An Ohio State center provides rapid, robust science to support the FDA’s new role in tobacco regulation
BY KENDALL POWELL
In September 2013, a joint program between the Food and Drug Administration (FDA), the National Institutes of Health and the National Cancer Institute awarded The Ohio State University a five-year, $18.7 million grant (CA180908) to establish the Center of Excellence in Regulatory Tobacco Science (CERTS). The center investigates the diverse and changing types of tobacco products on the market and how adolescent and adults choose to use those products. The researchers will study use of the full spectrum of tobacco products, including cigarettes, smokeless tobacco, cigars and electronic cigarettes.
Ohio State’s CERTS is one of 14 national centers funded by the Tobacco Centers of Regulatory Science. The FDA will provide more than $273 million for research over five years, with the National Institutes of Health providing administrative oversight and support. CERTS will include 18 researchers from Ohio State’s Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). The researchers represent six of Ohio State’s colleges.
“The FDA has an unprecedented opportunity to regulate tobacco products in the United States, and they want to make those decisions based on science—not hunches, social beliefs or politics,” says Peter Shields, MD, deputy director of the OSUCCC – James and co-principal investigator for CERTS. “There are few opportunities where scientists can so directly and quickly influence national policies and government decision making.”
Passage of the 2009 Family Smoking Prevention and Tobacco Control Act gave the FDA new authority to regulate the manufacture, marketing and distribution of tobacco products to protect public health. However, for the FDA to set policies that are scientifically sound and defensible in court, it needs solid data. “The research that CERTS is doing will set a foundation for policy that significantly affects how Americans use tobacco,” Shields says, noting that the center adds to many ongoing tobacco research efforts at Ohio State, including clinical trials that also target regulatory science.
Currently, about 20 percent of the United States population smokes, and tobacco use is the leading cause of preventable death, killing more than 440,000 people yearly, according to the Centers for Disease Control and Prevention. The tobacco-related causes of death include lung cancer, kidney cancer, bladder cancer, heart disease, atherosclerosis, stroke, pneumonia, bronchitis and emphysema.
“Our goal is to reduce the significant morbidity and mortality associated with tobacco use,” says Cathy Backinger, MPH, PhD, deputy director for Research in the Office of Science at the FDA’s Center for Tobacco Products.
“The law mandates that we use a public-health standard when we make a decision, looking not at the individual level but at the impact on the population as a whole.”
Investigating tobacco use at the population level requires a range of expertise. The center will conduct regulatory science—research directed at particular problems the FDA needs and requests.
Why and how people use particular tobacco products, and how products foster tobacco use and hinder cessation are complex problems. “They include questions of toxicity, product design and risk perception,” Shields says. “It’s work that requires transdisciplinary research.” The felds involved can include epidemiology, chemistry, genetics, marketing, toxicology, policy, biostatistics, and addiction and behavior research.
Consequently, the Ohio State center includes OSUCCC – James researchers for Ohio State’s colleges of medicine, nursing, public health, business, law, and arts and sciences.
The FDA is particularly interested in learning how dual- and poly-use of tobacco products affects public health, an overarching theme for three of the four CERTS projects. “The tobacco industry has creatively introduced a number of different types of products,” says CERTS co-principal investigator Mary Ellen Wewers, PhD, MPH, professor of Health Behavior and Health Promotion in the College of Public Health at Ohio State. “We’re interested in understanding who might be attracted to them and how these products are introduced and marketed to adolescents and adults.”
CERTS studies will address questions about people who combine the use of combustible products such as cigarettes, cigars and cigarillos with the use of smokeless tobacco products, including e-cigarettes, chewing tobacco, snuff and snus, a relatively new spitless tobacco product in the American market.
Backinger says the FDA wants to learn whether people who use two or more tobacco products are cutting their health risks because they replace some cigarette smoking with smokeless tobacco, which has fewer carcinogens. Or, does the nicotine in smokeless products actually drive up addiction and cigarette smoking? Does using smokeless tobacco make it easier or harder for smokers to quit cigarettes? “Right now, we just don’t know,” she says.
CERTS research will help answer such questions. Shields and Amy Ferketich, PhD, an epidemiologist in the College of Public Health and a researcher in the OSUCCC – James Cancer Control Program, are conducting studies comparing two cohorts of young males, aged 11 to 14. One group lives in the city of Columbus, which has been used in the past for test marketing new tobacco products. The other group is in rural Appalachian Ohio, where some counties have a smoking rate as high as 40 percent, and kids routinely start smoking at age 11.
The team will spend three years monitoring tobacco marketing strategies in the two areas and tobacco use among the two groups.
Shields will track how long it takes for youth who begin using tobacco to become addicted and whether the time to addiction depends on the type of products used—smokeless tobacco, cigarettes or both. He hypothesizes that dual-use will speed addiction. If he is correct, that data could help the FDA restrict the marketing of smokeless tobacco and develop regulations to lower the amount of nicotine in products.
