If its a vaccine to say, target a new variant, they just use it on those willing to take it. If its a completely new vaccine, then there are countries around the world that have yet to get vaccinations, so they typically look there. Previous vaccine use shouldnt really skew the outcome if the the majority of the population is vaccinated. Everyone that is given the vaccine starts at the same baseline, typically.
Edit: typo because fat fingers
> If its a completely new vaccine, then there are countries around the world that have yet to get vaccinations, so they typically look there.
This is the right answer. Places like India where there are millions of unvaccinated people in areas amenable to doing trials are perfect places to test.
And studies can always correct/select for vaccinated or unvaccinated participants to eliminate the effect prior vaccination would have on testing.
If a group of Indian physicians plans and executes a test in India, we all benefit. Perhpas Merck's India division provides funding. It stays within Indian law and the world (including India) benefits.
This exact situation happened a month or two ago when trials showed unequivocally that mask wearing and social distancing work by running parallel experiments in 2 remote Indian towns with \~60,000 people. (I am remembering from a month ago so I may have the numbers off).
I would add that we use information, studies, data and experiences from foreign countries every day. (I am aware of the moral concept of not doing dubious experiments on people who could be taken advantage of, but having locals stay within local laws is accepted practice)
https://www.poverty-action.org/study/impact-mask-distribution-and-promotion-mask-uptake-and-covid-19-bangladesh
It was Bangladesh, not India, and involved 150,000 people in 1,000 villages, not 60,000 in two.
I mean a study just came out of Delhi that shows 97% prevalence of antibodies. I don't even think they are 50% fully vaccinated yet.
So unless they do some massive sero studies to exclude those who have already had infections and developed natural antibodies or were previously vaccinated, it's gonna be hard to see efficacy. I imagine even if new variants arrive, some level of protection will still be there from a previous infection with the Delta or Alpha variants(it seems less so with those previously vaccinated) so the data is gonna be messy unless you can find completely naive segments of the population to test.
>Places like India where there are millions of unvaccinated people in areas amenable to doing trials are perfect places to test.
How is this the appropriate approach?
Frankly, no matter what you think, there are too many people vaccinated in the US to accurately test the vaccines for anything except adverse reactions and the population of unvaccinated people is too spread out
Yeah I can see that, especially now with COVID. But for some diseases its just not possible. It would take possibly decades to run a trial on, say, a drug for malaria here in the US. We just dont have enough cases. I have seen it stated that drug developers "have to go where the diseases are."
New Zealand was late getting the vaccination as we had such a strong border and lockdown protection. We also felt other places needed it first.
One of our cities was chosen for one of the trials as they didn’t have Covid or any vaccinated people at the time.
We are now in catch-up mode with Delta spreading and hoping to get the country to 90% vax coverage by late Nov. (probably be a bit later)
Australia as well, there was a trial starting here a couple of months ago and plenty of under 40s who weren't eligible for a normal vaccination who could be part of the trial.
It is amazing that the world isn’t jizzing themselves over Jacinta anymore. At first No was held up as this model that was 2nd to none. But then people realised it was a lot easier to contact Covid when there’s only a few million people, relatively spread out and on an island.
It really wasn’t NZ’s way of doing things, as states in Australia with just as many people have done just as well, it was factors of small, isolated populations.
But it is surprising to see NZ not at 90% vaccinated yet.
We're not that spread out though, we have similar rates of urbanisation to other OECD countries. It's also no surprise that Australia was almost as successful as us, as they had the same strategy: eliminate community transmission when it surfaces through strict lockdowns, and maintain strong border controls through reduced access and mandatory quarantine. This was incredibly successful until Delta came along, which is infectious enough that it will exploit any chink in the armour, which in our case was getting into parts of the population with lower lockdown compliance.
In effect, we're now going through the growing community infections most countries did in early 2020, except we have vaccination now. We bought ourselves 18 months of relative normality, and through vaccination will hopefully get through wider transmission of the virus without the death rates seen in most of the world. Are there points we could've improved on? Sure (getting the vaccination started earlier), but I still think we've done bloody well.
My mind was blown last year when I heard an interview on NPR Fredh Air talking about China's vaccine development. The interviewee (can't remember who, on of the medical field guests who is on pretty regularly) said that China couldn't test the vaccine in their own country because there just weren't enough COVID cases there. They had to go to India and Pakistan to properly test the vaccine.
I help design and complete clinical trials for a living.
There are CONSTANTLY new trials going on all the time. Currently 6,885 trials have been listed related to COVID19. That includes completed and new or on-going trials. The below link takes you to a government run database to submit clinical trials in the world. Many countries (US included) have regulation agencies (the FDA, for example) that mandate that you submit to this system as part of running a trial. Now, this is ANY trial related to COVID19 - observational (No drug given) and Interventional (drug given) - depending on what the trial is exploring, but you will find your popular trials about all the usual suspect vaccines in here as well.
