nicotine replacement products and government...

6.17: Tobacco Use Cessation

Priority Medicines for Europe and the World"A Public Health Approach to Innovation"

Background Paper

Tobacco Use Cessation:Importance and Implications

By Warren KaplanWith materials provided by

Dr. Samira AsmaCenters for Disease Control

USA

Coordinated by Derek YachYale University

12 October 2004

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Table of Contents

Introduction...........................................................................................................3What is the Size and Nature of the Disease Burden?............................................4

Health Consequences of Smoking......................................................................4What is the Control Strategy?...............................................................................5

Importance of smoking cessation in reducing disease burden...........................5Why Does the Disease Burden Persist?.................................................................6

Need for Intervention to Increase Cessation......................................................6Evidence Base for Effective Intervention............................................................6

What Can Be Learned from Past/Current Research into Pharmaceutical Interventions?........................................................................................................7

Nicotine replacement Therapy-Available Technologies......................................7Nicotine Replacement Products and Government Policies.................................9Policies and Problems for the Availability of NRTs............................................9Accessibility of NRT Products...........................................................................12

a. Geographical Accessibility.....................................................................12b. Financial Accessibility............................................................................13

What Are the Opportunities for Research Into New Pharmaceutical Interventions?......................................................................................................13Discussion/Summary............................................................................................15References...........................................................................................................16

Appendix

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IntroductionCigarette smoking and other tobacco use imposes a huge and growing global public health burden. Every year, tobacco use is currently estimated to kill nearly five million people worldwide, accounting for one of every five deaths among males over age 30 and one in twenty deaths among females over age 30. Based on current smoking patterns, annual tobacco deaths will rise to ten million by 2030. During the 21st century as a whole, we are likely to see 1 billion tobacco deaths, most of them in developing countries. In contrast the 20th

century saw 100 million tobacco deaths and most of them were in developed countries.

Much of tobacco’s substantial death toll is avoidable. Numerous studies from high-income countries, and a growing number from low and middle-income countries, provide strong evidence that tobacco tax increases, dissemination of information about health risks from smoking, restrictions on smoking in public places and in workplaces, comprehensive bans on advertising and promotion, and increased access to cessation therapies are all effective in reducing tobacco use and its consequences. Cessation by the 900 million current smokers in developing countries is central to meaningful reductions in tobacco deaths over the next five decades. Price and non-price interventions are, for the most part, highly cost-effective. Potentially, tens or hundreds of millions of premature deaths would be avoided if these interventions could be widely applied.

There is overwhelming evidence for the health benefits, effectiveness and cost-effectiveness of quitting smoking and of treatment for tobacco dependence, a disorder recognized by the tenth version of WHO’s International Classification of Diseases.1 Treatment for tobacco dependence is safe and efficacious. However, despite availability of cost-effective treatment for tobacco dependence, the public health sector in many countries, is not investing in smoking cessation services, nor in the development of an infrastructure that will motivate smokers to quit and support them on doing so. Furthermore, in most countries, provisions for treatment, training of health care providers, education and information on wide use of cessation therapies, as well as financial resources are limited and rarely incorporated into standard health care. Also, smoking cessation is not seen as a public health priority and is not necessarily approached as a key tobacco control strategy in governmental and institutional workplans. Beside specific interventions for smoking cessation, a general supportive environment that will stimulate smokers to quit is not usually considered a component of smoking cessation policies.

This paper examines the relevant set of policies on information, availability, accessibility and affordability of Nicotine Replacement therapy (NRT) products from the pharmaceutical policy perspective for developed and developing countries.

1 World Health Organization. International statistical classification of diseases and related health problems, 10th ed. Geneva: World Health Organization, 1994

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What is the Size and Nature of the Disease Burden?Tobacco use is the single largest preventable cause of death worldwide. Every year, nearly 5 million people die from tobacco-related illnesses.2 The prevalence of tobacco use worldwide is estimated at 29%, and it is rising.3 The global rate of tobacco use is significantly higher for men (47%) than women (12%),Error: Reference source not found but the tobacco industry has targeted women in their promotional strategies. In many regions of the world this targeting has proved effective, resulting in alarming rates of increase in tobacco use among women in both developed and developing countries.Error: Reference source not

found, 4 In Denmark, Germany, and Sweden, more women aged 14 to 19 years than ever now smoke, even in the midst of national declining rates. Similarly, in some countries in Asia, smoking among women aged 18 to 24 years has increased. The number of women smokers will likely triple over the next generation.Error:Reference source not found The prevalence of smoking among youth is also increasing. Data from the Global Youth Tobacco Survey show that one out of five children in the world smokes his or her first cigarette by age 10 years. The prevalence of tobacco use among schoolchildren aged 13 to 15 years ranges greatly throughout the world, from 10% to as high as 60%.5

