Matt, would you be open to having someone who takes the other side of this debate, or is at least more concerned about the risks of rushing a vaccine that doesn’t work or hurts people, give their side of the story? I’m not able to evaluate this argument, and I bet most of your readers are in the same boat. I can identify concerns - I mean, this is a developer saying he knows about this *amazing* technology, and why isn’t everyone getting out of the way to let it come to market. That take has earned at least as much suspicion as government regulators, especially in the health area (Theranos, anyone?)
What would be especially helpful is to get beyond directional arguments (faster! slower!) to get a better sense of the specific requirements that take a lot of time and what’s the risk of not running them. E.g., he complains about having to run animal trials. How much time is involved, and what’s the risk in running them concurrently instead of in series? Can we focus on some big-ticket items to evaluate the debate? If it really is about death by 1000 cuts, ok, let’s still engage on that: where is the obstacle?
One perspective taking measure: for all the complaints about FDA, didn’t the US have the vaccine broadly available earlier than any other country? It’s not as though there is another paragon country out there we are lagging, is there? Or if there is it would be good to know.
It's interesting that there's basically no constituency for this. People on the right largely never thought covid was a big deal, so them taking action now all of a sudden won't happen, and people on the left seem very hesitant to criticize the FDA or the public health establishment, so they're not going to support reform if they won't admit reform is even needed.
So we're just left with bad policy. It's unfortunate.
"Virtually everyone knows plenty of people who contracted COVID after being vaccinated and were out of commission for a week or more." Having just had COVID after being vaccinated and boosted, while getting sick wasn't super fun, easily the worst part was being essentially unable to work and being trapped in the house for *weeks* as COVID moved through our family and we desperately waited daycare's required quarantine to end, even though the kids are fully vaccinated and were symptom free shortly after testing positive. I think encouraging liberalizing daycare COVID restrictions will be very popular in a couple of months after all the little kids have had an opportunity to be vaccinated.
The majority of my career was in the biopharma industry doing drug regulatory affairs and safety. Mr. Collinson's column while interesting needs to be put into perspective. One major hurdle for vaccines is doing the necessary safety studies to demonstrate that the benefits outweigh risks. Lots of the side effects seen with vaccines are small, if present at all, and on the order of 1 in 10,000 or less. You cannot pick up these in a normal clinical trial of 3000 patients. This necessitates that vaccine trials be done on a far larger cohort and is one reason the FDA is more conservative than looking at a new cancer drug.
Vaccine manufacturing is not trivial. Vaccines are sterile products made under exacting conditions. However, one the process is validated, it is possible to make changes in the vaccine to adopt to new variants. This is why we are able to get new seasonal influenza vaccines each year. Public health authorities and the vaccine industry agree upon the circulating flu viruses and change the production strain. Major regulatory filings and review are not required. We are seeing this approach being applied by both manufacturers of mRNA vaccines right now. A similar approach can be taken by companies who are close to approval of adjuvant/protein vaccines.
During the first year of the pandemic, I put out a daily newsletter for former industry colleagues and friends surveying the research that was being done. I stopped once the first vaccines became available. I looked closely at vaccine development and saw a lot of interesting work going on. Some of the projects are still going on. Canada has licensed a tobacco produced protein vaccine and the ferritin nano particle vaccine developed by Walter Reed is in clinical trials right now:. Volunteers are still being sought to finish up the Phase 1 trial: https://www.wrair.army.mil/node/645
Nasal vaccines have been used in the past with varying degrees of success. A commercial influenza vaccine has been around since 2003 but is not recommended for those > 50 years of age. There is also a bacterial delivery system that will get Covid antigen to the gastric mucosal system.
A number of vaccine approaches were under development several years ago when Zika virus was thought to pose a major public health problem When the virus disappeared these projects were shelved and a major opportunity to test vaccine platforms for the development of neutralizing antibodies was lost. Had such work continued it might have provided valuable information that could have helped out Covid vaccine developers.
There are a number of other issues that can be discussed but I'll stop with these. Intrepid uses of google can find the archive of my Covid-19 newsletter fairly easily.
Logistical roadblocks should be fixed. There's no reason that studies should be delayed by monkeys being stuck at customs or supply chain issues with adjuvants.
