FINALLY! A REAL Clinical Trial on e-cigs!

[zoiDman]

If your into reading up on trials, here is an interesting summary of another trial that was done in April. Some nice info about Nicotine absorption about half way down.

http://www.healthnz.co.nz/2010%20Bullen%20ECig.pdf

Like I said, interesting reading. Just remember who paid for the study to be conducted before you make your own judgement about it.

 

[Vocalek]

If your into reading up on trials, here is an interesting summary of another trial that was done in April. Some nice info about Nicotine absorption about half way down.

http://www.healthnz.co.nz/2010 Bullen ECig.pdf

Like I said, interesting reading. Just remember who paid for the study to be conducted before you make your own judgement about it.

It is common practice for the company that will benefit from the eventual marketing of a product to be the one that pays for testing it, and to have the testing carried out by an independent research facility. The pharmaceutical companies, not the FDA, pay for the clinical trials required for FDA approval.

Any independent research facility that skews results based on who paid the bill will quickly lose its reputation and no medical journal would publish their results. Your link is to a reprint of an article published in tobacco Control, a journal published by the British Medical Journal Group. This is a strong indication that the results are reliable.

The toxicology test that was conducted in-house by the FDA turned out to be quite unreliable. Most likely this is because the FDA had a vested interest in coming up with negative results and only tested the products of the two companies that had filed a law suit against the agency.

 

[CES]

Just a note. The author of that paper (http://www.healthnz.co.nz/2010%20Bullen%20ECig.pdf ) is the primary investigator for this set of clinical trials.

 

[rolygate]

@Zoidman
Thanks for that doc. Some interesting findings. Noted that it was funded by Ruyan.

1. They used 16mg carts, these were analysed and found to be 1.4% ie 14mg. A little higher than 12 mg 'low strength', as we refer to it.
2. Their results, and previous research, indicates that an ecigarette provides 10% of the nicotine per puff compared to a tobacco cigarette (for that type of equipment / liquid).
3. They admit some units were probably faulty.
4. They admit that research staff knew little about the products - how to specify them / test them / prepare them.
5. The usage time for an ecig is stated as 5 minutes; and they admit that they did not know how long one should be used for; and that the Nicorette inhaler was used for 20 minutes as recommended by the manufacturer.
6. Blood nicotine levels were measured at 1.3, 2.1, and 13.4 ng/mL for the penstyle, Nicorette, and cigarettes, average values, respectively. Some users had zero nicotine in the blood after using the penstyle.
7. There were more instances of mouth / throat irritation with the Nicorette inhaler than with the Ruyan V8 penstyle, and least of all with the penstyle on zero nic.


The results were that smokers generally liked them, the scores were similar for the penstyle and the Nicorette inhaler, with a slight advantage to the penstyle. If the trial had had the advantage of expert advice then perhaps it would have had a very different outcome. For example:

1. We would not regard using low strength liquid for 20-a-day or more smoker as likely to produce a satisfactory result, especially with a beginner, and when using new, untested equipment, and not set up by an expert. The resulting extremely low blood nicotine levels compared to a cigarette, and with some users tested as having none whatsoever in the blood, is to be expected. A fair trial would need expert input, user instruction, and of course high-strength liquid.

2. The very low figure of 10% nicotine per unit volume of vapor compared to a cigarette is to be expected under these conditions. It is not the same result that would be achieved by an expert user who required a higher nicotine value, and one can imagine this figure being 200% higher under different conditions (ie a high strength liquid being used and the correct four to six-second inhale time being used). By definition, a cigarette smoking machine cannot be used unless the inhale time is variable to at least 6 seconds. There is no comparison between cig and ecig inhale technique.

3, 4. Some duds no doubt contributed to the zero nicotine / blood measurements for some users - plus the other negative factors listed here. Testing and trialling a car needs someone who knows how to put the gas in and drive it.

