Index and abstracts from the Society for Research on Nicotine and Tobacco (SRNT) and World Tobacco or Health conferences. White AR. Ament AJ. 140. Rampes H. Ernst E. Thompson DC. primary source the Tobacco Addiction Review Group trials register and Cochrane reviews of cessation interventions. Cheadle A. 134. Groot W. Cornuz J. Behavior Therapy. and reference lists of relevant reviews and studies. © BMJ Publishing Group 2007 33 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 33 . Centers for Disease Control and Prevention. Relapse prevention interventions for smoking cessation (Cochrane Review) In: The Cochrane Library. 1995–1999. the ISI Science Citation and Social Science Citation Indexes. 143. White AR. www. Gilbert A. Campbell JL. primary source the Tobacco Addiction Review Group trials register. Comparison of tests used to distinguish smokers from non-smokers. Pinget C. 135. 136. Search date: 2004. Chichester. Issue 1. Feyerabend C. EMBASE. Lancaster T. Available at: http:// 141.111(1):23–41. Hypnotherapy for smoking cessation (Cochrane Review) In: The Cochrane Library. Jarvis MJ. primary source the Tobacco Addiction Review Group trials register. EMBASE. Accessed on: June 15. Abbot NC. 1998. EMBASE. MEDLINE.17:299–308.166:828– 835. the Central Register of Controlled Trials (CENTRAL). Search date: 2004.15:152– 159. Ronckers ET. Office system interventions supporting primary carebased health behavior change counseling. Chichester. 145. et al. Search date: 2004. UK: John Wiley & Sons Ltd.cdc. MEDLINE. 144.77(11):1435–1438. et al. Chichester. BIOSIS Biological Abstracts. Am J Prev Med 1999. White AR. Carney P. Stead LF. 2001. Tob Control 1999. Patrick DL. CISCOM and reference lists of relevant trials and reviews. et al. Years of Potential Life Lost. primary source the Tobacco Addiction Review Group trials register. Issue 2. AMED (Allied and Alternative Medicine database). Med Decision Making 2005. Science and Social Sciences Citation Index. Assessing outcome in smoking cessation studies. Issue 1. Hajek P. Stead LF. 2007. AMED. Search date: 2005. Prochaska JO. Prevention of relapse after quitting smoking: a systematic review of trials.htm. Dickey LL. Issue 3. Stead LF. 139. PsycINFO.gov/mmwr/preview/mmwrhtml/ mm5114a2. UK: John Wiley & Sons Ltd.8:393–397. In addition. other important articles.com/ceweb/about/search_process. Individual sections were sent to advisors and editors for review.com and www. we have presented the results of a systematic review on the effectiveness of interventions to increase smoking cessation among adults. disease burden of smoking. and other demographic data. For this paper. findings from reputable.tobaccocontrol. based on the BMJ Clinical Evidence search and appraisal methodology described at http:// www. the Health Technology Assessment (HTA). We only included trials with a follow-up of at least 6 months after the start of the intervention. policy and economic issues of interventions. EMBASE. focusing on systematic reviews and randomized studies for the effectiveness of interventions. we reported this.jsp.bmj. and from discussions with our expert panel.bmj. Turning Research into Practice (TRIP). We specifically noted trials conducted in specific populations and settings and investigated whether interventions were differentially effective for these groups. Appendix: Methodology We searched MEDLINE. the NHS Centre for Reviews and Dissemination (CRD). Where research was lacking or poor in quality. legal. the National Guideline Clearinghouse. and the U. After gathering the research. We extracted information from trials on the study population. patients’ readiness to quit. differences in longer term cessation rates may be diluted by smokers who have made subsequent quit attempts. randomized controlled trials and other studies throughout December 2006. We referred to high-quality systematic reviews when they were available and references recommended by experts.S. objective sources based on large. Michael Cummings) and a second on a smoking cessation toolkit for clinicians (written by Sherman). Some additional searches were carried out in January and February 2007. guidelines. Action on Smoking and Health. but extracted relevant information from our systematic treatment searches. the first one on public policy (written by K. controlled surveys or guidelines were included. We excluded trials with self-reported cessation as these routinely overestimate biochemically validated cessation. Please see www. The draft document was sent out to the following panel of expert clinicians for peer review in June 2007 and the text revised in view of their comments and queries. benefits of cessation. Department of Health and Human Services in January and February 2007. On the other hand. we summarized the studies found and described the conclusions reached by authors of the systematic reviews. Resuming smoking before that time can be considered part of the quit attempt rather than a subsequent relapse. We commissioned two sections. the Database of Abstracts of Reviews of Effects (DARE).clinicalevidence. We did not systematically search for papers on predictive factors for successful quit attempts. the Cochrane Library. For the background sections on incidence and prevalence. and the National Institute of Health and Clinical Excellence (NICE) guidance databases for relevant systematic reviews. EMBASE. 