Are vaccines the light at the end of the tunnel?

[markeb]

13 minutes ago, OceanCruise said:

Why would you believe wikipedia and snopes rather than looking at the actual scientific research studies? This article just came  out in the American Journal of Medicine and further proves my point: 

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

https://www.sciencedirect.com/science/article/pii/S0002934320306732

 

Because you quoted a completely disreputable source. 

 

Interesting article. The primary references are mixed in results. The early toxicity studies never made sense as people take HCQ for lupus and RA and you rarely see cardiotoxicity at those doses.

 

When you actually go to the references in the paper (it's a pseudo-review article reporting now new research, BTW), they are mixed and while some show some good results, they all are retrospective and they all recommend prospective studies to show if the effects, either none or positive, are real. 

 

So yes, I've read more articles than you can imagine on this. They're almost all from way back in the spring, and they've all had some design flaws.

 

I have no idea what your background is, but it's clearly not in medical or biological sciences...

[Ken the cruiser]

Just saw this New York Times article which highlights that CDC as just sent out some logistical planning information to every state as well as to some larger metropolitan areas. Even if the dates are off, at least it's another sign of impending progress towards us getting back to cruising.

 

https://www.msn.com/en-us/news/us/c-d-c-tells-states-how-to-prepare-for-covid-19-vaccine-by-early-november/ar-BB18E490?ocid=msedgntp

 

The Centers for Disease Control and Prevention has notified public health officials in all 50 states and five large cities to prepare to distribute a coronavirus vaccine to health care workers and other high-risk groups as soon as late October or early November.

Edited September 2, 2020 by Ken the cruiser

[npcl]

1 hour ago, OceanCruise said:

Why would you believe wikipedia and snopes rather than looking at the actual scientific research studies? This article just came  out in the American Journal of Medicine and further proves my point: 

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

https://www.sciencedirect.com/science/article/pii/S0002934320306732

Actually what is your point.

 

The only thing the paper really says is that approaches for standard of care for out of hospital treatment should be developed and then referenced some treatments that might be considered.  However, it does not really give any information about the quality of such treatments other than some very limited work that might hint at activity.

[npcl]

2 minutes ago, Ken the cruiser said:

Just saw this New York Times article which highlights that CDC as just sent out some logistical planning information to every state as well as to some larger metropolitan areas. Even if the dates are off, at least it's another sign of impending progress towards us getting back to cruising.

 

https://www.msn.com/en-us/news/us/c-d-c-tells-states-how-to-prepare-for-covid-19-vaccine-by-early-november/ar-BB18E490?ocid=msedgntp

 

The Centers for Disease Control and Prevention has notified public health officials in all 50 states and five large cities to prepare to distribute a coronavirus vaccine to health care workers and other high-risk groups as soon as late October or early November.

Better to prepare and be ready too early than to not prepare and be unable to distribute.  

[Ken the cruiser]

7 minutes ago, npcl said:

Better to prepare and be ready too early than to not prepare and be unable to distribute.  

Exactly!!

[markeb]

45 minutes ago, npcl said:

Better to prepare and be ready too early than to not prepare and be unable to distribute.  

 

Really curious about this. I haven't tracked how these vaccines are fitting in the process, but if memory serves, HHS had pulled management of the stockpiles from CDC and up to ASPR. I do love consistency...

 

(And, yes, CDC does have the better historic links into state, local, tribal, etc., health departments.)

[npcl]

53 minutes ago, markeb said:

 

Really curious about this. I haven't tracked how these vaccines are fitting in the process, but if memory serves, HHS had pulled management of the stockpiles from CDC and up to ASPR. I do love consistency...

 

(And, yes, CDC does have the better historic links into state, local, tribal, etc., health departments.)

Looks like they may be planning on following the current process for vaccines.  Feds buy, and allocate to each state for distribution and use.

 

The major active program that the federal government has is the childhood vaccine program, which is run by the CDC.  In that program the CDC funds the purchase, but the states are responsible for distribution. There is the possibility of running through BARDA, but they do not work with vaccines and the states like the CDC does with the CVP.

 

Most other vaccine distribution in the US is via normal commercial mechanisms where the doctor orders through the normal distribution outlets.

Edited September 2, 2020 by npcl

[Arizona Wildcat]

1 hour ago, npcl said:

Looks like they may be planning on following the current process for vaccines.  Feds buy, and allocate to each state for distribution and use.

