Coronavirus | Opeds and editorials

The many questions about Favipiravir

The DCGI has granted approval for use of the drug to treat mild COVID-19 patients, but on what basis?

The pandemic has not only exposed the dire situation of the public health infrastructure, but also the opacity with which drug/medical device approvals are granted in India. We have had many controversies over the last few months: the use of hydroxychloroquine for treating COVID-19 patients, grant of licences for diagnostic kits for COVID-19, and the specificity of serological tests for detecting antibodies against the virus. Another controversy is brewing due to the opacity surrounding the regulatory approval granted to Favipiravir for the treatment of COVID-19 patients with mild or moderate symptoms.

No scientific consensus

The Drugs Controller General of India (DCGI) has approved Glenmark Pharmaceuticals, an Indian pharmaceutical company, to sell generic versions of Favipiravir for the treatment of COVID-19. This drug, originally invented by a Japanese company, was meant to treat influenza. After the outbreak of COVID-19, doctors in China and Russia started using it to treat COVID-19 patients although there is no scientific consensus on the efficacy of the drug.

As per Glenmark’s filing with the Bombay Stock Exchange, the company has received “accelerated approval” from the DCGI for “restricted emergency use in India”. On what basis did the DCGI grant approval? Will the underlying data be made publicly available to the medical community? While the New Drugs and Clinical Trial Rules, 2019 allow the DCGI to grant approvals for the use of certain drugs based on approvals granted overseas, they do not absolve it from making their rationale for such decisions public.

There is no information on the DCGI’s website explaining the scientific basis of its approval of Favipiravir for COVID-19. Evidence-based medicine requires the testing of pharmaceutical drugs through randomised clinical trials (RCT) wherein one set of patients get a placebo (or an alternate therapy) and the other set of patients gets the investigational drug. Neither the doctors nor the patients know who gets what drug. If the set of patients that gets the investigational drug shows a better outcome, it can be presumed that the drug has a demonstrable therapeutic effect on the disease in comparison to the comparator. This is the gold standard for demonstrating the efficacy of a drug in treating a particular disease. The data collected from such clinical trials are usually published in a peer-reviewed journal where they are subject to scientific scrutiny. This system has worked during this pandemic to disprove claims that hydroxychloroquine was useful in treating COVID-19.

With regard to Favipiravir, we know that Glenmark was conducting a clinical trial for this drug in India. According to the Clinical Trials Registry of India (CTRI), Glenmark’s study was meant to be carried out on 150 patients at 12 different hospitals in Chhattisgarh, Gujarat, Maharashtra and Delhi with the aim of comparing Favipiravir with “standard care” provided to patients with mild or moderate COVID-19. The decision to enrol patients with “mild” COVID-19 is baffling given that virtually all these “mild” cases often resolve themselves without any intervention. Further, the CTRI does not explain the nature of the “standard care” being provided to the patients. It is important to disclose this information from a scientific and ethical viewpoint. If we do not know the treatment with which Favipiravir is being compared, how do we know if it is any better than perhaps a placebo?

Also read | Glenmark’s antiviral drug Fabiflu to be used for patients with mild and moderate symptoms

The Japanese regulator, which approved this drug for influenza, mandated a warning to be printed on the packaging of this drug for early embryo toxicity and teratogenicity, specifically cautioning its use in women in the early stages of pregnancy. The exclusion criteria listed on the CTRI list pregnant and lactating women, which is not necessarily the same thing. The protocol on CTRI also specifies that the 150 patients enrolled in the study will be randomised 1:1. This patient cohort is not adequate to substantiate statistically either the primary or the secondary endpoint of the study.

Flaws in observational studies

Glenmark claims in a letter to the Bombay Stock Exchange that it was granted approval based on evaluation of data and expert opinion. We tried to retrieve the scientific studies that have tested the effectiveness and safety of this drug among mildly ill COVID-19 patients. PubMed, a database that contains more than 30 million citations and abstracts of biomedical literature, lists a single study published in a journal called Engineering. It shows that a group of Chinese investigators did an observational study on 80 patients and concluded that those who got the drug tended to have faster disappearance of virus and quicker improvement of shadows in their chest x-rays. The study was not a randomised controlled trial and therefore, small size apart, had two serious flaws — bias (the sample studied is not representative of the population it was drawn from or the population at large) and confounders (unable to control for all other factors that might differ between the two groups). The only way to eliminate these is to design a prospective randomised controlled study. We are unable to find well-designed robust scientific studies on the effectiveness and safety of this drug in COVID-19 patients. Therefore, the explanation that the grant was approved based on “evaluation of data” does not seem tenable.

Subsequent to a scandal in 2012, the DCGI instituted a system of review by a Subject Expert Committee (SEC) to decide whether a new drug should be approved for the Indian market. The SEC was meant to have external experts who were specialists in the field of therapy being considered. After a SEC approval, the DCGI is required to take the final call on whether to approve a drug. Thereafter the information on which such decisions were made was required to be disclosed because the Right to Information Act requires such a disclosure. However, in this case, the minutes of the meetings, the composition of the SEC and the clinical trial results submitted to the SEC/DCGI are not available on the DCGI’s website. A representative of Glenmark disclosed on a channel that the approval for restricted use was based on an “early readout” from the study; the study is expected to be completed in the coming weeks and months. So, on what basis did the DCGI approve restricted use of this drug?

