Pregnant women who smoke participated in a recent study looking at very low-nicotine cigarettes (VLNC). The study adds to a raging debate over whether mandating VLNC would reduce harms, but has also been attacked as unethical.
The study was published in the Preventative Medicine journal in July. Its authors stated that, “Randomized controlled trials have shown that reducing the nicotine content of cigarettes decreases the number of cigarettes smoked per day without engendering compensatory smoking.” And they aimed to find out “whether those effects extend to smoking during pregnancy.”
The researchers recruited 30 pregnant women who said they had no plans to quit smoking. They were split into two groups: a control group who were asked to continue smoking their usual cigarette brand for 12 weeks, and an “intervention” group who were asked to smoke VLNC instead.
The participants were provided with free cigarettes, paid for by the federal government—which has an interest in VLNC, given the Food and Drug Administration’s proposed rule to cap nicotine in combustible tobacco at very low levels, with the aim of reducing smoking.
According to regulatory information published by the federal government on September 4, that proposed rule has been withdrawn.
The idea was always highly controversial. Critics have said that people might end up smoking more cigarettes per day in order to get the same satisfaction, noting that VLNC are no less harmful than regular cigarettes. Some tobacco harm reduction-oriented experts worry that implementation might lead people to believe, wrongly, that VLNC are less harmful; that the move could merely push people toward illicit cigarette markets; and that the “coercive” plan is “not consistent with harm reduction principles.”
Headline findings included that, “Very low nicotine cigarettes did not reduce smoking in pregnant women,” but also that, “Their use did not lead to compensatory smoking.”
The FDA proposal has also had its supporters, however, including some in the tobacco harm reduction space. Some researchers have called it a “harm reduction strategy” that would be a significant means of cutting tobacco use, saying that very low levels of nicotine will make cigarettes “less addictive.” The FDA’s modeling suggests that a VLNC mandate could prevent 1.8 million smoking-related deaths by 2060 and save trillions in health care costs.
Opponents question the validity of the FDA’s evidence, and stress that promoting safer alternatives to cigarettes, like vapes, is the relevant path to reducing smoking.
The recent study did not settle this argument. Its headline findings included that, “Very low nicotine content cigarettes did not reduce smoking in pregnant women,” but also that, “Their use did not lead to compensatory smoking or notable withdrawal or craving.”
Lead author Dr. Sarah Heil, of the University of Vermont’s Tobacco Center of Regulatory Science, said the results did not support the claim that VLNC increase smoking, and that a slight reduction was observed in the VLNC group.
“Participants who were given VLNC cigarettes reported smoking an average of 18.4 cigarettes per day just before the study started, but only 16.7 cigarettes per day during the study, and the biomarker data confirm this small decrease,” Heil told Filter.
“It is important to note that the VLNC cigarettes used in this study contained just 0.4 mg of nicotine/gram of tobacco,” she continued. “The commercial cigarettes our participants usually smoked contained an average of 18.4 mg/g, or nearly 50 times more nicotine. It would be extraordinarily difficult, if not impossible, for someone to smoke enough 0.4 mg/g cigarettes to achieve the same level of satisfaction that they get from their usual brand.”
Dr. Michael Siegel called for the study to be retracted due to a violation of research ethics, and for its participants to receive compensation.
But should the study in this form even have been conducted?
Dr. Michael Seigel, a professor of public health and community medicine at the Tufts University School of Medicine, expressed serious concerns in his blog. He argued that it was unethical to instruct pregnant women to continue with a habit known to cause harm, including fetal harm.
To meet “basic ethical standards in medical research,” he wrote, the women in the control group should have been advised to quit smoking and provided with interventions to help them do so. “The intervention protocol for this clinical trial was also unethical,” he added, “because it offered a treatment that is worse than standard care.”
“One could argue that the women were not prevented from quitting smoking if they chose to,” Siegel wrote. “However, this lands [far] short of the ethical standard. It is not enough to allow nature to take its course if standard practice calls for medical intervention—namely, the US Preventive Services Task Force’s recommendation to advise quitting and provide behavioral modification therapies.”
Siegel called for the study to be retracted due to a violation of research ethics, and for its participants to receive compensation.
The authors of the federally-supported trial replied to Siegel’s criticisms, and he then published their response in his blog.
“This was NOT a smoking-cessation trial,” the study authors wrote. “Instead, it was designed to investigate how a national nicotine reduction policy might impact pregnant women.”
Although smoking cessation is “ideal,” they argued, “not all pregnant women are able to quit, even with the best interventions currently available, and we need to consider other ways to reduce the adverse impacts of smoking during pregnancy.”
“Important to emphasize is this trial on which Dr. Siegel commented was NOT a smoking-cessation trial,” the study authors wrote. “Instead, it was a study designed to investigate how a national nicotine reduction policy might impact women who continue to smoke after learning they are pregnant.”
“To ensure that any evidence of compensatory smoking would be picked up if it were present, it is convention in trials assessing the risks and benefits of cigarettes with different nicotine levels to provide research cigarettes to participants for free,” they added.
The authors went on to explain that the study design “underwent many layers of peer review for scientific merit and research ethics” before being selected for funding by the National Institute on Drug Abuse (NIDA) and the FDA. Additionally, the trial “was monitored by an independent Data and Safety Monitoring Board made up of professional experts in tobacco research and research ethics.”
“I still question the decision of the review boards to approve the study, because it violates a central principle: A study may not expose subjects to unnecessary risks.”
Responding, Siegel said he did not blame the authors of the study, as the relevant institutions had given them the go-ahead.
“However, I still question the decision of the review boards to approve the study in its current form,” he told Filter, “because it violates a central principle that review boards must certify: A study may not expose subjects to unnecessary risks.”
Although the participants were informed about the risks of smoking during pregnancy and asked whether they intended to quit, he said, “the essential method of this arm of the study was instructing pregnant women to continue to smoke as usual and moreover, providing them with free cigarettes.”
“Providing patients with less than the standard level of care is unethical,” he concluded. “It exposes them to levels of risk that are not necessary and that are higher than patients typically encounter in the same situation outside of the research setting.”
Photograph via ITOLDYA/Public Domain
Update, September 4: This article has been edited to reflect new information about the withdrawal of the FDA’s proposed rule.
