From CNN.com Today/Eissenberg study with feedback

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Territoo

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  • Jul 17, 2009
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    Dr. Eissenberg,

    My name is Theresa Whitt, MD and I'm the medical director for Consumer Advocates for Smoke-free Alternatives Association (CASAA). I am also an electronic cigarette user.

    I read your study and find it to be a very sound one, but limited by the lack of experience of electronic cigarettes on the part of both the researcher and the subjects. You have indicated that you intend on doing further research on the topic of electronic cigarettes. I would like to offer you my services as an advisor in the use of electronic cigarettes.
     

    Belletrist

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    While it might not be scientifically substantiated (yet), there is a wealth of information and experience here that may help you in formulating further study methodologies ... helping everyone in the long run. Isn't that what we all want?

    very much agree. and we HAVE members on the forum who have been tested for nicotine levels after vaping--while obviously their posts here are anecdotal for everyone but them, i hope it inspires future research.
     

    slybootz

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    Dr. Eissenberg,

    My name is Theresa Whitt, MD and I'm the medical director for Consumer Advocates for Smoke-free Alternatives Association (CASAA). I am also an electronic cigarette user.

    I read your study and find it to be a very sound one, but limited by the lack of experience of electronic cigarettes on the part of both the researcher and the subjects. You have indicated that you intend on doing further research on the topic of electronic cigarettes. I would like to offer you my services as an advisor in the use of electronic cigarettes.

    Collaboration! That's what I like to see!
     

    hifistud

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    hifistud:

    By the rules that you suggest, no "unflawed" study is possible. Once the cartridge contents are analyzed for nicotine content, they cannot be inhaled. Once the vapor is analyzed for nicotine content, it cannot be inhaled.

    If I analyzed 20 cartridges labeled "16 mg" and found 16 mg nicotine in each, and then repeated my study with a 21st cartridge and found no nicotine in participants' blood, you could as easily say there was no nicotine in that 21st cartridge.

    With respect, this demonstrates your lack of understanding of the system.

    Consider the following methodology:

    1 take a 50ml sample of, say, 24mg labelled e-juice and a selection of, say, 20 atomisers and 20 batteries.

    2. Assay a sample of 1ml of the 50ml of e-juice for nicotine content to confirm its concentration.

    3 measure each atomiser for resistance - discard any which are more than 0.1ohms from the average value.

    4 Fully charge each battery, and measure its output under load from ONE selected atomiser. Discard all which are more than 0.1 volts away from the average.

    5 for each participant, fill each cartridge with a known measured amount of e-liquid (its "designed capacity") from the 50ml assayed sample and perform ten, measured, mechanical draws taking, say, 5 seconds per draw, each to fill a 60ml syringe before the subject uses the cart.

    6 Assay the mist collected in each numbered syringe for nicotine content, and note any increase/decrease with sequential draws (puffs).

    and then continue as before...

    Would other methods lead to different results? Perhaps they would, perhaps they would not. That is why we conduct studies. Until we conduct studies, we can only act on faith/belief.

    Again, with respect, it would have helped had you understood the variability of the equipment with which you sought to work, and how an electronic cigarette atomiser is packaged and delivered. Had you known that there is enough non-nicotine bearing primer fluid already extant in each atomiser to provide over 20 short "puffs", you may have approached your methodology differently. A regular and experienced user, however, could have advised you that each atomiser needs "breaking in" and the primer fluid exhausted before the atomiser will work as designed.

    Similarly, e-cigarette usage requires a different "puffing" technique - longer, slower and more measured than a tobacco cigarette. Were your subjects instructed accordingly?

    I am well acquainted with the symptoms of an over-indulgence of nicotine, and can tell you that the e-cigarettes I use most definitely deliver nicotine, admittedly in smaller acute quantities than cigarettes, but on a par with both gums and lozenges over time.

    I have no objection to your choice to use an e-cigarette because you have faith/believe that it does something.

    My interest is in verifying what it does.

