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Global smokers’ study criticised as biased

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How tobacco companies in the UK prepared for and responded to standardised packaging of cigarettes and rolling tobacco

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Andre Calantzopoulos: ‘A future without smoking can be a reality’

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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.”

Seeing Through Big Tobacco’s Smokescreen

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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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Teens, are you listening?Big Tobacco admits smoking is “highly addictive.”

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