New Delhi: Despite the harsh lockdown, good planning and coordination between all government departments helped India prepare for the World Health Organization’s (WHO) Solidarity trial in “less than a month”, said Sheela Godbole, national coordinator for the global trials in India.

“Good planning and coordination and support at levels helped us initiate the first patient on the trial in less than a month after the decision (was made) to participate in the WHO Solidarity trials,” Godbole told ThePrint in an exclusive interview over email.

Godbole is the chief scientist at the National AIDS Research Institute (NARI), which comes under the country’s top health research body, Indian Council of Medical Research (ICMR).

“To put the trial together, I have found myself unapologetically calling health secretaries (of states and Centre) which always paved the way.”

The Solidarity trial, an international clinical trial meant to help find an effective treatment for Covid-19, compares options against standard of care and assesses their relative effectiveness against the disease.

“As of 1 July 2020, nearly 5,500 patients have been recruited in 21 countries among the 39 countries that have approvals to begin recruiting. Overall, over 100 countries in all six WHO regions have joined or expressed an interest in joining,” WHO said on its website.

By enrolling patients in multiple countries, the trial aims to rapidly discover whether any of the drugs slow disease progression or improve survival.

Setting up the trial

On 27 March, R.R. Gangakhedkar, who was then the chief epidemiologist of ICMR, had announced that India would participate in the multi-country trial to identify potential treatment.

Godbole said they had fast-tracked the process so that before the end of April, India had completed all regulatory requirements, earmarked budgets and even decided the drugs to be tested. “Also, we had completed training (of officials involved) and, in fact, the first participant was randomised,” she said.

The trial began with two of the total four drugs which were already available in India.

“Even during lockdown, we could quickly import remdesivir and interferon beta 1 a … With a lot of support from various agencies, (we) transferred the study drugs from Pune to the sites using land routes.”

To choose a trial site, Godbole said they focused on places where the most cases were reported. “We began with three registered sites, which grew to 16 sites by May and today we have 27 sites registered.” Three more sites are close to being registered, she said, which will take the total number of trial sites to 30.

So far, the Indian arm of the global trial has randomised 600 participants. This means 600 volunteers have been allocated at random to a particular arm of the trial. This ensures that the trial isn’t biased.

Fast tracked process, but not without hiccups

The first step taken to kickstart the trial in India was to put together a team of “highly motivated professionals” at NARI, ICMR, and WHO India and other regional offices of WHO. “All of these professionals took up this task as a moral responsibility in the face of this pandemic,” she said.

Even though the process was accelerated, she said they ensured the quality of the trial wasn’t compromised. All regulatory requirements were met and rules were followed while establishing each and every site for the trial, she emphasised.

“Many sites approached us for participation too and were very enthusiastic. Within two weeks of receiving the letter from ICMR, we had submitted (trial protocol) to the Drug Controller General of India (DCGI) — an apex regulator to approve clinical trials in India,” she said.

The DCGI fast-tracked the review process on their end.

Training for the principal investigators and the doctors at the sites was conducted at all possible times since they were already very busy, Godbole said. “We conducted online training as per their convenience, such as on weekends and even after 10 pm at night on Sundays.”

But despite all precautions and cooperation, setting up the trial has not been smooth. “It was certainly very challenging, particularly as it was all done during the strict lockdown phase,” Godbole said.

For instance, because of the urgency and the lockdown situation, a clinical research agency could not be hired. So all the work was done in-house at NARI. “We could only hire dedicated staff for the project in the last week of June,” she said.

Clinical research agencies help in organising and administering clinical trials by working with doctors to ensure that the drugs meet certain standards, achieve desired results and ensure the overall benefit of the patient.

Her own involvement in ICMR’s consultative meeting and workshop on conducting clinical trials during pandemic/epidemic situation during the Nipah outbreak came to her aid while designing the trials, Godbole said.

Clues in randomised trials

The medical fraternity must look at findings from randomised controlled trials and use the evidence to change the way we treat, advises Godbole, who says this was her top learning from such giant trials.

During a pandemic, when the virus is pretty unknown, “there is no recourse but to choose treatment options based on observational evidence and studies with small numbers,” she pointed out.

“However, the best level of evidence is provided by well-designed randomised controlled trials (RCT).”

The RCT being done under the Solidarity trial across more than 20 countries has “an adaptive design”.

“Interim analyses of data, as well as pooled analyses or comparisons with other international trials, help provide data on utility or futility of a particular treatment option for hospitalised patients of Covid 19,” she said.

“This is the unique strength of this trial and soon the findings will be published.”

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