11 July, 2001
Another mirror shattered?  Tobacco industry involvement suspected in a book which claims that nicotine is not addictive

There is a common belief that untoward happenings come along three at a time.  If two mirrors smash to the floor, it will not be long before a third splinters at our feet, or so the folk wisdom goes.  Scientific books should be the undistorting mirrors of scientific truth or they have no worth.  Addiction is now up to two with the count of books published recently in its field of interest which have failed to declare major conflict of interest.  Let's hope that the run stops at two, but that is probably optimistic.  This editorial is signed conjointly by Addiction's senior editorial staff but GE (Griffith Edwards) took the lead in making initial enquiries on the facts.

The earlier case involved the decision of ILSI Europe (International Life Sciences Institute, Europe) not to declare the fact that its publication Alcohol and Health (Macdonald, 2000) had received support from the drinks industry.  The questions we asked ILSI have still not been fully answered, but that organisation was willing to put the alcohol industry in a position potentially to influence the selection of contributing authors and the refereeing process (Edwards and Savva, 2001).

And now comes a second case relating to failure of those concerned in a book's publication to declare conflict of interest.  This time we are into tobacco.  Dr Hanan Frenk and Dr Reuven Dar from Tel Aviv University have brought out a jointly authored book entitled A Critique of Nicotine Addiction (Frenk and Dar, 2000).  We will not deal with the substance of the book which, the authors tell us, "will serve to 'decanonise' and 'disenshrine' the nicotine addiction hypothesis".  We will keep strictly to the conflict of interest question.

A foreword by Dr Michael Myslobodsky who is a member of the editorial board of the series in which this book finds a place tells us that "the authors marshaled convincing evidence that nicotine is not addictive", but Dr Myslobodsky gives no indication as to whether there had been external sources of support for the work contained in this book.  There then comes an Acknowledgements which expresses thanks to friends, colleagues and spouses, but makes no mention of the authors having been paid by anyone for what they had written.

So what would the man on the Clapham omnibus (Addiction's favourite benchmark person) have at that juncture been likely to believe about the provenance of the book?  Most people would assume that failure to mention conflict of interest meant that no such conflict existed, for those are the rules of the game - the rules by which we all trust our colleagues to play. Conflict of interest is not in itself wrongdoing but it must be declared. We would therefore be likely to assume that this book was a product of the disinterested labour of scientists who had not been within a thousand miles of the tobacco industry.

However, just to make assurance doubly sure GE emailed Dr Frenk on 23 April 2001 to say:-
"I am contacting you in my capacity as Editor-in-Chief of the journal ADDICTION.  Could you please tell me whether the recent book authored by yourself and Dr Reuven Dar was supported by the tobacco industry?"

To that letter we received on 24 April 2001 a lengthy reply, which with Dr Frenk's permission is reproduced below in full:-

"To answer your question directly: No, the book was not supported by the tobacco industry, or anybody else for that matter.  However, since you do not specify the reasons for your question, I assume (please correct me if I am wrong) that you see the answer as relevant to a decision on a potential review of our book for the readers of Addiction.  I further assume you do not only want to know whether the book was funded by the tobacco industry, but whether there also could be a possible conflict of interest resulting from funding of other activities.

As you will see below, I have no intention of evading your question, or my extended version of it.  At the same time, as I have encountered this question several times recently, I must add that I do not believe that the answer is relevant for scientists who read our book.  After all, we did not produce the data for our book.  The outcome of experiments is sometimes affected by the expectations of the experimenter, and these expectations may possibly be affected by a conflict of interests, resulting in fraudulent reports.  Neither my co-author nor myself, however, have ever conducted an experiment on smoking or nicotine.  We only reproduce the data of others and any errors in our reproduction (and there may well be some) is verifiable. Our arguments may be new (at least I have not encountered many of them in the nicotine literature), but they are transparent to every professional.  For example, laymen may not understand why Corrigall and Coen's 1989 experiment (and all but one of the subsequent replications) needed a saline control group to determine what proportion of lever presses could be attributed to nicotine's reinforcing effects, and what proportion was the result of a hungry animal trained to press that lever for food.  I believe, however, that every professional is capable of judging whether this statement is logical and methodologically sound and, consequently, of deciding whether this omission fatally flaws this paradigm.

