Indian regulators are pushed to release Covid-19 vaccine trial protocol

As Indian regulators consider emergency approval of a Covid-19 vaccine from the Serum Institute of India, consumer groups are urging authorities to release key documents – such as the clinical trial protocol and study data – amid concerns over transparency and adverse events.

An independent panel of experts set by the Drug Controller General of India meets on Friday to consider the vaccine, which is the Serum Institute’s version of a shot originally co-developed by AstraZeneca (AZN) and the University of Oxford. Earlier this month, the panel delayed its decision while waiting for U.K. regulators to grant emergency use for the AstraZeneca version, which occurred this week.

Consumer advocates, however, maintain Indian regulators should disclose more details before proceeding, especially since the Indian Council of Medical Research – a government entity – is providing support for a so-called bridging trial that is being conducted in the Indian population. Consumer groups are concerned that it is not clear whether the Serum Institute has submitted all safety and immunogenicity data from analyses of the bridging study to regulators, according to a letter sent today to government officials.

The trial protocol has never been released, although STAT obtained a version drafted in July which includes information about the study design, a plan to handle adverse events, and planned interim and data analyses, among many other details.

“Because of the hope that is being placed on this vaccine candidate, the conduct of clinical trials to determine its safety, quality and efficacy, as well as the regulatory standards to review data and the approval process, must be above reproach,” the All India Drug Action Network recently wrote to government officials in which they argued regulators should stringently scrutinize the data and disclose conditions for emergency authorization.

There are also concern over possible differences in the trial designs of the AstraZeneca and Oxford trials in different countries and the design of the Serum Institute trial in India. As a result, it remains unclear how Indian regulators will view data that formed the basis of an emergency authorization issued this week by U.K. authorities.

The advocacy groups have also noted that a trial participant sent a legal notice to Serum threatening to file a lawsuit over alleged neurological harm, which prompted Serum Institute last month to threaten to retaliate with its own lawsuit for more than $13 million. The Drug Controller General, however, has since indicated that a causal link between the alleged adverse events and the vaccine could not be established.

Nonetheless, since there were reports of serious adverse events involving neurological symptoms in the AstraZeneca and Oxford vaccine trials outside India and one case in India, they argue that the full Indian protocol should be made public to assess how the study is powered and the extent to which such reactions are rare. The advocates also want the Drug Controller General and the Data Safety Monitoring Board to release the complete details of their investigation.

We asked the Drug Controller General and Serum Institute for comment, and will update you accordingly.

We should note that an amended protocol was drafted in October, but that has not been made public either.

This development occurs amid an unprecedented global race to develop Covid-19 vaccines as governments around the world struggle to cope with a fast-growing number of illnesses and deaths caused by the pandemic. So far, vaccines developed by Moderna (MRNA) and a partnership between Pfizer (PFE) and BioNTech (BNTX) have been authorized for emergency use in the United States.

At the same time, the pandemic is also prompting concern low and middle-income countries will not be able to obtain sufficient quantities as wealthy nations strike deals with vaccine makers. High-income countries have procured nearly half of the vaccine doses for which agreements have been reached, according to the Duke Global Health Innovation Center.

A World Health Organization program called COVAX is working to obtain supplies for poorer countries and reached a deal for the Serum Institute version of the AstraZeneca vaccine. Serum Institute had already agreed with AstraZeneca to manufacture and supply 1 billion doses of the vaccine for low-and-middle-income countries, with a commitment to provide 400 million doses before the end of 2020.

Moreover, the vaccine, known as Covishield, is expected to be priced for as little as $3 per dose, while Pfizer and Modern are charging at least six times that amount. And unlike these other vaccines, which require sub-zero temperatures for shipping and storage, the AstraZeneca and Serum vaccine versions can be stored at 2 to 8 degrees Celsius, which is more typical of vaccine refrigeration requirements.

Transparency about trial data, meanwhile, has been an issue.

Despite the clamor for Covid-19 therapies and vaccines, a growing chorus of physicians, academics and public health experts have maintained that manufacturers should disclose protocols and data so that results – and regulatory decisions – can be better understood. Pfizer and Moderna, for instance, responded by releasing their protocols.