Real-world evidence comes from across the globe in settings with real-world context, usually from observational studies, trial data, claims, and electronic records databases, surveys, public health records, and more. This kind of evidence is often used to support decision-making in health care, alongside toxicological and clinical data. Such evidence can include post-marketing studies of the safety and efficacy of drugs. And it can also be used to support the approval of new medical uses for a drug.
Let’s compare real-world evidence to a typical clinical study. Clinical studies are an important part of our assessment program, where we observe whether there are health benefits in adult smokers who switch completely from cigarettes to our smoke-free products. Participants know when they’re in a clinical study. They often are required to follow certain guidelines, visit the clinic often to provide biological samples, or may even spend consecutive days and nights there. Participants may use the products differently in a study than they would in their normal lives, simply because they’re more aware of their own choices, or want to follow the guidelines of the study.
Real-world evidence, on the other hand, comes from records and data that are created as part of peoples’ normal lives for the most part. In the examples we describe below, real-world data sources can include market data and sales volumes to understand shifts in which products are being used.
They can also include insurance claims or hospital data that are gathered and anonymized for use in research or policymaking. Sometimes, clinical studies can even be designed in a way that allows them to generate real-world evidence without significantly impacting the participants’ behaviors.
Laboratory studies and heavily controlled experiments yield reliable answers to precise scientific questions. Real-world evidence, on the other hand, gives scientists a different angle on how things work in more complex and realistic situations. Both types of data are important and complementary aspects of our product assessment approach and have an important place in tobacco product research overall.
We introduced our leading heated tobacco product (HTP) on the Japanese market in selected cities in 2014, gradually growing to nationwide launch in 2016. Before this nationwide launch, total tobacco sales in Japan declined at a rate of 1.8% on average between 2011 and 2015. After the launch of our HTP in Japan, total tobacco sales continued to follow that same trend. But notably, the sale of cigarettes declined more sharply after the nationwide launch of our HTP: 9.5% average annual decline from 2015 to 2018.
An independent research group from the American Cancer Society also analyzed cigarette sales data from retailers to examine the cause of the significant decline in cigarette sales based on sales data from 2014 to 2018. Besides the launch of our HTP, factors such as pricing, more strict regulations, the availability of competing HTPs, or even just chance, were investigated as potential causes. Researchers determined those factors were unlikely to be main causes of the decline in cigarette sales.
The authors concluded that the introduction of our HTP was the most likely explanation for the decline in cigarette sales in Japan. And further, the downward trend of combined tobacco sales continued even after the launch of our HTP. This data indicates that the launch of this product did not lead to an increase in overall tobacco consumption, and that many smokers, who would have otherwise continued to smoke cigarettes, have switched to our HTP.
Now, a reduction in cigarette sales is not direct evidence of harm reduction in a population. This is why we investigated whether the introduction of HTPs was associated with changes in indicators of smoking-related diseases at the population level.
We obtained hospitalization rates for selected smoking-related endpoints: chronic obstructive pulmonary disease (COPD), COPD exacerbations and ischemic heart disease (IHD). This data came from two databases: Medical Data Vision (MDV) and Japan Medical Data Center (JMDC). For these endpoints, we compared rates of hospitalizations before and after the introduction of HTPs in Japan. We observed that hospitalization rates started decreasing shortly after the launch. Those decreases so far are modest, but measurable. This makes sense for the population data, considering that it can take years for the excess risk for these endpoints to decrease when an individual quits smoking. This type of real-world data should, therefore, be followed up in the future and reproduced in other countries.
COPD hospitalizations rate over time in Japan, data acquired from JMDC database. The increasing trend of COPD hospitalizations changed to a downward trend in 2017, shortly after the introduction of HTPs to Japan. Note that there are many limitations to this type of research, and it is important to remember that the results do not indicate a causal relationship.
The real-world evidence from Japan regarding COPD is corroborated by real-world data from a clinical study led by the Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), at the Catania University in Italy.
In 2017, the CoEHAR recruited COPD patients and followed them for three years as they went about their normal life. During the three-year study period, the patients visited the clinic three times, where their smoking and health status was checked. Once the study was completed, the patients’ medical records were extracted and reviewed. Based on the patients’ smoking status, two groups of patients were formed: 19 who had started using HTPs and significantly decreased or completely stopped their consumption of conventional cigarettes; and another 19 patients who had continued smoking only cigarettes, with no HTP use at all.
The comparison of the health parameters between the two groups revealed key findings, as explained by Professor R. Polosa, founder of the CoEHAR:
Further, the overall health status, respiratory symptoms, quality of life, and physical activity consistently improved over the three-year study period in the group of participants who were using HTPs, while they did not improve among those participants that continued smoking cigarettes. These findings are particularly meaningful because the health effects were monitored in patients in their real-life conditions, where they are exposed to daily life environmental factors.
"HTPs use decreased the number of acute exacerbations of COPD by more than 40%."
- Professor R. Polosa, Founder of the CoEHAR
When it comes to health decision-making, several lines of evidence come into play and complement each other: evidence from controlled scientific experiments answers precise, pre-defined questions, while evidence collected from the real-world helps understand health effects of a product in real-life settings. So far, real-world evidence has indicated that introducing HTPs can have a beneficial impact. Launching HTPs was not only the most likely cause for a reduction in cigarette sales, but it was also related to a decrease in hospitalization rates due to COPD and IHD.
We will continue to gather and evaluate real-world data, in particular, epidemiological data from long-term follow-up studies, that include information on other variables that might impact the risk of developing smoking-related diseases as well as lifestyle or other environmental factors (e.g., diet, pollution). The totality of the evidence on our smoke-free products to date, including both experimental and real-life data, points in the direction of harm reduction.
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