 

The major active program that the federal government has is the childhood vaccine program, which is run by the CDC.  In that program the CDC funds the purchase, but the states are responsible for distribution. There is the possibility of running through BARDA, but they do not work with vaccines and the states like the CDC does with the CVP.

 

Most other vaccine distribution in the US is via normal commercial mechanisms where the doctor orders through the normal distribution outlets.

Arizona Governor announced the state would be providing free vaccinations for those covered by Arizona medical programs including ACCESS (Medicaid everywhere else) and Kids care.  His office said that clinics would be coordinated through county health departments.  They have done this before.  Those getting the vaccine will receive $10 gift cards!  Arizona has only 15 counties so coordination through them makes sense.  There are numerous military facilities in Arizona and about 600K active and retired military residents.  Would guess they would organize as well since about 15-20% of population.

[Babr]

Is anyone else uncomfortable or questioning the timing of this? November 1? Really?

[Caymus88]

3 minutes ago, Babr said:

Is anyone else uncomfortable or questioning the timing of this? November 1? Really?

Wow!, That’s your response to fantastic news?
I’m ecstatic a vaccine is imminent

[phoenix_dream]

1 hour ago, Babr said:

Is anyone else uncomfortable or questioning the timing of this? November 1? Really?

I’m more uncomfortable about catching the virus!

[Ken the cruiser]

56 minutes ago, Babr said:

Is anyone else uncomfortable or questioning the timing of this? November 1? Really?

 

Not really if you put the politics aside for a moment. There are 3 vaccines going through stage 3 testing in the US right now, with no red flags popping up yet (that I'm aware of) regarding their respective earlier stage 1/2 trials. Because of these positive developments CDC is now sending out logistical guidance to the state governments to "shake their respective trees" to get them to start preparing for the potential handling of millions of doses coming their way. That is going to be no easy feat without a lot of upfront preparatory and coordinated planning.

 

From my point of view that's progress in the right direction, especially if these and other vaccines in the pipeline continue to do well. As they say, we need to keep an eye on the prize.

[Babr]

30 minutes ago, Ken the cruiser said:

 

Not really if you put the politics aside for a moment. There are 3 vaccines going through stage 3 testing in the US right now, with no red flags popping up yet (that I'm aware of) regarding their respective earlier stage 1/2 trials. Because of these positive developments CDC is now sending out logistical guidance to the state governments to "shake their respective trees" to get them to start preparing for the potential handling of millions of doses coming their way. That is going to be no easy feat without a lot of upfront preparatory and coordinated planning.

 

From my point of view that's progress in the right direction, especially if these and other vaccines in the pipeline continue to do well. As they say, we need to keep an eye on the prize.

Too bad they didn’t respond with the same alacrity when it was time to get out testing and PPE. 

Maybe I’d feel better about it If the FDA had not already given emergency approvals for treatments with unproven effectiveness. Maybe it makes sense in an effort to try to save people who are already sick, but now they are willing to cut short the clinical trials and give approval for a vaccine to be given to millions of healthy people. Is it safe? Politics aside, it is hard for me to have confidence.

 

[npcl]

2 hours ago, Caymus88 said:

Wow!, That’s your response to fantastic news?
I’m ecstatic a vaccine is imminent

Keep in mind telling the state to plan and be ready as early as October/November, does not mean that a vaccine will actually be ready then.  Only that the planning should be done in case it might happen.

[mayleeman]

How many times have vaccines been approved for distribution before going through all the usual stages? Aren't the Stage III data processed through many statistical and demographic tests before final approval?

 

This current plan seems a lot like the reverse of drug tests where they cut it short when a major danger is discovered early. "Gee, the vax early data looks good! Let's fast-track it!"

Edited September 3, 2020 by mayleeman

[Babr]

How many times has a vaccine been developed in a matter of months and fast-tracked so it can be released at a convenient time?

Edited September 3, 2020 by Babr

[markeb]

Just now, mayleeman said:

How many times have vaccines been approved for distribution before going through all the usual stages? Aren't the Stage III data processed through many statistical and demographic tests before final approval?

 

This current plan seems a lot like the reverse of drug tests where they cut it short when a major danger is discovered early. "Gee, the early data looks good! Let's fast-track it!"

