E-Cigarette Clinical Trials

[MattZuke]

There is plenty of good data on varenicline

And just a small pile of dead people.

If you are going to quote 200 suicides you then have to divide it by the number of users, and the baseline suicide rate among smokers. But check out this paper...based on a large sample (80,000), includes people with mental health problems, andy compares with the right comparison groups...other people trying to quit smoking.

Yes, this is the world of tobacco Control, where 200% increase in self-harm above baseline isn't statistically reliant for Chantix suicides, but a 25% increase above baseline for lung cancer from passive smoking (1:100,000/1:80,000) is.

I might be a little out of my depth, but I can say with reasonable certainty that a 2 fold increase represents a statistical reliant relationship, and 25% does not. I think I'll stick with my e-cigs, thanks.

 

[Ande]

JF, I want to be clear here-

Most of us are professionals in other fields, who have self-educated ourselves, out of self interest, in a lot of areas related to smoking cessation, medical testing, epidemiology, electronics, and a lot more.

I suspect that you're an academic with rather more formal background (and more time dedicated to background reading over the years) than I. (I could google around and figure out who you are, I guess, but for the purposes of this conversation it doesn't seem necessary.)

I entered this field of debate less than a year ago. When you're playing catch up, as I am, one thing you do is to try to find out which sources you can trust. (Cause honestly, it takes me a long time to read original research, my analysis and troubleshooting is slow, and once it's done still has limited credibility with others. My academic background is not in this area.) So I do try to find, trust, and read secondary sources more than original research.

To do this and come to a realiable conclusion, one has to read a LOT of secondary sources, of course, and always be open to the possibility that there are errors or biases within their work. But as regards Chantix: there's a lot of negatives around- Here are a coupleThe Rest of the Story: Tobacco News Analysis and Commentary

http://www.cmaj.ca/content/early/2011/07/04/cmaj.110218.full.pdf

Another thing you learn when you're trying to do your research relatively quickly (most of us have full-time, unrelated jobs): When someone acts like they're lying, they often are.

There are numerous reasons to question the side-effect reporting that's gone on with Chantix.

There was also the peculiar FDA statement about their findings that Chantix does not cause increase in hospital psychiatric admissions. Since the psychiatric side effects that are most often worryingly correlated with Chantix (rightly or wrongly) would not necessarily lead to hospital admission, this sort of reeks of weasel wording, doesn't it? People aren't hospitalized for violent attacks on others, usually. Virtually never hospitalized for having committed suicide. Rarely, in this day and age of HMOs, high costs, and private insurance, hospitalized for depression or suicidal thoughts.

So the fact that Chantix doesn't lead to psychiatric hospitalization is sort of meaningless...and makes one wonder why they didn't use other, more direct, markers.


Best,
Ande

 

[MattZuke]

Rolygate...when you spend a lot of time on an e-cig forum....by definition populated largely by people who didnt quit smoking using other treatments, it is not surprising that you form a negative view.

Respectfully, this is a bit of an ad hominem, and a bit of an attempt to poison the well.

Maybe you should actually ASK how many treatments we've tried first before resorting to e-cigarettes. There is actually research on this subject, someone else linked to it.

I can say for certain that I have a negative opinion because the method in which NRPs are deployed, and the dishonesty of tobacco control in regards to relative risks of alternative products.

Its actually a bit ironic, given that e-cigs basically are NRT

This is true, though more accurately defined as a CRP. But accepting it as an NRP you must accept the existing research on the effectiveness on NRPs, quite pathetic for 12 week programs, roughly what is it, 25% with counseling. Yet, e-cigarettes seem to equal NRP+counseling, just without the counseling, among users not intending to quit.

But it's not ironic at all. It's been discussed for years how an NRP that is inhaled would "cool". But the FDA wouldn't let Pfizer do it.

The evidence from hundreds of such studies is crystal clear for NRT etc

Yeah, for 12 week programs sub 3% cessation after 20 months. 8-11 quit attempts required, each time relapse to a deadly product. CDC observing a plateau in cessation rates in 2008 as cited by the AHA in 2010 who decided not to suggest Snus as it's not "without risks".

