Coronavirus human challenge study gets green light in UK
politico.eu
politico.eu
I found this extremely unconvincing. A group of unelected people, mostly from the same social class, being able to determine the rules of something so important seemed inherently flawed to me.
In this particular situation, I saw it as signing up to be a soldier for my country (which always covers some personal risk) - with the number of lives that could have been saved by April 2020 human challenge trial being in the tens or hundreds of thousands of dollars.
How would it be better if they were elected?
only if the people aren't blinded by partisanship and realize it.
Experience alone is not enough. You must demonstrate evidence of actual expertise. Ethicists behave no more ethically than the average person[1], which strongly suggests that the entire field is worthless.
A rational person should ignore the established field of bioethics. Maybe even take the opposite of their advice.
[1]https://qz.com/1582149/ethicists-are-no-more-ethical-than-th...
I don't see how that follows. We don't expect our ethicists to behave more ethically any more than we expect our aeronautics engineers to fly.
We do generally expect a teacher to be able to explain a concept outside of their job, a writer to write a good note or letter, a photographer to take a good photograph when out casually with friends and family. Similarly we’d want people making moral judgement to demonstrate that capacity.
I don't understand why someone who studies ethics should behave better, any more than someone who studies the human musculature to be able to lift more weight.
I otherwise wholeheartedly agree with everything you've written. Self-proclaimed expertise should be viewed with a very healthy scepticism, and the burden of proof isn't on you to show why they're wrong, it's on them to show why they're right without resorting to an argument from authority.
The reasons there are many outperformers are few fold.
Firstly, failing funds often close up shop and start anew, which artificially inflates the N success metric. The average number of hedge funds that a current manager has run is 2, since they've closed one failure on average.
Second, economic theory is a limiting condition, it's still remarkably easy to be lucky over a 5 year period given the low frequency nature of trades that many of these funds perform. It's not like a chronic gambler where the law of large numbers kicks in after two weeks.
Third, professional fund managers still do have edge over all other parts of the market (this has been shown in academic research), it's just that this edge is less than their fees, but it tilts the small sample statistics towards showing a large N successes compared to what we'd expect if they were trading randomly.
EMH and CAPM doesn't say that it's impossible to run an outperforming mutual fund over many years. All it says is that it's impossible to do so in expectation. Note that this is a statistical property pertaining to the law of large numbers. Nowhere in economic theory does it preclude a number of lucky outperformers, which is consistent with what we observe in reality (ie that there's a huge number of outperforming funds, and an even larger number of underperforming ones).
A finance professor would say "yes, there's hundreds of outperforming funds out there, likely some combination of luck and survivorship bias."
The efficient market hypothesis and the idea of efficient markets in general is not supported by evidence.
In a roulette game, each outcome is drawn from the same, well understood distribution, so we can easily calculate the probability that a sequence of outcomes is observed when the null hypothesis distribution applies.
In trading this is much harder, given the null hypothesis distribution is unknown and hard to estimate, and trades aren't i.i.d. since regimes come and go and therefore the luck of a specific style can be autocorrelated over a number of years. Trades are also correlated in the cross section through betas.
I'm going to go ahead and say that it's an impossible task if we're dealing with 10-20 year timeframes and the fund had a low frequency style. It's just way too easy to be lucky over a course of multiple years. All you really need is 1 lucky call combined with index tracking on the remaining capital to outperform ("overweight AMZN").
So you can't prove much about very passive investors.
But if someone is making a 2:1 payout decision every month, and manages to be right 75% of the time, you can be quite sure it's not luck.
If there aren't enough exploitable inefficiencies in an entire career to make that proof, then that's an interesting data point all on its own.
What you're requesting is that this happens in a specific way. That specific way might not be the way that is optimal.
When a philosophy problem becomes well understood it tends to move into its own specialized field. For example the nascent fields of geometry, physics, and economics were all once part of philosophy. We get kind of a selection bias. Philosophers have a reputation for having their heads in the cloud, because we only think of the areas they've made the least progress in.
If ethicists were more ethical than other humans, people here would be complaining that they are holier-than-thou and that they didn't represent the population's ethical wishes.
Being less complicit in something that:
- causes immense, horrific suffering;
- has traditionally been, and still largely is, considered completely normal;
- requires some personal sacrifice to forego;
- happens because, and to the extent that, ordinary people continue to demand it
seems like a pretty big win to me, and a good argument that philosophical contemplation of ethical issues can be worthwhile.
(None of this implies that bioethics as a field is producing any value on net. Personally I'm unimpressed by what I've seen of it.)
