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Why the Health Ministry’s Hydroxychloroquine Recommendation Is Not Legal

Why the Health Ministry’s Hydroxychloroquine Recommendation Is Not Legal

A person carries a box of hydroxychloroquine tablets in Seattle, Washington, March 31, 2020. Photo: Reuters/Lindsey Wasson.

On March 23, 2020, the Ministry of Health and Family Welfare (MoHFW), released an advisory directing healthcare workers and household contacts of COVID-19 patients to start taking hydroxychloroquine (HCQ) as a prophylactic. This was based on the recommendations of the National Task Force for COVID-19 and the Indian Council of Medical Research (ICMR).

During the ongoing pandemic, HCQ has been in the news on multiple occasions, including during a semi-tense standoff when US President Donald Trump coerced Prime Minister Narendra Modi to share India’s stock of HCQ with the US. More recently, Trump even announced at a press conference that he has begun self-administering one pill of HCQ every night.

HCQ is an anti-malarial drug and is considered safe to use when prescribed for indications it has been approved for. However, it hasn’t been tested or approved anywhere in the world for use against COVID-19. The US Food and Drug Administration (FDA) has cleared HCQ use under an Emergency Use Authorisation procedure, in adults who have been hospitalised with COVID-19. But the body has discouraged the drug’s use in any other circumstances due to the adverse effects of HCQ.

On March 23, a day before India’s nationwide lockdown began, MoHFW and ICMR  recommended HCQ’s use as a prophylactic even though they hadn’t been able to reliably verify claims of its safety and efficacy. In the two months since, a joint monitoring group under the MoHFW chaired by the Director General of Health Services, along with the National Task Force for COVID-19, has reviewed the prophylactic use of HCQ and issued a revised advisory on May 22.

The data the MoHFW used came from a study of 1,323 healthcare workers, of whom 214 had reported adverse effects. ICMR conducted a retrospective analysis and found a relationship between “the number of prophylactic doses taken and frequency of occurrence of SARS-CoV-2 infection in symptomatic healthcare workers”. The advisory also reported an investigation at three government hospitals in Delhi and at AIIMS that had found healthcare using HCQ as a prophylactic were less likely to contract COVID-19.

On the back of this data, the MoHFW revised its previous advisory and extended its scope, advising healthcare workers in all hospitals and blocks that had a COVID-19 ward to consume the drug as a prophylactic subject to contraindications such as retinopathy and pre-existing cardiomyopathy. The revised advisory also recommends the use of HCQ as a prophylactic to surveillance workers in containment zones and police and paramilitary personnel deployed for activities related to COVID-19. Finally, the advisory continues to apply to household contacts of COVID-19 patients, as before.

This represents a big change in the number of people affected, so it’s important that the MoHFW be sure this measure is both safe and efficacious, considering HCQ’s side effects can be serious – and because it’s important to maintain a commitment to proof during a pandemic.

In India, drugs like HCQ are regulated under the Drugs and Cosmetics Act 1940 and the Drugs and Cosmetics Rules 1945. All drugs – including those approved for one use-case but which have since been repurposed for another – must be tested in a stepwise manner before they can be marketed. So if HCQ, approved to be used to treat patients with lupus and rheumatoid arthritis and (in some cases) malaria, is proposed for preventing or treating COVID-19, it must be re-tested under the Act and the Rules first.

Under the Drugs Rules, all drugs must be tested on animals and then humans before approval. These tests check their physical and chemical properties, mode of operation, metabolism, dosage-response, movement through a patient’s body and side effects. Each step of testing must be approved by the Drugs Controller General of India before the next one can commence.

In emergency situations such as the ongoing pandemic, the Drugs Rules allow researchers to import the results of animal toxicology studies and human trials conducted abroad. The tests for product characterisation and animal pharmacology will still need to be conducted in India.

However, there is no evidence that animal pharmacology studies were conducted for HCQ-as-prophylactic in India – nor is there evidence of any human trial conducted abroad which ICMR and the MoHFW could then have used to recommend HCQ to India’s essential and frontline workers, etc.

The rigorous testing procedures the Drugs Act and Drugs Rules describe share the same underlying objectives as those worldwide: efficacy and safety. That is, drugs must be shown to be both effective and safe before they can be approved. When dealing with a pandemic, a third objective shows up: speediness. That is, a safe and effective drug must be made available for patients and healthcare workers as soon as possible.

However, the government must ensure that its need to provide a solution quickly doesn’t violate the first two objectives. Safety is of particular concern when dealing with a drug such as HCQ, which is known to have harmful side effects.

As such, the MoHFW hasn’t followed the applicable legal framework before prescribing HCQ.

No study in the world has shown HCQ to be either safe or efficacious. In fact, some have found mixed results. A small-sample study conducted in Wuhan in February found that HCQ could significantly shorten recovery time. On the other hand, a large-scale study conducted in a New York hospital in early May found that patients taking HCQ had the same risk of death as those not.

More recently, based on a controversial study published in The Lancet that has been widely censured for its methods, the WHO suspended its multinational clinical trial for HCQ as a treatment for COVID-19. The organisation has also advised doctors and medical associations around the world to avoid administering HCQ to COVID-19 patients until sufficient evidence becomes available.

Also read: Why India’s Stated Policy on Hydroxychloroquine Makes No Sense

On May 29, ICMR wrote to the WHO arguing against the trial’s suspension and the WHO’s subsequent advisory because the dose prescribed for Indian health workers was 25% of the amount administered in the trial. The letter added that ‘Indian studies’ had found evidence of HCQ’s efficacy in treating COVID-19.

However, ICMR’s correspondence spoke of HCQ as treatment whereas the study it claims to have conducted explored HCQ as prophylaxis. More importantly, ICMR’s study itself is not a clinical trial, as the Drugs Act and the Drugs Rules both require. It is a retrospective study and doesn’t meet the rigours of a clinical trial set out in law.

Further, the US law that governs the FDA provides for an ‘emergency use authorisation‘, which the FDA may use to authorise untested treatments during emergencies, when there are no approved alternatives. The MoHFW is not empowered by any such law. However, the ICMR did draft guidelines in 2017 to ensure untested drugs are used in a way that minimises ethical violations. But then ICMR sidestepped them – even as the MoHFW has made decisions on an ad hoc executive fiat basis sans the requisite caution.

If HCQ is to be marketed as a prophylactic for COVID-19, it must be tested rigorously first, according to existing laws. The studies the MoHFW and ICMR are using to make their decisions don’t meet this criterion. It’s true that tests take time – but they need this time to minimise risk to and to maximise safety of patients, and to make sure the drug really works. And when the patients are frontline health workers themselves, it becomes even more important to ensure the drug is safe.

Tanmay Singh is a Delhi-based advocate. He tweets at @TanmayPratapS.

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