COVID Human Challenge Trial- The New Dare (and what Captain America can teach us)
A global crisis is in effect. It upends world order and rolls over to display its underbelly- a reminder of humankind’s frail mortality. Fear grips civilian circles and distrust brews at street corners. Governments advise their people to contribute to public safety and keep society alive. The youth are called upon to volunteer and help usher in a new future- a path towards progress and victory against unfriendly forces.
If the above sound even remotely familiar, then allow me to tell you it is the background to the origin of Marvel’s Captain America. A comic character created by Joe Simon and Jack Kirby of the then Timely Comics, that later evolved into Marvel. On the silver screen, the character was played by the genetically gifted Chris Evans, in arguably the most popular film franchise. The origin of Captain America dates back to the 2nd World War and the recruitment effort to get the American youth to sign up to fight the War. The story’s protagonist is a frail young man who is unable to enlist and contribute to the frontlines due to his physical shortcomings. He then voluntarily signs up to a United States lab experiment that would augment his physicality to the peak of human perfection in bid to make him a super-soldier.
What happens to the young man after that, makes for a good comic character and as it would seem, a compelling superhero. But to me, the story thus far is sufficient. It introduces the idea of a human challenge trial.
With pharma giants pedalling towards the end of the pandemic tunnel, the novel coronavirus seems to have inspired a great race involving science, politics and international media. The latest news of Pfizer and team claiming that its vaccine is over 90% effective based on initial clinical trials, will not be the last of its kind. Pfizer is competing with as many as 48 other candidates who are all engaged in clinical evaluation which you can check here.
Despite the news, it is safe to assume that a mass-manufactured vaccine will not be in sight at least till the summer of 2021. ( There is a possibility that some countries might have earlier access) This deadline too has gotten a lot of ambivalent responses as some fear that a vaccine developed so quickly might have adverse long term effects. They hesitate to trust it. To be fair, it is not blind panic. The average vaccine in pre-covid times took about 5–10 years to travel from pre-clinical lab testing to manufacturing, fulfilling three phases of clinical trials and regulatory reviews along the way. The following graphic accurately describes the process.
What if I now told you that I know a short-cut that could save us valuable time? A short cut that has previously helped develop vaccines for cholera, typhoid and influenza; a short cut that sits atop equally strong arguments and a close ethical debate. Would you take it?
ENTER: HUMAN CHALLENGE TRIALS.
Human Challenge Trials are controlled clinical trials where healthy subjects provide informed consent and voluntarily expose themselves to a promising vaccine candidate and subsequently a dose of the pathogen (in this case, the novel SARS CoV 2- Corona Virus) to check the vaccine’s efficiency.
Would you volunteer to willingly expose yourself to the coronavirus under controlled conditions if it would aid the understanding of the virus and hasten the discovery of a cure, potentially saving millions?
It is quite the trick question. If you easily agree you might have an unchecked saviour complex. And rejecting it outrightly might make you seem like a selfish coward if you happen to be an ideal subject. No pressure. Then again, if you don’t have a definite answer yet, then you got parts of the scientific community on your side.
This choice I proposed is not one that I’ve conjured up. 1Day Sooner presents the same case in a more compelling way that plays on your idea of moral responsibility and civic sense. Even right now, you could sign up to be an advocate or even a volunteer. And this seems to be resounding with over 38,000 people across 166 countries.
Are they nuts? Not quite.
Usually, when a vaccine is tested the traditional way, they use subjects who are divided into a trial group and placebo group. Both of whom are closely monitored to see how their immune system responds and how it prepares itself to defend the pathogen. Here, the subject experiences a direct benefit if the vaccine succeeds. Human Challenge Trials, however, deliberately induce the pathogen in healthy systems without differentiating them into groups after administering a potential vaccine on all candidates for scientific purposes. The result would show if the vaccine stands the test of defending the body against the viral/bacterial invader. That is the fundamental difference. And since Human challenge trials don’t wait a long time and don’t have a placebo group they save a lot of time and need lesser participants.