4. The minimum vaping time that I am aware of is 15 minutes, 20 being more common. Thus, the usage time for the Nicorette is accurate and must come from manufacturer's tests - which they wouldn't get wrong... Because ecigs have a quarter or less of the available nicotine, they have to be used for three or four times as long as a cigarette's usual ~5 minutes. About the same as a Nicorette, funnily enough.

5, 6. It's easy enough to set up a fair trial for ecigs in the lab, change all the variables so that the user gets a decent amount of nicotine in the blood. How hard can that be? Without that being done at the very least, it's hard to see how any 'trial' of this kind can be taken seriously.

After all, we are only talking about doing exactly what every consumer everywhere does instinctively. People know exactly how much coffee they need and adjust the strength and volume as needed. The same goes for alcohol and nicotine - it's an extremely exact science for the user because they get plenty of feedback and know exactly when enough is enough. Let the consumer adjust the amount as needed - they take what they need *and it's the perfect amount*. A trial that purports to test user satisfaction with a consumer product needs to allow for user variants. Some people want 10 units of cornflakes, some want 50. You can't base user satisfaction elements of any product trial on what somebody else decides is the right amount - the user's preference is *the most important factor of all*.

7. Interesting to see that the Nicorette caused by far the most mouth & throat irritation. Must be a bit like tailpiping.


I think the most important fact revealed by all these trials and proposed trials is that the researchers are under the misapprehension that there is some sort of similarity between a cigarette and an ecigarette. There isn't. If ecigarettes are assumed to be similar in some ways to tobacco cigarettes, and are tested accordingly, then the test results are pretty much worthless - as can be seen.

I think I'd have something to say about it if my coffee delivered zero caffeine, and I'd sure as hell be aware of it.

 

[Kate51]

rolygate, a fine post!
They will again find I believe, that e-cigs are more in line with patches and gums (yes, Nicorette almost identical), not anything close to cigarette smoking. Maybe this new test will support that as well. Hopefully it will inspire some confidence as a smoking alternative! (A GOOD one, MHO!)
So far I've been un-impressed by non-caffeinated coffee! Seems such a waste of perfectly good coffee beans. But yes, agreed, if there was no caffein, I would know it before the second cup! My headache would be full-blown by then.
As would my nervous system (and everyone's around me!) know there was no nicotine in my cartridge.

 

[mwa102464]

Right on Rolygate right on

 

[rolygate]

This post is by Shining Wit (John @ Intellicig) and moved here by request

_______________
Hi Chris,
[please repost this for me in the correct thread]

Two of the prople running the trial are Hayden McRobbie and Murray Laugesen. We spoke at length with Hayden at the Smoking Cessation conference last week and he is a positive supporter of electronic cigarettes as he sees them as potentially an effective *harm reduction* product and that's one of the main reasons we all choose to use them, because we believe they are safer than cigarettes.

After he had spoken to us, he delivered a lecture in the main hall and was very generous in his appraisal of ecigs; we were swamped with inquisitive delegates immediately following his address.

Murray Laugesen has also been in regular contact and he too is on the side of harm reduction. Murray conducted tests for Ruyan so he's hardly in the pocket of BigP or BigT.

I can't believe the wave of negativity towards the announced trials, which are not being funded by P or T, as the New Zealand Government has already published a document stating their intention to have electronic cigarettes on sale by 2011 and are working on suitable regulation that will be in the interest of Public Health. The Kiwis are a very progressive nation and are embracing this new technology.

There have been continuous calls for trials and tests ever since I joined the forum in October 2008 and now that someone is conducting them they are being slated!

The fact that previous trials indicated that relatively low amounts of nicotine were being absorbed into the bloodstream is interesting, especially when these trials will be 'blind', so users will not know what they are using. I have witnessed blind tests where the user has not known the level of nicotine and more than 50% were satisfied with what they were vaping. They were not full trials, which makes these trials important in terms of the psychological efficacy as well as the physical efficacy.

They will not be the 'be all and end all' trials, but they will be a starting point for others to reference and will demonstrate to the detractors that someone is taking this seriously and trying to learn more about ecigs and their effects.

