Transcript

The Tamiflu Trials

Aired June 17, 2020

[CITED THEME]

Audrey: Why? Why are you, why are you so passionate about this?

 

Tom: Mmm. Would you like to be fooled? Do you like being fooled? Audrey do you enjoy being made to look like an idiot? 

GORDON KATIC: This is Cited. I’m Gordon Katic.

[CITED THEME]

 

OBAMA: We are closely monitoring the emerging cases of swine flu in the US. This is obviously a cause for concern and requires a heightened state of alert.

GORDON: The year was 2009. President Obama had just been elected. And he was facing a Swine Flu pandemic. This is a speech he gave in front of the National Academies of Sciences. 

OBAMA: But one thing is clear: our capacity to deal with a public health challenge of this sort rests heavily with our scientific community. This is one more example of why we can’t allow our nation to fall behind. 

GORDON: Obama was praised for his response; he’s still praised for that response. So, what did he actually do? Well one big thing is he did was stockpile a drug treatment. A drug called Tamiflu. 

OBAMA: The good news is that the current strain of H1N1 can be defeated with by a course of anti-viral treatment that we already have on hand. We began this week with 50 million courses of this treatment in the Strategic National Stockpile.

GORDON: Before him President Bush did the same—he bought even more. That was in preparation for Bird Flu.
Tamiflu is a treatment, not a vaccine. And it wasn’t even designed for a pandemic—it was designed for the regular old flu. So, Bush and Obama bought it for off-label use. There just wasn’t time to make a whole new drug. So they looked around what we had, and they said—hey, maybe this one will work.

This might sound familiar. Because it’s exactly what’s happening right now. Dozens of drugs are being researched for off-label use to treat the Novel Coronavirus—Remdesivir, Hydroxycloroquin, Actemra, Kevzara, the list goes on. So how do experts pick from that list? What will be the Coronavirus treatment? Billions of dollars of public money are on the line, not to mention— hundreds of thousands, maybe millions, of lives.

You’d hope that the best, independent, evidence-based experts are the ones who decide. But the story of Tamifu shows money can buy you influence, and maybe even buy you experts

Today, we open up the black-box of pharmaceutical research. How do experts decide what makes a good drug, and how do pharmaceutical companies make billions from pandemic panic? 

Freelance producer Audrey Quinn brings us the story.

***

AUDREY QUINN: The story starts with Deborah Cohen, in London.
Deborah is one of those journalists, who’s so in love with journalism she made me stand up a little straighter. There’s this thing she says… a lot: 

Deborah:it's one of the beauties of being a journalist.
This is one of the beauties of journalism.
And that's one of the beauties of working on a journal.

AUDREY: But before journalism, she was on a different career path.                       

Deborah: Clearly I’d had an inkling, uh, at, uh, at medical school that I possibly wasn't going to be a full time clinician.

Audrey: How'd your parents react?

Deborah:
My mom was very much like, I just heard on the radio that doctors are the most respected members of society, and journalists are in the gutter with politicians and estate agents. And I said to my mom, Well it's a good job, I like swimming around in the gutter then.

AUDREY: But her first journalism job, she didn’t get too far from medicine. She started with the British Medical Journal, the BMJ. It’s one of the top medical journals in the world. It also does medical news reporting. Within a few years, Deborah’s on staff, of course loving it.

Deborah: Give me a story and, there'll be a health angle. There’s a health angle to pretty much anything.

AUDREY: In her early years at the BMJ, Deborah had a pretty typical new reporter beat. She covered medical conferences... press releases.  Then, she starts looking into Tamiflu. This is the investigation that would  jumpstart her career.

TAMIFLU AD: The flu virus. It’s a really big deal. And with fever, aches, and chills- mom knows, it needs a big solution. An antiviral. Ask about prescription Tamiflu. 

AUDREY: Deborah’s reporting on Tamiflu goes way back, from before it was even approved by the Food and Drug Administration.  She tells me it was originally made by a company called Gilead, and then licensed in 1996 by a Swiss drug company.

Audrey: RO- and am I, how am I saying it right? Roche, how do you say the, the company company

Deborah: I say Rosh, Rosh 

Audrey: Rrosh Okay, let's, let's say Rosh then. Um, so Rosh

GORDON: When Tamiflu was being developed, there was a lot of excitement around it. 

Deborah: What was kind of known at the time was there wasn't a whole lot to treat influenza. There was, some much earlier drugs, but they were really not very effective.

GORDON: Seasonal influenza, just the regular flu that comes around every year, is an enormous public health challenge—It kills about 40,000 Americans each year.

Deborah: ‘Cause what often happens with influenza, the influenza itself mightn't kill or cause serious health problems, but, but it makes you more susceptible to get an infection with something else. You might end up with it with what's known as a secondary infection.

GORDON: Secondary infections. This is an important thing to understand: it’s not usually the flu that kills you, it’s the respiratory infections that come along with the flu. Like bronchitis, or pneumonia.

AUDREY: But Tamiflu looked like it could prevent some of these: that was its superpower.
If it could prevent secondary infections, this would be a game-changer for the fight against seasonal flu. 

GORDON: But first: the FDA needs to actually approve Tamiflu for the market.
And Roche needs to provide the research to prove that the drug really does have this superpower.

AUDREY: Roche brings the data that they do have to the FDA. And the FDA says, no, you don’t have enough data for this superpower claim. But overall, Tamiflu’s approved.

GORDON This approval though, it’s pretty lukewarm. 

AUDREY: The way the head FDA reviewer writes about Tamiflu in his approval letter, he is so non-committal. He repeatedly notes that Tamiflu only offers a “modest treatment benefit,” -- it can shorten influenza symptoms by about a day.

GORDON: He says, “the clinical relevance of the modest treatment benefit is a highly subjective question.” 

AUDREY: Highly subjective. Basically he’s saying: if you think it’s worthwhile to take a drug to reduce your flu by a day, well, that’s your call.