Health Consequences of Smoking

Smoking harms nearly every organ of the body, causing many diseases and reducing the health of smokers in general. Forty years after the first Surgeon general’s report in 1964, the list of diseases and other adverse effects caused by smoking continues to expand. Epidemiologic studies are providing a comprehensive assessment of risks faced by smokers who continue to smoke across their lifespan. Laboratory research now reveals how smoking causes disease at the molecular and cellular levels. Fortunately for former smokers, studies show that the substantial risks of smoking can be reduced by successfully quitting at any age.Error: Reference source not found

Tobacco use was a known or probable cause of more than twenty-five specific diseases and is an important cause of, and risk factor for, chronic disease.6

Independently and often in combination, these risk factors are the major causes of cancer, cardiovascular disease, diabetes, respiratory disease, and other chronic diseases.7 The list of disease caused by smoking has been expanded to include abdominal aortic aneurysm, acute myeloid leukemia cataract, cervical cancer, kidney cancer, pancreatic cancer, pneumonia, periodontitis, and stomach cancer.Error: Reference source not found Prolonged smoking causes lung cancer, other cancers (i.e., cancer of kidneys, cervix and bone marrow), chronic respiratory and cardiovascular diseases (in particular ischemic heart disease), and many other diseases. Smoking diminishes health generally. Adverse health effects begin before birth and continue across the life span. Smoking also causes cataracts and contributes to the development of osteoporosis, thus increasing the risk for fracture in the elderly.Error: Referencesource not found In populations in which cigarette smoking has been common for several decades, about 90% of lung cancer, 15% to 20% of other cancers, 75% of chronic bronchitis and emphysema, and 25% of deaths from cardiovascular disease at ages 35 to 69 years are attributable to tobacco use.Error: Reference source not found Tobacco-related cancer constitutes 16% of the total annual incidence of cancer cases – and 30% of cancer deaths – in developed countries, and 10% of deaths in developing countries.Error:Reference source not found

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Chronic diseases are expected to account for an increasing share of the disease burden, rising from 43% in 1998 to 73% by 2020.Error: Reference source notfound The expected increase is likely to be most rapid in developing countries. For example, in India, the number of deaths from chronic causes each year is projected to almost double, from 4.5 million in 1998 to about 8 million in 2020.Error: Reference source not found The steep projected increase in chronic diseases worldwide is largely driven by the rapidly increasing numbers of people presently exposed to tobacco via smoking or secondhand smoke (SHS) as well as to other risk factors.

What is the Control Strategy?Importance of smoking cessation in reducing disease burden

Quitting smoking has immediate as well as long terms benefits, reducing risks for disease caused by smoking and improving health in general.Error: Referencesource not found Smoking cessation is a priority for preventing disease and reducing its burden.8 At any age, quitting confers substantial and immediate health benefits including reduced cardiovascular disease risks,Error: Referencesource not found improved lipid profiles and platelet reactivity9 and reduced risk of strokeError: Reference source not found and smoking-attributable cancers.Error: Reference source not found The World Bank suggests that, if adult consumption were to decrease by 50% by the year 2020, approximately 180 million tobacco related deaths could be avoided.10 Thus promotion of smoking cessation and treatment of tobacco dependence can have great impact in reducing the burden of disease and improving population health. (See Appendix 6.17.1)

According to the Commission on Macroeconomics and Health, smoking is on a short list of specific conditions-including HIV/AIDS, malaria, tuberculosis, childhood infectious disease, maternal and perinatal conditions, and micronutrient deficiencies-that needs to be a priority in low income countries to save million of lives, reduce poverty, spur economic development, and promote global security.11 In addition, cessation interventions are described specifically in the WHO Framework Convention on Tobacco Control (FCTC). Signing the FCTC and its ratification will obligate countries to work on cessation as part of a comprehensive effort in tobacco prevention and control.12

In recent years governments at all levels have adopted a variety of macro-level interventions. These include tobacco tax increases, restrictions on smoking in public places, limits on youth access to tobacco products, bans on advertising and other promotions, counter advertising, efforts to increase information about the harmful consequences of tobacco use. Most of these interventions aimed at reducing the demand (consumption) for tobacco products and are considered preventive policies.

