Table Of ContentCanadian Agency for Agence canadienne
Drugs and Technologies des médicaments et des
in Health technologies de la santé
CADTH Technology Report
Issue 130
Pharmacologic-based Strategies for Smoking
September 2010
Amended Cessation: Clinical and Cost-Effectiveness
October 2011 Analyses
Supporting Informed Decisions
Cite as: Tran K, Asakawa K, Cimon K, Moulton K, Kaunelis D, Pipe A, Selby P.
Pharmacologic-based Strategies for Smoking Cessation: Clinical and Cost-Effectiveness
Analyses [Internet]. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2010.
(Technology Report; no. 130). [cited 2010-09-21]. Available from:
http://www.cadth.ca/index.php/en/hta/reports-publications/search?&type=16
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Legal Deposit – 2010
Library and Archives Canada
ISBN: 1922-6101 (print)
ISBN: 1922-611X (online)
H0486 – September 2010
Canadian Agency for Drugs and Technologies in Health
Pharmacologic-based Strategies for Smoking Cessation:
Clinical and Cost-Effectiveness Analyses
1
Khai Tran, MSc, PhD
1
Keiko Asakawa, MA (Econ), MBA, PhD
1
Karen Cimon, MLT
1
Kristen Moulton, BA
1
David Kaunelis, MLIS
2
Andrew Pipe, CM, MD, LLD (Hon), DSc (Hon)
3
Peter Selby, MBBS, CCFP
September 2010
Amended October 2011
1
Canadian Agency for Drugs and Technologies in Health (CADTH), Ottawa, Ontario
2
The Minto Prevention and Rehabilitation Centre, University of Ottawa Heart Institute, Ottawa, O ntario
3
Departments of Family and Community Medi cine and Psychiatry, Faculty of Medicine and the Dalla Lana School
of Public Health, University of Toronto, Toronto, O ntario
Reviewers
This document was externally reviewed by content experts and the following individuals granted
permission to be cited.
External Reviewers
Eric Nauenberg, PhD Rebecca Warburton, PhD Economics
Associate Professor (SO) Associate Professor
University of Toronto University of Victoria
Toronto, Ontario Victoria, British Columbia
Lawrence Joseph, PhD
Full Professor
McGill University
Montreal, Quebec
CADTH Peer Review Group Reviewers
Stuart Peacock, BA, MSc, DPhil Jed E. Rose, PhD
Co-Director, Professor,
Canadian Centre for Applied Research in Duke University Medical Center
Cancer Control (ARCC) Durham, North Carolina
Vancouver, British Columbia
Authorship
Khai Tran, research lead, coordinated the research project; selected studies; extracted, tabulated
and analyzed data; and wrote the clinical sections of the report.
Keiko Asakawa, lead for the economic section, selected articles; extracted data for the economic
review; performed the economic modelling, and population and budget impact analyses; wrote
the economic, budget impact, and population impact sections; and contributed to revisions.
Karen Cimon contributed to article selection, study quality assessment, data extraction and
tabulation, and analysis of data for the clinical review.
Kristen Moulton contributed to article selection, study quality assessment, data extraction,
tabulation of data, and preparation of tables for the economic review.
Peter Selby contributed to the review and conceptualization of the research questions,
identification of articles or topic areas that were missed in the search, review of the first draft,
and critical review of the final draft.
Andrew Pipe participated in the conceptualization of clinical approaches to smoking cessation,
preparation and revision of portions of the manuscript addressing clinical considerations and
descriptions of smoking-related diseases, and editing and revisions of the final draft.
David Kaunelis developed the literature search strategies, performed all searches and search
updates, managed report referencing, composed the search methodology sections and Appendix
1, reviewed drafts, and approved the final version of the report.
i Pharmacologic-based Strategies for Smoking Cessation:
Clinical and Cost-Effectiveness Analyses
Acknowledgments
The authors are grateful to Keith O’Rourke f or programming and statistical advice; to Doug
Coyle for his feedback, support, and advice on the economic model; to Krystle Griffin and Pat
Reynard for project management support; and to Brian Hutton for critical reading of the report
and feedback.