I therefore believe that if you are considering reviewing this book for the readers of Addiction, this decision should be based solely on the merit of the arguments presented in the book.  If our book's standing will be either enhanced or diminished by presumptions concerning our motives for writing it, I think this would be both unfortunate and unfair.  I believe that the book (or any book) should be given a chance to be evaluated on its merit, rather than shrugged off as a tobacco industry supported propaganda. Moreover, I dare say that even if our book were tobacco industry propaganda (it is not), exposing it as by pointing to factual falsifications would be a better alternative than dismissing it.

Now, to answer the broader version of your question: Several years ago we were approached by a law firm and consequently were paid for our time reading and evaluating some of the literature summarized in the book. Although the law firm refused to reveal its client's identity, it seems obvious that that client is from the tobacco industry.  This in your eyes may be a possible conflict of interest.  It is therefore important to stress that this law firm was strictly opposed to our publishing the book, and in fact warned that its publication might end our engagement as experts.  We surmise that this reaction was for two reasons: First, the material in the book would pre-expose antagonists in law suits to arguments the law firm might use.  Second, our critique might compel researchers to do a better job in attempting to establish the role of nicotine in smoking.  We decided to publish our book for similar reasons.

We believe that our engagement as experts has had no bearing on the conclusions we reach in our book for the following reasons:
1. We were paid for our time, not for our opinions.  In fact, reading the original research literature changed opinions that we held for over 20 years, which were based on the reviews and books we had read before.  The "credibility gap" between the original research reports and the reviews based upon them (including the 1988 SG Report) was a major impetus for writing the book.
2. As stated before, neither of us has ever published empirical research on nicotine (the only references to our own empirical work in the book refer to opiates and OCD).  Hence, we can state unequivocally that the data on which the book is based were not biased by any conflict of interests from our side.
3. Any bias in our interpretation of the research is open to all to scrutinize and verify, especially to a reviewer of our book.  We welcome the most critical review of any aspect of our book.
4. We sought to share our views with the professionals in the area and have our arguments tested by them - logically, factually, and  if possible, empirically.  Had we believed that our arguments were biased or false, or wished to disseminate propaganda for tobacco companies, we would not have written a scientific book which would be read by experts, but rather a "popular science book" for a more general and less critical public.

We shall be happy to have you publish our letter, or any part of it, together with a review of our book, should you decide to publish one."

We concluded from this answer that (1) Dr Frenk and Dr Dar had not declared, when the book was published, what, to us, appeared a highly important aspect of the book's genesis; and (2) Dr Frenk's message questioned what many would consider a basic ethical expectation of modern scientific publishing.

GE decided that before forming a further view we needed the fuller facts and the authors should be given a chance to establish their transparency.  With Dr Frenk assuming that there was tobacco industry involvement GE felt that everyone - authors, publishers, readers, this journal, the man and woman on the Clapham omnibus, the totality of the science and policy community - would wish to see openness established here as the order of the day.  What's wrong with openness?

In the light of Dr Frenk's stated wish for openness (see his first paragraph) we responded by asking a set of questions which we hoped could establish the facts.   To that end, GE  emailed Dr Frenk as follows on 30 April 2001:-

"Thank you for your helpful reply to my enquiry.  I'm writing to you in friendship as editor of a journal which is interested in the ethics of scientific publishing and which tries to raise awareness of these issues in the scientific community - for all of us (including myself) that is a learning experience.  Conflict of interest is not in itself wrongdoing, but I believe that it is in the public interest that such conflict should always be declared.  In this instance you tell me that the review process on which your book was founded was probably supported by the tobacco industry.  In saying that this, in my view, may constitute a conflict of interest I'm making no criticism of your personal integrity.  But from that base I would like to ask some further questions towards drafting an editorial on this topic.

1. Have you or your colleague ever previously accepted tobacco industry support in terms of grants, fees, travel support or hospitality?

2. Have you any insight into why the industry should have identified the two of you as people appropriate to undertake this work?  Was the approach out of the blue, or were there earlier contacts or an earlier relationship?

3. In retrospect, do you think it is wise for scientists to accept a commission from a lawyer without the identity of the client being declared?

4. Was the scope, intention and desired outcome of the review exercise discussed or agreed with the lawyer, or the use to which it would be put?  Is there a contract document which could be made public?

5. Was any secrecy or confidentiality clause agreed?

6. What overall remuneration was offered?  People are understandably shy about their private earnings, but the level of fee can indicate the importance of a project to the client.

