The team behind the Oxford Covid-19 vaccine hope to begin tests on volunteers who will be intentionally exposed to the virus in a “challenge trial”, a move seen as controversial since there is no proven cure for the illness.
Although challenge trials, in which healthy volunteers are given a pathogen, are routine in vaccine development, taking the approach for Covid-19, where there is no failsafe treatment if a volunteer becomes severely ill, has been questioned.
In human challenge trials volunteers are intentionally exposed in a controlled laboratory setting, meaning the trial can be completed in weeks and requires far fewer people.
What do you think of the ethics of Challenge Trials for COVID-19?
One analogy I can think of is of people joining the army during wartime.
Two issues concerning ethics that come to my mind are -
Who are the volunteers… if they are mainly poor and desperate people from within the country or even worse from outside… then it’s an ethical issue.
The article mentioned south Africa and Brazil.
The statement signed by the scientists is also concerning…
“If challenge trials can safely and effectively speed the vaccine development process
Seems a very desperate times measure. Even if the vaccine is effective, the placebo group is pretty much sure to get sick.
As well, how do they determine the viral load for exposure? If more young health care workers are experiencing severe sickness, that may be an indication that degree of exposure influences the subsequent virulence.
Finally, there is concern that internal damage may not entirely remediate after recovering from Covid among younger people.
Honestly, I’m not sure I would take one for the team were I young and robust, not that I have to worry about that.
At first glance, this is a somewhat standard example of the interplay between acceptable risk, reasonable benefit, and fully informed consent. @Ashwin_s draws the reasonable parallel with military service, and we can add police and firefighters during normal times. In this pandemic, HCW and first responders also incur risk. While they are not certain of infection, as are the volunteers in this trial, they are at substantial risk and not all of them are making an entirely voluntary choice.
So maybe the main difference here is the one raised by @RonSewell, which is that the likelihood of infection in this trial is 100%, so the “risk” is not that of getting infected but of getting very ill. IMO that’s a significant difference from the military/HCW comparison.
@Ashwin_s also identifies an ethical concern that is not unique to this trial, which is whether the risk will fall disproportionately on already-vulnerable people and/or people already lacking privilege. This concern applies strongly to military service (at least in the States), so IMO if the trial takes care to enroll a representative sample of the population, it will be ethically far superior to military service in the US.
Technically, the risk of infection is not 100% if the vaccine is effective. Rather, the risk of exposure is 100%. They propose only including people in their twenties, who they claim have extremely low risk of having serious complications to infection.
It is a an if, but the real point of the statement was that these scientists (15 Nobel Laureates) thought that predicated on this premise we should do challenge trials. For reference, here is their letter: 1DaySooner: Open Letter on Challenge Trials for COVID-19
Indeed, and it should get intense ethical scrutiny. If the same scrutiny were applied to military service, that would be great too.
That’s not a claim. It’s a fact, unless we want to dither about the meaning of “extremely low risk.” What matters to me is how we weigh that risk against benefit and especially with a very critical eye on fully informed consent, while being intensely focused on how the volunteers are chosen and whether–as is likely IMO–there are disparities in how this risk is incurred.
I understood that… however imo, the benefit in terms of time saved is more important than an argument based on authority.
The risk vs benefit being clearly defined is important. In this case, the risk is fairly well defined… the benefit is an “if”… hence the strategy of resorting to an argument from authority I.e the noble prize winners.
I’m having a hard time finding a definitive answer as to whether this trial would be double blind and including a placebo group, which of course would involve infection for the placebo group even if the vaccine if effective. If it is not double blind, on the other hand, to what degree would that compromise the confidence in the results?
It couldn’t be a legitimate trial without those components, could it? I don’t think there is any reason to doubt that it will be double blind and placebo controlled.
I see no appeal to authority in this letter. It’s just a fact that Nobel’s signed it. That at least merits reading the letter, but no one is claiming that merely because 15 signed the letter it is therefore correct.
Like most scientists who have had extensive ethics training as part of their vocation, I reflexively don’t like the idea at all. I also think it isn’t necessary.
Cell based studies can determine if antibodies are effective.
Animal studies can do the same as cell based studies.
People will naturally be exposed to the virus, and epidemiological data can tell us a lot.
The most ethical approach is to let people select themselves for the study with some sort of open enrollment. The study should be designed so it fits around the participants’ work and life schedules, and their time and travel should be compensated for. However, compensation should never be an enticement to join a study since that would compromise consent. These are all standard considerations in many human trials.
When we are looking at the demographics of the study population we must also remember that different social groups view scientific research differently. Due to abhorrent behavior on the part of scientists in the past, there is much more distrust of the scientific community within minority populations. Needless to say, humans are complex and so too are human trials.
One ethical dilemma is that challenge trial members would be compensated at quite a high rate, perhaps over $10,000. Given the risk, this makes sense. However, this creates high enough an incentive that some participants judgment might be compromised. I wonder how this will be managed.
Me, too. That’s way too much compensation, IMHO. Any medical care needed as a result of the trial should be free, but that much compensation compromises consent. If those same people wouldn’t participate in the trial without that high level of compensation then they aren’t consenting to the study.
The topic of the thread is the proposal that a clinical trial of a vaccine be accelerated by way of a challenge trial. None of those points are relevant to that question. In fact, the last one highlights precisely the problem that the proposal aims to solve, which is the long wait for data as people are naturally exposed.
There are precisely two areas of inquiry/concern about the challenge trial proposal.
Whether and how the trial can be conducted according to ethical norms.
Whether it can save a lot of time compared to the standard approach.
Those two questions are related, because the first concern requires work that must be done before a challenge trial can be started. Some here on the forum (@Art for sure) are unconvinced that the trial will save time because of the time needed to finish that work. I don’t know. What I do know is that is unrelated to experiments on antibodies, since those experiments cannot ever take the place of a trial in humans.
Ethical delays aside, will a challenge trial save time?
For better or worse, it may depend on how well we control the spread of the virus with social distancing and other measures. We are largely failing at this in the US now. With this in mind, the value of a challenge trial substantially decreases, because it becomes easier to find high exposure populations when the virus is not controlled.
These high exposure populations are significantly better for a trial, because they are more diverse than a challenge trial will ever be, exactly match the intended patient population, and may be effectively equivalent to a challenge trial in exposure.
This doesn’t undermine the letter, which is conditional on whether or not these trials would speed things up. I’m not sure they will in our current situation. My guess is that we will still allow them any ways. It will be a mad dash to the finish line, and in a race like this there should be some surprises. In fact there already have been surprises.
I can see the benefits, but I don’t know if it really outweighs the risks. I will also be very open in saying I am completely biased against challenge trials, so there’s that. A challenge trial goes against everything I have been taught in research, so there’s a built in reflex to reject the idea.
With that in mind, here are my thoughts. These initial trials are really about safety. If the vaccine isn’t safe then it doesn’t matter if it is protective. Production of these vaccine candidates is going full bore as we speak just in case one of them proves to be both safe and effective. If the vaccine is shown to be safe in limited trials then it can start to be administered to a very large population that will ensure natural exposure to the virus. Not only that, but you will get data from at risk populations, such as the elderly.
The people who drafted that letter include global experts on the topic. The phrases these experts used include “much faster,” “months longer,” and “greatly accelerate.” I do not doubt that the challenge trial will save time, all things considered. The rationale, scientifically, is clear and beyond dispute as far as I know.
The proposal makes this point explicitly. A challenge trial can provide the data we need without being hindered (ironically) by effective social distancing.