April 2015 | ISSUE 17

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Human challenge studies: a good doorman

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By Nicole Lim​
Assistant Director, Communications & External Relations


 

More than 200 years ago in Georgian England, an eight-year-old boy held out his arms for Dr Edward Jenner to inoculate him with pus scraped out of the cowpox blisters on the hands of a milkmaid. A few weeks later, Dr Jenner called the boy back and deliberately infected him with smallpox to test the protective effect of the 'vaccine'. With this, Dr Jenner not only discovered the first smallpox vaccine, but birthed the idea of human challenge studies.

"What Dr Jenner did would be considered completely unethical today, but it was ground-breaking and revolutionised our ability to prevent diseases. Jenner's studies paved the way. Vaccines, as we all know now, are the most cost-effective strategy in public health," said LKCMedicine Professor of Infectious Diseases Annelies Wilder-Smith.

Since then, human challenge studies have come a long way. They are now conducted in purpose-built medical facilities staffed by a trained team of healthcare professionals. Volunteers have to meet stringent selection criteria and go through a thorough screening before being accepted into any study.

But most importantly, only infectious diseases that are self-limiting or for which an effective treatment exists can be used in these studies. To ensure the wellbeing of the volunteers further, the infectious agents are manufactured under stringent good manufacturing guidelines (GMP) to produce a slightly weakened strain of the original agent that is both pure and safe. Because challenge studies are conducted under such controlled conditions, they are also called controlled human infection studies.

"The aim is not to make volunteers as ill as possible but to produce a mild to moderate infection which will allow us to determine the efficacy of a new vaccine or drug," said LKCMedicine Clinical Research Coordinator Ms Shobana Balasingam. In fact, infections seen in trial volunteers are milder than those seen in even uncomplicated outpatient patients.

The main attraction of these studies is the ability to gain a better understanding of the potential of a new vaccine or drug quickly without the need to recruit thousands of patients. With as few as 20 volunteers, such studies provide some initial indication whether the new vaccine or drug works.

"Challenge studies act as gating, letting only promising drugs and vaccines through for further development," said Prof Wilder-Smith. 

While effective in determining potential, challenge studies cannot replace larger studies that involve people who are naturally infected with the disease.

To discuss the best practices and debate the potential of challenge studies, LKCMedicine hosted a workshop on 11 March 2015, in conjunction with the Singapore Courage Fund Infectious Disease Conference 2015, which brought together international experts, including Professor Frederick Hayden from the University of Virginia School of Medicine and Professor James McCarthy from Australia's QIMR Berghofer Medical Research Institute. They discussed best practices and challenges in areas such as influenza, dengue and malaria, with an audience of some 60 researchers from across Singapore and around the world.​

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A discussion and debate on whether Singapore should embrace human challenge studies was held at the end of the event

With the results of challenge studies fast becoming part of the pre-licensing data, experts at the conference urged Singapore to take the lead in Asia by investing in this specialised field ahead of regional competitors.

Together with Associate Professor John Connolly from the Institute of Molecular & Cellular Biology under A*STAR and Tan Tock Seng Hospital, Prof Wilder-Smith hopes to be able to do just that later this year.

"In Singapore, we're ideally placed to offer such a platform. We have the regulatory framework, the necessary clinical skills and the high quality medical facilities to support safe controlled human infection studies," said Prof Wilder-Smith. ​