A Harm-Based Classification of Preps

Final Research Report

A Harm-Based Classification of PREPs

In Support of an Effective Policy Debate on Potential Reduced-Exposure Products (PREPs), Tobacco and Tobacco Replacement Products

Marc Saner, John Capelli and Kirk Michaelian

Canadian Tobacco Control Research Initiative (CTCRI) Grant 834-2002-1003

Draft 3 – August 2005 – Public Review Version The views expressed in this document are the views of the author and do not necessarily reflect those of the Institute On Governance or its Board of Directors.

The Institute On Governance (IOG) is a Canadian, non-profit think tank founded in 1990 to promote responsive and responsible governance both in Canada and abroad. We define governance as the process whereby power is exercised, decisions are made, citizens or stakeholders are given voice, and account is rendered on important issues.

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A Harm-Based Classification of PREPS ii Institute On Governance Contents

Acknowledgments...... 2 Abstract...... 3 1.1. Why Do We Need a Classification of PREPs?...... 4 1.2. The Relationship Between PREPs and Harm Reduction...... 5 1.3. The Need for Harm Profiles and the Harm-Based Classification of PREPs ...... 6 2. Methods ...... 7 3. Results...... 8 3.1. A Working Definition of “Potential Reduced-Exposure Products” ...... 8 3.2. A Basic Classification of PREPs ...... 11 3.2.1. Justification...... 11 3.2.2. Criteria ...... 12 3.2.3. Basic Classification...... 14 3.3. Conceptualizing Harm ...... 20 3.4. A Harm-based Classification of PREPs...... 23 3.4.1. Criteria for Harm Profiles ...... 23 3.4.2. Harm Profiles For the Basic Classification...... 26 3.4.3. Harm-based Classification...... 28 4. Conclusions...... 33 4.1. Recommendations...... 33 4.2. Directions for future research ...... 37 5. Literature review...... 38 Acknowledgments

This research is supported by a “Better Practices in Tobacco Control” Grant of the Canadian Tobacco Control Research Initiative (File Number 834-2002-1003) with funds from the National Cancer Institute of Canada, the Canadian Cancer Society and the Social Science and Humanities Research Council of Canada. The Institute on Governance is grateful for this support.

For comments at various stages of their research, the authors wish to thank the participants of a one-day seminar (November 26, 2003) for their feedback on our work-in-progress: Byron Rogers and Dr. Thea Mueller (Health Canada), Lucie Larose and Krishan Kumar (Agriculture and Agri-Food Canada), Dr. Daniela Jukic and Sylvie Poissant (Pfizer Canada), Robert Walsh (Canadian Council for Tobacco Control), David Sweanor (Non-Smokers' Rights Association), Eugene Oscapella (Canadian Foundation for Drug Policy) and Debbie McCulloch (City of Ottawa).

Important insights were gained during a Health Canada-organized Expert Consultation on the Ethics of Harm Reduction and Product Modification (February 23-24, 2004). The roundtable of experts consisted of Jeff Fowles, Brion Fox, Joy Johnson, Lynn Kozlowski, Edwin Levy, Paddi O’Hara, Bill Rickert, Ted Schrecker, and Susan Sherwin (and the first author of this report).

We also thank the members of the Institute On Governance-led informal, virtual working group: Tania Calvacante, Denis Choinière, Jeff Fowles, Brion Fox, Murray Kaiserman, Thea Mueller, Byron Rogers, and Mitch Zellner.

The content of this report is the full responsibility of the authors. This acknowledgment does not imply any form of endorsement of the work presented here by the individuals named above.

A Harm-Based Classification of PREPS 2 Institute On Governance Abstract

This paper develops a draft harm-based classification of so-called "potential reduced-exposure products" (PREPs) as a tool in the discussion of the utility of these products in harm reduction strategies, and in the broader discussions over nicotine and tobacco regulatory and policy development.

To this end, the paper develops definitions of the terms "PREP" and "harm" and provides an inquiry into the concept "harm reduction." Following from this, the concept of a harm profile for PREPs is developed. The harm profile used in the paper contains the following ten elements: morbidity, mortality, problematic addiction, harm to the health or longevity of bystanders, harm to the health of children or foetuses, differential harm according to gender, differential harm according to racial or aboriginal origin, differential harm according to economic status or age, cost to the health care system, and increase in societal tobacco usage rate. In other words, it is a system that cascades from the harm to users, to bystanders, to groups and, finally, to society.

The classification project was carried out in three steps. First, we listed the PREPs that should be classified within a harm-based classification. Because of the large number of products in development or on the market, it was necessary to develop a basic classification of PREPs. In a second step, harm profiles were developed for each of the approximately 60 classes in the basic classifications. Finally, based on the similarities observed in the harm profiles of the various classes, a new, harm-based classification was developed. This resulted in 10 harm-based classes of products.

The paper concludes with a list of 10 discussion points that the tobacco control community may want to consider, and with ideas for future research.

A Harm-Based Classification of PREPS 3 Institute On Governance 1. Introduction

1.1. Why Do We Need a Classification of PREPs?

This paper develops a draft harm-based classification of so-called “potential reduced-exposure products” (PREPs).1 That classification will comprise, it is hoped, a useful tool in the discussions on PREPs, harm reduction, and nicotine and tobacco policy development.

Why are PREPs an issue for debate? From a Canadian perspective, there are at least three drivers of such a debate:

(1) An important report by the Institute of Medicine (2001) – Clearing the Smoke – Assessing the Science Base for Tobacco Harm Reduction – coined the term “PREP” and put the issue on the map internationally. The report neither contains an explicit definition of PREPs nor does it contain a classification scheme.

(2) “Harm reduction” is one of the four pillars of Canada’s Federal Tobacco Control Strategy.2 Obviously PREPs, in the sense of products designed to reduce harm, are of relevance to that strategy. Yet there is no consensus to-date on what role, if any, PREPs should play in its implementation. If they are to play some role, a harm-based classification would be of value for policy development or regulatory purposes (if not, then government officials would have explain why PREPs do not reduce harm).

(3) A number of new products that could be considered “PREPs” are currently being developed or are entering the market. For this reason, the need for reflection and discussion regarding the integration of PREPs into the Tobacco Control Strategy is more urgent.3 These products are very varied in design and use and it is sometimes unclear if they would be best considered tobacco products, natural health products or therapeutic pharmaceutical products. A classification helps to “manage the pipeline” from the point of view of officials with regulatory power.

1 Some authors use the word “potentially” instead of “potential”. For technical background material on PREPs, see Schiffman et al., 2002, "Tobacco harm reduction: Conceptual structure and nomenclature for analysis and research," in Nicotine & Tobacco Research 4 (4) Suppl. 2 pp.113-29; and Stratton et al., 2001, Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction.

2 The four pillars of Canada’s Federal Tobacco Control Strategy are protection, prevention, cessation, and harm reduction. Specifically, this strategy aims to achieve the long-term outcome of reduced tobacco-related illness and death. A key instrument of the Federal Tobacco Control Strategy is the Canadian Tobacco Act of 1997. The Tobacco Act allows regulators to intervene in the following four domains: (1) manufacturing, (2) labelling, (3) marketing and promotion, and (4) sale of tobacco products. In the past, interventions from the Tobacco Control Program (TCP) have taken place mainly in the latter three, but only to a lesser extent the first domain. As a consequence, it is meaningful to consider what activities in the manufacturing stage could aid in achieving the goals of the Tobacco Control Strategy. One possibility is to control the toxicity or modes of delivery of manufactured tobacco or nicotine products. PREPs are of interest in this context. 3 “A Canadian Tobacco Harm Reduction Framework: Exploring the Ethical and Policy Implications of Modifying Tobacco Products” (draft), Health Canada Tobacco Control Program, InterOffice Working Group on ‘Harm Reduction’, Summer 2003.

A Harm-Based Classification of PREPS 4 Institute On Governance In the absence of a clear definition and classification of PREPs many discussions will suffer from ambiguity. Are we talking principally about modified cigarettes or do we include nicotine therapies, smokeless tobacco and other products? Should “reduced exposure” include the idea of cessation or should it designate only products designed for tobacco users who cannot, or do not want to, quit their harmful habit? Is it sufficient to prove that there is a reduction in exposure to harmful substances or do proponents need to show a comparative health benefit? Finally, whose exposure should be reduced – the consumer, the bystander, or both? The vague claim that something may reduce exposure does not go very far in this context since claims can be unproven or shown to be groundless. We believe that a common conception is necessary. A first step toward achieving this common conception would consist of a classification that is capable of covering any conceivable “PREP.”

1.2. The Relationship Between PREPs and Harm Reduction

The basic logic of the relationship between PREPs and harm reduction is the following:

1. Exposure to many ingredients of tobacco is harmful. 2. PREPs, by definition, reduce such exposure. 3. Therefore, a PREP, in all likelihood, will lead to a reduction in harm.

This argument, however, is very superficial. It is not clear that any reduction in the exposure to a harmful compound will translate into a harm reduction. And what harm do we have in mind? Which component of human health is most relevant? Do we consider bystanders and do we want to go so far as to include harms other than negative health effects? How does a reduced exposure fare at a societal level? Are people lured into a false sense of security that actually increases the exposure to harmful ingredients?

We should think in terms of a more complete argument to illustrate the relationship between PREPs and harm reduction. Such an argument could involve the following premises and conclusion:

1. Exposure to many ingredients of tobacco is harmful. 2. Exposure by some pathways is more harmful than exposure by other pathways. 3. Some products expose bystanders more than others. 4. Exposure is not only a function of the exposure gained from a single token of a product (e.g., a single cigarette) but the cumulative exposure over time. 5. Exposure is not only a function of the exposure of an individual but of the society as a whole (including future potential users). 6. PREPs by definition reduce exposure to some potentially harmful ingredient in tobacco (to the user, and/or bystanders, and/or society as a whole). 7. If PREPs: a. indeed reduce exposure to a dangerous compound b. and this reduction is effective in translating into a health benefit c. and this reduction is not offset by unwanted side-effects such as

A Harm-Based Classification of PREPS 5 Institute On Governance i. a decrease in the interest in quitting tobacco consumption altogether ii. an increase in consumption by the user iii. an increase in tobacco users overall (possibly including new users) iv. an increase in harm to bystanders or society v. an undesirable change in the nature and profile of the harms (etc.) then a form of harm reduction may be achieved – depending on how the various harms and benefits are weighed against each other.

No doubt this argument is still far from being complete – but, in its current form, it dispels the view that the linkage between PREPs and harm reduction is obvious and imminent.

1.3. The Need for Harm Profiles and the Harm-Based Classification of PREPs

Describing a reduction in exposure from a product is a scientific question. It is possible to simply measure the relationship between the normal consumption of a product and the resulting uptake of specific compounds by the average human body. No ethical judgment (is it “good” or “bad”) is necessary for this description. All that is required is the choice of a medically relevant endpoint and accurate measurements.

Defining and evaluating a reduction in harm, however, is an ethical question. The judgments required are intimately linked to such questions as: Who or what counts? Is it good or bad? Should we care? What counts most? How do we arbitrate conflicting benefits or harms? The natural sciences cannot help here – although they are absolutely necessary for the overall debate because they provide key elements of the factual basis of the discussion.

As a result, the step from PREP to harm reduction is very significant. In philosophical terms, it is a step from the “is” to the “ought”, from the world of the natural sciences to the world of values, beliefs, politics, policies, and the like. We believe it greatly improves the debate if this point is made explicit. One of the important consequences is that it moves the debate from the circles of scientists (who, one could say, have the monopoly on facts) to a broader sphere – the so-called stakeholders. The discussion and decision-making process thus becomes a governance question.

As a result, the basic classification that is capable of covering any conceivable “PREP” (mentioned above) is an incomplete tool to support the discussion. It needs to be accompanied by a second tool that makes the idea of harm explicit. It is for this reason that we develop the concept of harm profiles and a harm-based classification of PREPs in this paper. Such a classification moves the discussion into the world of ethics and values, which is much more relevant to policy development because it allows for the identification of the products groups that are of interest. In other words, this classification is required for the all-important priority setting that takes place in policy debate.

A Harm-Based Classification of PREPS 6 Institute On Governance 2. Methods

This research grew out of an Institute On Governance scoping study prepared by the first two authors for Health Canada’s Tobacco Control Program.4 This preliminary work was focused on ethics but required the development of a rudimentary classification of PREPs. This first classification was used as the basis for interviews with government officials. It contained only 5 different classes of products (which, incidentally, is more than the product classes contained in Clearing the Smoke). The first task of the current research was to verify the completeness of this early classification.

The current research encompassed the following subsequent phases:

(1) Review of the literature and world-wide-web with particular attention to the classification of PREPs, upcoming products that could be considered PREPs, and the concept of harm reduction in the context of PREPs. (2) Conceptual work towards a basic (not harm-based) classification of PREPs, including the development of a working definition of PREPs and the creation of an “identification key.” (3) Creation of a first listing of PREPs that are currently used, marketed, or developed. Posting of this listing (in the form of a chart) on the world-wide-web and revision based on feedback. The version included in this paper is version 3, which is also the first version that uses an improved numbering system. (4) Conceptual work on the concept of harm profiles, including a definition of harm and a description of the breadth of harms that are caused by tobacco or nicotine use. (5) Creation of a first listing of a harm-based classification of PREPS. This required the development of an approach to express the magnitude of the various harms. (6) Discussion of this work in progress at a full-day seminar held on November 26, 2003 in Ottawa with representatives from government (Byron Rogers and Dr. Thea Mueller from Health Canada, Lucie Larose and Krishan Kumar from Agriculture and Agri-Food Canada), from industry (Dr. Daniela Jukic and Sylvie Poissant from Pfizer Canada), and non-government organizations (Robert Walsh from the Canadian Council for Tobacco Control, David Sweanor from the Non-Smokers' Rights Association, and Eugene Oscapella from the Canadian Foundation for Drug Policy) and Debbie McCulloch (City of Ottawa). Note: This event was not a consensus conference and participation by these individuals should not be construed as an endorsement of the views presented here. The briefing material and summary report of this event are available at our website (www.iog.ca; Knowledge Area Values, Ethics and Risk). (7) Refinement of the previous work based on this discussion, the discussions held informally with some members of an Institute On Governance-led informal, virtual working group, and discussions during an expert consultation on the ethics of harm reduction and product modification that was organized by Health Canada and took place on February 23-24, 2004.

4 Saner and Capelli, 2002, Tobacco Harm Reduction: Ethical Issues Associated with “Potential Reduced Harm Products.” A report by the Institute On Governance for the Tobacco Control Programme at Health Canada, 20 pp, available at www.iog.ca.

A Harm-Based Classification of PREPS 7 Institute On Governance The basic approach used during this research is a combination of knowledge about the natural sciences (taxonomy, in particular) with expertise in ethical analysis. Elements of good governance principles are contained in the present work but do not occupy centre stage.

3. Results

3.1. A Working Definition of “Potential Reduced-Exposure Products”

Stratton et al. (2001) appear to have coined the term but do not explicitly define “Potential Exposure-Reduced Products” (PREPs) in Clearing the Smoke. PREPs are introduced on p. 82 in that report as a component of the broader umbrella of harm reduction. Stratton et al. distinguish only relatively few classes of PREPs: modified tobacco products, smokeless tobacco products, cigarette-like products and pharmaceutical products (including nicotine replacement products).

Shiffman et al. (2002), Warner (2002) and Kozlowski (2002) also use the term without explicitly defining it. Based on a review of the broader literature (Chapter 5) no agreement on the scope of application of the term “PREP” exists.

It is not obvious that the term PREP was a good choice to begin with. The extension of the term “PREPs” (i.e., what falls under the concept) is unclear. Ostensibly, to say that a product is a PREP is just to make an empirical claim about it (roughly, that it is such that the exposure of the consumer or bystander to suspected or proven toxic tobacco ingredients is potentially reduced per consumed unit when compared to traditional tobacco products). In practice, however, the term seems to have an evaluative component as well. For example, it is controversial if the various forms of smokeless tobacco should count as PREPs, despite the fact that these products clearly reduce the exposure of bystanders if consumed instead of cigarettes. More particularly, it seems that what is usually meant by “potential reduced exposure product” in the policy literature is in fact something like “potential reduced harm product”. The concept of harm is neither straightforward, nor empirical, as is made clear in the text above. Accordingly, we had initially attempted to formulate a new concept, like that of a PREP, which would be straightforwardly empirical and hence have more precisely defined boundaries. For example, we considered using the term “novel nicotine and tobacco products”. That term, while it seems to be free of ethical connotations, is, however, equally inappropriate, as it fails to cover non-nicotine cessation aids and because novelty in itself may not be a reason for special consideration. Nor did alternative terms considered by us fare any better. It may simply be the case that there is no one empirical characteristic that all PREPs have in common (perhaps what we have instead is a set of products among which certain family resemblances hold). Due to the difficulty of developing a satisfactory alternative terminology, we have opted to continue to use the standard terminology, albeit explicitly taking into account its evaluative connotations.

A Harm-Based Classification of PREPS 8 Institute On Governance Developing a classification requires a set of criteria that allow for the identification of entities to be classified – we need to conceptualize PREPs clearly and explain the scope of this concept. Thus, developing a definition was the first task for this research project.

The question of the definition of this term is a delicate one, since different definitions might themselves have different policy implications. For example, a harm-reduction policy that is based on the use of PREPs will take a different form if we count various types of smokeless tobacco as being PREPs than it will if we count only non-nicotine medications/cessation therapies. In addition to these policy implications, the question of defining “PREP” is to some extent a political question. For example, should we rule out novel cigarette-like products from the outset, simply because we cannot afford to be seen (whether accurately or not) even to be considering an endorsement of cigarettes? Finally, products with some claim to the status of being a PREP have proliferated rapidly; many of these products bear little resemblance to each other and are difficult to anticipate (consider, for example, “nicotinis”, alcoholic beverages containing nicotine), thus rendering the task of formulating an acceptable definition difficult.

Despite these difficulties, a provisional definition (at least) of “PREP” is clearly necessary in order to begin to discuss PREPs in the context of harm reduction; otherwise, the very topic under discussion will not be clear. We recognize that no consensus on a definition can be expected at present; accordingly, we propose our definition merely as a provisional one. Given that the definition is provisional, and that the discussion of PREPs in the context of harm reduction is in its early stages, it seems best to cast our net widely.

There are two obvious ways of defining “PREP”. First, we might offer an extensional definition of “PREP”. That is, we might simply draw up a list of products we propose to call PREPs. The apparent advantage of this approach is that we need not explicitly propose a criterion for inclusion on the list. Thus, this approach might appear to sidestep potential controversy on what counts as a PREP, making it easier to secure agreement at the outset. The disadvantage, however, is that such a definition would leave whatever criterion we did have in mind merely implicit, making it difficult to determine whether new products should be added to the list or not. Long- term disagreement is thus likely to be increased by this approach.