7. Did the contract require your report to go out to peer review determined by your sponsor?  If so, can you provide copies of reports received?

8. Did the agreement involve an academic figure or academic steering group in the setting up or monitoring the project?

9. Did you declare the background financing to your publisher?

10. You state that the law firm was strictly opposed to the book's publication.  Is that opposition recorded in writing and were grounds given?

11. Does your host organisation have a policy on acceptance of tobacco industry funding?  Was your acceptance of this contract declared to your host organisation?

If you and your colleague can help in this way, when I have an editorial in draft form I will show it to you so you can check it for factual accuracy.  If you wish to publish a reply to the editorial in ADDICTION'S letter column I would give you opportunity so to do in the same issue as carries the editorial."

That was a long list of queries, but given the public interest importance of matters relating to scientific integrity, GE thought it necessary to put these purposely searching questions, so as to get everything relevant fully out into the daylight.  Following that message, GE had further exchanges with Dr Frenk in which he sought to defend his position but did not answer any of the questions put to him.  For economy of space, we will not reproduce these further exchanges in full, but this passage seems to reflect his core argument:-

"Thank you for your reply and for explaining the motives for your question. I understand from your letter that you intend to write an editorial on the issue of conflict of interests (not on our book), using our book (or rather, its authors) as an example, test-case, or target.  You will not be surprised that we regret your decision.  We did not write the book for this purpose. We intended it to be read and judged on the basis of its arguments by the scientists who work in this area.  This, in our opinion, is the only scientific and ethical way of treating any scientific book, no matter who wrote it, no matter on what issue, and no matter the presumed motivation of the authors."

Dr Dar has confirmed that Dr Frenk's position entirely reflects his own.

Three ways to smash a mirror

We take it as a done deal that declaration of potential or actual conflict of interest is a gold standard in scientific publishing.  We regard any attempt to detract from that position to be profoundly damaging to the integrity of science, and we believe indefensible.  Dr Frenk in our view seeks to defend the indefensible essentially through three arguments and let's look at each of them briefly in turn.

A scientific review is incorruptible.  Dr Frenk seeks to argue that his review of the nicotine literature was ethically risk-free - "After all, we did not produce the data for our book … we reproduce the data of others … our arguments are transparent to every professional."  We consider that Dr Frenk's argument is flawed, as it is vulnerable to the risk that an author's favoured viewpoint may gain credence by setting impossibly high standards of proof for hypotheses that an author wishes to reject.  Unless a conflict declaration has been transparently disclosed, the reader could be misled.  We do not consider that Dr Frenk has a good argument for exempting scientific reviews from the general expectation on declaration of conflict.

Just take the work (research or review) and don't ask about the genesis.  This is the position which Dr Frenk unequivocally favours.  "We intend it to be read and judged on the basis of its arguments … This, in our opinion, is the only scienfitic and ethical way of treating any scientific book."  The fact that conflict or potential conflict is openly declared does not of course at all prevent discussion of a book "on the basis of its arguments" but merely provides the reader with background information which he or she may want to take into account when evaluating the arguments.  To accept Dr Frenk's argument would be to accept absolute retreat from the ethical gold standard - for his book and every other book written and yet to be written.

Trust the evident personal integrity of the authors.  At certain points, Dr Frenk seeks to get away from the abstract arguments and advance evidence for his own integrity.  That is really past the point - it is irrelevant to the large argument that he has no experience in nicotine research or that he wrote a scientific rather than a popular text.  That trivialises the important general issue and to chase after those kinds of personalised attempts at defence would be invidious.  No author should claim to be personally so exceptional as to be excused declarations expected of their peers.

Why worry about declaration of interest?

Science does well to worry about conflict, whatever the field.  Authors when they make their declaration should remember that the expectation is to declare potential as well as actual conflict.  Far better than themselves acting as judge with a high ceiling on what counts as conflict, they should be willing to err on the side of openness and leave it to readers to judge whether potential bias has shaded over to the actual.