I think that sums it up

it would not be the least bit surprising if in a few years they are owned by pharma and/or tobacco

Not likely. The patent holder actually refused offers from big tobacco, and big pharma wasn't interested since the FDA stance was clear on inhaled products. I can say with modest certainty China loves the present status quo. But honestly it wouldn't matter that much to me if big tobacco or big pharma took over. So long as it makes the cigarette industry less viable, wonderful.

You really don't seem to grasp how simple the technology is. It really is just a coil, in a tube, with some fill material, and some liquid attached to a battery, typically with some control circuitry. A 5th grader should make with with moderate ease with a more simple switch.

I really hope they work better than what has gone before

Well, if nothing else, it contributes to the sum of human knowledge, and that's never a loss. And I don't expect that e-cigarettes will work for everyone. I'm actually quite supportive of the market place having many options available. We can't ban cigarettes, but we can make the cigarette the least attractive choice.

 

[MattZuke]

You do have to keep in mind that we are enthusiasts. Many of your questions are best addressed to physicians and scientists.

Here's the link again to
Electronic Cigarette Interview with Dr Joel Nitzkin - Chair of the Tobacco Control Task Force for the American Association of Public Health Physicians

New Zealand LTD sponsored by Ruyan, Boston University of Public Health, and University of Catania.

LPD Laboratory Services of Blackburn MicroTech Solutions LTD, Bontek Compliance Laboratory Shenzen, China, and Health New Zealand LTD sponsored by Ruyan

In case you missed it, HealthNZ completed, a Randomised Cross-Over Trial, sponsored by Ruyan, performed at the University of Auckland. Here are the details.

In case you complain it wasn't a big trial, Ruyan is a company with 216 employees, and their flag ship product is the V8 (801 series), V10 (dunno), e-gar/Vegas/Ecigar, and e-pipe.

Frankly, I've only "heard" of the 801 (pen style) series, can't buy a v10 anywhere.

Ruyan as of 2010 pulled out of the US directly, and markets though Prime Time, who doesn't seem to be marketing their product. Prime Time does single "little cigars", which I found useful my first month on e-cigs.

 

[rolygate]

Rolygate...when you spend a lot of time on an e-cig forum....by definition populated largely by people who didn't quit smoking using other treatments, it is not surprising that you form a negative view. ...............

Yes, I can't really argue with that. Being outside the profession, the large number of seemingly-proven accusations about the ineffectiveness of NRTs, and the dangers of Chantix, together with the exposure to a fairly narrow viewpoint here, have admittedly coloured my opinion. All I can do is look at the opinions of the various professors of medicine who have commented on these issues, and note they more or less accord with local opinion here. It may of course be that Nitzkin, Siegel, Rodu, Bergen et al are completely wrong, but perhaps the medics could come to some sort of an agreement first before chastising the ignorant masses

(Only joking.)

It seems hard to agree with medical professionals who make statements such as "NRTs are safe and effective" since, purely as an outsider of course, it appears to me that there is plenty of evidence that such a statement is entirely false in every respect. There may well be treatments that are safe, but there seems to be an overwhelming amount of evidence they don't work. There may well be treatments that are (marginally) effective, but those treatments do not appear, to an outsider, to be safe. And in comparison to Harm Reduction choices, they seem worse than useless. The only Harm Reduction option for which we have long-term population-level data - Snus in Sweden - appears to be a vastly superior choice in every possible respect. And since the smoking-related death rate in Sweden is the lowest in the developed world by some degree, it does appear that the overwhelming majority of the 200-odd trials of Snus in Sweden that conclude a Snus user has about the same risk as a non-smoker are probably somewhere near the mark. In theory, e-cigarettes could be safer than Snus. I am personally not entirely optimistic about that because the industry has, apart from certain notable examples such as those manufacturers who actually own a GC-MS machine, demonstrated a cavalier attitude to QC; but even so, e-cigs will likely prove somewhere close.

.............. It's actually a bit ironic, given that e-cigs basically are NRT..........

