LP Vol. 2 - And All The Rest
Man, what a week! Elections always confound our expectations in bizarre ways, but our collective societal sphincter is feeling a lot more relaxed this Sunday morning.
With the election now behind us, we can go back to solving the simple problems of…
(checks notes)
The global pandemic. Fuck.
Winter is Coming - Vaccine Challenges
The randomized controlled trial (RCT) is a relatively recent contribution to medical research. It first appeared in a 1948 British Medical Journal paper entitled "Streptomycin treatment of pulmonary tuberculosis" and has become the de facto standard for assessing the efficacy of treatment options in the face of new maladies facing humankind everywhere.
Your typical RCT recruits a number of participants, randomly assigns them to a placebo/control group and a treatment group, then monitors them over the course of a surveillance period observing degrees of infection. A Phase 3 vaccine trial typically takes between five and ten years to complete and are super important in generating important data about so-called "secondary endpoints" - statistically meaningful information about treatment performance in specific cohorts like children, the elderly and people of color as well as other important factors like duration of efficacy.
Tyler Cowen and Alex Tabarrok have been writing for months about vaccine issues and highlighting some alternatives to the RCT better suited for the moment. In particular, they have hit on the merits and trade-offs of human challenge trials and highlighted this recent paper looking at the cost/benefit of various clinical trial designs.
TLDR: human challenge trials, where participants are directly exposed to the pathogen and are fairly compensated for their participation, avert over a million hypothetical COVID infections thru accelerated data collection on vaccine efficacy and quicker approval.
As vaccine candidates across the world begin to see governmental approvals, Phase 3 trial design is facing a new and peculiar challenge - is it ethical and fair to continue giving people a placebo when a known vaccine exists? Would you stay committed to a clinical trial that might be protecting you from a potentially deadly pathogen or maybe just giving you a shot of salt water and wishing you luck?
Pfizer has already asked the FDA for approval to give its vaccine to Phase 3 placebo participants if they are awarded an early authorization, despite the issues it may cause to their trial results. Other trials may be suspended for a more practical reason - can they maintain a sizeable enough participant pool willing to roll the dice with a possible placebo and risk infection, or will people simply drop out in favor of the first approved vaccine they can get?
The UK recently announced they are starting challenge trials in January. The NIH and FDA have instead been rejecting calls for granting early authorizations so as to not taint the results of the extended trials.
Like so many other aspects of COVID response, I am disheartened by the lack of creative problem solving by our public health apparatus. I wish we were making room for more experimentation, fresh thinking and enabling American ingenuity in the search for a solution that gets our kids back in school, our first responders protected and our lives back to normal sooner rather than later. It feels like there's no urgency, creativity and originality in any aspect of our national response. And it sucks.
Listening Recs - And All the Rest
Tom Petty's Wildflowers got a deluxe rerelease last month featuring an extensive collection of outtakes, demos and live recordings. Wildflowers was originally conceived as a double album and Petty recorded nearly 30 songs over 2 years with producer Rick Rubin. It was released in 1994 as just a single album, and putting out the 'lost half' of music from those sessions was the last project Petty was working on before he died unexpectedly in 2018.
His daughter Adria and members of the Heartbreakers spent the past two years completing that work and have been doing some press, which has been great companion content revealing the mastery and craft that went into one of my favorite albums of all-time.
Rick Rubin has done 3 episodes of Broken Record talking about his experience producing the album, interviewing Adria about completing the project after her dad's passing, and chatting with Heartbreaker Benmont Tench about the ups and downs of surviving 50 years of the rock and roll life (and the perils of loving cocaine just a little too much):
Brian Koppelman interviewed Mike Campbell, Heartbreaker guitarist on the origins of the band, creative expression and making a long-term partnership successful.
It's easy to take for granted the art and culture that shape us and form the soundtrack to the most important moments of our lives. I appreciate any and every opportunity to get a deeper look into the creative blood, sweat and alchemy that coaxes those gifts into the world.
And finally, I've had this song top of mind all week long:
Until next week.
Woody