If openness on conflict is generally important to science, the importance is raised by several orders of magnitude in relation to tobacco research.  The tobacco industry, like many other corporate entities, has in recent years made a concerted effort to use public relations techniques to protect itself from the negative repercussions resulting from the adverse health effects of its products.  There is clear evidence that these "issues management" activities have included scientists as a target group to be courted, neutralized and engaged in their public relations campaigns, which consist of sponsorship of edited volumes, travel grants, consulting contracts and research support.  As suggested by the case in point, industry representatives stand to gain tremendous value from a small investment at the right time.  By using their funding largesse to set the science and policy agenda, they are able to promote marginal findings and unorthodox ideas that would otherwise receive little serious scientific attention. (Crampton and Stauber, 2001).  Once the findings are given credence by unquestioning or busy academics (who would be highly unlikely to undertake these tasks on their own time and resources), they are promoted by the industry's public relations engine, which includes free distribution of hardcover books, letters to the editors of newspapers and medical journals, paid media advertisements and other promotional activities (often promoted by "third party" organizations funded by the industry), all designed to raise questions about the motives and validity of the legitimate scientific process.  It is the corruption of the scientific process that is the most damaging result of issues management.   Instead of allowing policymakers and the public digest the scientific evidence for themselves, the industry agenda and public relations techniques are used to manipulate public opinion through the controlled presentation of scientific findings and expert opinion.

Dr Frenk speculates as to why his mysterious sponsor should have been opposed to publication of his and Dr Dar's commissioned output in book form.

Could it be that the tobacco industry, having recently admitted in sworn testimony that nicotine is addictive, do not now want to draw attention through publication of this book that they have been paying scientists who have reported to the contrary?  It is of concern when scientists agree to enter the shadowy realms of sponsorship with lawyers acting for unidentified clients and fail publicly to admit the connection in the published work, in that science and scientists are then dragged willy-nilly into a spooky world of conspiracy.  That is a further reason why declaration of interest so greatly matters.

Addiction's position

This journal sees itself as having a modest continuing role in raising the consciousness of addiction science and we have attempted to do so in relation to a range of ethical questions (Babor, T.F., Edwards, G. and Stockwell, T., 1996; McCreanor, T., Casswell, S. and Hill, L. (2000).  Our aim is to clarify issues, stimulate debate, get scientific ethics on the agenda, and help the field to define its remedies.  At the end of the day, only the field itself can set the rules and expectations for its science, and the trustful consensus by which we will live, work, and publish our work.

Here is the core question which we see the present case as pointing up for our readers' consideration:-

Is Addiction right in believing that the ethics of academic publishing put upon authors and publishers an absolute and inalienable responsibility to declare potential or actual conflict of interest?  Do we agree that the done deal must not be trimmed, obfuscated or bent in any circumstances, regardless of the arguments advanced?

Fortunately, progress has been made toward near universal acceptance of this principle by journal editors, learned societies and funding agencies.  It is book publishers who appear to be out of step.  Publishers of scientific texts should ask for conflict of interest statements from authors and editors of their books as standard practice, with public disclosure.  Ahead of such needed action, Addiction will institute a scheme by which authors or editors of any book received for review will be asked to sign an ethical statement before the review process proceeds. Let's see book publishers catch up with the times, sign up to the same deal as the rest of us, and avert a third mirror being splintered.
 

Griffith Edwards, editor-in-chief, Addiction
Thomas F Babor, Addiction regional editor for the Americas
Wayne Hall, Addiction regional editor for Australasia
Robert West, Addiction deputy editor and regional editor for Europe, Africa and Asia
 

Conflict of interest

Griffith Edwards received a grant from the Health Promotion Research Trust (a tobacco industry funded organisation) which led to a publication on alcohol dependence (Edwards et al, 1992).  In his previous role as director of the Addiction Research Unit he for a time supported a research programme on nicotine dependence led by M.A.H. Russell.  He has co-edited books on nicotine dependence (Edwards et al, 1976, Edwards et al, 1993).  Robert West has received research funds, travel funds and consultancy fees from pharmaceutical companies which manufacture nicotine replacement products and other treatments for nicotine dependence.  Thomas Babor and Wayne Hall have no conflicts to declare.  Jerome Jaffe, Addiction's deputy regional editor for the Americas, has given evidence in a US court on the dependence potential of nicotine, and for the last four years has been a consultant to Star Scientific (a firm related to Star Tobacco) on development of nitrosamine-free tobacco.  Several of Addiction's assistant editors are tobacco researchers: we have not consulted them over the present editorial.

