Placebo

The forecast agent

A written scoring model, run every night at 02:00 UTC. No language model is called.

Inputs

Five public inputs, each a link in the forecast JSON: the registry record (phase, enrolment, sponsor class, endpoint), the target's Open Targets association with Alzheimer's (MONDO_0004975), the sponsor's earlier posted readouts, the class base rate from the pipeline reviews, and PubMed papers on the drug in the last 24 months.

The formula

log-odds = logit(prior) + 1.10 (G - 0.30) + 0.30 clamp(ln(n/300), -1.5, 1.5)
         + 0.20 industry + 1.20 ((hits+1)/(readouts+4) - 0.25) + 0.12 ln(1 + papers/20)
p = clamp(logistic(log-odds), 0.03, 0.92)
TermDefinition
Class priorlogit(prior[endpoint][phase])
Genetic support1.10 × (G − 0.30), G = highest Open Targets association of the drug's targets with Alzheimer's
Size0.30 × clamp(ln(n / 300), −1.5, 1.5), n = enrolment
Sponsor class0.20 if the lead sponsor is industry
Sponsor record1.20 × ((hits + 1) / (readouts + 4) − 0.25), the sponsor's posted readouts before tonight
Literature0.12 × ln(1 + papers / 20), PubMed papers on the drug and Alzheimer's in the 24 months before

The three sentences of reasoning are filled in from these numbers by a fixed template. The same inputs always give the same JSON, and so the same hash.

Priors

Endpoint classPhase 2Phase 2/3Phase 3
cognitive-functional18%16%12%
neuropsychiatric32%30%30%
biomarker50%50%50%
other22%20%20%

The anchor is Cummings et al. 2014: 413 Alzheimer's trials over 2002 to 2012 and "an overall success rate during the 2002 to 2012 period of 0.4% (99.6% failure)". That is the rate of reaching approval, a higher bar than one endpoint, and it is a 2002-2012 figure.

The bond

The agent bonds 2,000 $PLCB on each open market, from the house address, in the contract. After finalization the bond comes back in full if its Brier is at or under 0.25; above 0.25 half is burned. Until $PLCB is set on the contract, forecasts are hashed and scored, and the bond is posted from the first night after.

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