It would be quite remiss if I don’t mention that challenge trails have had good success in the past in developing vaccines for typhoid and cholera. Corona Virus though will be a new territory as the virus is relatively new and far more deadly. Another important point would be that a ‘rescue therapy’ existed for typhoid and cholera and the diseases were well understood by the scientific community when such trials were conducted. Rescue therapy is a fail-safe; an approved mode of treatment/cure that is already safe and tested. Corona Virus is neither well understood nor has a rescue therapy. As of date, the fact remains that rescue therapies are not an ethical prerequisite for Covid 19 trials and there is still debate if rescue therapies can be considered a standard in such an unprecedented case.
But doesn’t it seem like common sense to use a controversial mode of research only with some safety measures like that of a rescue therapy?
This is where the concept of RISK PARITY comes into play. As a student of psychology, I often found myself amazed by the red tape of research ethics and detailed deliberations that goes into consent forms. The concept of risk parity is a similar ethics one.
What is the principle of risk parity?
As I understood it, it is a utilitarian idea which argues that if we are willing to take risks and expose some (read health workers and frontline warriors) to the virus in order to save lives then we should allow other people (read volunteers who provide consent) to take the same voluntary risks in order to attain comparable benefits.
Quite the trolley problem isn’t it? Why should only health workers helm the fight if altruistic non-medical persons can contribute? We already know that the longer we take to find a cure, the more people we will lose.
The pandemic has already affected our moral assumptions. It has broken down our daily lives and imposed such restrictions that were previously unthinkable in liberal democracies. Some of us have lost lives, been forced out of jobs and pushed to the depths of social and economic difficulties involuntarily. India is a very good example to show how the pandemic has caused an unprecedented recession in some countries. In such a case, is it justified to back methods like human challenge trials to aid the discovery of a cure? As the famous axiom goes, do desperate times call for desperate measures?
The argument against Human challenge trials that stayed with me is that the scientific and social value of a challenge trial is not great. Pharma companies are already making great headway and speed and we are likely to have a vaccine even without such challenge trials. So if at all such trials begin, they will only aid the discovery of second and third-generation vaccines. Why take all this risk for a second/third-gen vaccine? And there is the obvious reality that SARS 2 CoV is more deadly and has more grave manifestations than influenza and RSV (respiratory syncytial virus) challenge studies that make the case for Corona Virus challenge trials.
The likely subjects for the Human Challenge Trials are healthy younger sets of the population who have a better recovery rate and lower death rate. There are specific conditions like the chosen candidates will have a higher baseline of risk for contracting Covid naturally (because they live in high-risk areas) and that they will be monitored closely and given top-notch medical care should the result turn awry for them. Not to forget that in the absence of a vaccine, these very people participating are likely to contract the virus in due course of time. Therefore, the case that such participation could save lives potentially, and the chances that by the time that such trials are underway in full force there will safe therapeutic options, greatly help in winning over consent.
But is this fair? We also have evidence to suggest that some minorities like Blacks, Asian and minority communities are at more risk to severe damage and possible death due to the virus. This creates a structural injustice. And will a vaccine so developed be representative of all demographics and age groups like children, pregnant women and the elderly population? We cannot ignore that the virus affects each host/ individual differently and the manifestations vary vastly. This is the more basic risk that silently exists in almost every treatment for every disease- individual differences.
While the debate might continue, news media tells us that come January 2021, the UK will be conducting the first Human Challenge trials in a secure East London facility under hVivo, a spinout from Queen Mary University of London with the Imperial College London as it academic partner.
Though I might not be qualified to give you a ruling, I would like to tie this up using what I reeled you in with. What can Marvel’s Captain America teach us? And was he perhaps the first-ever human challenge trial candidate?
The answer to the latter is simple. No, Steve Rogers (Captain America’s alter ego) was not the best suited healthy subject, he just happened to be someone who had nothing to lose and was quite frankly disposable to the US Army in the story. (Or he was one with the “good heart”, as Stanley Tucci’s character in the movie will have you believe.)
But the lesson to learn is not from the character Captain America himself. It is from the villain in his universe- The Red Skull. As the first failed test subject of the serum experiment that the captain later undergoes, he tells us that the difference between a red Nazi monster and America’s poster boy for the war effort is simple- time and better scientific research.