Project WARP SPEED is a federal effort to get a vaccine approved and distributed as quickly as possible for COVID-19. We are moving a system that is designed for sequential, incremental analysis to rapid parallel development along with risk tolerance that we have never taken before on a society wide scale. One of the biggest short-cuts that is likely to be taken is Emergency Use Approvals (EUA) off of incomplete trials.
I am looking at the Moderna ClinicalTrials.Gov application for their Phase 3 trial as an example of where risk is likely to be taken.
Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 30000 participants
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older
Estimated Study Start Date : July 27, 2020
Estimated Primary Completion Date : October 27, 2022
Estimated Study Completion Date : October 27, 2022
The trial is estimated to last for 27 months. The trial is big enough that we should be fairly confident that any statistically significant results are actually happening instead of merely a function of luck. Recruiting for this trial will be starting next week. One of the major concerns in April is no longer in play; people were worried that effective suppression of community spread would make any trial underpowered as the two arms (vaccine and placebo) would be compared for a very rare event. Our need to go to bars obliberated that worry.
The trial is looking at several pre-specified primary endpoints.
Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of mRNA-1273 [ Time Frame: Day 29 (second dose) up to Day 759 (2 years after second dose) ] Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal [ Time Frame: Up to Day 759 (2 years after second dose) ] Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose) ] Number of Participants with Unsolicited AEs [ Time Frame: Up to Day 57 (28 days after each dose) ]
The first person who is dosed on July 27 will enter the first end point (no COVID infection at any point after the 2nd injection) on September 8. The first safety primary endpoint that can be met is on September 1st while the unsolicited adverse event endpoint is September 22. The study intends to track new COVID infections and adverse events for two years, but the first burst of data will be showing up in the analysts hands by late September or early October.
If the placebo arm of the study is located in regions with massive community spread and the placebo arm volunteers engage in high risk behaviors, there could be sufficient effectiveness data even before recruitment for the study closes. The short cut would be to wait for the first cohort’s earliest safety outcomes and then accelerate emergency approval of the vaccine fundamentally on the basis that any adverse events short of playing Russian roulette with an single shot flintlock is acceptable for any protective gains.
Other vaccines are on similar trial time frames. The United States is likely to approve at least vaccine with only short term knowledge of efficacy and no knowledge about medium or long term trade-offs.
That is the trade-off we’re making. This could likely buy a year or two with far less knowledge of consequences for a set of injections that billions of people will take than we normally tolerate.