ISCTM Historical Perspectives: Milestones, Measures and Methods Series
Episode #1: History of clinical trials
Randomized clinical trials are an evolving technology that aims to provide an evidence base with which to distinguish justified belief from opinion.
Our discussion focuses on the roots of clinical trials which date from Lind’s 17th century comparison of dietary supplements for scurvy. Over time, innovations such as random assignment, placebo control and blinding added progressive methodological rigor and became essential features of modern clinical trial design and set the stage for the first modern controlled clinical trial in 1948, streptomycin for pulmonary tuberculosis.
Episode #2: Emil Kraepelin: Foundation of modern CNS diagnosis
We discuss the impact and enduring value of Emil Kraepelin’s insights, which owe much to the methods he used to assess and classify patients. His great insights resulted from moving beyond current signs and symptoms to age of onset and course of illness. This enabled him to distinguish the three major division of psychiatric illness: dementia (Alzheimer’s disease), Mood disorder (manic-depressive insanity, and Thought disorders (dementia praecox/Schizophrenia).
Episode #3: Pseudo-Specificity in CNS Research
FDA raised concerns about pseudo-specificity in the mid-1900s. Sian Ratcliffe talks about how she coped with regulatory concerns about specificity for treatments for PTSD independent of antidepressant effects. Working with in-house statisticians and external collaborators enabled her to bring the clarity required to support a distinct indication.
Episode #4: Foundations of Modern Psychopharmacology
This cast discusses the era of modern psychopharmacology from seminal bench pharmacology research in the 1950s through to development of SSRIs. Bill Potter shares his own work on recognition of toxic metabolites and his interactions with pioneers like BB Brody, Julius Axelrod, and Arvid Carlson. His recollections of studies which began in the National Heart and Lung Institute and progressed to the NIH and industry provides prospective and insight on the co-evolution of biochemical psychopharmacology and clinical trials.
Episode #5: The Bayesian Estimation of Conditional Probability
Thomas Bayes “Essay Towards Solving a Problem in the Doctrine of Chances” (1763) was published posthumously in the Philosophical Transactions of the Royal Society. LaPlace made Bayes theory practical/applicable and that work eventually became the basis of a statistical technique, now called Bayesian estimation, for calculating the probability of the validity of a proposition on the basis of a prior estimate of its probability and new relevant evidence. Judith Jaeger guides our discussion of conditional probability and describes her novel application of Bayesian statistics using “posets” to classify and analyze data on cognitive states.
Episode #6: The Role of Organizations in Advancing Clinical Trial Methodology
Bill Potter has been a leading voice in both neuropharmacology and clinical methodology. We discuss how governmental organizations such as the NIMH’s Early Clinical Drug Evaluation Unit (ECDEU) and New Clinical Drug Evaluation Unit (NCDEU) meetings helped advance the science of clinical trial methodology necessary to advance psychopharmacology. Dr Potter traces the roots of pre-competitive collaboration and credits governmental initiatives, especially NIMH staff for convening meetings which bridged the competitive silos which often stymied the efforts of academics, industry, and regulators. Dr Potter points out an unexpected consequence: Successful clinical trials sometimes spurred success in marketing which can motivate development of me-too drugs. Notably sponsorship of meetings carrying on aspects of the mission of NCDEU has passed from NIMH to non-governmental organizations, ASCP and ISCTM.
Episode #7: The Founding of ISCTM
Dr. A. George Awad, founding President, discusses the founders concerns and objectives at the inception of ISCTM. He stresses the important of following democratic principles, assuring participation of multiple stakeholders and assuring the organization guard against being captured by special interests and recognition from the beginning that the society’s work would be progressive but not too slow and never finished. Dr. Awad recommends being bold and not leaving innovations to the private sector only.
*The content of each podcast represents individual opinions and not that of the institution, agency, company affiliation of participants or ISCTM.