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How Philip Morris is selling regulators on its hot new smoking device

Part 4: Philip Morris executives are traversing the globe to lobby health authorities on the benefits of iQOS, the little machine the tobacco giant says is key to the company’s future. The novel argument: While iQOS uses tobacco, it shouldn’t be categorized as a cigarette because it doesn’t burn the leaf.

TOKYO/TEL AVIV/BOGOTA – In Tokyo’s upscale Ginza shopping district, around the corner from the sparkling storefronts of Tiffany & Co and Cartier, shoppers searching for a new device called iQOS can buy it in a boutique behind a glass façade. The store combines a high-tech aesthetic with the feel of an exclusive club: The young woman at the door says a members-only smoking lounge is upstairs.

The device is advertised under the slogan, “This changes everything,” with a hummingbird in fluorescent green and blue floating in midair. From the small “i” of its name when it was rolled out to the minimalist white box it comes in, the iQOS evokes the marketing-and-design savvy of the American technology giant Apple Inc.

But this little machine is sold by the tobacco giant Philip Morris International Inc. And it isn’t a smartphone.

The iQOS is essentially an electronic cigarette that heats – without burning – plugs of tobacco, releasing tendrils of nicotine-laced aerosol. And the world’s largest publicly traded tobacco company by market value, which has spent more than $3 billion in developing new smoking devices, says iQOS is nothing less than its future.

Philip Morris International says the lack of combustion means iQOS produces far lower levels of carcinogens than regular cigarettes. It’s early days, but iQOS is already bringing in piles of cash. The device drove up sales of the company’s new-generation smoking products to nearly $1 billion in the last quarter, from some $200 million just a year ago.

Wowing consumers with the prospect of a less harmful smoke built on flashy technology is essential to iQOS’ rapid success. Consumers,though, aren’t the only target. Interviews with government officials and trade groups reveal how the company is seeking to sell national authorities on the benefits of the device, before regulators can toss up hurdles.

A key objective: convince governments of iQOS’ benefits so they don’t slap the same taxes and restrictions on the device as they do on cigarettes.

Philip Morris is employing a novel argument: The tobacco plugs inserted into the iQOS device shouldn’t be classified as cigarettes because they do not burn or produce smoke. And the device itself, the company says, is an electronic product and so should not be regulated like tobacco.

In Japan, Philip Morris blitzed officials with the science of iQOS to persuade them to classify the device in a way that would lead to a lower tax rate than cigarettes. In Israel, the company flew in an executive to convince a senior health official of the upside of the device. And in Colombia, the health ministry says Philip Morris launched iQOS without seeking the agency’s approval.

The approach is outlined in internal company documents seen by Reuters.

Evidence that iQOS “is ‘not smoked’ is the most critical element,” says a 2014 PowerPoint briefing on iQOS and other new smoking devices.

Reuters has published that document and others in a searchable repository, The Philip Morris Files.

Other traditional cigarette companies, notably British American Tobacco Plc and Japan Tobacco Inc, have launched similar devices. None have reported anything close to the global sales of iQOS.

The iQOS is championed by Andre Calantzopoulos, Philip Morris International’s chief executive, who in media interviews makes the point that he smokes the device. In September last year, Calantzopoulos told investors it was the company’s “aim to become the undisputed leader” of a new tobacco category it dubs “reduced-risk products.” The goal he said, is to have “RRPs” ultimately replace regular cigarettes.

TWITTER ADVICE: A page from a Philip Morris social media training handbook provides guidance on how to engage online users.

Philip Morris now has an application pending at the U.S. Food and Drug Administration for permission to market the device in America as being less harmful than cigarettes.

A Reuters investigation published Wednesday identified shortcomings in the training and professionalism of some of the lead investigators in the clinical trials that underpin the tobacco giant’s application to the FDA. Former Philip Morris employees and contractors described irregularities in those experiments.

The company chose Japan as its first iQOS market, launching in late 2014. If the company could achieve its goals in “priority” markets like Japan, it would provide “good reference points to other countries,” said the 2014 Philip Morris presentation on reduced-risk products like iQOS.

It unveiled the device in an unlikely venue – Nagoya, a city of more than 2 million people on a bay of the Pacific Ocean. Nagoya is close to Toyota Motor Corp’s headquarters, a town of skyscrapers and automotive plants; a place with neither the buzz of Tokyo nor the charm of Kyoto.

At first, business lagged. An internal company review of Asia, dated June 2015, put iQOS sales figures toward the end of the Japan market rundown. It showed iQOS sales dropping about 40 percent from that January to May.

Philip Morris pushed ahead with a national expansion in September 2015. In an in-house newsletter for the Japan operations the next month, Ashok Rammohan, director of reduced-risk products, told employees that “building iQOS will take time and focus as we need to educate LAS” – legal-age smokers.

By early 2016, the buzz surrounding iQOS in Japan was growing, thanks in part to a group of Japanese entertainers. That April, six popular Japanese comedians were on a national TV show when the presenters began to talk about smoking. One of the comedians, Terumoto Goto, a household name, held up a red iQOS.

“It doesn’t release smoke,” he explained. “It’s like steam coming out of my mouth.” The five men sitting around him on the TV set, decorated with bright rainbow stripes, held up iQOS units as well.

Goto said he bought an iQOS because his wife wouldn’t let him smoke cigarettes inside their house and the neighbors didn’t like him standing around and smoking outside.

Toshiyuki Itakura, just behind Goto, chimed in about smoking the device in public: “There doesn’t seem to be any harm.”

Searches on Google for the Japanese word for iQOS spiked that day.

The talent agency that represents Goto and Itakura, Yoshimoto Kogyo Co Ltd, said in a statement: “Our company received absolutely no payment from Philip Morris or affiliated companies” for the appearance. The network that carried the show, TV Asahi Corp, said it did not consult with the tobacco company beforehand.

That promotional bump came during a period when Philip Morris was working to use social media to propel iQOS into the national consciousness.

“That IQOS moment.” “My IQOS way of living.” Those are two of the catchphrases the company’s social media team considered using as catalysts to promote online chatter about the device. The guidance appears in a 2017 online-content strategy paper, marked “confidential,” that cites examples from Japan.