Demand for smoking cessation interventions is increased in an environment that discourages and denormalizes tobacco use. Smoke-free indoor air policies, tobacco taxation to increase price, and public information campaigns increase interest in stopping smoking. Banning the use of misleading labeling on tobacco products, for example, ‘light’ and ‘mild’, can also help prevent smokers from relapsing and increase quitting.13 The impact of a smoking cessation program is the product of its effectiveness and population reach (e.g., the proportion of smokers in the population who use it). Brief low-intensity interventions that focus on education and increasing motivation to quit and produce a low but

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http://www.who.int/tobacco/resources/publications/tobacco_dependence/en


measurable success rate, and have a higher potential for population impact. Most smokers that have quit in Western countries have done so without any therapies or even doctor’s advice.Error: Reference source not found In contrast, multi-session, high-intensity treatments targeting nicotine-dependent smokers requiring individual treatment are characterized by a higher success rate, but reach only a small fraction of the population. This balance of the two approaches may differ across time, between countries and within countries. As prevalence falls, dependence in remaining smokers is likely to be high. In countries with a high smoking rate and low population awareness of the risks of tobacco use, awareness of the hazards of smoking and the benefits of cessation, plus focused efforts that reach large numbers (e.g., quit phone lines) are the priority. In countries or populations where smoking prevalence has started to fall and awareness of the health risks of tobacco is higher, higher intensity clinical interventions may be needed.

Near term reductions in smoking-related mortality depend heavily on smoking cessation. There are numerous behavioral smoking cessation treatments available, including self-help manuals, community-based programs, and minimal and intensive clinical interventions.14 In clinical settings, pharmacological treatments, including nicotine replacement therapies (NRT) and bupropion, have become much more widely available in recent years in high-income countries.Error: Reference source not found , Error: Reference source not found

Why Does the Disease Burden Persist?Need for Intervention to Increase Cessation

Tobacco dependence is recognized as a disease in the WHO’s International Classification of Diseases (ICD-10) and the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM-IV).15 In developed countries, a large proportion of smokers want to stop smoking and many try to stop16 but the corresponding proportions in developing countries are low.17, 18, 19 Smokers who try to quit often find it difficult because of the addictive properties of nicotine.20

Because of the low rate of quitting and the inherent difficulties in stopping, governments need to encourage smokers to quit and to provide more assistance to those who need help.

Evidence Base for Effective Intervention

The evidence base for both the effectiveness and cost effectiveness of clinical smoking cessation interventions is strong in Europe and the US.21, 22 A similar evidentiary base is not available for developing countries.Error: Referencesource not found In the US there is also a strong evidence base for the effectiveness of community based and population based interventions such as running sustained mass media campaigns, raising tobacco prices, reducing the cost of treatment, and establishing telephone quitlines.23, 24

Current research from Western countries provides mixed evidence on the impact of community-based behavioral interventions without NRT on successful smoking cessation.Error: Reference source not found However, community interventions may be more effective and more cost-effective (due to lower labor costs) in low income countries. In India, studies among 37,000 tobacco smokers and chewers found that cohorts who received health professional advice, information and cessation camps had quit rates of 9% to 17%, in contrast to 3%

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to 9% among cohorts who did not receive these interventions.Error: Referencesource not found

Promoting smoking cessation, creating an environment supportive of non-smoking, and providing appropriate services has produced encouraging results in the UK.25, 26, 27 Although in 2000 the WHO recommended that the treatment of tobacco dependence be considered a public health priority,28 much more needs to be done to promote smoking cessation worldwide.

What Can Be Learned from Past/Current Research into Pharmaceutical Interventions?Nicotine replacement Therapy-Available Technologies

In recent years, given the addictive nature of tobacco, tobacco control interventions have given an increasing importance for the tobacco addiction treatments, such as the nicotine replacement therapy products (NRTs). The recent World Bank tobacco report “Curbing the Epidemic: Governments and Economics of Tobacco Control” also addressed the importance of the NRT products as one of the efficient tobacco control policies. Moreover, the report recommends that governments include nicotine addiction treatments into tobacco control policies.

Nicotine replacement therapy (NRT) aims to replace the nicotine from cigarettes by other means of delivery nicotine skin patches, chewing-gum, lozenges, sublingual tablets, inhalators or nasal spray. NRT provides a background level of nicotine that reduces craving and withdrawal. The evidence is strong and consistent that pharmacological treatments significantly improve the likelihood of quitting, with success rates two to three times those when pharmaceutical treatments are not employed.Error: Reference source not found, Error: Reference source not

found, 29

A recent overview suggested the 2-3% of smokers abstained at 6 months with brief clinical advice to stop. Adding NRT to such advice increased quit rates to 6%, and intensive support plus NRT raised quit rates to 8% at 6 months.

