Link: Copy link
As stated in above articles, yesterday Nabi asserted to the world that "a Phase II clinical trial showed that 33 percent of 68 smokers inoculated with the company's NicVax vaccine were able to quit, as opposed to 9 percent who took a placebo." "The company did not say how long the smokers remained smoke-free. Nabi said it will release full Phase II clinical trial results at various scientific meetings in 2005."Nabi's press release intentionally omits some rather critical info:
- How long they quit - a week, a month, three months, six months?
- How quitting was defined - continuous nicotine cessation, point prevalence or some new creative definition?
- What behavioral interventions, counseling and/or support were used (if any), that had their own proven effectiveness and for which NicVax should not be allowed to claim credit?
- What are the results of the study's blinding assessment?
- What happened to the 66% who relapsed with the vaccine still inside them - has their daily smoking actually increased?What's most frightening is that we knew from the Phase I study that one-third of the nicotine smoked was not binding with the vaccine which we are told would have made the new molecule too large to pass through the blood brain barrier. In other words, we knew that a relapsed smoker would need to smoke roughly three times their old nicotine intake in order to have sufficient nicotine present in the brain to satisfy their old level of tolerance.As for blinding, we just learned that a $1.4 billion dollar NRT industry has likely been built entirely upon junk science in that the studies were not blind as claimed (see - http://whyquit.com/pr/051904.html). If true, why would a psychoactive chemical (nicotine) not also be psychoactive in vaccine studies?What are the odds that a substantial percentage of those assigned to receive the placebo in the NicVax studies remained blind to the fact that within 8 to 10 seconds of that first puff, a big big "aaahhh" sensation still arrived? Think about it. If they had joined the study in hopes of receiving this new miracle cure then what are the odds that they would have remained in the study once their expectations were dashed?It's a bit different from realizing that they were not experiencing their dopamine/adrenaline high, as in the NRT studies, but the drug is still psychoactive and researchers in both study areas must come to terms that relying upon frustrated expectations to produce victories is not science but more closely akin to outright fraud. Frankly, I'm beginning to believe that it may be impossible to use a placebo study format when dealing with any psychoactive chemical.Yes, thirty-three (33%) percent is a solid recovery rate but only when put in an honest and comparable context. I am light years away from having the recovery understanding of Joel in helping educate and a group of quitters yet I have yet to do a quit smoking clinic where at least 50% of participants were not still nicotine-free at two weeks. Although it has been some time science we've done an evaluation here at Freedom, our last two evals produced 38 and 39% six month continuous nicotine cessation rates for new members posting to the group at least once.We are not limited to just analyzing the active NicVax group (those receiving the vaccome either, as we know that roughly 10% of the placebo group should have successfully quit smoking for months if they had quit entirely on their own without any products, procedures or programs (see http://whyquit.com/whyquit/A_OTCPatch.html ). If the 9% in the Nabi study was for a period shorter than 6 months, or if counseling or group support was used as part of the study (both of which produce effectiveness in their own right) then it would seem to suggest that the placebo group may have sustained some degree of expectations defeat.The NicVax study press releases have generally been less than forthright, omitting substantial detail that would have allowed smokers to better evaluate the vaccine's merits, if any. It is my guess that a creative definition of quitting is being employed. Why? Well, the very foundation of a vaccine is that it inoculates the user against risks posed by a known harm. If a smoker now believes that they can smoke nicotine but that the nicotine will not enter their brain then shouldn't we expect some precentage to try and test or challenge the vaccine now and then?If so, wow do we come up with a quitting definition that will allow them to do so yet also allow the researchers to proclaim to the world that they quit? In NRT studies many researchers employed a quitting definition called "point prevalence" which only asked if the quitter had quit smoking during a particular time period, almost always the "point" in time -- and a stated number of days preceding -- when they were scheduled to have their next appointment at the study center for a quitting evaluation, an event which many studies paid participants financial compensation.As you know, the NRT studies actually invented their own creative definition of quitting. No longer was continuing to be hooked on nicotine a concern as up to 7% of gum users still dependent upon the gum at six month were declared to have successfully quit. Now that science was able to extract nicotine from the tobacco plant and put it into new and creative delivery devices, for the very first time quitting smoking no longer required the addict to quit nicotine too.What is troubling about past vaccine press releases is that they vastly over-inflated expectations. We each know that thousands of junkie minds are searching for a way to rationalize continued smoking. Those who attempt to convince them that a cure is just a few years away may actually be contributing to helping cost thousands their health and quality of life or, worse yet, life itself.Overall the vaccine researchers have been extremely irresponsible by not telling nicotine addicts not to wait on "possibilities" but to quit now and quit today. I get mad at myself for even thinking such thoughts but with certain stories I was left with a deep hurt upon feeling that they almost wanted smokers to delay cessation.After ten days to two weeks nicotine dependency recovery is almost entirely psychological. Pharmacology continues to all but ignore this reality. It would be fantastic if we could safely inoculate the world's children against nicotine addiction but don't hold your breath as it is not happening here.Still only one rule for me as well as you, no nicotine just one day at a time ... Never Take Another Puff! John (Gold x5)
TA-NIC 12 Month Results DisturbingThe below TA-NIC press release presents far more questions than answers. Here are a few of mine.1. If only one-third of nicotine smoked is able to pass the blood brain barrier once the "vaccine" is taken, what change in the number of cigarettes smoked per day has occurred to the 81% of 250 ug TA NIC users who reported relapse?2. Why would a study as scientic as this rely upon the honor system and "self reporting" by participants instead of conducting either expried carbon monoxide or blood or urine cotinine testing?3. What safety concerns caused Xenova to abandon the higher performance results from the 1000 ug group? Why not share them?4. Why did this press release fail to report the 50ug results?5. Has the Xenova Group dedicated sufficient resources toward long-term health effects follow-up for 100% of participants who've taken the "vaccine?"John
Xenova Group plcAnti-Smoking Vaccine TA-NICPreliminary 12 Month Clinical Trial ResultsSlough, UK, 3 March 2005 -
Reduced nicotine distribution from mother to fetal brain in rats vaccinated against nicotine: time course and influence of nicotine dosing regimen.
