Rumour: Favipiravir/Avigan and how to report on new ‘miracle’ drugs

One drug drawing the attention of both the medical and social media world is favipiravir, sold under the brand name Avigan. An Indian pharmaceutical company has recently developed and commercialised a generic version of favipiravir to be marketed under the brand name Faviton.

Favipiravir is an antiviral medication used to treat influenza (predominantly in Japan) and it is stockpiled by the Japanese government to be used if drugs fail to work on new strains of influenza. Japan is shipping favipiravir to 43 countries, from India to The Philippines and Thailand, for clinical trials and testing to see if it might work on patients with mild and moderate COVID-19 symptoms.

Interim results of clinical tests of favipiravir on COVID-19 patients reported to Japan’s Ministry of Health suggested that favipiravir was not effective enough to clear the virus in patients. But Japan’s Prime Minister Shinzo Abe has said he is still hoping for the approval of favipiravir by the end of May.

When working in a pandemic, with a new virus spreading quickly, doctors are sometimes forced to try to treat the illness with drugs designed for other conditions. Until medicine specifically designed to prevent or treat COVID-19 goes through the relevant approval processes, you may hear the names of a number of different prescription medications being mentioned on social media. It is your role as a journalist to be able to carefully report on this community concern without fuelling hope towards untested, or potentially dangerous, treatments.

Learning from the past

When it comes to reporting on drugs being tested for COVID-19, it will be helpful for journalists to learn from the Tamiflu saga in 2009. This is a great example of how solid investigative journalism, based on the expose by British medical journal BMJ, can highlight the influence big pharmaceutical companies can have over regulators and even the World Health Organization.

There are so many drugs under trial at the moment, and billions of dollars being spent in the rush to find the cure. In this rush, Journalists have an important role to play to make sure decisions are being based on genuine scientific evidence, not political or industry pressure.

In 2009, there was widespread concern about a new flu pandemic, and billions of dollars were being spent to stockpile Tamiflu around the world. It was initially believed that Tamiflu would reduce hospital admissions and complications of influenza, such as pneumonia, during influenza pandemics. However, clinicians around the world started raising questions about the accuracy of these claims pointing out that the original evidence presented to government agencies was incomplete.

Because of this, the UK and Australian governments specifically asked the Cochrane Collaboration to update its earlier reviews on the influenza drug that was co-developed by Roche and Gilead Sciences Inc.

Cochrane is a British international charitable organisation. Cochrane reviews are the gold-standard in medicine: they summarise all the data on a given treatment, and they are in a constant review cycle, because evidence changes over time as new trials are published. Cochrane was formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients, and policy makers. It includes 53 review groups that are based at research institutions worldwide.

As the review team began its work, it received an unexpected criticism and challenge by Keiji Hayashi, a Japanese pediatrician. Hayashi pointed out that the key piece of evidence underpinning the previous Cochrane review’s conclusion – that Tamiflu reduced the risk of secondary complications such as pneumonia – was based on a manufacturer-authored, pooled analysis of 10 manufacturer-funded trials, 8 of which were unpublished.

This is a key issue to look out for in this pandemic. You will see ‘results’ from many drug trials where the research into whether that drug is effective has been funded by the drug company. To really know if a drug is effective, the results must receive a peer review. This means that other scientists, who are not affiliated with the drug company, review the results and determine if the findings are reliable.

In this case, the Cochrane team responded to Hayashi’s claim by requesting data from the unseen trials. The drug company (Roche) said they would only provide the data if the Cochrane review team signed a secret confidentiality agreement. The review team leader Dr Tom Jefferson refused to sign.

The following facts emerged from the Cochrane review:

  • The WHO was recommending Tamiflu but had not vetted the underlying data.
  • The European Medicines Agency approved Tamiflu, but had not vetted the underlying data.
  • The US Centers for Disease Control was encouraging the use and stockpiling of Tamiflu on the basis of the 6-page manufacturer funded analysis of 10 clinical trials, but had not vetted the underlying data.

Following the review, an investigation was carried out by the respected British medical journal BMJ and its findings were followed up by the UK media. It revealed that scientists advising the WHO on its pandemic planning, had earlier done paid work for influenza drug manufacturers – conflicts of interest that the WHO had not publicly disclosed.