But when it comes to lowering the barrier for starting human trials, I'd want to see some concrete scientific and bioethical basis for this change of procedure. I understand we all want faster role out of therapeutics! But each decision is a cost/benefit problem, and the costs of a harmful or ineffective therapeutic, especially one widely administered to healthy people, being released is potentially very high.
Are nanoparticle-based vaccines safe though? I've seen a lot of hype around nanoparticle delivery for a number of drug classes (with good reason!) but there are serious questions about how the body clears them. Which again, is why we run large clinical trials in the first place, to tease out these effects before they're shown to be harmful.
A proper universal vaccine would likely need to deliver sterilizing immunity. If it does not the nexus of diffusion rate and selective pressure may drive a dangerous mutation.
A few bigger themes remain:
1) COVID is a vascular disease. Just as HIV research in the 80s gave us Immunotherapy for cancer, so will COVID vaccines unlock tools that curtail inflammation. COVIDs vascular behavior will help expose the tricks we need. CVD, T2D and Alzheimers are mostly inflammatory diseases. T2D is a pandemic much larger than COVID.
2) We should figure out how to do challenge studies. The issue is ethics. Medical community sees them as unethical. Losing 24k people a day waiting for RCT trial seems unethical to me. Especially since the RCT of 40k is just a stochastic way to find the 2000 people you would use in a challenge study.
3) Unlocking Biobank data: we have 100 years of biobank data. Biological samples locked up in universities. Data from failed trials. We learn more from failure than success, but access to this biobank data is limited. A breakthrough in HIV came when a WashU doctor recalled a 14 year old boy who presented with AIDS like symptoms in 1962. They found his blood sample and confirmed HIV.
4) We should be able to build MRNA platform technology, or nanoparticle, as a foundation for annual vaccine derivatives. Validate the platform, with broader longitudinal RCT. Then insert annualized active entity tested with challenge study. This is basically how we build annual flu vaccine.
5) Allow people to "Donate their data to science" while alive. Build a database of longitudinal (Phenotypical, meta, and specific assays). Use as foundation for digital twin/synthetic control arms.
What are the political action items? Is there a bill to ask my representatives to support? Are we calling for new leadership in the FDA? If so, who is the scapegoat? Compared to what happened to banks in 2009, the response on institutional COVID failures has been pathetic.
Correcting a lot of the federal administrative and bureaucractic dysfunction (and general gov't competence) really needs to be an electoral issue.
Perception of inefficiency/incompetence is probably to blame with a decent amount of the default/knee-jerk resistance to more and bigger government. (The dedicated small government types won't care, but the vast squishy middle could be persuaded)
Because bureaucracy is super resistant to change and risk, executive action alone can only do so much, and making a real impact is probably going to require a fight and the expenditure of political capital.
But long-term I think it will be a clear net positive for the party that actually wants the government to...you know...do stuff.
I'm relatively young (under 40), healthy and I've been vax + boosted. However, I got covid a few months ago and it took me out HARD for over a week. I had a high fever, cough, head fog and waves of nausea that made it difficult to do anything. I personally would be fine with challenge trials or almost anything to speed up the process, as long as we are sufficiently warned of the risks and can make informed decisions.
It's probably not terribly important to the main thrust of the article, but where is the 380 deaths per day figure coming from? I'm seeing under 300, currently, and that number being below 400 since April.
I'm interested, but is the median American? What do we understand about reinfection? Seems like bundling with yearly flu shot is best hope. I also think we could pay people to take it. I do not understand why so many incentives were left on the table the last time.
Great post. One thought about getting things done faster is that it doesn’t quite make sense to drive this research exclusively through academic labs. As with OWS, it would likely be faster to work with biotech/pharma companies or to arrange partnerships between academic and industry groups where it makes sense. I’ve worked in both worlds, and academics just really aren’t set up to do translational research in the same way that companies are (e.g. navigating the red-tape that the author provides several examples of). For a grant-making institution, it of course makes sense to work with academics, but to drive things across the finish line, I think it’s reasonable to bring in industry as well. Again this is a role government can/should be playing.
Kuddos to Matt for loaning his microphone to a subject matter expert whose ideas will benefit from a broader audience. Thumbs down to the Biden administration for administrative lethargy.
Matt, would you be open to having someone who takes the other side of this debate, or is at least more concerned about the risks of rushing a vaccine that doesn’t work or hurts people, give their side of the story? I’m not able to evaluate this argument, and I bet most of your readers are in the same boat. I can identify concerns - I mean, this is a developer saying he knows about this *amazing* technology, and why isn’t everyone getting out of the way to let it come to market. That take has earned at least as much suspicion as government regulators, especially in the health area (Theranos, anyone?)