Second, we could (as we have in fact done) offer an intensional definition of “PREP”. That is, we could propose some necessary and sufficient condition that would enable something to be considered a PREP. The advantage of this approach is that our criterion for inclusion of a product on the list of PREPs is made explicit. While this is likely to increase short-term disagreement, it should be advantageous in the long run, since it gives us a method for determining whether or not a product belongs on the list. In what we believe to be the “spirit” of the PREPs concept in Clearing the Smoke, we propose the following working definition of PREP:

A Harm-Based Classification of PREPS 9 Institute On Governance A PREP is a pharmacologically active product (that may be non-commercial or commercial and include non-prescription and prescription drugs) that is marketed (or consumed) for its apparent ability to reduce the exposure of users and/or bystanders (including unborn children) to the harmful effects of conventional tobacco products (if used over time to replace the consumption of traditional tobacco or nicotine products or to lead to cessation or to prevent or lessen addiction).

Some people will argue that this definition is too generous in the sense that it provides many products with unproven ability to reduce harm or even exposure a desirable “PREP status”. We have to emphasize that PREPs status does not entail that a product actually reduces harm. We believe that such a broad umbrella is compliant with the concept of “potential” and appropriate at this stage since we will follow up with a harm-based classification. Also, some people may argue that a true PREP is a modified version of a conventional tobacco product (e.g., a cigarette with a new filter). But such a narrow definition would not capture the spirit of the PREP concept expressed in Clearing the Smoke, which includes, for example, conventional smokeless tobacco. Again, we believe it is best to start broadly and live with the inclusion of borderline cases such as nicotine vaccinations or non-nicotine pharmaceuticals. Although this definition is very broad, it excludes products such as (non-nicotine) chewing gums or lollipops that may help some people to quit smoking (but that are not pharmacologically active).

We conclude this section with a short note on the concept of a product: The concept of a product is not a simple or straightforward one. The ordinary notion of a “product” includes at least the following elements: physics/shape, chemistry, use instructions/product claims, packaging / advertisement, and price. Additional elements, which do not seem to be relevant in the present context, include the production process (which might raise issues, for example, of animal welfare, ethical issues at the production workplace, or genetic engineering), and the transportation process. Given that the purpose for which we construct harm profiles for PREPs is to aid in the evaluation of products as part of a harm-reduction strategy, these dimensions of PREPs need not be considered here.

A Harm-Based Classification of PREPS 10 Institute On Governance 3.2. A Basic Classification of PREPs

3.2.1. Justification

As argued in the introduction, it is necessary to start with a basic classification of PREPs that can then be developed into harm-based classification. In addition to what we stated above, we see a number of justifications for this approach:

• First, we need categories of PREPs for which to draw harm profiles. The alternative would be to begin with individual products which, given the number of products on the market or in development, is an unwieldy approach. • Second, the basic classification brings to light certain features of the products that might turn out to be relevant for assessing their harm profiles. • Third, the basic classification draws attention to certain types of products that are not yet on the market, or even in development, but which might nevertheless be developed in the future. Thus, the classification is useful in its own right, in order to anticipate future developments in this area. • Fourth, the basic classification provides a common vocabulary for the discussion of PREPs. This vocabulary, while not entirely neutral (value-free), is more neutral than that provided by a harm-based classification. • Fifth, the basic classification uses criteria familiar to tobacco control practitioners and regulators. This is important since even the basic classification is complex and requires some patience on the part of the user (while a harm-based classification is even more novel and, thus, it is likely to be more difficult to use).

To our knowledge, this is the first time that all products that could be considered PREPs have been collected in one place.

A Harm-Based Classification of PREPS 11 Institute On Governance 3.2.2. Criteria

The following table outlines the criteria we have selected for the basic classification of PREPs:

Table 1: Criteria for a Basic Classification

Type of Criteria Specific Criteria Explanation 1. conventional These criteria are used, in addition to the shape criteria amount or type of (see below), because the type and amount of tobacco tobacco contained in a product may matter for both regulatory and 2. unconventional ethical purposes and it is important to distinguish conventional from novel products. For example, a Tobacco amount or type of conventional cigarette made with a novel type of tobacco tobacco might reduce harm; and a cigarette made with genetically modified tobacco might need to be regulated differently 3. no tobacco than a cigarette made with conventional tobacco, regardless of whether the cigarette itself is novel. While nicotine may have some negative health effects, it is 1. nicotine of concern primarily because it is addictive. This criterion needs to be included in addition to the tobacco criteria Nicotine because, while all tobacco products at present contain at least some nicotine, not all nicotine products contain 2. no nicotine tobacco. Moreover, it is possible at least in principle to have tobacco products that contain no nicotine. Whether a product is a conventional cigarette, an 1. conventional unconventional cigarette, or not a cigarette matters for cigarette regulatory purposes. These criteria are necessary, in addition to the tobacco criteria, because both conventional Cigarette-likeness 2. unconventional and unconventional cigarettes, as well as non-cigarette cigarette products, may contain either conventional or unconventional tobacco. Furthermore, there may be some 3. not cigarette-like connection between the shape of the product and how addictive it is.

1. inhalation This is of concern primarily with respect to addiction. The 2. oral way by which a product delivers nicotine affects how addictive the product is; this is related mainly to the speed Pathway 3. nasal with which the nicotine is delivered. There may also be less straightforward connections between the way in which 4. dermal a product delivers nicotine and how addictive the product is. 5. injection

A Harm-Based Classification of PREPS 12 Institute On Governance The selection of the above criteria is, admittedly, a compromise because it mixes chemistry with both physical appearance and pathways for uptake. The compromise has a clear goal, however. The criteria listed in Table 1 are those that are thought to be “common-sense” or “obviously important” to practitioners in the tobacco control, policy and regulatory communities.5 It is also the smallest set of criteria that we could justify – none of the criteria could be left out in a meaningful basic classification. Many other classification criteria that could be used can enter the discussion in a second step, in a harm-based classification. Examples for additional possible criteria are included in the following list:

• mechanism (the means by which the product (allegedly) reduces harm) • exposure (to toxicants) and dose • positive gateway potential (degree to which the product acts as a gateway to smoking conventional cigarettes) • negative gateway potential (degree to which the product acts as a gateway away from smoking conventional cigarettes)6 • intended effects (e.g., cessation, reduced exposure to toxicants)7 • potency (power of the mechanism to reduce harm) • knowledge of toxicology (extent to which the toxicology of the product is known) • complexity of toxicology (may be due to novelty/complexity of the product) • appeal to smokers (relevant because it affects how readily the PREP will be taken up) • behaviour change (behaviour changes required of smokers) • risk to others • dependence (extent to which the product is addictive) • manufacturer • market positioning

5 There was general agreement among the members of the informal working group on PREPs led by the IOG that these were useful and appropriate criteria. 6 The relevance of this and the previous three criteria were brought to our attention by Byron Rogers. 7 This list in part follows that given in Schiffman, et al., 2002.

A Harm-Based Classification of PREPS 13 Institute On Governance 3.2.3. Basic Classification

Table 2, below, is based on the criteria described above and includes all products that fit our working definition of PREP. Conventional tobacco products are also included partly because virtually every product on the market has at some point been considered “exposure-reduced” (although there is now proof that many of these claims – for example, the claim for “light” cigarettes – lead to neither an exposure reduction nor a harm reduction). Also, and more importantly, they are included because it facilitates the comparison of harm in a harm-based classification if all products are named.

The “number-dot” system used to number classes facilitates the future insertion of additional emerging PREPs within the classification without having to renumber the subsequent product classes. We surmise that this classification approach will, therefore, be adaptable.

The same information is presented in a visually more accessible form of a separately available Chart by the same title (some readers may appreciate the colour codes and the tree-style display). Please visit http://www.iog.ca/knowledge_areas.asp?pageID=17 to download the chart. Both the table and chart, however, require a few minutes of patience “to crack the concept”.

A Harm-Based Classification of PREPS 14 Institute On Governance Table 2: A Basic Classification of PREPs (Understood in the Widest Sense and Grouped with Conventional Tobacco Products)

Criteria used in classification Additional criteria Tobacco Nicotine Product type Pathway Class Example Manufacturer Mechanism 1 conventional 1.1 nicotine 1.1.1 1.1.1.1 1.1.1.1.1 filter cigarettes many many filter allegedly reduces exposure to tar, etc. amount and conventional inhalation 1.1.1.1.2 "light"/ "mild" cigarettes many many dilution of mainstream smoke by means of type of tobacco cigarette ventilation holes, paper porosity, expanded tobacco 1.1.1.1.3 reduced sidestream Lucia Citrus Fresh Japan Tobacco produce less tobacco odour and less smoke smoke cigarettes Menthol, Mild Sevens Passport Rothman's similar to the JT products; no longer on the market 1.1.1.1.4 fire-safe cigarettes Merit Philip Morris special paper with "speed bumps" reduces the rate at which the cigarette burns 1.1.2 1.1.2.1 1.1.2.1.1 cigarettes with filters not yet named not yet being special filter reduces carbon monoxide released unconventional inhalation containing nanometric manufactured by a regular cigarette by up to 26.9% cigarette materials 1.1.2.1.2 cigarettes with ion- not yet named not yet being removes hydrogen cyanide, acrolein exchange filters manufactured 1.1.2.1.3 cigarette with fluid NicoBloc NicoBloc fluid is added to the cigarette's filter before added to filter smoking; stops up to 90% of tar and nicotine in cigarettes from reaching the bloodstream 1.1.2.1.4 mini-filters + Crafe Good Life reduces amount of tar and nicotine inhaled; conventional cigarette Away/Ciganot Mini- Products provides visual demonstration of amount of tar Filters Honeyrose Mini- Honeyrose reduces amount of tar inhaled Filters/EZ-Quit Mint Products Filter 1.1.2.1.5 powder to alter taste of Smoke-Less not yet being powder dissolved on tongue gives cigarettes cigarette + cigarette manufactured unpleasant taste 1.1.3 not 1.1.3.1 1.1.3.1.1 vaporizers many many tobacco is "vaporized", releasing nicotine but no cigarette-like inhalation tobacco smoke 1.1.3.1.2 cigars many many used by some smokers as an alternative to cigaretes 1.1.3.1.3 cigarillos many many used by some smokers as an alternative to cigaretes 1.1.3.1.4 tobacco pipes many many used by some smokers as an alternative to cigaretes 1.1.3.2 1.1.3.2.1 chewing tobacco Red Man, Southern Swedish Match used by some smokers as an alternative to oral Pride cigaretes 1.1.3.2.2 moist snuffs Copenhagen/Skoal USSTC used by some smokers as an alternative to cigaretes 1.1.3.2.3 tobacco toothpaste Dentobac Goran Pharma tobacco-based toothpaste 1.1.3.3 1.1.3.3.1 dry snuffs Red Seal USSTC used by some smokers as an alternative to nasal cigaretes Tobacco Nicotine Product type Pathway Class Example Manufacturer Mechanism

2 2.1 nicotine 2.1.1 2.1.1.1 2.1.1.1.1 "low carcinogen" Omni Vector Tobacco reduction of carcinogenic PAHs, nitrosamines, unconventional conventional inhalation cigarettes catechols amount or type cigarette Advance Brown & uses Starcure tobacco processing method, of tobacco Williamson reduing tobacco specific nitrosamine content by 70%, including CO SCOR Philip Morris reduced toxin conventional cigarette 2.1.1.1.2 additive-free cigarettes American Spirit Santa Fe Natural no additives in tobacco Tobacco Company 2.1.2 2.1.2.1 2.1.2.1.1 cigarette-like products Premier R.J. Reynolds extracts of tobacco that are mainly heated unconventional inhalation Eclipse R.J. Reynolds nicotine and glycerine are heated by a carbon fuel cigarette element ignited with a lighter; some tobacco is burned; reduces both carcinogens and second- hand smoke by 80% Accord Philip Morris hand-held, battery-operated, microchip-controlled device heats a cigarette-like tobacco roll; fewer toxins are produced and inhaled; 90% less smoke than conventional cigarettes 2.1.2.1.2 tobacco-based Quest cigarettes Vector Tobacco genetically engineered tobacco products containing little nicotine 2.1.2.1.3 tobacco-based unnamed (not yet Vector Tobacco combines features of Omni (low carcinogens) and products with low developed); see Quest (genetically engineered tobacco) nicotine and low See carcinogens www.questcigs.com 2.1.3 not 2.1.3.1 2.1.3.1.1 moist snuffs with Stonewall Star Scientific oral snuff made with Starcure tobacco cigarette-like oral unconventional tobacco Catch Swedish Match oral snuff with low tobacco-specific nitrosamines 2.1.3.1.2 tobacco packets with Revel USSTC oral tobacco in a packet conventional tobacco 2.1.3.1.3 tobacco packets with Exalt Swedish Match oral tobacco in a packet; low in tobacco-specific unconventional tobacco nitrosamines 2.1.3.1.4 tobacco gum Firebreak Swedish Match tobacco-based chewing gum; contains 1 milligram of nicotine/piece, 2.5% tobacco 2.1.3.1.5 tobacco-based nicotine Ariva Star Scientific Starcure tobacco, nicotine, other substances; lozenges supposedly has the lowest level of tobacco- specific nitrosamines of any tobacco Interval Brown & similar to Ariva Williamson 2.1.3.1.6 hookah/ narghile/ many many tobacco on a metal plate with a hole in the bottom shisha that connects to a water-filled metal container and is heated by charcoal; the tobacco is mixed with fruit and molasses/honey 2.1.3.2 2.1.3.2.1 dry snuff w/ Stonewall Star Scientific nasal snuff made with Starcure tobacco nasal unconventional tobacco

A Harm-Based Classification of PREPS 16 Institute On Governance Tobacco Nicotine Product type Pathway Class Example Manufacturer Mechanism

3 no tobacco 3.1 nicotine 3.1.1 3.1.1.1 3.1.1.1.1 tobacco-free cigarettes not yet named not yet being pouch of liquid nicotine is contained in a plastic unconventional inhalation manufactured tube; the tube is pinched, breaking the pouch and cigarette causing the nicotine to flow into absorbent filters; the device is puffed like a cigarette 3.1.2 not 3.1.2.1 3.1.2.1.1 nicotine inhaler Nicotrol Pfizer nicotine in inhaler cigarette-like inhalation 3.1.2.2 3.1.2.2.1 nicotine gum Nicorette GlaxoSmithKline nicotine in a gum base oral 3.1.2.2.2 ad libitum nicotine gum Nu Life Nu Life nicotine in gum (chewed ad libitum, unlike Nicorette) 3.1.2.2.3 nicotine lollipops Nicostop/ NicoPop/ compounded by nicotine in a lollipop Likatine pharmacists 3.1.2.2.4 tobaco-free nicotine Commit GlaxoSmithKline nicotine in a lozenge lozenge 3.1.2.2.5 sublingual nicotine Nicorette Microtab Nicorette nicotine in a sublingual tablet tablets 3.1.2.2.6 dual-delivery nicotine not yet named not yet being combines fast-relief effects of nicotine gum with pill manufactured; slow-release effects of nicotine patches; pill is www.rgu.ac.uk/pr placed inside cheek, giving both peak initial essrel/090903Bu dosage and slow-release dosage ccal.doc. 3.1.2.2.7 nicotine water Nicowater S & F Garret and bottled water with nicotine equal to that of two QTF cigarettes; no longer on the market 3.1.2.2.8 oral nicotine solution not yet named not yet being cessation aid manufactured 3.1.2.2.9 nicotine fruit juice not yet named Platinum nicotine in fruit juice Products 3.1.2.1.10 nicotine herbal NicoMed Nautilus GmbH nicotine in an herbal beverage; also marketed as beverage Laboratoriumsbe an energy drink darf 3.1.2.2.11 nicotine "hard" Nicotinis n/a tobacco leaves are soaked in vodka overnight, alcoholic beverage then mixed with other liquors 3.1.2.2.12 nicotine beer-like Smoke Energy Nautilus GmbH similar to NicoMed, but with 5.4% alcohol from alcoholic beverage Brew Laboratoriumsbe beer darf 3.1.2.2.13 nicotine wafers name? QuitMed nicotine in a wafer (custom dose) 3.1.2.2.14 nicotine in a straw The Straw Recovery single use plastic straw containing beads of Pharmaceuticals nicotine; nicotine is released when a beverage is sipped through the straw 3.1.2.3 3.1.2.3.1 nicotine nasal spray Nicotrol Pharmacia nicotine in a sprary nasal Corporation 3.1.2.4 3.1.2.4.1 nicotine patch Nicoderm/Nicotrol GlaxoSmithKline/ nicotine in a skin patch dermal Pfizer 3.1.2.4.2 nicotine lotion Evulotion Evulotion nicotine in hand and body lotion 3.1.2.4.3 nicotine sunscreen Nicotan Evulotion nicotine in a sunscreen 3.1.2.4.4 nicotine lip balm several several lip balm containing nicotine salicylate

A Harm-Based Classification of PREPS 17 Institute On Governance Tobacco Nicotine Product type Pathway Class Example Manufacturer Mechanism

3.2 no 3.2.1 3.2.1.1 3.2.1.1.1 herbal cigarettes many many various herbs in a cigarette nicotine conventional inhalation cigarette 3.2.1.1.2 herbal smoking mixture Honeyrose Honeyrose various herbs, to be rolled into a cigarette instead Smoking Mixture Products of tobacco 3.2.1.1.3 lettuce cigarettes Bravo Cigarettes Safer Smokes cigarete containing lettuce

3.2.2 3.2.2.2 3.2.2.2.1 tobacco-free bidis Vardan Dalmia bidis containing plant material but no tobacco unconventional inhalation Consumer Care cigarette 3.2.2.2.2 smokeless cigarettes Crafe Good Life smoky taste is released as air is drawn through Away/Ciganot Products filter contained in tube Smokeless Cigarette Smokers Edge Smokers Edge cigarette-like product containing "only natural herbs and essential oils" 3.2.3 not 3.2.3.1 3.2.3.1.1 non-nicotine bupropion (Zyban) GlaxoSmithKline anti-depressant that decreases cravings cigarette-like oral medications/ therapies Clonidine, monamine oxidase inhibitors (MAOIs), beta blockers, mecamylamine + NRT, buspirone, anorectics, caffeine/ephedrine, benzodiazepines, cimetidine, nortriptyline, noradrenergic antidepressants, dextrose, phenylpropanol, lobeline, silver acetate, naltrexone, selective seratonin reuptake inhibitor (SSRI) antidepressants, odansetron, varenicline, rimonabant (many manufacturers, various mechanisms) 3.2.3.1.2 pepper extracts not yet named not yet being black or red pepper constituents; vapor or aerosol manufactured delivery system; create sensations similar to tobacco smoke 3.2.3.1.3 herbal cessation CigSation Nutramerica "features all-natural substances that are known to remedies be useful to smokers trying to quit"

3.2.3.1.4 non-tobacco chew several several chew made of, e.g., mint instead of tobacco

3.2.3.2 3.2.3.2.1 non-tobacco snuff several several snuff made of, e.g., mint instead of tobacco nasal 3.2.3.3 3.2.3.3.1 vaccination against Nicotine-Qbeta Cytos blocks entry of nicotine to brain injection nicotine addiction Immunodrug Biotechnology

A Harm-Based Classification of PREPS 18 Institute On Governance The following features of the basic classification are noteworthy.

