COVID-19: vaccine development – UK leading the way with controversial Human Challenge Trials

Despite welcome news of several viable vaccines in production, having been approved for emergency use globally, the race to develop protections against and treatments for COVID-19 is far from over. Alongside the approved vaccines, there are more than 250 potential vaccines at various stages of development. These vaccines will require worldwide roll out in order to contain and protect against the continued spread of COVID-19.

Human Challenge Trials (HCTs), the intentional exposure of a human volunteer to a pathogen, are considered by some experts to be our best chance of accelerating the search for effective vaccines and treatments.

Current position

Since our 28 May 2020 article, the UK has broken new ground by becoming the first country in the world to undertake a COVID-19 HCT.

On the 14 December 2020, the regulator in this area, the Medicines and Healthcare products Regulatory Agency (MHRA), approved a HCT, which will evaluate the safety and immune response of a single-dose nasal COVID-19 vaccine. In January 2021, the first patient was dosed in Phase 1 of the trial. Initial data from this HCT is expected early in the second quarter of 2021.

The UK Government has pledged £33.6 million to back studies in a separate HCT known as The Human Challenge Programme. This programme is a partnership between Imperial College London, the Department for Business, Energy and Industrial Strategy, hVIVO (a leading clinical company with expertise in viral human challenge models) and the Royal Free London NHS Foundation Trust. Subject to regulatory and ethical approval, the programme intends to begin a COVID-19 human challenge study as early as January 2021, with results expected in May 2021.

Other countries, such as the US, are considering the risks and benefits of such trials, however the UK is currently the only country with a HCT up and running, with more to commence imminently.

Ethical considerations

Ethical challenges are as important as medical (and legal) ones when it comes to HCTs. Should we be purposely exposing healthy individuals to a disease that has few proven treatments?

Supporters of HCTs consider the societal benefits far outweigh the risks. They point to the unique opportunity the trials provide to quickly and effectively study how vaccines work in the body to provide immunity to COVID-19 and the potential treatments. Advocates of HCTs even go as far as saying that, given the number of human lives at stake, it would be unethical not to do challenge trials.

Critics, however, say that HCTs may now be unnecessary due to the success of vaccine development, or that HCTs should be put on hold until we know more about the effects of the virus. However, with the recent announcement that the life-saving drugs tocilizumab and sarilumab have been made available in NHS healthcare settings with immediate effect, this argument is becoming increasingly redundant.

Questions have also been raised regarding access to already scarce national health resources such as ventilators if a HCT participant becomes seriously ill. Further, if a high rate of serious COVID-19 infections occurred during a HCT, this may result in the need for extra support from essential, critically trained personnel from the front line and there is debate as to whether this can be justified during a pandemic.

Whilst the proposed UK trials will not accelerate the development of the first generation of vaccines, given the hundreds of candidate vaccines in development, HCTs may prove essential for providing information as to the efficacy of the vaccines and to what extent they prevent transmission. This will contribute to overall research and ultimately save lives.  

Volunteer demographic

The participants in the UK HCTs will be low risk, healthy, young individuals between the age of 18 and 30. Some argue that the risks of the disease in young healthy volunteers are justified as being on a par with, or lower than, other commonly accepted exposure risks taken by healthcare workers caring for COVID-19 patients.

However, despite the perceived low risk of the volunteer demographic, the WHO has warned of safety concerns associated with the risk of long-term effects of COVID-19, which are thought to affect at least a fifth of those infected between the ages of 18 and 34.

Criticism has also been raised that the trials may not reveal much about how vaccines could protect those most at risk, such as older people and those who are vulnerable owing to health conditions such as diabetes.

Comment

With regulatory approval of a HCT confirmed by the MHRA, is it only a matter of time before approval is sought for further HCTs, perhaps even for diseases other than COVID-19.

From a COVID-19 perspective, with the emergence of several viable vaccines, arguably the need for HCTs is more critical than ever as researchers say the trials will be particularly useful for head-to-head studies to compare which vaccines work best. However, the risks are high and given how much remains unknown about the virus, the UK Government, regulators and insurers will need to be prepared for all eventualities stemming from these trials – good and bad.

Related item: COVID-19: vaccine development - human challenge trials