Conflicts of Interest
Dr. Pipe has received speaking and consulting fees from Pfizer. He has also received consulting
fees from Glaxo Smith Kline and Johnson & Johnson. Dr. Pipe was involved in the following:
A 12-week, double blind, placebo controlled, multic entre study with a 40 week follow -up
evaluating the safety and efficacy of Varenicline Tartrate 1 mg bid for smoking cessation in
subjects with cardiovascular disease. $158,400 Pfizer Inc. (USA) 2005 -08 (Principal
Investigator)
STOP (Smoking Therapy for Ontario Patients) Study: The effectiveness of nicotine replacement
therapy in Ontario smokers. $3,000,000 Ministry of Health Promotion, Ontario Ministry of
Health and Long-term Care, Pfizer Inc. 2005-06 (Co-investigator)
A 52-week multicentre study evaluat ing the safety and efficacy of Varenicline (CP -526,555) for
the maintenance of smoking cessation. $777,169 Pfizer Inc. (USA) 2003 -05 (Principal
Investigator)
Pilot Study of Telephone Counselling for Smokers Attempting to Quit with Nicotrol: Impact on
Abstinence at Six-month Follow-up. $36,000 McNeil Consumer Products Company. 1995
A Study to Compare the Effects of Pravastatin, Lovastatin, Simvastatin, and Placebo on
Eccentric Exercise-Induced Changes in Muscle. $199,962 Bristol -Myers Squibb. 1992-93
A Study to Compare the Effects of Simvastatin and Placebo on Eccentric Exercise -Induced
Changes in Muscle. $63,608 Bristol -Myers Squibb. 1991-92
Dr. Peter Selby has been a paid consultant and member of advisory boards with Johnson &
Johnson Consumer Healthcare Canada, Pfizer Inc. Canada, Pfizer Global, Sanofi -Synthelabo
Canada, GlaxoSmithKline Canada, Genpharm and Prempharm Canada, Nabi Pharmaceuticals
and Schering Canada (buprenorphine training 2000). He received consulting fees from V -CC
Systems Inc. and eHealth Behaviour Change Software Co. Dr. Selby has received grants as a
principal and co-investigator from Health Canada, Smoke Free Ontario, Ministry of Health
Promotion (MHP), the Canadian Tobacco Control Research Initiative (CTCRI), Canadian
Institutes of Health Research (CIHR), Alberta Health Services (formerly Alberta Cancer Board),
and the Vancouver Coastal HealthAuthority to fund research.
Dr. Stuart Peacock has received two unrestricted educational grants from Hoffman-La Roche and
AstraZeneca.
Dr. Jed Rose has received a grant from Philip Morris USA to support adult smoking cessation.
He has also done consulting within the last three years for GlaxoSmithKline, Novartis, Philip
Morris International,Targacept, Catalyst Pharmaceutical Partners, Lorillard, the University of
Kentucky, MEDACorp, PharmaLink, and Noble Medical Consulting Group. Dr. Rose was
named on patent applications for nicotine inhalation technology, genetic predictors of quit-
smoking success, neurosteroid hormones for smoking cessation treatment, and on an issued
patent for agonist-antagonist treatment of nicotine dependence and oral nicotine administration.
Pharmacologic-based Strategies for Smoking Cessation: ii
Clinical and Cost-Effectiveness Analyses
TABLE OF CONTENTS
ABBREVIATIONS ..................................................................................................................... vi
GLOSSARY ...................................................................................................................... vii
1 INTRODUCTION ...............................................................................................................1
1.1 Background and Setting in Canada ...........................................................................1
1.2 Overview of Technology ...........................................................................................3
1.2.1 Nicotine replacement therapy ................................................................................ 3
1.2.2 Bupropion ............................................................................................................... 4
1.2.3 Varenicline ............................................................................................................. 4
2 THE ISSUE ........................................................................................................................5
3 OBJECTIVES ....................................................................................................................5
4 CLINICAL REVIEW ...........................................................................................................7
4.1 Methods ...............................................................................................................7
4.1.1 Literature searches ................................................................................................ 7
4.1.2 Selection criteria ..................................................................................................... 7
4.1.3 Selection method ................................................................................................... 8
4.1.4 Data extraction strategy ......................................................................................... 8
4.1.5 Strategy for validity assessment ............................................................................ 8
4.1.6 Data analysis methods ........................................................................................... 9
4.2 Results ............................................................................................................. 12
4.2.1 Quantity of research available ............................................................................. 12
4.2.2 Study characteristics ............................................................................................ 12
4.2.3 Data analyses and synthesis ............................................................................... 19
5 ECONOMIC ANALYSIS .................................................................................................. 41
5.1 Review of Economic Studies: Methods ...................................................................... 41
5.1.1 Literature searches .............................................................................................. 41
5.1.2 Selection criteria ................................................................................................... 41
