As may be obvious from our increased tempo of posts on the EA Forum, 1Day Sooner wants to integrate ourselves more tightly with the effective altruist community. To this end, we are hosting a town hall on Zoom tomorrow (Thursday) at 1 PM eastern to discuss challenge studies from an effective altruist perspective (including a focus on whether very large amounts of EA money should be spent on vaccine development). Here is a link to sign up if you're interested.
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With 1Day's goal of making our thinking transparent and malleable to EA in mind: someone asked me recently to ponder the thought experiment of what might be a perfect-world use of challenge studies in light of the Omicron COVID strain. I thought it might be neat to post a couple of my ideas below to solicit thoughts, criticisms and questions from the EA forum audience.
Note that this is just my personal thinking; it's very informal/non-rigorous/not-comprehensive, and it doesn't reflect an official 1Day Sooner position.
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With unlimited resources, I'd propose a crash program to use challenge studies to: 1. establish correlates of protection sufficient to approve COVID vaccines without a phase 3 for efficacy and 2. authorize a universal sarbecovirus vaccine (one that protects against the subset of coronaviruses including SARS1 and COVID) with the goal of accomplishing 1. within six months and 2. within 15-18 months.
My (very rough) guess is this would cost about $125 million for the following:
- Produce omicron + attenuated SARS1 challenge strains ASAP ($5M each) + beta coronavirus challenge strain ($3M)
- Initial booster challenge study with omicron and delta to ascertain correlates of protection ($10M each)
- Dosing study for attenuated SARS1 and beta ($8M each)
- Funding for challenge studies of 5 universal coronavirus vaccine candidates using each of SARS1, 2-3 COVID strains, and betacoronavirus strains ($10M per vaccine candidate)
- Controlled natural exposure model with betacoronavirus ($10M) (Will flag here that there's a dual-use/biosecurity concern with getting good at controlled natural exposure studies insofar as they can help you learn how to develop more transmissible pathogens).
- Regulatory science/advocacy to establish correlates of protection with FDA/EMA + develop algorithm integrating human challenge with animal challenge and phase 3 data + other miscellany ($25M)
The costs are very approximate and reflect premiums for speed; even paying premium biocontainment capacity would still be a significant issue.
By doing all that, you'd (1) reduce the cost of developing boosters and new vaccines, which would hopefully help significantly with global availability, (2) accelerate booster development for new strains, (3) improve the quality of boosters/future vaccines, (4) reduce the risk of future variants (via the universal vaccine), (5) create a rapid process and platform for testing broader universal coronavirus vaccines (against betacoronaviruses more generally), (6) create a precedent for the effective use of challenges as part of a prototype or universal vaccine strategy (and validate the universal vaccine strategy in general), and (7) develop a natural exposure model to build off of as proof of concept for an approach that may not require a separate challenge strain in the future.
Some downsides and complicating factors would be:
- Producing multiple strains at the same time draws down a limited pool of talent and resources (ie they compete with each other);
- You’d probably still need to run phase 3s for safety for future vaccine candidates;
- Regulatory approval of manufacturing facilities (for future vaccine candidates) would still be an issue;
- Might need more animal model or other types of studies to prove effectiveness of universal coronavirus vaccine;
- It’s possible even if you get immunity against multiple strains immune escape may be possible
With more limited resources, I would propose an omicron-specific plan meant to show how quickly it is possible to get a covid challenge model implemented and to provide evidence of absolute and relative efficacy of omicron boosters while ideally also establishing correlates of protection that would make it easier to approve additional omicron boosters and be relevant for vaccine development for new variants.
I'd estimate this approach as costing roughly $15 million for: rapid omicron strain production ($5 milllion) + vaccine booster study ($10 million) + regulatory science/advocacy to develop clear standards for booster approved ($1M).
Downsides and tricky points: earliest answer on efficacy likely 3 months from start best case; 4-6 months more likely, unclear whether correlates will be properly establish sufficient to persuade the FDA.