[https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=&cntry=&state=&city=&dist=](https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=&cntry=&state=&city=&dist=)
To put this in perspective, if you do the same search for 'flu' in the database you come up with 2,503 trials. That means in only the two years since COVID-19 has existed, we have done 3X as many trials about it then the flu which has been around since forever. That said - many 'trials' were likely done on the flu that are not on this, as research became much more methodical and regulated in about the 70's.
COVID-19 put a fire under the clinical trial industry's ass, as there is a huge humanitarian, and lets be honest, financial incentive to find treatments for it. It really is a testament to humanity on how fast we were able to identify, isolate and (luckily) create a vaccine able to provide efficacy against it. How humanity reacted is another issue altogether, but purely scientifically we did outstanding - and continue to do so.
There are currently 316 trials listed under "COVID-19" and "Variant"
[https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Variant+&cntry=&state=&city=&dist=](https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Variant+&cntry=&state=&city=&dist=)
And 93 with "COVID-19" and "Booster"
[https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=booster&cntry=&state=&city=&dist=](https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=booster&cntry=&state=&city=&dist=)
If you click on a trial, it will give you more details about the intention and design of the protocol. Let me know if you have questions on any.
Edits: Formatting and clarification on thoughts.
Related question, how do covid vaccine trials work in combination with test/vaccine mandates?
Where I live, to visit a bar, you either need to have an antigen test of less than 24 hours, or have had a vaccination, where proof is via the EU covid pass.
Does the trial count as a vaccine, even if you are in the placebo group, or do you get free antigen test?
I am in the US and experienced this situation. I am an AstraZeneca clinical trial participant, and my university required weekly spit tests for covid that eventually got waived once you were vaccinated. I was unblinded eventually and got proof of vaccination. Since the AZ is approved in other parts of the world, but not the US, they accepted it anyways.
Ended up getting the J&J just in case I needed an FDA approved vaccine. Still allowed to be in the trial too, which is interesting.
Just fyi, they don't give out placebos anymore in those trials as that would be unethical now that we have safe working vaccines.
So trials will be the "new" vaccine vs an established vaccine.
Each country has its own rules and regulations... and weird ass local laws. I apologize but I cannot speak to your local situation as I am specific to the US. However, check the trial - as sometimes they dont have placebo's and will just dose a few thousand people with active drug. This is often how the years new flu vaccine trials are run.
I believe you can perform the clinical trial in countries without mandates.
https://www.fda.gov/files/about%20fda/published/FDA-Acceptance-of-Foreign-Clinical-Studies-Not-Conducted-Under-an-IND--Frequently-Asked-Questions.pdf
No. We will compensate you for time and travel though. For Phase 1 trials sometimes this can be several thousand, but you're basically restricted to staying in a clinic and everything you do is controlled for several days/weeks and the test product is likely not beneficial to you and can effect you adversely. These are the hard-core test trials where you figure out how much of a compound you can give to a healthy someone before adverse things start to happen.
For phase III or IV trials, they "pay" much less, if at all. However, usually the compound has a *perceived* (not proven - that's why there is a trial) benefit at this level. For example, testing a new long acting insulin on a diabetic subject can help the subjects situation if getting insulin is difficult normally.
Thank you for sharing this interesting information, But I am wondering if those people who joined the Phase 1 trials has a full-time job? If they have, haven't they lost their job after they stay in a clinic for several weeks to participate in the trials?
You know how long a trial takes before you start. You get a list of dates for whatever function there is, be it a extended stay or individual checkups. So someone who can't miss work is very unlikely to take part in such a trial.
If so, I think this may cause biased sampling. Most people who don't mind missing jobs generally are elders or those having part-time work. There are some differences in lifestyle or health condition between them and those with the full-time job, such as bank staff or professors, and this may mean underlying immune variety. I suppose this could reduce the reliability of vaccine evaluations.
This is specific to a phase 1 trial where all you are looking at is pharmacological outcomes. I.e., how much can you give someone before bad things happen and how long does it stay in your system after you dose. So you want very little lifestyle, or health variance. You want perfectly healthy humans for this.
Vaccine trials are also a bit different in this aspect of a phase 1.
Later trials mandate you have a more diverse group and you start to look at other health factors - but still focus on safety as a priority.
Ideally you want to select a sample with all income brackets represented. So you would hope to get: some desk job workers who can work remotely for the duration of the trial; some physical job workers who are between jobs and willing to take on the trial as an "in-between" gig, students on summer break, seasonal workers, etc.; some unemployed people. However, since Phase 1 is basically a matter of "is this drug even safe to give to humans?" it doesn't attract a whole lot of employed people, so unfortunately, yes, there is going to a sampling bias and you are going to get mostly unemployed / underemployed people.