What would be especially helpful is to get beyond directional arguments (faster! slower!) to get a better sense of the specific requirements that take a lot of time and what’s the risk of not running them. E.g., he complains about having to run animal trials. How much time is involved, and what’s the risk in running them concurrently instead of in series? Can we focus on some big-ticket items to evaluate the debate? If it really is about death by 1000 cuts, ok, let’s still engage on that: where is the obstacle?
One perspective taking measure: for all the complaints about FDA, didn’t the US have the vaccine broadly available earlier than any other country? It’s not as though there is another paragon country out there we are lagging, is there? Or if there is it would be good to know.
It's interesting that there's basically no constituency for this. People on the right largely never thought covid was a big deal, so them taking action now all of a sudden won't happen, and people on the left seem very hesitant to criticize the FDA or the public health establishment, so they're not going to support reform if they won't admit reform is even needed.
So we're just left with bad policy. It's unfortunate.
"Virtually everyone knows plenty of people who contracted COVID after being vaccinated and were out of commission for a week or more." Having just had COVID after being vaccinated and boosted, while getting sick wasn't super fun, easily the worst part was being essentially unable to work and being trapped in the house for *weeks* as COVID moved through our family and we desperately waited daycare's required quarantine to end, even though the kids are fully vaccinated and were symptom free shortly after testing positive. I think encouraging liberalizing daycare COVID restrictions will be very popular in a couple of months after all the little kids have had an opportunity to be vaccinated.
The majority of my career was in the biopharma industry doing drug regulatory affairs and safety. Mr. Collinson's column while interesting needs to be put into perspective. One major hurdle for vaccines is doing the necessary safety studies to demonstrate that the benefits outweigh risks. Lots of the side effects seen with vaccines are small, if present at all, and on the order of 1 in 10,000 or less. You cannot pick up these in a normal clinical trial of 3000 patients. This necessitates that vaccine trials be done on a far larger cohort and is one reason the FDA is more conservative than looking at a new cancer drug.
Vaccine manufacturing is not trivial. Vaccines are sterile products made under exacting conditions. However, one the process is validated, it is possible to make changes in the vaccine to adopt to new variants. This is why we are able to get new seasonal influenza vaccines each year. Public health authorities and the vaccine industry agree upon the circulating flu viruses and change the production strain. Major regulatory filings and review are not required. We are seeing this approach being applied by both manufacturers of mRNA vaccines right now. A similar approach can be taken by companies who are close to approval of adjuvant/protein vaccines.
During the first year of the pandemic, I put out a daily newsletter for former industry colleagues and friends surveying the research that was being done. I stopped once the first vaccines became available. I looked closely at vaccine development and saw a lot of interesting work going on. Some of the projects are still going on. Canada has licensed a tobacco produced protein vaccine and the ferritin nano particle vaccine developed by Walter Reed is in clinical trials right now:. Volunteers are still being sought to finish up the Phase 1 trial: https://www.wrair.army.mil/node/645
Nasal vaccines have been used in the past with varying degrees of success. A commercial influenza vaccine has been around since 2003 but is not recommended for those > 50 years of age. There is also a bacterial delivery system that will get Covid antigen to the gastric mucosal system.
A number of vaccine approaches were under development several years ago when Zika virus was thought to pose a major public health problem When the virus disappeared these projects were shelved and a major opportunity to test vaccine platforms for the development of neutralizing antibodies was lost. Had such work continued it might have provided valuable information that could have helped out Covid vaccine developers.
There are a number of other issues that can be discussed but I'll stop with these. Intrepid uses of google can find the archive of my Covid-19 newsletter fairly easily.
Logistical roadblocks should be fixed. There's no reason that studies should be delayed by monkeys being stuck at customs or supply chain issues with adjuvants.
But when it comes to lowering the barrier for starting human trials, I'd want to see some concrete scientific and bioethical basis for this change of procedure. I understand we all want faster role out of therapeutics! But each decision is a cost/benefit problem, and the costs of a harmful or ineffective therapeutic, especially one widely administered to healthy people, being released is potentially very high.
We need some clear cost/benefit analyses.
I’m aware of Fast Grants but I don’t think the CEO of a payments firm was the “scientific expert” the commentariat had in mind the other day.
