A challenge trial, also known as a human challenge study or controlled human infection model (CHIM), is a specialized type of clinical research. These trials involve intentionally exposing healthy volunteers to a pathogen under controlled conditions. Their primary goal is to study disease progression, observe immune responses, and evaluate new vaccines or treatments.
Understanding Challenge Trials
Challenge trials differ from traditional clinical trials as participants are deliberately infected with a pathogen. Researchers select healthy adult volunteers who meet specific criteria to minimize risks. Enrolled participants are quarantined in a specialized facility and receive a controlled dose of the pathogen, often via oral ingestion, inhalation, or injection.
Following exposure, participants are under continuous medical supervision to monitor symptoms, disease progression, and immune responses. Researchers precisely control the pathogen dose and exposure timing, allowing for detailed observation. Unlike field trials, challenge trials provide a controlled environment to gather specific data efficiently.
Reasons for Utilizing Challenge Trials
Challenge trials offer advantages in medical research, accelerating vaccine and treatment development. They significantly reduce the time to gather efficacy data compared to traditional field trials, often compressing multi-year processes into months. This speed is beneficial during public health crises, as seen with COVID-19 vaccine development.
These trials require fewer participants than large-scale field studies, typically dozens to around 100 volunteers. The controlled environment allows researchers to manage factors like pathogen strain, dose, and exposure time, providing exact timepoints for infection and recovery. This precision helps understand disease mechanisms, such as how pathogens infect the body and what viral load causes infection. Challenge trials also provide insights into treatment efficacy or immunity development, even when natural disease transmission is low.
Ethical Frameworks and Participant Safety
Intentional exposure of healthy individuals to pathogens in challenge trials raises ethical considerations, addressed through rigorous frameworks and oversight. Robust informed consent is central, where volunteers receive comprehensive information about all potential risks, including serious adverse effects. This process often includes a test of understanding to ensure participants grasp their involvement.
Researchers implement strategies to minimize harm. This includes selecting only healthy volunteers, often young adults, and using well-characterized, sometimes attenuated, pathogen strains. Participants are housed in inpatient facilities for 24-hour medical monitoring and immediate treatment to clear infection before severe symptoms. Independent oversight bodies, such as Institutional Review Boards (IRBs) or ethics committees, review and approve trial protocols to ensure safety and ethical conduct. A thorough benefit-risk assessment ensures potential societal benefits outweigh individual risks.
Past and Present Applications
Human challenge trials have a long history in medical research, dating back centuries. Early examples include 1700s smallpox studies, which assessed variolation as an inoculation method. Throughout the 20th century, these trials were refined and used for diseases like typhoid fever, cholera, malaria, and influenza, contributing to vaccine development and understanding infections. Malaria challenge studies, for instance, have routinely accelerated vaccine testing in countries like the UK and US.
More recently, challenge trials addressed various infectious diseases, including influenza, typhoid, and malaria, providing insights into immune responses and vaccine efficacy. During the COVID-19 pandemic, the world’s first SARS-CoV-2 challenge study in the UK in 2021 gained attention for its potential to rapidly advance vaccine and treatment development. These studies offer unique opportunities to investigate viral infection kinetics and immune responses.