GORDON: And the FDA added a kind of asterisk. 

Deborah: The FDA made some quite firm's stipulations saying it has not been shown to prevent secondary complications. So they actually instructed, um, Roshe to put that on the packaging.

AUDREY: Roche has to explicitly write in the packing, Tamiflu does not prevent influenza’s secondary infections-- the things that can make it deadly. This was supposed to be Tamiflu’s superpower. 

Deborah: Roshe, they, they weren't overjoyed, they thought they’d bought a bit of a dud. 

GORDON: Despite the FDA’s stipulations, Roche didn’t seem to really care-- in their promotional materials, they pushed the line that Tamiflu reduced secondary infections, along with other claims they didn’t have data for. But the The FDA found out, and sent them a warning letter in 2000.
It’s not looking like this little drug is going to hit Superman status anytime soon.

Deborah: That was slightly turned on its head, when Roche published, I say Roche published, but researchers published, something called the Kaiser review. 

GORDON: The first author on the reviewe was a Swiss virology professor named Laurent Kaiser...

Kaiser [in french]: Laurent Kaiser, professeur ode virologie...

GORDON:  Hence the “Kaiser review.” He’s here introducing himself in the Swiss Public broadcasting documentary The Saga of Tamiflu.

AUDREY: Kaiser’s team looked through ten different Tamiflu drug trials, and they concluded that patients that took Tamiflu  -- their secondary infections were less bad. Over 50 per cent less patients needed treatment for those infections. 

GORDON: Tamiflu got back its superpower.

***

 

Tom Jefferson: Now you understand this was a, this was a sea change.

AUDREY: This is Tom Jefferson, he’s an epidemiologist.

Audrey: do you say Ross or Roche?

Tom: I don't know uh. No idea.

Deborah: So Tom Jefferson's quite a character. He's based in Rome, um,  he's a British trained doctor.  He knows every detail about everything

GORDON: Tom works for something called the Cochrane Collaboration. This is like Consumer Reports for medical treatments.

AUDREY: It reviews everything—from drugs to practices like handwashing 

Tom: It was great fun at the time, you know, new frontiers. Antivirals, we did vaccines. It was great fun!  We saw things that people had not seen before, it was a lot of work, it was great fun.

Audrey: So it was, it was exciting to you to get to test the drugs that you were giving to patients and see what’s really working?

Tom: Yeah. To look at the evidence. Yeah, and you looked at the evidence using publications, because you trusted publications. Because they were the New England Journal of Medicine, Jama, The Lancet.

GORDON: Tom was on the Cochrane team charged with looking at the Tamiflu research. It reviewed it when it first came out, and reached similar conclusions to the FDA— Chochrane saw that, yeah it seemed to help people get over the flu faster, but it didn’t seem have that superpower of fighting secondary infections ...But then comes the Kaiser review.

Tom: That’s right. So this changed the content of the Cochrane Review.

GORDON: When Tom and his team put out a new Cochrane Review of Tamiflu in 2006, they changed the verdict; They said indeed, Tamiflu could reduce  influenza’s secondary infections.

AUDREY: They’d seen it in the Kaiser paper. 

GORDON: And now: Tamiflu has its expert stamp of approval. The little drug is now ready for prime time.It just needs its moment. 

****

CNN female announcer: And it's official now the deadly bird flu is in Europe.

CNN male announcer: And the fear amongst scientists remains that if the virus mutates and is easily passed between humans, tens of millions could die in a pandemic.

CNN other female announcer: In fact, some health experts say it's just a matter of time.

GORDON: In 2005 Doctors have started to notice that a particularly lethal form of influenza that affects birds, is spreading to people. And it kills over half of  the people it effects.

C-Span: One way or another, it's going to be coming into the Americas, at the very latest July.

GORDON: Experts expected up to 150-million deaths.

Obama: The United States cannot afford to have a Katrina-level of preparedness or a Katrina-like response to an international outbreak of avian flu. 

AUDREY: This is a very young looking Senator Barack Obama.

Obama: With so many warnings and so much knowledge of the threat we face, there is no excuse for failure this time around. 

GORDON: Governments are casting around, trying to come up with something to protect people from this potential new pandemic.

AUDREY: And medical experts thought: maybe Tamiflu could work -- Why not give it a shot?

GORDON: OK, to be clear—the  Cochrane and Kaiser reviews had said: Hey, Tamiflu has superpowers. But that was just for treating regular, seasonal influenza. Not for this strange new pandemic flu. So governments were talking about using it off-label.

Deborah: There was this real panic about this, this drug that was going to, to save, to save all these lives. And if they didn't have it, um. What would they do? 

GORDON: it becomes the kind of thing where if you don’t stockpile, you look bad. As the threat of bird flu grew there was enormous political pressure to get your hands on the drug. Roche even started funding studies on how much Tamiflu different countries had bought. And it made sure these studies got around.

Obama: Countries like Japan, France, England, and others, have now stockpiled enough Tamiflu to cover a quarter of their populations. With enough to cover just 2 percent of our population, the United States is, again, not one of those countries.

AUDREY: Congress wanted to put Tamiflu in the US National Stockpile, these giant warehouses for emergency medical equipment. By November 2005, then-President George W. Bush had heard the message.

Bush W: I'm asking Congress for a billion dollars to stockpile additional antiviral medications so that we have enough on hand to help treat first responders. And those on the front lines as well as populations most at risk in the first stages of a pandemic.

GORDON: The US congress approved a multi-billion dollar hoard of Tamiflu for the US Strategic National Stockpile. 

AUDREY: Bird flu never actually turned into a real pandemic, it fortunately never got that point where it efficiently spread from human to human. But a few years later, 2009, a real flu pandemic did come. Swine Flu. A now-president Obama,  he added more Tamiflu to the stockpile.

***

AUDREY: Now we’ve caught up with where we began this story….  In 2009 the US Strategic National Stockpile had enough Tamiflu powder to treat one in five Americans through an entire course of the flu.