Shields will also collect saliva samples from the teens and family members to identify genes that might contribute to addiction and perhaps product preferences. At the same time, Ferketich will assess the initiation rate of smokeless-tobacco use and dual-use among the rural and urban youth. She will examine how tobacco advertising and marketing, and the boys’ attitudes about and awareness of that marketing, predict their use of smokeless tobacco and dual-use.
The other investigators on her team include Christopher Browning, PhD, professor of Sociology; Karol Krotki, PhD, a statistician at RTI International; Bo Lu, an associate professor in Public Health; Annie-Laurie McRee, an assistant professor in Public Health; Brady Reynolds, an association professor from the University of Kentucky; and Michael Slater, a professor of Communications at Ohio State.
Ferketich hypothesizes that kids most likely to start tobacco include “kids who have more exposure to tobacco marketing, who go to fast food restaurants more often, who view more TV programs, movies, and websites that portray smoking, and who have less awareness of marketing’s aims to change their behavior.” A smaller set of each cohort will carry a smartphone device for 10 days to chart real-time exposures to tobacco advertising.
Ellen Peters, PhD, professor of Psychology in the College of Arts and Sciences, and a researcher in the OSUCCC – James Cancer Control Program, is studying a question that addresses a regulatory conundrum that has already landed in the courts: how best to design the graphic warning labels on tobacco product packaging (see sidebar below).
The Tobacco Control Act states that the FDA must design images to match nine simple health warnings such as “Cigarettes cause cancer,” and “Tobacco smoke can harm your children.”
“These labels are part of the FDA’s mandate to help the public better understand the health risks of tobacco,” says Peters, who also directs Ohio State’s Behavioral Decision Making Initiative. “But the court disagreed with how the FDA first went about it.” Now, the FDA needs strong evidence that will hold up in court and prove that its labels effectively get the message across.
For CERTS, Peters and her team will randomly assign smokers and nonsmokers to view different levels of warning labels, ranging from text-only to graphic photos. Afterward, the participants will be quizzed about their reactions to the labels. The study will pay particular attention to adolescents, young people who have experimented with smoking but have not smoked for very long.
To learn how use of e-cigarettes and other smokeless tobacco infuences smoking habits, Wewer’s team is surveying 800 adults from three groups: those who only smoke, those who use only smokeless tobacco, and those who use both products. “Does dual-use in fact help smokers quit cigarettes, or does it keep them addicted and using multiple products?” she asks. The FDA needs hard data to answer the questions, Wewers says.
She is also leading a project to catalog the advertising, marketing and price promotions that tobacco users are exposed to at the point-of-sale retail environments. The team, which includes Micah Berman, JD, assistant professor at the College of Public Health and at the Moritz College of Law; Christopher Browning, PhD, professor of Sociology; and consumer preference expert H. Rao Unnava, PhD, professor of Marketing at the Fisher College of Business, will compare price deals and discounts found in convenience stores, tobacco outlets and grocery stores in both rural and urban settings.
“We want to learn if there is a connection between product pricing and what products people buy,” says Berman, an expert in tobacco control policy. If the study finds that pricing directly influences buying patterns, then the FDA can use that information to regulate pricing.
In addition, Berman co-leads a project under the CERTS grant that trains the next generation of tobacco regulatory scientists. He is developing a course that covers the FDA’s authority, how regulations are developed and approved, and the role of science in that process. Electra Paskett, PhD, MSPH, a professor in the College of Medicine and in the College of Public Health, directs the Training Core.
As the Ohio State tobacco regulatory scientists pursue studies about new tobacco products hitting the market, they are particularly concerned about the appeal these products might hold for adolescents.
Marketing tactics that were banned long ago for cigarettes because of their appeal to youth—celebrity endorsements, fruit and candy flavors, and cartoon mascots—are being used with these new products. Researchers are also concerned that e-cigarettes might be a gateway product that leads young people first to nicotine addiction, then to smoking.
“The OSUCCC – James is working to help Americans better understand the negative effects of tobacco,” Shields says. “And through the Center of Excellence in Regulatory Tobacco Science, we’re helping the FDA fulfill its mandate to protect public health.”
A Case for Stronger Science
Studies by Ohio State’s Center for Excellence in Tobacco Regulatory Science (CERTS) will help the Food and Drug Administration (FDA) design regulations that will stand up against litigation by the tobacco industry.
For example, the 2009 Tobacco Control Act gave the FDA authority to design color images to match nine health warnings to be printed on tobacco product packaging. The messages will replace the current “Surgeon General’s Warning” used since the 1970s.
The graphic images were to depict the negative consequences of tobacco use. In June 2011, the FDA released nine pictures to go with the warnings, such as diseased lungs. The tobacco industry sued, arguing that the graphic warnings restricted the companies’ right to free speech.
In August 2012, a U.S. appeals court ruled in favor of the tobacco companies, citing that the FDA offered no significant evidence showing that graphic warnings would reduce smoking rates by a “material degree.”
“It was a mismatch between the research and the question the court ended up asking,” says Ohio State assistant professor of Public Health and of Law Micah Berman, JD, who is guiding CERTS research on how best to build a scientific case that will withstand a court test.
For the revised images, the FDA will have CERTS research to back its case.