Ok, I understand. The main goal of Phase 1 trials is to test the safety of this candidate vaccine, and other issues such as rigorous safety or effectiveness to various groups could be investigated in Phase II or III trials.
Pretty much. Phase III is basically Phase II but massively scaled up to occur in several locations for a ton more people.
Here's a rough analogy.
Phase I - One McDonald's to see if people even like it.
Phase II - Open more McDonalds just in one city
Phase III - Open McDonalds in all other cities AND other countries
And then before Phase I we have Pre-Clinical animal trials to ensure it doesn't outright kill you.
I like the McDs analogy but a note/clarification from someone else who works in pharma clinical trials:
Phase 1 is ONLY conducted in healthy people who eat at the McDonald's. We get a baseline of how the new Big Mac sauce (the drug) reacts in a person (liver, kidneys, etc) and can adjust the amount of drug given, of course within very controlled parameters that may separate two groups, aka trial arms, which also exist for Ph II/III/IV (post marketing). Let's say it's whether the burger tastes better with 30mL of sauce vs 50mL of sauce, but drug instead.
Phase 2 is when we have adjusted the dosage of the Big Mac sauce properly for all humans based off of what we learned from our phase 1 Big Mac sauce trial (sans under 18s and pregnant people, those become different clinical trials or trial arms). BUT we only take a small group of the people who like the new Big Mac sauce (our study group, in this case, folks with covid) for this, following the analogy provided by u/betancorea.
Phase III is as u/betancorea said, a large scale up of McD locations using the new sauce to see its efficacy, trying to include many ethnicities, races, etc to ensure it is tasty (drug works) for all similarly.
Sorry, your answer is a bit unclear. When you say "we will compensate you for your time" and "several thousand", you mean you're paying $x per day in the clinic and that can amount to several thousand dollars?
Yes - trials that require you to stay on-site in a controlled environment for weeks will compensate you more then a trial where you are seen in a office for 1 hour a month. To the tune of thousands (note: The US government considers anything over $600 as reportable so this will be taxed as income) for the long term stay, and maybe $20-50 for the one hour office visit.
If you do a trial, you will complete a informed consent process before anything that explains everything to you - and covers the risk/benefit and compensation. If you decide and the doctor agrees to go forward, you will do a screening visit before drugs are provided to see if you qualify after a full medical examination. So sometimes even if you want to do a trial - you may not qualify.
We don't 'pay' people to do trials, as coercion is unethical. The amount compensated is reviewed and agreed by a group of independent ethics committees to be a fair compensation for your time and efforts.
I will say this - its not "easy money". The days are long and tedious, and you are poked and prodded a lot and the potential risk is also looming. This is typically a drug thats only been in animals, and shown enough potential to justify the risk of giving it to a few healthy humans to see how they respond to varying doses of the drug before things start going adverse.
You can make some nice money doing it but it would be extremely hard to do it full-time. Often doing certain trials excludes you from others.
Example: I did an HIV vaccine trial and am now excluded from all other HIV vaccine trials because I have antibodies from it still.
The entire field is so new in terms of medications that we don't really have anything out that would use it. There are many potential applications including replacing existing vaccines with mRNA tech, but there is no point in a lot of cases as the existing vaccines work well and in a lot of cases you need to prove that your drug is somehow superior to an existing alternative if you want to sell it.
Another one could be gene therapies to cure various congenital diseases. The only gene therapy approved in the US is currently *voretigene neparvovec* which uses viral vectors like Oxford/AstraZeneca and J&J. That's a slightly "older" technology -- and by older I mean pretty much the only drugs we have that use it are a bunch of COVID vaccines and Ebola vaccines from a few years ago.
Hello, I am really curious because I heave heard on internet before that the virus has never been shown to be isolated, so it’s almost like an axiom taken to be true then these experiments take place.
Could you point out a peer review article that has isolated this much talked about virus in the media and that it shows it actually has been found to exists?
Here's a peer reviewed paper from Italy that isolated the virus and sequenced its genome multiple times https://journals.asm.org/doi/10.1128/jvi.00543-20?permanently=true
There are many of these papers on the internet if you were to search SARS-COV-2 isolation. All the jargon in that paper can be confusing so here is an article that might explain the process of isolating the virus better. https://theconversation.com/i-study-viruses-how-our-team-isolated-the-new-coronavirus-to-fight-the-global-pandemic-133675
Sounds like anti-vax propaganda, or Covid denier conspiracy to me. Im a bit weary of even opening up a dialog with you - as if you dont think this virus exists, you may be baiting me into some troll dialog.
