Human challenge trials: 19 'what if' COVID-19 questions answered

DUBAI: What if no virus emerged from Wuhan? And it's all just a nightmare we could now wake up from?

What if we already have a vaccine, at least one that works — i.e. safe and effective? Amidst this crippling pandemic that left millions homelocked for months, it's like a long bad dream we all wish we could wake up from.

Posing such “what if” scenarios can't be helped: What if the virus was contained in Wuhan from Day 1? Or Day 7?

It’s water under the bridge now, of course. The virus has spread far and wide, infecting 26.1 million people and killing about 864,000 as of September 3.

Proposed what-if scenarios:

1. What if no virus emerged from Wuhan, China?

After months of quarantines and economic meltdown, it would be a fabulous morning to wake up from this 2020 nightmare.

2. What if, after the coronavirus emerged in Wuhan, containment measures were immediately put in place?

Go back to Scene #1.

It would have meant:

3: What if, when the virus first emerged, flights to and from Wuhan were grounded?

Perhaps the same as scene #1, with some slight differences.

4: What if scientists were able to develop a vaccine for SARS-CoV-1 (in 2003-05) and MERS (2015)?

It’s possible, with cross-reactivity in vaccines (against the same family of coronaviruses) kicking in, it may also work against SARS-CoV-2, based on the cross-reactivity found in memory T-cells of SARS-CoV-1 suvivors.

5: What if it takes too long for people to be convinced that a good COVID vaccine actually works?

The world does not need 100 different vaccines against one virus. That would be too confusing. the world needs more solidarity and collaborations

Narrowing down the time and selections would mean less waste, and a better chance to curb infections sooner.

6: What if vaccine trial subjects are kept to the maximum of 3,000 required, instead of 30,000 or 60,000 now being targetted by a number of vaccine makers?

3,000 is the number (maximum) required for Phase 3 drug trials, based on US Food and Drug Administration (FDA) guideliness.

7: What if, a COVID-19 vaccine is found effective in a much shorter time with 'human challenge trial' (HCT)?

8. What if a successful HCT would render other vaccine candidates obsolete?

No, not at all. A successful HCT for one vaccine does not necessarily spell doom for another.

The biggest challenge is what's faced each day by millions who deal with fear, hunger, death and economic dislocation as a result of further infections and lockdowns.

9: What if the human challenge trial does fail and those young volunteers would be infected?

It's a valid question to ask. HCT is a controversial method because of how serious the disease can be -- and because its effects aren't fully understood.

There are ways to get around this dilemma. Scientists are reportedly now developing a less lethal coronavirus strain for human 'challenge' studies, the National Institute for Allergies and Infectious Diseases (NIAID) said in a statement on August 15, 2020.

In normal clinical trials, volunteers receive either a medicine or a placebo and their health is then followed over the course of months, or years. Scientists look for how well the vaccine or treatment worked when the person was naturally exposed to the pathogen. If one no, or only a few get exposed, the trial's results would be in doubt.

Vaccines that used the human challenge trials include shots for:

10. experts are also concerned about elderly people getting a vaccine that works for them?

It’s a valid concern. A recent article in The Lancet (August 11, 2020) reported that 11 of the 19 WHO advisors were concerned that results for younger volunteers in an HCT might not be a valid predictor of efficacy, especially on older people.

Here’s a logical question to ask: If those 11 WHO experts do not agree to a human challenge trial — only because of their concern over the elderly — then wouldn’t a decision be self-defeating for the world?

11: What if that decision ('no' to any type of HCT under any circumstances) means confining the entire world to the concerns of the 11 WHO experts?

It’s the view held by a number of some WHO experts. And it's a valid one. No professional bio-statistician worth his salt would fail to insist on getting the widest possible age groups across the widest possible population groups in a sampling or efficacy/safety study.

Yet it’s up to the individual member government to follow the WHO experts or not. It’s an ethical question.

Though one must also ask: how can the rest of the world trust the same group or institution that uncritically parroted the Chinese party narrative — don’t-worry-there’s no-human-to-human transmission, no-need-for-a-mask-just-give-it-to-medical-workers, and the virus-jumped-from-a-wet-market (a point proven to be false by China’s own scientists) — to guide the rest of humanity about ethics on a coronavirus solution?

12: What if human-challenge trials (HCTs) were to be conducted now?

Many within the WHO support the idea, as they believe the potential benefits far outweigh the risks, in case an HCT trial fails.

Here’s one point: If a vaccine is found effective in younger people (following an HCT conducted only on younger population, who can better resist the virus if the trial vaccine does not work), that does not mean the validity of other vaccine candidates taking the standard, long-term large-scale trial route would be invalidated.

Here’s another point: Data from those large-scale clinical trials (with tens of thousands of subjects) would still be useful in extrapolating benefit-risk analysis for the larger population, including the elderly.

“There are a variety of uses of human challenge trials other than deriving estimates of vaccine effectiveness,” states the The Lancet article.

“Moreover, even if one or more vaccines was found to be efficacious only in healthy, younger populations via a human challenge trial, this would still be useful in conjunction with other vaccines — since more than one vaccine is likely to be necessary — and healthy-population vaccines will help in ensuring sufficient supplies of other vaccines for higher-risk populations.”