 

I can see, with favorable data, a push to Emergency Use Authorization for healthy health care workers sooner rather than later. That's unusual, but not unheard of. The independent reviewers are really going to want to look at data on the the products using Adenovirus vectors and mRNA; those have no track record to approval. I have a harder time with an EUA to high risk populations as those groups also have the most theoretical risks to a novel vaccine. They may not respond, could have more adverse effects, etc. 

 

I don't know how you approve a full BLA on that timetable, especially for the novel approaches, which includes AZ/Oxford, Moderna, and Pfizer. The recombinant subunit vaccines are on a slower timeline last time I looked; if their trails were on a faster timeline, I could see, with good data, an early approval of a BLA for them.

[K.T.B.]

11 minutes ago, Babr said:

How many times has a vaccine been developed in a matter of months and fast-tracked so it can be released at a convenient time?

 

Swine flu vaccine in 2009?  Just guessing.  I do know there were a few deaths because of it, but the odds of them figuring that out were extremely slim even if they took years to develop it.  It was a very rare nerve disorder that affected something like 1 out of 10,000,000 people.  

[npcl]

1 hour ago, mayleeman said:

How many times have vaccines been approved for distribution before going through all the usual stages? Aren't the Stage III data processed through many statistical and demographic tests before final approval?

 

This current plan seems a lot like the reverse of drug tests where they cut it short when a major danger is discovered early. "Gee, the vax early data looks good! Let's fast-track it!"

Vaccines usually not.

 

However, it all depends upon the completion point.  With the phase III trials there will be 2 end points.  1. The primary end point is when sufficient information exists to determine efficacy.  For trials of this size about Dec-Jan.  2. The point at which they stop tracking participants in the trials for duration of immune response and longer term safety data.  About 24 months after patient enrollment.

 

In post #645 I posted a reference to an article that describes how they might be able to get data prior to the originally planned primary end point.  In each clinical trial there is a Data and Safety Monitoring Board that oversees the trial.  It is made up of individuals that are independent experts in the field in which the drug being tested is in.  This group has also been referred to as the ethics board.

 

This group will periodically review the data.  They are the only group with access to the data on which patients got the vaccine and which got placebo.  As a result they can look at both efficacy and safety of the product.  If the data shows adverse events beyond what is reasonable for the drug being tested they will stop a trial because it is not ethical to subject patients to a level of risk that is unreasonable for the illness being treated (needless to say that level is much different for an oncology product then for a vaccine).  On the other hand if the data is exceptionally good they will also intervene for ethical reasons.  After all if the drug is very effective, in the case of an illness that can have serious medical impacts, it would not be ethical to withhold treatment from the participants in the trials that received placebo, as well as withholding it from other individuals that could benefit.

 

If the results are good enough for the DSMB to intervene then the data upon which they made their decision with be public. This panel is also comprised of experts in their fields, mostly from medical universities and are not government employees. Therefore you have an independent body that is not subject to the political pressure that might be present in a government agency.  It would also mean that the data would be very good.

 

At that point the company making the drug could file for an emergency approval.  

 

An emergency approval is exactly that.  It is not final approval and usually comes with a number of restrictions.  In this case it might mean a limited distribution (medical professionals and the very highest risk individuals for example).  It also means that during this time the company will not only continue to operate and collect data from the clinical trial, but will probably have to do extra surveillance  related to those people that received the product under the emergency approval.

 

Usually you do not have such action during a vaccine trial, but then again the situation the world is in now is also unique in the history of vaccine development.

 

The following is a very good, detailed description of the role of data and safety monitoring board (this one is posted by the National Institute for Drug Abuse but it is still applicable). I picked it because it is one of the best descriptions that is easily found.

 

https://www.drugabuse.gov/research/clinical-research/guidelines-establishing-data-safety-monitoring

 

For studies that are conducted in a blinded manner, the presentation of data relating specifically to outcome measures should be presented to the DSMB in the manner and timing described in the DSMP for that study. Studies that include interim analysis of efficacy data should provide the proposed number of interim analyses to be made, the specific comparisons to be made at each such analysis, the stopping rules on the basis of efficacy findings, including both standards for the determination of 'overwhelming efficacy' and an 'inevitable failed trial', and the methods of statistical correction to be used to control the final overall Type 1 error. When defining this interim review in the protocol, consideration should be given to whether the data can be prepared for the DSMB review in a sufficiently timely manner so that any resulting decision can in fact impact on the study Ð if the study is largely completed before the conclusions are made, the interim review maybe unnecessary.