The products currently licensed in the UK listed in Table 1 (NICE 2002).

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Table 1. Nicotine Replacement Therapies Technology Available in the UK

NRT Dose/Brand/ManufacturerNicotine transdermal patches 5mg, 10mg, 15 mg (Nicorette,

Pharmacia) 7mg, 14mg, 21mg per 24 hours

(NICOTINELLE TTS 10, TTS 20 &TTS 30 Novartis Consumer Health)

7mg, 14mg, 21mg (NiQuitin CQ, GlaxoSmithKline (GSK))

Nicotine chewing gum 2mg, 4mg (Nicorette, Phamacia) (Nicotinell, Novartis Consumer Health)

Nicotine sublingual tablet 2mg (Nicorette, Microtab, Pharmacia)Nicotine lozenge 1 mg (Nicotinell, Novartis Consumer

Health)Nicotine inhalation cartage plus mouthpiece

10mg (Nicorette, Inhalator, Pharmacia)

Nicotine nasal spray 0.5mg per puff metered nasal spray (Nicorette and Pharmacia

Nicotine lozenge 2mg and 4mg (NiQuitin CQ, GSK)

While successful in treating nicotine addiction, the markets for NRT and other pharmacological therapies are highly regulated. In turn, pharmaceutical treatments are less affordable and less available than nicotine-containing tobacco products that are distributed in a relatively unrelated market. Recent evidence indicates that the demand for these products is related to economic factors, including their price.30 Policies that decrease the cost of NRT and increase their availability, such as mandating private health insurance coverage of NRT, including NRT coverage in public health insurance programs, and subsidizing NRT for uninsured or underinsured individuals, would likely lead to substantial increases in the use of these products. Given their demonstrated efficacy in treating smoking, these policies could generate significant increases in smoking cessation and the health benefits that result from cessation.

NRT expenditures per capita vary widely between income group countries as well as between the US and other high-income countries. The US spends $2.11 per capita or $10.88 per smoker on NRT products in 1996, whereas other high-income countries on average spend $0.42 per capita or $1.63 per smoker. Middle-income countries’ expenditures on NRT are significantly less than that of other-income countries. Upper-middle income countries spend $0.03 per capita or $0.16 per smoker on NRT products. Lower-middle income countries’ spending are $0.003 per capita or $0.03 per smoker.

30 Tauras JA, Chaloupka FJ. The demand of nicotine replacement therapies. Working paper. Cambridge (MA): National Bureau of Economic Research, in press.

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Nicotine Replacement Products and Government Policies

A successful tobacco control policy on addiction treatment strongly depends on smoker’s demand for NRT products and government’s policies on availability and accessibility of these products. Most smokers start smoking at an early stage of their lives and later regret that they are smokers. For example, a survey from Indonesia indicates that over 80% of smokers want to quit smoking. Moreover, most smokers who say they want to stop, their efforts to quit have failed, often despite of frequent attempts.31

Policies and Problems for the Availability of NRTs

Patent policies, designed to give returns to research and development expenditures, are politically charged issues. Almost all industrialized and developing countries now recognize patents on both pharmaceutical products and process- usually for 20 years.

Given the monopolistic elements of the pharmaceutical market, price control policies on drugs are commonly found in countries at all income levels. The primary objective of the price controls is to control drug prices and expenditures. With regard to NRT and such pricing policies, there is not sufficient time series data to compare the trend on NRT expenditures for countries with and without price control policies. Second, countries did not include NRT products in their essential drug lists and also there is no reimbursement system for the NRT products in any country, as they are mostly available over the counter. Therefore, NRT products are not subject to any price control policies at all.

Given the market share of NRT products in pharmaceutical expenditures, especially in developing countries, including NRT products into essential drug list may increase the availability of these products. Most low and middle income countries have financial constraints to purchase drugs in the international level. When the NRT products are included in the essential drug lists, Ministries of health and finance should work together so that budgetary funds and foreign exchanges are available.