34 © BMJ Publishing Group 2007 Our approach Letterpart Ltd – Typeset in XML A Division: Text F Sequential 34 . we searched MEDLINE. We included the best evidence available.com for other high-quality publications on tobacco use and smoking cessation.This report carries on the BMJ Publishing Group’s longstanding tradition of addressing the health implications of tobacco use. was to summarize and synthesize evidence from high-quality systematic reviews and large well-designed RCTs. Michael Cummings. Director. IARC. MD. Division of Cancer Prevention and Population Sciences. However. Fayetteville. MD. MPH (Associate Professor. CA) + Maria Leon-Roux. MA) + Scott Sherman. Associate Professor. Boston. Appraising studies on treatments Disease burden of smoking The harms of smoking have been repeatedly and convincingly demonstrated in many thousands of studies. Using relative risk to measure disease burden The relative risk (RR) for a disease does not always give the best measure of the societal disease burden of smoking. and other studies when these are not available. Brigham and Women’s Hospital. Attempting to ascertain if a residual elevated risk persists after quitting in the © BMJ Publishing Group 2007 35 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 35 . NY) Methodologic challenges of assessing the literature Our aim. For example. Buffalo. but the overall disease burden from smoking-related lung cancer and CHD is similar. research is still finding new harms from smoking and quantified estimates of harms will continue to develop as exposures and populations change and study methods develop. Los Angeles. Environment and Cancer Group. University of California. Harvard Medical School. Department of Health and Social Behavior. Harvard School of Public Health. Age differences are also important. high-quality research on the effectiveness of interventions aimed at achieving cessation. Harvard Medical School. MPH (Chair. Department of Medicine. the smoking-related disease burden is far higher in the elderly. in older age groups the RR from smoking for CHD is smaller than for younger people. France) + Nancy Rigotti. Department of Medicine. the RR for smokers for lung cancer is far higher than that for coronary heart disease (CHD). Tobacco Research and Treatment Unit. PhD. NYU Medical Center. Roswell Park Cancer Institute. Because the health benefits of smoking cessation can be a long time in the future and in most trials the quit rate is low. NY) + Carolyn Dresler. MD (Associate Professor. University of Arkansas for Medical Sciences. MPA (Associate Professor of Health Policy and Management Department of Health Policy and Management. Boston. like that of BMJ Clinical Evidence. MA) + Nancy Lee (Clinical Pharmacist. Lyon.+ K. MPH (Tobacco and Cancer Team. Lifestyle. Massachusetts General Hospital. Department of Health Behavior. AR) + Michael Fisher. Instructor in Medicine. WHO. because of the low baseline risk in never smokers. MS (Associate Physician in the Division of Pharmacoepidemiology and Pharmacoeconomics. we have followed a two-stage process: First providing the evidence on the health benefits of successful cessation and then summarizing up-to-date. UCLA Medical Center. but because CHD is far more common among older people. MD. Again. This means studies measuring cessation at only one point during the study may underestimate the benefits of ongoing cessation.g. tend to be more likely to quit than asymptomatic smokers. “Have you smoked any cigarettes in the last 30 days?”) the rate of overreporting can be 36 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 36 .. other unadjusted confounders may lead to overestimation of the benefits. This effect can have a long term impact for conditions as chronic obstructive pulmonary disease (COPD) and CHD with a long time lag between first symptoms and morality and can lead to a potentially substantial underestimate of the benefits of cessation. and are more likely to relapse.g. + Reverse causation: Smokers with symptoms of pre-existing disease. Effectiveness of interventions for smoking cessation Best available evidence We have selected well-conducted systematic reviews and randomized controlled trials as our primary evidence source as these provide the best evidence of effectiveness for treatments. + Population trends: A related problem is the reduction in smoking rates seen in many Western populations over time. This means that many of those initially assessed as smokers will subsequently quit and gain some of the benefits of cessation. This means that higher rates of disease will often be observed among recent quitters than among persistent smokers.g. With better questions (e. These have found strong evidence of a reduction in mortality and risk of smoking-related disease following smoking cessation. However.long term is more difficult for conditions with a lower elevated relative risk (e. Confounders Quantification of the benefits of cessation mainly rests on the large evidence base from cohort and case control studies. lung cancer).. rather than risks if they had never smoked. + Health behavior: However. How to measure cessation Simply asking people whether they currently smoke will identify a fair number that quit just a few days previously. compared with persistent smoking. studies that assess smoking status only once may underestimate the effect compared with studies that assess smoking status at multiple points. as it is likely that people who have quit smoking will display other healthy behaviors compared with persistent smokers. CHD) than