What other Government is spending any money on trials?

For those who would wish to continue in their use of nicotine, where's the problem? You can buy lozenges, patches etc over the counter with no limit as to how long you can use them for and ecigs will probably be regulated in a similar fashion as a GSL (General Sale Licence) product*. Vape on!

John.

[* John means OTC, over the counter, ie out on the open shelf]

 

[cyberwolf]

Rolygate and Shining Wit are exatly right. While we have seen our share of poor outcomes from poorly managed trials and testing, this is the only way that the threat of the "ban" is going to go away. It should be viewed as a positive development any time a trial is proposed. That alone shows that these devices are being taken seriously.

 

[rolygate]

John,

I appreciate your points - especially that these researchers are either neutral or well disposed to ecigs.

The point I am trying to make is that these are medics and they seem to be trying to run trials of consumer products as if they were medicines of some kind. To explain: medicines are normally available in one type or a small range of types, and the patient is given little or no choice in the matter.

Consumer products are exactly the opposite: there are hundreds of variations and the consumer chooses, and changes their choice, depending on factors such as taste, effect, how they feel on the day, and other preferences.

These two types of products are fundamentally different.

If I were a beer drinker and had never tried wine, and some researchers wanted to see if I would like it or even change a substantial amount of my consumption to wine, then if they gave me (test #1) Mateus Rosé and told me "That's wine", then I might decide wine is not to my taste.
* Mateus Rosé is a fizzy Portuguese rosé wine

But if, on the other hand, they gave me a selection of wines to try (test #2), and asked me to try them and pick two or three I liked, then I'm fairly sure the result would be substantially different.

In test 1, I might well say "No thanks, I'll stick to beer". In test two I might find that a Nuits St George or a Chateauneuf du Pape are quite pleasant, and decide to give it a whirl.

There's not really much comparison between the items offered in tests 1 & 2. Unfortunately the ecig trials seem to be going the Mateus Rosé route. The medics need to consider the principles of self-medication and of expert patient advice, which are the nearest I can get to a medical version of the normal consumer choice process. In 'self-medication' the patient chooses their own medications and dose, according to the symptoms on the day, and with the benefit of experience. All chronic diseases / conditions need a measure of it.

In 'expert patient advice', a patient who has had the condition for many years advises both doctors and new patients on the effects of the medications, since they will often be better qualified to do so than even a consultant-level doctor.

Both these processes approach the consumer choice process. Consumers don't do well if given one option, as explained. Try telling a very experienced patient that they can only have one type of medication and of one particular dose, and see what the reaction is. They'll find another doctor, one who has some sort of grasp of reality. Medication and dose varies from patient to patient, from day to day. Consumer choices vary from consumer to consumer. The consumer is very well placed to decide what they like or not, when given the choice.

So basically I agree with what you're saying but the researchers need to take on board the concept that they are dealing with a consumer product that has a huge range of choices, and if the trial is supposed to find out if they like the class of product, giving them one option out of many is not the way to go. And giving them an option that is proven not to work at all in several cases (the zero nicotine blood levels found) is surely not the basis for an accurate trial.

Let's see a trial with expert advisors on hand, where the blood nicotine levels measured are in the same sort of range as those produced by tobacco smoking, and then I won't criticise. Any 'trial' where low-strength liquids are given to beginners or where HV mods are not available for those that want them is hardly representative of the true product range or the true experience of the consumer. It's like giving weak green tea to a coffee drinker and saying, "Do you like tea then?".

 

[DaveP]

Understanding the product is key to public acceptance. I am really tired of reading reviews about Ecigs only to read "The electronic cigarette uses a liquid nicotine suspended in propylene glycol, a component of antifreeze". You know why they picked antifreeze as an example of PG content; it's where the FDA said it was also contained. They could have named 200 products or more that contained it. I bought a bottle of sno-cone juice the other day. Its ingredients label said "propylene glycol". Every kid on a playground is getting PG at recess! Do we have to continue to bring up antifreeze? PG is in there because it won't kill your dog if they lick it from the driveway like ethylene glycol will.