Although information on the regulation of advertising of the NRT products for the developed and developing countries is not available, only few developing countries allow NRT products to be advertised directly to consumer. For example, in Australia, 2mg gums are allowed to be advertised in 1997, and nicotine patches in 1998. Studies show that direct advertising in Australia32 and the US has increased the sales of these products. Some available information shows that most countries treat NRT products as medical drugs and do not permit advertising or permits with restrictions. Some restrictions on advertising of NRT products also create hurdles on availability of these drugs. In other words, permitted advertising with specific restrictions may create negative impact on consumers to purchase these products. For example, warning labels of NRT products in Italy, an advertising requirement, is one of the examples that may handicap marketing products in the country. All OTC products are required to provide a voice-over warning. NRT requires the following warning (that takes between 12-15 seconds to be read, thus effectively reducing the effect of the advertising in half (most commercials are 30 second ones):31 Warner KE, Peck CC, Woosley RL, Henningfield JE, Slade J, 1998, Treatment of tobacco dependence: innovative regulatory approaches to reduce death and disease:preface, Food Drug Law J. 53: suppl, 1-8.

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"This is a medicine for the reduction of smoking dependence. Read the Leaflet carefully and pay particular attention to the contraindications. Avoid smoking during the treatment. Do not use if you suffer from heart diseases, or if you are pregnant or breast feeding."

In terms of distribution restriction, Japan is very unique. It restricts NRT sales only to smokers who suffer from a tobacco attributable disease. In other words, NRT products are not available for smokers unless they are ill. In general, globally, NRT products are legally available either by prescription or over the counter. Consumers are required to get prescriptions from a physician to access the NRT products when the sales are restricted to by prescription only. The structure of the over- the-counter sales is more complex. Over-the-counter (OTC) NRT products are sold either in only by pharmacy or by general sales. For example, in the US, NRT products are available not only in pharmacies but also in other stores (grocery stores, supermarkets, etc). Consumers have an easy access to these products since they are widely available to the public. On the other hand, over-the-counter sales in most countries are restricted to pharmacy only. In most cases, consumers request these products from pharmacists since they are restricted. With well-trained pharmacists, this type of sale is likely to provide consumers safe products with therapeutic effectiveness, and lower costs in comparison to other products in low-and middle-income countries where self-prescription is common.

Currently developing countries face two problems which may alter the availability of NRT products; (1) few pharmacies to cover the population, and (ii) few trained pharmacists. For example, in Indonesia, over 200 pharmacies are providing drugs to 200 million people. This may be one of the reasons for a pharmaceutical company to withdraw NRT products from Indonesia six months after entering the market.

Trained pharmacists are also the only source of information for smokers in low-income countries regarding the availability of NRT products, because (1) the access to physician care is low, and (2) since NRTs are considered medical drugs, they are likely to be subject to advertising ban in some countries. Therefore, the importance of trained pharmacists and the number of pharmacies to cover the majority of population are important issues for the availability of NRT products.

Table 2 provides information of the legal status of NRT products in selected European countries and Japan. NRT nasal spray is sold by prescription in most countries, except Germany. In general, patches and gums are sold over the counter by pharmacy only.

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Table 2: Availability of NRT Products in European CountriesMARKET DOSAGE FORM LEGAL STATUS

Austria Patch Pharmacy OnlyAustria Nasal spray PrescriptionBelgium Patch Pharmacy OnlyBelgium Nasal spray PrescriptionCanada Patch PrescriptionCzech Republic Patch Pharmacy OnlyDenmark Patch Pharmacy OnlyDenmark Nasal spray PrescriptionDenmark Inhalator Pharmacy OnlyEstonia Patch Pharmacy OnlyFinland Inhalator Pharmacy OnlyFinland Patch Pharmacy OnlyFinland Nasal spray PrescriptionFrance Patch PrescriptionGermany Patch Pharmacy OnlyGermany Plaster Pharmacy OnlyGermany Nasal spray Pharmacy OnlyGermany Injection Pharmacy OnlyGreece Patch Lower doses for pharmacy, higher doses

for prescription only Greece Nasal Spray PrescriptionGreece Inhaler PrescriptionHungary Patch PrescriptionIreland Nasal spray PrescriptionIreland Patch Pharmacy OnlyItaly Patch Pharmacy OnlyItaly Inhalator Pharmacy OnlyItaly Solution? Pharmacy OnlyJapan Patch PrescriptionLatvia Patch Pharmacy OnlyLithuania Patch Pharmacy OnlyNetherlands Patch Pharmacy OnlyNetherlands Inhaler PrescriptionNetherlands Nose-spray PrescriptionNorway Spray PrescriptionNorway Inhalator Pharmacy OnlyNorway Patch Pharmacy OnlyPoland Patch PrescriptionPortugal Patch PrescriptionPortugal Nasal spray PrescriptionPortugal Inhalator PrescriptionRussia Patch Pharmacy OnlySpain Patch Pharmacy OnlySweden Patch Pharmacy OnlySweden Nasal spray PrescriptionSweden Inhalator Pharmacy OnlySwitzerland Nasal spray Prescription (?)Switzerland Patch PrescriptionUK Nasal Spray PrescriptionUK Patch Pharmacy Only

