It was early April and SARS-CoV-2 was just starting to spread across India. The country was under a lockdown. It was a time of collective uncertainty, as clinicians, researchers, policy makers, and the public all hoped for a cure. Slowly, multiple therapies started to emerge: hydroxychloroquine, which was traditionally used to alleviate joint pains; Lopinavir-Ritonavir, the scourge of the previous HIV epidemic; and remdesivir, a new treatment and a beacon of hope, according to some. Amid all of this, a century old friend, tried and tested every time humanity faced a dangerous pathogen, started to gain traction too: the yellow translucent fluid “convalescent plasma.”
We chose to study convalescent plasma because unlike all other new treatments, which were in uncertain supply, it could be the most equitable drug. The task was daunting. Traditionally, such research in India has been supported by collaborations, usually with the global north (like Oxford University, John Hopkins University, or others) or funding partners or, most commonly, the World Health Organization. This time, we were alone. Everyone was focused on their own endeavours.
Our team of researchers put together a study protocol with help from haematologists, transfusion medicine specialists, and internists. Once the protocol was ready, our instinct was to implement it at a few elite centers of repute. But a major concern entered our minds. Would it be equitable to restrict clinical trials, an important vehicle for providing access to treatment, to a few hospitals? Would it represent the reality of India, which encompasses both the urbanscapes of Delhi, as well as the rural villages of Bihar?
Bearing these questions in mind, we opened our recruitment to every hospital that had the requisite infrastructure and agreed to provide treatment free of cost to all of the participants in the trial. The response was overwhelming. Despite having busy clinical schedules, doctors on the frontline were keen to participate, and more than 100 hospitals responded to our call for participating in the PLACID trial. Eventually, despite a tight budget, 39 hospitals would enrol 464 patients in just three months. The journey to get to that point, however, was not easy.
The first hurdle was to set up multidisciplinary teams at every site, consisting of a clinician, a transfusion medicine specialist, and a microbiologist—all of whom were already overwhelmed with working in short staffed settings, while donning perspiration drenched personal protective equipment. However, the sites did manage to get these teams together. As it turned out, the sites which performed best (in terms of the number of patients enrolled and the quality of their data, for example) were not the ones that had the best infrastructure or prior experience in research, but those that put together the most coordinated teams. Staff contracting covid-19 in the line of duty and having to enter a period of quarantine became a frequent hiccup.
Enrolment was slow to begin with. As cases of covid-19 were still rising, the country was under lockdown, and people were generally avoiding hospitals, getting plasma donors to hospitals was a challenge. The sites, however, put in exemplary efforts to collect plasma. Each site called hundreds of potential donors, arranged cars for pick-up and drop off, and designed innovative information campaigns to get plasma.
The biggest hurdle for the central team was quality assuring the data we received. With people’s movements restricted due to lockdown, monitoring the study was difficult. To assure data quality, we carried out multiple training sessions to discuss the protocol and fill in the electronic data capture forms. All the investigators met online weekly to discuss the progress of the trial. Moreover, we connected on an individual basis with the investigators twice every week and individual site audits were done online. Most importantly, to assure quality, the central team focused on fostering relationships with all of the investigators. This helped to create an environment that was conducive to discussing the challenges investigators faced and finding solutions, rather than a blame culture of finding faults. These relationships bore fruit, as site investigators took ownership of the trial, sometimes even paying out of their own pockets to bridge the gap in funds.
The goal of research is to generate knowledge through hard data, but conducting this trial taught us that this should not be the sole purpose. We learnt that the key to good quality, large scale trials, which can answer questions important to people rather than funders, was rooted in capacity building, training, and having respect for local health systems. We learnt that reputed elite institutions, first world collaborations, third party organisations, or big funding are a big help if available, but they are not indispensable. Finally, we learnt that, as in other areas of life, generating evidence is also best done by fostering trustworthy relationships—with effective communication, clear ownership, and teamwork at their heart.
Anup Agarwal is a consultant at the Clinical Trial and Health Systems Research Unit, Indian Council of Medical Research, New Delhi, India.
Aparna Mukherjee is a scientist at the Clinical Trial and Health Systems Research Unit, Indian Council of Medical Research, New Delhi, India.
Gunjan Kumar is a scientist at the Clinical Trial and Health Systems Research Unit, Indian Council of Medical Research, New Delhi, India.
Competing interests: See linked Research paper.