GORDON: And it wasn’t just the US going whole hog on Tamiflu. Canada stockpiled at least six million doses. Back in London, Deborah Cohen with the BMJ sees the UK stockpile thirty million.

Deborah: If you've got people that are  frightened of a pandemic and frightened of the death toll,frightened to the impact on health services… And you've got a drug that promises to reduce secondary complications, promises to reduce, spread, promises to reduce hospitalizations, reduce the burden on health services, reduce the burden on clinicians. It's not hard to kind of see how governments might be seduced into stockpiling it. Into thinking this is the right thing to do.

AUDREY: This little drug that could… it was now, an international blockbuster.

GORDON: But does it actually work? I’m Gordon Katic, and this is Cited. Audrey Quinn and I will be back in one minute.

[CITED THEME]

GORDON: This is the part of the program where I sell you vitamin supplements. Just kidding… as you know, we don’t do ads. But like I’ve said before-- instead, you can do me a little favors.
I finally have Cited mugs. I mentioned this before. It took a while, but they’re here. They’re pretty cool. And so you: my die hard listener, I want you to have one. I’ll give it to you for free. You just have to do one thing for me, I’ve asked for this before: Send the podcast to a friend who you think might like it—and then me the screengrab of the text or email and send it to me. 
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I’ll randomly pick three people from everyone who emails me. If you’re one of the lucky three, you’ll get a mug. It’s that easy.

Send that to info@citedmedia.ca. If you really want to just buy a mug, let me know. Right now, I have a few. But I’m trying to figure out if I should start selling swag.

OK, that’s all the housekeeping I have. Back to our regular schedule programming.

[CITED THEME]

GORDON: Before all this stockpiling, there’d been one country that used Tamiflu more than any other, Japan By 2008, about 75% of the people who took Tamiflu were Japanese. Doctors had a lot of experience with it.

Keiji Hayashi: [Speaking in Japanese]

TRANSLATION: My name is Keiji Hayashi. I run a small pediatric clinic in Osaka. This is my wife Yasuko – she’s a pharmacist.

AUDREY: Keiji Hayashi was a pediatrician in Osaka. Japan. He’s now retired, didn’t respond to our interview requests. But this is from a video interview he did for the 2011 documentary, The Saga of Tamiflu. Doctor Hayashi stands in his small pediatric clinic’s waiting room, with an impressive collection of Winnie the Pooh stuffed animals.

Hayashi: [Speaking in Japanese]

TRANSLATION: When Tamiflu was first marketed, I was using it, but I later found out that there are many side effects, so I have been trying my best to stay away from Tamiflu.

Hayashi: [Speaking in Japanese]

TRANSLATION: Sometimes, there are mothers who come to tell me that they have had terrible experiences with Tamiflu. For example, a two-year-old boy suddenly grabbed a pair of scissors and started going wild with them. Or, a mother told me about a gigantic eraser that was attacking her and she had to run away from it all night. When her husband heard this, he was in disbelief, and also took the pill. And he was hallucinating that he was flying above the clouds.

GORDON: Hayashi and other Japanese doctors had started to report seeing strange side effects in kids who took Tamiflu. Delusions, kids hurting themselves, even suicides. 

AUDREY: Hayashi doesn't know for sure if this is because of Tamiflu, but it’s scary enough.And so, he stops prescribing it.
So Hayashi decides to take a deeper look into the Kaiser review paper. This was the main source of hope that Tamiflu can reduce the severity of secondary infections. 

Hayashi: [Speaking in Japanese] 

TRANSLATION: His [Kaiser’s] literature reviewed ten data. I found that two had been published. When I looked at the two data, I found that Tamiflu lacked superiority in preventing complications such as bronchitis. So actually the eight remaining data, that are not published, are the ones that prove Tamiflu’s effectiveness in preventing complications. 

GORDON: He’s saying that only two of the trials that the Kaiser team had reviewed had actually been published. That means only two were peer reviewed. And from what he could see, neither of them proved that Tamiflu had much -- if any -- of an affect on secondary infections.

AUDREY:  So he wondered, well -- where does it say that Tamiflu can do this? Hayashi realizes that Kaiser’s team must have drawn that conclusion from the eight un-published trials on Tamiflu...  trials that had been run by Tamiflu’s maker, Roche. 

Hayashi: [Speaking in Japanese] 

TRANSLATION: And another thing is when looking at the authors’ affiliation; four aside from Kaiser were from Roche. And another was a consultant who is paid by Roche. So I thought the literature was basically written by Roche.

GORDON: So now Hayashi goes to Tom Jefferson at the Cochrane Review.

AUDREY: In July 2009, Hayashi leaves a comment at the bottom of Tom’s Cochrane review on Tamiflu. He addresses it directly to Tom.

GORDON: He writes, “Dear Mr Jefferson - We have some questions on the conclusion in your Oseltamivir review [...] We have found that this conclusion is based on the other review (Kaiser - 2003) and not on your own data analysis.”

Tom Jefferson: So we looked at each other, we scratched our heads, re-read Kaiser and we said--- he's got a point.

GORDON: He feels like he’s screwed up. He gave this drug his stamp of approval, but he didn’t really check the data.

Tom: How can you trust this stuff if you haven't seen it? How do you know if you haven't seen it? We said, well, you know, it's published in  a serious journal. We gave them the benefit of the doubt. 

GORDON: Now, Tom sets out to actually look at the data. But he has to find it first. 

AUDREY: The first thing he does is email the researchers that did the Kaiser review. They say, they can’t give it to him, they don’t have it. So he decides to call for backup. He calls the editor of the BMJ, the British Medical Journal.

Tom: I, I asked for advice. I said, Oh, this needs investigating. I'll put Debra Cohen onto it. That's how she started.