I would probably argue with that. My personal view is that e-cigarettes are a way to keep smoking without the obvious harm associated with tobacco cigarettes. In that way, they are a Harm Reduction choice, which by definition means they are an alternative with less perceived health or safety issues, and which are designed and sold as, and purchased and used as, a permanent replacement. The whole idea behind Harm Reduction is that use is not ceased.

NRTs are designed to be used and then ceased, as they are a treatment, not a permanent option. There is a difference between alcohol treatment leading to cessation, and low-alcohol beer, which is a Harm Reduction consumer choice designed to reduce risk in one way or another, and is not designed in any way to be ceased. There is a simple way to distinguish between treatment and Harm Reduction: will you still be using it in ten years? When the answer is an unequivocal yes, it's Harm Reduction.

Harm Management, or the medical use of harm reduction, is yet another area of discussion.

 

[DC2]

I would probably argue with that. My personal view is that e-cigarettes are a way to keep smoking without the obvious harm associated with tobacco cigarettes. In that way, they are a Harm Reduction choice, which by definition means they are an alternative with less perceived health or safety issues, and which are designed and sold as, and purchased and used as, a permanent replacement. The whole idea behind Harm Reduction is that use is not ceased.

While rolygate has legal issues to contend with when making statements, I do not.

The fact is you can use them as an ALTERNATIVE to smoking deaths sticks, which makes them a harm reduction tool.
Or you can use them in similar ways that NRT products are used... to stop smoking.

And heck, if you want you can even use them to stop using nicotine altogether.
Just drop the nicotine strength of your juice down in whatever manner and timeframe YOU see fit.

All other methods are a joke compared to electronic cigarettes.
And time will bear witness to that fact.

 

[Traver]

While rolygate has legal issues to contend with when making statements, I do not.

The fact is you can use them as an ALTERNATIVE to smoking deaths sticks, which makes them a harm reduction tool.
Or you can use them in similar ways that NRT products are used... to stop smoking.

And heck, if you want you can even use them to stop using nicotine altogether.
Just drop the nicotine strength of your juice down in whatever manner and timeframe YOU see fit.

All other methods are a joke compared to electronic cigarettes.
And time will bear witness to that fact.

Right on.

Still have to convince the rest of the public.

 

[DC2]

Still have to convince the rest of the public.

I'm working on it...


http://www.e-cigarette-forum.com/fo...m/242515-newish-member-contest-awareness.html

 

[MattZuke]

Also the whole issue of expecting small companies to fund LARGE SCALE clinical trials for a recreational products is a bit unreasonable. It's quite remarkable that Ruyan all they did for a recreational product. Njoy and Smoking Everywhere fought the legal battle with the FDA. Meanwhile the 22nd Century Group got awarded 2.5million to their phase 3 clinical trial for low nicotine cigarettes as a cessation device. They are with in the same size class as Ruyan (Dragonite Int).

This is where Tobacco Control "should" come in. This is EXACTLY the sort of thing the Master's Settlement should be used for, even if human trials must be conducted overseas.

 

[rolygate]

There is a split, or a number of splits, between vapers on how they would 'define' what they do. Leaving aside that all this is pointless anyway (as there are several million people doing it, it probably works), the group who believe that e-cigarettes are to be used for 8 or 12 weeks and then quit is probably the smallest of all.

And that's not just because they have all quit and gone

This is the classic definition of an NRT; but if it is becoming a fluid concept that can encompass just about anything, well, then I guess adding water to my rum makes it a medical treatment.

 

[Ande]

Rum is, in fact, a medical treatment anyway. Cures all sorts of things...

;-)

Harm reduction, on the other hand, isn't a medical treatment. Just a way of doing what I enjoy with reduced risks.

I used to ride motorbikes a lot- a moderately risky behaviour. I used to manage that risk by using safety gear, biking sober, knowing the roads, reading the weather reports...you know the stuff.

I also use tobacco/nicotine- another behaviour that carries risks. (We can argue about how much, but it ISN'T risk free.) I manage those risks by choosing lower risk products (my ecigs, a little snus, maybe a very occasional fine cigar) and avoiding higher risk ones (Daily cigarette smoking, mostly.)

