Adaptive Trial DesignsGlobal Forum on Bioethics in Research:

Emerging Epidemic Infections and Experimental TreatmentsNovember 4, 2015

Lord Kelvin

• I often say that when you can measure what you are speaking about and express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind; it may be the beginning of knowledge, but you have scarcely in your thoughts advanced to the state of Science, whatever the matter may be.

Nietzsche

• Against that positivism which stops before the phenomena, saying “there are only facts” I should say: no, it is precisely facts that do not exists, only interpretations…

Truth

• The truth cannot be told so as to be understood but not believed.William Blake

Randomized Control Trial

Time

SampleOf

Persons

Inception Cohort

RandomAllocation

Treatment

Measureoutcomes

Sampling is done here

Control

Ethical issues related to study design for trials on therapeutics for Ebola Virus Disease• In this context, an adaptive trial design that has the capacity to yield

meaningful and interpretable data quickly in the midst of the (Ebola) epidemic might be considered as preferable. An adaptive design could include elements of randomized controlled trials, cluster randomization, stepped wedge, and single arm comparison trials. Adaptive trial designs are more complex to coordinate among sites.

Cartwright’s Causal Criterion

• C causes E if and only if P (E/C) +/- {F1 + F2…FN} > P(E/-C} +/- { F1+ F2…FN} where F1…FN are a complete set of covariates• An idealized model that sets out

precise ceteris paribus conditions