Also read | Registration of Ethics Committee to approve clinical trials made mandatory now

A culture of secrecy around drug approvals serves no purpose except to benefit pharmaceutical companies. At ₹103 a tablet, the manufacturer stands to make a fortune once there are bulk orders for this drug. However, if the drug does not work as advertised, the DCGI could end up promoting widespread misuse of this drug and a false sense of security amongst the population. The regulator would be responsible for promoting irrational medicine as it has been on previous occasions. We would caution our countrymen against any such purchases until the DCGI makes public the clinical information on the basis of which the accelerated approval has been granted along with the minutes of the SEC meeting where this drug was approved.

S.P. Kalantri is Professor of Medicine at the Mahatma Gandhi Institute of Medical Sciences and Medical Superintendent of Kasturba Hospital, Sevagram, Maharashtra; Dinesh Thakur is a public health activist

This article is closed for comments.
Please Email the Editor

Printable version | Jul 10, 2020 12:33:18 AM |

In This Package
The social contract needs to be rewritten
The pandemic is about eyes shut
Joblessness and opportunity in Tamil Nadu
Green-lighting ecological decimation amidst a pandemic
COVID-19 has no religion
A case for extension: On rural jobs scheme
Surely, even if slowly: On a COVID-19 vaccine
Bend it like Italy: On flattening the COVID-19 curve
Promise and delivery: On India’s first COVID-19 vaccine
States hold the key: On Unlock 2.0
PCR testing is a double-edged sword
Science vs nonsense: On Patanjali’s COVID-19 claim
Senseless deaths: On Tamil Nadu custodial deaths
Shut and open: On tennis during the pandemic
The perils of follow the leader syndrome
You are reading
The many questions about Favipiravir
In new lockdown, a second chance for Tamil Nadu
United front in Delhi: On Kejriwal government-Centre camaraderie
A prescription of equitable and effective care
Multilateralism post COVID-19
Making public transport safe during COVID-19
A better rate: On COVID-19 recovery
Look back in relief: On the migrant labour crisis
Needed, a transfusion for public health care
Wrong priorities: On keeping religious places open during a pandemic
Crossing the line: On Delhi’s decision to limit health services
Profit, not profiteering: On regulation of COVID-19 testing charges
In Persian Gulf littoral, cooperative security is key
Paging the private sector in the COVID fight
Curves and recoveries: On India’s coronavirus numbers
India’s Parliament is missing in action
Axing the economy’s trunk
Scripting a new narrative for COVID control
Open with caution: On Unlock 1
It’s time for a universal basic income programme in India
The waning of subaltern solidarity for Hindutva
Export blocks: On India’s trade amid the pandemic
A moment to trust the teacher
The echo of migrant footfalls and the silence on policy
Enjoying the fruits of their labour
Helping supply chains recover
The heavy burden of social suffering
An effective lockdown
The lockdown has highlighted stark inequalities
Will sport be the same in empty stadia?
Cinema after COVID-19
The eternal longing for the distant home
Working safely: On workplaces during the pandemic
A hole in the whole: On health sector woes
China, better prepared for the post-COVID world
How public health boosts an economy
Keep it retrospective
Backing the ‘angels in white coats’
Standstill: On opening of stadia for training
Flawed stimulus is justice denied
We need social physicians
A callous response
Peaking: On India’s coronavirus tally
Farm gate in focus: On amending Essential Commodities Act
A question of quarantine: On migrant workers and other travellers
TASMAC tribulations: On Tamil Nadu liquor sale
The pandemic and the challenge of behaviour change
One for the poor: On Centre’s corona package
Lockdown syndrome: On virus-induced economic crisis
Are India’s labour laws too restrictive?
Stop the return to laissez-faire
States cannot be left to the Centre’s mercy
Local motif: On Modi’s call for self-reliance
Liquidity lifeline: On Nirmala’s MSME package
A plan to revive a broken economy
Provide income support, restore jobs
Perilous state: On State finances
COVID-19 and the path ahead
Reaffirm cooperative federalism
Riding roughshod over State governments
Tragedy on the tracks: On the killing of 16 migrant workers
Coming to terms: On India refusing to admit community transmission
The trends shaping the post-COVID-19 world
The epidemic and ensuring safety in courts
Responding to COVID-19 at the grassroots
The face of exploitation
Contempt for labour: On dilution of labour laws
Slower growth and a tighter fiscal
Back home: On return of Indian expatriates
Blame game: On Donald Trump’s anti-China rhetoric over COVID-19
Resuscitating multilateralism with India’s help
A war-like state and a bond to the rescue
Fear and loathing in the land of the free
Everyone wants a good stimulus
Rent control amidst pandemic
Slow release: On lockdown 3.0
No comfort in numbers: On Bengal’s coronavirus cases
Pandemics without borders, South Asia’s evolution