References

Babor, T.F., Edwards, G. and Stockwell, T. (1996) Science and the drinks industry.  Addiction, 91, 5-9
Edwards, G. and Savva, S. (2001)  ILSI Europe, the drinks industry, and a conflict of interest undeclared.  Addiction 96, 197-202.
Frenk, H. and Dar, R.  (2000) A Critique of Nicotine Addiction.  Boston, Dordrecht, London, Kluwer Academic Publishers.
MacDonald, I. ed. (2000) Health Issues related to Alcohol Consumption.  2nd edition.  Oxford, Blackwell Science.
McCreanor, T., Casswell, S. and Hill, L. (2000) ICAP and the perils of partnership.  Addiction, 95, 179-183
Rampton and Stauber (2001).  Trust us, we're experts!  How industry manipulates science and gambles with your future.  New York, Tarcher/Putnum.

Authors Defend Their Research RE: Critique of Nicotine Addiction
 

Another ‘gold standard’ shattered? Re-opening the ‘done deal’ of conflict of interest disclosure

The editors of Addiction state that one of their aims in discussing our ‘case’ is to ‘stimulate debate’ regarding ethical issues, and specifically the requirement of declaring any financial conflict of interest (CoI). At the same time, the editorial stresses repeatedly that the policy of demanding CoI disclosure is and must remain unquestionable: ‘We take it as a done deal that declaration of potential or actual conflict of interests is a gold standard in scientific publishing.’ Any other view, in the editors’ minds, is ‘indefensible’; in fact, they regard ‘any attempt to detract from that position to be profoundly damaging to the integrity of science’.

Thus, while purportedly posing the question of CoI disclosure for the readers’ consideration, the phrasing of the ‘question’ makes its rhetorical nature abundantly clear: ‘Do we agree that the done deal must not be trimmed, obfuscated or bent in any circumstances, regardless of the arguments advanced?’ What an invitation for an open-minded discussion! and in case an uninitiated reader might mumble, ‘well, I guess this is a complex question. . .’ the editors provide the correct answer without delay: ‘Fortunately, progress has been made toward near universal acceptance of this principle by journal editors, learned societies and funding agencies [. . .] Publishers of scientific texts should ask for conflict of interests statements from authors ...as standard practice.’

In anticipation of our response, the editors take especially strong measures to immunize the unsuspecting reader against any harmful effects of a dissenting position: ‘To accept Dr Frenk’s arguments would be to accept absolute retreat from the ethical gold standard’—surely, we cannot allow that, can we? Our own belief is that there are no ‘done deals’ in science—in fact, we believe this expression would make most scientists a little queasy. Indeed, the purpose of our book was exactly to re-examine what many scientists and government agencies consider ‘a done deal’; that is, the theory that nicotine has a major role in smoking. In the same spirit, and despite the editors’ admonitions, we would like to re-examine briefly the (real, not rhetorical) question of CoI disclosure.

According to the editorial, ‘most people would assume that failure to mention conflict of interests meant that no such conflict existed [and] that this book was a product of the disinterested labour of scientists’. We doubt that any sophisticated reader would actually make these assumptions: most of us know that the disinterested scientist is a fiction. Religion, morals and other belief systems are widely acknowledged to affect scientific theories. Moreover, no scientist is free of personal motivations such as economic pressures, seeking funding, striving for promotion or craving acknowledgement—potential CoIs which no disclosure can reveal. Just like financial CoI, these attitudes and motivations may lead (and in rare cases have led) to distortion of findings or even to fraud. Unfortunately (some would say, fortunately), there is simply no way to abolish this problem. The only—partial—remedy is the scientific method itself: reliance on proven methods, openness of data, peer review, replication.

As we may be suspected of advocating a peculiar viewpoint because of a CoI about the CoI issue, it is important to stress that our position is not original or unique. Prominent scientists and journal editors have objected to the purportedly ‘gold standard’ of declaring financial CoIs. The editors of the journal Nature, to cite an example that cannot be dismissed easily, are in complete agreement with our position. Under the title ‘Avoid financial correctness’, they concluded that there was no evidence ‘that the undeclared interests led to any fraud, deception or bias in presentation, and until there is evidence that there are serious risks of malpractice, this journal will persist in its stubborn belief that research as we publish it is indeed research, not business’ (Editorial 1997, p. 469).