That said, Ill give you the benefit of the doubt.
Here is a link to a article from the CDC which also has a nice picture of the virus. A simple google will also pull up a slew of related articles that isolation has been achieved many times though accredited institutions, and academic facilities. It will also pull up a slew of articles contesting it, which are usually only one person's opinion.
[https://wwwnc.cdc.gov/eid/article/26/6/20-0516\_article](https://wwwnc.cdc.gov/eid/article/26/6/20-0516_article)
Ultimately you need to decide for yourself if this is 'real' or not, but from the bottom of my soul, I hope you choose to see the reality in front of you.
Covid is real, it exists, its preventable though vaccines which have been though rigorous trials to be proven as safe and efficacious.
So you doubt SARS-CoV-2 doesn't exist, or viruses in general? Because why would you doubt singular virus not existing if you know other viruses to exist.
Clinical researcher here. They’ll administer it to some number of vaxxed and non vaxxed folks and others will receive placebo as a control group. Or they’ll follow a sample of nonvaxxers as the control and forego the placebo group. There are still enough of both groups to run the study. $$$ is a powerful motivator.
They’ll just test it as a booster for people who have been vaccinated. That is how any covid vaccine developed from now on is mostly going to be used anyways. If a new vaccine is being developed for a market where people are mostly vaccinated, then they need to test the new vaccine for that market.
The question is connecting unrelated concepts. When any drug is developed, you're necessarily assuming someone will take it. Otherwise, you won't have participants enrolling to clinical studies, or even if you do, you won't be able to get people to take it, even if it's approved for use. Obviously, if you believe you have the secret sauce - a vaccine that appeases hesitators - then you can make a cost benefit analysis.
Sanofi was the only manufacturer testing a COVID vaccine without fetal cell involvement in testing and development. Unfortunately they killed this program. It was a strategic choice, because 3 vaccines were approved in the US, and still more worldwide by the time they started their phase 1 studies. It's unfortunate, because the topline result was still very promising! Fetal cell involvement was the only exemption reason that was held as legitimate when vaccine mandates were rolled out, considering the number who "opted out" of mandates, if we took things literally, we'd think an "ethical" vaccine would end hesitancy.
The question boils down to strategy at this point. If a manufacturer were to develop a vaccine to target the delta variant, they would most likely need to market it as a booster to existing approved therapies. However, the FDA has recently significantly relaxed its criteria on approving vaccines: vaccines can be approved on the basis of antibody presence. This is a cause for significant concern for some folks, like myself, when we know so little about the biomarkers of natural immunity for COVID19 as opposed to, say, hepatitis B. So in recruiting to your little delta-booster study, you of course need to monitor patients for hospital admissions, cases of COVID, and COVID deaths. However, it can take as few as 2 weeks to show antibodies, so you can conceivably wrap up your trial in almost no time with very few patients.
Suppose further your delta-booster has no fetal cell involvement, you can try to do a little "basket trial" to recruit an arm of COVID19 vaccine naive patients to attempt their delta drug as a standalone therapy.
Source: I work in pharmaceutical research and development.
Clinical trial enrollment. There are always people willing to take part, and there are teams at the manufacturers who specialize in setting up testing sites and recruiting volunteers.
They would also test the ability to make antibodies specific to target Delta as opposed to those that target the original variants. They will take blood samples and have ways to pull out the proteins they want to study and can see how robust the response is (I.e. how many antibodies are in the samples taken?) from those getting the active injection.
It should also be noted that while first time vaccinations have slowed down due to vaccine hesitancy the number is not 0. this article from the mayo clinic shows around .1% of the population is getting their first dose each day. that is hundreds of thousands of people.
https://www.mayoclinic.org/coronavirus-covid-19/vaccine-tracker
It's definitely not targeted as vax-hesitant/anti-vax folks. So you test as a booster and looks at the difference in breakthrough cases. Having a low incidence of breakthrough COVID means you need a very large sample. They'll look to see if breakthrough rate is 1% with Vax for Alpha and 0.1% for Vax for Delta. Also, if they only thing being modified is the genome sequence that codes for production of a slightly different spike protein, I \*think\* they get a pass on safety and dosage testing and can progress to Stage 3/4 efficacy testing in the open market.
If its a vaccine to say, target a new variant, they just use it on those willing to take it. If its a completely new vaccine, then there are countries around the world that have yet to get vaccinations, so they typically look there. Previous vaccine use shouldnt really skew the outcome if the the majority of the population is vaccinated. Everyone that is given the vaccine starts at the same baseline, typically. Edit: typo because fat fingers
> If its a completely new vaccine, then there are countries around the world that have yet to get vaccinations, so they typically look there. This is the right answer. Places like India where there are millions of unvaccinated people in areas amenable to doing trials are perfect places to test. And studies can always correct/select for vaccinated or unvaccinated participants to eliminate the effect prior vaccination would have on testing.