Yes, I know this was written and scheduled before then and is sheer coincidence.
Are nanoparticle-based vaccines safe though? I've seen a lot of hype around nanoparticle delivery for a number of drug classes (with good reason!) but there are serious questions about how the body clears them. Which again, is why we run large clinical trials in the first place, to tease out these effects before they're shown to be harmful.
A proper universal vaccine would likely need to deliver sterilizing immunity. If it does not the nexus of diffusion rate and selective pressure may drive a dangerous mutation.
A few bigger themes remain:
1) COVID is a vascular disease. Just as HIV research in the 80s gave us Immunotherapy for cancer, so will COVID vaccines unlock tools that curtail inflammation. COVIDs vascular behavior will help expose the tricks we need. CVD, T2D and Alzheimers are mostly inflammatory diseases. T2D is a pandemic much larger than COVID.
2) We should figure out how to do challenge studies. The issue is ethics. Medical community sees them as unethical. Losing 24k people a day waiting for RCT trial seems unethical to me. Especially since the RCT of 40k is just a stochastic way to find the 2000 people you would use in a challenge study.
3) Unlocking Biobank data: we have 100 years of biobank data. Biological samples locked up in universities. Data from failed trials. We learn more from failure than success, but access to this biobank data is limited. A breakthrough in HIV came when a WashU doctor recalled a 14 year old boy who presented with AIDS like symptoms in 1962. They found his blood sample and confirmed HIV.
4) We should be able to build MRNA platform technology, or nanoparticle, as a foundation for annual vaccine derivatives. Validate the platform, with broader longitudinal RCT. Then insert annualized active entity tested with challenge study. This is basically how we build annual flu vaccine.
5) Allow people to "Donate their data to science" while alive. Build a database of longitudinal (Phenotypical, meta, and specific assays). Use as foundation for digital twin/synthetic control arms.
"Network Medicine" is the future. Need more data https://amzn.to/3nHbidX
If anyone wants to help on this feel free to email me cwilliams@iselectfund.com @jcarterwil
What are the political action items? Is there a bill to ask my representatives to support? Are we calling for new leadership in the FDA? If so, who is the scapegoat? Compared to what happened to banks in 2009, the response on institutional COVID failures has been pathetic.
Correcting a lot of the federal administrative and bureaucractic dysfunction (and general gov't competence) really needs to be an electoral issue.
Perception of inefficiency/incompetence is probably to blame with a decent amount of the default/knee-jerk resistance to more and bigger government. (The dedicated small government types won't care, but the vast squishy middle could be persuaded)
Because bureaucracy is super resistant to change and risk, executive action alone can only do so much, and making a real impact is probably going to require a fight and the expenditure of political capital.
But long-term I think it will be a clear net positive for the party that actually wants the government to...you know...do stuff.
I'm relatively young (under 40), healthy and I've been vax + boosted. However, I got covid a few months ago and it took me out HARD for over a week. I had a high fever, cough, head fog and waves of nausea that made it difficult to do anything. I personally would be fine with challenge trials or almost anything to speed up the process, as long as we are sufficiently warned of the risks and can make informed decisions.
It's probably not terribly important to the main thrust of the article, but where is the 380 deaths per day figure coming from? I'm seeing under 300, currently, and that number being below 400 since April.
https://www.worldometers.info/coronavirus/country/us/
I'm interested, but is the median American? What do we understand about reinfection? Seems like bundling with yearly flu shot is best hope. I also think we could pay people to take it. I do not understand why so many incentives were left on the table the last time.
HOW DO WE HELP MAKE THIS HAPPEN-SOONER THAN LATER? Thx for all this.
Great post. One thought about getting things done faster is that it doesn’t quite make sense to drive this research exclusively through academic labs. As with OWS, it would likely be faster to work with biotech/pharma companies or to arrange partnerships between academic and industry groups where it makes sense. I’ve worked in both worlds, and academics just really aren’t set up to do translational research in the same way that companies are (e.g. navigating the red-tape that the author provides several examples of). For a grant-making institution, it of course makes sense to work with academics, but to drive things across the finish line, I think it’s reasonable to bring in industry as well. Again this is a role government can/should be playing.
Kuddos to Matt for loaning his microphone to a subject matter expert whose ideas will benefit from a broader audience. Thumbs down to the Biden administration for administrative lethargy.