bayes

Bayesian Methods to Address Clinical Development Challenges for COVID-19 Drugs and Biologics

The COVID-19 pandemic has elevated the challenge for designing and executing clinical trials with vaccines and drug/device combinations within a substantially shortened time frame. Numerous challenges in designing COVID-19 trials include lack of prior data for candidate interventions / vaccines due to the novelty of the disease, evolving standard of care and sense of urgency to speed up development programmes. We propose sequential and adaptive Bayesian trial designs to help address the challenges inherent in COVID-19 trials. In the Bayesian framework, several methodologies can be implemented to address the complexity of the primary endpoint choice. Different options could be used for the primary analysis of the WHO Severity Scale, frequently used in COVID-19 trials. We propose the longitudinal proportional odds mixed effects model using the WHO Severity Scale ordinal scale. This enables efficient utilization of all clinical information to optimize sample sizes and maximize the rate of acquiring evidence about treatment effects and harms.

Musings on Multiple Endpoints in RCTs

This article discusses issues related to alpha spending, effect sizes used in power calculations, multiple endpoints in RCTs, and endpoint labeling. Changes in endpoint priority is addressed. Included in the the discussion is how Bayesian probabilities more naturally allow one to answer multiple questions without all-too-arbitrary designations of endpoints as "primary" and "secondary". And we should not quit trying to learn.

Improving Research Through Safer Learning from Data

What are the major elements of learning from data that should inform the research process? How can we prevent having false confidence from statistical analysis? Does a Bayesian approach result in more honest answers to research questions? Is learning inherently subjective anyway, so we need to stop criticizing Bayesians' subjectivity? How important and possible is pre-specification? When should replication be required? These and other questions are discussed.

Continuous Learning from Data: No Multiplicities from Computing and Using Bayesian Posterior Probabilities as Often as Desired

(In a Bayesian analysis) It is entirely appropriate to collect data until a point has been proven or disproven, or until the data collector runs out of time, money, or patience.

Bayesian vs. Frequentist Statements About Treatment Efficacy

To avoid "false positives" do away with "positive". A good poker player plays the odds by thinking to herself "The probability I can win with this hand is 0.91" and not "

Statistical Errors in the Medical Literature

Misinterpretation of P-values and Main Study Results Dichotomania Problems With Change Scores Improper Subgrouping Serial Data and Response Trajectories Cluster Analysis As Doug Altman famously wrote in his Scandal of Poor Medical Research in BMJ in 1994, the quality of how statistical principles and analysis methods are applied in medical research is quite poor.

My Journey From Frequentist to Bayesian Statistics

The difference between Bayesian and frequentist inference in a nutshell: With Bayes you start with a prior distribution for θ and given your data make an inference about the θ-driven process generating your data (whatever that process happened to be), to quantify evidence for every possible value of θ.

A Litany of Problems With p-values

With the many problems that p-values have, and the temptation to "bless" research when the p-value falls below an arbitrary threshold such as 0.05 or 0.005, researchers using p-values should at least be fully aware of what they are getting.

Clinicians' Misunderstanding of Probabilities Makes Them Like Backwards Probabilities Such As Sensitivity, Specificity, and Type I Error

Optimum decision making in the presence of uncertainty comes from probabilistic thinking. The relevant probabilities are of a predictive nature: P(the unknown given the known). Thresholds are not helpful and are completely dependent on the utility/cost/loss function.

p-values and Type I Errors are Not the Probabilities We Need

In trying to guard against false conclusions, researchers often attempt to minimize the risk of a “false positive” conclusion. In the field of assessing the efficacy of medical and behavioral treatments for improving subjects’ outcomes, falsely concluding that a treatment is effective when it is not is an important consideration.