By Jaime E. Hernandez, MD, FACP, FIDSA
It is estimated that by 2050, 10 million excess deaths may occur every year due to resistant pathogens, potentially outpacing deaths caused by cancer.[i] Clearly, new antibiotics capable of overcoming resistant “superbugs” are needed. How do we plan and execute a study on a potential treatment for an infectious disease that changes so quickly? I recently led a discussion panel on the challenges of conducting clinical studies in this area with Dr. Richard G. Wunderink of Northwestern Memorial Hospital and Evan Jones, CEO of OpGen, Inc., at the Massachusetts Biotechnology Council in Cambridge, Mass.
One of the most difficult issues of building a successful clinical trial in complicated hospital infections with highly resistant bacteria is recruiting the right patients within an optimal time frame. Short timelines for enrollment of critically ill patients, regulatory restrictions on combination therapies and a lack of rapid, accurate diagnostic tools that are widely available can make the already difficult recruitment process even more complicated. Optimal site selection can play a major role in meeting this challenge and leading to a successful clinical trial.
The first step in selecting the right site includes identifying a location where the targeted superbugs are prevalent. Because combination therapies often are prohibited, it is critical to enroll patients in your trial as soon as they are identified as eligible and as early in the treatment course as possible, preferably before they receive any other antibiotic treatment. At times, this can be in direct conflict with optimal clinical practice. Running your trial at a site with a high prevalence of antibiotic resistant pathogens and the appropriate infrastructure to find all potential subjects quickly increases the odds of finding patients with the right criteria before they receive interventions that could make them ineligible for study participation. The right physician and study coordinator are also key – someone who can become the patient’s primary care provider and someone to be an advocate throughout the trial. This ensures that care stays within the scope of the trial and avoids inadvertent administration of prohibited concomitant therapy or intervention. Finally, optimal utilization of rapid and accurate diagnostic tests in clinical trials is needed to quickly identify and characterize antibiotic resistant bacteria. Selecting a site where this infrastructure is built into the hospital or system, or could be easily incorporated, is essential in identifying all potential subjects as soon as they appear.
As these types of trials increase in priority, it will be important to view the process holistically. Collaboration amongst pharmaceutical companies, CROs, diagnostic companies, and other sponsors and stakeholders will be crucial to building successful trials. Beginning your trial with the right partners and optimal site selection are the first steps toward more rapidly addressing the threat of highly resistant bacteria.
O'Neill J. Review on Antimicrobial Resistance Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. London: Review on Antimicrobial Resistance. 2014. Available here.
About the Author
Jaime E. Hernandez, MD, FACP, FIDSA, is Executive Medical Director and Therapeutic Area Medical Lead for Syneos Health™, Infectious Diseases and Vaccines. Jaime is an infectious disease specialist with extensive leadership experience in all facets of clinical development, medical affairs, safety & pharmacovigilance, and business development. He has more than 20 years of experience in large pharmaceutical, biotechnology companies and CROs. He is experienced in Phase I-IV clinical trials for both small molecules and biologics, including the first use of pharmacogenomics in HIV. Jaime has led the development, regulatory approval and global launch of several HIV compounds, including the first triple combination tablet in HIV, as well as multiple antimicrobials and vaccines. He has in-depth experience with global regulatory strategy, with multiple successful FDA, EU, Japanese and other Health Authority interactions.