Deborah:  it landed in my intray, and rather than farm it out to somebody else, I thought Oh, I quite fancy doing this

AUDREY: So Deborah and Tom team up, and first step: they go back to the Kaiser team again.  

Deborah:  we went to Lauren Kaiser, who's the lead author of the Kaiser review, and Frederick Hayden, who was the corresponding author.

Tom: I said, could we please have the data to check from these unpublished trials? And they said, we don't have the data. Roche has the data.

Audrey: How could that be?

Tom: Umm. Kaiser, and Hayden hadn't seen any of the raw data of the meta analysis. 

GORDON:  Then Tom and Deborah reached out to the authors of the individual trials that make up the Kaiser review. Well, those trial authors couldn’t provide data either. They said Roche had done the analysis of the initial data, and then they’d just analyzed the data summaries Roche provided.

AUDREY: Then Tom Jefferson finds somebody unexpected-- and Deborah gives her a call..

Melanie Sinclair:  I was one of the writers working on the Tamiflu account. 

AUDREY: This is Melanie Sinclair. She now works in another scientific field—but she says to Deborah-- I worked at a medical publishing company that contracts with Roche. 

Melanie: I was quite junior, it was my first job from leaving university. It wasn't, the informative educational type job I had been hoping it would be when I first took the job.  I thought it would be more, um, medical information. So maybe leaflet and medical education. Um, you know, informing, uh, informing the public, informing patients, that kind of thing. 

AUDREY: But that’s not what it was. She tells Deborah, “I was a medical ghostwriter. I worked on the Tamiflu account.” And she tells Deborah she doesn’t have a problem with ghostwriting.

GORDON: But the question becomes: who is running the show-- the researches? Or the company?

Melanie: See this is where, this is where it all gets a bit gray area, isn't it?

AUDREY: On the Tamiflu trials, she says it wasn’t the researchers—it was Roche’s marketing department. 

Melanie:  Because this was all about communications, then that's the department it came through.

AUDREY: What really bothered her, was that Roche was keeping the data from from Tom and Deborah . 

Melanie: What does that say about the data that we received and that we were writing from? It shouldn't be a decent marketing department that gets to make the decision. It should be data.

Deborah: So the ghostwriter had written the papers, and when you've got the ghostwriter writing the papers, it begs the question-- well, how much have the named authors, the named scientists, actually seen themselves?

Tom: In other words, these guys had not written the manuscript and are not seeing the raw data. Yet on the basis of these trials, governments have stockpiled, and are still stockpiling, huge quantities of these drugs

***

Tom: So you okay with the story so far,

Audrey: Yup. Yup. I'm following.

Tom : It gets…. it gets weirder. 

GORDON: The ghostwriter couldn’t give the data to Tom. The researchers couldn’t either. So Tom and Deborah only had one place left to go.

Tom: We asked Roche for the data, we asked as single, simple researchers. We said, could you, could we please have the data from these 10 trials so that we can answer our study question. We can do an honest review and we can answer Dr. Hayashi's question. 

AUDREY: This was the start of four years of back-and-forth between Tom and his Cochrane team, paired with Deborah and her BMJ team, trying to get the raw data from Roche I read all of these emails… there were 47.

GORDON: “Hi, would it please be possible to have the data I requested asap?”

AUDREY: “Dear Tom, thank you for your time today. I have asked my colleagues in clinical development for the information you are after.”

GORDON: “We have not heard anything from you. Could you please let us know the status of our various queries?”

AUDREY: “Hi Tom, I have left you a voice mail to arrange a teleconference this afternoon or tomorrow. Are you available?”

GORDON: “I hope you enjoyed your holiday. It is now four weeks since you told us that you would get back to us in two weeks.”

AUDREY: “Dear Tom...I will extract the data you are after but need to send you a confidentiality agreement.”

Tom: They sent us a confidentiality agreement with a secrecy clause. If I signed that I wouldn't have been able to use the data, and I wouldn't even have been able to, um, uh, to mention the agreement.

GORDON: This defeats the purpose of the whole process -- Tom wants this data so he can review it. Publicly. But then after about three weeks Roche tells Tom ok, we’ll give you excerpts of the studies. And this seems like a breakthrough!  Tom says thanks, I’ll take a look. 

Tom Jefferson:  We said, I'm sorry, we, we, we can't, we can't do an honest job out of this. 

GORDON: Tom says there’s a whole bunch of important information missing from the excerpts Roche sent. He can’t use them. 

Tom: We can’t see the data,  then how the hell can we assess it? Can we vouch for it?

AUDREY: But Tom still owes Hayashi a reply. 

Tom:  The Cochrane rule is that you have to answer a remark that's made on your review within six months of that remark being made. 

GORDON: So in December, 2009 Tom and his team published an updated review on Tamiflu, based on what they’d gotten from Roche so far. They say there’s not enough evidence to show Tamiflu reduces secondary infections of influenza. That’s THE thing that this drug is supposed to do...But… it might …. we just don’t know, because we just we haven’t been able to see the full data.

AUDREY: Deborah and Tom’s hunt to get all the Tamiflu data—it looks like it’s hitting a roadblock. 

***

GORDON: And so—Deborah switches gears a bit. She’d been investigating Tamiflu from a research angle. But maybe that wasn’t the right place to look.

Deborah: It was only later when I looked at the marketing material. And as a rookie investigative reporter that was about like, Oh dear, I stepped in a hornet's nest

GORDON: In Tamiflu’s early marketing plan, the public relations team lays out the major challenges facing the drug. Flu seasons are unpredictable. Public interest is low. And, Tamiflu is not the only game in town. In fact, another flu drug had also gotten FDA approval at the same time,  it’s called Relenza.

AUDREY: You have to inhale Relenza — not so fun. But Relenza had Newman. The mail carrier from Seinfeld.

[[doorbell]
Woman: Who is it?

Newman: It's me. Influenza. You know the flu. Coming in! 

GORDON [IN JERRY VOICE]: Hello, Newman! 