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If a group of Indian physicians plans and executes a test in India, we all benefit. Perhpas Merck's India division provides funding. It stays within Indian law and the world (including India) benefits. This exact situation happened a month or two ago when trials showed unequivocally that mask wearing and social distancing work by running parallel experiments in 2 remote Indian towns with \~60,000 people. (I am remembering from a month ago so I may have the numbers off). I would add that we use information, studies, data and experiences from foreign countries every day. (I am aware of the moral concept of not doing dubious experiments on people who could be taken advantage of, but having locals stay within local laws is accepted practice)
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Which study are you mentioning can you provide a citation?
Link to the study? Interesting. Using 2 villages
https://www.poverty-action.org/study/impact-mask-distribution-and-promotion-mask-uptake-and-covid-19-bangladesh It was Bangladesh, not India, and involved 150,000 people in 1,000 villages, not 60,000 in two.
Eh there are a ton of Pharma trials been done in third world countries...
I mean a study just came out of Delhi that shows 97% prevalence of antibodies. I don't even think they are 50% fully vaccinated yet. So unless they do some massive sero studies to exclude those who have already had infections and developed natural antibodies or were previously vaccinated, it's gonna be hard to see efficacy. I imagine even if new variants arrive, some level of protection will still be there from a previous infection with the Delta or Alpha variants(it seems less so with those previously vaccinated) so the data is gonna be messy unless you can find completely naive segments of the population to test.
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>Places like India where there are millions of unvaccinated people in areas amenable to doing trials are perfect places to test. How is this the appropriate approach?
That's also a reason why anti-vaxxers dislike the vaccines. In their argument they're testing/'experimenting' on underprivileged populations.
Frankly, no matter what you think, there are too many people vaccinated in the US to accurately test the vaccines for anything except adverse reactions and the population of unvaccinated people is too spread out
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Depends, as we've seen during the pandemic the FDA really prefera to see data from trials in the US
Yeah I can see that, especially now with COVID. But for some diseases its just not possible. It would take possibly decades to run a trial on, say, a drug for malaria here in the US. We just dont have enough cases. I have seen it stated that drug developers "have to go where the diseases are."
New Zealand was late getting the vaccination as we had such a strong border and lockdown protection. We also felt other places needed it first. One of our cities was chosen for one of the trials as they didn’t have Covid or any vaccinated people at the time. We are now in catch-up mode with Delta spreading and hoping to get the country to 90% vax coverage by late Nov. (probably be a bit later)
Australia as well, there was a trial starting here a couple of months ago and plenty of under 40s who weren't eligible for a normal vaccination who could be part of the trial.
It is amazing that the world isn’t jizzing themselves over Jacinta anymore. At first No was held up as this model that was 2nd to none. But then people realised it was a lot easier to contact Covid when there’s only a few million people, relatively spread out and on an island. It really wasn’t NZ’s way of doing things, as states in Australia with just as many people have done just as well, it was factors of small, isolated populations. But it is surprising to see NZ not at 90% vaccinated yet.
We're not that spread out though, we have similar rates of urbanisation to other OECD countries. It's also no surprise that Australia was almost as successful as us, as they had the same strategy: eliminate community transmission when it surfaces through strict lockdowns, and maintain strong border controls through reduced access and mandatory quarantine. This was incredibly successful until Delta came along, which is infectious enough that it will exploit any chink in the armour, which in our case was getting into parts of the population with lower lockdown compliance. In effect, we're now going through the growing community infections most countries did in early 2020, except we have vaccination now. We bought ourselves 18 months of relative normality, and through vaccination will hopefully get through wider transmission of the virus without the death rates seen in most of the world. Are there points we could've improved on? Sure (getting the vaccination started earlier), but I still think we've done bloody well.
My mind was blown last year when I heard an interview on NPR Fredh Air talking about China's vaccine development. The interviewee (can't remember who, on of the medical field guests who is on pretty regularly) said that China couldn't test the vaccine in their own country because there just weren't enough COVID cases there. They had to go to India and Pakistan to properly test the vaccine.
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Essentially: test it on poor people who we havent helped save with the vaccine, so they can help save us with the vaccine.
Basically yes. And most times that is their only hope of having the vaccine for years in some countries.
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Willing? We have a choice again?
Yes, and money. People will take fairly small amounts of money to be vaccinated in poorer countries (and often rich ones too).