A separate document, a 54-page training handbook for social media teams in 2016, warns that the company’s postings walk a fine line. “Since the law is set up to prevent tobacco companies from promoting their products on social media, and iQOS is a product that uses tobacco, you’ll always be walking through a minefield of sorts,” the document says.

Away from the public eye, Philip Morris employees equipped with pages of scientific findings were lobbying government officials in Japan. They set out to convince regulators to tax iQOS at a lower rate than cigarettes and exempt it from ordinances that ban smoking in public places and restaurants.

Koki Okamoto, a member of the Tokyo Metropolitan Assembly, said the city’s planned public smoking regulations almost certainly will exempt iQOS. “My personal view, as a lawyer, is that there will be reluctance to apply penalties to something without scientific evidence on health hazards,” said Okamoto, a lead for tobacco control issues in the party that won the capital’s elections this July.

To date, Philip Morris is responsible for the majority of the science that has been published about iQOS.

Philip Morris executives say the product is meant only for people who would not otherwise quit smoking. That is inconsistent with where the company has chosen to introduce iQOS.

Industry sales numbers show Philip Morris is selling iQOS almost entirely in countries where cigarette sales are already in decline – in other words, where people are quitting. While the global average for cigarette sales was down 1.9 percent from 2005 to 2016, in 30 countries where iQOS is now sold the drop in sales was about 30 percent, according to a Reuters analysis of industry numbers from Euromonitor International.

Philip Morris said in response that there are more than 180 million smokers in the countries where iQOS has been launched. “Those 180 million people deserve an opportunity to switch to a potentially less harmful product than cigarettes,” the company said.

As the company honed its strategy in Japan – impressing officials with its scientific findings while advocating for lower taxes – it set out to conquer new markets.

More than half a year before iQOS launched in Israel, Moira Gilchrist, a corporate affairs vice president for reduced-risk products, flew into the Holy Land and took a March 2016 meeting with a senior health ministry official to talk about the company’s science.

A few weeks after that meeting, the official, Itamar Grotto, sent a letter to the country’s tax authority saying iQOS was in a new product category exempt from marketing and advertising restrictions on tobacco products. In a later court filing, Philip Morris cited the letter in explaining its decision to launch iQOS in Israel.

Asked why he said iQOS was exempt from tobacco regulations, Grotto told Reuters that the ministry was being cautious after losing a case against e-cigarette companies a few years earlier. Grotto also said he thought at the time that the question of regulating iQOS was “theoretical.” He had understood from Philip Morris that it did not plan to market the device in Israel until it had approval from a European or American regulatory authority, Grotto said.

Told of Grotto’s remarks, Philip Morris said in a statement, “We did not state that PMI would wait for the approval of a foreign regulatory authority.”

In Israel, iQOS has faced obstacles. This March, a group headed by an activist named Shabi Gatenio challenged the health ministry and Philip Morris in the country’s top court over the sale of iQOS without the same marketing restrictions imposed on regular cigarettes. An Israeli tobacco company also challenged the government and Philip Morris in a similar filing.

During an interview in Tel Aviv, Gatenio, 45, marveled at the reach and access of Philip Morris. He said within two and half hours of his filing the court petition, before it had become public, he got a text message from Erez Gil-Har, co-chief executive of Policy Ltd, Philip Morris’ powerful lobbying company in Israel. The message, viewed by Reuters, accused Gatenio of becoming a “tool” in the hands of the local tobacco company – a charge he dismisses.

Gil-Har, who attended the meeting with Grotto and Philip Morris’ Gilchrist, declined to comment. The tobacco company, Dubek Ltd, declined to talk as well.

Before the court could give a final ruling, the health ministry reversed its position and said it would treat iQOS as it does traditional cigarettes. The ministry said it planned to revisit its decision after seeing how the U.S. FDA regulates the product.

The about-turn left Philip Morris scrambling. According to a government official familiar with the matter, Philip Morris hired more than two dozen women for an urgent task: They manually peeled off the old labels from thousands of tobacco-insert packs in a warehouse near Tel Aviv and stuck on new ones with more prominent health warnings. The packs were then released.

Half a world away in Colombia, Philip Morris kicked off its sale of iQOS this March with a large white balloon at a music festival. Emblazoned with “iQOS” in blue and green letters, the balloon was hoisted 20 feet in the air by a crane.

Tobacco advertising and promotion are banned in Colombia, the first country in Latin America to get iQOS. According to a health ministry official, Philip Morris launched iQOS without getting approval from the agency to sell the tobacco inserts in the country as is required by law.

“This is a product which is derived from tobacco and which must have a prior evaluation by this ministry,” said senior health ministry official Jose Fernando Valderrama.

Philip Morris said it is in compliance with Colombian law. The company said it is required to submit the tobacco inserts for health ministry approval following the release of the agency’s tobacco warnings in November each year. Its Colombian affiliate will do so “in the next month,” the company said in a Dec. 7 statement to Reuters.

On a stroll through the capital Bogota a few months ago, iQOS could be seen being sold at the front of a restaurant with bright displays of packs of the tobacco inserts and the hummingbird emblem facing the sidewalk. In a trendy quarter of the city, a large white billboard advertised a coming “iQOS Boutique,” next to a Starbucks and an Apple retailer.

A former Philip Morris employee in Bogota said the company’s position is that because the device itself does not include tobacco, unlike the inserts, marketing restrictions don’t apply to it.

The company confirmed that position, saying iQOS is an electronic device, and “as such, the current tobacco law does not regulate its commercialization as a tobacco product.”

Back in Japan, sales of the device have taken off. Philip Morris says the iQOS tobacco inserts made up 11.9 percent of the Japanese tobacco market in the third quarter, up from 3.5 percent a year ago.

That growth took on additional significance for company revenue in light of the lower tax rates. The iQOS kit retails for about 11,000 Japanese yen, roughly $100. The company said that cigarettes in Japan are taxed at 60 percent, while the iQOS tobacco inserts – priced about the same as a pack of Marlboros – are at 51 percent.

Philip Morris shows no signs of slowing down. Paul Riley, president of the company’s operations in Japan, this January called on Emiko Takagai, who as a former vice health minister is an influential voice on national health policy. They met in Takagai’s seventh-floor office in Tokyo, one decorated with stuffed animals and posters of healthy food groups.