AUDREY: Yeah, sorry don’t get it.

Ad Narrator: He's influenza. And he’ll make you miserable with symptoms like fatigue, high fever, cough, headache, and bodyaches.

Newman: People say I have an infectious laugh, whaddya think? Heheheheheh.

Ad Narrator: Introducing Relenza, a new prescription medicine to help you start feeling better sooner….

 GORDON: While Relenza had the starpower of Newman, Tamiflu had a plan for this. Because they had something more important: EXPERTS.
According to their marketing plan, they were going to quote, “align Roche with credible third-party advocates”. Doctors, flu researchers, and government agencies.

Deborah:  And we've got a term for people like that. We call them key opinion leaders.

AUDREY: And so Deborah starts wondering—which  key opinion leaders are we talking about

GORDON: She starts digging into the top public health experts: people at the World Health Organization. The WHO had created influenza guidelines in 2004. These were recommendations for all governments.. 

Deborah:  And one, I remember one particularly distinct, um, recommendation was we must stockpile antivirals, which obviously included Tamiflu.

AUDREY:  And then Deborah starts looking into the people who actually wrote the recommendation.

GORDON: Okay here’s the list of contributors to the WHO influenza pandemic plan. We have Frederick Hayden, Professor of Internal Medicine & Pathology at the University of Virginia--

AUDREY: And a paid Roche consultant.

GORDON: Karl Nicholson, Professor of Infectious Diseases at the Leicester Royal Infirmary--

AUDREY: And a paid Roche consultant.

GORDON: Abe Osterhaus, a professor at the Institute of Virology, Erasmus University--

AUDREY: And contributor to Roche marketing material.

GORDON: Dr. Rene Snacken, a senior expert at the European Centre for Disease Prevention and Control. 

AUDREY: Okay, he’s also a writer of a Roche promotional booklet. 

Deborah: The people that have marketed Tamiflu, or people had done research on behalf of Roche, they were the same people who were drawing up the guidelines for what to do in a pandemic.  And I thought should those same people be advising governments? Surely they've got a kind of conflict of interest.
It was really controversial to raise the specter that perhaps scientists were less than objective, and they had financial ties. And the backlash was phenomenal. I mean, for, for, for the record, you know, not proud of this-- I was, I was phoned up by Alex Jones, shock jock. And, he was trying to, he was trying to goad me into saying all sorts of stuff, 

AUDREY: Deborah gets a lot of pushback. Some say her reporting feeds into the right-wing conspiracy that medical science is some kind of secret plot.

GORDON: But she wasn’t the only serious journalist raising flags about Tamiflu. And the WHO wasn’t the only independent health agency that seemed to have ties with Roche. 

***

Jeanne Lenzer: You checking the levels now? Okay. 

AUDREY: Jeanne Lenzer also wrote for the BMJ. She’s an investigative reporter, like Deborah.

Jeanne Lenzer: She's a doll. I love her. If you talk to her again? You say hello to her for me? I have got to, I've got an email her.

AUDREY: Jeanne had a similar career trajectory to Deborah. Medicine first, then journalism.

Audrey: Did your, did your medical coworkers start to notice that,  Oh, Jeanne's-- we're kind of losing Jeannie to the world of journalism.

Jeanne Lenzer: [laughs] Yeah. Uh, I drive people crazy with my  skepticism about things

GORDON: Unlike Deborah in London, Jeanne’s in the US.

Audrey: Do you say Roche or Rosh?

Jeanne Lenzer: Roche

Audrey: You say Roche. 

GORDON:  Jeanne had seen Deborah Cohen’s investigation into the WHO,  and it got her wondering about Roche and public health experts closer to home. 

AUDREY: So she’s paying particular attention to the US Centers for Disease Control, the CDC. At the height of the swine flu pandemic, 2009, the CDC is ramping up flu prep efforts and it puts out this PSA video.  .

CDC video host: remember the expression, take two and call me in the morning?

GORDON: Um… I’m not sure I do. 

AUDREY: Yeah I had to look this up-- apparently this was like, the cliche thing to hear from your doctor-- “take two aspirin and call me in the morning”.

CDC video host: Well, when it comes to influenza, the Centers for Disease Control and Prevention says it's best to take three. It could save your life. Dr Bresee, what does CDC mean by take three?

Dr. Joe Bresee: Take three is a way for people to remember the three main actions they can take to fight the flu.

AUDREY: This PSA came out in 2009, at the height of the swine flu pandemic.  The host sits with Dr. Joe Bresee-- yes that’s his real name-- on a set that looks like a Charlie Rose interview. They’re at a round wooden table with water glasses, infinite black space beyond them. They’re saying there’s three main steps to beat influenza.
The first two steps were your basics. 

  1. Get the flu Vaccine. 
  2. Cover your mouth and nose when you cough…

CDC video host: And three? 

Dr. Joe Bresee: Three is take antiviral drugs. If you get sick with a flu and your doctor prescribes them. These drugs can make you feel better faster or make your symptoms milder.

Jeanne Lenzer: The important one to me was number three.  Take your antiviral drug, which basically was Tamiflu cause that was the drug. 

Tom Frieden: To put it very simply, if I or one of the members of my family got flu or a flu-like illness, I would get them or me treated with Tamiflu as quickly as possible.

AUDREY: This is then-head of the CDC, Tom Frieden, on a CDC telebriefing with reporters.

Jeanne:  They were saying that, um, Tamiflu is lifesaving.

Tom Frieden: The evidence indicates that it will shorten how long you're sick, might keep you out of the hospital and could even save your life. 

AUDREY: This didn’t line up for Jeanne. She had seen what the other main US federal health agency, the Food and Drug Administration, had said about Tamiflu. That there wasn’t enough evidence that it did more than reduce flu symptoms by about a day. 

GORDON: You remember that big asterisk the FDA put on it? Well, it’s still there—despite what the Kaiser review had said, despite the WHO’s recommendation, and despite the stockpiling. According to the FDA, no secondary infection-stopping superpower; they’re pretty clear about this. 