• The large number of (different types of) PREPs. The existence of such a large number of products came as a surprise to us – the review literature (including Clearing the Smoke) gives no indication of the potential magnitude and diversity of the product pipeline. • The heterogeneity of PREPs. The large number of different classes of PREPs supports the view that a harm-based classification of PREPs is called for. Their appearance and mode of action (or marketing pitch for that matter) tell us nothing about their ability to reduce harm. • The presence of a large number of unexpected products. One might suppose, for example, that the group of non-tobacco products would include only nicotine and non-nicotine cessation aids. However, that group also includes a new vaccination against nicotine addiction, herbal cigarettes, and tobacco-free cigarettes. This shows that the common-sense basic criteria group together rather dissimilar products, again providing support for a harm- based approach. • The resilience of the basic classification. We encountered no difficulty in accommodating unexpected products within the basic classification. • The lack of information available about certain PREPs. Relatively little seems to be known about, for example, herbal cigarettes, sublingual nicotine tablets, or NicoBloc. This lack of information limits our ability to discuss these products appropriately. A harm-based approach could, to some extent, lessen this difficulty, since information about harm sufficient to guide a policy discussion can be available even when detailed empirical information about the products is not. • The overlap of the classification with the current division between PREPs regulated as pharmaceuticals, and PREPs “regulated” as tobacco products. All PREPs currently regulated as pharmaceuticals fall into two large groups (each containing multiple classes). The first group comprise the nicotine-based cessation aids, which are all products containing no tobacco but containing nicotine, and which are not cigarette-like. The second group comprise non-nicotine medications, which are all products containing no tobacco and no nicotine, and which are not cigarette-like. This seems to indicate that cigarette-likeness is indeed a useful criterion. • The relevance of both the “pathway” criterion and the “cigarette-likeness criterion”. It might be supposed that using the pathway criterion could allow us to dispense with the cigarette-likeness criterion, since anything inhaled will be a cigarette. There are, however, numerous products which use the inhalation pathway and are either unconventional cigarettes or not cigarette-like at all.

Disclaimer: The classification presented here is a work in progress. The current version 3 has been vastly improved and expanded from versions 1 and 2 and we would expect that further improvements and expansion would come from use and from a screening of the product pipeline. Note that many of the products have only been “announced” on the world-wide-web and are not available to consumers. Because of the rapidly changing nature of such “announcements” and news clips on the world-wide-web, some of the sources have not been included in the web and literature review presented at the end of this paper. This classification represents our best effort to provide an as-complete-as-possible coverage of current, coming and possible PREPs – it is not, however, a list that differentiates market-ready from merely anticipated, and legal from illegal products.

A Harm-Based Classification of PREPS 19 Institute On Governance 3.3. Conceptualizing Harm

A lot of work on harm reduction of tobacco products, alcohol, and illicit drugs has been published in the open literature – most of which contain implicit or explicit concepts for harm and harm reduction.

For example, the Canadian Centre for Addiction and Mental Health defines harm reduction as follows:8

Harm reduction is any program or policy designed to reduce drug-related harm without requiring the cessation of drug use. Interventions may be targeted at the individual, the family, community or society.

The World Health Organization lists the following definition in its lexicon:9

In the context of alcohol or other drugs, describes policies or programmes that focus directly on reducing the harm resulting from the use of alcohol or drugs. The term is used particularly of policies or programmes that aim to reduce the harm without necessarily affecting the underlying drug use; examples includes needle/syringe exchanges to counteract needle-sharing among heroin users, and self-inflating airbags in automobiles to reduce injury in accidents, especially as a result of drinking-driving. Harm reduction strategies thus cover a wider range than the dichotomy of supply reduction and demand reduction. Synonym: harm minimization

Within the tobacco policy community, the authors of Clearing the Smoke (Stratton et al. 2001, p. 2) provide the following definition:

For the purposes of this report, a product is harm-reducing if it lowers total tobacco-related mortality and morbidity even though use of that product may involve continued exposure to tobacco-related toxicants.

What is noteworthy is that these sources define harm reduction but not harm. This is common throughout the literature. Also, the definitions quoted above more or less explicitly exclude cessation from the concept of harm reduction – although cessation is the gold standard in tobacco regulation and illicit drug use (but not in alcohol use). This is important in the context at hand because a number of the PREPs discussed here are explicitly marketed as cessation aids. Furthermore, it would be odd to exclude a PREP from a harm reduction strategy only for the reason that it may lead to cessation. See Warner (2002) for an excellent discussion of a broad conception of harm reduction (approximately synonymous to tobacco control itself) and the narrow conception currently being used by most authors. One should probably open to the possibility that harm reduction – once implemented in practice – will mean quite different things within the illicit drugs, alcohol and tobacco communities, respectively.

Often the definition of harm reduction is implicit rather than explicit. For example, Schiffman et al. (2002) do not use a definition but, instead, describe harm reduction from different

8 http://www.camh.net/public_policy/publicpolicy_harmreduc2002.html 9 http://www.who.int/substance_abuse/terminology/who_lexicon/en/

A Harm-Based Classification of PREPS 20 Institute On Governance perspectives including a listing of approximately 20 different approaches and products that could lead to harm reduction. What is important about the Schiffman paper is that it goes beyond a discussion of the cardinal harms of mortality and morbidity that are expressed in the definition provided in Clearing the Smoke (quoted above). This breadth is also echoed in the papers by Kozlowski et al. (2001) and Fox & Cohen (2002), which call for a broad ethical discussion of the issues.

We note that there are two quite different types of approaches to harm reduction. One might (a) change the environment within which tobacco products are consumed, for example through advertisement standards, influencing the price of products, or educating consumers or (b) change the actual products consumed. Examples of the latter are products that (might) reduce harm – namely, PREPs. In this respect, our approach differs from that of Schiffman, et al. (2002) who provide a survey of the harm profiles (without using this term) for various alternate harm- reduction strategies. Our approach is to develop harm profiles for particular products, various PREPs that could be used or endorsed within a harm-reduction strategy. Thus, we focus first and foremost on the concept of harm at this stage. The more controversial concept harm reduction would be useful when the harm profile of a group of products can be analysed in the context of harm reduction strategies.

In short, our approach is as follows. On the basis of an inquiry into the meaning of “harm”, we consider harms broadly and systematically and develop harm profiles for various PREPs using the basic classification presented above. These profiles then allow us to group products with similar harm profiles into a harm-based classification of PREPs. Such a classification should support a comparative evaluation of harm-reduction strategies resulting from endorsement of (some) PREPs. Such a comparative evaluation is a very large project and is not attempted here. Nevertheless, working out a first attempt at a harm-based classification for PREPs is a necessary first step towards undertaking such an evaluation.

We also offer this caveat: although our approach is focused on products, we do not use the concept product modification, which is quite common in the discussion surrounding PREPs. The reason for avoiding this concept is that many of the PREPs are brand new (not modified) products and the decision about what is modified and what is not modified is quite difficult – arguably the tobacco industry has been modifying products for centuries and does so quite frequently.

What exactly do we mean by “harm”? Considering the proven and significant harmfulness of tobacco to human health, it is meaningful to start an analysis with the central harms of mortality and morbidity. This, however, is still not sufficiently precise. Who is at the centre of attention? At least three entities have to be initially distinguished: (a) individual smokers, (b) bystanders, and (c) the public at large. If the analysis is taken further, it becomes important to distinguish additional potentially affected parties and types of harm. This point can be illustrated by means of an example. If a nicotine chewing gum were discussed in the context of harm reduction, then it would be meaningful to distinguish the effect on young people of the availability of this product from its effect on adults, its effect on people who are currently smoking from its effect on people who have never smoked, its effect on consumers from its effect on bystanders, and so

A Harm-Based Classification of PREPS 21 Institute On Governance on.10 For example, for bystanders this product is not only a potential reduced exposure product but, instead, certainly reduces exposure to tobacco and nicotine when compared to cigarettes. Further, unlike other PREPs, such as “low tar cigarettes,” nicotine gum is classified as a cessation aid. As such, it undergoes a safety evaluation during the registration process and has specific label claims (this in itself is deserving of ethical analysis). In short, the list of differences in the type of harm that may be caused is significant. A lack of specificity at this level will prevent answering the question “does this product reduce harm overall?” with any meaningful precision.

The point we are trying to make is that, while it may be generally accepted that the lessening of a harm is defensible (if it works), it is much more difficult to state “what harm to whom,” as the object for reduction (moreover how egalitarian this goal and outcome is, how it affects the principle of autonomy, how it rates in terms of overall net public health gain as compared to individual benefits, and so on). In a nutshell, the “ethical profile” of a new product has to be analyzed for each specific case. Without such case-specific analysis it is not possible to fully justify a course of action. A harm-based classification should help in prioritizing the harms of greatest interest and grouping products with similar profiles and, thus, facilitate this analytic work.

The prioritizing that is necessary in constructing the concept of the harm profile of PREPs should draw on a complete list of possible harms, i.e., harms beyond morbidity and mortality of the user. Additional harms that may be worth considering are “harm” in terms of accidents (“fire- safe” cigarettes), “economic harm” (addiction), “social and psychological harm,” “legal harm” (important in the related context of illegal drugs), and so forth. Also, one should not overlook the fact that these other forms of harm may ultimately translate into harm to health in real life.

Based on these observations, we propose the following conception of harm (the technical terms employed in the conception are discussed below). A working conception of harm:

A harm is a setback to an interest. In each instance of harm, there is: • an entity, the agent, who causes the harm (agents can be persons, children, or groups), where the agent either intends, foresees, or does not foresee the harm • an act by which the harm is caused (where acts can be commissions or omissions, and can inflict, fail to remove, or fail to prevent the harm) • a vehicle (a product or policy) that is used to inflict harm • an entity, the recipient, who experiences the harm (the recipient can be a person, a child, a foetus, a group, or society) • an interest of the recipient which suffers a set back to a greater or lesser extent (interests include, but are not limited to, self-direction, wealth, health, longevity, and equality)

10 Klesges et al., 2003, "Use of nicotine replacement therapy in adolescent smokers and nonsmokers," in Archives of Pediatrics and Adolescent Medicine 157(6): pp.517-22.

A Harm-Based Classification of PREPS 22 Institute On Governance On this conception of harm, then, there are three main questions we must ask when analyzing any particular harm: • who is harmed? • how is the harm caused? • what interest is set back?

Having in place this general conception of harm allows us to speak of the harm profile of a product. If we can secure general agreement on the chief potential harms of PREPs, we can then analyze those harms in terms of the general conception. The next step will narrow this broad definition of harm by prioritizing the harms that matter in the tobacco policy context.

3.4. A Harm-based Classification of PREPs

3.4.1. Criteria for Harm Profiles

Arriving at a list of chief harms to define the scope of harm profiles is no trivial task. Attention will have to be given to the “who”, “how” and “what” questions outlined above, and the profile should cover the whole breadth of reasonably interesting harms (so as not to stifle the ethical analysis that would use the harm-based classification as a tool).

It is important to note that it is not a requirement that all components of a harm profile are equally important in terms of severity. It would not be a problem per se to mix a critical harm such as mortality with a lesser harm such as financial impact. A harm profile is not supposed to deliver a single number or grade to describe the “real quality” of a product. Instead, it is a tool to allow for a harm-based classification that, in turn, is a tool for policy discussion and detailed ethical analysis.

It is more important that all types of significant issues are represented in a list that is as succinct as possible – we do not want to pair several dozen types of products (in the basic classification) with a large number of types of harm.

Based on our reading of the literature and discussions with experts we propose that the 10 types of harms presented in Table 3 represent the minimal set of the relevant harms that PREPs may reduce (via a reduction in exposure). They represent a mixture of the “who”, “how” and ”what” question discussed above and include the topics that most often would enter an ethical analysis. We propose that these types of harms should be the indicators employed in the harm profiles (they do work as indicators in the sense that less of each helps the goal of harm reduction while more of each counteracts the goals of harm reduction):

A Harm-Based Classification of PREPS 23 Institute On Governance Table 3: Components of a Harm Profile

Type of Harm Recipient Explanation Morbidity Does not require an explanation. Mortality User Problematic Addiction deserves attention even if a product itself has a low addiction impact on health (as pure nicotine, perhaps, does). Harm to the From an ethics perspective, the impact of product to the user and health or the bystander are altogether different because a (mature) user longevity of makes an autonomous choice – at least at the beginning of an bystanders addiction – while a bystander is exposed involuntarily. Bystander Harm to the The well-being of children is valued very highly in virtually all health of societies. Furthermore, children and foetuses are often most children or susceptible to the effect of pharmacologically active substances. foetuses Differential Differential harm plays no role in a utilitarian system that harm according measures the performance of an approach by mortality and to gender morbidity figures. It plays, however, a role within an ethical Differential analysis. If a PREP improves the chances of good health of harm according established smokers but leads to an “epidemic” of usage in a to racial or specific group (for example, young women who may use a PREP Groups aboriginal as an appetite control tool), then such a situation should be origin discussed within the ethical analysis of the product. In a nutshell, Differential the concept of equality matters in ethics. Note: Economic status harm according and age are joined here simply because young people and to economic children often have less money available than adults (and because status or age we wanted to start with a small set of criteria). This point is of interest because tobacco addiction is very costly Cost to the to the health care system but cessation aids could also become health care costly if the provinces would start to provide them to smokers. system Profits from taxation schemes may be included in this criterion. An important concern about PREPs is their potential for “gateway Society harm” – the possibility that they will lead to nicotine addiction or Increase in that they will seduce users to continue tobacco use on the belief societal tobacco that the product is quite safe to their health. A harm reduction usage rate system is normally not acceptable if it leads to an increase of usage at the societal level.

A Harm-Based Classification of PREPS 24 Institute On Governance We should note that the list in Table 3 is not simply a reflection of the frequency by which issues are quoted in the literature. Our survey indicates that the following recipients of harms are often discussed (in order of priority): users, women, adolescents, foetuses, and bystanders. In comparison, there is little discussion of, for example, the differential harm to first nations or African-Americans. Therefore, our list is not simply based on the current “hot issues” but on the needs of an analyst reviewing the ethics of PREPs or the needs of policy makers preparing a position on certain types of PREPs.

Some participants at our one-day seminar on November 26, 2003 commented that it is necessary to be more precise on the notions of differential harm – that more categories are necessary. For example, differential harm for women and men or for youth and adults could be distinguished, and so on. We agree that a policy analysis would need this level of precision. However, we feel confident that the current scheme is sufficient for the purpose of classification into groups that could then be further analyzed.

We do not specifically include considerations on potentially misleading packaging, labelling and advertisements in the harm profile – although these could be considered elements of a “product.” Including this broader concept of product would render the classification quite unmanageable in practice. Also, “societal harm” could be extended to include important indirect harms that may be associated with products and policies (e.g., the consequences associated with the smuggling of products) – we did not see a need to emphasize this point at this stage.

In the same vein, we do not capture intended use in the classification – this could be an important point for future consideration because proponents must often choose regulatory authorities based on intended use (e.g., a health claim can trigger regulation). A focus on intended use would allow us to separate products “for cessation” from products “for harm reduction.” However, a glance at the array of possible PREPs provided in the basic classification shows that many products would be hard to classify based on intention – and intentions may not materialize in the marketplace among real users. Therefore, we decided not to focus on these issues at this stage.

A potential harm that plays a major role in the use of illegal drugs – social stigma – could be a valuable addition to the harm profile concept. It could capture such issues such as the potential social stigmatization of, for example, users of nicotine inhalers. We have not included the criterion in this version of the harm profile, however, in part due to the complexity of the concept and in part because of the lack of data.

A Harm-Based Classification of PREPS 25 Institute On Governance 3.4.2. Harm Profiles For the Basic Classification

The following Table 4 constructs harm profiles for the various classes of products listed in the basic classification (Table 2). Harm profiles have the components listed in Table 3 and are supplemented by the following:

• for each harm, a judgement as to the relative severity of the harm • for each judgement, a statement of our confidence in its accuracy

We use the severity of the harms caused by conventional cigarettes to generate what is effectively a baseline harm profile. This gives us a yardstick by which to measure the severity of the harms caused by a given PREP (note: PREPs stands for “reduced exposure” relative to cigarettes). Needless to say, meaningful quantitative measures are impossible at this stage. But we can make rough qualitative estimates of harm, which allow us to judge, for each harm- product pair, that the product causes the harm to an extent equal to that of a conventional cigarette, less than that of a conventional cigarette, or not at all (in cases where insufficient empirical data are available, no judgement is made).11

The harm profiles given in Table 4 are not meant to be authoritative or final. Rather, they represent our best judgement at present. Note that they only need to be sufficient for the purpose of a harm-based classification - they are not designed to replace a full harm-based evaluation of each product.

11 One potential drawback of this approach is that it cannot accommodate cases where a PREP causes some harm to an extent greater than that to which it is caused by conventional cigarettes. No such cases are known at present.