5.1.3 Selection method ................................................................................................. 41
5.1.4 Data extraction strategy ....................................................................................... 42
5.1.5 Strategy for validity assessment .......................................................................... 42
5.1.6 Data analysis methods ......................................................................................... 42
5.2 Review of Economic Studies: Results ........................................................................ 42
5.2.1 Study selection ..................................................................................................... 42
5.2.2 Study characteristics ............................................................................................ 43
5.2.3 Results from included studies .............................................................................. 44
5.2.4 Quality assessment .............................................................................................. 47
5.3 Primary Economic Evaluation: Methods..................................................................... 47
5.3.1 Types of economic evaluation ............................................................................. 47
5.3.2 Target population ................................................................................................. 48
5.3.3 Comparators ........................................................................................................ 48
5.3.4 Perspective .......................................................................................................... 48
5.3.5 Effectiveness ........................................................................................................ 48
5.3.6 Time horizon ........................................................................................................ 52
5.3.7 Modelling .............................................................................................................. 52
5.3.8 Valuing outcomes................................................................................................. 61
5.3.9 Resource use and costs ...................................................................................... 62
5.3.10 Discount rate.......................................................................................................... 65
5.3.11 Variability and uncertainty .................................................................................... 65
5.4 Primary Economic Evaluation: Results.................................................................... 68
iii Pharmacologic-based Strategies for Smoking Cessation:
Clinical and Cost-Effectiveness Analyses
5.4.1 Among the general population of smokers, what is the
cost-effectiveness of varenicline compared wit h that of bupropion
and that of NRT? ................................................................................................. 68
5.4.2 Among the general population of smokers using varenicline,
or bupropion or NRT, what is the cost-effectiveness of adding a
behavioural support program to drug therapy? ................................................... 72
5.4.3 What is the impact of copayment (of insurance claim) or
payment (i.e., purchase drug as over-the-counter product) on the
cost-effectiveness of drugs used for smoking cessation therapy? ..................... 73
5.4.4 Among smokers, what is the cost-effectiveness of treating
specific patient populations with varenicline or bupropion or
NRT, including a combination of these agents with behavioural
support programs? .............................................................................................. 74
6 HEALTH SERVICES IMPACT ......................................................................................... 76
6.1 Population Impact ................................................................................................... 76
6.2 Budget Impact ......................................................................................................... 77
6.2.1 Adopting strategies with optimal cost-effectiveness ............................................ 83
6.2.2 Implementing payment or copayment programs ................................................. 84
7 ISSUES FOR WILLINGNESS OF SMOKERS TO PAY .................................................. 84
7.1 Methods ............................................................................................................. 84
7.1.1 Literature searches ................................................................................................ 84
7.1.2 Selection criteria .................................................................................................... 85
7.1.3 Data selection and analysis ................................................................................... 85
7.2 Results ............................................................................................................. 85
8 PLANNING ISSUES FOR OPTIMAL TREATMENT STRATEGIES ................................ 86
8.1 Methods ............................................................................................................. 86
8.1.1 Literature searches .............................................................................................. 86
8.1.2 Selection criteria ................................................................................................... 87
8.1.3 Data selection and analysis ................................................................................. 87
8.2 Results ............................................................................................................. 87
8.2.1 General issues ..................................................................................................... 87
8.2.2 Issues of specific populations .............................................................................. 88
8.2.3 Accountability ....................................................................................................... 90
9 PUBLICLY FUNDED PROGRAMS IN CANADA ............................................................. 91