Jeanne: They said, you cannot claim that it either reduces pneumonia or mortality. That was the FDA's conclusion after reading the data. And CDC is saying the opposite.So what's going on?

AUDREY: Jeanne writes a couple articles about how odd it is that the CDC seems to be pushing Roche’s adspeak about Tamiflu. And then, she gets an email, from someone within the CDC.

Jeanne: An infectious disease specialist physician, contacted me and said that he thought my article was spot on. He kept saying, this drug does not appear to have good effect against flu of any form. And I said. This really smells like money to me. He Said, Oh, no, no, no. The CDC is independent. And it just didn’t seem like that to me. It didn’t make sense, and it didn’t add up. And it didn’t to him clinically. So what’s going on?

GORDON:  The Centre for Diseases Control is widely considered the best and most important public health agency in the world. They’re considered the gold standard  because they give evidence-based advice, and they do so impartially

Jeanne: In fact, they write it on their, um, uh, recommendations that they do not take industry funding. They don't take it, period. End of sentence. That's what they say. 

AUDREY: BUT Jeanne notices there’s something called the CDC Foundation. Which takes donations. She starts emailing with the CDC press person about what exactly that means.

Jeanne: So when I finally got them to admit that they were getting millions of dollars from industry. It turns out that those donations, 100% of them are directed, meaning that the companies that “donate”, quote unquote, to the CDC they donate with specific directives that it has to be on the topic that benefits their drug.
I have my correspondence with CDC, I documented with CDC after pulling some teeth over there that in fact, the entire Take Three campaign had been funded by Roche to the tune of $198,000.

AUDREY: Remember that  competitor drug, Relenza? Once that marketing push really got going, Relenza didn’t stand a chance.

***

GORDON: At this point, I feel a little bit like I’m living in the Truman Show. The Truman Show is about a man who thinks everything is normal, In reality, he’s the star of a television show; but he’s the only person in the show who doesn’t know it’s a show. Everyone who works with him, everyone who cares for him, everyone who loves him—they’re actually working for a company, the makers of this television program. 

TRUMAN: You can't stand me.

TRUMAN’S WIFE: That's not true. Why don't you let me fix you some of this new Mo Cocoa Drink all natural cocoa beans from the upper slopes of mountain Nicaragua. No artificial sweeteners.

TRUMAN: What the hell are you talking about? Who are you talking to?

TRUMAN’S WIFE: I've tasted other cocoas. This is the best.

GORDON: So many of the experts in Tamiflu’s story-- the research experts, the public health experts, and the policy wonks. Coming into this, I would thought they were giving us their independent judgement. I thought, they just tasted all the other cocos, and this is the best. But what we’re learning: many of the key experts here are Roche-backed. 

AUDREY: But this isn’t some sinister plot made by some all-powerful director. It’s a system that has sprung up organically because there’s so much industry money in this system. Perhaps the most shocking part of the story: it’s not that Roche is doing something crazy-- it’s that a lot of what they’re doing… is typical.
Like, Roche doing their own studies. Well, seventy percent of drug trials in the US are funded by the very same people who are trying to sell the drug.
Ghost writers-- hard to find exact stats, but the best research estimates that around 20% of large drug trials have medical ghostwriters. Industry-funded experts advising governments? Also par for the course. 

Stephen Toovey: If anybody is any good, uh, as an expert, everybody will want to talk to them. 

AUDREY: This is Steven Toovey. He’s an infectious disease doctor, also a longtime researcher and consultant with Roche

Stephen: Whether it's governments, industry, the military, um, private research bodies, non-governmental organizations, intergovernmental organizations, there are only so many real experts to go around. Their credibility, I think rests upon them giving unbiased and credible advice. That ultimately always has to be based upon data or based upon evidence. So I-

Audrey: So you’re saying, if you're good, the government wants you and drug companies are gonna want you.

Stephen: Exactly, exactly. What you want is the best advice from the best minds on working in an area, or on the subject.

Audrey: I'm trying to think of whether it feels like a cynical view or an optimistic view to say that, um, that an industry funding in research, in pandemic planning is, um, is kind of inherent to the, to, to the research. Do you feel like it's, it's cynical to say, Oh, well, pharmaceutical companies are always going to be involved or optimistic?

Stephen: Well, I...I think there are lots of parties who are involved and certainly there are many academic organizations who have undertaken pandemic planning, and research and modeling independently. Sometimes, and this again comes to potential conflicts of interest, industry will go to those people because it knows they are the best modelers. You know, these big pharmaceutical companies don't necessarily have the right skills in-house. Um, and they will go to the best people in academia and ask them to do a job for them. So I think you, I think you want to have all of these parties involved.

AUDREY:  We can’t say Roche influenced the judgement of all these experts—we have no real evidence of that. But yes, this Truman Show kind of world, as you put it: sure, industry has played a role in creating it. But if the drug works, the drug works. 

Stephen: I think there's this possibly a, an anti Tamiflu lobby, for want of a better term.

AUDREY: Stephen does not think Tamiflu’s some magic cure for influenza, but he does think there’s good solid enough evidence it can help, and we need all the help we can get when it comes to flu pandemics.
I talked with another researcher who’s worked with Roche, he was the author of one of the trials in the Kaiser review. He assured me plenty of other research confirmed that Tamiflu does what the Kaiser Review said it does. He sent me six research articles to back that up. A third of them were industry-funded.

***

GORDON: Tom Jefferson and the Cochrane team spent years going back and forth with Roche fighting to get the raw data from the early Tamiflu trials. 

AUDREY: FINALLY, in April 2013…. four years after Hayashi’s comment on the Cochrane, Roche gave in, and handed over to 80 different Tamiflu trials, every trial Roche had funded

Tom Jefferson: These are the, the, the accounts of the drug, which are thousands of pages long.

