FDA deputy commissioner Shah on COVID-19 vaccines, plasma, lab tests and data usage

Last week, Anand Shah, MD, the deputy commissioner for medical and scientific affairs spoke on the record with journalists at an Alliance for Health Policy webinar. His opening remarks were published, so I will not recap them here – you can read them yourself. Instead I will share his Q&A answers. These are not direct quotes but summarize what he said. I did not fact check or editorialize.

Q: When will we get more rapid diagnostic tests on the market?

There are many types of tests: PCR-based, antibody, antigen, genetic technologies and saliva-based. There are differences in where the tests are performed: lab/instrument based, administered at point of care, self-collection. FDA goal is to provide the industry and marketplace with clear expectations as to what the agency is looking for (sensitivity/specificity, post-predictive value), understanding about how developers should collect the data, under which settings data is collected. All this is considered during an FDA review.

More than 200 tests have emergency use authorization (EUA).

The saliva test is an innovation with potential to greatly expand. No swab needed with saliva, and patients can self-collect under supervision of a healthcare professional. It does not require an extraction step (with PCR, need to extract DNA or RNA). Saliva test preserves reagent. There are currently 5 saliva-based tests authorized by the FDA. Questions were asked by individual journalists.

Q: Why is the FDA allowing tests developed by individual labs without review?

He differentiated between lab-developed tests and commercial tests. Commercial tests are by a manufacturer for wholescale production and wide distribution. Lab-developed tests are used in one laboratory for a more limited catchment area. Last week the HHS announced the FDA will change its enforcement of lab-developed tests. The FDA as an agency has championed guidance and best guidance practices. They are mindful that any FDA decisions that are legally enforceable should go through notice and commenting periods. They are hoping that last week’s HHS decision will allow for rapid access to more testing, while preserving the agency’s ability to ensure that tests in the marketplace, including lab ones, are accurate/reliable. More information is coming as the FDA works on implementation.

Q: Trump said the FDA is holding up convalescent plasma treatment due to politics. Is this true?

The FDA has been supportive and continues to support the development and investigation of convalescent plasma for COVID-19. It’s been used for more than 100 years for a variety of uses. We continue to learn about safety/efficacy of it for this disease. FDA partnered with Mayo Clinic to allow wide national access of patients wanting convalescent plasma for treatment. This expanded access protocol enrolled more than 60,000 patients and they’re actively looking at safety/efficacy in the data generated through that protocol and other studies. FDA has a scientific team led by Dr. Peter Marks around the data. The public will be notified when there’s a decision.

Q: What is the data required for convalescent plasma before an EUA is issued?

FDA issued guidance to developers about this a few weeks ago. They targeted the clinical investigator community as they launched clinical trials. Guidance includes how to think about safety/efficacy. FDA will look at the totality of the data. No firm bar mentioned, but will look at data from randomized controlled trials, and the Mayo expanded access protocol, a real world evidence setting. Scientific team will consider all data accrued. The decisions around convalescent plasma will take into account a number of factors: open ecosystem, continual data collection, insights, intelligence.

Q How you coordinate with other agencies?

Hahn is on the White House COVID-19 task force. That’s a forum for interagency coordination with federal partners. It’s done on the staff and leadership levels. Talking to them daily.

Q: Is it productive of Trump to insist a vaccine will be available before the election?

FDA won’t get into the timing. There are a number of active clinical trials accruing and available today, in various phases of development. A few are in phase 3. FDA wants to ensure the integrity of the trials to ensure they are accruing as expected/planned. FDA is giving proactive support to developers in future and ongoing trials. “I can’t offer anything in the way of timing.” When FDA has data, they will huddle.

Q: With multiple vaccines in trials, will the FDA choose 1 vaccine or potentially multiple? Will people be given choices?

FDA goal is for every vaccine candidate to pass through rigorous clinical trials. FDA gave guidance on June 30 around contours and expectations of the trials. “We’ll look at as many candidates as needed.” Will look at data in real time. A number of vaccine candidates are in the pipeline. FDA goal is to authorize or license vaccines that are safe and effective, and they hope it leads to choices just like with the flu vaccine.

A vaccine advisory committee will meet prior to licensure, to give approval/authorization. This will be public-facing and they may augment the committee with additional experts with coronavirus expertise. Working through dates and logistics now, and October 22 is penciled in. It will allow the agency to get opinions from outside expert panel to help guide decisions.

Q: How to look at the data to ensure it’s the truth?

We’re a world of uncertainty today. Novel pathogen that we’re learning about in real time. Our understanding of the virus is very different from even one month ago. All FDA decisions are rooted in science, data and commitment to scientific integrity. FDA will continue to make decisions based on data collected in real world settings and decisions are dynamic. The agency will continue to revisit risk/benefit calculation. When needed, FDA will revisit and take shifting action as data supports it.

Q: What is the FDA doing or are they concerned about in terms of diversity in the clinical trials?

FDA is committed to working with and pushing vaccine developers to ensure diverse accrual in study populations. Population of patients/subjects studied should reflect America’s diversity. Elderly, ethnic minorities, those with medical comorbidities. Provide insights into how vaccines may work in other vulnerable populations like pregnant women. Working with developers to ensure diverse populations are included in trials. When decisions are made by FDA, they will take into account subpopulation data.

Data will help determine who gets the vaccine first. They will share insights with federal partners who ultimately take the baton for allocation/distribution.

Q: Hand sanitizer shortages – are they still happening?

FDA warnings about some in past 6 months. Early on there were shortages. FDA issued public-facing guidance to the industry/developers to provide flexibility on making it. Overwhelming interest from traditional and nontraditional developers to replete the supply chain. Also have seen some bad products come to market. Whether these are associated with flexibilities extended to COVID-19, unknown right now. Warnings issued for those with methanol (wood alcohol) with swift to take action at the Mexico border, and removing those products from the market.