for those with a higher one (e. including undiagnosed disease. Public policy interventions are more difficult to study and are usually based on interrupted time series data or other observational studies. even if the smoking-related disease burden is similar. + Relapse: Another potential cause of bias is that many people who have recently stopped smoking cessation relapse. because this reflects the real choice that smokers or recent quitters face. Health benefits from smoking cessation Which population groups to compare The effects of smoking cessation are most usefully compared between quitters and continuing smokers. some methodologic problems remain in quantifying the size of benefits.. tobacco use is a relapsing and remitting condition.143. light. the primary metabolite of nicotine. Most relapses occur within days after quitting which imply treatment may need to be most intense early in the process. in this review we have focused on studies that reported cessation measure at a minimum of 6 months. Exhaled carbon monoxide in nonsmokers and smokers145 Smoking intensity Nonsmoker Light Moderate Heavy Exhaled carbon monoxide (ppm) 0–6 7–10 10–20 > 20 Another biochemical marker of smoking is cotinine. Similar to many chronic conditions where cure is rare. One of the available biochemical measures is exhaled carbon monoxide (Table 8). Measurements are not specific to cigarettes and half-life is short (3 to 5 hours). but with too few studies providing such long-term data. and urine. and people enrolled in randomized smoking cessation trials. We have not prioritized any one method but listed results for subgroups as presented in each study. but requires laboratory analysis. such as adolescents.145 Cotinine will generate a false-positive test result in patients using nicotine replacement. The longer one abstains from cigarettes continuously. is a strong predictor of relapse and implies the need for enhancing the treatment. although it is higher in a few special populations. A lapse. and moderate smoking is defined and assessed differently in the included studies. Most relapses occur within 3 months of the original quit day.held at 5% to 10%. Even failing quit attempts matter as they reduce exposure to tobacco smoke and may be a predictor of future success. which can be detected in serum. Levels fall to normal in 24 hours. Table 11.144 Biochemical measures are used in smoking cessation studies rather than in routine clinical practice. which is why most treatment programs are focused on the first 12 weeks of the quit process. which is smoking one or two cigarettes. saliva. It has a long half-life (16 hours) and can detect smoking in the preceding 3 to 4 days. the greater the odds of remaining smoke-free. pregnant smokers. How to assess smoking intensity Heavy. Length of follow-up Smoking cessation is a process rather than a state. Follow-up of 1 or 2 years would be more desirable. © BMJ Publishing Group 2007 37 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 37 . ultimately leading to fewer smokers and less subsequent tobacco-related morbidity and mortality. Treatment cannot be offered to all smokers unless they are identified. clerical staff should verify smoking status.g. This toolkit is based on a practice with one or more physicians.. Consider getting buttons for all staff that say. and consistent. but still underutilized. Along with verifying address and insurance information. Common approaches are colored stickers on the outside of charts or a flag in an electronic medical record. Step 1: Identify a coordinator The coordinator should develop a multidimensional plan to improve tobacco control efforts. etc. Obtain posters. To excel at smoking cessation. The following 12-step approach is aimed at helping to consistently deliver evidence-based cessation services to each and every smoker. The main reason why most office-based efforts fail is that they rely too much on the physician. and any free offers (e. obvious. In a multi-physician practice. The purpose of this toolkit is to help develop a comprehensive plan to improve tobacco control efforts at your site. Every smoker interested in quitting should receive three things: 1) medications. it may help to identify one physician most responsible for smoking cessation to act as a clinical resource for the coordinator.. flyers. physician counseling to environmental tools (posters. ensure that tobacco use is part of it.. Determine what rewards (including a financial bonus) the person will receive for success.Toolkit: 12-step guide to a primary care systems approach for smoking cessation All of a health care site’s activities aimed at helping people to quit smoking can be grouped together as tobacco control. ensure that there are handouts available. clerk. . Identification should be clear.g. . and cards that promote cessation. delegation is key.”). Goal: To improve tobacco control efforts in medical practice Someone should be appointed to be in charge of smoking cessation. “Interested in quitting smoking? Ask me—I can help. © BMJ Publishing Group 2007 38 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 38 . Any forms needed by staff (e. pamphlets. along with additional office staff (e. This may range from the traditional. Make it part of his/her duties. nurse). Step 2: Create a plan Step 3: Create a supportive environment Review the waiting room and all exam rooms.g.” This is the second most important step. Set measurable goals. Current smokers can be given a handout encouraging them to quit (“Ask your doctor . Step 4: Identify all smokers Step 5: Make smoking status part of checking in If patients fill out a questionnaire for each visit. fax referral forms) should be stocked in every room where they are needed and checked on a regular basis. If there is a government or other telephone quit line. and 3) follow-up. 2) counseling. which will be further refined in conjunction with the physician(s) and all office staff.) to reminder systems that guide practice. for example. free medications through the quit line) should be mentioned. offered smoking cessation medications. I am going to ask _______ to talk to you some more about quitting. 