Had the clinical trials run in a "less ethical" way, say by taking young and healthy people like myself, vaccinating them and then deliberately exposing them to COVID, then we might have seen vaccination start much sooner. Far fewer would have died and the colossal impact of lockdowns would have been mostly avoided.
And what exactly would that have told you about the safety and effectiveness of the vaccine for the people at risk, those who are neither young nor healthy?
And how many people would you need to challenge to show that the vaccine prevents deaths or even serious disease? The young and healthy rarely get the full brunt of the disease.
To your specific question, you still derisk it for the elderly. If it causes problems in young adults, you quit because it would probably cause even more problems in riskier groups. If it doesn't, you move forward into older groups.
Let's not pretend you would learn nothing that would speed things along. Some of these questions aren't answered quantitatively even now.
Of course. These are all great uses for challenge studies, I was responding specifically to testing the vaccine using a challenge study on healthy young adults.
> If it causes problems in young adults, you quit because it would probably cause even more problems in riskier groups. If it doesn't, you move forward into older groups.
It turns out that both Pfizer and Moderna trials have shown much more adverse reactions in the young than the old.
Testing on the wrong population may result in rejecting a vaccine that could be perfectly safe on the at-risk population, but inappropriate for the general population.
> Let's not pretend you would learn nothing that would speed things along
Of course not. You could learn a lot, just not about the safety and efficacy profile of the vaccine on the at-risk population.
So if the goal was to reduce transmission, you can save a lot of lives of those at risk by vaccinating the young and healthy. It would be reasonable to basically use challenge studies to get a lower transmission rate, while in parallel using standard trials to prove the efficacy in at risk populations.
Getting more data quicker is usually a good way to make more informed decisions, even if the data isn’t exactly what you want it to be to make the perfectly optimal choices.
Has this been tested yet? Is there evidence that this is true beyond the broad population surveys like those from Israel? (The accuracy of those data were hotly debated here last week.)
Surely a study to determine actual transmission rates would be much more complex than one to determine whether young & healthy people are infected after inoculation (which again: not that useful of a data point by itself)?
You could take 50 people, vaccinate half and give half a placebo, infect them with Covid, then put them in 50 rooms with 50 other unvaccinated people (so each has two people) for 2 weeks and see what happens.
The reason you can’t do it without a challenge trial is exactly because of what you said - you can’t track infections in the community.
Also note that had this been run last spring you've doubled the size of the trial and therefore the number of hospitalized patients who would not have life-saving therapeutics. By comparison, the BioNTech/Pfizer vaccine had over 40,000 people in its trial. Not sure you could even run a trial that big with even a tenth as many people.
In a challenge trial you can make people cough in each other’s faces, or literally inject them with Covid depending on the study, which raises your chance of getting people infected and seeing the impact. You would expect the control group to have a very high infection rate, and to see the difference in the study group much more easily.
I’m not saying 100 people would be enough, but you would need significantly fewer people fewer to get a good level of confidence.
And again -- the backup therapeutics that enable any challenge trial were not broadly available until a month or two before vaccines went into wide deployment. (You will note that nobody is volunteering for a challenge trial for any drugs or vaccines for our other ongoing pandemic, HIV. Lack of backup therapeutics is a big reason for that.)
People were actually volunteering for a challenge trial for Covid prior to theraputics being available - because Covid actually is low-risk for the groups in the challenge trial (young people) and the vast majority of people recover. I don't think theraputics are necessary for a challenge trial, as long as there is sufficient benefit, the risk is sufficiently low, and volunteers are aware of the personal risks (aware this criteria is ambiguous!).
HIV is incurable, however there are excellent therapeutics. Despite this, the prognosis of HIV is much worse than someone with Covid.
- apparently high asymptomatic rate
- somewhat unpredictable who will get severe case
- random neurological symptoms in a respiratory virus
And most/all of the vaccines we are using will be the first approved for human use on their respective platforms. It's worth looking at.
Also, for a pathogen that is so highly transmissible, it's worth understanding what we mean by "reduced transmission". Is it 10% less? 90%? Surely this would be important to know before following a strategy of vaccinating the young and healthy first. (Especially given the difficulty of doing so in a population that is least likely to suffer serious harm from the pathogen.)
We vaccinated no one in that period as it is.
It would have sped up subsequent production too.
Given those assumptions, there still needs to be a smaller safety trial before a large challenge trial. BioNTech started those in April, that ended in May. Deployment in the summer is already aggressive, assuming no challenge trials and we had just deployed vaccines shown to be safe in very small trials.