A Harm-Based Classification of PREPS 26 Institute On Governance Table 4: Approximate Harm Profiles for the Basic Classification of PREPs Key: Severity of Confidence in *** high confidence harm: assessment: ** moderate confidence * low confidence

Harms to the user Harms to the bystander Harms to groups Harms to society

Harm to the Harm to the Differential Differential Differential Increase in Problematic health/ health of harm harm according harm according Cost to the health care Morbidity Mortality societal tobacco addiction longevity of children / according to to racial / to economic system usage rates bystanders foetuses gender aboriginal origin status or age

Class Class # Name 1.1.1.1.1 Filter cigarettes *** *** *** *** *** *** *** *** *** *** 1.1.1.1.2 "Light"/"mild" cigarettes *** *** ** *** *** *** *** *** *** *** Reduced sidestream * * *** *** * *** *** *** * * 1.1.1.1.3 smoke cigarettes 1.1.1.1.4 Fire-safe cigarettes *** ** *** ** ** *** *** *** *** Cigarettes with filters 1.1.2.1.1 containing nanometric * * * * * materials Cigarettes with ion- * * * * * 1.1.2.1.2 exchange filters Cigarette with fluid * * ** * * 1.1.2.1.3 added to filter Mini-filter + conventional * * * ** ** * * 1.1.2.1.4 cigarette Powder to alter taste of ** ** * ** ** * * 1.1.2.1.5 cigarette + cigarette 1.1.3.1.1 Vaporizers * * ** ** * * 1.1.3.1.2 Cigars ** ** ** * * * * 1.1.3.1.3 Cigarillos ** ** ** * * * * 1.1.3.1.4 Tobacco pipes ** ** ** * * * * 1.1.3.2.1 Chewing tobacco ** ** ** *** ** ** 1.1.3.2.2 Moist snuffs ** ** ** *** ** ** 1.1.3.2.3 Tobacco toothpaste * * * *** * * 1.1.3.3.1 Dry snuffs * * * *** * * "Low carcinogen" * * *** * ** ** 2.1.1.1.1 cigarettes 2.1.1.1.2 Additive-free cigarettes *** *** *** *** *** *** *** 2.1.2.1.1 Cigarette-like products * * ** ** * * Tobacco-based products * * ** * ** ** 2.1.2.1.2 containing little nicotine Tobacco-based products 2.1.2.1.3 with low nicotine and low * * * * * * carcinogens Moist snuffs with * * * *** * * 2.1.3.1.1 unconventional tobacco Tobacco packets with * * * *** * * 2.1.3.1.2 conventional tobacco Tobacco packets with * * * *** * * 2.1.3.1.3 unconventional tobacco

A Harm-Based Classification of PREPS 26 Institute On Governance 2.1.3.1.4 Tobacco gum ** ** ** *** ** ** Tobacco-based nicotine * * ** *** * ** ** 2.1.3.1.5 lozenges 2.1.3.1.6 Hookah/narghile/shisha * * * * Moist and dry snuffs with ** ** ** *** ** ** 2.1.3.2.1 unconventional tobacco 3.1.1.1.1 Tobacco-free cigarettes * * ** *** * * 3.1.2.2.1 Nicotine inhaler *** *** *** ** * ** * 3.1.2.2.2 Nicotine gum *** *** *** *** * *** * 3.1.2.2.3 Nicotine lollipops ** ** *** *** * ** * Tobacco-free nicotine ** ** *** *** * ** * 3.1.2.2.4 lozenge Sublingual nicotine ** ** *** *** * ** * 3.1.2.2.5 tablets 3.1.2.2.6 Dual delivery nicotine pill ** ** *** *** * ** * 3.1.2.2.7 Nicotine water ** ** *** *** * ** * 3.1.2.2.8 Oral nicotine solution ** ** *** *** * ** * 3.1.2.2.9 Nicotine fruit juice * * * *** * ** * Nicotine herbal * * * *** * ** * 3.1.2.2.10 beverage Nicotine “hard” alcoholic * * * *** * ** * 3.1.2.2.11 beverage Nicotine beer-like * * * *** * ** * 3.1.2.2.12 alcoholic beverage 3.1.2.2.13 Nicotine wafers ** ** *** *** * ** * 3.1.2.2.14 Nicotine in a straw ** ** *** *** * ** * 3.1.2.3.1 Nicotine nasal spray *** *** *** *** * *** * 3.1.2.4.1 Nicotine patch *** *** *** *** * *** * 3.1.2.4.2 Nicotine lotion * * ** *** * ** * 3.1.2.4.3 Nicotine sunscreen * * ** *** * ** * 3.1.2.4.4 Nicotine lip balm * * ** *** * ** * 3.2.1.1.1 Herbal cigarettes * * ** * * * * 3.2.1.1.2 Herbal smoking mixture * * ** * * * * 3.2.1.1.3 Lettuce cigarettes * * ** * * 3.2.2.1.1 Tobacco-free bidis * * ** * * 3.2.2.1.2 Smokeless cigarettes *** *** *** *** * * * Non-nicotine ** ** * ** ** ** 3.2.3.1.1 medications/therapies 3.2.3.1.2 Pepper extracts ** Herbal cessation ** 3.2.3.1.3 remedies 3.2.3.1.4 Non-tobacco chew * * * ** ** ** 3.2.3.2.1 Non-tobacco snuff * * * ** ** ** Vaccination against * * * *** * ** ** 3.2.3.3.1 nicotine addiction

A Harm-Based Classification of PREPS 27 Institute On Governance 3.4.3. Harm-based Classification

Obstacles to a harm-based classification include the significant gaps in some of the harm- profiles. In particular, not much is known about the differential effects of most classes of PREPs on groups (insufficient information is available for all classes, except the first four). For this reason, it seems best to leave such effects out of consideration as we formulate a harm-based classification of PREPs. The only classes for which too little is known at present to justify including them in any group, are classes 3.2.3.1.2 and 3.2.3.1.3 (pepper extracts and herbal cessation remedies) and class 2.1.3.1.6 (hookah/narghile/shisha). Additionally, it is hard to see where class 3.2.2.2.2 (smokeless cigarettes) belongs. The other classes fall readily into groups.

These groups are, of course, only intuitive ones. We have not explicitly set out criteria for classes belonging to the same group. Various criteria are possible. For example, we could require classes to have identical harm profiles in order to be included in the same group, we could decide that identical degrees of harm to users and bystanders is sufficient, and so on. Hence the following draft harm-based classification is likely to evolve under the impact of discussion, and the present classification should be considered to be only a basis for such discussion.

• Group 1. This group includes filter cigarettes, “light” and “mild” cigarettes, and additive cigarettes, all of which are maximally harmful, for all harms considered. Fire-safe cigarettes do better only when it comes to early death, and only in virtue of being fire-safe; it thus seems safe to include them in this class. Cigars, cigarillos and tobacco pipes also fall into this group. Note, however, that other cigarette-like products do not fall naturally into this group.

• Group 2. This group includes all the nicotine-based cessation aids, as well as such similar products as nicotine water and nicotine beverages (that may not be legal but nevertheless available). Note that, from a harm-based perspective, nicotine-based cessation aids are not in a group by themselves. Given the similarity of the harm profile of tobacco-free cigarettes, it seems safe to include that class into group 2.

• Group 3. Although their harm profiles are not identical, cigarettes with filters containing nanometric materials or ion-exchange filters, “low carcinogen” cigarettes, and “cigarette-like products” can be grouped together. These products are all basically novel cigarettes.

• Group 4. Another natural group includes most of the remaining novel cigarettes, tobacco-based products containing little nicotine and tobacco-based products with low nicotine and low carcinogens.

• Group 5. This group includes cigarettes with fluid added to filter, vaporisers, chewing tobacco, moist and dry snuffs, tobacco gum and tobacco-based nicotine lozenges. This grouping includes both conventional alternatives to cigarettes and novel alternatives to cigarettes.

A Harm-Based Classification of PREPS 28 Institute On Governance • Group 6. This group is made up of “mini-filter & conventional cigarette” and “powder to alter taste of cigarette.” It is interesting to note that these two classes have identical harm profiles (at this low level of precision), despite the fact that products in the former are designed to reduce the harmfulness of cigarettes per cigarette consumer, while products in the latter are designed to reduce the harmfulness of cigarettes, by reducing the number of cigarettes consumed.

• Group 7. This group consists of only one class, namely the vaccination against nicotine addiction. Assuming we have assigned degrees of harmfulness correctly (note that we have assigned them with the lowest level of confidence in their accuracy), this class is the only class which does little or no harm for all types of harm considered. This vaccination is a new development, but apparently could have significant ramifications for tobacco control.

• Group 8. Herbal cigarettes, herbal smoking mixture, lettuce cigarettes and tobacco- free bidis have all but identical harm profiles.

• Group 9. This group includes moist and dry snuffs with unconventional tobacco, non- tobacco chew, and non-tobacco snuff.

• Group 10. The only class in this group is “non-nicotine medications / therapies”. It is noteworthy that the only group that does better in terms of harm is Group 7 (vaccination against nicotine addiction).

This harm-based classification is summarized in the following Table 5.

A Harm-Based Classification of PREPS 29 Institute On Governance Table 5: A First Harm-based Classification of PREPs

Key: Severity of harm: Confidence in *** high confidence assessment: ** moderate confidence * low confidence

Harms to the user Harms to the bystander Harms to groups Harms to society Harm to the Harm to the Differential Differential harm Differential harm Cost to the Increase in Problematic health / health of harm according to according to Morbidity Mortality health care societal tobacco addiction longevity of children / according to racial / economic status system usage rates bystanders foetuses gender aboriginal origin or age Group Class Class # # Name

1.1.1.1.1 Filter cigarettes *** *** *** *** *** *** *** *** *** *** 1.1.1.1.2 "Light"/"mild" cigarettes *** *** ** *** *** *** *** *** *** *** Reduced sidestream * * *** *** * *** *** *** * * 1.1.1.1.3 smoke cigarettes 1 1.1.1.1.4 Fire-safe cigarettes *** ** *** ** ** *** *** *** *** 1.1.3.1.2 Cigars ** ** ** * * * * 1.1.3.1.3 Cigarillos ** ** ** * * * * 1.1.3.1.4 Tobacco pipes ** ** ** * * * * 2.1.1.1.2 Additive-free cigarettes *** *** *** *** *** *** ***

3.1.1.1.1 Tobacco-free cigarettes * * ** *** * * 3.1.2.2.1 Nicotine inhaler *** *** *** ** * ** * 3.1.2.2.2 Nicotine gum *** *** *** *** * *** * 3.1.2.2.3 Nicotine lollipops ** ** *** *** * ** * Tobacco-free nicotine ** ** *** *** * ** * 3.1.2.2.4 lozenge Sublingual nicotine ** ** *** *** * ** * 3.1.2.2.5 tablets 3.1.2.2.6 Dual delivery nicotine pill ** ** *** *** * ** * 3.1.2.2.7 Nicotine water ** ** *** *** * ** * 3.1.2.2.8 Oral nicotine solution ** ** *** *** * ** * 3.1.2.2.9 Nicotine fruit juice * * * *** * ** * 2 Nicotine herbal * * * *** * ** * 3.1.2.2.10 beverage Nicotine “hard” alcoholic * * * *** * ** * 3.1.2.2.11 beverage Nicotine beer-like * * * *** * ** * 3.1.2.2.12 alcoholic beverage 3.1.2.2.13 Nicotine wafers ** ** *** *** * ** * 3.1.2.2.14 Nicotine in a straw ** ** *** *** * ** * 3.1.2.3.1 Nicotine nasal spray *** *** *** *** * *** * 3.1.2.4.1 Nicotine patch *** *** *** *** * *** * 3.1.2.4.2 Nicotine lotion * * ** *** * ** * 3.1.2.4.3 Nicotine sunscreen * * ** *** * ** * 3.1.2.4.4 Nicotine lip balm * * ** *** * ** *

A Harm-Based Classification of PREPS 30 Institute On Governance Cigarettes with filters 1.1.2.1.1 containing nanometric * * * * * materials Cigarettes with ion- * * * * * 3 1.1.2.1.2 exchange filters "Low carcinogen" * * *** * ** ** 2.1.1.1.1 cigarettes 2.1.2.1.1 Cigarette-like products * * ** ** * *

Tobacco-based products * * ** * ** ** 2.1.2.1.2 containing little nicotine 4 Tobacco-based products 2.1.2.1.3 with low nicotine and low * * * * * * carcinogens

Cigarette with fluid * * ** * * 1.1.2.1.3 added to filter 1.1.3.1.1 Vaporizers * * ** ** * * 1.1.3.2.1 Chewing tobacco ** ** ** *** ** ** 1.1.3.2.2 Moist snuffs ** ** ** *** ** ** 1.1.3.2.3 Tobacco toothpaste * * * *** * * 1.1.3.3.1 Dry snuffs * * * *** * * Moist snuffs with 5 * * * *** * * 2.1.3.1.1 unconventional tobacco Tobacco packets with * * * *** * * 2.1.3.1.2 conventional tobacco Unconventional Tobacco * * * *** * * 2.1.3.1.3 packets with tobacco 2.1.3.1.4 Tobacco gum ** ** ** *** ** ** Tobacco-based nicotine * * ** *** * ** ** 2.1.3.1.5 lozenges

Mini-filter + conventional * * * ** ** * * 1.1.2.1.4 cigarette 6 Powder to alter taste of ** ** * ** ** * * 1.1.2.1.5 cigarette + cigarette

Vaccination against * * * *** * ** ** 7 3.2.3.3.1 nicotine addiction

3.2.1.1.1 Herbal cigarettes * * ** * * * * 3.2.1.1.2 Herbal smoking mixture * * ** * * * * 8 3.2.1.1.3 Lettuce cigarettes * * ** * * 3.2.2.1.1 Tobacco-free bidis * * ** * *

Moist and dry snuffs with ** ** ** *** ** ** 2.1.3.2.1 unconventional tobacco 9 3.2.3.1.4 Non-tobacco chew * * * ** ** ** 3.2.3.2.1 Non-tobacco snuff * * * ** ** **

Non-nicotine ** ** * ** ** ** 10 3.2.3.1.1 medications / therapies

A Harm-Based Classification of PREPS 31 Institute On Governance The discussion of these results is grouped into the following five observations:

• There is no direct correspondence between the regulatory classification and the harm-based classification. Some products which have little in common, on the regulatory classification, turn out to have similar harm profiles, while products which have much in common, on the regulatory classification, turn out to have significantly different harm profiles. This suggests that a genuine harm-based regulatory framework for PREPs would look rather different than a more orthodox regulatory framework.

• More empirical data is needed to determine complete harm profiles for the regulatory classes. In particular, there are certain products for which little scientific information is available (for example, the various classes of herbal products). Furthermore, there are certain harms (the group harms, in particular), which require additional empirical research, for most classes. It is a limitation of our approach that fire-safe cigarettes have the same “severity of harm rating” (yellow) for the user as smokeless tobacco because they are both an improvement over conventional cigarettes. It is likely, however, that fire-safe cigarettes are only marginally different and smokeless tobacco is significantly different. More data would make it perhaps possible to use more categories of severity of harm.

• A discussion of the specific harms, and the correct analysis thereof, needs to be broadened. Do the harms taken into account in the harm profiles include all the relevant ones? Do they include any that are not relevant? Is the way we have analyzed them correct? If not, how should they be analyzed? The inclusion of users in this discussion would be critical.

• Discussion of the harm profiles themselves needs to be undertaken. Is the assignment of degrees of harmfulness reasonable? If not, what alternative assignment is to be preferred? If that is unknown, is the harm-based approach truly feasible? If not, what implications does that fact have for the Canadian tobacco control strategy?

• Discussion of how to formulate a harm-based classification, given that we have acceptable harm profiles, needs to be undertaken. A harm-based classification does not simply fall out of the harm-profiles. What is the correct harm-based classification? Is there a specific procedure by which this is to be arrived at? If not, is it feasible to construct a harm-based classification (perhaps by proceeding intuitively)? If this is not feasible, what are the implications for the tobacco control strategy?

A Harm-Based Classification of PREPS 32 Institute On Governance 4. Conclusions

4.1. Recommendations

This research represents just Phase I of a Better Practices Project. As such, the following recommendations are not grounded in the practical application of the theoretical work presented above. Nevertheless, we provide here some ideas and observations as a basis for discussion that practitioners, public interest groups, policy and regulatory communities may find worth considering (the submission of recommendations is a requirement under this grant).

(1) We recommend that attention be given to regulatory foresight and the possibility of regulatory loopholes. a. A designated office or organization carrying out foresight on behalf of the broader community of stakeholders would be valuable (a screening of the product pipelines as it has been done in this study as the basis for Table 2). b. This foresight activity should inform all relevant regulatory and policy bodies at Health Canada (e.g., nicotine regulation at the Therapeutic Products Directorate, regulation of herbal products at the Natural Health Products Directorate, and, of course, the Tobacco Control Program) as well as public interest groups. c. The communication among these regulatory and policy-making bodies may need to be strengthened to prevent regulatory loopholes from arising. d. A case study on possible regulatory loopholes could be done using the examples of the regulation of herbal cigarettes (including herbal cigarettes spiked with nicotine) or smokeless tobacco.

(2) The diversity of products shown in our tables illustrates the importance of the identification of the priority products of real concern and real opportunity. a. A prioritization of such products should be facilitated by the means of harm profiles. However, it will be necessary to monitor the actual consumption of these products (e.g., in other countries if they are not available in Canada). b. Monitoring of products in the Canadian marketplace does not have to be done by government alone. c. It will also be important to prioritize the components of products – does the concern or opportunity lie in the products themselves or in the packaging and labelling? Product descriptions and advertisement are, of course, important issues. It is conceivable that the concept of harm profile could have utility in the design and analysis of this information.

(3) An increased communication and horizontal integration among regulatory, policy and decision-making bodies (see above) may be required to evaluate the role of PREPs within harm reduction strategies (sometimes called “regulatory governance”.) a. One reason for the need for communication arises when comparative harms, benefits, and risks must be evaluated (e.g., are herbal cigarettes worse than nicotine lozenges?). Such a comparison may require a lot of information – empirical information about toxicological risk and also analyses into harms other

A Harm-Based Classification of PREPS 33 Institute On Governance than toxicity. Combining science and ethics within regulatory decision-making is notoriously difficult and requires good communications at the science-policy interface. We believe that the concept of a harm profile is useful in bridging the discussion on the issues of (a) endpoint selection in risk assessment, (b) comparative risk assessment, and (c) socio-economic and ethical assessment. b. Horizontal integration also improves the ability to communicate with non- government stakeholders, improves the regulatory transparency and improves the ability to engage non-government stakeholders. Recently, Canada’s Smart Regulation Initiative has emphasized attention to horizontal issues in regulation. For example, it recommends that the precautionary principle be used in a similar way across the federal government. We believe that the harm-based classification presented here (or at the least the concept) would be a useful tool for this cooperation, coordination and consultation.

(4) A move towards a harm-based regulatory approach (instead of a claim-based, use- based or chemistry-based regulatory approach) could be considered. a. Based on increased communication among the different government players, the need for changes in the regulatory system could be discussed (this is ambitious because it may require legislative change). Better horizontal regulatory governance and better focus on potential harm and benefit (instead of intended use, health claims and the like) would improve the potential for those products to enter the market that could genuinely improve the health of Canadians (and still control the products that do not). b. Starting these discussions with the concept of harm profiles, rather than just “risk assessment,” is a good basis for capturing the breadth of the issues – i.e., the issues beyond the inherent toxicity of a product or the side effects that could be expected from use according to label instructions. c. There is an opportunity here to push the concepts and boundaries of regulation in general. Tobacco and nicotine involve more complexity for regulation than, say, pharmaceuticals, fishing permits, or the building of houses, because there is an interesting spectrum going from tobacco (largely unregulated), to tobacco advertisement and packaging (heavily regulated), to nicotine (regulated like pharmaceuticals), to natural health products (that only recently became regulated and which involve a category where tobacco and nicotine products may or may not fit). To base the streaming of products within oversight systems purely on the claims made by proponents, the commercial status of products, the mode of production, etc., is remote from the idea of harm profiles, risks and benefits.