Biochemical Pharmacology, May 2005, 1;69(9): pages1385-1395.
Keyler DE, Dufek MB, Calvin AD, Bramwell TJ, LeSage MG, Raphael DE, Ross CA, Le CT, Pentel PR.
Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
Nicotine is a teratogen in rats and possibly in humans. Vaccination against nicotine is being studied as a possible treatment for nicotine dependence. The safety of maternal vaccination against nicotine during or prior to pregnancy is not known. In this study, female rats were vaccinated and then administered acute or chronic nicotine during pregnancy at doses simulating nicotine exposure in smokers.Maternal vaccination reduced nicotine distribution to both maternal brain (44-47%) and fetal brain (17-39%) for up to 25 min after a single maternal nicotine dose administered on gestational day (GD) 20, but had a smaller effect on nicotine distribution to brain after continuous nicotine infusion.Nicotine distribution to maternal or fetal brain after repeated nicotine bolus doses was reduced immediately following an individual dose in vaccinated rats, but the chronic accumulation of nicotine in fetal brain was not altered. Nicotine distribution to whole fetus, in contrast to fetal brain, was generally not altered by vaccination. Nicotine-specific antibody concentration in fetal serum was 10% that of maternal serum, and in fetal brain was <1% of maternal serum.Although nicotine transfer to the whole fetus was not reduced by vaccination, protein binding data suggest that nicotine-specific antibody transferred from mother to fetus served to bind nicotine in fetal serum, reduce the unbound nicotine concentration, and thereby reduce nicotine distribution to fetal brain. These data comment on the safety of vaccination against nicotine during pregnancy, and suggest that vaccination may reduce the distribution of nicotine to fetal brain under some nicotine dosing conditions.Source link:
PMID: 15826609 [PubMed - indexed for MEDLINE]
Keep in mind that there are at least two products here, NicVax and Ta Nic. The below article is about Ta Nic but both products seem to be working with the "higher dose" now. If true and producing just 16% smoking cessation at one year, that's 5 points less than varenicline (Chantix & Champix) at 21%.But if interested in making semi-valid comparisons among products that have never actually gone head to head, it's critical to keep an eye on a few additional factors: (1) participant expectations going into the study: what did the informed consent process and risk explanations prior to randomization or study recruiting prepare smokers to expect? (2) the ease or difficulty of determining group assignment: could you tell that some amout of smoked nicotine was not arriving in the brain, was the expected dopamine "aaah" sensation significantly smaller than normal, or if in the placebo group were your "aaahs" the same as before and you simply kept smoking and never quit; and (3) education, counseling, study contacts (brief quitter pep rallies) and group support, each having their own effectiveness, independent of the products being evaluated. How much study contact was there, when was it received, and at the time received, what percentage of each group was still present and fully participating in the study; if one group was then substantially larger than the other, did these independent cessation factors influence that group's overall success rate to a greater degree?The 26 provider counseling and/or support contacts in Pfizer's varenicline studies were very likely a record, the most ever in any quit smoking clinical trial. But I get the feeling that Ta Nic and Nic Vax were trying to stand more on their own with vastly less user contact. Still, as to blinding and expectations both the vaccines and varenicline present rather interesting issues.In NRT trials, most of the active group (those receiving replacement nicotine) could sense some level of easing off of the underlying current of withdrawal anxieties which was most stable with the patch but more noticible with oral and nasal nicotine, which was often administered in reaction to urges and craves. The more times the smoker had previously tried to quit and experienced the onset of full blown withdrawal the more they would have come to recognize their withdrawal syndrome.Varenicline is closer to the effects of nicotine, sitting upon and blocking the exact same acetylcholine receptors nicotine would have occupied, while causing 35 to 60% of the dopamine flow nicotine would have generated. After day 5 of using varenicline, when it gets up to therapeutic levels, some user emails to me have described smoking a cigarette as if smoking a carrot - it does absolutely nothing for you, as you don't get the normal and expected "aaah" sensation."This is why any suggestion that varenicline trials were "blind" and users could not correctly guess their group assignment is likely the biggest hoax smoking cessation has "yet" seen. The pharmaceutical industry was allowed to get away with NRT studies not being blind and appears to have become embolden by it.What Pfizer is not telling users is that some day soon they'll stop taking varenicline, the dopamine flow it generates will end, and that in clinical trials