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MARKET DOSAGE FORM LEGAL STATUSUK Inhaler Pharmacy Only

Accessibility of NRT Products

It is critical to make cessation products more affordable to those who, so far, have been unable to afford them. It might be worthwhile to organize a campaign similar to that undertaken for AIDS treatment in Africa, which placed significant international pressure on pharmaceuticals companies to reconsider their pricing policies for AIDS drugs in poor African countries where the pandemic was escalating. Similarly, there is an argument to be made for making available cheap generic variants of NRT products and for the relaxation of patent laws for cessation products on the basis of extremely high death toll exacted by smoking and other tobacco use. The WHO FCTC addresses the accessibility and affordability of treatment for tobacco dependence when it states that parties shall endeavour to “collaborate with other Parties to facilitate accessibility and affordability for treatment of tobacco dependence including pharmaceutical products pursuant to Article 22. Such products and their constituents may include medicines, products used to administer medicines and diagnostics when appropriate”.Error: Reference source not found a. Geographical AccessibilityNRT products face the similar distribution and access problems as general drugs. Health care financing system, pharmaceutical policy and distribution systems of a country play a significant role on geographical accessibility.

In low-income countries, self prescription is common. Drugs registered for sale by prescription only are, in practice, often obtainable as easily as over-the-counter drugs. Private providers consist of small hospitals, clinics, individual physicians, and traditional healers. Drugs are purchased from pharmacies, health facilities, or drug peddlers. NRTs are, if available, sold mostly at pharmacies only. Expanding households’ geographic access to drugs is usually the main concern of pharmaceutical policy in low-income countries.

In middle-income countries, government regulatory capacity tends to be greater and more of the population has contact with organized health care delivery- both public and private. Drugs are purchased directly from pharmacies. Self-prescription is common, but a higher proportion of the population has regular contact with formal health providers, particularly large, organized providers. Having sufficient pharmacies to cover most of the population is still a problem for middle-income countries. Pharmacies are usually located in highly populated areas, which make it difficult for smokers to access these products. In most industrialized countries, health care delivery systems are highly organized; therefore there is no issue of geographical access. Drugs are available in general sales through over the counter and prescription.b. Financial AccessibilityFinancial accessibility of the NRT products depends on the country’s health financing system. Although most pharmaceutical drugs are subject to pricing policies, NRT products are not. One of the reasons is that NRT products are not included in the most essential drug lists in any country. Most countries have essential drug lists and one of their characteristics is to provide information to providers regarding which drugs are reimbursed by an insurance company. Up-to-date, NRT products are not reimbursed by either insurance companies or governments, except a few insurance companies in the United States.

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What Are the Opportunities for Research Into New Pharmaceutical Interventions?The current National Institutes of Health database (www.clinicaltrials.gov) provides more information on smoking-cessation pharmaceutical interventions in clinical trials in the United States (Table 3).

Table 3: NRT in USA Clinical Trials

Clinical Trial Sponsoring Organization

Name of the drug

Phase of trial

Number of

patients

Combinations of Pharmacologic Smoking Cessation Treatments

Department of Veterans Affairs

BupropionMecamylamineNicotine Patch

Phase I -

Tobacco Cessation in Postmenopausal Women (Part II) - 2

NIDA Nicotrol Phase I -

Comparing Smoking Treatment Programs for Lighter Smokers - 1

NIDA Nicotine transdermal system

Phase II 270

Effect of Combined Pharmacotherapy/Behavioral Treatment on Smoking Cessation For Methadone Maintenance Therapy Patients - 2

NIDA Bupropion Phase II 34

Effect of Combined Pharmacotherapy/Behavioral Treatment on Smoking Cessation For Methadone Maintenance Therapy Patients - 2

NIDA Bupropion Phase II 34

Pharmacologic Relapse Prevention for Alcoholic Smokers

NIAAA NRT patchBupropion (Wellbutrin)

Phase II 292

Quit Smoking Department of Veterans Affairs

MecamylamineNicotine Patch

Phase II -

Fluoxetine as a Quit Smoking Aid for Depression-Prone Smokers

Department of Veterans AffairsEli Lilly and Company

Nicotine transdermal system

Phase III

240

Smoking Cessation Treatment with Transdermal Nicotine Replacement Therapy - 1

NIDA Nicotine transdermal system

Phase III

585

Behavioral Counseling NIAAA NRT patch - Phase 144

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http://www.clinicaltrials.gov/


