The scientific community has been aware of the existence of a publication bias since the 1950s. What is a publication bias, and how does this affect science? This form of bias arises when the outcome of an experiment determines whether the results are published. On the surface, this doesn’t sound terrible. Shouldn’t exciting, unexpected results take precedence over a study demonstrating that treatment A doesn’t work? Unfortunately, this is the sort of thinking that has created a stigma around negative data.
As students, we are taught that the scientific method is king. If your experiment is well designed and controlled, your data will either prove or disprove your hypothesis. If your experiment is well designed and controlled, your data should be worthy of publication, regardless of the outcome. Unfortunately, this is not the case. Studies have shown that negative results (those that fail to prove the researcher’s hypothesis) are three times less likely to be published (yes, we recognize the potential irony here). Why is this a problem?
The goal of both a clinical trial and of a patient registry is to produce evidence for scientific advancement, regulatory approval, and/or clinical decision-making. Producing sufficient evidence will yield a best practice or a clinical guideline that establishes a standard of care.
Evidence can be produced in a variety of ways. At the top of the pyramid are clinical trials and prospective cohort studies. A clinical trial provides a test of a hypothesis to produce an efficacy statement that the intervention improves outcomes. It establishes a mechanistic efficacy associated with a clinical outcome and the intervention is safe.
In October 2018, West Virginia University neurosurgeon Ali Rezai, MD, treated the first patient in a groundbreaking US clinical trial for Alzheimer’s disease. A team of 35 medical experts at the Rockefeller Neuroscience Institute, led by Dr. Rezai, performed a phase II trial – for the first time in the United States using focused ultrasound to open the blood-brain barrier and target the hippocampus of a 61-year-old patient with early-stage Alzheimer’s disease. A second patient with Alzheimer’s underwent the procedure in January 2019 at West Virginia University.The team used Insightec’s focused ultrasound device, Exablate Neuro.
Recently, we caught up with Dr. Rezai to talk about the first patient’s progress and his plans for future applications of focused ultrasound.
Jill O'Donnell-Tormey, PhD, is chief executive officer and director of scientific affairs at the Cancer Research Institute. In 2017, CRI and the Focused Ultrasound Foundation partnered with the goal of advancing the development of new focused ultrasound and cancer immunotherapy treatments. A major part of the partnership is a joint fund that supports research to move toward new combination therapies. That fund awarded its first research grant in June of 2018. Dr. O’Donnell-Tormey appeared at the 6th International Symposium on Focused Ultrasound in October to discuss the partnership. Below is an edited transcript of our interview with her.
Why did you partner with Focused Ultrasound Foundation?
As immunotherapy was starting to gather momentum and there were more FDA approvals of immunotherapy, the Focused Ultrasound Foundation thought there might be a place to combine immunotherapy and focused ultrasound. So that was the impetus.
Joo Ha Hwang, MD, PhD, is Professor of Medicine, Gastroenterology and Hepatology at Stanford University. He is also president of the International Society for Therapeutic Ultrasound, a partner organization of the Focused Ultrasound Foundation. Dr. Hwang became interested in focused ultrasound through his work with pancreatic cancer patients: He wanted to find a therapy that would prolong their lives or even cure them. Today he is more optimistic than ever about the possibility of using focused ultrasound to treat pancreatic cancer. Below is an edited transcript of our conversation with him.
Why are you so enthusiastic about this technology?
I've been in this field since 2000, so I've been actively doing focused ultrasound research for 18 years. Much of that research has been looking at enhancing drug delivery for pancreatic cancer using focused ultrasound. We have achieved great results, but the problem has been that there are no real effective chemotherapeutic agents. Even our best agents have very modest efficacy.