AUDREY: Tom Jefferson and his team read through about sixteen thousand pages of trial data on Tamiflu. And in 2014, they published a new review article about Tamiflu.

GORDON: They again concluded it did seem to shorten how long adults suffered from influenza symptoms, by about 17 hours. But they added that Tamiflu not decrease the chance of getting a secondary infection, at least not in a statistically significant way. And he also added: Hayashi was right--Tamiflu increased a person's likelihood for nausea, headaches, and psychiatric events.

Audrey: What did it, what did it mean to you to you to have possibly gotten the early reviews wrong?

Tom: It meant a in, in, in meant it meant a lot to us because, uh, we, um, we made amends. Uh, we apologized for having got it wrong. 

GORDON: So 15 years after the FDA had first looked at Tamiflu, the Cochrane team had basically found the same thing. Tamiflu gets you one less day of flu symptoms and no secondary infection fighting superpowers. Fifteen years of going back and forth over the data, we basically end up exactly where we began. Except with billions of dollars of Tamiflu in the emergency stockpiles.

Deborah:  I remember this about two years ago and this young public health doctor was telling me about Tamiflu in the fact that there was very little evidence for it and the country had stockpiled it, and I was listening, having the story, I'd investigated real relay back to me so it become part of his training. So, in many ways… my girlfriend said, Oh, she said, “Oh, so sorry that you've just been mansplained” and I was like, if what you have reported becomes just established and accepted as facts, this is what’s happened....That's not a bad place to be as a journalist.

GORDON: Drug companies must now publish all of their data before they can put a drug to market. That’s how it is in the US and the EU. 

 Tom Jefferson: Tamiflu became a sort of poster boy, became the sort of poster story for the absolute necessity to access data, especially on drugs, on vaccines, on anything, but especially on things which are given to scores of people, millions of people.

GORDON: Tom is suing Roche for $1.5 billion on behalf of the US government. This is under something called the False Claims Act. If Tom won, he could get up to 30 per cent of the damages. So he stands to gain a ton. He has a conflict of interest regarding Tamiflu, and the Cochrane Collaboration. won’t let him write about it any more. But he insists the lawsuit is about principle.

Audrey: Why? Why are you, why are you so passionate about this?

Tom Jefferson: Mmm. Would you like to be fooled? Do you like being fooled Audrey? Do you like being made to look like an idiot? 

***

AUDREY: I reached out to Dr. Kaiser, the author of the Kaiser review.I wanted to know what he thought of all this.  Turns out Kaiser was also not down with how much his Tamiflu study got waved around. It was just one paper he said. “This study was over-cited and used abusively,” he told me. Quote, “It was not under my power to control this.” 

GORDON:  We asked the CDC about their Roche-funded Take 3 campaign. But they did not respond to our request for comment. In 2016 about a dozen senior CDC researchers submitted an open letter to the CDC Chief of Staff expressing concerns over ethics of the agency..

AUDREY: Stephen Toovey,  the Roche-affiliated researcher, he stands by Tamiflu. And his research contradicts the idea that it causes psychiatric events. We never got Roches' full side of the story. But they did send us an email:

GORDON: “Tamiflu has been the standard of antiviral care for influenza for many years.It has made a significant difference both to the treatment of seasonal influenza, as well as in the management of the H1N1 pandemic.” They went on to say, “Roche has complete confidence in the safety and efficacy of Tamiflu. And the Company plans to vigorously defend itself against these allegations if Thomas Jefferson decides to pursue the litigation.”

AUDREY: Roche did not respond to our concerns  over research funding, or questions about Roche-affiliated researchers advising the WHO or the CDC. But they did give us a list of Tamiflu’s benefits, all sourced to studies that could be tied back to Roche.
Oh and by the way, they said there is no set pronunciation for Roche. 

GORDON: That’s Audrey Quinn, I’m Gordon Katic—this is Cited. After the break -- Wha can Tamiflu teach us about. our current pandemic? 


***

GORDON: It really means a lot when you write to me. Even when you take exception with things I’ve said. 

A person calling themselves A.S. wrote to me after the sixth episode of Secondary Symptoms. In that episode, I said that George Flloyd was publicly lynched. But AS said: “He did not get lynched. I think it’s important to call something what it is. He got killed, murdered, suffocated. Calling it lynching takes away from the actual unspeakable horror of lynchings and the history thereof.”

You’ve got a point, I was using a bit of rhetorical flourish there. I think probably most people wouldn’t defined what happened as lynching. But I think the word captures the brutality of that moment.

In fact, Floyd’s brother described it as “a modern-day lynching,” and Nancy Pelosi recently referred to chokeholds as lynching. So more and more people are turning to that word.

Jason Newton at Cornell University enjoyed episode five, Made of Corn. He wrote on Twitter, “Its important to understand the Malthusian, neoliberal logic behind transgenic corn. This logic dictates that all land is part of global markets and must be used "efficiently." That destroys local self-determination.” 

And a couple people seem to be using our materials in their classes… Dr. Kendra Coulter is using our episode “the Covid Kings” in her class, Animals at Work. If you do want to use our stuff in classes, feel free. But do let me know— because I’d love to report that kind of thing to our funders, like the Social Sciences and Humanities Research Council.

I really enjoy seeing your thoughts. Do keep sending them my way. You can write us at info@citedmedia.ca, or hit us up on twitter. That’s @citedpodcast, or you can find me directly @gordonkatic. That’s G-O-R-D-A-N K-A-T-I-C

That’s it for now… back to our regular scheduled programming.

***

 

GORDON: We are again rushing to find a pandemic treatment drug. And again, politicians are looking at using existing drugs for off label use. Hydroxychloroquine  took the early lead--

Trump: We would like to see very quick approvals. Especially with things that work.

Trump: If it works, that'd it'd be great. If it doesn't work, we know for many years, malaria, it's incredible what it's done for malaria. It's incredible what it's done for lupus, but it doesn't kill people. 