(5) We recommend that a discussion on the burden of proof for claims of exposure reduction or harm reduction will take place. a. It is an odd reality that the two countries with the best (strongest) management of tobacco (Canada and Norway) also appear to be harshest when it comes to the treatment of alternatives that may be less harmful. There is the danger that such a position could lead to an inferior long-term overall outcome compared to countries that are more lenient across the board (if PREPs really work).

A Harm-Based Classification of PREPS 34 Institute On Governance b. A system that puts the burden of proof squarely on the shoulders of industry may not be in the best interest of Canadians. This is especially true if the standard of proof is high. It took a long time to prove that cigarettes are harmful. It is likely that it would also take a long time to identify the precise harm a less toxic product will cause. However, a comparative assessment of harm (relative to cigarettes, based on harm profiles) could be manageable. For example, products that are not inhaled will certainly be less harmful to bystanders than cigarettes are. c. The previous points links to the discussion on the interpretation of the precautionary principle. If precaution is one-sided (only considering the risk of commission, i.e., doing an action) then it can become an anti-novelty principle. In the context of genetically engineered food, Europe has been accused of using the principle in just this way. If precaution is two-sided (also considering the risk of omission) then it is hard to distinguish from traditional cost-benefit analysis. Exploring this issue in the harm reduction context may be worthwhile. d. Related to this issue is the balancing of (i) the real danger of misleading consumers towards a false sense of the safety of PREPs versus (ii) the “right to know” the harm profile of some PREPs and the “right to choose” how a nicotine addiction is treated (i.e., being able to buy PREPS). For example, it is likely that we know enough about smokeless tobacco to provide information to consumers about its relative harm (compared to cigarettes) and it absolute harm (compared to abstinence). The act of omission involved in not informing the public should be weighed against the act of commission, and the weighing should not only be based on an assessment of the corporate risk to a government department (e.g., reputation and litigation risk) but also on the risk to the public.

(6) One approach to foster debate among different stakeholders and to provide a form of regulation is to discuss voluntary means of regulation and compliance. a. The PREPs industry could contemplate the development of a code or a statement of principles to guide the production of PREPs and (perhaps more importantly) to determine the content and means of informing consumers. b. Government could play the role of a “mid-wife” in bringing such initiatives to light. c. Successful examples of pledges, codes, statements, commitments, corporate social responsibility initiatives, industry-public interest accords, etc., exist in other contexts. There are also examples where such initiatives ultimately became judged as “window-dressing” exercises or as attempts to pre-empt looming mandatory regulations. Successful examples could be studied for their applicability in the PREPs context.

(7) We recommend a stakeholder consultation on the issue of PREPs and harm reduction that includes tobacco growers, producers, regulators, policy makers, public policy groups and consumers. a. There seems to be, at the very least, a need for information. In some instances public consultation will be helpful. In some other instances, full public engagement may be appropriate.

A Harm-Based Classification of PREPS 35 Institute On Governance b. It is important to remember that rural communities play an important role in tobacco consumption – this is also an opportunity to capture the effect of tobacco and nicotine policies on the tobacco growers (and future nicotine growers?)

(8) The development of detailed harm profiles for priority products may be helpful. a. The harm profiles used above are useful to illustrate the concept and to classify PREPs into harm classes. They are not detailed enough to serve the analysis of products in a harm reduction context. More detailed harm profiles are needed at that stage. b. The red/yellow/green indicators for severity (used above) are insufficiently precise to serve a detailed analysis. c. The concept of harm cold be refined by explicitly differentiating (i) inherent toxicity, (ii) harm from prescribed dosage and use, (iii) harm from actual use including off-label prescription and abuse. Tracking actual use is critically important but is sometimes omitted because regulators may not have a mandate to discuss misuse of regulated products. d. The distinction of avoidable and unavoidable harm should be considered.

(9) The use of the term “harm reduction” should be evaluated with a clear understanding of its uses outside the tobacco community. a. There is quite a large difference between a methadone program and the possibility that a standard for manufacturing of products would be set under the Tobacco Act. The very negative connotation of “harm reduction” (in some circles) should be considered. b. In this context, we recommend that the tobacco control community intensify its communication with colleagues working the medial marijuana field and the control of illegal drugs. A clearer understanding of when it is appropriate to use the same term (harm reduction), and when it is not, should emerge from such a discussion – among other benefits. c. The Government of Canada could consider the development of an Integrated Harm Reduction Framework to cover the diverse activities. In the literature, “harm reduction” has been used in very different contexts (prostitution, air bags, etc.) and, thus, the possibility of ambiguous communications coming from the same organization (the federal government or other governments) is real.

(10) Finally, (and despite the significant amount or work that flowed into this research) we recommend that the point made by Warner (2002) be considered: The attention required to manage the threats and opportunities that arise from a glut of new products should not cause a decrease in the attention given to the important on-going work on cessation and prevention.

A Harm-Based Classification of PREPS 36 Institute On Governance 4.2. Directions for future research

A number of the recommendations listed above entail a need for future research. Also, the discussion of the harm-based classification contains elements of what is needed to improve that classification. This section lists a few specific and additional issues.

• Research to eliminate the gaps in our empirical knowledge of the health effects of PREPs (on both consumers and bystanders) is required if a harm-based classification of PREPs is to be completed. Examples are actual (long-term) effects, “gateway effects” (consumption leading to the consumption of other nicotine products), differential harm to different groups of users, etc.

• Further consultations and some additional conceptual work on harm and harm profiles needs to be carried out in order to refine the existing and future harm-based classifications of PREPs.

• A harm-based classification of PREPs provides only the basis for an assessment of alternative harm-reduction strategies, since strategies themselves seem to be the appropriate unit of analysis. Having a harm-based classification of PREPs gives us one prerequisite for an assessment of harm-reduction strategies, but that assessment remains to be done. The classification also allows integration of policy approaches across types of products such as natural health products, cannabis and hard drugs.

• Neither a harm-based classification of PREPs, nor an assessment of PREPs in the context of alternative harm-reduction strategies, answers all the ethical questions about PREPs. Such knowledge appears rather to be a prerequisite for answering more specific ethical questions about PREPs. This suggests a new avenue of research focussed on priority PREPs and ethics proper.

• Research into the applicability of the concepts developed here to other contexts may be of some interest (see also Recommendation 4.c on this point).

A Harm-Based Classification of PREPS 37 Institute On Governance 5. Literature review

As a result of our comprehensive review of the available literature on tobacco and nicotine products, specifically as it relates to PREPs and their relative harm profiles, we have compiled two Tables summarizing the most relevant information (up to 2003).

Table 6 lists documents that are presently available over the world-wide-web. This Table includes details such as the author/s, the year of publication, title, hyperlink, subject/s, and abstract, as well as a brief summary of the type/s of harm discussed in each document. This table includes papers from the open literature (that would be otherwise listed in Table 7) as long as they are available on the world-wide-web.

Table 7, on the other hand, lists journal articles, reports and books that are available to researchers at libraries. This Table also provides the author/s, the year of publication, title, subject/s, abstracts and a brief summary of the type/s of harm discussed in each document.

A Harm-Based Classification of PREPS 38 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Action on 2000 Policy Paper on http://www.ashsc Nicotine Nicotine Replacement Therapy (NRT) has TO THE USER -- Nicotine - Under "Nicotine Smoking and Regulation and otland.org.uk/iss Replacement been shown to be effective in the treatment Replacement Therapy" section - "Although Health Control of Tobacco ues/tob_reg00.ht Therapy - of tobacco dependence and withdrawal. nicotine is the addictive substance in tobacco, (Scotland) Products ml Cigarette-like Numerous clinical trials have shown that it causes relatively little harm itself (WHO ASH devices - NRT (which now includes gum, patches, 1999). Nicotine increases blood pressure and Regulation nasal spray, inhalator, tablet and lozenge) cardiac output and causes peripheral increases smokers' chances of remaining vasoconstriction. It also increases levels of abstinent from cigarettes for a year by free fatty acids, noradrenaline, adrenaline, between 50-100%. fibrinogen and thromboxane (Raw 1997)." "Experts have accepted for some time that nicotine is not carcinogenic." Tar - under "Low Tar Cigarettes and Filters" section - "as the trend towards consumption of 'light' cigarettes increases so does the evidence that smokers of low-tar cigarettes are as likely to get cancer as high-tar smokers." Bate, Roger 2003 "Chewing Over http://www.ash.o Smokeless "Of all the types of tobacco, smokeless TO THE USER -- Smokless Tobacco - "Of Professor Nilsson's review Tobacco," in The rg.uk/html/regula Tobacco sucked or chewed tobacco, or wet snuff, all the types of tobacco, smokeless sucked or of the evidence is available Wall Street Journal tion/html/wsj030 (Harm Profile) causes the least cancer. The evidence is chewed tobacco, or wet snuff, causes the in the Journal of April 3, 2003. 403.html overwhelming, says Professor Robert least cancer." Regulatory Toxicology and Nilsson, a toxicologist at Stockholm Pharmacology, 1998 (see University, and formerly with the EPA-like Table 2). Swedish Chemicals Inspectorate, that ‘snus is the least dangerous form of tobacco.’ Snus is the Swedish name for sucked snuff and Sweden is the only country in Europe where it can be sold." Bates, Clive 2002 Harm Reduction: http://www.ash.o Tobacco This document introduces broad notions of Not Specific To Any Type of Harm ASH An Introduction to rg.uk/html/regula Harm harm reduction, then focuses on harm the Issues. tion/pdfs/hrbrief. Reduction reduction strategies available for tobacco pdf (these are divided between i) type of use, and ii) type of product). The document then reviews the main conflicts associated with harm reduction strategies (i.e., "drug use vs. harm," "harm reduction vs. cessation," "intended vs. unintended consequences," "quantitative vs. qualitative view (risk-use equilibrium)," "public health master plan vs. human rights of smokers," "profiteering vs. challenging Big Tobacco," "market vs. regulation," and "precautionary vs. evidence- based").

A Harm-Based Classification of PREPS 39 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Bates, Clive, 1999 The Safer http://www.ash.o Tobacco Research by ASH has uncovered over fifty Not Specific To Any Type of Harm and Martin Cigarette: What the rg.uk/?patent Harm patents for technologies that would reduce Jarvis tobacco industry Reduction the chemicals in cigarette smoke that cause could do…and why cancer, heart disease and emphysema. The it hasn't done it. A technologies include catalysts, active survey of 25 years chemical filters and pre-processing of the of patens for tobacco. Includes direct quotes from the innovations to published patents. reduce toxic and carcinogenic chemicals in tobacco smoke. ASH and Imperial Cancer Research Fund, London. Bates, Clive, 1999 "The future of http://tc.bmjjourn Tobacco/nicot The authors argue: "further reductions in tar TO THE USER -- Regulation reducing Ann McNeill, tobacco product als.com/cgi/repri ine Regulation and nicotine yields as measured by the nicotine content in cigarettes - "Smokers Martin Jarvis regulation and nt/8/2/225.pdf International Standards may respond…by increasing smoke intake to and Nigel labelling in Europe: Organisation/Federal Trade Commission attain a satisfactory dose of nicotine. This Gray implications for the (ISO/FTC) method will be largely cosmetic would increase harm." (p.225). Tar - "Tar is a forthcoming and certainly misleading to consumers. If a collective name for thousands of chemicals European Union new directive uses the ISO/FTC that form the thick, sticky residue of tobacco directive," in methodology as a basis for regulation, it smoke. It has markedly different compositions Tobacco Control risks lending further official support to the which are likely to cause different degrees of 1999; Vol.8: pp. concept of "low tar" cigarettes, which may be harm." (p.227). Eclipse - "The tar in potential 225-235 used by smokers as an alternative to product innovations such as Eclipse is of a smoking cessation." very different nature; in Eclipse it is predominantly glycerol. " (Ibid.). Additives (in cigarettes) - "Little is known about the potential harmful effects of many additives when they are burned with tobacco or in conjunction with other additives...Thus some additives, although not directly toxic in themselves, may nevertheless increase tobacco-related harm by making cigarettes more palatable, attractive, or addictive to consumers." (p.229). California 2002 Summary of New http://www.trdrp. Novel A document that lists: Modified cigarettes; TO THE USER -- Advance Lights "Full Tobacco- Tobacco Products org/Docs/NCTO Nicotine/Toba Products that heat rather than burn tobacco; nicotine, lower CO." Omni Lights - "have Related H%20New%20P cco Products New smokeless tobacco products; Oral more tar than Kool Lights." Quest - "low or no Disease roducts%20Han nicotine products removed from the US nicotine." Eclipse - "Full nicotine, higher CO, Research dout.pdf market by the FDA. The document provides tube made of plastic, aliminum and fiberglass Program images of the products and lists results in delivery of glass fibers to the manufacturers, description, and mouthand lungs." Accord - "Full nicotine, manufacturers' claim about the product. reduced CO and some other chemicals."

A Harm-Based Classification of PREPS 40 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Fagerström, 2000 "Randomised trial http://tc.bmjjourn Eclipse - "Eclipse can dramatically decrease cigarette TO THE USER -- Eclipse - "the patient would Karl Olov, investigating effect als.com/cgi/repri Harm consumption without causing withdrawal probably have a carbon monoxide John R of a novel nicotine nt/9/3/327.pdf Reduction - symptoms or decreases in nicotine concentration that was even higher than that Hughes, delivery device Nicotine concentrations or motivation to quit derived from smoking his or her own Thomas (Eclipse) and a Replacement altogether. Unlike the inhaler, Eclipse cigarettes…the switch to Eclipse may not Rasmussen nicotine oral inhaler Therapy produces an increase in carbon monoxide reduce the smoker's risk for cardiovascular and Peter W. on smoking concentration. Thus Eclipse may not be a disease and may even increase it." (p.332). Callas behaviour, nicotine safer cigarette." and carbon monoxide exposure, and motivation to quit," in Tobacco Control; Vol. 9(3): 327-33. Fowles, 2000 The Chemical http://www.ndp.g Tobacco This report discusses possible components TO THE USER -- Tar - "contains many Jefferson, Constituents in ovt.nz/tobacco/to Harm of a harm reduction strategy for tobacco harmful carcinogenic constutuents, including Michael Cigarettes and baccochem.pdf Reduction - products (p.7). The report reviews and metals, PAHs, dioxins, and some non-volatile Bates and Cigarette Smoke: Public Policy summarizes the available data and the nitrosamines." (p.11). Dominique Priorities for Harm international policies relating to chemical Noiton Reduction. A constituents (excluding nicotine and tar) of Report to the New cigarettes and cigarette smoke. Suggested Zealand Ministry of measures are provided to help guide Health governments develop policies should any harm reduction strategy for tobacco products be pursued (p.42) Hamilton, 2001 Nicotine: The http://www.force Nicotine A pro-tobacco document that provides Not Specific To Any Type of Harm Positive aspects of Wanda Wonder Drug s.org/evidence/p references to journal articles/studies that link nicotine; a list of studies harma/pdf/gold.p nicotine with positive medical applications. that suggest positive df effects of nicotine, among other.

A Harm-Based Classification of PREPS 41 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Henningfield 1998 "Reducing the http://tc.bmjjourn Nicotine The role of nicotine in causing and TO THE USER -- Low Nicotine-Yield JE, Benowitz addictiveness of als.com/cgi/repri Reduction sustaining tobacco use was evaluated to cigarettes - "even though compensatory NL, Slade J, cigarettes," in nt/7/3/281.pdf Strategy project the impact of a nicotine reduction over-smoking is a concern, the extent may not Houston TP, Tobacco Control strategy on initiation and maintenance of, prove to be great." (p.286). Nicotine et al. 1998; 7: 281-93. and relapse to, tobacco use. A range of abstinence - "can precipitate symptoms of potential concerns and barriers is depression in people with histories of major addressed, including the technical feasibility depressive disorders...might exacerbate of reducing cigarette nicotine content to non- symptoms of other forms of psychiatric illness addictive levels, and the possibility that or complicate the management of other forms compensatory smoking would reduce of drug dependence treatments" (Ibid.). potential health benefits. Conclusions: (i) gradually eliminating nicotine from cigarettes is technically feasible; (ii) a nicotine reduction strategy holds great promise in preventing adolescent tobacco addiction and assisting the millions of current cigarette smokers in their efforts to quit using tobacco products; (iii) potential problems such as compensatory over-smoking of denicotinised cigarettes and black market sales could be minimised by providing alternate forms of nicotine delivery with less or little risk to health, as part of expanded access to treatment. Henningfield 2001 "Swedish Match http://tc.bmjjourn Smokeless Studies show that in the US, "smokeless TO THE USER -- Smokless Tobacco - Less J.E. and Company, Swedish als.com/cgi/repri Tobacco - tobacco products appear to have actually harmfull than cigarettes. Nicotine K.O. snus and public nt/10/3/253.pdf Harm fuelled the public health problem caused by Replacement Therapies - Preferred to Fagerstrom health: a harm Reduction tobacco use by serving as entrées for youth Smokless tobacco as a less dangerous reduction to develop nicotine dependence and product. experiment in frequently to progress to cigarette TO WOMEN -- Smokless Tobacco - "the progress?" in smoking...In Sweden, the tobacco marketing direct benefits have been limited to the male Tobacco Control and regulatory situation has been different population, because few females use 2001; 10(3): 253- from that of most other countries in several smokless tobacco." (p.255). 57. respects, and Sweden has become one of the first developed nations to see a significant decline in tobacco attributable mortality...we believe that the situation in Sweden might be considered a real world experiment in harm reduction that is in progress"

A Harm-Based Classification of PREPS 42 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Kozlowski, 2001 "Applying the Nicotine This article seeks to balance the risk and TO THE USER -- Medicinal nicotine (MN) - Lynn T., et risk/use http://tc.bmjjourn Replacement use of NRT. Kozlowski et al. conclude that "For the individual smoker, there is no doubt al. equilibrium: Use als.com/cgi/repri Therapy there are no plausible circumstances in that MN, in the form of pharmaceutically medicinal nicotine nt/10/3/201.pdf which wider use of NRT for harm reduction tested products such as gum, patch, nasal now for harm could lead to the unintended consequences spray, is less dangerous than continuing reduction," in overwhelming the benefits. smoking." (p.201). "Most concerns of mortality Tobacco Control effects in users of MN focus on possible 2001; 10(3): 201- effects on cardiovascular disease." (p.202). 03. "MN does not seem to produce many of the cardiovascular risks of cigarette smoke...MN does not appear to promote platelet aggregation. MN has no carbon monoxide. MN (gum) was shown to not have adverse effects on coronary circulation. MN (nasal spray) was found to not have adverse effects on blood lipids." (Ibid.). "research supports that MN has very low cardiovascular risk" (Ibid.). "Other research has found no excess risk of myocardial infarction from the nicotine patch in the general population or even in patients with cardiovascular disease." (Ibid). NRT - "Ramstrom found no cases where Nicorette gum was being used by someone who had not used tobacco previously." (Ibid.). Kozlowski,L 1998 "Filter ventilation http://tc.bmjjourn Filter Filter ventilation appears to be the TO THE USER -- Cigarette filter - "blocking T, Mehta, and nicotine als.com/cgi/repri Ventilation predominant method for reducing machine- even a portion of the filter vents can markedly NY, content of tobacco nt/7/4/369.pdf smoked yields of tar, nicotine, and CO in increase a smoker's exposure to the harmful Sweeney in cigarettes from three countries. However, some brands components of cigarette smoke." (p.374). CT, Canada, the United contain about twice as much nicotine (total Schwartz Kingdom and the content or percent nicotine) as do others, SS, Vogler United States," in indicating that tobacco types or blends and GP, Jarvis Tobacco Control tobacco casings can be used to manipulate MJ, West Winter 1998; 7(4): nicotine content and nicotine delivery of RJ. 369-75. cigarettes. Labstat 2000 "Labstat http://tobaccofre Cigarette-like This report provides the results of a study on TO THE USER -- Eclipse - "Yields of 'tar', CO International International Inc. ekids.org/reports Product - the harmful effects of R. J. Reynolds and NNK (a human carcinogen) from Eclipse Inc. Test Report. /eclipse/gc7repo Eclipse (Harm cigarette-like product Eclipse. The study were much higher than those of the other test Project Identifier: rt.pdf Profile) found that Eclipse produces as much, if not brands* under both smoking regimens ('ISO' GC7," a Study more, of cancer-causing toxins as two and 'Increased')." (p.17). Commissioned by comparative ultralight brands of cigarettes. *Carlton and Now (both low tar cigarette the Massachusetts The study also found that Eclipse released brands). Department of higher levels of carbon monoxide, a leading Public Health cause of cardiovascular disease in smokers.