9.1 Methods ............................................................................................................. 91
9.2 Results ............................................................................................................. 91
10 DISCUSSION .................................................................................................................. 92
10.1 Summary of Results ................................................................................................ 92
10.1.1 Clinical ................................................................................................................... 92
10.1.3 Economic ............................................................................................................... 95
10.1.4 Comparison with relevant recent literature............................................................ 96
10.2 Strengths and Weaknesses of This Assessment .................................................... 97
10.2.1 Clinical ................................................................................................................... 97
10.2.2 Economic ............................................................................................................... 98
10.3 Generalizability of Findings ................................................................................... 100
10.3.1 Clinical ................................................................................................................ 100
10.3.2 Economic............................................................................................................ 104
10.4 Knowledge Gaps .................................................................................................. 105
10.4.1 Clinical ................................................................................................................ 105
10.4.2 Economic............................................................................................................ 105
11 CONCLUSIONS ............................................................................................................ 106
12 REFERENCES .............................................................................................................. 107
Pharmacologic-based Strategies for Smoking Cessation: iv
Clinical and Cost-Effectiveness Analyses
Appendix 1: Literature search strategy ...................................................................................1
Appendix 2: Selected reports for clinical review .................................................................. 11
Appendix 3: Data Extraction Form and Quality Assessment for
Clinical-Effectiveness Studies ........................................................................ 12
Appendix 4: Included studies for questions 1-4, 11, 12 ...................................................... 14
Appendix 5: Network diagrams connecting placebo-controlled
and head-to-head trials ................................................................................... 29
Appendix 6: Characteristics of the included trials ............................................................... 31
Appendix 7: Quality assessment of the included trials ...................................................... 159
Appendix 8: Clinical effects on cessation rates and relapse ............................................. 165
Appendix 9: Data extraction form for economic studies .................................................... 219
Appendix 10: Excluded economic studies .......................................................................... 220
Appendix 11: Selected reports for economic review .......................................................... 223
Appendix 12: Included economic studies ........................................................................... 224
Appendix 13: Quality assessment of economic studies .................................................... 250
Appendix 14: Transition probabilities for chronic condition model .................................. 251
Appendix 15: Calculation of all-cause mortality by smoking status ................................. 265
Appendix 16: Methods for the analysis of the Canadian
Community Health Survey ............................................................................ 270
Appendix 17: Utility scores for health states by age, gender and/or
smoking status .............................................................................................. 273
Appendix 18: Intervention costs for economic models other
than the general population .......................................................................... 274
Appendix 20: Detailed results of economic analyis by age and gender ........................... 278
Appendix 21: Clinical efficacy data used for sensitivity analyses .................................... 287
Appendix 22: Sensitivity analyses for general population model ..................................... 289
Appendix 23: MCS results for general population .............................................................. 298
Appendix 24: Calculation of smokers who attempt to quit smoking ................................. 303
Appendix 25: EVPI by age and gender for general population .......................................... 306
Appendix 26: Sensitivity analyses for models for cost-effectiveness of adding
behavioural intervention ............................................................................... 307
Appendix 27: MCS for models for cost-effectiveness of adding
behavioural intervention ............................................................................... 309
Appendix 28: Sensitivity analyses for pay or copay models ............................................. 310
Appendix 29: MCS results for pay or copay model ............................................................ 311
Appendix 30: Sensitivity analyses of models for patients with
cardiovascular or smoking-related diseases .............................................. 312
Appendix 31: MCS results for models for patients with cardiovascular
or other smoking related diseases ............................................................... 315