But suppose a challenge trial was run rapidly over the next three months (to determine which of the BioNTech candidates was best). Assume this all goes optimally. This plan still assumes the existence of scale manufacturing facilities that likely did not exist last summer. Let's wish that away too, so we have scaled manufacturing capacities to June 2021 levels by May 2020. While we have our magic wand out, let's wave away the fact that the vaccine initially took over 100 days to manufacture, so that in our world we can decide what to produce today and have it ready tomorrow instead of next quarter. So we've got positive challenge trial results in July 2020 with faster-than-2021 production capacity to go to scale.
Now, perception-wise, we are asking young healthy people to take a vaccine designed on a novel platform that was rushed through a novel ethics-skirting approval process, for a virus that likely won't seriously harm them if they get it. I'm not sure that would be as effective as people seem to think it is.
The Tetanus vaccine targets the toxin, not the pathogen.
Some research may indicate that the current a-cellular whooping cough vaccine prevents symptoms, but not transmission. The older vaccine prevented transmission, but had too many side effects.
The oral polio vaccine may actually result in outbreaks of the vaccine strain.
http://www.emro.who.int/syr/syria-news/polio-outbreak-succes...
Claims about prevention of transmission needs to be demonstrated in a trial, not simply asserted.
Supposedly, the Pandemrix fiasco happened because the antibodies generated by the vaccine cross reacted with some human proteins.
The lengthy drug approval regimen exists not because of some power drunk bureaucrats. It exists because of a long history of dangerous and ineffective drugs that looked really great in theory.
Likewise, it is not surprising that injecting a live polio virus can cause an infection. That is a different claim than saying a vaccinated person will get infected and transmit later once immune. Further, the coronavirus vaccines do not use live viruses.
Whooping cough is the example people love to bring up. I’ll paste in full my prior comment on this. The worst case example reduces transmission at least 30%! And probably more: it was completely sterilizing in 30% but may well have reduced transmissibility in other groups. And that’s the very worst case vaccine.
———————-
I looked into this, and it does seem the vaccine reduces transmission. It just doesn’t stop it entirely. The paper below is Wikipedia’s source. Upon a close read, in the daycare there were three groups of vaccinated children: * Those positive for antibodies but pcr negative —> had been exposed, cleared virus without infection * those pcr positive but asymptomatic * those pcr positive and symptomatic About 30% were in the seropositive group which didn’t have pcr positivity. So it seems like transmission was reduced at least 30%. It’s also possible the other two groups would have had lower transmission rates than if they had had no vaccine. If you have a more precise source I’d be interested to see it, but if this is the worst case it’s pretty good! > We used PCR, EIA, and culture to confirm B. pertussis infection in two highly vaccinated groups of children in two day-care centers. Three (10%) of 30 2- to 3-year-old children were seropositive for recent infection; one had nasopharyngeal colonization and a clinical illness that met the modified WHO case definition. In the day-care center for the 5- to 6- year-old group, 9 (55%) of 16 children were IgM positive, 4 (25%) of whom had nasopharyngeal colonization. Of these four children, three had nonspecific cough, and only one met the modified WHO definition for pertussis. None of the children in our study, including those who met the WHO definition, had been examined by a physician before our investigation. >Children who were seropositive and re- mained both asymptomatic and PCR negative probably had sufficient immunity from vaccines or natural boosters to protect them against persistent colonization and clinical disease. Their seropositivity could not be due to vaccine because the children were tested more than a year after having been vaccinated.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627963/pdf/109...
There's no comparison between transmission by vaccinated and non-vaccinated children, so there's no possible way of concluding that vaccination reduced transmission relative to non-vaccination.
You would not expect to see seropositive but pcr negative students if unvaccinated.
And that's the bad outcome where the slower trials in more at risk people don't work out. In the good outcome, when you decide it is safe and effective in vulnerable people, production and administration have already been scaled out.
(could study viral load in a challenge trial where you don't have to test thousands of uninfected people to find asymptomatic cases…)
Having no knowledge of the field of ethicists, i would imagine that these are the kinds of things they debate all day long, theres a million variations on the same question.
> The limiting factor in the speed of the clinical trials is the rate at which people acquire COVID naturally.
That's only one of the factors. It takes weeks to go from infection to disease outcome. If you're also interested in safety, you have to enroll tens of thousands of people, give them the vaccine, and wait to see if there are side-effects. And of course, you have to scale up production. In the grand scheme of things, the wait for people to get naturally infected in phase-3 trials was relatively short (a few weeks).
> Far fewer would have died and the colossal impact of lockdowns would have been mostly avoided.
