COVID Q1. “I’m concerned the vaccines aren’t safe because they were rushed!”
This is a pretty reasonable concern. I mean, if they cut corners, then how can we really know that the vaccines are safe, right? 1/

There’s two types of rushing. If you normally go for a stroll on your lunch break, but today you’re in a rush so you sprint through the same route… well you still covered the same distance. But if you take a shortcut across a busy highway, that’s dangerous!2/

So HOW were the COVID vaccines rushed? Well, let me be clear. There were at least 5 major steps that led to accelerated vaccine development – and NONE OF THEM involved lowering safety standards. Safety standards did not change.3/

Step 1 was SCIENCE. Huge advances in immunology, vaccine design, virology, bioinformatics, & biochemistry came to fruition on this effort. Some vaccines can be designed with modular components so you just drop in a target and voila! [well, there was a littler more to it] 4/

A CRITICAL piece was the open release on Jan 10 of the first Sars-CoV-2 genomes by scientists from China and Australia. [tweet] https://virological.org/t/novel-2019-coronavirus-genome/319 That jump-started the whole enterprise, allowing groups around the world to begin studying & cloning key pieces. 5/

This was soon joined by tens of 1000s of papers/preprints learning about the biology of the new virus. Basically, every scientist who was able chipped in what they could on this new scourge, and it helped everyone move faster.6/

Step 2 was lowering financial risk. Absolutely critical. Vaccine development is crazy expensive. Many programs are cut or never even start because of the financial risk. Each new stage of development is a huge financial risk for biotech and pharmaceutical companies.7/

In this case it was soon clear this disease would affect millions. So no shortage of customers. And governments around the world committed to purchasing a successful vaccine. Imagine being offered a potential multi-billion dollar contract for a product you haven’t invented yet!8/

There could be no greater incentive to put all of your resources into developing a successful vaccine. Success would be a public relations coup of epic scale! But the public scrutiny also ensured compliance and good oversight. All of these made the next few steps possible. 9/

Step 3 – Rapid decisions. Normally, development step is completed, analyzed, considered, pondered, ignored, remembered, and debated before moving on. W/lower risk and high reward, the go/no-go decisions within companies were no-brainers! All of the normal lag was snipped out.10/

Step 4 – Simultaneous trials. Normally, vaccine development is linear: development, preclinical analysis, Phase 1, 2, & 3 trials, and regulatory filing, happen one after the next, with sometimes prolonged consideration of the prior stage before committing to the next. 11/

This time, steps were planned to overlap. Preclinical studies began the second a product was created. Phase 1/2 trials started almost simultaneously & multiple Phase 3 trials initiated based on interim analyses of Phase 2 data, w/regulatory filings following without delay.12/

BUT CRITICALLY, the STANDARDS OF SUCCESS WERE NOT ALTERED. The same standards for safety and for efficacy were used as usual. Tens of thousands of volunteers were treated with each vaccine during the Phase 3 trials! The data far exceeded the pre-planned thresholds. 13/

Step 5 is less intuitive, but impactful. Phase 3 trials are analyzed based on “events"- a subject being diagnosed with COVID. Trials are blinded- no one knows which arm the subject was on. So a trial is analyzed after a pre-planned number of events among all of the subjects.14/

Once that number is reached, an INDEPENDENT GROUP un-blinds the data and analyzes it (NOT the doctors or company running the trial!). They then see how many subjects with COVID received the vaccine and how many received placebo and use that to determine effectiveness.15/

What this means is that the more COVID cases out there, the faster the trial finishes. For rare diseases, this step is a lot slower. The huge spike in cases this Fall in the US and globally meant that the Phase 3 trials went even faster than expected, as terrible as that is. 16/

Add it all up and what you get is a sprint around the track instead of a leisurely walk. BUT, it was the same track as always. No lowered standards, no shortcuts on safety. Just a huge number of people pushing hard with incredible infrastructure, investment, and motivation.17/17