 

[zoiDman]

I am not a Statistician, but I have done enough Statistics to know some things to look for in a study. Consider the informational findings that I linked to.

http://www.healthnz.co.nz/2010 Bullen ECig.pdf


1) What is the purpose of the study and What is the Null Hypothesis:

For this study, “ Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery.” It appears that inferences would like to me made about how a sub-set of the population (Current Smokers) feel when using an e-Cigarette in regards to desire to smoke and withdrawal symptoms from not smoking.

So the Null Hypothesis would be stated as something like; “e-Cigarettes do Not reduce the Desire to Smoke Analogs and do Not reduce withdrawal symptoms.” Studies like this usually set out to disprove the Null Hypothesis.

But that is the only result from a study that can be considered valid. Because that is the only thing being controlled. So if researchers saw that people tended to gain weight who were in the study, it is a nice side note but the study did not prove or disprove that weight gain is related to e-Cig use.

So nothing that was reported in the summary, that is not related to “Desire to Smoke” and “Withdrawal Symptoms”, is considered to be proven or disproven. A New study with new controls would be needed to conducted to make inferences about anything else.


2) How Large is the Sample Size, How were they Chosen and Were They Paid to Participate?

A sample size of 40 is a Very small sample size to reflect upon the True Population. But what is more concerning is that no mention was given to how the 40 individuals were chosen. Was it 40 housewives picked for the same geographic area? 40 college students? Perhaps 40 people from a self-help group for people wanting to quit smoking.

A key word is missing from the method of selection. And that word is “Random“.

There is also no mention if the 40 individuals were paid to participate in the study. So all that can be said is that 40 people participated and that should raise a Huge Red Flag.


3) How was the Study Administered?

Here is another problem. “Participants were requested to abstain from smoking and alcohol from 20:00 on the night before each study day and from food and caffeine for at least 1 hour before the session.“. Since the participants were only asked to not smoking before the Study was given, there is no control that they actually did not smoke. Without this control in place, any results could be considered suspect.



4) What is the Statistical Confidence Interval and What was the Power of Test (P) ?

Here the study follows statiscal excepted levels of both Confidence Interval and Test Power. No problems here. In fact. The Power of the Test is Very strong. This implies that the probability of excepting a false result are very low.


5) How was the Study Funded?

This is where I have the biggest problem with the study. The Study was funded by a e-Cigarette manufacture who has a huge vested interest in the results. Many times, Companies want a Study performed with follow on Studies to be performed based on the results. I’m not saying this is what is happening in this study, but there can be biases based on who is funding the study.

This is a worst case scenario for any Investigator and Study Administrator. If you provide results that your funder does not like, they might cut off your funding for future studies. It’s a bad situation to put a University in that has many interests and monetary requirements.


My Conclusion:

I don’t feel the results from this study can be considered statistically reflective of a true population. Since the study was deficient in many areas, sample size and randomness, lack of control, possible bias due to funding source, I feel the results must be considered suspect.

In my opinion, this study was not meant to be anything more than a Preliminary finding. A justification for a future, better controlled study with a larger sample size. I’m sure the funders of this study would have been very disappointed with spending tens of thousands of dollars only to get non-conclusive results. Better to do a small, poorly run but inexpensive study and see what kind of results you get. Then if you feel a well run study with a large sample size would bear the same results, run it.


So the last question you might be asking yourself is why did I post the link to a study only to point out some glaring omissions in it?

Two fold. First. There was a reference to the absorption amount of Nicotine for subjects in the study. I am not saying that this number should be considered as authoritative. It was not the purpose of the test. But it is the first, somewhat clinical reference to absorption rates and would like to see more information to corroborate or disprove the percentage amount.

The second was to bring to the attention of others how “Studies” of this nature can be misleading and need more detailed scrutiny. I cringe every time I hear references to a “Study” or a “Trial” when there is no reference to Sample Size, Statistical Confidence Level / Power of the Test or even who funded it.

