Chemical studies
Chemical studies fall into two broad categories: the first measuring the level of toxicants found in the emissions of the RRP and the quantification of what reductions are seen relative to that of a reference cigarette.[9,10,11] The second examines whether there are toxicants not found in cigarette smoke present in the emissions of the RRP.[12,13,14]
Toxicological studies
Toxicological studies can be:
- In silico: using computer models built on previous studies to assess the likely impact of any toxicants in RRP emissions[15]
- In vitro: using laboratory biological systems typically developed and validated for many different chemicals and mixtures to observe the impact of the emissions on cells cultured in the laboratory on biological changes to the cells[16,17,18]
- In vivo: which uses live animals and is not undertaken by BAT unless required to do so by regulators.[19] This looks at changes in organs or other biological material after exposure[20]
Clinical studies
Clinical studies ask people, typically regular adult smokers, to take part in studies where they attend clinics and provide samples of blood, urine or other biological samples. These are then used to measure biomarkers that either measure the amount of exposure to specific toxicants (biomarkers of exposure) or biological indicators of potential disease pathways (biomarkers of potential harm).[21,22] Other clinical studies look at nicotine uptake.[23,24]
The above focus is on the potential reduction of risk to a smoker as compared to continued smoking. To look at the reduction in harm to a population, other studies may be needed that look at what happens in terms of uptake, use and cessation when an RRP is commercially introduced.
Comparison to scientific frameworks for other product categories
The assessment of RRPs consists of some relatively unique challenges given the range of diseases associated with smoking. Assessment frameworks for other product categories provide some guidance. These are often focused on efficacy against a specific biological endpoint (such as blood pressure reduction) or disease (such as Alzheimer’s) and their evaluations are weighted to several phases of clinical study to determine what effect the new drug may have, and what side-effects might occur.[25] For functional foods, where additives may be applied that might have a biological benefit, again typically the biological endpoint (such as reduction in cholesterol levels) is reasonably closely defined.[26]
In each of these cases there are often regulators who set common approaches to what data is expected and how it will be judged. However, with RRPs there are, to date, few regulators who have set out an assessment framework. The U.S. Food and Drug Administration is an example of one that does have guidelines but no prescriptive approach.
