The edge of discovery: Controlling the local false discovery rate at the margin

Despite the popularity of the false discovery rate (FDR) as an error control metric for large-scale multiple testing, its close Bayesian counterpart the local false discovery rate (lfdr), defined as the posterior probability that a particular null hypothesis is false, is a more directly relevant standard for justifying and interpreting individual rejections. However, the lfdr is difficult to work with in small samples, as the prior distribution is typically unknown. We propose a simple multiple testing procedure and prove that it controls the expectation of the maximum lfdr across all rejections; equivalently, it controls the probability that the rejection with the largest p-value is a false discovery. Our method operates without knowledge of the prior, assuming only that the p-value density is uniform under the null and decreasing under the alternative. We also show that our method asymptotically implements the oracle Bayes procedure for a weighted classification risk, optimally trading off between false positives and false negatives. We derive the limiting distribution of the attained maximum lfdr over the rejections, and the limiting empirical Bayes regret relative to the oracle procedure

Incentive-Theoretic Bayesian Inference for Collaborative Science

Contemporary scientific research is a distributed, collaborative endeavor, carried out by teams of researchers, regulatory institutions, funding agencies, commercial partners, and scientific bodies, all interacting with each other and facing different incentives. To maintain scientific rigor, statistical methods should acknowledge this state of affairs. To this end, we study hypothesis testing when there is an agent (e.g., a researcher or a pharmaceutical company) with a private prior about an unknown parameter and a principal (e.g., a policymaker or regulator) who wishes to make decisions based on the parameter value. The agent chooses whether to run a statistical trial based on their private prior and then the result of the trial is used by the principal to reach a decision. We show how the principal can conduct statistical inference that leverages the information that is revealed by an agent's strategic behavior -- their choice to run a trial or not. In particular, we show how the principal can design a policy to elucidate partial information about the agent's private prior beliefs and use this to control the posterior probability of the null. One implication is a simple guideline for the choice of significance threshold in clinical trials: the type-I error level should be set to be strictly less than the cost of the trial divided by the firm's profit if the trial is successful

Principal-Agent Hypothesis Testing

Consider the relationship between the FDA (the principal) and a pharmaceutical company (the agent). The pharmaceutical company wishes to sell a product to make a profit, and the FDA wishes to ensure that only efficacious drugs are released to the public. The efficacy of the drug is not known to the FDA, so the pharmaceutical company must run a costly trial to prove efficacy to the FDA. Critically, the statistical protocol used to establish efficacy affects the behavior of a strategic, self-interested pharmaceutical company; a lower standard of statistical evidence incentivizes the pharmaceutical company to run more trials for drugs that are less likely to be effective, since the drug may pass the trial by chance, resulting in large profits. The interaction between the statistical protocol and the incentives of the pharmaceutical company is crucial to understanding this system and designing protocols with high social utility. In this work, we discuss how the principal and agent can enter into a contract with payoffs based on statistical evidence. When there is stronger evidence for the quality of the product, the principal allows the agent to make a larger profit. We show how to design contracts that are robust to an agent's strategic actions, and derive the optimal contract in the presence of strategic behavior