Why India’s national policy on hydroxychloroquine makes no sense

recently Video published by ANIRaman Gangakhedkar, a principal epidemiologist at the Indian Medical Research Council (ICMR), made some strange statements about hydroxychloroquine. He said the ICMR only recommends it as a preventative agent for physician- and laboratory-confirmed patient contacts, as there is little evidence of the drug’s efficacy against COVID-19. He also repeatedly referred to some of the studies in which doctors and contacts were taking the drug, but did not provide other details.

Contrary to Ganga Kedkar’s claim, these statements are strange because the Indian government has proposed the use of hydroxychloroquine as a treatment for COVID-19 patients in the intensive care unit (ICU). That ‘Revised guidelines for clinical management of COVID-19The Department of Health states that the combination of hydroxychloroquine and the antibiotic azithromycin may be given as a “off-label indication for patients with severe disease and ICU management.”

Second, although Gangadocal’s statement on the lack of data on the therapeutic effects of hydroxychloroquine is correct, there are even fewer data on the effects of hydroxychloroquine as a prophylactic. Human studies completed thus far have not attempted to answer this question, but some are ongoing (see here, here And here). The only human clinical trials for which results were available studied the efficacy of treatment alone and yielded conflicting results.

Not all drugs used for treatment lead to good prevention. But Hydroxychloroquine may be impaired The ability of healthy people to repel COVID-19 by delaying the production of an important immune system molecule called interferon alpha, which makes the drug prophylactically poor, but in fact against the virus that induces COVID-19 It can help many sick people who suffer from an excessive immune response, called the cytokine storm. Conclusion: Prevention and treatment are not the same.

So, if ICMR does not fully consider that ICMR is sufficient for treatment, does ICMR recommend a drug of unknown efficacy as a prophylaxis? The rationale is unclear, as preventive drugs target healthy people who have a much lower risk of death from COVID-19 than those who are already ill. If the ICMR believes that the drug is not effective enough for sick patients, why do groups of people at low risk of death from COVID-19 take precedence over sick people?

As me Reported earlier, Of the agency COVID-19 Guidelines for Prevention Hundreds of healthy Indians have started to repel drugs. In some states, doctors, nurses, and laboratory technicians are being offered drugs all at once. Unlike physicians, these other health professionals have never prescribed hydroxychloroquine for malaria, lupus, or rheumatoid arthritis. Therefore, they may be unaware of the side effects of the drug and the risks they personally experience in experiencing these side effects. In its recommendations, the ICMR stated that drugs should only be taken by health care workers on the basis of a registered health care worker’s prescription, but there is ample evidence that this is not happening in the country.

Survey? What kind of research?

There is another peculiar aspect to the statement of the Prime Minister of ICMR. In the ANI video, Ganga Hedker refers to a “study” to test whether hydroxychloroquine works among doctors. He was saying the same at a Department of Health press conference on April 1 Data from “empirical studies” If the efficacy of hydroxychloroquine in health care workers was available, the ICMR will determine whether the drug is given to the general public as a preventative, rather than limited to contact of health care workers and patients. .

This statement raises some questions. If ICMR wants to evaluate the effectiveness of hydroxychloroquine as a prophylaxis, it should ideally be a randomized, controlled, blinded study. “Randomized” and “administration” means that a healthcare provider randomly selected for the trial is given the drug and compared to another person receiving a placebo (“administration”). To do. Both divisions of this study should implement all currently accepted precautions against COVID-19, including the use of personal protective equipment (PPE: masks, gloves, goggles, etc.). “Blind” means that participants in either arm cannot recognize whether they are on medication or placebo. The result of the trial Placebo effect: Biochemical improvement of health due to psychological effects of taking medication.

Raman R. Gangakhedkar. Photo: YouTube

Even if it was difficult to conduct such randomized clinical trials, ICMR could have adopted alternative drugs to determine if the drug worked through observational studies. This includes comparing the prevalence of illness among healthcare workers taking medications with those who do not. However, this study is not blinded or randomized and results are less reliable, but still better than nothing.