2) to coordinate dispensing of smoking cessation medications. there should be some way to track what services were provided. I strongly encourage you to let us give you a medication to help you quit. Some typical ones are: whether each smoker was advised to quit. this should be kept brief—30 to 60 seconds. If the stamp is used.. Adding smoking to the list of vital signs increases cessation rates. Advice should be clear. With patients interested in quitting (determined in Step 6). Identify the key processes to be measured. although it does not lead to higher quit rates. or simply a smoking cessation stamp or template on each smoker’s visit note. advise each patient to quit. Step 6: Make smoking assessment and advice a vital sign Patients often identify advice from their physician as a key factor in helping them quit. I think it’s one of the most important things you can do for your health. An ideal minimum is 2 calls. “It’s great that you’re interested in quitting smoking. and personalized. The key tasks are: 1) to set a quit date. all staff should go over the measured results. Was the patient screened by the clerk at check-in? Did the physician provide brief advice? Were medications offered? This can be done in several different ways—with the electronic medical record. On a regular basis (e. It’s important to remember to document the calls and the outcomes.In most settings. the clerk could stamp the note initially and then each successive person could check or initial if their part was done. monthly or quarterly). Also. and 3) to provide brief counseling. It will particularly help you because <tailor to each patient>. The second call should be at 6 months. a pharmacist. This is precisely why recording the services provided (Step 9) is important. a paper smoking cessation log.” Step 7: Brief physician advice A staff member in your office or practice needs to provide additional counseling to supplement the physician’s brief advice. In the interest of efficiency. strong. and offered referral to an available smoking cessation program or telephone quit line. Many people find it helpful to provide a handout to augment the counseling. and describe available options. The first should be 1 to 2 weeks after the patient’s quit date (if one was set). It is exceedingly difficult to improve if performance is not monitored. © BMJ Publishing Group 2007 39 Step 11: Follow-up Letterpart Ltd – Typeset in XML A Division: Text F Sequential 39 . but it could be a health educator. Step 8: Post-physician advice If at all possible. as it doubles your chance of success. a physician might say. to assess smoking status and to offer people who are still smoking another chance to quit. Step 10: Measure A staff member from the office should call all smokers in follow-up. Step 9: Record services provided This is by far the most important step. It does not matter how performance is measured —electronically or on paper—as long as it is done. or even a clerk. Staff can also assess interest in quitting. it will be the nurse providing this advice. to provide counseling during this most vulnerable period. It need not take long—up to 10 minutes is sufficient. In many settings. a nurse or health technician sees each patient before the physician and records vital signs.g. As your doctor. Everyone can be rewarded for good performance. National Library of Medicine and the U.gov/medlineplus/smokingcessation.nih.S. Step 12: Reward yourselves Toll-free quit lines + National Network of Tobacco Cessation: 1–800-QUITNOW (1-800-784-8669) and 1-800-332-8615 + National Cancer Institute: 1-877-44U-QUIT (1-877-448-7848) Additional resources + Centers for Disease Control and Prevention: Smoking & tobacco use (U.html + National Cancer Institute: Quitting smoking.cdc. Looking over the results in Step 10 is very helpful to keep staff motivated. but financial measures are also important.cancer.S.gov/cancertopics/smoking/quitting 40 © BMJ Publishing Group 2007 Letterpart Ltd – Typeset in XML A Division: Text F Sequential 40 .gov/tobacco/ + MedlinePlus: Smoking cessation (a service of the U.S. National Institutes of Health) http://www. Some ideas include singling out top performers for an extra bonus or having a party to celebrate when you reach a certain number of long-term (6 months) nonsmokers. Put up posters to celebrate your success and to remind patients of what is available. Department of Health and Human Services) http://www.nlm. smoking prevention (U.S.System redesign is hard work. National Institutes of Health) http://www. Letterpart Ltd – Typeset in XML A Division: plm_BackCover F Sequential 1 . MN 55440–1459 www.Commissioned by MN008-T800 PO Box 1459 Minneapolis.unitedhealthfoundation.org Letterpart Ltd – Typeset in XML A Division: plm_BackCover F Sequential 2 .