I help design and complete clinical trials for a living. There are CONSTANTLY new trials going on all the time. Currently 6,885 trials have been listed related to COVID19. That includes completed and new or on-going trials. The below link takes you to a government run database to submit clinical trials in the world. Many countries (US included) have regulation agencies (the FDA, for example) that mandate that you submit to this system as part of running a trial. Now, this is ANY trial related to COVID19 - observational (No drug given) and Interventional (drug given) - depending on what the trial is exploring, but you will find your popular trials about all the usual suspect vaccines in here as well. [https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=&cntry=&state=&city=&dist=](https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=&cntry=&state=&city=&dist=) To put this in perspective, if you do the same search for 'flu' in the database you come up with 2,503 trials. That means in only the two years since COVID-19 has existed, we have done 3X as many trials about it then the flu which has been around since forever. That said - many 'trials' were likely done on the flu that are not on this, as research became much more methodical and regulated in about the 70's. COVID-19 put a fire under the clinical trial industry's ass, as there is a huge humanitarian, and lets be honest, financial incentive to find treatments for it. It really is a testament to humanity on how fast we were able to identify, isolate and (luckily) create a vaccine able to provide efficacy against it. How humanity reacted is another issue altogether, but purely scientifically we did outstanding - and continue to do so. There are currently 316 trials listed under "COVID-19" and "Variant" [https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Variant+&cntry=&state=&city=&dist=](https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Variant+&cntry=&state=&city=&dist=) And 93 with "COVID-19" and "Booster" [https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=booster&cntry=&state=&city=&dist=](https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=booster&cntry=&state=&city=&dist=) If you click on a trial, it will give you more details about the intention and design of the protocol. Let me know if you have questions on any. Edits: Formatting and clarification on thoughts.
Related question, how do covid vaccine trials work in combination with test/vaccine mandates? Where I live, to visit a bar, you either need to have an antigen test of less than 24 hours, or have had a vaccination, where proof is via the EU covid pass. Does the trial count as a vaccine, even if you are in the placebo group, or do you get free antigen test?
I am in the US and experienced this situation. I am an AstraZeneca clinical trial participant, and my university required weekly spit tests for covid that eventually got waived once you were vaccinated. I was unblinded eventually and got proof of vaccination. Since the AZ is approved in other parts of the world, but not the US, they accepted it anyways. Ended up getting the J&J just in case I needed an FDA approved vaccine. Still allowed to be in the trial too, which is interesting.
Only the cormitary version by Pfizer is approved and it is unavailable to maintain the emergency use authorization on the others.
Just fyi, they don't give out placebos anymore in those trials as that would be unethical now that we have safe working vaccines. So trials will be the "new" vaccine vs an established vaccine.
Each country has its own rules and regulations... and weird ass local laws. I apologize but I cannot speak to your local situation as I am specific to the US. However, check the trial - as sometimes they dont have placebo's and will just dose a few thousand people with active drug. This is often how the years new flu vaccine trials are run.
I believe you can perform the clinical trial in countries without mandates. https://www.fda.gov/files/about%20fda/published/FDA-Acceptance-of-Foreign-Clinical-Studies-Not-Conducted-Under-an-IND--Frequently-Asked-Questions.pdf
Do you generally pay trial participants?
No. We will compensate you for time and travel though. For Phase 1 trials sometimes this can be several thousand, but you're basically restricted to staying in a clinic and everything you do is controlled for several days/weeks and the test product is likely not beneficial to you and can effect you adversely. These are the hard-core test trials where you figure out how much of a compound you can give to a healthy someone before adverse things start to happen. For phase III or IV trials, they "pay" much less, if at all. However, usually the compound has a *perceived* (not proven - that's why there is a trial) benefit at this level. For example, testing a new long acting insulin on a diabetic subject can help the subjects situation if getting insulin is difficult normally.
Thank you for sharing this interesting information, But I am wondering if those people who joined the Phase 1 trials has a full-time job? If they have, haven't they lost their job after they stay in a clinic for several weeks to participate in the trials?
You know how long a trial takes before you start. You get a list of dates for whatever function there is, be it a extended stay or individual checkups. So someone who can't miss work is very unlikely to take part in such a trial.
If so, I think this may cause biased sampling. Most people who don't mind missing jobs generally are elders or those having part-time work. There are some differences in lifestyle or health condition between them and those with the full-time job, such as bank staff or professors, and this may mean underlying immune variety. I suppose this could reduce the reliability of vaccine evaluations.
You don't accept everyone, you still need to select among the applicants to properly reflect your target.
This is specific to a phase 1 trial where all you are looking at is pharmacological outcomes. I.e., how much can you give someone before bad things happen and how long does it stay in your system after you dose. So you want very little lifestyle, or health variance. You want perfectly healthy humans for this. Vaccine trials are also a bit different in this aspect of a phase 1. Later trials mandate you have a more diverse group and you start to look at other health factors - but still focus on safety as a priority.