 

The number of DSMB members and composition of the Board depends on the type and of complexity of the trials to be conducted. Members should be of multidisciplinary background. Areas of expertise desirable for DSMB members might include clinical medicine (appropriate specialty), biostatistics, bioethics, pharmacology (if applicable), clinical trials methods, and sometimes a patient advocate or a community representative. Board members should have no financial and/or scientific ties to the outcome of the clinical trial to avoid any real or perceived conflict of interest.

 

The Chairperson of the DSMB should have previous experience in monitoring clinical trials. That person should be a good facilitator, communicator and consensus builder. The Board may include one ex officio member with no voting privileges who functions as the Board's executive secretary. The ex officio member should attend all Board meetings including the open, closed and executive sessions. Due to the nature of the ex officio's responsibilities, this should be the only individual outside the Board membership who is privy to the interim analysis data.

 

 

[npcl]

1 hour ago, K.T.B. said:

 

Swine flu vaccine in 2009?  Just guessing.  I do know there were a few deaths because of it, but the odds of them figuring that out were extremely slim even if they took years to develop it.  It was a very rare nerve disorder that affected something like 1 out of 10,000,000 people.  

If you are referring to Guillain-barre syndrome.  That also occurs in cases where people get the flu, actually at a higher rate than is demonstrated in those that receive the flu vaccine. 

 

Because it did occur at a slightly higher than normal rate in those that received the vaccine, the vaccine got blamed, but 

the data is uncertain as to the relationship.

 

https://pubmed.ncbi.nlm.nih.gov/22407672/

 

Guillain-Barre Syndrome is not well understood and seems to be caused by a number of different infections. 

 

According to Mayo clinic

https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/symptoms-causes/syc-20362793#:~:text=The exact cause of Guillain-Barre syndrome isn't known,infection with the Zika virus.

Guillain-Barre syndrome may be triggered by:

Most commonly, infection with campylobacter, a type of bacteria often found in undercooked poultry

Influenza virus

Cytomegalovirus

Epstein-Barr virus

Zika virus

Hepatitis A, B, C and E

HIV, the virus that causes AIDS

Mycoplasma pneumonia

Surgery

Trauma

Hodgkin's lymphoma

Rarely, influenza vaccinations or childhood vaccinations

 

 

[K.T.B.]

Some very interesting research done on the virus:  https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63

[TeeRick]

10 hours ago, Babr said:

How many times has a vaccine been developed in a matter of months and fast-tracked so it can be released at a convenient time?

Convenient time?  I personally find this pretty funny and no offense meant to you.  But you believe that fast tracking a vaccine for a globally deadly disease was because of political motivation, and in the US only?   Any release time is just fine for a vaccine that is effective.  Would you rather wait to release a vaccine until after an election?  Sorry but in my opinion that is just absurd but I do truly understand that lot of people in our country these days think that just everything has a devious political motive.  But I will trust the vaccine scientists and medical community.  Also it is easy to overlook a US centric position and actually see the vaccines(s) approval and distribution will be worldwide.  I will be happy for an approved vaccine at any date and time.  Period.

[TeeRick]

2 hours ago, K.T.B. said:

Some very interesting research done on the virus:  https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63

Wow this article is extremely interesting! Thank you for posting it!

 

Also take a look at this JAMA article just published on the clinical results of treating severe COVID patients with simple corticosteroids.  The dexamethsone results have been previously released. Others work too.

https://jamanetwork.com/journals/jama/fullarticle/2770279?guestAccessKey=ec87204d-c42d-4d34-bef5-077a40bc86b0&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=090220

Edited September 3, 2020 by TeeRick

[Crazy planning mom]

So thankful for the insightful and informative posts from those in the scientific community who post here.

[Ken the cruiser]

My DW found this link last night. I wonder if this web site will be used to help folks locate COVID vaccine locations once they start to become available in the US? We did a search to find nearby locations where we can get a flu shot now, but our grocery store pharmacy wasn't listed; although many nationwide chain stores were. So we're not sure how complete this database is and how often it's updated.

 

However, if state and local government agencies will be involved in the distribution process, at least in the beginning, you would think this could be one of the notification tools they might consider using.  Anyone have any ideas?

 

https://vaccinefinder.org/

 

Note: It appears it is managed by the Boston Children's Hospital.

Edited September 3, 2020 by Ken the cruiser