A Harm-Based Classification of PREPS 43 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

McNeill, 2001 "Regulation of http://www.ash.o Nicotine "It is argued that the current regulatory TO THE USER -- Nicotine - "There exists a Ann, Nicotine rg.uk/html/regula Replacement framework (UK) restricts access to NRT large body of evidence that nicotine is not a Jonathan Replacement tion/pdfs/nrtcritiq Therapies - without adequately considering that the likely significant risk factor for cardiovascular Foulds and Therapies (NRT): A ue.pdf Regulation consequence is continued dependent use of events, does not cause cancer and does not Clive Bates Critique of Current a far more harmful and widely available cause respiratory disease" (p.1758). NRT Practices," in version of the same drug: tobacco. NRT Products - " evidence indicates clearly that Addiction 96: 1757- products should be made as widely available the products are safe." (p.1758). "A 68. as cigarettes. This paper also comparative study of four NRT products found recommends that regulators encourage generally low ratings of pleasantness and the development of less harmful forms of satisfaction from using the NRT products for nicotine devices to compete with four weeks and concluded that the abuse cigarettes." liability for all four products was low." (p.1759). "There is no evidence that combination treatments are harmful." (p.1764). Swedish snus - "nicotine intake does not cause an increase in oral/pharyngeal cancer, and there is no conclusive evidence of an increased risk of myocardial infarction." (p.1758). TO WOMEN -- Nicotine - "There are...concerns over nicotine safety in pregnancy." (p.1758). TO ADOLESCENTS -- NRT - "One study of 22 adolescent smokers using nicotine patch therapy concluded that this seemed safe for use with adolescent smokers. A second study...concluded that nicotine patch therapy did not appear to be effective with this target group." (p.1759). Novotny, 2000 "Smoking http://www1.worl Nicotine This chapter reviews briefly the effectiveness TO THE USER -- NRT - "Controlled clinical Thomas E., Cessation and dbank.org/tobac Replacement of various Nicotine Replacement Therapies; trials of NRT in smokers with documented Jillian C. Nicotine- co/tcdc/287TO3 Therapies - discusses issues concerning the cardiovascular disease have found no Cohen, Ayda Replacement 08.PDF Cessation - sale/regulation of such therapies; and evidence that NRT products are harmful, even Yurekli, Therapies," in Regulation explores public policy options for the sale of if used for as long as five years." (p.292). David Prabhat Jha and NRTs. Sweanor, Frank Chaloupka and Joy de eds., Tobacco Beyer Control in Developing Countries. Physicians 2002 The History of the http://www.smok Safer Thid document traces the development of Not Specific To Any Type of Harm for a Smoke- Canadian Safer e- Cigarette reduced-harm products by tobacco Free Canada Cigarette Program free.ca/pdf_1/Re manufacturers. Specifically, this document ducing%20harm traces projects by Imperial Tobacco Canada %20increasing% and British American Tobacco to produce a 20profit.pdf safer cigarette.

A Harm-Based Classification of PREPS 44 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Polito, John 2003 "Are Teens Getting http://whyquit.co Nicotine Lists a series of recent Nicotine TO ADOLESCENTS -- NRT - "students may Provides a useful list of R. Hooked on NRT?" m/pr/June_2003. Replacement Replacement Therapy (NRT) studies: "A be establishing chemical dependency upon references. in WhyQuit.com, html Therapies new study finds that three-quarters of nicotine without ever using tobacco products. June 11, 2003 surveyed Memphis high school juniors who Among the 216 NRT users, 40 represented used nicotine replacement therapy (NRT) did that they had 'never smoked a cigarette, not not do so for purposes of trying to quit. Even even a few puffs.' Yet, 11 of the same 40 more alarming is the study’s revelation that report using NRT several times a week and 7 among student NRT users 18% were never- others say that they use it every day." smokers." Pope, 2000 Balancing Public http://www.rights Ethics Pope examines the 'harm principle' and the Not Specific To Any Type of Harm A philosophical document Thaddeus Health Against moke.org/mason 'soft paternalism principle.' The article also Mason Individual Liberty: -pope.pdf discusses the notion of defining "harm to The Ethics of others" (p.5) Smoking Regulation Royal 2002 Protecting http://www.rcplo Smokeless The report states: "As a way of using Not Specific To Any Type of Harm College of Smokers, Saving ndon.ac.uk/pubs Tobacco nicotine, the consumption of non- Physicians Lives: The Case for /books/protsmok (Harm Profile) combustible [smokeless] tobacco is on the (UK) a Tobacco and ers/ProtSmokers order of 10-1,000 times less hazardous than Nicotine .pdf smoking, depending on the product." The Regulatory report suggests that some smokeless Authority. tobacco manufacturers may want to market their products "as a 'harm reduction' option for nicotine users, and they may find support for that in the public health community."

A Harm-Based Classification of PREPS 45 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Royal 2000 Nicotine Addiction http://www.rcplo Nicotine This report addresses the fundamental role TO THE USER -- "nicotine result in an acute Section 7.3 of this report College of in Britain: A report ndon.ac.uk/pubs Replacement of nicotine addiction in smoking. Sections of increase in heart rate and blood pressure provides the information Physicians of the Tobacco /books/nicotine/ Therapy - particular interest: 7.2) Nicotine replacement when nicotine is delivered via cigarette for Class 21 ( non-nicotine (UK) Advisory Group of Regulation therapy; 7.3) Non-nicotine medications for smoking, chewing gum, nasal spray or medications/therapies) in the Royal College treating nicotine addiction; 8.2) The intravenous infusion. Transdermal nicotine our of Physicians regulation of nicotine, tar and additives in causes less intense changes...Nicotine PREPs Chart cigarettes; 8.3) Anomalies in current nicotine induces vasoconstriction in coronary arteries" regulation; 8.4) Novel nicotine delivery (S2.2) "Acute systemic toxic effects of nicotine devices from tobacco companies; 8.5) include: CNS effects: headache, dizziness, Tobacco regulation in the USA; 8.6) Future insomnia, abnormal dreams, nervousness; nicotine regulation in the UK; 9.5) gastrointestinal (GI) distress: dry mouth, Recommendations (#3,10, 13 and 15). nausea, vomiting, dyspepsia, diarrhoea; musculoskeletal symptoms: arthralgias, myalgia. In general, in relation to NRT for smokers, these effects tend to be mild." "nicotine exerts cardiovascular effects primarily by activating the sympathetic nervous system, resulting in an increase in heart rate, blood pressure and cardiac contractility, thereby increasing myocardial oxygen consumption and demand for blood flow." (S2.3) "Snuff use results in acute cardiovascular effects similar to those with cigarette smoking: that is, an increase in heart rate and blood pressure." (S2.3) NRT "Long- term use of NRT does not seem to be associated with any significant harmful effects." (S7.2) Shiffman, 2002 "Smokers' beliefs http://tc.bmjjourn Modified "Most smokers believed Lights and Ultra Not Specific To Any Type of Harm Saul, Janine about "Light" and als.com/cgi/repri Cigarettes Lights were less harsh and delivered less tar L Pillitteri, "Ultra Light" nt/10/suppl_1/i1 and nicotine. On average, smokers believed Steven L cigarettes," in 7.pdf that Lights afforded a 25% reduction in risk, Burton, Tobacco Control and Ultra Lights a 33% reduction in risk. Jeffrey M 2001; 10 (Suppl 1): Light and Ultra Light cigarette smokers Rohay, and i17-i23. evaluated the risks of their own cigarette Joe G types more favourably. Quitting intention Gitchell was modestly related to beliefs about these cigarettes. Believing that Lights and Ultra Lights delivered less tar and nicotine and that they were less harsh each independently contributed to the belief that these cigarettes were safer."

A Harm-Based Classification of PREPS 46 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Slade J, 2002 "Eclipse: does it http://tc.bmjjourn Eclipse (Harm A critique of the emissions data from TO THE USER -- Eclipse - "There is as yet Connolly live up to its health als.com/cgi/repri Profile) Eclipse, using a comparison with ultra lights unsatisfactory evidence that Eclipse is less GN, and claims?" in nt/11/suppl_2/ii6 cigarette yields and showing increasing harmful than conventional cigarettes" (p.ii64). Lymperis D Tobacco Control 4.pdf yields of several chemicals in Eclipse over NRT - "The Institute of Medicine panel 11(suppl.2): ii64- several years. determined that there was insufficient ii70. evidence to conclude that any currently marketed product, inluding Eclipse, actually delivered on the promise of reduced exposure, much less on that of reduced harm." (p.ii69). Slade, John, 1995 "Nicotine and http://www.ama- Nicotine During a period of 22 years (1962 to 1984), Not Specific To Any Type of Harm Info on Nicotine, Tobacco Lisa A. Bero, Addiction. The assn.org/sci- Addictiveness employees of Brown &Williamson Tobacco Industry’s perception of Peter Brown and pubs/journals/ar and B ritish American Tobacco conducted Nicotine, & list of sources. Hanauer, Williamson chive/jama/vol_2 research and commented on the Deborah E. Documents," in 74/no_3/sc5043. pharmacology of nicotine. They consistently Barnes, and Journal of the htm regarded nicotine as the pharmacological Stanton A. American Medical agent that explained tobacco use. In the Glantz Association - early part of the period under study, officials Special of the companies wrote about nicotine Communication - addiction explicitly. Inhalation of cigarette July 19, 1995. smoke by the consumer was recognized throughout the period as necessary for the normal function of a cigarette. The documents contain little indication that research was conducted on either the taste or the flavor of nicotine. The documents reveal an intention on the part of B&W and its corporate parent to affect the function of the body with nicotine. Sullum, 2003 "Pinch Hit. Oral http://www.reaso Smokeless "How is a tin of Skoal Bandits like a sterile Not Specific To Any Type of Harm Jacob snuff as an n.com/links/links Tobacco hypodermic needle? In public health lingo, alternative to 020503.shtml (Harm Profile) both can be viewed as 'harm reduction' cigarettes," in (Ethics) devices that lower the risks of drug Reason. February consumption. But while public health 5, 2003. specialists have little trouble accepting the idea that clean needles can reduce disease among heroin users, they tend to rebel at the notion that oral snuff can reduce disease among tobacco users."

A Harm-Based Classification of PREPS 47 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Sweanor, 1997 Alternative Nicotine http://www.nsra- Regulation This article reviews significant interventions TO THE USER -- "There is a substantial body David Delivery as a adnf.ca/news_inf that are available to prevent the use of of evidence indicating that some forms of Harm-Reduction o.php?cPath=23 tobacco products. The premise of the article nicotine delivery are significantly less Strategy. _51&news_id=6 is that: "The continued use of alternative harmful than others. Even among tobacco 6 nicotine delivery on a long term basis, as an products there are differences in health alternative to tobacco products, would impact. When tobacco products in general, massively improve public health. Since the and current cigarettes in particular, are nicotine replacement therapies are short- compared to other forms of nicotine delivery term, many users are forced to return to (NRT, for example) the difference in health tobacco products to satisfy a desire for impact is immense." nicotine." The author advocates the introduction of a system that allows "alternative, less hazardous, nicotine delivery devices on the market." The author lists 11 advantages associated with this sytem. Lastly, the author argues for a regulatory shift away from the present regime that favours producers of tobacco products, to a regulatory regime that would provide a level playing field for all nicotine products: "It is essentially impossible for other products, under the existing regulatory regimes, to compete in any meaningful way with tobacco products." Sweanor, 1998 Smoking Cessation http://www.nsra- Cessation In this article, the author claims that "despite Not Specific To Any Type of Harm David Pharmaceuticals adnf.ca/news_inf Strategy the demonstrated effectiveness of and Tobacco o.php?cPath=23 pharmaceutical cessation products in Control _51&news_id=6 reducing tobacco's health toll, these 5 products have had very limited sales. These sales are a tiny fraction of the over $300 billion (U.S.) global tobacco market. The missed opportunities for pharmaceutical cessation products, and of the public health gains which would accompany these sales, are tremendous. In seeking to address this issue we need to look at more effective cooperation between the pharmaceutical business and tobacco control professionals." To this end, the author proposes 4 steps that would facilitate the achievement of such a goal.

A Harm-Based Classification of PREPS 48 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

Tobacco 2003 "Smokeless http://www.tobac Smokeless Recent studies suggest that the use of Snus Not Specific To Any Type of Harm Reporter Alternative," in coreporter.com/b Tobacco is less risky than smoking cigarettes. Tobacco Reporter ackissues/Nov20 (Harm Profile) "Sweden is the only country in the world to 02/story3.asp have reached the World Health Organization’s (WHO) goal of bringing its share of smokers down to less than 20 percent of the population by 2000. Fewer than one in five adults still smoke. So what is the secret? The answer is moist snuff, or as the Swedes call it, "snus," and it is no secret—it’s tradition. Snus has more than 1 million users in Sweden alone, half of which are former smokers." Thun, 2001 "Health impact of http://tc.bmjjourn Modified "Cigarettes with lower machine measured TO THE USER -- Reduced yield products - Michael J. "reduced yield" als.com/cgi/repri Cigarettes "tar" and nicotine yields have been marketed "lower lung cancer risk among smokers who and David cigarettes: a critical nt/10/suppl_1/i4. as "safer" than high tar products over the use 'reduced yield' products, relative to those M. Burns assessment of the pdf last four decades, but there is conflicting that smoke unfiltered, 'higher yield' cigarettes. epidemiological evidence about the impact of these products They do not consistently report lower risk evidence," in on the disease burden caused by smoking. coronary heart disease, total stroke, or Tobacco Control This paper critically examines the chronic obstructive pulmonary disease 2001; 10 (Suppl.1): epidemiological evidence relevant to the (COPD)." (p.i6). i4-i11. health consequences of "reduced yield" cigarettes." U.S. 2000 Reducing Tobacco http://www.cdc.g Nicotine This Chapter reviews NRTs, including TO THE USER -- Nicotine gum - "Common Chapter 4 - Management Surgeon Use. A Report of ov/tobacco/sgr/s Replacement pharmacological interventions (pp.113-24), side effects…are relatively mild and transient, of Nicotine Addiction General the Surgeon gr_2000/chapter Therapy and their relative levels of efficacy. In and many can be resolved by correcting the (section on General 4.pdf general, the chapter concludes that NRTs user's chewing technique." (p. 116). Nicotine Pharmacological are effective aids to smoking cessation. patch - "Most side effects...are relatively mild; interventions, e.g., patch, less than 5% of patients need to discontinue spray, inhaler) p. 113. patch therapy because of side effects." (p.118). Bupropion - "Dry mouth was reported by 10 to 15%...and insomnia was reported by about 30 to 40% of bupropion users." (p.122). Also: clonidine, nortriptyline, and other antidepressants. U.S. 2000 Reducing Tobacco http://www.cdc.g US This Chapter provides an overview of the US Not Specific To Any Type of Harm Chapter 5 - Regulatory Surgeon Use. A Report of ov/tobacco/sgr/s Regulation regulatory regime of Tobacco and Nicotine Efforts. General the Surgeon gr_2000/Chapter products, from advertising and promotion, to General 5.pdf product regulation (pp.178-93). Chapter also discusses the regulation of Nicotine Replacement Products (p.185).