Appendix 32: Sensitivity analyses of models for hospitalized patients ............................ 316
Appendix 33: MCS results for hospitalized patients .......................................................... 318
Appendix 34: Smoking prevalence by provinces in 2007 (age 15+) .................................. 319
Appendix 35: Number (%) of daily smokers, by age, who made at least
one quit attempt in the past 12 months (2004 – 2007) ................................ 320
Appendix 36: Summary of the number of claims and expenditures
for NRT, bupropion, and varenicline ............................................................ 321
Appendix 37: Average cost per claim and changes in the number of claims
|for NRT, bupropion, and varenicline (2004/2005 – 2007/2008) .................. 323
Appendix 38: Estimated number of claims and cost per claim by jurisdiction§ .............. 324
Appendix 39: Data extraction sheet for questions 11 and 12 ............................................ 326
Appendix 40: Selected reports for questions 11 and 12 .................................................... 327
v Pharmacologic-based Strategies for Smoking Cessation:
Clinical and Cost-Effectiveness Analyses
ABBREVIATIONS
AHRQ Agency for Healthcare Research and Quality
CAR continuous abstinence rate
CBA cost-benefit analysis
CCHS Canadian Community Health Survey
CEA cost-effectiveness analysis
CEAC cost-effectiveness acceptability curves
CEAF cost-effectiveness acceptability frontier
CHD coronary heart disease
CI confidence interval
CINAHL Cumulative Index to Nursing and Allied Health Literature
CMA cost-minimization analysis
COPD chronic obstructive pulmonary disease
CRD Centre for Reviews and Dissemination
CrI credible interval
CT controlled trial
CUA cost-utility analysis
EVPI expected value of perfect information
EVPPI expected value of perfect partial information
FNIHB First Nations and Inuit Health Branch
HEED Health Economic Evaluations Database
HUI3 Health Utilities Index Mark 3
ICER incremental cost-effectiveness ratio
LY life-year
MCMC Markov Chain Monte Carlo
MCS Monte Carlo simulation
MI myocardial infarction
MTC mixed treatment comparisons
NRT nicotine replacement therapy
OCCI Ontario Case Costing Initiative
OR odds ratio
PPA point prevalence abstinence
PVD-AAA peripheral vascular disease or abdominal aortic aneurysm
PUMF Public Use Microdata Files
QALY quality-adjusted life-year
RCT randomized controlled trial
TIA transient ischemic attack
VOI value of information
Pharmacologic-based Strategies for Smoking Cessation: vi
Clinical and Cost-Effectiveness Analyses
GLOSSARY
Continuous abstinence rate: the proportion of people who have not smoked since the commencement of
a cessation intervention.
Cost-benefit analysis: an economic analysis that assesses incremental costs and outcomes of alternative
interventions, where cost and outcomes are measured as monetary units.
Cost-effectiveness acceptability curves: a set of curves representing the probability of each alternative
intervention being cost-effective across a range of cost-effectiveness threshold values.
Cost-effectiveness acceptability frontier: a continuous or discontinuous curve representing the optimal
choice of intervention (i.e., an intervention providing the highest net benefit) at each level of a range of
cost-effectiveness thresholds.
Cost-effectiveness analysis: an economic analysis that compares incremental cost and outcomes of
alternative interventions, where outcomes are measured as natural units (e.g., life-years gained, deaths
avoided).
Cost-minimization analysis: an economic analysis that compares costs among interventions of interest.
Cost-utility analysis: an economic analysis that assesses incremental costs and outcomes, where
outcomes incorporate health state preferences (e.g., quality-adjusted life-years).
Deterministic sensitivity analysis: an analysis that assesses the degree of impact of changes in one or a
set of fixed input parameters on overall cost-effectiveness results.
Dominated therapies: interventions that are more expensive and generate less benefit compared with at
least one of the other interventions being considered. Two types of dominance are strict dominance and
extended dominance. A strictly dominated therapy indicates that the therapy is more expensive and
generates less benefit compared with at least one of other therapies. When a therapy is dominated by
extended dominance, it indicates that the therapy is more expensive and generates less benefit compared
with a combination of other therapies being considered.
EQ-5D: a generic, multi-attribute, preference-based measure of health-related quality of life. EQ-5D
consists of five dimensions: mobility, self-care, usual activities, pain or discomfort, and anxiety or
depression, with three levels in each dimension, describing 243 unique health states. A score of one
1
represents perfect health as defined in the EQ-5D instrument, and a score of zero represents death.
Expected value of partial perfect information: an uncertainty analysis in economic modelling that
quantifies the level of decision uncertainty attributable to one or a set of stochastic input parameters in
economic models over total decision uncertainty.
Expected value of perfect information: an uncertainty analysis in economic modelling that quantifies the
level of decision uncertainty by estimating opportunity cost of making an uncertain decision, given
currently available information.
Health-related quality of life: “value assigned to duration of life as modified by the impairments,
functional states, perceptions, and social opportunities that are influenced by disease, injury, treatment, or
2
policy.” (p.22)
Health Utilities Index Mark 3 (HUI3): a generic, multi-attribute and preference-based measure of health-
related quality of life. HUI3 consists of eight dimensions: vision, hearing, speech, ambulation, dexterity,
emotion, cognition, and pain, with five to six levels in each dimension, describing 973,000 unique health
states. A score of one represents perfect health as defined in the HUI3 instrument, and a score of zero
3
represents death.
vii Pharmacologic-based Strategies for Smoking Cessation:
Clinical and Cost-Effectiveness Analyses