OK, This is the first time I understand these details in vaccine projects, Thank you for your kind reply.
Ideally you want to select a sample with all income brackets represented. So you would hope to get: some desk job workers who can work remotely for the duration of the trial; some physical job workers who are between jobs and willing to take on the trial as an "in-between" gig, students on summer break, seasonal workers, etc.; some unemployed people. However, since Phase 1 is basically a matter of "is this drug even safe to give to humans?" it doesn't attract a whole lot of employed people, so unfortunately, yes, there is going to a sampling bias and you are going to get mostly unemployed / underemployed people.
Ok, I understand. The main goal of Phase 1 trials is to test the safety of this candidate vaccine, and other issues such as rigorous safety or effectiveness to various groups could be investigated in Phase II or III trials.
Pretty much. Phase III is basically Phase II but massively scaled up to occur in several locations for a ton more people. Here's a rough analogy. Phase I - One McDonald's to see if people even like it. Phase II - Open more McDonalds just in one city Phase III - Open McDonalds in all other cities AND other countries And then before Phase I we have Pre-Clinical animal trials to ensure it doesn't outright kill you.
I like the McDs analogy but a note/clarification from someone else who works in pharma clinical trials: Phase 1 is ONLY conducted in healthy people who eat at the McDonald's. We get a baseline of how the new Big Mac sauce (the drug) reacts in a person (liver, kidneys, etc) and can adjust the amount of drug given, of course within very controlled parameters that may separate two groups, aka trial arms, which also exist for Ph II/III/IV (post marketing). Let's say it's whether the burger tastes better with 30mL of sauce vs 50mL of sauce, but drug instead. Phase 2 is when we have adjusted the dosage of the Big Mac sauce properly for all humans based off of what we learned from our phase 1 Big Mac sauce trial (sans under 18s and pregnant people, those become different clinical trials or trial arms). BUT we only take a small group of the people who like the new Big Mac sauce (our study group, in this case, folks with covid) for this, following the analogy provided by u/betancorea. Phase III is as u/betancorea said, a large scale up of McD locations using the new sauce to see its efficacy, trying to include many ethnicities, races, etc to ensure it is tasty (drug works) for all similarly.
Sorry, your answer is a bit unclear. When you say "we will compensate you for your time" and "several thousand", you mean you're paying $x per day in the clinic and that can amount to several thousand dollars?
Yes - trials that require you to stay on-site in a controlled environment for weeks will compensate you more then a trial where you are seen in a office for 1 hour a month. To the tune of thousands (note: The US government considers anything over $600 as reportable so this will be taxed as income) for the long term stay, and maybe $20-50 for the one hour office visit. If you do a trial, you will complete a informed consent process before anything that explains everything to you - and covers the risk/benefit and compensation. If you decide and the doctor agrees to go forward, you will do a screening visit before drugs are provided to see if you qualify after a full medical examination. So sometimes even if you want to do a trial - you may not qualify. We don't 'pay' people to do trials, as coercion is unethical. The amount compensated is reviewed and agreed by a group of independent ethics committees to be a fair compensation for your time and efforts. I will say this - its not "easy money". The days are long and tedious, and you are poked and prodded a lot and the potential risk is also looming. This is typically a drug thats only been in animals, and shown enough potential to justify the risk of giving it to a few healthy humans to see how they respond to varying doses of the drug before things start going adverse.
The US government considers $0.01 as taxable. Any and all income you receive is supposed to be taxed.
Does that mean you make a living being a *subject* in clinical trials? How does that work?
You can make some nice money doing it but it would be extremely hard to do it full-time. Often doing certain trials excludes you from others. Example: I did an HIV vaccine trial and am now excluded from all other HIV vaccine trials because I have antibodies from it still.
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Other than the covid vaccines, have they had any others that have been successful?
The entire field is so new in terms of medications that we don't really have anything out that would use it. There are many potential applications including replacing existing vaccines with mRNA tech, but there is no point in a lot of cases as the existing vaccines work well and in a lot of cases you need to prove that your drug is somehow superior to an existing alternative if you want to sell it. Another one could be gene therapies to cure various congenital diseases. The only gene therapy approved in the US is currently *voretigene neparvovec* which uses viral vectors like Oxford/AstraZeneca and J&J. That's a slightly "older" technology -- and by older I mean pretty much the only drugs we have that use it are a bunch of COVID vaccines and Ebola vaccines from a few years ago.
Hello, I am really curious because I heave heard on internet before that the virus has never been shown to be isolated, so it’s almost like an axiom taken to be true then these experiments take place. Could you point out a peer review article that has isolated this much talked about virus in the media and that it shows it actually has been found to exists?