During that conversation, Riley laid out the company’s pitch on iQOS, said Takagai. In documents later sent to her office, Philip Morris said the product reduces the levels of harmful substances by at least 90 percent compared to regular cigarettes.

When Reuters in August interviewed Takagai, a member of the upper house of parliament for the nation’s ruling party, it seemed the tobacco giant’s message was hitting home.

If the company’s scientific claims bear out, she said, “we must make efforts to thoroughly tell people.”

Scientists describe problems in Philip Morris e-cigarette experiments

Part 3: Former employees and contractors have detailed irregularities in the clinical experiments that underpin Philip Morris International’s application to the FDA for approval of its iQOS smoking device. The agency is expected to decide by next year on whether the tobacco giant can sell its new product in the U.S.

TOKYO/NEUCHATEL, Switzerland – The U.S. Food and Drug Administration is weighing whether to approve a potentially path-breaking smoking device by Philip Morris International Inc. With a decision expected next year, former employees and contractors have described to Reuters a number of irregularities involving clinical trials that underpin the tobacco giant’s application to the agency.

By heating tobacco instead of burning it, the company says the device, known as iQOS, avoids subjecting smokers to the same levels of carcinogens and other toxic substances found in a regular cigarette. The company has spent more than $3 billion developing new smoking platforms like iQOS. As part of that initiative, Philip Morris has published extensive scientific findings, based in part on clinical studies.

Tamara Koval, who worked at the company from 2012 to 2014 and helped coordinate clinical trials for the device, questioned the quality of some of the researchers and sites contracted to carry out those experiments. Koval was a co-author of the company’s protocol used to run the studies globally. When she highlighted an irregularity in one of the studies, Koval said, Philip Morris excluded her from meetings.

Reuters also found irregularities during interviews with some of the principal investigators contracted to conduct the trials for the company. One principal investigator said he knew nothing about tobacco. Philip Morris had to jettison the experiment that investigator performed after it emerged he hadn’t followed a basic procedure for obtaining informed consent from participants during clinical trials.

A second investigator submitted urine samples that exceeded what a human being is capable of, according to two former company employees, and then initially refused to acknowledge there was a problem. A third said he doesn’t hold such company-sponsored clinical trials in high regard, describing them as “dirty” because their purpose is more commercial than scientific.

After reviewing Reuters’ findings, Philip Morris said in a statement that “all studies were conducted by suitably qualified and trained Principal Investigators.” The company said it understands that “FDA inspectors have already audited some facilities” involved in the trials. Philip Morris also said it had taken steps to address “any reported irregularity in our studies.”

“Our policies encourage speaking up about suspected violations of law or our policies and we do not tolerate retaliation against those who speak up,” the company said.

In addition to former Philip Morris employees involved with the iQOS program, Reuters interviewed six of the 11 principal investigators who were responsible for five of eight clinical trials the company submitted to the FDA. Reuters also reviewed hundreds of pages of publicly available Philip Morris study reports and FDA filings.

That reporting identified shortcomings in the training and professionalism of some of the lead investigators, as well as their knowledge of the study results.

A group of tobacco research and policy experts reviewed detailed summaries of Reuters’ reporting and Philip Morris’ response. The experts, including a former head of the FDA and two former scientific advisers for the agency, said those findings raise concerns about Philip Morris’ clinical trial program.

“Taken as a whole, it’s clear they do not have the sophistication to carry out adequate and well-controlled clinical trials,” said David Kessler, the FDA’s commissioner from 1990 to 1997, referring to the company. “I am not inferring any malicious intent here, just that they lack sophistication, because this is not their bread and butter.”

If the FDA has already audited some of the trial sites used by Philip Morris, the agency “should carefully review its audits and possibly expand them,” said Kessler, a former dean of the medical school at Yale University.

Tom Eissenberg, who served on the FDA’s tobacco products scientific advisory committee until earlier this year, said: “The FDA should audit.”

Reuters did not find any evidence that the outcome of the experiments presented by the company to the FDA was manipulated or falsified.

The new insights into the company’s clinical trial program for iQOS come at a crucial time for Philip Morris. The world’s largest publicly traded tobacco company by market value and maker of Marlboro cigarettes has applied to the U.S. FDA to be able to sell iQOS in America, and also for permission to market it as a modified-risk tobacco product. That designation could mean that Philip Morris is allowed to market iQOS as presenting less harm or risk of disease to users than traditional tobacco.

For now, the FDA is evaluating the company’s studies. Reuters outlined its findings about the iQOS trials to the agency. The FDA said it cannot comment on a pending application.

Philip Morris says the device, which heats small tobacco inserts, is meant for smokers who would not otherwise quit. Its chief executive officer, Andre Calantzopoulos, has told investors and media alike that he intends to one day replace cigarettes with products like iQOS. So far, iQOS makes up a fraction of the company’s $75 billion revenues and Philip Morris continues to market conventional cigarettes across the globe.

Internal Philip Morris documents reviewed by Reuters show the significance of iQOS goes beyond its profit potential. The device is now sold in more than two dozen nations after it was first launched in Japan and Italy during late 2014.

The company has a 10-year plan for what it calls “normalization” of the tobacco industry, according to a 2014 strategy document. The industry has been shunned over the past two decades for producing and marketing products that kill people and previously lying about it. Under a section on “strategies and actions” to achieve that goal, the document lists, among other things, new smoking devices such as iQOS and the scientific research involved in developing them.

Told about that document, Philip Morris said: “The suggestion that the purpose of our development of IQOS and our scientific research program is to ‘normalize’ the tobacco industry is false.”

That previously undisclosed document and others can be found in a searchable repository published by Reuters, The Philip Morris Files.

As part of its submission to the U.S. FDA, the company said the results of its research showed the device significantly reduced the level of certain harmful substances that users were exposed to compared with cigarettes, and satisfied their nicotine cravings. “In fact the level of reduction is so considerable, it approaches 95% of the levels measured in smokers who quit altogether,” the company said in a statement to Reuters.

Taken along with the company’s laboratory studies, Philip Morris said, the research program “in its entirety demonstrates that IQOS is likely to reduce the risk of smoking related diseases.”

