Corona Daily 375: Human Challenge Trials

The world is excited about vaccines. Optimists, even those not remotely connected to medicine, are predicting a vaccine arrival in the next six months. As of today, 226 candidates are competing, with 195 of them at pre-clinical stage, and only four in phase III. The width and speed of the virus is such that in desperation mankind has agreed to conduct human challenge trials. What are these?

Any drug or vaccine can have its intended effects and adverse effects. Before approving, the authorities must ensure vaccines are capable of preventing a disease, and also safe. A wrong vaccine can harm healthy people. Once a vaccine is developed, it is tested on laboratory mice. A few weeks later, the mice will be deliberately infected. This may be followed by a trial on chimpanzees or other apes. This research can take months, if not years. By that time, Covid-19 may kill a million people.

The world has agreed to a pragmatic compromise. To go ahead with trials on human guinea pigs, without necessarily completing animal trials. AZD 1222 (Oxford/AstraZeneca), the leading candidate, having finished a trial on 1000 people, is now going for a large scale trial with 10000 volunteers each in a few countries. In the 1940s, Americans had conducted mass trials on prisoners. The Nazis’ infamous medical experiments made the civilized world establish rules for human challenge trials. Those participating must participate voluntarily, must be well informed and understand all the risks, and give a written consent. They are also free to leave the trial at any stage.

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Volunteers must commit to do or not do certain things for a long time. Women participants, for example, must undertake not to become pregnant for 12 months. Half of the participants are injected the real vaccine, and half of them a placebo. (Usually some other real vaccine that has nothing to do with Covid-19).  But neither the volunteer nor the researcher knows which is which. For a few weeks, they are monitored for side effects, headache, nausea, fever. Human brain is such a weird thing even a placebo can create an adverse effect.

The next step is to infect them. Fifty percent of them have had the unproven Covid-19 vaccine. If the vaccine is any good, it will work and resist the virus or the volunteer may escape with mild symptoms. If the volunteer was given a placebo, he has no protection other than nature and his luck. In theory, volunteers with a non-working vaccine or a placebo, when infected, can get seriously ill or in a rare case, die. That is why the name Human Challenge.

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With no drugs available, deliberately infecting people for vaccine testing is a complex ethical issue. Fortunately, the novel coronavirus is not lethal against the young. Oxford vaccine trials are restricted to the age group 18-55. (Imagine an ad seeking volunteers for an AIDS/HIV vaccine trial. Would anyone really volunteer for it?) Between 23 April-21 May, 1077 volunteers, with a median age of 35, almost all of them white, took part in Oxford’s earlier phase. There is a long way to go between 1000 participants, and a few billion in the real world. Also at some stage, effectiveness will need to be tested on the vulnerable groups, the old, those with medical conditions, and vulnerable non-whites.

Tomorrow, I will describe the firsthand experience of a British volunteer who participated in the latest Oxford trial.

Ravi