A Harm-Based Classification of PREPS 49 Institute On Governance Table 6: Web Documents

Author Year Title Hyperlink Subject/s Abstract Type/s of Harm Comments

U.S. 1988 The Health http://www.cdc.g Nicotine TO THE USER – Nicotine gum - "An This chapter provides Surgeon Consequences of ov/tobacco/sgr/s Replacement Chapter 7 - Treatment of Tobacco important...issue is whether it is possible to extensive General Smoking: Nicotine gr_1988/1988S Therapy Dependence (section on Nicotine initiate and maintain physical dependence on citations/references of Addiction. A Report GR- Replacement Strategies). This particular nicotine with replacement products alone. studies on the of the Surgeon Chapter%207.pd chapter of the Report reviews treatment Nicotine polacrilex has been used widely with effectiveness of various General. f approaches to tobacco dependence, no reported cases of such development." NRT (i.e., nicotine gum, including NRT (p.470). A short discussion on (p.481). nasal nicotine solutions, dependence on nicotine replacement nicotine patch, and products (p.481), and other pharmacologic nicotine aerosols). approaches. Conclusion: clinical trials of nicotine gum are "modestly encouraging" (p.486) Warner, 2002 "Tobacco Harm http://www.uiowa Tobacco "This paper examines the concept of Not Specific To Any Type of Harm Kenneth E Reduction: .edu/~intl/ACAD/ Harm tobacco harm reduction and describes the Promise and ghsp/fall2002bio Reduction - variety of methods employed in the pursuit of Perils," in Nicotine s/KenWarner_re Modified it. Through an examination of the experience & Tobacco ading.pdf Cigarettes of filters and low tar and nicotine cigarettes, Research, S53- and Novel and an explicit cosideration of today's issues S63 Nicotine and challenges, the paper focuses attention Delivery on the essential dimensions of the Products contemporary harm reduction debate: how science can establish whether novel products or methods will reduce risk to health, and what role for governmental regulation is possible and desirable." Yudkin, P., 2003 "Abstinence from http://bmj.com/c Nicotine The authors carried out an eight-year follow Not Specific To Any Type of Harm K. Hay, S. Smoking Eight gi/reprint/327/74 Replacement up of people who had participated in a Roberts, S. Years After 05/28.pdf Therapy - randomised controlled trial of the nicotine Welch, M. Participation in Patch patch. "Eight years after taking part in a Murphy and Randomized (effectiveness randomised trial of the nicotine patch, just R. Walton Controlled Trial of ) under half of the 9% who had stopped Nicotine Patch," in smoking for a year had relapsed, leaving 5% British Medical of all trial participants continuously abstinent Journal 327(7405): for eight years." A striking finding of the 28-9. study is that participants using placebo patches seemed to do better at quitting than those using active patches.

A Harm-Based Classification of PREPS 50 Institute On Governance Table 7: Library Documents

Author/s Year Title Subject/s Abstract Type/s of Harm

Baron, J.A. 1996 "Beneficial effects of nicotine The beneficial effects of cigarette smoking are briefly TO WOMEN -- Cigarette smoking - "Vomiting of pregnancy…has been and cigarette smoking: the real, considered in this survey. Evidence is growing that noted to be less common in smokers than in non-smokers" (p.59). TO the possible and the spurious," cigarette smoking and nicotine may prevent or USER -- Cigarette smoking - "Endometrial cancer is the only in British Medical Bulletin, Vol ameliorate Parkinson's disease, and could do so in malignancy that has repeatedly been shown to be inversely related to 52, (1): 58-73. Alzheimer's dementia. A variety of mechanisms for cigarette smoking." (p.61). "An inverse association between cigarette potentially beneficial effects of smoking have been smoking and body weight is well established." (p.64), as well as proposed, but three predominate: the 'anti-estrogenic "Parkinson's disease" (p.65) "Alzheimer's dementia" (p.66), and can effect' of smoking; alterations in prostaglandin "ameliorate Tourette's syndrome" (p.66). production; and stimulation of nicotinic cholinergic receptors in the central nervous system. Even established inverse associations cannot be used as a rationale for cigarette smoking. These data can be used, however, to clarify mechanisms of disease, and point to productive treatment or preventive options with more narrowly-acting interventions. Bates, C, 1999 Cigarette Engineering and Modified An ASH report on the additive technology used by Connolly G Nicotine Addiction. A survey of Cigarettes cigarette manufacturers to enhance the appeal and & Jarvis, M. the additive technology used by (Harm Profile) addictive nature of their products. cigarette manufacturers to enhance the appeal and addictive nature of their product. ASH and Imperial Cancer Research Fund, London. Bolinder, G. 1997 "Smokeless Tobacco-A Less Smokeless The risk of adverse health effects is evidently less TO THE USER -- Smokeless tobacco - "It seems beyond doubt that the Harmful Alternative?," in The Tobacco serious in smokeless tobacco users than in smokers. use of chewing tobacco together with different mixtures of flavoring, Tobacco Epidemic Vol. 28 (Harm Profile) alkaline substances, and a variety of natural products, when used in Progress in Respiratory populations with poor mouth hygiene, and inadequate nutritional status, Research: 199-212. is causally related to oral cancer." (p.201). "users exhibited higher mortality ratios than never-users in all age groups indicating that the habit might signify health influences not to be ignored. All tobacco products contain cancerogenetic substances." (p.208) Nicotine - "Nicotine exposure does not seem to contribute to an increased atherosclerotic process in the same way as smoking. There might, however, be a more pronounced tendency to develop hypertension compared to nonusers and smokers." (p.205). "Most studies of cardiovascular effects imply that the continous circulatory stress caused by nicotine is associated with an increase in cardivascular effects, compared with nonusers of tobacco." (pp.208-9). TO THE FETUS -- "In India higher stillbirth rates, lower birth weight, changes in sex ratio and changes in placental morphology have been found among tobacco chewing women."(p.207).

A Harm-Based Classification of PREPS 51 Institute On Governance Table 7: Library Documents

Author/s Year Title Subject/s Abstract Type/s of Harm

Borgerding 1997 "Chemical and Biological One of the Chemical analysis shows marked reductions in a TO THE USER -- Eclipse (TOB-HT) - "Based on 'tar' yield, the TOB-HT MF, Bodnar studies of a new cigarette that first smoke number of biologically active chemicals in Eclipse. cigarette is similar to other cigarettes in the ultra-low 'tar' category. JA, Chung primarily heats tobacco. Part 1. analyses for However, carbon monoxide yields are intermidiate between the observed HL, Chemical composition of Eclipse - yields for 1R5F and 1R4F" (the 2 standard reference cigarettes used in Mangan mainstream smoke," in Food industry study the study) (p.173). "All gross measurement results indicate, therefore, PP, and Chemical Toxicology 36(3): that the chemical composition of TOB-HT smoke particles is simpler than Morrison 169-182. the composition of smoke particles from other cigaretts." (Ibid.). CC, Risner "Concentrations of most target compounds are significantly less in TOB- CH, Rogers HT smoke when compared with reference cigarettes from either the JC, ultra-light 'tar' category or the light 'tar' category." (p.181). Simmons DF, Uhrig MS, Wendelboe FN, Wingate DE, and Winkler LS Breland, 2002 "Evaluating acute effects of Cigarette-like Study evaluates a clinical laboratory model for Alison B., potential reduced-exposure Products assessing whether potential reduced-exposure August R. products for smokers: Clinical (Harm Profile) products (PREPs) do reduce smokers' exposure to Buchhalter, laboratory methodology," lethal constituents of smoke and whether they Sarah E. in Nicotine and Tobacco adequately suppress withdrawal symptoms. Results: Evans, and Research Volume 4, Number 4 Accord was less effective at suppressing withdrawal Thomas Supplement 2/December, 2002: and produced minimal carbon monoxide boost despite Eissenberg 131-40. the fact that when using Accord, smokers took bigger and longer puffs than with conventional cigarettes. Eclipse fully suppressed withdrawal and increased carbon monoxide levels by 30 percent. Accord delivered about one-half and Eclipse about three- fourths the nicotine of the subjects' own cigarette brand. The researchers concluded that neither Accord nor Eclipse is likely to be effective in reducing exposure to the harmful constituents of cigarette smoke. Breland, 2002 "Acute effects of AdvanceTM: a Cigarette-like Investigators found that Advance produced similar TO THE USER -- Advance - "In the current acute study, relative to own Alison B., potential reduced exposure Products - withdrawal suppression and heart rate increase, 11 brand cigaretts, Advance suppressed withdrawal fully, while delivering S. E. product for smokers," in Advance percent less carbon monoxide, and 25 percent more 11% less CO and 25% more nicotine." (p.377). "CO contributes to a Evans, A. Tobacco Control; Vol.11 (Harm Profile) nicotine when compared to the light or ultra-light variety of smoking related disease, so any meaningful reductions should R. December 2002: 376-8. cigarette brands smoked by 20 volunteers. be encouraged; other PREPs completely decrease CO delivery." Buchhalter (p.378). and Thomas Eissenberg

A Harm-Based Classification of PREPS 52 Institute On Governance Table 7: Library Documents

Author/s Year Title Subject/s Abstract Type/s of Harm

Cone EJ, 1989 "Premier 'smokeless cigarettes' Premier - "Our initial examination of the unique design of this TO "DRUG" USER -- Premier - "Our initial examination of the unique Henningfiel can be used to deliver crack," in Cigarette-like device revealed that it could be modified for use as a design of this device revealed that it could be modified for use as a d JE Journal of the American Medical Products delivery system for drugs of abuse, such as crack, a delivery system for drugs of abuse, such as crack, a highly abused form Association 1989; 261(1): 41. (Harm Profile) highly abused form of cocaine." of cocaine." (p.41). "The cylinder has a total capacity for repacking with approximately 200 mg of crack." (Ibid.). Critchley, 2003 "Health effects associated with Smokeless "It is believed that health risks associated with J.A. and B. smokeless tobacco: a Tobacco smokeless tobacco (ST) use are lower than those with Unal systematic review," in Thorax (Harm Profile) cigarette smoking. A systematic review was therefore 58(5): 435-443. carried out to summarise these risks. A narrative review was carried out. Many of the studies lacked sufficient power to estimate precise risks, mainly due to the small number of ST users. Studies were often not designed to investigate ST use, and many also had major methodological limitations including poor control for cigarette smoking and imprecise measurements of exposure." Dickinson, 2003 Upcoming in Proceedings of the Nicotine A by-product of nicotine may help prevent the plaques Tobin and National Academy of Sciences (Harm Profile) linked to Alzheimer's disease from forming. The Kim D. 2003; 10: 1073. substance, nornicotine, is toxic, and could not itself be Janda used as a medication. But scientists believe further research might produce harmless compounds that mimic the action of nornicotine in fighting Alzheimer's. Study claims: "Nicotine and nornicotine treatments are intriguing and potentially valuable treatments for Alzheimer's disease." Fagerström 2002 "Nicotine concentrations with This paper reviews the data on blood nicotine or saliva , Karl Olov concurrent use of cigarettes and cotinine concentrations with concomitant smoking and and John R nicotine replacement: A review," use of nicotine replacement (NR) products. Eleven Hughes in Nicotine & Tobacco Research studies that provided data on blood nicotine Volume 4, Number 4 concentrations, carbon monoxide in exhaled air, and Supplement 2/December, 2002: number of cigarettes smoked were reviewed. Where 73-9. smokers had the intention or received instructions to reduce smoking, a greater reduction in cigarettes smoked and exhaled CO was observed. Despite substantially increased nicotine concentrations (e.g., up to 3 times the approved dose) there were no significant adverse reactions. Concurrent use of NR products and cigarette smoking appears to be safe.

A Harm-Based Classification of PREPS 53 Institute On Governance Table 7: Library Documents

Author/s Year Title Subject/s Abstract Type/s of Harm

Fagerström 2002 "Long-term effects of the "This study investigated the long term use of Eclipse, a , Karl Olov, Eclipse cigarette substitute and cigarette-like device that heats rather than burns John R the nicotine inhaler in smokers tobacco, and the Nicorette oral inhaler, a nicotine Hughes not interested in quitting," in replacement product, in a group of smokers not and Peter Nicotine & Tobacco Research interested in quitting smoking. Results replicate and W. Callas Volume 4, Number 4 extend our prior results; i.e. both Eclipse and inhaler Supplement 2/December, 2002: clearly reduced smoking of traditional cigarettes and 141-5. with no loss of effect over time. For Eclipse this was accompanied by maintenance of nicotine levels but increases in CO whereas for the inhaler this was accompanied by a reduction in CO intake." Fowles, J. 2001 "Novel tobacco products: Health Modified A review of a range of modified cigarette and nicotine risk implications and Cigarettes delivery devices, including Eclipse, Omni, Advance, international concerns." A report (Harm Profile) Accord, nicotine water, bidis and kreteks. Provides to the New Zealand Ministry of crude risk estimates for Eclipse based on published Health. Report FW0175 yields.

Report has been peer reviewed, but not released publicly by the NZ Ministry of Health. Fox, Brion 2002 "Tobacco harm reduction: A call Tobacco The article presents two complementary approaches in Not Specific To Any Type of Harm J., Joanna to address the ethical Harm evaluating ethical issues surrounding THR. First the E. Cohen dilemmas," in Nicotine & Reduction - authors outline three overarching topics in tobacco Tobacco Research Volume 4, Ethics harm reduction that would particularly lend themselves Number 4 Supplement to study: (a) Is the pursuit of tobacco harm reduction 2/December, 2002: 81-7. an ethical goal? (b) What are the ethical considerations of tobacco harm reduction vis-à-vis pharmaceutical companies? and (c) What are the ethical considerations for harm reduction vis-à-vis tobacco companies? The authors then present one possible framework for analyzing the ethical issues that accompany particular tobacco harm reduction strategies. Glover, 2002 "A comparison of a nicotine Nicotine The study assesses the efficacy and safety of a Elbert D. et sublingual tablet and placebo Sublingual nicotine sublingual tablet in smoking cessation. al. for smoking cessation," in Tablet (Harm Adverse events were mild and transient and reflected Nicotine & Tobacco Research Profile) those reported with existing nicotine replacement Volume 4, Number formulations. Authors concluded that the nicotine 2-mg 4/November, 2002: 441-50. sublingual tablet was effective as a smoking cessation aid. Goodin, 1989 No smoking : The ethical issues Ethics Goodin argues that the liberty of smokers can be Not Specific To Any Type of Harm Robert E. justifiably limited for two reasons: to prevent harm to third persons and to prevent harm to smokers themselves under circumstances which make their decision to smoke substantially non-autonomous.

A Harm-Based Classification of PREPS 54 Institute On Governance Table 7: Library Documents

Author/s Year Title Subject/s Abstract Type/s of Harm

Henningfiel 1998 "Tobacco-dependence Nicotine The focus of this article is on medication, including a TO THE USER -- Nicotine patch, gum & nasal spray - users "are d JE, and J. medications: public health and Replacement disussion of tobacco product regulation. The article capable of sustaining tolerance, but generally have few symptoms of Slade regulatory issues," in Food and Therapies - also discusses specific public health consequences of withdrawal after discontinuation, and minimal psychoactive and Drug Law Journal 1998; 53 Regulation current restrictions on medications development and reinforcing effects. Thus with the exception of the nicotine nasal spray, (Suppl): 75-114. marketing, and ways that the public health might be psychoactive effects and abuse liability are minimal." (p.82). Nicotine improved over the long-term and short-term by gum - "Jaw soreness, nausea, hiccups" (Table II). Nicotine patch - changing how medicines for treating tobacco "Skin irritation, nausea, sleep disturbances." (Ibid.). Nasal spray - "Nasal dependence are developed and marketed. Also irritation, throat irritation, watery eyes." (Ibid.). "a somewhat higher abuse provides list of PREPs on pages 88-9 (e.g., CigArrest, liability than that of other nicotine medications, but still substantially lower Waterpic One Step at a Time, Citrol). than that of cigarettes." (p.87). Vapor inhaler - "Cough, mouth or throat irritation." (Ibid.). Buprpion - "Headache, insomnia, seizure, tremor, rash." (Table II). Hoffman 1997 "The Changing Cigarette," in Modified "Epidemiologic surveys have revealed accelerated Not Specific To Any Type of Harm D., Preventive Medicine, 1997, Conventional increases in adenocarcinoma but less rapid increases Djordjevic 26(4): 427-34. Cigarettes in squamous cell carcinoma of the lung among MV., and (Harm Profile) cigarette smokers in recent decades. Changes in the Hoffman I. makeup of cigarettes and corresponding changes in smoke composition along with nicotine-compensating smoking patterns, such as the frequency of puff drawing and depth of inhalation, are suggested to have contributed to the observed epidemiologic profiles of these major histologic types of lung cancers. Higher nitrate content of tobacco blends is shown to be one of the major influences on lower smoke yields of carcinogenic polynuclear aromatic hydrocarbons (PAH) while causing increased yields of carcinogenic, tobacco-specificN-nitrosamines (TSNA)." Hughes, 1999 "Are higher doses of nicotine Nicotine This study determined whether higher dose nicotine John R., replacement more effective for Patches - patches are more efficacious than lower dose patches George R. smoking cessation?" in Nicotine Cessation among heavy smokers. Results show that in heavy Lesmes, & Tobacco Research 1(1): 169- smokers higher doses increase quit rates slightly. Dorothy K. 174. Longer durations of treatment may be necessary to Hatsukami, show greater advantages from higher doses. et al. Hughes, 2003 "A meta-analysis of the efficacy Nicotine A study that combines the results of eight over-the- Not Specific To Any Type of Harm John R., S. of over-the-counter nicotine Replacement counter NRT studies and found that 93% of study Shiffman, replacement," in Tobacco Therapies participants had relapsed to smoking nicotine within P. Callas Control 12(1): 21-27. six-months. "...the average six month quit rate with and J. OTC NRT is modest. The 7% long term quit rate we Zhang report is similar to the prior estimated rate of long term quitting with OTC NRT of 8%. These OTC long term quit rates are lower than those reported in recent meta- analyses of gum, patch or psychosocial therapies when given with more intensive interventions."