That's the essence of harm reduction. It's not (for me) "quitting." Just a way to get what I want and do what I want with the least risk possible.

Best,
Ande

 

[rolygate]

Thinking about it, I suppose that people who want to use e-cigs in NRT mode - switch for a short time then quit - will become a much larger group in the future, as doctors and clinics start prescribing them as NRTs. As soon as one model gets a pharmaceutical license, that side of it will explode. This is expected some time in 2012, although it will presumably just be limited to the UK at first, when Intellicig get their MA.

I reckon that a portion of them, though, will 'forget' to quit (and probably upgrade). Similar to using Snus as an NRT, perhaps.

 

[Ande]

I like the idea of doctor's being aware of the ecig's utility as an NRT. But if people forget to quit, and then upgrade...where's the harm? In the past, people finished the recommended time for prescription NRTs and then...started smoking again (the vast majority.)

Staying on the NRT, any NRT, is better for your health. Staying on the ecig is better for your health AND more fun.

But one thing I already don't enjoy is all the comments I get about the ecig- "So when are you going to stop using it?"

If it starts getting medical recommendations for short term use, that's going to be even more prevalent.


Best,
Ande

 

[MattZuke]

If it starts getting medical recommendations for short term use, that's going to be even more prevalent.

No one is stopping anyone from actually releasing an NRP version. Heck, HealthNZ is already proposing it even though they state clearly, " anecdotally help many smokers quit". Their program is 12 months.

 

[Thulium]

Referring to electronic cigarettes as a "Nicotine Replacement Therapy" or (marginally more accurately) "Electronic Nicotine Delivery System" reflects a failure to understand the intended and actual uses of the product. Although battery powered vaporizers shaped like cigarettes CAN be used to deliver a small percentage pharmaceutical-grade nicotine as part of a plan to stop smoking, they can also be used to deliver whole tobacco alkaloids, or with minute quantities of other ingredients, or without any active ingredients whatsoever. They can only be called "Therapy" if they are marketed with a therapeutic plan or administered under a therapist's supervision, and they are only nicotine delivery systems if the user chooses to use them in that way.

The trouble with the phrase "safe and effective" is that it is incomplete out of the original context of the FDA mandate that drugs, devices and combination products undergo premarket clinical trials to prove that they are safe and effective for their intended use. Leaving out the bit about "intended use" is the bugaboo here. If you're a hammer, the whole world looks like nails...If you're a doctor, everything looks like a therapy.... If you are a smoker, however, battery powered fog machines look like cigarettes, and are not intended to be any more "therapeutic" than sugar-free soft drinks are intended to be health food.

 

[MattZuke]

They can only be called "Therapy" if they are marketed with a therapeutic plan or administered under a therapist's supervision, and they are only nicotine delivery systems if the user chooses to use them in that way.

Yes, no one is stopping you, or anyone, from taking the basic design, modifying it to fit a therapeutic application. At present FDA guidelines would prohibit this, no Institutional Review Boards would approve such a trial, so research would have to be done overseas until such time as the FDA adjusts their policy. While clinical trials are specific to the Ruyan V8 (penstyle ~320mAh), something Ego sized would be more practical to add on data logging.

1) Puff duration
2) number of puffs
3) Power consumption

Maybe offer 2 power levels per dose. 3 Nicotine levels, two weeks at each respective level, max puff cutoff.
Not that I accept the precept of 12 week programs. Add software to read the data to report to your clination and your social networking site.

To keep costs down, you can release the hardware design under Creative Commons or GNU design, that would allow 3rd party manufacture, as with GATech designing the E-power/No-Ego . They produce your 1000+ units, they tweak them for more recreational use for general sale. Better still, just use the existing 14650 E-power, use the smaller 900 or 650mAh battery, and add on user tracking and LED display for puff count.

The end result isn't just a CRP version of an e-cig that is actually viable for conventional clinical trials, but an entire enterprise based in part on VERY low cost off the shelf hardware, a therapeutic plan, and the potential for counseling services, web based or otherwise.