There is so much talk here on the ECF as well as in the mainstream news about e-Cigs Benefits, Safety, Possible Bans, Possible Government Regulations. It would seem that more quality and independently motivated studies should be done before judgments are made based on incomplete or even suspect findings.

Remember: Statistics can be described as a Very Scientific way to Deceive the Ignorant.

 

[Kate51]

Remember: Statistics can be described as a Very Scientific way to Deceive the Ignorant

Yes, that very fact being discussed on another Thread, i.e. statistics from

http://www.e-cigarette-forum.com/forum/quitting/102042-numbers-dont-add-up.html

I have been very happy to see and more or less understand the published trials from NZ, am a supporter of any steps taken to verify what I know already...SAFER!! I prove that every day by still being alive while not coughing!
I also have throughly read the above mentioned study, and have supported it's findings adnauseum. It was a view of 3 components and the results. Yes, it is subjective because of the components. But the data gathered is what it is, and the numbers fall in line with the previous NZ tests. A far cry from the bench testing done by U.S. FDA.
Yes, Ruyan paid for the services, and it was very expensive. There are those who see a problem there. I see no one else stepping up to the task.
In fact have gone a few rounds with those who cannot see the correlations, who remain skeptics even in the face of personal experience. Perhaps they weren't yet fully aware how smoking kills.
I would like someone to post say a Methamphetamine Addiction clinical trial. Can't seem to find one. All I'm saying is that Clinical Trials of subjective data are extremely difficult to quantify, and will never be perfect by their very nature. Clinical statistics for any addiction would be terribly subjective and wide ranging.
But the gathered stats regarding e-cigs would be highly interesting to me!
Question Boldly, Verify.

 

[CES]

I am not a Statistician, but I have done enough Statistics to know some things to look for in a study. Consider the informational findings that I linked to.

http://www.healthnz.co.nz/2010 Bullen ECig.pdf


1) What is the purpose of the study and What is the Null Hypothesis:

For this study, “ Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery.” It appears that inferences would like to me made about how a sub-set of the population (Current Smokers) feel when using an e-Cigarette in regards to desire to smoke and withdrawal symptoms from not smoking.

So the Null Hypothesis would be stated as something like; “e-Cigarettes do Not reduce the Desire to Smoke Analogs and do Not reduce withdrawal symptoms.” Studies like this usually set out to disprove the Null Hypothesis.

But that is the only result from a study that can be considered valid. Because that is the only thing being controlled. So if researchers saw that people tended to gain weight who were in the study, it is a nice side note but the study did not prove or disprove that weight gain is related to e-Cig use.

So nothing that was reported in the summary, that is not related to “Desire to Smoke” and “Withdrawal Symptoms”, is considered to be proven or disproven. A New study with new controls would be needed to conducted to make inferences about anything else.

Studies don't actually prove or disprove anything. Hypothesis driven research either supports the null hypothesis or does not. You build a body of evidence and look at it as a whole. That's in the early stages for vaping.


And you can discuss unexpected results in the paper, as well use unexpected results as the basis for the next study. The discussion is just that. A place where the authors discuss and interpret the results. It's often the part of a study that people read, but also the least "real". The data and methods are where people need to spend their time.

2) How Large is the Sample Size, How were they Chosen and Were They Paid to Participate?

A sample size of 40 is a Very small sample size to reflect upon the True Population. But what is more concerning is that no mention was given to how the 40 individuals were chosen. Was it 40 housewives picked for the same geographic area? 40 college students? Perhaps 40 people from a self-help group for people wanting to quit smoking.

A key word is missing from the method of selection. And that word is “Random“.

There is also no mention if the 40 individuals were paid to participate in the study. So all that can be said is that 40 people participated and that should raise a Huge Red Flag.

Yes, 40 people is a small sample, especially if there are a number of conditions. But, it’s not unusual to use a small sample to get preliminary data.