However, there is no evidence that the ICMR conducts either randomized trials or observational studies on a large number of drug consumers in India. of Indian clinical trial registration, India’s Director of Drug Enforcement, requires all trials to be positively enrolled (that is, before they are conducted), but no Indian study on hydroxychloroquine as COVID-19 prophylaxis has been shown . So what is the study that Ganga Kedal has mentioned many times?

Clinical trials get tougher

In fact, the ICMR’s advice to healthcare professionals to take hydroxychloroquine may have made it difficult for other researchers to conduct such studies. For example, scientists at the George Health Institute in India (headquartered in New Delhi) are planning a trial but say they may have a hard time finding enough participants. Vivekan and Jha, Secretary General of the Institute and Principal Investigator of the research, Wire science Its purpose was to assess whether hydroxychloroquine was more effective than PPE in preventing COVID-19 among healthcare workers. The idea is to recruit 5,000 to 7,000.

But Jar said this could prove difficult. Indian health practitioners may refuse to participate in a trial where drugs are not available if they begin to believe the drugs work. “In any clinical trial there should be a real uncertainty in the minds of the community about whether the drug will work-a clinical balance. But a heavy body like ICMR (this is not just a group of random people Equipoise may no longer be considered present if) issued a recommendation in favor of hydroxychloroquine. Wire science.

This has already happened in one case. Kozhikode’s Aster Malabar Institute of Medical Sciences recently launched a randomized clinical trial to determine the efficacy of hydroxychloroquine as a prophylaxis. The investigators in charge of Alternative Dosage of the same drug. However, there are no placebos in the trial.

The reason for this is that according to Remesh Bhasi, the principal investigator and rheumatologist of the trial, Aster Malabar’s ethics committee is legal for all clinical trials conducted in India to be approved by such an ethics committee. Because I am requesting to. Hydroxychloroquine recommended for high-risk health care workers. Therefore, Absent Giving medication to healthcare professionals in clinical trials can be considered unethical because clinical trials cannot rule out the best treatment or prophylaxis currently available.

As a result of the ICMR’s recommendations, it was asked if it would be a problem to consider hydroxychloroquine as the best preventive measure available today-Bhasi did.

Side effect tracking

It is unclear if and how the ICMR claims the study is being conducted, but it seems that no one seems to be tracking the adverse effects of dose recommended by the ICMR itself. I have a big concern. The agency’s proposed preventive regimen is 400 mg of hydroxychloroquine taken twice on the first day. This is a higher dose than the rheumatologists commonly prescribed for people with rheumatoid arthritis. Indeed, such high doses have never been taken by such a large, healthy population. This means that unprecedented side effects can occur.

However, after his doctor died in Assam shortly after starting the ICMR-recommended hydroxychloroquine regimen, the hospital where he worked (Pratiksha Hospital in Guwahati) reported death to the Indian Pharmacovigilance Program (PvPI). I didn’t. Drug safety. This is despite the fact that the ICMR advice asks people taking the drug to report side effects.

The doctor at Praticusha Hospital Wire science He was unaware of the need to report adverse effects. When asked to PvPI staff if they were investigating the cause of the doctor’s death, there was no response, nor did they answer the question as to whether the ICMR was investigating the problem.

Given all this, it is difficult to believe the authorities’ claims about the rationale for the hydroxychloroquine policy. There were no downsides to the decision to propose this drug as a preventative drug. Patients with lupus and rheumatoid arthritis who need to take medications for years already can’t find hydroxychloroquine sulfate tablets in pharmacies due to unpredictable quarterly demand-this as a COVID-19 prophylactic The number of healthcare workers taking is increasing rapidly. Those who plan to conduct clinical trials may also run short because of the large amount of drug required. The smallest thing an ICMR can do is explain its unscientific stance. If that is not possible, ICMR should consider reverting it.

Notes: 1. In previous versions of this article, according to Gangahekal, ICMR recommended hydroxychloroquine as a prophylactic drug for contacting physician- and laboratory-identified patients. The last part was edited at 5:15 pm, April 15, 2020, in “Patient Contact Confirmed by Examination”. 2. This article was updated on April 18, 2020, at 12:25 pm and includes the Aster Malabar clinical trial.

Priyan coupler I am a science writer.

The coverage of this story was funded by a public health journalism grant to Priyankapurula from the Takul Family Fund.