A major tobacco company seems serious about the development of a low-risk cigarette, sponsoring of clinical trials with prototypes containing reduced levels of toxic components.
London-based British American Tobacco said on Monday that it will begin a 6-month controlled trial “reduced toxicant” cigarettes, in which the effects on the respiratory function will be measured in current smokers.
It follows an earlier, shorter study published last month, which evaluated prototypes for effects on blood bio-markers of exposure to toxicant substances.
The prototypes described in this study contained tars and nicotine at level like conventional cigarettes, but with a reduced content of a variety of nitrosamines, aromatic amines, carbonyls, and polycyclic aromatic hydrocarbons.
The new study, the protocol for which was published in Biomed Central Public Health, won’t come to satisfying FDA requirements for marketing reduced-risk cigarettes. The agency said in a guidance document published last year that it would need studies that assess multiple aspects of the overall impact of these products on public health, in addition to the direct impact on the health of the users of the product. They are:
• Exposure to second-hand smoke on the product
• The impact on the overall user habits, such as smoking frequency and intensity of smoking inhalation
• The impact on the consumption of users of other tobacco products
• The likelihood that users will comply with any special instructions for using the
• The likelihood that users will later go on to other, more high-risk tobacco products
• Is the product availability will affect non-smokers or ex-smokers to start smoking or discourage current smokers from quitting tobacco completely
• Whether marketing a product may be affected by “the understanding and perception of consumers”
The regulations allow companies to market cigarettes as simply reducing exposure to harmful chemicals, avoiding the need to demonstrate improved clinical outcomes with respect to the health of users with respect to smoke regular cigarettes.
But the company must still show that the reduction of the impact of “a sufficient degree of probability produce are measurable and significant reduction in morbidity and mortality,” when evaluated in later studies.
These requirements are set out in the legislation in 2009 that gave the FDA authority to regulate tobacco products. This law prohibited the agency from banning cigarettes in whole or in order that the nicotine levels to be reduced to zero. But it did not authorize the FDA to require proof of any allegation that the new tobacco product is less risk to health than the existing ones.
The agency has since established two ways for new tobacco products to enter the market. One allows manufacturers to simply certify that the product is “substantially equivalent” to those that have already been sold. This route was opened last month with a formal FDA clearance of two Newport brand products sold by Lorillard Tobacco, though the agency said that thousands of others have been introduced with preliminary applications.
The second way is akin to FDA premarket approval process for medical equipment that requires rigorous clinical trials. Any tobacco products for which applications for reduced health risks are made have to be approved through this process. No applications have yet been received, agency officials said.
But BAT – producer Kent, Lucky Strike, Pall Mall cigarettes and brands, as well as cigars, loose tobacco and smokeless tobacco products – seems to be prepared to meet the stringent requirements of the FDA. New clinical study, which will be held in Germany, will enroll 260 healthy volunteers, including 140 smokers, 60 former smokers and 60 never-smokers.
Smokers will be randomized to usual, but unlabeled Lucky Silver Strike cigarettes or reduced toxicant product and told to smoke free for 6 months. Blood and urine samples will be collected for analysis of systemic exposure to toxicants, and measures the level of serum creatinine and creatinine in urine.
Cigarettes will come with filters that investigators will collect to measure the frequency of smoking. Participants will keep diaries.
In addition, the spirometry will be performed at baseline and after 6 months for measurement of forced expiratory flow, forced expiratory volume in one second, and peak expiratory flow rate.
Nonsmokers will not use cigarettes in the study, but will undergo spirometry and biomarker studies for comparison purposes.
Stanton Glantz, MD, of the University of California at San Francisco and a prominent anti-tobacco campaigner, said MedPage Today in an e-mail that the study was published neglect an important category of direct health consequences.
“It does not consider important cardiovascular effects that may be both short-term and long-term risk for development of heart disease, in particular, changes in the platelets and vascular endothelial function,” said Glanz.
He also questioned the decision to match the levels of tar in reduced toxicant prototype to those in the conventional product.
“Tar measures many bad things in cigarette smoke and such correspondence may mask biologically significant changes,” he said.