Clinical trials can often become entrenched in the competing interests of quality science and a profitable product. We see here an example where the science and reasoning behind the stockpiling of Tamiflu was not questioned soon enough. If health regulators or politicians in your context are pointing towards a specific drug to treat or prevent COVID-19, it’s important for the media community work to make sure the evidence is there to justify the decision.

So how do I report on these rumours without encouraging dangerous behaviour?

As a reporter, not a scientist, how do you go behind the headlines to assess the safety and effectiveness of drugs like favipiravir and ensure you’re not contributing towards dangerous hype?

We previously released theseguidelines for reporting on clinical trials. The guidelines are now available in English, Bahasa Indonesia, Hindi, Vietnamese and Burmese.

We’ve adapted this advice from the Columbia Journalism Review to add to your tool belt when investigating the use of pharmaceutical drugs in this crisis:

Always read the entire paper

Press releases about drug studies—whether they are from universities, journals, or industry—use spin. Study abstracts aren’t much better. There is now free access to almost all COVID-19 studies and by reading the whole study, you would be able to spot the red flags. Reading the entire paper will also help you dig deeper.

Evidence Aid now has more than 200 plain language summaries of COVID-19 research. Summaries look at interventions, health and social care services and response, and the impact of COVID-19 on non-health outcomes and are translated into Arabic, Simplified and Traditional Chinese, French, Italian, Portuguese, and Spanish.

Do not be afraid to ask what seem like basic questions on jargon. Remember that your primary loyalty is to your audience, who don’t know the jargon, either.

Make sure you have an independent contact you can speak to to ask questions about the study who does not have a vested interest in its results.

Read the discussion, look for limitations

Look at what question the drug study is trying to answer. For favipiravir, it is the drug’s effectiveness in limiting the progression of COVID-19. This is very different from a drug that might be trying to prevent someone catching SARS-CoV-2 in the first place, or trying to treat COVID-19 in a specific group in the community (e.g those with heart disease or other underlying factors). Make sure the results answer the specific research question.

Look for peer review. You are not a scientist, so determining whether these findings are conclusive can be very difficult. A peer review means that other scientists, who are not affiliated with the drug company, review the results and determine if the findings are reliable. If there has been no review, then you could consider the research only half finished.

What are some limitations for favipiravir research?

Favipiravir is developed by a Fujifilm Holdings Corp. subsidiary company. Fujifilm is also doing its own clinical trials of the drug and this should raise a red flag.

When a big corporation owns a drug’s patent it often allows the researchers to change the focus, or question of the research. This is sometimes called ‘Outcome Switching’. This means that the researchers can choose to answer a different research question, if they do not get the results they need to reliably answer the initial research question outcome switching can have a big impact on the study results. This is another red flag because the evidence for the drug’s safety and efficiency is not really there yet.

Who has an interest?

Read those disclosures at the ends of papers, keeping in mind that while most clinical trials are funded by industry, such ties are linked to a higher rate of positive results. And these conflicts can become stories with impact themselves.

In the section above, ‘Learning from the past’, see how Japanese pediatrician Keiji Hayashi challenged a study on the safety of Tamiflu. He pointed to the disclosure at the end of the paper which revealed help with the statistical analysis was provided by the co-developers of the influenza drug.

What are the side effects?

Every treatment has them, and you’re unlikely to find them listed in a press release or abstract. Do a Google search and dig deeper using PubMed.gov, a search engine of the US National Library of Medicine.

What about favipiravir?

Favipiravir causes serious side effects in pregnant women and can cause birth defects. In the early stages of pregnancy, the drug is toxic to the embryo and causes embryonic death which can be deleterious to maternal health.

Consider that at times it may be counterproductive for your reporting to hone in on a specific drug undergoing trials. Hundreds of COVID-19 related clinical trials are underway around the world. A focus on one drug (especially one that is already in use for other conditions) can have the unintended consequence of creating the impression that it is proven to “work” in the context of COVID-19, and this can lead people to try it out for themselves. This would be extremely dangerous. 

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