But it’s a randomIZED trial. Not a random trial. It’s already not random because participants are smokers, then they have to volunteer, then meet the exclusion criteria (which should be included in the methods). So participants are randomly assigned to a “treatment group”. They’re not randomly selected off the street.

3) How was the Study Administered?

Here is another problem. “Participants were requested to abstain from smoking and alcohol from 20:00 on the night before each study day and from food and caffeine for at least 1 hour before the session.“. Since the participants were only asked to not smoking before the Study was given, there is no control that they actually did not smoke. Without this control in place, any results could be considered suspect.

That’s the problem with working with people. They lie, they exaggerate…etc. But you have to start somewhere.

This is also where randomization comes in. Hopefully, you’ve distributed the people who can’t abstain and volunteered anyway equally across the groups. That’s also where a larger sample size comes in handy.

4) What is the Statistical Confidence Interval and What was the Power of Test (P) ?

Here the study follows statiscal excepted levels of both Confidence Interval and Test Power. No problems here. In fact. The Power of the Test is Very strong. This implies that the probability of excepting a false result are very low.

Power and the p value, while related, are not the same thing. It depends on the statistics used. P-value is a mathematical construct that tells you the probability that any effects you detected are real and not by chance. A very small P can imply a large effect-but doesn't prove it. You can increase the power to detect effects by increasing sample size and/or using the ‘best’ statistics. A really ‘powerful’ test can detect very small differences-whether or not they’re real.

5) How was the Study Funded?

This is where I have the biggest problem with the study. The Study was funded by a e-Cigarette manufacture who has a huge vested interest in the results. Many times, Companies want a Study performed with follow on Studies to be performed based on the results. I’m not saying this is what is happening in this study, but there can be biases based on who is funding the study.

This is a worst case scenario for any Investigator and Study Administrator. If you provide results that your funder does not like, they might cut off your funding for future studies. It’s a bad situation to put a University in that has many interests and monetary requirements.

And yes, you’re correct that people start with a small study to see if there’s any effect to measure. You can’t get funding to run the study if there is no effect. And while you’re correct to take into account who funds the study, by definition only someone with an interest in the outcome will fund a study. So you look at the data itself.

My Conclusion:

I don’t feel the results from this study can be considered statistically reflective of a true population. Since the study was deficient in many areas, sample size and randomness, lack of control, possible bias due to funding source, I feel the results must be considered suspect.

The statistics are "significant", though the results may not generalize to the whole population. The question is only of interest to a subset of the population anyway. Smokers who want nicotine in a less harmful way, and the people on both sides who have a finacial interest in the outcome.

In my opinion, this study was not meant to be anything more than a Preliminary finding. A justification for a future, better controlled study with a larger sample size. I’m sure the funders of this study would have been very disappointed with spending tens of thousands of dollars only to get non-conclusive results. Better to do a small, poorly run but inexpensive study and see what kind of results you get. Then if you feel a well run study with a large sample size would bear the same results, run it.

Isn't that what the authors are doing? and the point of this thread?

So the last question you might be asking yourself is why did I post the link to a study only to point out some glaring omissions in it?

Two fold. First. There was a reference to the absorption amount of Nicotine for subjects in the study. I am not saying that this number should be considered as authoritative. It was not the purpose of the test. But it is the first, somewhat clinical reference to absorption rates and would like to see more information to corroborate or disprove the percentage amount.

The second was to bring to the attention of others how “Studies” of this nature can be misleading and need more detailed scrutiny. I cringe every time I hear references to a “Study” or a “Trial” when there is no reference to Sample Size, Statistical Confidence Level / Power of the Test or even who funded it.

There is so much talk here on the ECF as well as in the mainstream news about e-Cigs Benefits, Safety, Possible Bans, Possible Government Regulations. It would seem that more quality and independently motivated studies should be done before judgments are made based on incomplete or even suspect findings.

Remember: Statistics can be described as a Very Scientific way to Deceive the Ignorant.