A Harm-Based Classification of PREPS 55 Institute On Governance Table 7: Library Documents

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Klesges, 2003 "Use of nicotine replacement Nicotine In a survey of 4000 high school juniors, both smokers TO ADOLESCENTS -- NRT - "Nicotine replacement therapy is used by Lisa M., et therapy in adolescent smokers Replacement and non-smokers reported using nicotine patches and adolescent smokers and nonsmokers, is easily accessible, and is used al. and nonsmokers," in Archives of Therapy gum. 75% of the smokers said they used the products for reasons other than trying to quit smoking. Efforts are needed to Pediatrics and Adolescent for reasons other than to help kick the habit. Among discourage NRT use in nonsmoking youth and to encourage appropriate Medicine 157(6): 517-22. those reasons - teens reported using nicotine patches use of NRT in young smokers to maximize its potential for successful or gum in situations where smoking was not permitted. cessation." 18% reported using nicotine replacement products even though they were never smokers. "Nicotine replacement therapy is used by adolescent smokers and nonsmokers, is easily accessible, and is used for reasons other than trying to quit smoking. Efforts are needed to discourage NRT use in nonsmoking youth and to encourage appropriate use of NRT in young smokers to maximize its potential for successful cessation." Kozlowski, 2003 "First, tell the truth: a dialogue Ethics - The use of smokeless tobacco as a substitute for TO THE USER -- Smokless Tobacco - "The scientific evidence for a Lynn T. on human rights, deception, and Smokless cigarettes raises many scientific and ethical issues. true causal gateway effect is slight. About 3 in 4 of those who use the use of smokeless tobacco Tobacco smokeless cannot be 'gateway users', in that they either never go as a substitute for cigarettes," in beyond smokeless to cigarettes or they started using cigarettes before Tobacco Control 2003; 12(1): they started using smokeless." (p.35). 34-6. Kunze, M. 1997 "Harm Reduction: The Possible Nicotine This article reviews a variety of pharmacological and TO THE USER -- Nicotine gum - "There was no increase in the Role of Nicotine Replacement," Replacement psychological smoking cessation strategies. incidence of cardiovascular events either in those who has achieved in The Tobacco Epidemic Vol. Therapy abstinence but continued to use the gum or, more importantly, those who 28 Progress in Respiratory continued to use the gum and continued to smoke. On the basis of these Research: 190-8. results, the investigators concluded that long-term use of nicotine gum appears to be safe." (p.193). Nicotine patch - "a short-term (10-week) study involving 584 smokers with active cardiac disease found that transdermal nicotine did not increase the incidence of cardiovascular events compared to placebo." (Ibid.). TO THE FETUS -- Nicotine gum & patch - "postmarketing surveillance has shown no increase in perinatal events with either the gum or the patch." (p.194). Malson, 2002 "Nicotine delivery from smoking Additive-free The study was conducted to determine whether Jennifer L., bidis and an additive-free cigarette - smoking bidis, an additive-free cigarette, and Eun M. cigarette," in Nicotine & Bidis (harm conventional cigarettes caused similar biochemical, Lee, Eric T. Tobacco Research Volume 4, profile) physiological and subjective effects. Overall, the Moolchan, Number 4/November, 2002: results indicate that bidis and the additive-free and 485-90. cigarette delivered nicotine, CO and (presumably) Wallace B. other toxic components of tobacco smoke in equal or Pickworth greater amounts than conventional cigarettes. These results do not support an emerging belief that bidi cigarettes are safer than conventional brands. McNeill, 2001 Regulation of Nicotine Nicotine TO THE USER -- "Nicotine is addictive, but it is the tobacco smoke, not Ann and Replacement Therapies: An Replacement the nicotine, that causes most of the harm" - NRT - "NRT products are Anne Expert Consensus. Document Therapies - much safer than cigarettes, which are exceedingly 'dirty' delivery Hendrie prepared for the World Health Regulation systems for nicotine…the evidence clearly indicates that the products Organization. are safe." (p.38).

A Harm-Based Classification of PREPS 56 Institute On Governance Table 7: Library Documents

Author/s Year Title Subject/s Abstract Type/s of Harm

Monroe, 1995 Nicotine Nicotine A critical presentation that reflects the contemporary Judy view of nicotine. After a brief history, Monroe describes the tobacco industry, physical effects of tobacco and nicotine, and changing public attitudes. Nilsson, 1998 "A Qualitative and Quantitative Smokeless "The presence of highly carcinogenic tobacco-specific Robert Risk Assessment of Snuff Tobacco nitrosamines (TSNA) in snuff has been a matter of Dipping," in Regulatory (Harm Profile) serious concern. However, the levels of TSNA in such Toxicology and Pharmacology products may differ by orders of magnitude depending 28(1): 1-16. on origin and manner of processing, and the mere presence of such agents at low levels does hardly constitute a meaningful prerequisite for classifying all types of snuff as human carcinogens...In spite of the fact that approximately 20% of all grown-up Swedish males use moist snuff, it has not been possible to detect any significant increase in the incidence of cancer of the oral cavity or pharynx––the prevalence of which by international standards remains low in this country. Further, there is insufficient evidence for a causal link between the use of Swedish snuff and increased risk for cardiovascular disease." Pauly JL, 1998 "Glass fiber contamination of Modified The article reports the results of studies documenting TO THE USER -- Eclipse - "Contamination of Eclipse filters with glass Lee HJ, cigarette filters: an additional Cigarettes the contamination of the cigarette-like smoking product fibers and glass dust poses a potential and unnecessary health hazard Hurley EL, health risk to the smoker?" in (Harm Profile) labeled Eclipse with glass fibers, fragments, and to uninformed consumers." (p.967). "The association of fibrous glass and Cummings Cancer Epidemiology, - Eclipse - particles. In a study of Eclipse that had not been cancer has been addressed in a document authored by investigators KM, et al. Biomarkers & Prevention 1998; Cigarette removed from carefully opened packs, the authors from the Environmental Carginogenesis Program of the National 7(11): 967-79. Filters observed that > or = 95% of the filters were Institutes od Environmenatl Health Sciences..." (p.997). "glass fibres contaminated with glass fibers. Conclusion: may be as potent or even more potent than asbestos" (Ibid.). "Glass Contamination of Eclipse filters with glass fibers and fibers and microparticulates...may induce inflammation, fibrosis, glass dust poses a potential and unnecessary health hyperplasia, or other nonmalignant pulmonary diseases." (p.978). hazard to uninformed consumers. Conventional cigarette filters - "little difference in mortality has been found for lifelong filter versus nonfilter smokers and for persistent smokers who switch from nonfilter to filter cigarettes." (Ibid.). Pickworth 1999 "Pharmacodynamic effects of Denicotinized Data suggest that process of smoking and components W, Fant new de-nicotinized cigarettes" in cigarettes of tobacco smoke other than nicotine mediate some RV, Nelson Nicotine & Tobacco Research effects of cigarette smoking RA, Rohrer Vol.1(4): 357-364. MS, and Henningfiel d JE Pierce, 2002 "Harm reduction or harm Harm N/A John P. maintenance?"in Nicotine & Reduction Tobacco Research. Volume 4 (4) Supplement 2 December 2002: 53-4.

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Pierce, 2002 "Impact of Over-the Counter Nicotine Since becoming available over the counter, NRT Not Specific To Any Type of Harm John P., sales on effectiveness of Replacement appears no longer effective in increasing long-term and pharmaceutical aids for Therapy successful cessation in California smokers. Elizabeth smoking cessation," in Journal A. Gilpin of the American Medical Association Vol.288 (10); 1260- 64. Pommerlea 1997 "Nicotine Dependence," in Nicotine This article provides a brief overview of what is known Not Specific To Any Type of Harm u, O.F. Bolliger CT and Fagerstrom Dependence about nicotine dependence by examining different (eds) The Tobacco Epidemic. aspects of nicotine use as co-factors for smoking, the Vol. 28 Progress in Respiratory nicotine addiction cycle, diagnostic nosology, individual Research: 122-31. differences in vulnerability, and sensitivity to nicotine and the nicotine receptor. SACTob 2002 Statement of Principles Guiding Modified This article looks at 3 general categories of products (Scientific the Evaluation of New or Tobacco for which harm reduction claims are made by Advisory Modified Tobacco Products. Products - manufacturers of these products. They are: 1) Committee Regulation Products that resemble conventional cigarettes but on Tobacco which claim to reduce toxicity or addiction potential by Product altering the tobacco used, or by adding new Regulation) substances. 2) Products that deliver nicotine by WHO heating (rather than burning) tobacco with associated claims of reduced carcinogens. 3) Oral tobacco products. Article also reviews existing scientific knowledge of harm caused by tobacco products (including modified and novel products). Shiffman, 2002 "Efficacy of over-the-counter Nicotine The study aims to assess the efficacy of the nicotine Saul, Jane nicotine patch," in Nicotine & Patch (Harm patch for smoking cessation, under simulated Gorsline, Tobacco Research Volume 4, Profile) conditions of over-the-counter sale, absent any direct and Number 4/November, 2002: instruction or behavioral treatment. Reported adverse Charles W. 477-83. events were mild and consistent with prior Gorodetzky observations of nicotine patch use. The nicotine patch was safe and effective for smoking cessation at least during 10 weeks of treatment under open-sale conditions, without face-to-face instruction or counseling.

A Harm-Based Classification of PREPS 58 Institute On Governance Table 7: Library Documents

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Shiffman, 2002 "Tobacco harm reduction: Tobacco "To facilitate clear discussion and analysis, and to TO THE USER -- Bupropion - "safe and effective for smoking cessation. Saul, Joe Conceptual structure and Harm avoid confusion among approaches, we catalog 19 It carries a small risk of seizures (about 0.1%), but the risk is G. Gitchell, nomenclature for analysis and Reduction approaches to harm reduction, distinguishing and concentrated among smokers who have some pre-existing risk." (p.120). Kenneth E. research," in Nicotine & discussing them on 11 dimensions, including their Eclipse - "smokers of Eclipse actually get increased exposure to carbon Warner, Tobacco Research Volume: 4 objectives, mechanisms, toxicology, expected monoxide compared with levels received from their usual cigarettes." John Slade, Number: 4 Supplement: 2 population risks, and consumer appeal. Because there (p.121). Omni - "introduces palladium" as new harm and toxicant Jack E. p.113-29. have also been so many suggested applications of (p.122). Quest - "little or no nicotine...Other things being equal, Henningfiel medicinal nicotine to smoking intervention, we cigarettes without nicotine would be just as toxic as current cigarettes" d and John separately catalog and analyze nine applications, (p.122). Smokeless tobacco - "smokeless use carries significant risk of M. Pinney some of which constitute new approaches to harm oral cancers and other morbidity and mortality." (p.122). Medicinal reduction. The suggested framework is intended to nicotine (gum, patch, etc.) - "is regarded safe, perhaps with the clarify the debate, provide for common exception of use in pregnancy." (p.123). nomenclature, and facilitate analysis of diverse approaches to tobacco harm reduction." Slade, John 2000 "Innovative nicotine delivery Nicotine devices from tobacco delivery companies," in Ferrence R, devices Slade J, Pope M, Room R (eds). Nicotine and Public Health. Washington: American Public Health Association. Slade, John 1993 "Nicotine delivery devices," in Nicotine A description of nicotine delivery systems. Not Specific To Any Type of Harm Nicotine Addiction: Principles delivery and Management, Orleans, devices C.T., and J. Slade, eds. 1993. pp.3-23. Slade, J. 1998 "Tobacco product regulation: Regulation N/A and Context and Issues," in Food Henningfiel and Drug Law Journal, 1998, 53 d JE. (supp.): 44-76. Smith CJ, 2000 "The relative toxicity of Ranking toxic Provides a rank order of toxic compounds in CSC Not Specific To Any Type of Harm and compounds in mainstream constituents using octanol-water partition coefficients, International Hansch C cigarette smoke condensate," in Agency for Cancer Research (IARC) classifications, Food and Chemical Toxicology and data from the Registry of Toxic Effects of 38(7): 637-646. Chemical Substances (RTECS). Found varying levels of chemicals across various brands.

A Harm-Based Classification of PREPS 59 Institute On Governance Table 7: Library Documents

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Sonderskov 1997 "Nicotine patches in smoking Nicotine "The authors examined the effect of 24-hour nicotine J, Olsen J, cessation: a randomized trial Patch (harm patches in smoking cessation among over-the-counter Sabroe S, among over-the-counter profile) - customers in Denmark. More side effects were seen Meillier L, customers in Denmark," in Effectiveness in the nicotine group than in the placebo group, Overvad K. American Journal of but none of the reported side effects were serious. Epidemiology 145(4): 309-18. It appears that regular healthy smokers who were customers of nonprescribed nicotine patches and who received 21-mg/day nicotine patches benefited from the active treatment (44.1% stopped smoking after 4 weeks), but almost as many stopped smoking in the placebo group (37.3% after 4 weeks). No significant differences in smoking cessation rates were seen among smokers who started with the low-dose nicotine or placebo patches." Steckley, 2002 "Eclipse can deliver crack Eclipse (Harm N/A Stacey L. et cocaine," in Nicotine & Tobacco Profile) al. Research Volume 4, Number 4 Supplement 2/December, 2002: 189-90. Stratton, K., 2001 Clearing the Smoke: Assessing P. Shetty, the Science Base for Tobacco R. Wallace Harm Reduction and S. Bondurant eds. Sullum, 1998 For your own good: the anti- Ethics "In this controversial book, Jacob Sullum demolishes Jacob smoking crusade and the the leading claims of the antismoking movement; their tyranny of public health assertions have been advanced, he says, because the movement's principals would like the government to take control of the tobacco industry." Sumner, 2003 "Estimating the health Nicotine "Clean nicotine inhalers might improve public health as TO THE USER & TO THE FETUS-- Nicotine inhalers - "At the very Walton II consequences of replacing Inhalers - much as any feasible tobacco control effort. Although least, consumers should know of nicotine's potential immunosuppressive cigarettes with nicotine Regulation the relevant risk estimates are somewhat uncertain, effects, the possibility that nicotine is a gateway to drug and alcohol inhalers," in Tobacco Control partial nicotine deregulation deserves consideration as abuse, and the high probability that nicotine permanently affects fetal 2003; 12(2): 124-132. part of a broad tobacco control policy." brain development." (p.129). Sutherland 1992 "Nasal nicotine spray: A rapid Nasal Plasma nicotine concentrations following TO THE USER -- Nasal nicotine spray (NNS) & aerosol (NNA) - Eight G., M.A.H. nicotine delivery," in Nicotine administration by two types of nasal nicotine spray out of ten subjects"experienced a subjective feeling of lightheadedness" Russell, J. Psychopharmacology. Volume Spray were compared in ten subjects. Absorption was (p.514). "Subjects…soon adapted to initial problems with local irritancy Stapleton, 108 (1992) Number 4:512-18. particularly rapid during the first 2.5 min. Eight subjects and both products appeared sufficiently acceptable for everyday clinical C. Special Issue on Nicotine. reported subjective feelings of light-headedness or use." (p.517). "The lack of any tendency to escalate to excessive use Feyeraben slight dizziness, which are not typical after slower was reassuring." (Ibid.). d, O. Ferno absorption from nicotine gum or skin patches. Sweanor, 1997 "Regulation of Tobacco and Regulation The regulatory systems that have evolved for tobacco Not Specific To Any Type of Harm David Nicotine," in Bolliger CT and are very different from those for alternative nicotine Fagerstrom (eds) The Tobacco delivery systems. The net effect…has been to give Epidemic. Vol. 28 Progress in tremendous marketing advantages to the most Respiratory Research: 247-58. hazardous methods of supplying nicotine.

A Harm-Based Classification of PREPS 60 Institute On Governance Table 7: Library Documents

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Tonnesen, 1997 "Nicotine Replacement and Nicotine This article focuses on the pharmacological treatment TO THE USER -- Nicotine gum - "Side effects of the gum consist mainly P. Other Drugs in Smoking Replacement of smoking cessation. of mild, transient local symptoms in the mouth, throat and stomach due Cessation," in Bolliger CT and Therapy to swallowed nicotine (I.e., nausea, vomiting, indigestion and Fagerstrom (eds) The Tobacco (harm profile) hiccups)…The constant chewing might produce side effects such as oral Epidemic. Vol. 28 Progress in or throat soreness, aches in muscles of mastication, hypertrophy of the Respiratory Research: 178-89. masseter muscles and loss of dental fillings." (p.181). Nicotine patch - "Side effects are mainly mild local skin irritation, occuring in 10-20% of subjects. In only 1.5-2% of subjects, the patch had to be terminated due to more persistent and severe skin irritation." (p.183). Nicotine inhaler - "Reported side effects included mouth/throat irritation and coughing." (Ibid.). Nicotine nasal spray - "induces localized side effects such as sneezing, nasal secretion and irritation, and congestion, watery eyes and coughing. Up to 5% of the subjects rate these side effects as unacceptable" (p.184). Westman, 2001 "Oral nicotine solution for Oral Nicotine This study was conducted to determine the preliminary Eric C., smoking cessation: a pilot Solution tolerability of an oral nicotine solution with minimal Keith F. tolerability study," in Nicotine & behavioral intervention for smoking cessation. It was Tomlin, Tobacco Research Volume 3 concluded that an oral nicotine solution was tolerable Christine E. (4) November, 2001: 391-96. and provided nicotine replacement at levels that may Perkins, prove useful for smoking cessation. Further research Jed E. to clarify appropriate dosages and optimal beverages Rose for mixture, and controlled trials to assess safety and efficacy, appear in order. Waller, 1996 "Product Modification," in British Modified "For more than 20 years there has been a coherent TO THE USER -- Modified cigarettes (Low Tar) - "We have R.E. and Medical Bulletin Vol.52 (1996) Cigarettes programme of product modification in the UK, involving argued…the role (of low tar cigarettes) in reducing lung cancer mortality, P. Froggatt Number 1: 193-205 (Harm Profile) the introduction of low tar brands of cigarettes and the especially in youger age groups, has been established. This is now gradual reduction in average tar yields over the whole supported by national data." (p.200). range of manufactured cigarettes. To some extent potential benefits to established smokers have been offset by their tendency to 'compensate' for reduced nicotine yields. Investigating such aspects has formed one part of a wide-ranging research programme to monitor effects of modified products on health. Collectively the studies show benefits in terms of smoke intake and health outcome related to reduced tar cigarettes, but the success achieved in reducing average tar yields and narrowing the range has limited opportunities to detect differential effects."

A Harm-Based Classification of PREPS 61 Institute On Governance Table 7: Library Documents

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Warner, K, 1997 "The Emerging Market for Long- Nicotine "Increasingly, consumers will seek to satisfy nicotine TO THE USER -- Eclipse - Nicotine is delivered at about the same rate J. Slade term Nicotine maintenance," in Replacement addiction through the use of novel nicotine-delivery and amount as a cigarette having a Federal Trade Commission-rated and D.T. Journal of the American Medical Therapy - products. In the vanguard are tobacco industry devices yield of 0.9 mg. Carbon monoxide yield is moderately higher than that Sweanor Association 278(13): 1087- Eclipse that heat tobacco derivatives rather than burn tobacco, delivered by such a cigarette. Carcinogens are much lower than in most 1092. and pharmaceutical industry nicotine-replacement conventional cigarettes. products, with nicotine gum and the patch now available over the counter. Ostensibly, these 2 industries have diametrically opposed objectives, the tobacco industry striving to sustain nicotine addictions, the pharmaceutical industry to end them. However, a series of technological, economic, political, regulatory, and social developments augurs a strange-bedfellows competition in which these industries will vie for shares of a new multibillion dollar long-term nicotine- maintenance market. Regulatory options range from encouraging competition to banning all nicotine- delivery devices. A more realistic approach discourages use of the most dangerous products, while making less hazardous products readily available to adults. " Wiebel, F.J. 1997 "Health Effects of Passive Cigarettes - This paper discusses fndings on the health effects of TO THE BYSTANDER -- Cigarette smoke - "Children of parents who Smoking," in Bolliger CT and Passive passive smoking (defined as breathing in airborne smoke have an increased frequency of respiratory and middle ear Fagerstrom (eds) The Tobacco Smoking tobacco smoke, or second-hand smoking). infections and are at risk of impaired lung function…passive smoking Epidemic. Vol. 28 Progress in (Harm Profile) also affects the respiratory health of adult nonsmokers." (p.118). Respiratory Research: 107-21.

A Harm-Based Classification of PREPS 62 Institute On Governance