Makeshift cures

Drugs and therapies proven to be ineffective in COVID-19 treatment continue to be used widely in India, with government support

Why is India promoting unproven COVID-19 therapies?

WHILE COVID-19 patients continue to opt for treatments, such as plasma therapy or hydroxycholroquine, there is increasing volume of data that indicates they are ineffective. The government has allowed, even promoted these therapies by incorporating them in the Clinical Management Protocol for COVID-19, which has ensured their large-scale use.

The most recent evidence has come from a clinical trial of convalescent plasma (CP) therapy (or plasma therapy, as it is commonly called) on 464 patients. The trial, which was funded by the Indian Council of Medical Research (ICMR), the country’s apex body on biomedical research, concluded that the therapy neither reduced progression of infection from mild to severe nor lowered the mortality rate. The results were published in MedRxiv on September 8 and are yet to be peer reviewed.

The trial, conducted at 39 public and private hospitals across India, divided patients into two groups. One was administered best standard care (BSC) while the other was given BSC as well as plasma therapy. BSC is a part of the Clinical Management Protocol for COVID-19 and includes antivirals (Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir, Oseltamivir), broad-spectrum antibiotics, immunomodulators (steroids, Tocilizumab), and supportive management (oxygen, face mask, ventilation). Plasma therapy too is a part of the COVID-19 protocol, but was not used in

one set of patients for the purpose of the trial. Results showed that patients in both the groups produced the same amount of antibodies. The idea behind plasma therapy is to trigger production of antibodies in a COVID-19 patient. This happens due to the infusion of plasma of a recently recovered individual into a COVID-19 patient. If both the groups produced the same amount of antibodies, it shows the futility of plasma infusion.

However, plasma therapy did lead to better resolution of symptoms like shortness of breath and artificial oxygen requirement. The recipients were also able to free from the virus faster, which does not imply recovery or cure, but the duration of complete removal of the virus from the body. “The inordinate focus on CP seems futile as it does not seem to prevent progression to severe disease or death compared to standard treatment. The minor benefits mentioned in the study probably are not meaningful enough for CP usage at such a large scale in India in both public and private sector with the support of governments,” Anant Bhan, former president of International Association of Bioethics, told Down To Earth. “This data should be peer-reviewed at the earliest by

ICMR and published because it will have significant ramifications,” he said

The results are being peer-reviewed, said Balram Bhargava, ICMR director-general, at a press conference on September 11. Even the World Health Organization (WHO) says that the use of plasma therapy for COVID-19 treatment is at an experimental stage. So why is it part of government-approved protocol in India? It is used to treat Ebola globally and some countries started using it for COVID-19, following which the Indian government included it in its COVID-19 protocol released in April.

In normal circumstances, a drug goes through three phases of trials—phase 1 tests safety, phase 2 efficacy, and phase 3 is large-scale testing on thousands of patients. The trials are conducted by the developer under the observation of the Drugs Controller General of India (DCGI), which, through its expert committees, goes through the results and takes a decision. But in emergency situations, DCGI can grant permission on the basis of the first two phases.

There are several other drugs/therapies that the government has repurposed for

COVID-19. On August 8, Uttar Pradesh allowed use of Ivermectin, a drug used to treat parasitic infections. Public health being a state subject, states can make their own protocols and Uttar Pradesh is the only state where this drug is prescribed. WHO says none of the 28 clinical trials on the efficacy of this drug on COVID-19 is complete.

Monoclonal antibody (mAB) therapy is another treatment course that the government has allowed, though there are no clinical studies that conclusively say it is effective. Like plasma therapy, mAB too introduces antibodies in a patient suffering from the disease, but the difference is that in mAB the antibodies are produced in a laboratory. Pharma giant Biocon’s Itolizumab is a vaccine based on mAB. DGCI allowed it after the first two phases of trials on just 30 patients but the government has not included it in the protocol. The vaccine is in huge demand and extreme shortage. With an MRP of R8,000, it is being sold in black for as much as R1 lakh.

Hydroxychloroquine (HCQ), used for treating malaria globally, is also recommended commonly for COVID-19. India made it a part of its COVID-19 protocol in April, though it is proven to be ineffective. WHO discontinued the trial on the drug in July, stating it did not either reduce mortality nor progression of COVID-19. An analysis of 29 studies on

HCQ, published in Clinical Microbiology and Infection on August 26, arrived at the same conclusion.

What these cases show is that the government in its desperation to control COVID-19, of which India had over a million active cases by September end, is not just allowing drugs whose efficacy is doubtful, but even those that have now proven ineffective.

BOTH HCQ AND PLASMA THERAPY ARE GOVERNMENT RECOMMENDED AND USED ACROSS INDIA, BUT WHILE THE FORMER IS NOW KNOWN TO BE INEFFECTIVE, THE LATTER'S UTILITY IS DOUBTFUL AT BEST