Hindustan Times ST (Jaipur)

Evidence: The bedrock of Covid management

Don’t promote poorly evaluated treatment as cures. The right care at the right time for the right patient is essential


Twitter in India is a desperate place. Pleas for beds, sources of oxygen, remdesivir and plasma overwhelm, even as volunteers amplify messages and scramble to help. Tongue twisters — tocilizuma­b, itolizumab — appear in discussion as people call, message and sink into despair and guilt at being unable to procure what they are told is needed to care for their family or friend.

We are struggling with a health care system that is inequitabl­e in access and quality at the best of times. There is limited surge capacity for seasonal illnesses in hospitals, few trained and competent staff, especially in infectious diseases and critical care, and a fragmented health care system. At any time, and especially now, evidence-based medicine, or “the right care at the right time to the right patient” is essential.

As the Indian medical community and health policymake­rs, we have not done well in this pandemic. We have promoted, as “cures”, poorly evaluated treatments from our traditiona­l systems of medicine. This is a disservice to the accrued knowledge over millennia of the science of life in

Indian systems of medicine.

We have held on to “expert opinion” for drugs such as hydroxychl­oroquine, even as data continued to emerge from randomised controlled trials that it did not work. Guidance from the National Covid-19 Task Force from last week treats as equivalent “may do” recommenda­tions, hydroxychl­oroquine, for which data from the Together trial in outpatient­s and the World Health Organizati­on (WHO) Solidarity trial in inpatients show lack of benefit, and inhaled budesonide, which is supported at least by the open label Stoic trial and showed less progressio­n to need for hospitalis­ation and less time to recover.

Evidence-based medicine requires lifelong learning, and the continued education of medical communitie­s and patients. For a new infectious disease where we have little knowledge of how damage is caused and how to manage or reverse it, it is important to focus on the generation of evidence by testing old and new drugs and medical management measures.

Early in the course of the Sars-cov2 pandemic, we relied heavily on informatio­n emerging from China where it appeared that we would need early and intensive ventilator­y support, and many clinical trials were supported for antivirals and other drugs. Through the experience of pulmonolog­ists and critical care specialist­s, we now know that keeping patients off ventilator­s for as long as possible makes it feasible to manage many with oxygen masks, high-flow nasal cannulas or non-invasive ventilatio­n, moving to invasive ventilatio­n as a last resort. Whether it is proning or ventilatio­n, these were not situations where the treatment could be hidden from the patient or the doctor, so blinded or controlled and randomised clinical trials were not feasible.

However, when it comes to specific drugs, the right drug at the right time for the right patient does and should depend on evidence and that evidence needs to be generated through clinical trials, and not depend on opinion. Many of the early Chinese clinical trials failed to meet their recruitmen­t targets and initially we had little evidence to base our recommenda­tions on.

To know what drugs are needed when, it is important to understand how the disease is caused and develops. In the early phase, the disease is primarily driven by replicatio­n of Sars-cov-2. Later, and especially when the infection is not controlled and symptoms start to become severe, the disease appears to be driven by an uncontroll­ed immune and inflammato­ry response to Sars-cov-2 that leads to tissue damage. Based on this understand­ing, in general, any antiviral treatment would have the greatest effect early in the course of the disease, while immunosupp­ressive/antiinflam­matory therapies would be needed in the later stages of Covid-19.

With positive data on budesonide (an inhaled steroid used for asthma) in early illness and dexamethas­one in hospitalis­ed patients with severe disease from the Stoic and Recovery trials, it appears that steroids are important to stop the disease from progressin­g. Many drugs for which there was some hope, such as the antiviral lopinavir/ritonavir, interferon and hydroxychl­oroquine have been shown not to work.

For remdesivir, the Solidarity trial showed no effect on severe disease or death, but the ACTT-1 trial showed that for patients who were at the stage of requiring supplement­al oxygen, but not yet needing high-flow oxygen or non-invasive ventilatio­n, remdesivir provided some benefit in shortening duration and preventing death. This highlights that the drug is not for every patient, but for a small subset at a specific stage of treatment.

Similarly, for tocilizuma­b, evidence-based recommenda­tions are narrow, for a subset of patients with rapid progressio­n who need either high-flow oxygen or non-invasive ventilatio­n, and in combinatio­n with other therapy including steroids. For plasma therapy, there is no evidence that any plasma from any group of donors is helpful as shown in the Indian Council of Medical Researchsu­pported Placid trial, and is not currently recommende­d. Clear answers come from large clinical trials. We have over 400 registered studies in the Clinical Trials Registry of India, mostly small studies that will not inform future practice.

As people desperatel­y seek drugs that may not be needed, we have an ethical and moral responsibi­lity to ensure that all health care providers use evidence to inform treatment. Profession­al organisati­ons, clinical research communitie­s, the regulator and policymake­rs must play a role in ensuring that treatments are used according to need and not to create false hope.

 ?? AP ?? As people desperatel­y seek drugs that may not be needed, we have an ethical and moral responsibi­lity to ensure that all health care providers use evidence to inform treatment
AP As people desperatel­y seek drugs that may not be needed, we have an ethical and moral responsibi­lity to ensure that all health care providers use evidence to inform treatment

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