Philip Morris is responsible for the majority of the science that has been published about iQOS. “Those who criticize us should probably look at our science,” said Tommaso Di Giovanni, a company spokesman, during a tour of Philip Morris’ research and development headquarters in March.

The eight clinical experiments that Philip Morris submitted to the FDA were conducted between 2013 and 2015. For one study, scientists in Texas and Florida did not respond to messages left by Reuters. Other scientists, in Belfast and Tokyo, declined to talk. Half of the eight studies were done in Japan.

FDA guidelines for conducting clinical studies say a trial should adhere to standards such as Good Clinical Practice. That best-practices document says investigators “should be qualified by training and experience and should have adequate resources” to properly conduct a trial.

Masayuki Sugimoto, the principal investigator who oversaw testing at one facility used by Philip Morris to conduct a trial, said his Tokyo clinic is “heavily in the red.”

Sugimoto said he generally has little confidence that all the participants in experiments like the one he ran for Philip Morris on nicotine tell the truth about their smoking history – that is, whether they smoke.

Speaking about the final study report from the Philip Morris trial, Sugimoto said in an interview that he generally doesn’t have time to read such things in detail. He said he probably signed a document indicating he had received the final report. Sugimoto gestured with his thumb and forefinger to indicate a thick document: “I just don’t read them.”

Philip Morris said that it “did not receive any such comments or statements from the PI,” or principal investigator. Sugimoto’s study, it said, was completed “without any issues.” The company said the study data was reviewed and discussed with the investigator throughout the trial.

The Japanese company hired to monitor studies in the country, CMIC Holdings Co Ltd, said in a statement that researchers confirmed that trial participants were smokers by using urine tests.

Asked about the tests, Sugimoto said he thought they would prevent non-smokers from joining the trial but added, “I don’t know whether they were done that rigorously.”

Told of Sugimoto’s doubts about the honesty of study participants, Eissenberg, who served on the FDA’s tobacco products scientific advisory committee from 2011 to 2017, said “it raises a great deal of concern.”

A principal investigator “is required to make sure that the participants meet the inclusion-exclusion criteria that are in the protocol,” said Eissenberg. He was referring to the fact that clinical trial subjects’ backgrounds – such as whether they are smokers – should meet the parameters of the experiment for the data to be valid. “And a PI should have confidence in that,” he said.

SIGNED DOCUMENT: Masahiro Endo, one of the principal investigators on the iQOS clinical trials, signed off on the study report for the experiments he conducted. In an interview with Reuters, he initially said he was not aware of the results of the trials.

At another laboratory in Japan, issues with how the study was carried out were so acute that data from 56 participants was thrown out, raising questions about the competence of the principal investigator. Philip Morris halted the study at that location.

In the company’s study documentation released by the FDA, Philip Morris recorded the reason for discarding the data as non-compliance with good clinical practices, specifically “failure of the site to meet sample collection procedures and data recording procedures.”

Kishor Lad, who was Philip Morris’ data manager on the study, said the site crossed a line of what’s allowed during such trials: It collected samples before getting informed consent forms signed by the volunteers. “Completely a no-no in the GCP world,” Lad said, using the acronym for good clinical practice.

Philip Morris confirmed to Reuters that “informed consent was not obtained prior to execution of a study procedure” – specifically, the collection of urine samples. The problem was identified by CMIC, the contract research group, during a routine monitoring visit, Philip Morris said. A subsequent round of audits, it added, “led to prompt discontinuation of the study at the Seishukai Clinic.” The incident, the company said, was properly logged in the study report and the submission to the FDA.

“It suggests the investigator had no idea, did not understand or just didn’t care what his responsibilities were in conducting the study,” said Greg Koski, a former director of the U.S. federal Office for Human Research Protections, which advocates for research subjects. “This is such a flagrant violation, that investigator shouldn’t be doing clinical studies.”

Mamoru Oki was the principal investigator at the time at the facility, the Seishukai Clinic in Tokyo. Reached by phone, Oki said: “My specialty is urology and I don’t know anything about tobacco, so I cannot talk.”

Told of that remark, Philip Morris said: “Dr. Oki was qualified and trained specifically on the product.”

Dorothy Hatsukami, a member of the FDA’s tobacco products scientific advisory committee from 2010 to 2013, said a principal investigator’s professed lack of knowledge about tobacco is not ideal.

“For any tobacco-related clinical trial, an investigator with a background in tobacco product research would have better qualifications to evaluate the study results than a novice,” she said.

The study continued at a parallel site, the Tokyo Heart Center.

During an interview at the center, principal investigator Masahiro Endo said repeatedly that he had no idea what the results were from his study.

“We did medically safe and accurate blood samples, but were not told the results. So even if we are asked questions, we won’t be able to answer,” he said. “We were paid, it ended there.”

But in a statement signed last year and submitted by Philip Morris to the FDA, Endo said he had read the clinical study report from the company and confirmed “that to the best of my knowledge it accurately describes the conduct and results of the study.” Principal investigators in all of the Philip Morris clinical trials signed the same statement.

A day after speaking with Reuters, Endo sent an email clarifying that after checking his records he saw that he’d signed a receipt saying he received a report on the results and acknowledging that he’d be listed as the principal investigator. He had spoken during the interview “with a fuzzy memory,” Endo said.

Clinical trial experts interviewed by Reuters said it’s not uncommon for principal investigators to be unaware of test results sent to a third party specialty laboratory for analysis. But they also emphasized that if companies want better science, they need the investigators to be more involved with all aspects of a study.

“It seems like the investigator here is in the role of a technician, not as a principal investigator,” said Kessler, the former FDA commissioner.

Kessler said it’s hard to understand how such investigators could have signed off on the clinical study report “when they clearly were not versed in the study results.”

Other principal investigators described their work differently.

Fumimasa Nobuoka, a principal investigator on one of the trials in Japan, said he read the Philip Morris study report: “I thought it was well done, well written.”

James Borders, who was the principal investigator for a study held in Lexington, Kentucky, said the experiments in his trial were done ethically and followed sound scientific practice.

Borders, who became chief medical officer at the Baptist Health Lexington hospital, said such studies help consumers make an informed decision. His decision to be involved with the study, he said, hinged on the proposition that a device like iQOS could be the “lesser of two evils.”