    As is mine, and I am here to advise you that your method, unfortunately, does not in any way produce reliable results. Before you can measure the nicotine absorbed into the body, you must first confirm that there is nicotine in every stage of the system. This, I'm afraid, you have failed to do - the cartridges could have been filled with distilled water, for all you know. The atomisers may have failed mid-puff - there are no data on exhaled vapour, nor even mention of it. In short, the data you have produced tell us nothing, and are unreliable.

    I do want to tell you, though, that none of the above is meant as a personal attack on you, in any way. I believe that you have undertaken the study in good faith, but, I am afraid, from a standpoint of unwitting ignorance of the system under test.
     

    Lab

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    my question is are these.. puffs.. or are they inhales of the vapor.. also wouldn't the test be a bit more accurate if the e-cig was hooked to a electric pump to fill a bag with vapor, tested before inhale for nic content in the vapor.. then to test the absorption.

    I am sure there is a lot of people on this forum that could go out and buy a nicotine urine test that only use e-cigs and post the results from the test with there average consumption
     

    teissenb

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    hifistud:

    Thanks for the comments. I appreciate the issues you raise. I disagree completely with the conclusions you draw.

    I will not dwell on our differences as I suspect we will not convince each other without data that neither of us have. I will note that your post highlights the conclusions of the paper. More research needs to be done, and, if your fears are justified, the products should be regulated in a manner consistent with cartridge content and product effect. If users of these products honestly do not know what is in the cartridge (distilled water? really?) then there is a serious quality control problem. If people are using cartridges or e-liquids where the variability is as great as you fear, there is a serious quality control problem. That level of quality control with a lethal drug like nicotine can be life-threatening. Regulation that mandates strict quality control (as is true for drugs in this country) would solve the problem you face.
     

    Adrenalynn

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    Director Eissenberg,

    First and foremost, thank you for your participation, time, candor, and transparency here. Respondents have been all over the board and in a quick skim of the thread, I've observed a lot of anecdote and misunderstanding of the process - that you've chosen to address even these speaks volumes for your interest in Good Science.

    Under the conditions we used

    I think my initial concern lies here. Were the manufacturers of the delivery devices consulted in proper administration? From the letter I had forwarded to me purporting to be your brief initial study entitled: "Electronic nicotine delivery devices: ineffective nicotine delivery and craving suppression after acute administration", I did not observe that such a consultation occurred.

    If a delivery device is mis-employed, I'm sure we will agree that any results will tend towards inherent flaws.

    I think we'll find that it is commonly [anecdotally] accepted that former smokers employing an "electronic cigarette" tend to do so more frequently and for greater periods. Further, the inhalation method differs (longer, slower draws rather than rapid short "puffs"). If we were to compare a time release IM injection with an oral administration of some drug available in both formulations, we wouldn't state that the oral administration was "an inadequate delivery system", would we? We would look at the indications and presentation and decide the appropriate delivery system. Further, if we were to misuse the IM and inject IV, would we find the drug at fault, or the misuse of the delivery system to be the underlying condition of failure to perform? If I had adverse results from ingesting a "nicotine patch" - we'd all probably laugh and address me in ways best left out of academia. ;)

    I think I have further concerns with your paper, but until we can agree that the manufacturer's approved use of the delivery mechanism was specifically addressed I can go no further into the results for the above mentioned.

    In defense of the apparent mechanism you employed; I find manufacturers to be unclear in general regarding recommended use unless "pinned down"... I think those of us employing this cessation aid discover in relatively short time how best to get our required "fix". Perhaps that study is required as a precursor?

    Again - thank you for your time and attention.

    [note: I've been getting a "Server too busy" message so this may be entirely "stale" by the time it posts...]
     