Countries that had extremely strict lockdowns were able to reopen nearly completely with extremely low virus prevalence, and then to control the virus with good tracing. China has been mostly open since last spring, and fewer than 5000 people have died in total in the country (almost all of them in the first 3 months of the outbreak).
We can now tell that testing, up to now, results in over 2 million deaths. What would the risks have been for not testing?
We’ve got some vaccines that work, a few that don’t, and at least one candidate that looked promising but was abandoned for problematic side effects (false-positives on HIV tests).
You can’t just divide those out though, because all of this work was done in systems where people expected thorough testing. In a world where we didn’t test, the ”honest” attempts might not be as careful and there would also be a number of outright scams.
How does this not beat 2 million deaths?
Suppose we did and HIV tests start going off like fireworks a month later. Rumors start spreading about how it gives you AIDS, and uptake craters, probably for other vaccines as well. You’re right that this isn’t even the worst outcome. We also could have rolled out GSK’s failed candidates—-or one of Merck’s two. We’d be back where we started, but poorer, with less public support, and potentially dealing with widespread immunity to the vector. Solid preclinical candidates go sideways all the time, so it could have been even worse.
No argument whatsoever that 2MM deaths is awful and tragic. However, it’s the Slateist of Slate pitches to claim that “testing is the real killer.” We had plenty of easy ways to mitigate this (e.g., masks) but, for a variety of stupid reasons, chose not to use them.
Beats 2 million deaths.
And please, don’t give me the magical masks excuse. Masks might give additional protection, in no way do they solve the issue. And the ‘if only’ statements of some time ago have clearly been proven false. ‘If only we would have worn the masks corona would have been over’. No it wouldn’t because now it’s ‘if only we had worn three masks on top of each other’, which wouldn’t have been necessary if the first statement was true. It just isn’t. It’s easy blameshifting.
As for the rest, two words: New Zealand. Also Vietnam, Taiwan, Singapore, Atlantic Canada, and China (though you may not trust their numbers). A huge proportion of these deaths were avoidable.
I’m not even going to comment on the New Zealand utopia fantasy.
Most of the CoVID-19 deaths around the world have been avoidable, even without a vaccine. Countries that reacted properly (mostly in East Asia and Oceania) have had orders of magnitude fewer deaths per capita. Rather than rushing out a vaccine before doing any safety or efficacy testing, I'd rather that countries had controlled the virus with non-pharmaceutical interventions early on.
I count 4 months of phase 1/2 and 5 months of phase 3 (also note that there is some degree of confidence in the safety from the initial results of the phase 2 study).
I would think any challenge trial would be an additional study, not a replacement, a study that overlapped with phase 2 and 3 in information gathering (enrolling a smaller number of people but gathering more efficacy data per enrollee).
1 and 2: https://www.nih.gov/news-events/news-releases/experimental-c...
3: https://investors.modernatx.com/news-releases/news-release-d...
On the face of it, this is an uninformed opionion, whether or not it was "created in weekend" or not.
On the face of it, I would call it the truth.
As to say, not very "created in a weekend."
Very much ‘created in a weekend.’
It’s a choice whether you do a year long three phase trial. Or not. The vaccine (recipe) still exists.
I may have misremembered slightly but I seem to recall 42 days fromm sequence identification, leveraging a roughly 10-year project related to related coronavirus work (MERS).
So, not exactly a weekend.
Also, there were several candidates developed in parallel, but others failed at various trial stages. Less effective testing (and your proposal is less effective, both for safety and efficacy) might mean people get vaccines sooner, but it also means they get less effective and more dangerous vaccines sooner, meaning more people die of vaccines (bad for first order effects, and worse for the second order effect of increasing public vaccine reluctance) and that instead of stopping spread by vaccination we increase the selective pressure for diverse, resistant new variants without doing so.
How would a challenge trial in health 20-30 year olds help when most of the people dying are over 70?
Do you just wave your hands and extrapolate?
To the bioethicists, ok, boomer.
It's no more elitist than an electrician telling someone that they can't wire their house themselves "because construction and safety organizations have studied this for decades and understand it more than you" when burning down the entire block is a very real possibility.
The consequences of breaches in medical ethics have been dire: to this day minority and aboriginal populations have worse health outcomes because they have lower trust in the medical establishment and even relatively small breaches in trust like the CIA vaccination program in Pakistan can have devastating effects like the revival of polio.
Bioethics and "modern" medicine are relative new so we're well into the conservative whiplash stage of the natural "boom and bust cycle" but for a damn good reason. You're not going to appreciate the seriousness of the subject without really digging into the very recent history of bioethics.
