1. Safe and ethical
The top priority is making sure that the trial is designed and conducted safely and ethically.
National and international rules on ethics and safety are enforced through regulation and inspection. This minimises the risk of harm and makes sure participants are treated fairly and respectfully.
Before they can begin a trial, researchers must submit a detailed plan to independent ethics committees – such as the Medicines and Healthcare products Regulatory Agency – for approval. The committees scrutinise whether the planned trial offers a fair and transparent arrangement for research participants – including how their rights, safety, wellbeing and confidentiality will be protected.
Most trials also have an independent data monitoring committee, to ensure safety by monitoring things like reported side-effects, patient feedback and incoming results. Using this data, the committee recommends whether the trial should continue.
If a potential safety issue is discovered, the trial is usually paused while an investigation takes place – which is what we’ve seen with the Oxford University and Astra-Zeneca trial. This is common. It’s critical to quickly understand whether the participant’s illness has any relationship to the vaccine (or the placebo) or if it is completely unrelated, and to share data openly.
Participation in a clinical trial must follow freely given, informed consent. Before a participant joins a trial, they must have all the information they need to understand what they are volunteering for.
2. Scientifically sound
Wherever possible, clinical trials should be:
- Controlled: two or more groups are compared – one (or more) who receive a candidate vaccine, and a control group who receive a placebo.
- Randomised: each participant is put into one of these groups at random at the start.
- Blinded: the participants do not know whether they are having a test vaccine or a placebo. Nor do the researchers who administer the doses.
This makes sure that there is no bias that could distort the results, and that researchers can be sure that any differences in outcomes between the groups are only due to the vaccine received.
Trials must also be large enough to give statistical confidence in the data. Testing two people wouldn’t tell us much about whether a vaccine works, but testing 20,000 will mean we can have much more confidence in the results.
Involving those who stand to benefit the most from the vaccine is key to the success of any clinical trial.
For example we know that older people, men and those with co-morbidities are at greater risk of severe disease and death from Covid-19, so vaccine trials should involve these groups.
We’re also not just going to use Covid-19 vaccines in one country or sector of society – so trials need to involve diverse populations in different locations, and where the outbreak is happening, to make sure the vaccine is as effective as possible for as many people as possible.
This was an issue with a vaccine for rotavirus, which was very effective in US trials, but not as effective when it was rolled out to populations in Africa, where the disease is widespread.
Trials also need to be adaptable to different settings. For example, in the West African Ebola outbreak in 2014–16, conventional randomised control trials were not viable due to the large cost, time required and local acceptability. Given the urgency of the situation, other trial designs, better tailored to fit the circumstances, were used instead.
4. Collaborative and harmonised
In a pandemic, it’s vital for vaccine researchers to coordinate their activities, so their work can add up to more than the sum of its parts. The search for a Covid-19 vaccine requires international cooperation for conducting clinical trials and sharing data.
By harmonising their approaches, trial designs and data collected, researchers can contribute to the same large trials all over the world – results can be compared between sites and the data can be aggregated into one big study.
To speed up the development of a vaccine, it’s also key for researchers to share their findings for others to build on. During the pandemic, researchers and publishers have pulled together to publish their findings openly at an unprecedented rate.
5. Trustworthy and engaged with the public
Early public and community engagement is vital to ensure successful recruitment of participants, keep trials on track, and develop trust to support wider uptake of a vaccine once one becomes available.
Making sure that participants and their communities are engaged with and have a good experience during a trial is important to make sure that they keep supporting it. If participants drop out, this can delay the trial, or make it harder to base informed decisions on the results.
And wider public trust in clinical trials is essential if people are going to be willing to receive a new vaccine once it has been made available.