half who succeeded in using it for 12 weeks thereafter relapsed to smoking.But turning to blinding in Nic Vax and Ta Nic trials, the active vaccine group had a bit different experience than with NRT or varenicline. Instead of a somewhat diminished withdrawal syndrome or having up to 60% of the dopamine flow that nicotine provided (and 24 hours a day), in theory, vaccine users experience full-blown nicotine withdrawal, as if a member of the placebo group in an NRT or varenicline study, but with one big difference, what would normally have been relapse via smoking nicotine did not cause a dopamine "aaah" explosion in the brain 10 seconds later. How could an event such as this go unnoticed by any nicotine addict? It doesn't.As with varenicline I can't see how vaccine researchers can, with a straight face, proclaim these studies blind. As with varenicline, it is not a matter of "guessing" your study group assignment but actual knowledge that a foreign chemical is present in your body and that your normal smoking experience has been seriously altered.As for placebo group blinding, it too is somewhat unique in that some degree of motivation to quit smoking was to flow from cigarettes not providing their normal effect - relief from the onset of early withdrawal. Again, it's hard to believe that most placebo group members wouldn't have known their assignment.But knowing group assignment is not the end of the analysis as to whether or not the study's results are valid. The question becomes, did assignment awareness combine with expectations to influence the participant's actions? In other words, if you volunteered for a study after learning it involved testing of a new "medication" and that you could get a free 12 week supply of the "medication," how would you react to actual knowledge that you were in fact getting it, or that you were not getting it?If assigned to the placebo group and either still smoking or enduring full blown nicotine withdrawal, would you have stuck around for 12 weeks, 6 months or a year and allowed researchers to toy with you? In the active group, if your expectations had been met and you could actually feel the medication producing a totally new or somewhat different cessation experience, would such knowledge have given you new hopes, extra resolve and had you staying around longer than you otherwise would have, to try even harder and actually return for the study's next scheduled visit?My reason for writing the above is to try and aid you in seeing that things are not always as represented, that should you feel your resolve weakening, that all these news articles and advertisements about new magic cures will hopefully not play even a minor role in inviting relapse. For what we do know is that in all real world quitting method surveys these products have yet to perform better than uneducated and unsupported "one your own" quitting.We've each now arrested our dependency and there is absolutely no guarantee that any of us could ever come this far and heal this much again. There's only one way to stay on this side of the bars while keeping our now arrested dependency on the other ... no nicotine today, Never Take Another Puff, Dip or Chew!John (Gold x8)
Online story source link
April 30, 2008
An anti-nicotine vaccine will be tested on 400 people in the Nordic countries over the next year aimed at helping smokers kick the habit, the Karolinska Institute in Sweden said on Monday.
"A Swedish vaccine against nicotine will be tested on 400 people in three Nordic countries," the institute said in a statement.
Lena Wikingsson, head of Independent Pharmaceutica, which is running the experiment, told Swedish daily Svenska Dagbladet that people taking part in the study -- heavy smokers who would like to quit -- would be given counselling before they stop smoking and would be given a drug to help them quit.
They will then receive one injection a month for four months. Half of the participants will be given the vaccine and the other half a placebo.
They will be followed for a year to see whether they begin to smoke again, Wikingsson said.
The vaccine, called Niccine, has been developed over the course of 10 years by Swedish researchers at the Karolinska Institute, under the guidance of professor Torgny Svensson who founded Independent Pharmaceutica.
Niccine is supposed to help the immune system build antibodies against nicotine.
If a person who has taken the vaccine smokes a cigarette, the antibodies jump into action, latching onto the incoming nicotine and preventing it from reaching the reward system in the brain -- thereby stopping the smoker from getting the "kick" that makes smoking addictive.
One problem in developing nicotine vaccines is that the immune system doesn't react to normal nicotine.
In order to activate the immune system, the nicotine in the vaccine needs to be latched onto a "carrier" or "host" that stimulates the immune system to create as many antibodies as possible.
For the vaccine to be successful, a large number of antibodies must be created, and the carrier component is therefore the key part of Niccine, Wikingsson said.
"There are several possible applications if the vaccine proves to be effective," Wikingsson told Svenska Dagbladet.