Can I consent to getting a taxi ride to the doctor's office, when we might get in a car crash and die?
The electrician isn't presenting themselves as an expert on the ethics of 240 volt plugs and which rooms you're allowed to install one in.
It's a big difference.
"The purpose of this study was to observe the natural history of untreated syphilis; the African-American men who participated in the study were TOLD that they were receiving free health care from the federal government of the United States."
Trust your government, Learn from the past.
Now is obviously all much better ?
I do agree with OP that it's condescending to say that a non-PHD can't educate themselves enough for informed consent right now.
To me the time frame makes a difference though. Could one give informed consent in the first few months of a pandemic when we didn't know anything about the short and long term consequences? I think yeah it's their body they can jump in to benefit their family and all of us.
What about now that we have more data about immediate safety in younger adults and a bit more about potential longer term effects?
I agree with OP and don't think it's comparable to the serious problems you list.
Us non-scientists can understand enough to make this risk / society reward decision with our own bodies.
FWIW, in general it is perfectly legal for a homeowner to do their own electrical work on their own home.
[1] https://academic.oup.com/jid/article/221/11/1752/5814216 [2] https://pubmed.ncbi.nlm.nih.gov/33334616/ [3] https://pubmed.ncbi.nlm.nih.gov/32441894/ [4] https://foster.house.gov/hhs-fda
None of these points pertain to the scientific, medical or ethical rationales behind doing human challenge trials.
"46.107 IRB membership
(a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.
(b) Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution’s consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender. No IRB may consist entirely of members of one profession.
(c) Each IRB shall include at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in nonscientific areas.
(d) Each IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.
(e) No IRB may have a member participate in the IRB’s initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.
(f) An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB."
[0] https://www.hhs.gov/ohrp/regulations-and-policy/regulations/...
In the former case, you're definitely causing excess infections (some of which might die, directly due to you).
What if it's having a small but non-zero probability of killing 1 person, who understands and accepts the risk, vs waiting for thousands to die who really don't want to?
Also, I think the number of total deaths in both branches are about the same, as they're only waiting for 100ish people to get infected on either arm.
Also, I think the number of total deaths in both branches are about the same, as they're only waiting for 100ish people to get infected on either arm.
When you (entirely unreasonably) restrict your analysis only to the experiment subjects, it is true. However, the vaccine trials cannot be analyzed in a vacuum: the whole reason why these are even a thing is the raging pandemic that kills thousands of people every single day. To put it in a trolley analogy, the decision is not between high speed and low speed trolley that will end up rolling over the same number of people. Instead, in the other branch, in addition to one slow speed trolley, there are also thousands of extra trolleys that you just aren’t explicitly aware of, but they will roll over their victims nonetheless.
That may be a good enough to nix development for common cold vaccine, but how can one argue that it’s serious enough problem to cancel vaccine for disease that kills thousands of people every single day? This is another example of how “safety” and “ethics” regulations have little to do, and in fact are counterproductive to achieve safety and ethics in real world.
In the UK we've restricted the activity of healthy individuals for about 11 months now - the latest episode being an approximately 3 month period within which it's illegal to meet anyone else within your own home.
Psychological trials, even trivial things like filling in surveys or taking reaction speed tests are carefully monitored for ethical concerns, lockdown we just went all in on with no cost-benefit analysis.
It seems bizarre to me that in that context we should be worrying about the ethics of a challenge study with a few hundred or few thousand volunteers.
Loads of people I know have _already_ volunteered themselves for it in the outside world with no compensation and with no benefit to science because they're not able to mentally handle indefinite restrictions.
Do you compensate the participants for their time? If not, can you find enough people to run the trial? If you do compensate them are they truly consenting freely? Or do they just need the money?
Consent is a very complicated issue and you’re hand waving all the nuances away.
However, in this case, I suspect offering a monetary incentive wouldn't be necessary. Everyone knows about the terrible disease; just make a patriotic appeal and I expect you'd have plenty of unpaid volunteers.
And I’m not sure if you’d have a ton of unpaid volunteers or at least enough to power a trial. It’s not a simple “lets get a shot” it’s having to travel to a clinic several times over a period of time. It’s a serious commitment of time, that’s why trials are normally compensated.
Otherwise your entire pool of patients are just upper class mid-white collar career who can work from home and skip work in the middle of the day.
Why? The desperately poor person seems to think the money is worth it. Who are you to tell them it's bad for them to take it? The very stigma against "exploiting" such a person makes it less likely that other people will make them less-bad offers.