Philip Morris said that while it sponsored the clinical trials, the experiments were “performed by reputable research facilities” and monitored by contract research organizations – companies used to oversee such studies. It hired U.S.-based Covance Inc to serve as its global contract research organization, according to an internal Philip Morris 2013 assessment plan. Covance, a unit of Laboratory Corporation of America Holdings, declined to comment.

CMIC, the company hired to monitor the Japan studies, said in a statement: “All the clinical trials you referred to were conducted in accordance with GCP guidelines” – good clinical practices – “and we believe that the results of the trials are scientifically trustworthy.”

As part of her job coordinating between Philip Morris and those contracted to run its clinical trials, Koval, the former company scientist, conducted medical safety training across the world for principal investigators and others involved with the iQOS studies.

During one study training session in Tokyo, Koval said, she realized some of the researchers could not speak English well and she was unable to communicate with them. Koval said she does not speak Japanese and there was no interpreter present.

“I was like, Jesus, what are we doing here?” she said. At dinner later, Koval said, she saw two of the men, and they were unable to describe in English what their jobs were.

When asked about Koval’s session, Philip Morris said it was a meeting with its contract research organization and others. It added that “all PIs and team members with active roles in the study were fluent in English.”

But Sugimoto, one of the Japanese principal investigators, told Reuters in an interview, “I can’t speak English.”

And Endo, another of the lead researchers, said that when Philip Morris executives visited his site someone was present who helped translate “questions like whether to cut the crusts off bread” when giving food to study subjects.

CMIC said, “All the principal investigators received adequate training in Japanese before the trial began.”

In Poland, some urine samples collected as part of one Philip Morris clinical study exceeded the limits of what a human being is capable of producing in a single day, according to Koval and Lad, the former clinical data manager.

Lad, who worked at Philip Morris from 2012 to 2015, said he didn’t think anything “malicious” had happened. Maybe urine samples were swapped or there was a mistake with the containers used to collect the urine, he said.

But when the principal investigator for the Polish site was asked about the results, she would not admit there was a problem, Lad and Koval said. Instead, they said, the scientist explained that the test subjects were large Polish men.

Philip Morris said that “a few participants” in an early stage of the trial “produced unusually large volumes of urine.” Because medical tests showed no problems with the subjects, the company said, the investigator did not initially consider the samples to be “adverse events.”

After discussion with the medical monitors of the study as well as Philip Morris, the investigator “ultimately decided to mark these incidences as adverse events,” the company said. An investigation at the site confirmed that researchers had followed study protocol and good clinical practices, the company said.

The principal investigator running the study in Poland for Philip Morris, Katarzyna Jarus-Dziedzic, declined to discuss what happened with the urine case at her site, citing confidentiality.

Koval said that after she raised concerns about the Polish study with Philip Morris executives in Switzerland she was excluded from meetings.

Philip Morris said in a statement that Koval was “part of the team” that followed up on the urine samples. In fact, the company said, she was “an active member” of the group that finalized the data set from the studies for further analysis.

Koval confirmed that she was part of the team and involved with the data set. But she stood by her account that she was shut out of conversations and meetings about the urine samples.

In 2014, Philip Morris terminated her contract, Koval said. She said she returned to the pharmaceutical industry a few months later and now works for Swiss drugs giant Novartis AG.

After leaving Philip Morris, Koval was given a certificate of service that said, “Tamara drove clinical program development activities.” It said she had demonstrated “professionalism” and “unwavering commitment” in her work.

No more harmful than coffee
When Hans-Joerg Urban joined Philip Morris International Inc’s research headquarters as a scientist in 2005, he said a senior executive laid out the tobacco giant’s vision for the future: to create cigarettes no more harmful than a simple cup of coffee.

About a decade later that quest culminated in the iQOS, a device that heats tobacco but does not burn it. Philip Morris says the lack of combustion means smokers are exposed to far lower levels of toxic emissions than with regular cigarettes. “The ultimate result of this is reduced tobacco related harm and diseases,” the company said in a statement.

The world’s largest publicly traded tobacco company by market value has applied to the U.S. Food and Drug Administration to market iQOS as less harmful than cigarettes.

But four scientists and researchers who worked for the company on the iQOS program told Reuters that while Philip Morris was able to prove the lower amounts of exposure to harmful substances, that doesn’t necessarily mean that using the device is less likely to result in disease than regular cigarettes.

“Exposure is not directly linked to the risk of having a disease,” said Urban, a scientist who worked at Philip Morris until 2010 analyzing data from clinical and laboratory experiments. “The diseases are much too complicated.”

Dorothy Hatsukami, a former member of the FDA’s tobacco products scientific advisory committee, agrees. “At this point, research is still too nascent to say with certainty that reduced exposure translates into reduced risk,” she said.

Philip Morris is seeking FDA approval to market iQOS under two different standards. It has applied for approval as a device that reduces exposure to harmful substances. It has also applied on a second track with a higher bar – to get approval to market it as carrying reduced risk of tobacco-related disease. The first option, a special provision for companies that are unable to meet the threshold of reduced risk, comes with a restriction. Consumers cannot be “misled into believing” the product is less harmful than other tobacco products, FDA regulations say.

If the FDA approves the application, that would raise the possibility of Philip Morris International’s former parent company and U.S. partner, Altria Group Inc, capturing market share in a nation where overall cigarette sales plummeted more than 30 percent between 2005 and 2016.

Kishor Lad, a clinical data manager at the company between 2012 and 2015, said to prove the product presents less risk of tobacco-related disease, the company would need to conduct large clinical trials over several years to show that people who used iQOS lived longer than people who smoked cigarettes.

Philip Morris said it disagrees. Under U.S. regulations, the company said, the FDA “does not require premarket epidemiological data as a condition of marketing authorization.”

Lad added that it’s not correct to say that “if you’re less exposed to these harmful substances then, sort of, it’s less harmful for you.”