Clinical Trial Sponsoring Organization

Name of the drug

Phase of trial

Number of

patients

for Alcohol Dependent Smokers (nicotine patch)

Mood management

IV

Behavioral/Drug Therapy for Alcohol-Nicotine Dependence (naltrexone/nicotine patch)

NIAAA Naltrexone (Revia)Nicotine replacement patch

Phase IV

200

Bupropion and Weight Control for Smoking Cessation - 1

NIDA Bupropion Phase IV

450

Bupropion as a Smoking Cessation Aid in Alcoholics

NIAAA Bupropion (Wellbutrin)

Phase IV

200

Combination Nicotine Replacement for Alcoholic Smokers

NIAAA NRT patch and gum

Phase IV

175

Smoking Cessation in Alcoholism Treatment

NIAAA NRT patch Phase IV

112

Timing of Smoking Intervention in Alcohol Treatment (nicotine patch)

NIAAA NRT patch Phase IV

500

Tobacco Dependence in Alcoholism Treatment (nicotine patch/naltrexone)

NIAAA Naltrexone (Revia)NRT patch

Phase IV

166

Maintenance Treatment for Abstinent Smokers - 1

NIDA Bupropion 750

Mood and Smoking: A Comparison of Smoking Cessation Treatments


NRT - 128

Naltrexone and Patch for Smokers


Naltrexone Hydrochloride Transdermal Nicotine

- -

Nicotine Replacement Treatment for Pregnant Smokers

Oncken, Cheryl, MDHartford HospitalUniversity of ConnecticutDuke University

NRT (2 mg gum) - 268

Tobacco Dependence in Alcoholism Treatment (nicotine patch/naltrexone)

NIAAA Naltrexone (Revia)NRT patch

- 200

Use of Sibutramine in Smoking Cessation

NHLBI Sibutramine -

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NIDA: National Institute on Drug AbuseNIAAA: National Institute on Alcohol Abuse and AlcoholismNHLBI: National Heart, Lung, and Blood Institute

The database provided by the Pharmaceutical Research and Manufacturers of America (www.phrma.org) provides some further information on pharmaceutical interventions in Table 4.

Table 4: Additional Information on NRTs in clinical development

nicotine and mecamylamine transdermal patch none / nicotine and mecamylamine transdermal patch33

Elan PharmaceuticalsSouth Francisco, CA

Phase III Smoking Cessation

SR141716 none / cannabinoid receptor (CB1) antagonist(Acomplia ® (rimonabant))34

Sanofi-AventisNew York, NY

Phase III/Phase II /Phase II

ObesitySchizophreniaSmoking Cessation

6 US Department of Health and Human Services. The health benefits of smoking cessation: a report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Centers for Disease Control, Office on Smoking and Health, 1990 7 Peto R, Lopez AD, Boreham J, Thun M, Heath C Jr. Mortality from smoking in developed countries 1950-2000. Indirect estimation from National Vital Statistics. Oxford (UK): Oxford University Press; 1994. 11 Commission on Macroeconomics and Health. Macroeconomics and health: investing in health for economic development. www3.who.int/whosis/cmh/ (accessed 22 April 2003). (Commission on Macroeconomics and Health 2003).12 World Health Organization. Draft WHO framework convention on tobacco control. Intergovernmental negotiating body on the WHO Framework Convention on Tobacco Control. Geneva: WHO, March 2003;www.who.int/gb/fctc/PDF/inb6/einb65.pdf (accessed 22 April 2003)14 US Department of Health and Human Services. Reducing tobacco use: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, Office on Smoking and Health, 2000. www.cdc.gov/tobacco/sgr_tobacco_use.htm (accessed 3 May 2002)15 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: American Psychiatric Association, 1994 16 CDC. Cigarette smoking among adults – United States, 1995. MMWR Morb Mortal Wkly Rep 1997; 46:1217–20: CDC. Cigarette smoking among adults – United States, 2000. MMWR Morb Mortal Wkly Rep 2002; 51:642–5.17 Gupta PC. Is your population addicted? Cross country comparison of tobacco addiction and readiness to quit—global tobacco control implications. Satellite symposium at the 11th World Conference on Tobacco or Health, August 2000, Chicago, USA.18 Yang G, Lixin F, Tan J, et al. Smoking in China: findings of the 1996 national prevalence survey. JAMA 1999; 282:1247–5319 Yang G, Ma J, Chen A, et al. Smoking cessation in China: findings from the 1996 national prevalence survey. Tobacco Control 2001; 10:70–4.