    Belletrist

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    my problem isn't with the idea that e-cigs should be regulated, to be honest. i agree that they should be. my problem with the idea of regulation is the potential for PVs to go off the market during the testing process/regulation/legislation battles that will follow. scientists aside (in an ideal world) there are some powerful lobbies that would prefer PVs fall off the face of the planet, so i fear the regulation itself wouldn't be unbiased or reasonable. and it does seem absolutely absurd to stop the sale of PVs or regulate them, considering the known risks of cigarettes and the fact that they're readily available.
     

    hifistud

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    Teissenb:

    Oh, I know what's in the e-juice I use - but, from a trial standpoint, there are no data to show what was in the cartridges you used. There are no data to show what voltage under load was being produced by the batteries you used. There are no data to show what the resistance under load your atomisers exhibited. There are no data to show the efficiency of the complete systems you used, and there is scant data to show whether those systems actually produced a nicotine-bearing mist.

    I agree with you that some form of regulation is desirable if not inevitable, but, from an experimental standpoint, you have begun with unknowns and not quantified them in any way.

    Had you measured the nicotine available in A: the mist from the e-cigs, B: the smoke from each participant's own brand and c: the sham smoking, then your cited conclusions might have been more credible. As it stands, your conclusions are directly at odds with Dr Laugesen's.

    This is not a problem for quality control, so much as a need for thoroughness in evaluating the raw materials of the study. What conclusions would you be able to draw, if, for instance, all of your participants smoked nicotine free cigarettes?

    If the nicotine presented for absorption is not measured, how can the plasma levels be reliably equated to it? If you conclude that neither brand of e-cigarette raised blood nicotine levels significantly, why is that? Is it because they do not present a quantity of nicotine to be absorbed that would raise levels significantly, or is it because the absorption mechanism differs markedly from the mechanism utilised by cigarette smoke?

    The study does not answer that point.

    While it may seem that I am slightly belligerent towards you, please be assured that this is not the case. There are those who, possessing more letters after their name that I, will, I believe, make similar points in review, and it is unfortunate that this study has been made public at a very inopportune time for those of us resident in the UK - and also in the US, as it seems to raise more questions than it answers.

    I do believe that there is much more scope for research, and I also believe that any further research must take into account the responses you have received here - that is to say that, in order to prevent rebuttal, each step must be quantified as I've outlined above. Preparing a methodology that relies on mensuration at each stage is not particularly troublesome, and allows for a deeper understanding of the mechanisms at play in the usage of these devices.

    Let me say, further, I have no doubt about your bona fides or intentions, and seek merely to, if you will, play devil's advocate in order that your research becomes definitive. Consider this a message of support.
     

    YoMike

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    This ecigarette study has shown that the 16mg nic solution used should be considered weak not high as labeled by the manufacture. Currently available nic solutions range upwards to 48mg 3x the nic level of the solution used in this study. Also it became apparent that there's a learning curve to the use of an ecigarette, see pic of user puffing ecig note no vapor cloud seen. The breaking in of the atomizer is one of the basic procedures that this study totally by passed. Reinforcing the need for proper instruction to be included and followed to achieve desire results. The knowledge base at e-cigarette-forum.com should be highly recommended to any potential user to achieve optimum results. Researcher Dr Eissenberg has been member of e-cigarette-forum for the pass 7 months and still finds himself learning the finer points from the friendly members.
    Conclusion: In the hands of an inexperience naive user the ecigarette tested were no more effective at delivering nicotine than puffing on an unlit cigarette.
     

    teissenb

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    We certainly did *not*consult the manufacturer on how best to use the product. We try to *avoid* the conflicts of interest several have accused me of here. For this reason, I will not be working with any e-cigarette manufacturers in the future, just as I do not work with tobacco companies.

    I am getting the impression that some here have a perception that the products are so poorly standardized that they require specialized knowledge for routine use. If I were a manufacturer, I would be alarmed at this perception! As a researcher, I see that this perception allows study critics to elaborate any number of arcane activities that a researcher might have done prior to testing the devices. If it helps, I freely acknowledge that there is almost certainly some method, however obscure, that might be used to get these devices to deliver an active dose of nicotine. My study was not designed to identify that obscure method, it was designed to determine the extent to which the nicotine delivery of two 10-puff bouts from an e-cigarette differed from sham smoking and own brand cigarette smoking. We developed a standard protocol, described it, and used it. As I have said elsewhere, one study rarely addresses all the issues of complex problem.