IQOS emissions create risks of immunosuppression and pulmonary toxicity

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UCSF public comment on PMI MRTP application: Evidence that IQOS hurts vascular fuction as much as a cigarette

Matthew Springer and his colleagues at UCSF have submitted this public comment to the FDA. The tracking number is 1k1-8zxa-mq9v and a PDF of the comment is available here

The evidence PMI presents in its MRTP application for IQOS is misleading and does not support the conclusion that IQOS will not harm endothelial function; independent research done in a more relevant physiological model shows that IQOS harms endothelial function as much as conventional cigarettes
Matthew L. Springer, Ph.D., Pooneh Nabavizadeh, M.D., and Leila Mohammadi, M.D., Ph.D. Department of Medicine, Division of Cardiology
Cardiovascular Research Institute
UCSF Tobacco Center of Regulatory Science
University of California, San Francisco
Docket Number: FDA-2017-D-3001
November 20, 2017

Philip Morris Products S.A. (PMP S.A.) modified risk tobacco product (MRTP) applications1-3 for its heat-not-burn product IQOS (also designated iQOS and THS2.2) in the United States claim that IQOS does not adversely affect the functioning of the vascular endothelium. The endothelium consists of cells lining arteries that play an important role in controlling normal functioning of arteries (vascular function). Abnormal endothelial function increases the risk of heart disease and heart attacks. The evidence that PMI presents is misleading and does not support the conclusion that IQOS will not harm endothelial function. In addition, new independent research done in a more relevant physiological model shows that IQOS harms endothelial function as much as conventional cigarettes.

This comment focuses on PMI’s assertion that IQOS aerosol exposure involves less cardiovascular risk than smoke exposure. PMI researchers have published studies that compare the effects of tobacco smoke and IQOS aerosol on various physiological systems at the cell, animal, and clinical levels (for example, Smith et al.4). The conclusions that they draw from these studies all point toward IQOS being substantially less harmful than cigarettes. However, some of the criteria used in these studies are incongruous with expected and established physiological assays.

In addition, PMI’s descriptions of their research findings in the MRTP application are worded to imply that IQOS is not harmful to vascular endothelial function known to be caused by tobacco smoke. However, this implication is unsupported because PMI has not performed the most physiologically relevant tests. PMI has not shown that IQOS aerosol exposure leads to less vascular endothelial dysfunction than cigarette smoke exposure.

Endothelial function assessed by arterial flow-mediated dilation (FMD) is a validated measure of cardiovascular health effects. FMD is the process by which arteries dilate (get larger) in response to increased blood flow.5, 6 The endo¬thel¬ial cells that line the arterial wall mediate blood flow to peripheral tissues and the heart by producing nitric oxide (NO) and other factors that lead to vasodilation. Endothelial cells sense increased blood flow because of increased friction of the liquid against the lining of the artery (shear stress) as blood flow velocity increases, and the cells respond by activating the enzyme endothelial nitric ox¬ide syn¬thase (eNOS), which creates NO, leading to FMD.

FMD is quantified by ultra¬sound in humans as the percent vasodilation of the arm’s brachial artery in res¬ponse to restoration of blood flow after transient occlusion.7 FMD is a well-established clinical prognostic indicator of endothelial function that is concordant with other measures of cardiovascular health such as risk of myocardial infarction.6-9 Brachial artery FMD correlates with endothelium-depen¬dent vasodilation of the coronary arteries10 and with a number of adverse cardiovascular outcomes including myocardial infarction and atherosclerosis11-13 that are increased by cigarette smoke. In a seminal pair of papers in the 1990s, David Celermajer and colleagues showed that both smoking and chronic exposure to secondhand smoke (SHS) impair FMD.14, 15 Juonala et al.16 reported that FMD was impaired in young adults whose parents were smokers 19-27 years earlier. Several groups including ours and our collabor¬ators have shown that a 30-minute exposure to SHS at real-world levels impairs FMD in humans.17-19 In a rat model of FMD, we have shown that exposure to realistic levels of sidestream smoke from tobacco cigarettes, filtered little cigars, and marijuana cigarettes with and without cannabinoids (but not exposure to clean air) impairs FMD, an effect that occurs after as little as one minute of exposure.20-22 In short, measurement of FMD is a common test to determine whether inhalation of aerosols leads to chronic or acute endothelial dysfunction, and FMD measurement is expected to be included in the basis of any claims that a tobacco product does not negatively impact endothelial function.

PMI’s studies of endothelial function are based on isolated cell properties in culture and on biomarkers, and do not directly test for endothelial dysfunction potentially caused by IQOS aerosol inhalation. PMI claims to have studied the relative effects of IQOS aerosol and cigarette smoke on mechanisms involved in endothelial function, with the conclusion that IQOS exposure is more benign than cigarette smoke exposure in this regard. Notably, PMI’s studies of endothelial functional properties are on the level of cell culture and address the integrity of endothelial cell monolayers and monocyte efflux as well as molecular changes.23, 24 Their rodent studies addressed long-term differences in atherosclerotic plaque. Their clinical investigations include measurements of soluble intercellular adhesion molecule-1 (sICAM-1) as a biomarker indicative of endothelial dysfunction.25 Importantly, neither their clinical nor animal studies include measurements of FMD.

Their published reports have been carefully worded to avoid saying that IQOS does not cause endothelial dysfunction, but the MRTP application makes the claim that the systems toxicology studies reported in the application “cover a variety of human-derived in vitro model systems comparing the impact of THS aerosol with that of cigarette smoke on vascular inflammation, endothelial dysfunction and airway epithelium toxicity” (PMP S.A. MRTP application Executive Summary, Section 2.7, page 11). The conclusion that IQOS aerosol induces less endothelial dysfunction is not supported by their studies.

FMD in rats exposed to undiluted IQOS aerosol is impaired to the same extent as in rats exposed to cigarette smoke. Our work26, 27 demonstrated that ten 5-second exposures of rats to IQOS aerosol over a 5 minute period substantially impaired FMD to the same extent as similar exposure to cigarette smoke. Our exposure conditions were designed to approximate the use of a single IQOS HeatStick, with identical exposure conditions for the cigarette exposures. To confirm that our exposure conditions were relevant to real-world use, we measured blood levels of nicotine immediately after and 20 minutes after the end of the brief exposure, and determined that the nicotine concentrations after one complete cigarette exposure period were comparable to the blood levels in humans after smoking a single cigarette.

This validated our conditions for inhalation of undiluted cigarette smoke by the rats, and by extension, the relevance of our comparable conditions for inhalation of IQOS aerosol.

