USFDA may give impetus to plasma therapy in India, experts question efficacy

by Times of India

MUMBAI: The emergency use approval authorisation by US Food and Drug Administration (USFDA) to convalescent plasma as a potential therapy for Covid in US, is expected to provide impetus to its use as a ‘promising’ treatment option in India, even as doctors say clear scientific evidence is needed.

The US President announced USFDA approval on August 23, though the agency put it on hold just last week over doubts on its efficacy.

Doctors say the therapy involving use of recovered Covid-19 patients’ plasma to treat infected people will get even more widespread in India, given the ‘endorsement’ from US. This would be similar to the sharp surge in demand witnessed for anti-malarial drug hydroxychloroquine as a potential Covid-19 treatment, after President Trump’s repeated backing for it, though it had no scientific backing, and later failed in global trials, experts say.

The USFDA announced that convalescent plasma may be effective in treating Covid-19, and potential benefits of the product outweigh the risks, based on scientific evidence available.

In India, multi-centre clinical trials to study whether plasma therapy is a useful Covid treatment are underway by the Indian Council of Medical Research. Further, states like Maharashtra are running the ‘world’s largest’ plasma therapy trials, Project Platina, in 18 medical colleges, but response from donors reportedly has been lacklustre.

“Covid therapy is highly individualized. The use of plasma therapy can be life-saving in certain cases, and is being used on compassionate grounds. It is a promising treatment option if used earlier in the cycle of the disease. It has been used as therapy for over 100 years, but for Covid-19, we need to document this in a research programme. We also need better methodology for its use while screening donors so as to know the adequate level of neutralising antibody, or titers”. Dr Shashank Joshi endocrinologist and member, Maharashtra’s Covid-19 task force told TOI.

Significantly, World Health Organisation on Monday remained cautious about endorsing the use of plasma to treat infected people. “The results are not conclusive”, it’s chief scientist Soumya Swaminathan said, adding “We recommend that convalescent plasma is still an experimental therapy, and should be continued to be evaluated in well-designed randomized clinical trials”.

Dr CS Pramesh director, Tata Memorial Hospital said, “In India, this will mean that patients’ families will now rush to get this treatment, spending a lot of money, hunting for potential donors, with no proven benefit. In fact, the only two randomized trials with published results show no benefit with this treatment though it must be admitted that these trials were underpowered to find a difference even if one existed”.

The USFDA decision was based on an observational study that gave “some positive signals that convalescent plasma can be helpful in treating Covid-19” and might reduce the mortality if administered early after diagnosis. This article is posted on preprint servers and is yet to find its way into a medical journal. However, the tall claims made by the USFDA commissioner have considerably done more harm to the science and raised unrealistic hopes among the public, experts say.

“Politicians, policymakers, physicians and public fail to understand that this study is not a randomized controlled trial, but an observational study. Although this study enrolled close to 35,000 patients, it’s design is that of an observational study, and has major limitations. We badly needed rigorous randomized clinical trials to get clear and accurate answers and to put our patients on treatments that work. Instead, by ignoring science, we shall continue to treat patients based on evidence generated by anecdotes, poor observational studies, biases, not knowing if plasma benefits or harm”, said Dr SP Kalantri Professor of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram.

In India, plasma is being promoted asking people to donate plasma to save lives, and shaming Covid survivors who chose not to donate. We seem to have accepted plasma therapy widely without any good quality evidence supporting its use. This is likely to get even more widespread with the endorsement from the US, said Dr Lancelot Pinto consultant respirologist at Mumbai-based PD Hinduja Hospital.

Plasma reduces death rates if there are enough neutralizing antibodies in the donor plasma. “As of now, our labs are not accurately measuring the titres of antibodies in donor plasma- thus it is a wild guess if plasma administered to the Covid patient would indeed benefit the patients”, Kalantri added.

USFDA’s statement implies a 35% absolute improvement in outcomes, when the reality is a 3.2% improvement, and that too comparing early vs late plasma, Dr Pramesh said, adding, The danger of such a public statement is that ongoing randomized trials of convalescent plasma will struggle to recruit patients; notably, the USFDA still recommends that randomized trials of plasma continue (which implies that we don’t know whether there is a benefit), but which patient or physician will willingly enter a randomized trial after the FDA Commissioner has claimed a 35% benefit?

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