The fact that they found effects in the preliminary study, with the problems with equipment etc. tells you that there is likely a large effect. But we already know that. It’s not us who need to be convinced. There is a large sample here on ECF. A skewed, self- report sample, but a large sample none the less.

I agree with you that every study is suspect- 73.47% of statistics are made up on the spot. I don't agree with you on your interpretation of this study.That may be just because I’m happy that a report that shows people’s heads don’t explode from vaping even got published. And even happier that they’re willing to expand the study.

 

[CES]

I just wanted to add a couple of points in clarification. My post above is about the science. My personal opinion is that e-c-gs/PVs are and should remain consumer products. I can change the strength of my coffee as needed and don't think that nicotine by itself is particularly harmful. Consistent with that stance, I think that testing should should be more about safety and product consistency rather than "clinical effectiveness" and thus be able to take in the myriad of factors that Roly and others have mentioned.

If e-cigs had been marketed as smoking cessation, I wouldn't be making this post, or any posts here. I wouldn't have touched e-cigs with a 10 foot pole. I wasn't planning to quit smoking. Yet, I haven't smoked a cigarette for more than 6 months. cool.

However, if clinical trials are being done, I'd rather have them done by people- like the primary investigator and collaborators for this study- who support harm reduction, and who took the time to do the survey to get background information on e-cig use.

 

[Kate51]

Excellent clarifications, CES, very accurately pointed to clarify any lingering doubts regarding purposes and methods of Clinical Trials...this is another animal after my own heart, bench testing is firmly step one (nuts and bolts) but comes a time when any study needs a practical interface (human), as problematic as that can be, and this will be one more welcome step in the procedure.
The organizers are proven qualified and I wish them the best in this huge undertaking.

 

[Smix]

I've been in contact with the one of the Associate Professors of the trial. Unfortunately it sounds like they won't be recruiting participants until early 2011. The reason for this is they have to select a product, ethics and regulatory approval and set up systems. He also mentioned a recently funded cessation trial as a reason for the delay (which I have no knowledge of).

He did, however, point me to the survey which he said would be helpful if I completed Stop-tabac: Questionnaire for current and former users of electronic cigarettes (I had already done it but if you haven't, please do!)


Chris.

 

[Vocalek]

Understanding the product is key to public acceptance. I am really tired of reading reviews about Ecigs only to read "The electronic cigarette uses a liquid nicotine suspended in propylene glycol, a component of antifreeze". You know why they picked antifreeze as an example of PG content; it's where the FDA said it was also contained. They could have named 200 products or more that contained it. I bought a bottle of sno-cone juice the other day. Its ingredients label said "propylene glycol". Every kid on a playground is getting PG at recess! Do we have to continue to bring up antifreeze? PG is in there because it won't kill your dog if they lick it from the driveway like ethylene glycol will.

There is a lot of confusion going on about the "antifreeze" issue. When the FDA said they found antifreeze they were not talking about Propylene Glycol (PG) that we use as the base for our product. They found 1% Diethylene Glycol (DEG) in one of 18 cartridges tested.

The U.S. Food and Drug Administration today announced that a laboratory analysis of electronic cigarette samples has found that they contain carcinogens and toxic chemicals such as diethylene glycol, an ingredient used in antifreeze.

FDA and Public Health Experts Warn About Electronic Cigarettes

Here's where the confusion comes in. A dilute solution of DEG can be used as a coolant, but it is not the product most often used in antifreeze. A common use of DEG is as a humectant in tobacco, cork, printing ink, and glue. So the FDA misspoke when they characterized DEG as "an ingredient found in antifreeze."

Perhaps out of ignorance, but I suspect that it was part of a carefully crafted "spin jog" to find something, anything, to make the product appear to be dangerous to justify its campaign to drive it off the market. The point is that the quantity they found is nowhere near a dangerous amount.