India’s disease surveillance system needs a reboot
No relief for the nowhere people
BRICS against COVID-19
Recovering early: On India’s COVID-19 patients
It’s about food, nutrition and livelihood security
Taiwan’s coronavirus protocol shows how it is done
Needed: a pandemic patent pool
Getty Images/iStockphoto
Plasma therapy is no silver bullet
Take care of yourself too, fellow journalists
Strategic shift: On home isolation of mild coronavirus cases
Coping with today, planning for tomorrow
No end in sight: On India’s coronavirus strategy
Vividly imagining the life of migrant workers
A task for South Asia
Privacy concerns during a pandemic
Unlocking justice in the lockdown
Safe return: On migrant worker distress
The outline of another pandemic combat strategy
Pandemic and panic: On Tamil Nadu’s five-city lockdown
Protecting the poor from becoming poorer
Did SARS-CoV-2 begin from a lab?
Protection for protectors: On safety of healthcare workers
Rapid failures: On antibody testing kits
The COVID-19 paradox in South Asia
Fishing in troubled waters during a pandemic
How will India emerge out of the lockdown?
Making doctors wash hands
Locked out of cities, homes and livelihoods
Script of unity: On coronavirus and social prejudices
Exploiting a pandemic: On Trump’s immigration policy
The village is still relevant
A time for planetary solidarity
There may be no going back
No transparency in West Bengal
Focus on the curve: On India’s COVID-19 numbers
Economy in lockdown: On India’s worst case scenario
A shot of hope with a game changing vaccine
Caught in the heightened arc of communal polemics
Singing the corona tune
Helping a lending hand: On RBI’s second lockdown stimulus
A season of change: On IMD forecast system
A virus, social democracy, and dividends for Kerala
Across the gulf: On stranded Indian workers
Virtual reality: On telemedicine
A blueprint to revive the economy
A case to use JEE-Main instead of JEE-Advanced this year
Will the aviation industry recover from the pandemic?
Data-driven reporting during COVID-19
Stress test: On revised lockdown guidelines
Disastrous decision: On Trump halting funds to WHO
Cease the distractions, seize the moment
Getting the containment strategy in India right
In India’s response, a communications failure
Harmonising with nature
End the harassment of farmers now
A narrowing window: On extension of lockdown
Corona bond: On Eurozone COVID-19 rescue package
Halting the march of rumours
Polls during a pandemic
The pandemic and the contours of a health response
Economic liberalisation and its faults
Invasive, alien, most fearsome
Trade in tatters: On the global slump
Wanted, a collective national endeavour
Disingenuous and no antidote
COVID-19 and the crumbling world order
Women’s safety during lockdown
Lives and livelihoods: On economy after lockdown
Stage fright: On denying community transmission
Team India and winning the pandemic battle
In time of need: On hydroxychloroquine export
Will COVID-19 affect the course of globalisation?
Finding a scapegoat in WHO
Curating news for children during pandemic
A time for extraordinary action
For better use: On MPLADS funds
Needed, greater decentralisation of power
A key arsenal in rural India’s pandemic fight
Preparing for exit: On lifting the lockdown
Sanctions and pandemic: On America’s Iran policy
‘A script of action, responsibility and compassion’: Chief Minister Ashok Gehlot writes on Rajasthan’s fight against COVID-19
Taking a long view of the pandemic fight
Ten questions posed by the virus
A different economic approach
Why healthcare workers above 60 should be ‘benched’
Enemy at the gates: On Kerala-Karnataka border row
Reducing farm distress during a pandemic
Why everyone should wear masks
The criticality of community engagement
A niggardliness that is economically unwarranted
The spectre of a post-COVID-19 world
Light and sound: On Narendra Modi’s 9-minute light ceremony
A million and counting: On global coronavirus spread
Safe forests, safe people: On diseases of animal origin
Quarantine and the law
Making the private sector care for public health
Looking east to contain COVID-19
Limits to rugged individualism
Uncritical endorsement: On exodus of migrant workers and the Supreme Court
Beyond the blame game: On the Tablighi Jamaat episode
A long road: On India’s 21-day coronavirus lockdown
The missing notes: On politics and the fight against COVID-19
China’s zero: On China’s lead in containing coronavirus
Unprecedented step: On Wuhan lockdown
The return of the expert
Lessons from Hubei
A pandemic in an unequal India
Faith can’t override public health
Devising a people-centric response to COVID-19
Karnataka CM writes on how the State is fighting the pandemic
Tamil Nadu CM writes on how the State is stopping the pandemic in its tracks
The hunt for a cure begins with telling the truth
COVID-19 and a city’s anatomy
Long live the nation-state
The COVID cycle
Coronavirus | The worst of times, the best of times
It’s also a fight against punitive measures
The age of the neoliberal virus
The deep void in global leadership
Thinking national, acting local
Every man is a part of the main
Beyond social distancing to fight COVID-19
Next Story