Read on Twitter
That it would be difficult to enroll massive amounts of people into clinical trials in record time should be a surprise to no one. Itâs probably even harder to enroll because of the perception that these vaccines have been rushed. https://twitter.com/realdonaldtrump/status/1297138862108663808
So I *think* the general critique being made here is that the FDA's standards for vaccine approval are too high. Specifically, that FDA's standards that it wants 20-30k people per trial is serving to "delay" approval.
Let's unpack this a bit in a thread.
Let's unpack this a bit in a thread.
First, vaccines are considerably different than other therapeutics.
Drugs and biologics are generally given to specific patients to help them treat or cure a disease.
Vaccines are generally given to massive populations of patients who aren't sick.
Drugs and biologics are generally given to specific patients to help them treat or cure a disease.
Vaccines are generally given to massive populations of patients who aren't sick.
That means vaccines may be used on: The healthy. The Sick. The old. The young. The pregnant. Persons with rare conditions. Persons with undiagnosed conditions. Etc
That requires trials to be large, because you need to make sure the vaccine is safe and effective in *everyone*.
That requires trials to be large, because you need to make sure the vaccine is safe and effective in *everyone*.
FDA has been pretty clear about the size of the trials it wants. According to Peter Marks, who leads FDA's biologics division (CBER), FDA expects 10-15,000 patients per treatment arm.
So if you have a vax and a placebo, each group needs 10-15k patients.
From AIQ on July 8:
So if you have a vax and a placebo, each group needs 10-15k patients.
From AIQ on July 8:
FDA has also published a guidance document describing the criteria for COVID vaccine trials.
*BLA = Biologics License Application, which is the sponsor's application to approve a vaccine.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19
*BLA = Biologics License Application, which is the sponsor's application to approve a vaccine.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19
Ok, so you need to enroll 20-30k patients *per vaccine candidate*. Luckily, there are lots of vaccines in testing.
Unfortunately, that means they're all competing for the same patients.
As I wrote for AgencyIQ in early July, this was expected to be a problem.
Unfortunately, that means they're all competing for the same patients.
As I wrote for AgencyIQ in early July, this was expected to be a problem.
And according to press releases from Pfizer and Moderna in the last 48 hours, companies are having a bit of trouble getting people to enroll as quickly as they might have hoped.
Pfizer: 11,000 enrolled ( https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-share-positive-early-data-lead-mrna)
Moderna: 13,100 enrolled https://www.modernatx.com/cove-study
Pfizer: 11,000 enrolled ( https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-share-positive-early-data-lead-mrna)
Moderna: 13,100 enrolled https://www.modernatx.com/cove-study
The upshot of this is: If you don't have full enrollment, you may not have enough data to support a full application to the FDA.
And that could delay the ability of the FDA to make an approval decision (or puts pressure on them to use emergency use authorization).
And that could delay the ability of the FDA to make an approval decision (or puts pressure on them to use emergency use authorization).
None of this is nefarious or evidence of a "deep state."
It's expected. It's evidence that finding 30,000 people to enroll in a clinical trial is always tough, and made tougher in a pandemic when people may have lost their jobs, their transportation, or the desire to travel.
It's expected. It's evidence that finding 30,000 people to enroll in a clinical trial is always tough, and made tougher in a pandemic when people may have lost their jobs, their transportation, or the desire to travel.
Ironically, one challenge to enrollment may be caused by the President himself. Consider the plethora of polls indicating people would be hesitant to take a COVID-19 vaccine:
https://news.gallup.com/poll/317018/one-three-americans-not-covid-vaccine.aspx
https://www.politico.com/news/2020/07/29/coronavirus-vaccine-poll-385047
https://apnews.com/dacdc8bc428dd4df6511bfa259cfec44
https://news.gallup.com/poll/317018/one-three-americans-not-covid-vaccine.aspx
https://www.politico.com/news/2020/07/29/coronavirus-vaccine-poll-385047
https://apnews.com/dacdc8bc428dd4df6511bfa259cfec44
If the public thinks that vaccines are being rushed (say, at "Warp Speed," or to arbitrarily be approved by the election), then they might not want to enroll in a clinical trial.
And if the president is inferring that the FDA is the "deep state," that erodes trust in FDA.
And if the president is inferring that the FDA is the "deep state," that erodes trust in FDA.
I think the hydroxychloroquine saga is yet another example of this in action. FDA rescinded its emergency authorization due to safety concerns and a lack of convincing efficacy data.
This morning, the President reiterated his support for HCQ. https://twitter.com/realDonaldTrump/status/1297148038385991680?s=20
This morning, the President reiterated his support for HCQ. https://twitter.com/realDonaldTrump/status/1297148038385991680?s=20
Now, FDA folks are clearly concerned about the potential for political pressure.
Here's Hahn this week talking about how transparency is the antidote to that: https://www.graydc.com/2020/08/20/fda-chief-no-pressure-from-anyone-to-expedite-approval-process-for-covid-19-vaccine/
And here's Mark's saying he would resign if pressured: https://www.reuters.com/article/us-health-coronavirus-vaccines-fda-exclu/exclusive-top-fda-official-says-would-resign-if-agency-rubber-stamps-an-unproven-covid-19-vaccine-idUSKBN25H03H
Here's Hahn this week talking about how transparency is the antidote to that: https://www.graydc.com/2020/08/20/fda-chief-no-pressure-from-anyone-to-expedite-approval-process-for-covid-19-vaccine/
And here's Mark's saying he would resign if pressured: https://www.reuters.com/article/us-health-coronavirus-vaccines-fda-exclu/exclusive-top-fda-official-says-would-resign-if-agency-rubber-stamps-an-unproven-covid-19-vaccine-idUSKBN25H03H
There have been a few things I've been watching for months now (as AgencyIQ readers will know):
1) How Peter Marks will handle pressure and the spotlight
2) How Hahn will handle Trump on approvals
3) Whether Azar could step in and over-rule FDA on vaccine approval decisions.
1) How Peter Marks will handle pressure and the spotlight
2) How Hahn will handle Trump on approvals
3) Whether Azar could step in and over-rule FDA on vaccine approval decisions.
This week saw a few key developments.
1) Marks saying he would resign if pressured
2) Trump basically roasting FDA and Hahn this morning
3) Azar reversing FDA policy on Lab Developed Tests without FDA's consent.
1) Marks saying he would resign if pressured
2) Trump basically roasting FDA and Hahn this morning
3) Azar reversing FDA policy on Lab Developed Tests without FDA's consent.
I still think Azar could be a quiet wildcard here.
Remember when Obama's HHS Secretary Kathleen Sebelius overruled FDA on its approval decision for Plan B One-Step?
https://www.politico.com/story/2011/12/the-plan-b-call-politics-vs-science-070118
Azar is technically the boss of Hahn and can order the agency to do lots of things...
Remember when Obama's HHS Secretary Kathleen Sebelius overruled FDA on its approval decision for Plan B One-Step?
https://www.politico.com/story/2011/12/the-plan-b-call-politics-vs-science-070118
Azar is technically the boss of Hahn and can order the agency to do lots of things...
I'll leave you with a two final thoughts for now:
It's only August.
Can you imagine how much more pressure the FDA is going to be under in September and October?
It's only August.
Can you imagine how much more pressure the FDA is going to be under in September and October?
Finally, public trust in FDA as an institution is incredibly important, especially in a pandemic.
If the president is casting doubt on the agency, fewer people are going to want to get vaccinated, which is going to result in a worse pandemic response.
If the president is casting doubt on the agency, fewer people are going to want to get vaccinated, which is going to result in a worse pandemic response.
