ideasIdea
Pre-register animal efficacy studies like clinical trials
Clinical trials must be registered before they start so that failures cannot be hidden. Animal studies used to justify human trials should follow the same rule.
Publication bias and flexible analysis inflate preclinical effect sizes; systematic reviews repeatedly find that animal efficacy is overstated relative to later clinical results. A registry requiring the protocol, sample size, randomisation, blinding and primary endpoint before pivotal in vivo efficacy studies, enforced by funders and journals, would make preclinical evidence auditable. The ARRIVE guidelines exist but are advisory.
Hypothesis
Pre-registered in vivo efficacy studies report smaller average effect sizes and higher replication rates than unregistered studies, and pre-registration reduces the rate of failed phase 2 trials in programmes that relied on them.
Rationale
Registration reduced positive-result rates in clinical cardiology trials, an effect large enough to be visible; the same incentives operate preclinically with weaker safeguards.
What would test it
A funder mandates registration for pivotal in vivo studies in its portfolio for three years and compares effect sizes and independent replication with a matched unregistered portfolio.
Maturity
speculative
Who has to act
policy
Cost to try
Small (under $1M)
Years to first evidence
4
Bottlenecks it attacks
- Preclinical models that do not predict people · Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.
- Preclinical results do not reproduce · Fewer than half of landmark cancer biology findings reproduce when someone else tries.
- Failures are hidden · Negative trials, failed drugs and abandoned programmes are rarely published, so the same mistakes are repeated.