"Some authors suggest that minimum toxic dose is estimated at 0.14 mg/kg of body weight and lethal dose between 1 and 1.63 g/kg of body weight." Wikipedia

Let us assume that a ml. of ecigarette liquid is equivalent to a mg. (This isn't exactly true unless the substance is water, but close enough). So at 1%, the cartridge would contain 0.01 mg. of DEG. Now remember that minimally toxic is 0.14 mg. per kilogram of body weight.

1 pound = 0.45359237 kilograms So multiply your weight in pounds to determine your weight in kg.

Example: A 150 pound person weighs 68 kg. So to reach minimally toxic levels would require 9.52 mg of DEG (0.14 * 68). But since there is only 1/100 mg. of DEG in the 1 ml. cartridge, 952 cartridiges would be required to yield 9.52 mg. of DEG. At that quantity I'm thinking that the nicotine would get you long before the DEG had a chance to do so -- that's a quart of e-liquid.

If we take the lower figure for the lethal dose, 1 gram per kg., you would need 100 * 68 = 6800 ml., which is 1.78 gallons.

DEG is not known to bioaccumulate, so the quart or 1.78 gallons of e-liquid would need to be ingested in a single day. Unlikely to the point of impossible, I would say.

Notice I said ingested. Drinking e-liquid is pretty much unheard of. We all vaporize it. No lab has ever found DEG in the vapor.

Does that clarify the issue for you, Dave?

 

[Bill Godshall]

While it would be even better if 24 mg/ml e-cigarettes were use (instead of 16 mg/ml),
Chris Bullen's forthcoming clinical trial in NZ is likely to become a landmark study on e-cigarettes that (presuming it finds that e-cigarettes with nicotine are more effective than skin patches for quitting smoking, and especially if it also finds that e-cigarettes without nicotine are more effective than skin patches for quitting smoking) could immediately generate support for e-cigarettes among the many public health professionals/organizations/agencies and researchers who have remained silent/neutral on e-cigarettes, and could reverse the attitudes of many e-cigarette prohibitionists.

I can envision some/many e-cigarette prohibitionists and critics doing a 180 degree reversal of their views (as some of these folks would begin advocating e-cigarettes as smoking cessation aids if a clinical trial found them to be more effective than the patch).

One issue that the study's results would not resolve, however, would be the legal/regulatory policies for e-cigarette sales in various countries (as many new e-cigarette advocates would still argue that e-cigarettes should only be permitted to be marketed as "smoking cessation aids").

But here is the US, this study (coupled with a victory by SE/NJOY over FDA in the lawsuit) could become a enormous boost for e-cigarette sales and public approval.

 

[rothenbj]

We can only dream Bill. I'd just like to return to the days of anti-smoking. Seems tobacco and nicotine, unless pharma supplied, are just synonyms for smoke these days.

 

[Vocalek]

In the only other trial like this that I know of, the clinicians didn't have a clue about how to use the "mall" model e-cigs they selected so consequentially either did the test subjects.
We've all read about the disappointing experiences new users have before they first come here to ECF. I believe the conclusion of the test was the subjects weren't receiving enough nicotine therefore e-cigs are useless placebo devices.

Here it is. The famous Eissenberg test:
VCU researcher says electronic cigarettes don't deliver the nicotine they promise | Richmond Times-Dispatch

I would hope the clinicians get an e-cig user/specialist on their staff for this test.

Earlier this year, Spike and I met in Baltimore with both Dr. Eissenberg and Dr. Murray Laugesen of Health New Zealand to discuss this issue. Both now understand that the manufacturer's instructions to just "smoke it" like a regular cigarette is inadequate to achieve optimum results. A hopeful sign is that Dr. Eissenberg had already purchased a KR808 and was considering the concept of using newer products and providing instructions for use to achieve improved results.

I'm not sure what Dr. Bullen will be using as the hardware for the New Zealand tests. They may be sticking with the Ruyan product, but at least they now understand that instruction in proper use is just as necessary as instruction on proper use of the patch.

Yes, the patch can be used in ineffective ways, as I learned the hard way.