These results were presented on November 14, 2017 at the American Heart Association annual Scientific Sessions. Their press release containing a more detailed description of these findings (attachment #1), as well as the poster presentation itself (attachment #2), are appended at the end of this comment after the references.

Conclusion. Unless PMI is able to provide results from humans or living animals showing that IQOS aerosol exposure leads to less vascular endothelial dysfunction than cigarette smoke exposure, PMI’s MRTP application should not claim nor imply that IQOS carries reduced risk for vascular endothelial function.


1. Reuters. Philip Morris seeks U.S. approval to market alternative cigarette (12/6/16; accessed 6/9/17). 2016; Available from:
2. Altria Group. Altria’s Statement on Philip Morris International’s MRTP Application Submission with the FDA (12/6/16; accessed 5/5/17). 2016; Available from:
3. U.S. Food and Drug Administration. Philip Morris Products S.A. Modified Risk Tobacco Product (MRTP) Applications (5/24/17; accessed 6/9/17). 2017; Available from:
4. Smith MR, Clark B, Ludicke F, Schaller JP, Vanscheeuwijck P, Hoeng J, Peitsch MC. Evaluation of the Tobacco Heating System 2.2. Part 1: Description of the system and the scientific assessment program. Regul Toxicol Pharmacol 2016;81 Suppl 2:S17-S26
5. Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J Physiol 2005;568(Pt 2):357-69 (PMC 1474741)
6. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Luscher TF, Shechter M, Taddei S, Vita JA, Lerman A. The assessment of endothelial function: from research into clinical practice. Circulation 2012;126(6):753-67 (PMC 3427943)
7. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340(8828):1111-5
8. Widlansky ME, Gokce N, Keaney JF, Jr., Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003;42(7):1149-60
9. Nabel EG, Selwyn AP, Ganz P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol 1990;16(2):349-56
10. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, Selwyn AP. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26(5):1235-41
11. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 2007;115(18):2390-7
12. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation 2009;120(6):502-9 (PMC 2740975)
13. Yeboah J, Sutton-Tyrrell K, McBurnie MA, Burke GL, Herrington DM, Crouse JR. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study. Atherosclerosis 2008;197(2):768-76
14. Celermajer DS, Adams MR, Clarkson P, Robinson J, McCredie R, Donald A, Deanfield JE. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Engl J Med 1996;334(3):150-4
15. Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993;88(5 Pt 1):2149-55
16. Juonala M, Magnussen CG, Venn A, Gall S, Kahonen M, Laitinen T, Taittonen L, Lehtimaki T, Jokinen E, Sun C, Viikari JS, Dwyer T, Raitakari OT. Parental smoking in childhood and brachial artery flow-mediated dilatation in young adults: the Cardiovascular Risk in Young Finns study and the Childhood Determinants of Adult Health study. Arterioscler Thromb Vasc Biol 2012;32(4):1024-31
17. Kato T, Inoue T, Morooka T, Yoshimoto N, Node K. Short-term passive smoking causes endothelial dysfunction via oxidative stress in nonsmokers. Can J Physiol Pharmacol 2006;84(5):523-9
18. Heiss C, Amabile N, Lee AC, Real WM, Schick SF, Lao D, Wong ML, Jahn S, Angeli FS, Minasi P, Springer ML, Hammond SK, Glantz SA, Grossman W, Balmes JR, Yeghiazarians Y. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production. J Am Coll Cardiol 2008;51(18):1760-71
19. Frey PF, Ganz P, Hsue PY, Benowitz NL, Glantz SA, Balmes JR, Schick SF. The exposure-dependent effects of aged secondhand smoke on endothelial function. J Am Coll Cardiol 2012;59(21):1908-13
20. Pinnamaneni K, Sievers RE, Sharma R, Selchau AM, Gutierrez G, Nordsieck EJ, Su R, An S, Chen Q, Wang X, Derakhshandeh R, Aschbacher K, Heiss C, Glantz SA, Schick SF, Springer ML. Brief exposure to secondhand smoke reversibly impairs endothelial vasodilatory function. Nicotine Tob Res 2014;16(5):584-90 (PMC 3977486)
21. Liu J, Wang X, Narayan S, Glantz SA, Schick SF, Springer ML. Impairment of endothelial function by little cigar secondhand smoke. Tob Regul Sci 2016;2(1):56-63 (PMC 4703945)
22. Wang X, Derakhshandeh R, Liu J, Narayan S, Nabavizadeh P, Le S, Danforth OM, Pinnamaneni K, Rodriguez HJ, Luu E, Sievers RE, Schick SF, Glantz SA, Springer ML. One minute of marijuana secondhand smoke exposure substantially impairs vascular endothelial function. J Am Heart Assoc 2016;5(8) e003858. (PMC 5015303)
23. Poussin C, Laurent A, Peitsch MC, Hoeng J, De Leon H. Systems toxicology-based assessment of the candidate modified risk tobacco product THS2.2 for the adhesion of monocytic cells to human coronary arterial endothelial cells. Toxicology 2016;339:73-86
24. van der Toorn M, Frentzel S, De Leon H, Goedertier D, Peitsch MC, Hoeng J. Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes. Food Chem Toxicol 2015;86:81-7
25. Ludicke F, Picavet P, Baker G, Haziza C, Poux V, Lama N, Weitkunat R. Effects of Switching to the Menthol Tobacco Heating System 2.2, Smoking Abstinence, or Continued Cigarette Smoking on Clinically Relevant Risk Markers: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 2). Nicotine Tob Res 2017; Epub ahead of print April 21, 2017
26. Nabavizadeh P, Liu J, Ibrahim S, Springer ML. Impairment of Endothelial Function by Inhalation of Heat-Not-Burn Tobacco Aerosol (conference abstract). Circulation 2017;136:A16035
27. Nabavizadeh P, Liu J, Ibrahim S, Derakhshandeh R, Springer ML. Inhalation of heat-not-burn tobacco aerosol impairs vascular endothelial function (poster presentation Nov 14, 2017). American Heart Association Scientific Sessions, Anaheim, CA 2017

Heat-not-burn tobacco products may be ‘not so hot’ at protecting blood vessel function
Tuesday News Tip Poster Presentation T1051 Session: AT.APS.28.

Embargoed until time 12 p.m. PT/ 3 p.m. ET, Tuesday, Nov. 14, 2017
This news tip contains updated study information not reflected in the abstract.

