Contributed Commentary by Johan Du Toit 

October 27, 2021 | The COVID-19 pandemic has demonstrated the capability of the medical community to come together in a united effort against a public health threat. Less than two years after the novel coronavirus emerged, there is hope on the horizon, with several proven vaccines available and multiple promising antiviral treatments in late-stage clinical trials. However, even as we make large strides toward the end of the pandemic, there is another growing global health crisis: antimicrobial resistance (AMR). 

The World Health Organization (WHO) calls AMR one of the top ten public health threats. Caused largely by incorrect subscribing practices and overuse of antibiotics and other such drugs, AMR is reducing the number of tools effective against infection and holds the potential for large, life-threatening outbreaks of disease. In fact, the United Nations expects AMR to cause up to 10 million deaths per year by the year 2050. 

There is an urgent need to focus on combating the health threat of AMR. The COVID-19 crisis, and the ensuing race to find treatments, has offered innovative and insightful approaches to implementing successful clinical trials related to infectious disease. Here, we offer an overview of several relevant clinical trial considerations and lessons learned.   

Aggressive, Fluid Timelines 

In the case of infectious disease clinical trials, that disease may only be prevalent in a given location for a limited amount of time. For this reason, timelines must be adaptable, and sites must be ready to act quickly. To accomplish this, it is important to establish a recruitment plan early so that sites can be prepared with minimal time for activation and recruitment. Additionally, nontraditional approaches, such as hybrid or decentralized structuring, can add flexibility that helps improve speed and efficiency. 

Simplified Site Selection, Training 

Site selection should take into account which locations have a well-developed research and regulatory environment, and where surveillance is of good quality. In developing these studies, researchers should keep epidemiology in mind when determining their endpoints, and select endpoints that are simple and reasonable. Knowing which endpoints are critical and which are desirable, but optional, is an important part of this decision. Finally, thorough and consistent site training is important to study quality, which can be assisted by tools such as online training. 

Increased Recruitment Strategies

Recruiting an appropriate number of participants is a challenge shared by many clinical trials. One option for increasing the patient volunteer base is by allowing the enrollment of patients with different clinical diseases that are caused by the same AMR organism. For example, in studies involving drug resistant gram negative bacteria, patients with urinary tract infections, blood stream infections and hospital acquired pneumonias may be included in the target population. In addition, to support the rapid enrollment of participants, sites should be ready to open and start enrollment at the same time.

Appropriate Supply Logistics 

Supply logistics are a core consideration that impact whether materials are stored properly and can be quickly distributed. Having supplies for the study ready and in great enough quantities for the study contributes to avoiding delays. Some supplies might require specialized storage, such as a temperature-controlled area. In such cases, it is advisable to have additional supplies to replace any damaged by storage errors. As another consideration, supplies of personal protective equipment may be required to protect staff working with subjects who may have an infectious disease. As a result, the logistics and safety provisions for each site should be taken into account. 

Timely and Reliable Diagnostics 

Point-of-care rapid diagnostics play an important role in providing accurate case numbers, as they can quickly determine which volunteers are infected with a given pathogen. Additionally, without access to sound diagnostics, it may be necessary to screen and initially enroll very large numbers of patients to ensure the inclusion of the population of interest. Because of this, point-of-care diagnostics should be available for all sites. 

Active Surveillance 

Capturing all symptoms and sampling subjects for the detection of infection can be critical to a study. Sites must be aware of what the protocol-defining symptoms are, since requirements for specimen collection can vary from study to study. Proactively contacting subjects is one useful method to promote reporting of symptoms. Deploying technology that allows participants to self-report reliably—for example, eDiaries—is another way to improve surveillance. 

Fighting AMR

The knowledge we have gained from clinical trials in the COVID era has provided a blueprint for speed and success in an emergency health situation. It is time to start treating AMR as an emergency situation as well, as the threat is only continuing to grow. We can use the tools that our recent experiences have given us to bring the fight to antimicrobial resistance.

Johan Du Toit, MD, is Executive Director, Internal Medicine – Medical Affairs, ICON. Based in France, Dr du Toit received his medical degree and master's degree in internal medicine at the University of Stellenbosch in South Africa and is board certified in internal medicine. He trained in clinical pharmacology and is certified in pharmaceutical medicine at the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the UK. He worked for 15 years as a clinician including managing patients with infectious diseases in general hospital, intensive care, and outpatient settings. Since 2003 he has worked in South Africa and the UK as a full-time principal investigator, medical director, and director of scientific affairs in clinical development from first-in-human though Phase III. Since 2011 he has participated as a medical monitor and therapeutic expert on various global infectious disease (ID) programs and currently manages the team of medical directors covering ID programs for ICON in Europe, Africa and the Asia-Pacific region. He can be reached at dutoitjohan@prahs.com.