> And I’m not sure if you’d have a ton of unpaid volunteers or at least enough to power a trial.
In this thread, we have someone saying "I have signed up" and someone replying "thanks for taking a risk to help out the human race". It is patriotic, it is (or can easily be made) prestigious. (To make it visible, give out a hat, a button, a jacket, whatever.) I expect some guys would do it because it seems exciting or meaningful, others because they think it'll help them impress the ladies.
It's much more murky territory for more containable viruses such as ebola. But a deadly pandemic that spreads across the globe in weeks? Seems like it would be hard to argue against challenge trials with informed consent.
I think the strongest argument against it is that setting any such bar only makes it possible to lower the bar in the future.
As such, the benefit of deliberately infecting people over waiting for natural exposure appears to me to be zero.
> The Copenhagen Interpretation of Ethics says that when you observe or interact with a problem in any way, you can be blamed for it. At the very least, you are to blame for not doing more. Even if you don’t make the problem worse, even if you make it slightly better, the ethical burden of the problem falls on you as soon as you observe it. In particular, if you interact with a problem and benefit from it, you are a complete monster. I don’t subscribe to this school of thought, but it seems pretty popular.
https://blog.jaibot.com/the-copenhagen-interpretation-of-eth...
Also, has there ever been a case of a vaccine that only works on one age group?
Like let’s say we wanted to verify if some liquid was a poison, and we thought it had a 50/50 chance of killing someone, and we offer someone £500k to drink it, is that ethical? Probably not. I mean ethics are always subjective, but I don’t think that’s right. Does it make it ethical if it will probably save two lives? Uhh, I’m still uncomfortable with it...
So after that point you are just arguing about how risky the experiment is allowed to be before it becomes unethical, and what benefit it will have for other people in relation to that risk.
Again, I agree with you and the trial because the risk seems low enough and the reward seems high enough - this is just the counter argument.
No, it really doesn't. Most vaccines don't. Maybe one could argue that a COVID-19 vaccine should. But if you had a vaccine that worked on everyone under the age of 60 but worked zero above that, it would still be a 'real' vaccine and we'd be using it everywhere for the cohort it works for.
In fact, I can't even imagine what train of thought leads to this statement.
Bending ethics regulations because of emergencies is a really dangerous precedent, and a bell I'd rather leave unrung.
We don't need to bend the rules when things get bad, we need to have better rules. Subtle but massive difference
"Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13 [2020]. This was just two days after the genetic sequence had been made public in an act of scientific and humanitarian generosity that resulted in China’s Yong-Zhen Zhang’s being temporarily forced out of his lab. In Massachusetts, the Moderna vaccine design took all of one weekend. It was completed before China had even acknowledged that the disease could be transmitted from human to human, more than a week before the first confirmed coronavirus case in the United States. By the time the first American death was announced a month later, the vaccine had already been manufactured and shipped to the National Institutes of Health for the beginning of its Phase I clinical trial." https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac...
It's almost impossible to imagine the devastation that could have been averted if the vaccine was released in March 2020.
[0] https://www.nbcnews.com/health/health-news/merck-discontinue...
Why would that be a disaster? If a bunch of people get injected with a placebo, it's at worse neutral. Arguably it's better, because we'll collect data faster and move on to better vaccines.
If they think they got a functional vaccine and change their behavior as a result, a placebo has the potential to do untold harm all by itself. Further, it erodes loss of confidence so that when a working vaccine is discovered, it's even harder to get people to take it.
The FDA has faults, but when you look at people's objections it boils down to erring on the side of being too safe. How much trust would a regulator have if it erred on the side of being too unsafe?
No, it is easy: statistically zero. We spent all of last year working and figuring out how to make the vaccine while covid spread.
Maybe if Oxford/AZ vaccine was approved this way we could make a difference. My understanding is it takes 3 months to make the vaccine (grow the cultures), but might be confused - in any case we have the ability to have vaccinate the world by about now with that one which means that only future devastation is lost. Note that the South Africa variant would still have evolved and would be spreading uncontrollably for a few more months since the AZ vaccine doesn't stop that one (the science is not clear here so I'm taking the worst case to make a point), so it isn't even clear if anything would be saved.
For instance, we can see that we allow rescue divers to die so that trapped children may be saved. The trolley problem has been solved: some number of cave divers' lives are worth less than some larger number of trapped childrens' lives.
Should we risk soldiers' lives going to Afghanistan so we can stop Osama Bin Laden and discourage hypothetical future violence against us? Yes, of course. Trolley problem solved.