A major concern expressed by scientists about the demand for CoI disclosure is that the ‘implicit suggestion of wrongdoing by authors who have financial interests in their subjects risks creating an atmosphere of  “scientific McCarthyism”’ (News 1997, p. 376). Read again the questions directed at us by Dr Edwards and you will gain a good idea of what this concern refers to. Dr Edwards views these questions as harmless, and says that he expected to receive simple, honest answers to his questions, as everyone ‘would wish to see openness established here as the order of the day. What’s wrong with openness?’ As Nature editors pointed out, however, ‘appeals for openness are selective’ (News 1997, p. 376) Indeed, a troubling aspect of Addiction’s ‘openness’ rhetoric is that its ‘gold standard’ of demanding CoI dis-closure is applied rather selectively. Specifically, as the following examples suggest, such demands are generally not directed at proponents of the views endorsed by Addiction.

Dr J.E. Henningfield, a major advocate of the nicotine addiction thesis, has since 1996 been Vice President of Pinney Associates, a corporation which consults to SmithKline Beecham, a large producer of smoking cessation aids. In almost 40 papers since 1996, including one paper in Addiction (Heishman et al. 1983), Dr Henningfield did not include a transparent disclosure of CoI. Dr Robert West, an editor of Addiction and co-signer on the present editorial, acknowledged funding by Pharmacia & Upjohn and SmithKline Beecham in two papers that appeared in Psychopharmacology (West et al. 2000, 2001) but neglected to mention the relationship of these companies to smoking cessation products.

Another Pinney Associate, Dr S. Shiffman, published three papers in Addiction, two of which (Sayette et al. 2000; Shiffman 2000) without any CoI disclosure what-soever. Interestingly, these papers were submitted on 5 October 1999 and 1 September 1999, respectively. Shiffman’s third paper in Addiction (Shiffman et al. 2000) was submitted on 6 April 1999, before the other two. Since his affiliation to invivoData and Pinney Associates were acknowledged in the earlier paper, it is unclear why the editors of the journal did not insist on a disclosure of CoI in the other two. It is also interesting to note the careful phrasing of the disclosure. The authors detail the business of invivoData but not of Pinney Associates. Specifically, the sentence: ‘Drs Shiffman and Paty also provide consulting services to SmithKline Beecham Consumer Healthcare’ suggests that this is a third affiliation, whereas in fact Pinney Associates is the business that consults to SmithKline Beecham. Even more importantly, there is no disclosure that SmithKline Beecham produces nicotine replacement aids, which is highly material for the CoI question. Unless readers made a special effort to discover hidden CoIs, they would erroneously interpret these disclosures as meaning that no CoI existed.

We want to emphasize that we do not present these examples to discredit Drs Henningfield, West or Shiffman in any way, just as we did not resort to discrediting these or any other authors because of potential CoIs, hidden or disclosed, in our book (Frenk & Dar 2000). In all cases, our critique of published work was based solely on the data and arguments the authors chose to make public. The reason we give these examples here is merely to suggest that the ‘gold standard’ of CoI disclosure is applied in a manner that turns it into a double standard. This double standard is exacerbated by other accepted practices. For example, journals that demand a disclosure of potential CoI by authors do not demand similar statements from referees of submitted papers. These referees, like referees of grant applications, remain anonymous to all but the editors or grant committee members and their potential CoIs are rarely if ever disclosed.

In a sample of journals with disclosure policies investigated by Krimsky 2001), only 0.5% of the articles in biomedical research disclosed personal financial interests. Six journals that required a ‘template’ statement (requiring each author to select one of several statements within a standardized format that described any potential financial interest) had a disclosure rate of 100%. These figures suggest that the vast majority of scientists are reluctant to label themselves as untrustworthy, but can be coerced to do so. We hope that this brief exposition clarifies why we do not believe in such coercion. In the issue of Nature mentioned earlier, Dr Kenneth Rothman, editor of Epidemiology, states our position concisely: ‘It’s crucial in science to judge a work by its merit and not by the author or authors.’ We believe that this is the true gold standard of scientific criticism.
 

REUVEN DAR & HANAN FRENK
Department of Psychology
Tel Aviv University
Ramat Aviv 69978
Israel

REFERENCES
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Society for Research on Nicotine and Tobacco Third Scientific
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Nature, 385, 376.
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Addiction, 95, S189–S210.
Shiffman, S. (2000) Comments on craving. Addiction, 95,
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Shiffman, S., Elash, C. A., Paton, S. M., Gwaltney, C. J., Paty, J. A.,
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