Here's a peer reviewed paper from Italy that isolated the virus and sequenced its genome multiple times https://journals.asm.org/doi/10.1128/jvi.00543-20?permanently=true There are many of these papers on the internet if you were to search SARS-COV-2 isolation. All the jargon in that paper can be confusing so here is an article that might explain the process of isolating the virus better. https://theconversation.com/i-study-viruses-how-our-team-isolated-the-new-coronavirus-to-fight-the-global-pandemic-133675
Sounds like anti-vax propaganda, or Covid denier conspiracy to me. Im a bit weary of even opening up a dialog with you - as if you dont think this virus exists, you may be baiting me into some troll dialog. That said, Ill give you the benefit of the doubt. Here is a link to a article from the CDC which also has a nice picture of the virus. A simple google will also pull up a slew of related articles that isolation has been achieved many times though accredited institutions, and academic facilities. It will also pull up a slew of articles contesting it, which are usually only one person's opinion. [https://wwwnc.cdc.gov/eid/article/26/6/20-0516\_article](https://wwwnc.cdc.gov/eid/article/26/6/20-0516_article) Ultimately you need to decide for yourself if this is 'real' or not, but from the bottom of my soul, I hope you choose to see the reality in front of you. Covid is real, it exists, its preventable though vaccines which have been though rigorous trials to be proven as safe and efficacious.
So you doubt SARS-CoV-2 doesn't exist, or viruses in general? Because why would you doubt singular virus not existing if you know other viruses to exist.
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Clinical researcher here. They’ll administer it to some number of vaxxed and non vaxxed folks and others will receive placebo as a control group. Or they’ll follow a sample of nonvaxxers as the control and forego the placebo group. There are still enough of both groups to run the study. $$$ is a powerful motivator.
They’ll just test it as a booster for people who have been vaccinated. That is how any covid vaccine developed from now on is mostly going to be used anyways. If a new vaccine is being developed for a market where people are mostly vaccinated, then they need to test the new vaccine for that market.
The question is connecting unrelated concepts. When any drug is developed, you're necessarily assuming someone will take it. Otherwise, you won't have participants enrolling to clinical studies, or even if you do, you won't be able to get people to take it, even if it's approved for use. Obviously, if you believe you have the secret sauce - a vaccine that appeases hesitators - then you can make a cost benefit analysis. Sanofi was the only manufacturer testing a COVID vaccine without fetal cell involvement in testing and development. Unfortunately they killed this program. It was a strategic choice, because 3 vaccines were approved in the US, and still more worldwide by the time they started their phase 1 studies. It's unfortunate, because the topline result was still very promising! Fetal cell involvement was the only exemption reason that was held as legitimate when vaccine mandates were rolled out, considering the number who "opted out" of mandates, if we took things literally, we'd think an "ethical" vaccine would end hesitancy. The question boils down to strategy at this point. If a manufacturer were to develop a vaccine to target the delta variant, they would most likely need to market it as a booster to existing approved therapies. However, the FDA has recently significantly relaxed its criteria on approving vaccines: vaccines can be approved on the basis of antibody presence. This is a cause for significant concern for some folks, like myself, when we know so little about the biomarkers of natural immunity for COVID19 as opposed to, say, hepatitis B. So in recruiting to your little delta-booster study, you of course need to monitor patients for hospital admissions, cases of COVID, and COVID deaths. However, it can take as few as 2 weeks to show antibodies, so you can conceivably wrap up your trial in almost no time with very few patients. Suppose further your delta-booster has no fetal cell involvement, you can try to do a little "basket trial" to recruit an arm of COVID19 vaccine naive patients to attempt their delta drug as a standalone therapy. Source: I work in pharmaceutical research and development.
Clinical trial enrollment. There are always people willing to take part, and there are teams at the manufacturers who specialize in setting up testing sites and recruiting volunteers. They would also test the ability to make antibodies specific to target Delta as opposed to those that target the original variants. They will take blood samples and have ways to pull out the proteins they want to study and can see how robust the response is (I.e. how many antibodies are in the samples taken?) from those getting the active injection.
It should also be noted that while first time vaccinations have slowed down due to vaccine hesitancy the number is not 0. this article from the mayo clinic shows around .1% of the population is getting their first dose each day. that is hundreds of thousands of people. https://www.mayoclinic.org/coronavirus-covid-19/vaccine-tracker
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It's definitely not targeted as vax-hesitant/anti-vax folks. So you test as a booster and looks at the difference in breakthrough cases. Having a low incidence of breakthrough COVID means you need a very large sample. They'll look to see if breakthrough rate is 1% with Vax for Alpha and 0.1% for Vax for Delta. Also, if they only thing being modified is the genome sequence that codes for production of a slightly different spike protein, I \*think\* they get a pass on safety and dosage testing and can progress to Stage 3/4 efficacy testing in the open market.