Controlled human infections: A report from the controlled human infection models workshop, Leiden University Medical
Meta Roestenberg1, Annie Mo2, Peter G Kremsner3
1Leiden University Medical Centre, The Netherlands.
Abstract:
The principle of deliberately infecting humans with infectious agents in a controlled setting, so-called controlled human infections (CHI), is not novel. Many CHI models have a long history and were established decades ago such as the intentional exposure to yellow fever and dengue performed in the 1900's (Reed, 1902) [2]. In these times bioethics and scientific reasoning were in their infancy. Nowadays, clinical trials are highly regulated and CHI are executed worldwide. Controlled human malaria infections and influenza infections are the two most frequently practiced. Others are experiencing a revival or are being carefully developed. Because CHI models test the efficacy of promising vaccine or drug candidates early in clinical development, they offer the potential to decrease the number of failing phase 2 and 3 trials, reducing risks for patients and saving costs and efforts. In addition, CHI models provide unprecedented opportunities to dissect the physiological, immunological and metabolic changes that occur upon infection. However, it is clear that controlled infections require careful deliberation of safety, ethics, quarantine, scientific output and the production of infectious material. An independent international workshop was hosted by the Leiden University Medical Centre in The Netherlands, bringing together clinical investigators, basic scientists, regulators, funders and policy makers from 22 different countries to discuss the opportunities and challenges in CHI. The aim of the workshop was to discuss CHI as a tool to advance science, drug and vaccine development, share the challenges of establishing a CHI model with specific focus on neglected tropical diseases and the possibilities to transfer models to endemic sites. Noticeably, among the 128 participants were clinical investigators from ten different countries in Sub-Saharan Africa. An important dimension of the meeting was to give the floor to young established clinicians and scientists to voice their perspective on the future of CHI models.
Insights
Controlled human infections (CHI) are a long-standing method for early vaccine and drug testing. An international workshop convened experts to discuss advancing CHI models, particularly for neglected tropical diseases.
Area of Science:
- * Infectious Diseases
- * Clinical Trials
- * Global Health
Background:
- * Controlled human infections (CHI) have a historical precedent, with early examples dating back to the early 1900s.
- * Modern CHI models are highly regulated and widely used globally, with malaria and influenza infections being the most common.
- * CHI models offer significant potential for early-stage vaccine and drug efficacy testing, reducing late-stage trial failures and associated costs.
Purpose of the Study:
- * To convene an international workshop to discuss the opportunities and challenges of controlled human infections (CHI).
- * To explore the utility of CHI as a tool for advancing scientific understanding and developing new drugs and vaccines.
- * To address the specific challenges of establishing CHI models for neglected tropical diseases and their potential transfer to endemic regions.
Main Methods:
- * An independent international workshop was organized by the Leiden University Medical Centre.
- * The workshop brought together 128 participants, including clinical investigators, basic scientists, regulators, funders, and policymakers from 22 countries.
- * Emphasis was placed on including perspectives from clinical investigators from Sub-Saharan Africa and early-career scientists.
Main Results:
- * The workshop facilitated a global discussion on the current state and future directions of CHI models.
- * Key opportunities and challenges in implementing and expanding CHI were identified.
- * Specific attention was given to the application of CHI for neglected tropical diseases and global health equity.
Conclusions:
- * Controlled human infections (CHI) are a valuable tool for accelerating medical research and development.
- * Addressing the challenges in establishing and transferring CHI models is crucial for global health advancement.
- * International collaboration and diverse perspectives are essential for the future of CHI research.
