The research challenge

Dinesh C Sharma

Science commentator

As the coronavirus pandemic continues to unfold across the world, the search for treatment and vaccines has also intensified, along with the need for cheaper diagnostic tests, affordable personal protective gear, cost-effective ICU equipment and makeshift hospitals etc. Several national research laboratories and defence research establishments have started work in this direction. They are developing sanitisers, personal protection equipment and ventilators and have provided research equipment for conducting diagnostic tests. Projects for identifying and testing potential treatment have also been started. Clinical trials have also been launched on studying the efficacy of the plasma therapy in infected patients. All these research initiatives are aimed at boosting the country’s capacity in surveillance, infection prevention and control, laboratory support for diagnostics, isolation and management of critically ill patients, besides treatment.

Research councils and funding agencies have responded by fast-tracking calls for research proposals, approvals and release of funds for projects related to Covid-19. These processes which normally take months, sometimes years, are taking only weeks and days now. Most of the products related to the virus testing and treatments, such as diagnostics and vaccines, need to go through the regulatory pipeline as well. These regulatory and quality approvals are granted by the Central Drugs Standard Control Organisation (CDSCO) and the Indian Council of Medical Research (ICMR). Normally, new drugs and vaccines are subjected to clinical trials to test their toxicity, dosage, efficacy and suitability to humans before they are allowed for mass usage. If the studies involve animal testing, companies and research institutes need to follow set procedures. In the case of human clinical trials, proposals are also examined by institutional ethics committees from the ethics point of view. These procedures are supposed to be stringent and usually take a long time.

Should technical, ethical and regulatory processes be suspended or bypassed during epidemic or pandemic situations? What’s the use of a vaccine or a rapid diagnostic kit if it becomes available once the pandemic subsides? The global health community has been grappling with these questions in the wake of the outbreaks and epidemics of new pathogens such as Ebola, Nipah, MERS etc. which have no known treatment and vaccines.

Research during epidemics needs a different approach and speed. Keeping this in view, the World Health Organisation (WHO) has been working on a framework called ‘R&D Blueprint.’ The idea is to develop new norms and standards for speeding up R&D processes, improving coordination and fostering an enabling environment during outbreaks of infectious diseases and pandemics.

Pandemic and emergency situations may also prompt the use of certain existing drugs and therapeutics if no existing drug or vaccine is available, as in the case of the novel coronavirus. Such drugs may be already in use for an existing disease. So, obviously, it would have gone through all necessary regulatory approvals, including human trials for safety and toxicology. When such existing drugs are applied for a new disease (for which they have not been approved originally), it is called off-label use.

The recommendation of the Health Ministry to use hydroxychloroquine in combination with azithromycin for treatment of novel coronavirus is an example of such off-label use. This was based on limited evidence from China and some past studies about the antiviral properties of the drugs. Globally, several trials are going on to evaluate the efficacy of this combination for the novel coronavirus.

While evidence is still emerging, local authorities in Mumbai are reportedly planning to administer hydroxychloroquine as a prophylaxis to a large number of people in Dharavi, which has been identified as a hotspot for the novel coronavirus. Such large-scale use, outside any health facility, raises several ethical questions. Is it a structured clinical trial? Will there be follow-up of adverse reactions? Have people been told of the potential side-effects? Can it be given to everyone — irrespective of age or other underlying health problems? Will people be told about the efficacy and side-effects of the drug?

Addressing these questions is important as more drugs are emerging for their potential ‘off label’ use for the novel coronavirus. For example, a Singapore-based AI-based drug discovery firm has listed reserpine — a drug that was once used to treat high blood pressure — among potential candidates. Incidentally, reserpine was discovered in India — from Rauwolfia serpentina or sarpgandha — and clinically tested for the first time by a Bombay physician, Rustom Jal Vakil, in 1948.

Research during epidemic outbreaks needs special protocol and procedures. These steps are critical as such research would involve handling human samples, virus strains and other biological material. We need clear procedures and technical guidelines for all this, in addition to flexible regulatory and ethical frameworks for emergencies. Such frameworks should take into account collaboration with commercial partners as well as inter-country partnership which may involve exchange of bio-material during research and sharing of intellectual property of new products as well as data. In addition, guidelines related to pre-qualification of medical products and innovations being developed need to be followed strictly.

Some CSIR labs have been promoting the so-called sanitising tunnels, whose use has, in fact, been banned by the health ministry. Some others are making claims about new types of PPEs and ventilators, but the use of such products may be dangerous without the necessary tests and trials. While we need to move fast, let’s not ignore the basic tenets of research — sound scientific evidence and ethics.

Join Whatsapp Channel of The Tribune for latest updates.