13: What if a trial, right now, confirms at least one vaccine works?

The biggest benefit, of course, is this: Lesser economic dislocation — and lesser deaths too.

COVID-19's transmission will be curbed, even if only among the younger population.

“Even if a vaccine is found to work only on younger people,” states the experts in The Lancet Infectious Disease.  “Such a vaccine would also be economically beneficial, through allowing a large group of people to return to the workforce.”

Several HCT benefits were also outlined in a WHO document published in October 2016 (by the Expert Committee on Biological Standardisation in Geneva).

“Animal models are often quite imprecise in reflecting human disease, and many infectious organisms against which a developer might wish to develop a vaccine are species-specific for humans.”

The experts added: “Human challenge trials may be safely and ethically performed in some cases, if properly designed and conducted. Tremendous insight into the mode of action and the potential for benefit in the relevant species – humans – may be gained from challenge trials.”

“However, there are also limitations to what challenge trials may be able to ascertain because, like animal model challenge-protection studies, a human challenge trial represents a model system. Because there are often such significant limitations to animal models, the model system of the human challenge trial may significantly advance, streamline and/or accelerate vaccine development.”

Source: Sabin Vaccine Institute

14. What if the guidelines for good clinical practices (GCP) and “informed consent” based on human subject protection (HSP) standards being used in current vaccine development is outdated?

These two elements — good clinical practices (GCP) and human subject protection (HSP) — are critical requirements.

Ethical conduct in research involving human subjects is important. In the case of the FDA, the regulations for the conduct of clinical trials incorporating these two elements, and have been in effect since the 1970s.

This is exactly the point about how technology trumps up standards.

For example, one evidence of “informed consent” of a subject involved in a clinical trial study is a signed paper document. In the pre-cloud era, recruitment of human volunteers took ages. Before internet came, a signature on paper is the best proof. Today, not anymore.

15: What if recruitment of volunteers is cloud based?

That’s what’s happening now, though it’s not clearly outlined in any existing guidelines we’ve seen so far (we’d like to be proven wrong on this).

Today, instead of recruiters "pulling” the subjects, going door-to-door, the subjects are now “pushing” themselves, signing up, as people get used to downloading apps, and then signing up in droves.

It’s like how instant messaging, Youtube and Tiktok trumped up all traditional media.

Cloud-based recruitment method had been extensively used by most vaccine developers, significantly cutting the cost and time.

16: What if there are people willing to be subjected to a 'human challenge trial' (HCT), literally offering their bodies to be deliberately exposed to the coronavirus after they’ve been vaccinated?

That’s also what’s exactly happening now. Or what tens of thousands of people have asked scientists to do on them. Offer up their bodies for deliberate infection from coronavirus.

It's the vaccine trial recruitment process in the 20th century being turned on its head. Now, with cloud recruitment, a number of problems is faced by a 60s-70s trial recruiters’ mind:

17. What if insisting on 'informed consent' is right, but the definition of how it’s obtained is wrong?

The “1daysooner” movement is social media-driven HCT recruitment drive.

1daysooner is a group of people who signed up to offer themselves as guinea pigs for “human challenge" trials. Thousand already signed up for this simple, yet scary, idea: “Give me one of the candidate vaccines, then expose me to the virus.”

This way, the group believes, it would quickly narrow the field of promising vaccines and speed up development.

As of August 24, 2020, some 35,00 “human challenge” volunteers from 150 countries already signed up with 1daysooner.

16. What if the recruitment for the SARS-CoV-2 vaccine prevented the use of the internet, or the cloud?

If trials, vaccine development, and collaborations among scientist must be done manually, using snail mail or telegram to communicate — that would indeed by tyranny of present-day Luddites, no different from those who burn suspected 5G mobile phone towers.

What if announcements (to recruit volunteers) were only valid if they’re done over the radio or printed newspapers?

That’s the scenario during the vaccine developments at least until the 1980s. During the time of Dr Edward Jenner, who developed the smallpox vaccine in 1796 (the world's first), there was no radio (invented in 1886) and it was 50 years ahead of New York Times’ first print-run.

The year the word "vaccine" was first used, there were still no established trial protocols — just humanity's urge to heal the sick with the knowhow and resources available then. 

18. What if today's vaccine makers world were to go back to 1796?

Back then, there's no Tiktok or instant messaging. The village limited one’s world. Horse was the main engine to move things and people around. No one had a passport. It was more than 200 years before transcontinental flights (with first Boeing 747 rolled out in 1969).

Yet in 1796, the vaccine was proven to work — because it simply worked — on one badly afflicted boy, aged 8, whose then recovered.

Before the introduction of a smallpox vaccine in 1796, on average 7.6% (1-in-13) of all deaths were caused by smallpox. Following its introduction, there was marked decline in smallpox deaths. Today, no one hears about smallpox-triggered deaths. Now, the anti-vaxxers can conveniently deny the existence of smallpox.

If old ways are used to tackle new challenges (like the novel coronavirus), then, Houston, we have a problem.

19: What if this article was dictated on a phone, while the writer is having a nightmare?

Go back to scenario #1.

Would you sign up for a 'human challenge trial'? Write to readers@gulfnews.com