Try it again with COVID-19 and you learn something. The truth is that we don't really care all that much about some elderly dying (rightly so). We care so little about their lives that we wouldn't even risk a thousandth as many people to save them. That's how it goes.
Revealed Preferences tell us all we need to know. There is a dollar sum for a life. Some lives are more valuable than other lives. And there is a banal variant of utilitarianism that flows through us all.
We are not fools. No species that risks nothing gains anything.
Inaction is the most attractive option because the decision maker is can avoid blame.
We could have taken an aggressive stance against covid, done challenge trials, mobilized manufacturing, used more controversal restrictions on movement.
OR
We could have taken a more laze fair approach, letting the elderly lock themselves down and die in greater numbers.
Instead, we got some middling third option where politicians try to minimize accountability, and we get both very high deaths and very high economic disruption
There has been some effort to estimate the net impact of the FDA, and, for example, to compare the number of people who have died due to delays of livesaving drugs vs the worst cases of bad drugs getting into the market. https://www.fdareview.org/issues/theory-evidence-and-example... cites a bunch of studies—many of whose links have rotted, so you'll want the Internet Archive, e.g.: http://web.archive.org/web/20100603223422/http://www.cato.or... . The second link makes a case that the first number is significantly higher.
FDA kills. Remember that.
I don’t quite see the fundamental difference between injecting 15000 people or 150000. Or 1500000. Especially if they really want it.
"The drug Remdesivir will be used as soon as volunteers start developing symptoms."
Remdesivir broadly wasn't available in February 2020 as an approved drug. It still isn't in the EU, and broad US availability didn't come until the fall. It cannot be overstated how new are many of the drugs involved in the Covid response. It's not just the vaccine platforms, of which at least 2(!) are seeing their first use.
Accepted therapeutic options have AFAIK always been a part of challenge trial protocols. The difference is that in e.g. March 2020, the doses given to healthy challenge trial participants would have been quite literally taken from a hospitalized patient on a respirator. That's obviously unethical.
(The other option is to ask physicians to violate their Hippocratic oaths during the trial, which is a slippery slope.)
I don't see how taking supply of drugs away from someone in need to support a trial that could save more lives is 'obviously' unethical by the way - ethics aren't obvious and it's not at all clear to me that taking medicine away from a few people in an effort to save many more is inherently unethical. This is effectively the ethical debate between Utilitarianism and Deontology.
With a strict reading of the hippocratic oath, physicians would rarely advise a patient take part in any phase 0/1 medical trial ever (see Theralizumab). In reality, trials need to be carried out to advance medicine and doctors do assist with them alongside researchers.
Let's not forget that doctors are present during executions in the USA to give medical support, because the alternative is that people who aren't doctors will have to give medical support. And doctors would never elect to do unnecessary cosmetic surgeries and give ladies very big boobies.
I think more benefit comes out of a doctor assisting with a challenge trial than putting even bigger breasts into Cardi B.
I'm just saying that if the Hypocratic oath and system can flex to include executions, it can flex to include clinical trials :)
Besides, who is to say that the doctors assisting executions aren't behaving rationally, ethically and trying to reduce suffering compared to what would have happened if they were not around? Maybe these are the kind of ethics you want to consider in this situation - i.e. a consequentialist viewpoint too rather than just the deontological argument.
Have you ever lost your ability to breathe? I can assure you it's much worse.
Your comment adds nothing to the thread, you're just trying to annoy GP and you're not even correct in your assertions.
People seriously need to grow up. If there's anything I've learned from this ordeal it's that we are so insanely coddled in western society that literally no one knows what true hardship is in life anymore. We are truly screwed if things actually start hitting the fan at some point.
1. Well done you for having "a climate controlled, comfortably furnished apartment, a big screen tv, high speed internet access, video games, and food delivery". If it wasn't obvious, not everybody does.
2. Since, as you're implying, you're not losing your sanity, I'm not sure you have anything to say about the matter. Or to put it another way: You don't get to shit on other people's hardships just because you have it easy in life.
3. "Losing your sanity" can happen outside of lockdown-related ills. You are aware of that, right?
I need to read up on it, but I expect that this challenge trial has been given ethical approval because there is now some evidence from the larger (non challenge) trials that a vaccinated person being exposed has a low risk of harm (for the relevant age group).
> The first stage of this project will explore the feasibility of exposing healthy volunteers to COVID-19. In this initial phase, called the Virus Characterisation Study, the aim will be to discover the smallest amount of virus it takes to cause a person to develop COVID-19. [...] Once the characterisation study is completed, this Human Challenge Study model can be utilised to conduct COVID-19 Human Challenge Studies from mid-2021 subject to regulatory approvals.