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http://www.phrma.org/

http://www.cdc.gov/tobacco/sgr_tobacco_use.htm


Discussion/SummaryThe risks of medications are frequently evaluated against a condition in which there is no medication and no risk. By this standard, approved smoking cessation medications are remarkably low in risk. However, the comparison and risk benefit should be judged against a condition that kills 50% of those afflicted. By this standard, the risks of treatment medications are virtually nil, which is why the US Clinical Practice Guideline (1996 and 2000 versions) recommends that all smokers be offered medication therapy. This perspective is increasingly

20 US Department of Health and Human Services. The health consequences of smoking: nicotine addiction. A report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, Office on Smoking and Health, 1988 21 Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence. Clinical practice guideline. Rockville, MD: US Department of Health and Human Services, 200022Lancaster T, Stead L, Snowden A, et al. Cochrane Tobacco Addiction Group. In: The Cochrane Library, Issue 2, 2002. www.dphpc.ox.ac.uk/cochranetobacco/ (accessed 20 May 200225 Owen L. Impact of a telephone helpline for smokers who called during a mass media campaign. Tobacco Control 2000;9:148–5426 McAfee T, Wilson J, Dacey S, et al. Awakening the sleeping giant: mainstreaming efforts to decrease tobacco use in an HMO. HMO Pract 1995:138–43.27 Hedley AJ, Abdullah ASM, Lam TH, et al. Impact of smoking cessation services on smokers in Hong Kong and predictors of successful quitting. QUIT.COM, a publication on the treatment of tobacco dependency, Hong Kong Council on Smoking and Health, Hong Kong. 2001;2:1–8.28 World Health Organization Europe. Partnership to reduce tobacco dependence. Copenhagen: World Health Organization, 2000.32 Chapman S, Borland R, 1999, Advertising of Nicotine Replacement Therapy: has if promoted more smoking cessation.2 Murray CJ, Lopez AD. Alternative Projections of mortality and disability by cause, 1990-2020: Global Burden of the disease Study. Lancet 1997; 349:1498-504 3 Jha P, Chaloupka FJ, eds. Tobacco control in developing countries. Oxford: Oxford University Press, 20005 The Global Youth Tobacco Survey Collaborative Group (US Centers for DiseaseControl and Prevention; the World Health Organization, the Canadian Public HealthAssociation, and the U.S. National Cancer Institute). Tobacco use among youth: a crosscountry comparison. Tobacco Control 2002; 11; 252-270.10 World Bank, Development Report, Entering the 21st Century, 1999/2000, available at http://www.worldbank.org/wdr/2000/index.html, last accessed 6 October 2004.4 Samet J. Yoon SY. Women and the tobacco epidemic. Geneva: World health Organization; 2001.8 Doll R, Peto R, Wheatley K, et al. Mortality in relation to smoking: 40 years’ observations on male British doctors. BMJ 1994; 309:901–119 Terres W, Becker P, Rosenberg A. Changes in cardiovascular risk profile during the cessation of smoking. Am J Med 1994; 97:242–9

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http://www.worldbank.org/wdr/2000/index.html


being taken by expert committees, including just recently a new NCI/NIDA/FDA panel (August 2004, unpublished).

References

13 Novotny TE, Cohen JC, Yurekli A, et al. Smoking cessation and nicotine replacement therapies. In: Jha P, Chaloupka F, eds. Tobacco control in developing countries. New York: Oxford University Press, 2000:287–307 23 US Preventive Services Task Force. Guide to clinical preventive services, 3rd ed. Rockville, MD: US Department of Health and Human Services, 2002. www.ahrq.gov/clinic/cps3dix.htm (accessed 7 May 2002).24 Hopkins DP, Briss PA, Ricard CJ, et al. Reviews of evidence regarding interventions to reduce tobacco use and exposure to environmental tobacco smoke. Am J Prev Med 2001;20(Suppl 2):16–6629 Raw M, McNeil A, West R. Smoking cessation: evidence-based recommendations for the healthcare system. BMJ 1999; 318:182-8533 Clinical Pharmacology and Therapeutics (1994);56:86-99; Psychopharmacology, (2000) 148: 234-242; Lancaster T, Stead LF. Mecamylamine (a nicotine antagonist) for smoking cessation (Cochrane Review). In: The Cochrane Library, Issue 3, 2004.34 Cohen, C.; Perrault, G.; Voltz, C.; Steinberg, R.; Soubrie, P SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behavioural Pharmacology, (2002). 13(5-6):451-463,

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nicotine replacement products and government...

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