Trump: all I can tell you is, so far I seem to be okay.

GORDON: Research labs across the country have identified 69 different drugs that are candidates for off-label use to treat the novel coronavirus. 

Stephen: There are no licensed drugs for it at all. Nothing whatsoever.

AUDREY: Again, Stephen Toovey. The Roche-affiliated drug researcher.

Stephen: If we had a drug that people thought might work when there was some evidence that it would work. Would you take it? Would you want, would you want it to be available?

Audrey: Yeah. I think I'd want to know a little bit more about it, but it would be very tempting to get excited. Oh, there's a possibility this could be helpful. Yeah.

Stephen: I think the answer is when you're looking at a very severe disease with a significant mortality in the population. You probably do want to have drugs available. Now. I mean, we use drugs all the time, so called off-label. Physicians do that because they understand the disease. They understand the drug,  

Jeanne : It's interesting that you're doing this follow on from Tamiflu because it is echoes.

AUDREY: Journalist Jeanne Lenzer.

Jeanne: It reminds me, you know, back when I was reporting on Tamiflu, the same process that I went through in studying the Tamiflu issue is here now with the drugs that are being used .

GORDON: Gilead, remember, that’s the drug that originally created Tamiflu, well their drug Remdesivir has emerged as the front-runner.

TODAY HOST: Dr Fauci it’s good to see you with some good news to report. You said Remdesivir is not a knock-out. This isn’t a miracle drug, but it sounds like a breakthrough. Can you explain why?

DR. FAUCI: Well it’s a really important proof of concept, because this is the first very highly powered -- about 1,100 individuals-- and it was a placebo-controlled, randomized trial. Which I’ve been talking about for some time now—which is really the gold standard,of how you prove something is safe and that it works or either doesn’t work. Although the results were clearly positive—from a statistically significant standpoint, they were modest.

GORDON: Despite the modest improvement in one trial. The FDA has granted Remdesivir permission for emergency use-- and the EU has fast-tracked approval. Dr. Fauci declared the drug is “the new standard of care.”

AUDREY: But Jeanne says there are problems with the study. It’s not enough to know the study was “randomized, placebo-controlled” because researchers can make major tweaks throughout the process. For example, the Remdesivir trial completely changed the methodology part way through.

Jeanne: That’s drawing a circle around your arrow after you fired it. You’re not supposed to do that in medicine. You’re supposed to have a hypothesis and you’re supposed to test that hypothesis. But instead, get buckshot and you like where the one buckshot landed. And so you draw a circle around it and say, see, we got the target.

GORDON: The trial did show that patients would get released from hospital four days sooner if they took Remdesivir. But the trial didn’t show a significant decrease in mortality. It might have, but the research was stopped part way through because of the drug’s purported benefit.

Jeanne: We know that if you stop a trial early for benefit, it tends to create a false impression of benefit. That you really need to run a trial out to the end because he can't just look and say, Oh, if this moment it was good, I like it. Let's stop the trial.

AUDREY: Remdesivir might very well work, but Jeanne says we should do more trials. And most of all, if Tamiflu has taught us anything… it’s that we need to actually see the full data, now. Federal law says researchers don’t have to report the data for a year. And that time can be extended for three years. But by the time we get to see the data will it be too late?

GORDON: The experts I talk to predict that we’re likely to see Remdesivir stockpiling within months. Of course, nobody has a crystal ball. But the market seems to agree-- Gilead’s stock is up, and analysts estimate the drug could make $7 billion in two years. The company has already donated nearly 1.5 million vials to the federal government, and they plan to sell it as a Covid-19 treatment by as early as this month.

Jeanne: These are age old problems that just keep repeating themselves and repeating themselves. I mean, I've been in the field for 30 years. And you just watch the same things happen over and over again. 

AUDREY: I live in New York City, the epicenter of the pandemic in the US. Do I want a effective drug treatment? Of course! I’d hope the research is done right—and transparently. But at the same time, I look down at the hospital four blocks away from me. Staff there have relied on crowdfunding to buy masks. Other nearby hospitals have improvised ways to have patients share ventilators. 

GORDON: So maybe this is a bigger story than “does this drug work, does that drug work?” Maybe it’s a question of priorities. We should ask ourselves: Why do we underfund things that we know work, and throw money at questionable drugs that might shave a few days off an illness?

AUDREY: As medical providers still struggle to get the gear they need, States may soon be gearing up to buy Remdesivir, or perhaps some other drug. And the Strategic National Stockpile, still holds at least $1.5 billion dollars worth of Tamiflu. That’s about a fifth of the total value of the stockpile...  And just last year, the stockpile managers ordered forty million dollars more.

***


CREDITS

This episode was produced by Audrey Quinn, and me Gordon Katic.

With editing from Acey Rowe, and Gordon Katic. 

Franklynn Bartol was our research assistant.

Our theme song and original music is by our composer, Mike Barber. 

Fact checking on this episode by Aurora Tejeida and Polly Leger.

 Dakota Koop is our graphic designer.  

Cited’s production manager is David Tobiaz. 

And Cited’s executive producers are Gordon Katic and Sam Fenn.

Thanks to Hannah Arbor for Japanese translation, as well as  to Shungo Kano, who voiced  Keiji Hayashi’s clips.

This episode was funded in part by the Social Science and Humanities Research Council. It’s part of a wider project looking at trends in pharmaceutical research and policy. Dr. Joel Lexchin at the University of Toronto and Professor Sergio Sismudno at Queens University are the research advisors on that project.

Cited is produced out of the Centre of Ethics at the University of Toronto, which is on the traditional land of Mississaugas of the Credit, the Anishnabeg, the Chippewa, the Haudenosaunee and the Wendat People.

Cited is also produced out of the Michael Smith Laboratory at the University of British Columbia -- that’s on the unceded territories of the Musqueam, Squamish, and Tsleil-Waututh Nations.