    Rest assured that I have noted the suggestions here for future study. I also note that some of suggestions might best be implemented not by federally funded scientists but by a manufacturer who is interested in constructing a device that delivers nicotine reliably, as the devices I tested did not.

    To sum up, I stand by the method used and the conclusions as written. Specifically:

    Importantly, these results were from
    two specific products tested under acute
    conditions in which puff number was
    controlled. Variability in product design may
    influence vapour content7 and chronic use
    and/or more intensive puffing (ie, more puffs,
    greater puff volume) may influence nicotine
    delivery. Given these and other factors, there
    is an ongoing need to evaluate electronic
    nicotine delivery devices (E-cigarettes). These
    evaluations should be conducted in a manner
    that takes into account variability in design
    (including cartridge nicotine content),
    examines the effects of user behaviour over
    time and compares these products to existing
    methods of delivering therapeutic nicotine
    safely and effectively.
     

    hifistud

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    I am getting the impression that some here have a perception that the products are so poorly standardized that they require specialized knowledge for routine use. If I were a manufacturer, I would be alarmed at this perception! As a researcher, I see that this perception allows study critics to elaborate any number of arcane activities that a researcher might have done prior to testing the devices. If it helps, I freely acknowledge that there is almost certainly some method, however obscure, that might be used to get these devices to deliver an active dose of nicotine.

    It is no different from realising that there is a difference between the way you use a hand saw and the way you use a chain saw. An electronic cigarette requires a different method of use compared to a traditional cigarette. It really is that simple.

    Or, if you like, compare flooring the gas pedal in a Prius to flooring the gas pedal in a Veyron.
     

    Belletrist

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    Let me say, further, I have no doubt about your bona fides or intentions, and seek merely to, if you will, play devil's advocate in order that your research becomes definitive. Consider this a message of support.

    what a gentleman! :D

    dr. eissenburg, i appreciate your coming here and especially appreciate the data being shared. i think many of us are frustrated. after being told over and over that there isn't enough rigorous scientific evidence for this or that, we read about a study which seems to be flawed from the experienced vaper's point of view.

    the more rigorously personal vaporizers and nicotine liquid are tested, the better. so i am glad to see this study, although i know its results will be widely misinterpreted--the science has to start somewhere.

    thank you!
     

    Adrenalynn

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    I appreciate that you are standing by the methodology. I don't think I can contribute anything further in light of that. There is a reason that people who begin smoking "learn to smoke". "Proper smoking" is a learned behavior. Electronic Cigarette use is a learned behavior too.

    Do you find it "disturbing" that we have to learn the correct use of a syringe - or even the multitude of correct uses given various delivery mechanisms? Would you not consult the PDR on correct dosing and administration of a medication you were unfamiliar with because that might somehow taint the results?

    I think it's unfortunate that consulting on proper use of a delivery device would lead some to accuse you of bias on those grounds alone.


    I'm afraid we're at an impasse, but I do hope you'll consider what the various respondents have suggested in this regard and reevaluate your results in light of this at some later date. I think a study of the best method of delivering maximum bioavailability from e-cigarettes is a study I'd like to read.

    Again, thank you for your correspondence!

    [edit to add:] I suspect I have more of an issue with the media's treatment of your results than with the study alone. Your results are what they are given the methodology you chose. I don't think those come into question. It's unfortunate that the unwashed mass media is incapable of reading further into the study to find its limitations, but that is certainly not your "problem"...
     
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    hifistud

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    Teissenb:

    You should also be aware that you are being misquoted:

    The study, the first study of e-cigarettes to be conducted by U.S. doctors, found that almost no nicotine was actually delivered by the devices and instead users were actually inhaling a nicotine-devoid toxic vapor of compounds like diethylene glycol or nitrosamines, a family of cancer-causing nitrogen compounds.

    that's at: DailyTech - Study: E-Cigarettes Fail at Nicotine Delivery, No Better Than Unlit Cigarette
     
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