ANAHEIM, California, Nov. 14, 2017 — Heat-not-burn devices may eliminate users’ exposure to tobacco smoke, but the vapor they produce has the same negative impact on blood vessel function as smoking, according to a preliminary animal study presented at the American Heart Association’s Scientific Sessions 2017, a premier global exchange of the latest advances in cardiovascular science for researchers and clinicians.

Heat-not-burn products are not new, but have been recently updated and test marketed in several countries outside the United States with greater success. Despite tobacco industry claims of heat-not-burn products being less harmful than regular cigarettes, the health effects of the devices are still unproven, according to researchers.

Heat-not-burn devices raise the temperature of tobacco enough to release nicotine-containing vapor but not enough to burn, avoiding smoke exposure. To test the devices’ ability to reduce harm, researchers assessed whether exposure to the vapor affects the ability of rats’ blood vessels to widen when there is increased blood flow – a measure of blood vessel health that is impaired with exposure to smoke from cigarettes, small cigars and marijuana.

Researchers found:
• After ten 15-second exposures over five minutes to the vapor from iQOS, a heat-not-burn device that has been test-marketed in several countries, blood vessel function decreased by 58 percent.
• Similarly, after ten 5-second exposures over five minutes to iQOS vapor, blood vessel function decreased by a similar amount, 60 percent.
• The reduction was comparable to that induced by cigarette smoke (57 percent for the 15-second exposures, 62 percent for the 5-second exposures).
• Exposure to clean air had no impact on blood vessel dilation.
• The amount of nicotine in the rats’ blood after exposure to cigarette smoke was similar to the amount in blood after humans have smoked one cigarette, confirming that the exposure conditions were relevant to the real world. However, the amount of nicotine in the blood after exposure to iQOS vapor was substantially higher (70.3 nanogram/milliliter for iQOS, 15.0 nanogram/milliliter for cigarettes).

Using heat-not-burn products may not avoid the adverse cardiovascular effects of smoking cigarettes.

The research was conducted by Pooneh Nabavizadeh, M.D. in a group led by Matthew L. Springer, Ph.D. Other contributors were Jiangtao Liu, M.D., Sharina Ibrahim, B.Sc. and Ronak Derakhshandeh, M.S.

The study was funded by the National Heart, Lung, and Blood Institute at the National Institutes of Health and the U.S. Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA.

Presentation Location: Basic Science Section, Science and Technology Hall

FDA needs to extend the public comment period on PM MRTP for iQOS

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Nicotine is still nicotine, no matter the delivery system, and it’s still bad for you

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Wait, What? Tobacco Giant Backs Foundation to End Smoking

An old adage in journalism states that when a dog bites a man, it’s not news. But when a man bites a dog, now, that’s news. Well, the proverbial man just bit the dog in the form of a nearly $1 billion pledge to reduce smoking from the maker of Marlboro cigarettes.

Philip Morris International will donate $80 million a year for the next 12 years to the recently launched Foundation for a Smoke-Free World. The new foundation stresses independence from its donors and their agendas, but so far, the company behind Marlboro is its only backer.

The donation comes as Philip Morris is said to be preparing for a smoke-free future. More than 3 million smokers have switched to the company’s e-cigarette IQOS, according to Bloomberg. IQOS heats tobacco to produce a vapor instead of burning it, which the company believes makes it less harmful than conventional cigarettes. The company asked the FDA to approve marketing that sells the product as a device that may reduce the chance of smoking-related diseases.

Derek Yach, the man heading the new foundation, is a vocal supporter of e-cigarettes. The devices, which don’t contain tar, provide a safer alternative for smokers to use while weaning themselves off traditional cigarettes, Yach wrote in a 2015 editorial. Opponents argue that “safer” is not the same as “safe,” and claim that e-cigarettes act as a gateway drug for conventional cigarettes.

Yach is a former World Health Organization official who led the organization’s campaigns against health issues arising from unhealthy diets and smoking. He worked on a global tobacco treaty while at the organization, but has a history of making deals with the devil in the name of progress. Yach worked for PepsiCo for six years after leaving WHO, where he says he pushed the company to make products healthier, including chips with less salt and fat and drinks with less sugar. It’s hard to miss the parallels to Yach’s latest endeavor and its backer.

The Philip Morris donation to the Foundation for a Smoke-Free World was met with skepticism from some.

Deborah Arnott, the CEO of Action on Smoking and Health, a public health charity based in the U.K., criticized the announcement. “Tobacco industry claims can never be accepted at face value,” she said. “The tobacco industry has a terrible track record of funding research designed to support its efforts to block policies to cut smoking.”

Arnott has a point. The tobacco industry has a long and checkered past in meddling in medical and research fields to benefit its bottom line. From the 1920s through the 1940s, the industry leaned heavily on advertising that claimed cigarettes were “physician approved.”

More recently, the industry funded research designed to support the claim that secondhand smoke posed no danger to non-smokers, a review of millions of pages of industry documents revealed. Research proving the opposite was used to support smoking bans in public and private places.

Some worry that the new foundation bankrolled by Philip Morris will also produce research and disseminate information that misleads the public. The International Union against Tuberculosis and Lung Disease denounced the gift as “a billion-dollar bribe the tobacco company hopes will secure it a seat at the table with public health policymakers around the world… Through propaganda, it only has the potential to undermine, delay and obfuscate the work of public health policymakers and advocates who champion evidence-based measures to reduce tobacco use.” The Union said that the company will continue to spend exponentially more money to hook people in poor countries on smoking than on preventive efforts through the foundation.

Although smoking is on the decline in the U.S., tobacco use is still the leading preventable cause of death in the country, according the Center for Disease Control.

Worldwide, tobacco kills about 6 million people a year, which is more than AIDS and malaria combined. The number is projected to rise to 8 million by 2030.

Despite that, there’s not a widespread effort among funders to curb smoking, which is another reason the Philip Morris gift is notable. The two biggest names in the space right now are Bloomberg Philanthropies and the Gates Foundation. Back in 2015, the two teamed up to take on companies like Philip Morris that sue low- and middle-income countries to prevent their governments from enforcing strong tobacco control laws.

The tobacco giant’s intentions and the young foundation’s integrity remain to be seen.