 

[sandybeach]

This is really a fascinating thread. Has anyone done research on the effects of second-hand vape, what we exhale?

 

[voiceinthecosmos]

It's simply impossible to do a double blind study comparing cigarettes to vaping as a double blind study requires both the researchers and the participants NOT to know which they are using/receiving. Therefore, that type of study is impossible. However, a double blind study could be done with participants vaping various amounts (even zero) nicotine.

The problem with phenomenology (the study of a phenomenon from the viewpoint of the subjects) (such as using questionnaires to determine such things as whether or not vaping helps people stop smoking) is that while it is helpful to show that vaping does help people stop smoking who could not stop by any other means, it is simply not enough. We need real, scientifically valid evidence of (as mentioned above) exhaled vapor not harming bystanders by studying EXACTLY what is exhaled. We also need evidence of exactly what is INHALED (not just what the ingredients are) when vaping (although, this TOO is helpful).

Without valid scientific evidence of both qualitative and quantitative, peer reviewed data, we simply will not have enough ammunition to combat our opponents.

I think one of the problems is that too many of us are focusing on the fact that studies have been done. Yes, studies have been done, but in order for the scientific community to accept data, very specific guidelines must be followed. All too often, the studies that are done are simply too easy for our opponents to dismiss since they do not adhere strictly to the established guidelines. One thing that everyone needs to realize is that these studies must be repeatable by design. And being repeatable, they must then be repeated over and over with similar results before those results will be accepted. That's just the nature of science. We need more studies and studies that cover the issues that bring fear into the hearts of those who are afraid, yes afraid, of "e-cigarettes." To study qualitative phenomena such as whether or not vaping helps people to stop smoking is only a TINY beginning. We need to prove to them that our vaping is not harming them. Really, that is the issue that has most average people backing our opponents. They are simply terrified that we are harming them.

I know that the "rules" in the scientific community may be frustrating to many in the vaping community, but we cannot simply throw out established guidelines just because we don't like them. We need to play within the rules and realize that it takes money to play within these rules. Alone, we cannot do much, but collectively, we can do quite a bit. Granted, the FDA is not playing by the rules, but if we do play by the rules, and if we manage to find a way to fund multiple, legitimate, scientifically valid studies, eventually we will have enough data to have our data accepted.

 

[Deblym]

I am very very interested in this entire thread, I just wanted to thank all of you for having this discussion here, where anyone can read and better understand the issues! And just an anecdotal comment. I work in an in patient mental health facility, all be it a small one, and I don't remember anyone coming in with suicidal/homicidal thoughts d/t champix..... But huge portion of people who may have these problems won't seek help because of the stigma of mental illness.

Another interesting thing is that smoking by the patients is no longer allowed. When they discussed starting this there was plenty of conversation around depression, schizophrenia, and other mental illnesses are often medicated by the suferer with nicotine. Just based on my 17 years in the field, my instincts tell me here is a large amount of benefit to the use of nicotine, and it borders on cruel to take this away....yes we replace the pure nicotine...but there may be other components we're missing ie:wta's.

Sorry if this is slightly off topic, I just think there's so much potential here and I want it all proven, via studies, yesterday please

 

[rolygate]

..... And just an anecdotal comment. I work in an in patient mental health facility, all be it a small one, and I don't remember anyone coming in with suicidal/homicidal thoughts d/t champix..... But huge portion of people who may have these problems won't seek help because of the stigma of mental illness.

That is interesting. The FDA did use this as a reason to deny the psychotic effects of Chantix, claiming that since few patients ended up at in-patient care due to varenicline, it had no provable side-effects of that nature.

It is a good argument - and of course there were many counter-arguments presented. I tend to prefer the amusing ones, as we need some light relief:

- Those critically affected had already killed themselves, or suffered death-by-cop after killing others

- As varenicline use is shown (two clinical trials) to incur a 1 in 30 risk of a cardiac event, and this is a far higher rate than the suspected incidence of psychosis, perhaps they all died from a heart attack before they could be admitted to a care unit.

Well, it never hurts to laugh...