There are some more detailed writeups at https://www.gov.uk/government/news/worlds-first-coronavirus-... and https://hvivo.com/the-human-challenge-programme/
People incur additional risk for enjoyment, money or to contribute to a social cause in many aspects of life.
If you work as a deep-sea-diver, go skydiving, join the army or even frequently drink a lot of alcohol this can increase personal risk significantly.
Voluntary challenge trials with well informed, healthy, young participants testing novel vaccines and treatments during pandemics has a very high net utilitarian impact.
A < 1/10,000 risk for several hundred 20-30 year old participants is dwarfed by the death and suffering prevented by more quickly having efficacy information.
I'm 27, and shy away from many risks, but signed up for '1 day sooner' soon after the pandemic reached the UK, and would be proud to participate in a challenge trial if needed.
People framing it as 'unethical' should lay out exactly what their ethical framework is.
Only 10% of positive cases (not including untested infections) have any impairment after 3 weeks.
https://covid.joinzoe.com/post/covid-long-term?fbclid=IwAR1R...
I didn't because I thought it clear and obvious from context. We're talking about medical ethics, which is a well developed field of research and practice. There are established procedures in the US and UK to get ethics approval for studies and those panels are not just making it up as they go along (mostly).
I suppose when I say 'it is unethical' what I really mean is 'the medical community in the developed world has come to a strong consensus that it is unethical'. Even with informed consent.
The ethics from the other side are broader and subtler - they are not of the individual they are of the masses. Whether the Army acts ethically by recruiting soldiers and sending them to kill and die is a subject of much debate. A large number of people think that it is unethical, and that is why they protest against war.
To give one example of the complexity of medical ethics: occasionally when running clinical trials, the results are so GOOD that it becomes unethical to not stop the trial and give the drug to the control group.
I seriously doubt there is evidence of this claim. I don't think we can go around saying it can destroy people's lung function who show no symptoms. If a person's lung function is damaged to the point where we would describe it as 'destroyed', then that person is not asymptomatic. That's a clear symptom.
Maybe I misunderstand, and you are saying folks who start out with no symptoms, then develop damage latter.
Anyway, we can reasonably say that asymptomatic people might still receive minor damage to their lungs, and such damage could be observed on a CT scan or other test later. Irreversible damage? Probably not.
Our bodies are in a constant state of being damaged and repairing themselves. If we went through life with the goal of avoiding any and all damage to our bodies, that would be a terrible way to live.
We definitely go through life trying to avoid damaging our bodies.
Depends on your risk tolerance.
Some people are agoraphobics, while others are BASE jumpers.
I personally know that a major research hospital is doing (unpublished) research on medium to long term effects of mild-moderate COVID (non-hospitalized) on lung function and that the initial radiological results 3-6mo after symptoms are fairly shocking to those running the study.
So there is at least some published evidence from multiple sources and there continues to be study on this and based on the known action of the disease. Covid "long-termers" do also come from mild-moderate and perhaps even "asymptomatic" cases so I'm not sure FUD really makes sense here.
https://www.webmd.com/lung/news/20200811/asymptomatic-covid-...
https://www.uchealth.com/en/media-room/covid-19/short-and-lo...
p.s. these articles were trivial to find and are in no way exhaustive.
They cite two studies from China in April of last year. One study had 16 participants, the other had 4. 20 people total studies between the two. Not really enough for any of us to make any claims with confidence. WebMD article says, "Nobody knows exactly what those changes mean yet or whether they will persist and form scar tissue or simply heal and go away after the infection is gone."
I'm not saying we shouldn't be cautious. But in my opinion, if a person was truly asymptomatic then they weren't really sick. If it affected them so little that they weren't ever aware they had the virus, it seems like a stretch to believe that they would have permanent, debilitating damage. It's in the realm of possibility, but I'm not going to lose sleep over it.
It's unfortunate asymptomatic people still carry the virus & spread it around. But is that quality really unique to Covid-19? I doubt it. I suspect it's probably a quality of many diseases and sicknesses that we just didn't fully appreciate before. How many people every year carry around the common cold or the flu with no symptoms, and end up spreading it around. Probably a lot.
I'll concede that it's possible to still be harmed by Covid, even if you have very few or no symtpoms. Maybe my gripe is that I'm just exhausted from hearing talk of Covid as if it has 'magical' properties that we all need to be afraid of.
People who don't routinely measure athletic performance wouldn't even notice losing the equivalent of an entire lung lobe as long as the loss doesn't come in a very short time.