August 5, 2020

CAUTION! WORRIED!

New York Times Aug 2:  "Scientists Worry About Political Influence Over Coronavirus Vaccine Project"  A horrifying article!  "Emergency Use Authorization" to make vaccine available in October, before the Phase 3 vaccine trial is complete, and that is required for FDA approval.  Continue reading....

EUA%20Part2SIZE.jpg 

 

This is long, but really important.  I am writing as a retired MD, who has experience with Clinical Trials for cancer treatment.  It is dangerous to make assumptions on Trial conclusions from incomplete data. 

There is great fear that there will be political pressure to release the front runner vaccines in October with an emergency use authorization (EUA).  I watched 6 hours of hearings by the House Energy and Commerce Subcommittee several weeks ago, and the 5 Vaccine Company representatives were asked over and over how they were going to insure the vaccines will be safe.  I watched an hour long interview of Dr. Stephen Hahn, by Dr. Howard Bauchner, last week.  Hahn is the FDA Commissioner and Bauchner is the editor of JAMA.  The Vaccine companies said that the Phase 3 Trials would not be rushed and safety compromised.  Dr.Hahn said that panels of vaccine scientists just worked on a set of standards that must be met in order to approve a vaccine - and this was done so any decision will be made based "only on the scientific data."

There was a very long article in the New York Times Aug 2nd, that was picked up by other news sites. They say there is a lot of political pressure to get a vaccine approved in October.  It says that if the FDA won't give "Emergency Use Authorization," the secretary of HHS in the White House can overrule his decision.  I recommend caution for the following reasons- and I usually take vaccines without worry.

1.  The two major US vaccines, Moderna-NIAID and Pfizer BioNtech, each began their phase 3 trials the last week in July. Moderna just published results of their Phase 1 Trial in NEJM (peer reviewed).  There were only 45 subjects vaccinated, evaluated, and reported.  They have not yet released their Phase 2 data.  I can't find any data from Pfizer as of today.  I assume they have completed Phase 1 and Phase 2 trials, although volunteers are usually followed for 1-2 years for late side effects.

2.  Moderna and Pfizer are part of Operation Warp Speed, and committed to test 30,000 volunteers in a Phase 3 trial.  Half of the volunteers will be vaccinated and half will get a placebo injection.  But no one will know who received which injection.  Volunteer enrollment just began( July 23 and 27).

3.  Each volunteer will get two doses, days 1 and 29 (Moderna) and days 1 and 21 Pfizer, so if they are enrolling volunteers beginning in August, the last volunteers enrolled will be getting their vaccinations in late August, September or even later.  By October those patients may not be followed long enough to adequately assess safety and efficacy! 

4.  The FDA will require that each vaccine will have a minimum of 50% efficacy (preferably >70%) in preventing Covid-19in the vaccinated group and acceptable adverse effects. Many tests to rate the immune response need to be done in specialized research labs and will take time.  These are blinded studies, and there are oversight committees set up who could stop the study if adverse effects are serious.

5.  If an EUA were granted due to political pressure, I wouldn't get that vaccine until the patients were all enrolled, followed for awhile, and preliminary results analyzed.  I want the vaccinated subjects to have at least 50% protection from Covid-19  when compared to the placebo group - AND side effects to be limited to injection site pain and flu-like symptoms. 

I'd also want to see careful review by other scientists.  The mumps vaccine set the speed record for vaccine development - 4 years. New technology made rapid vaccine development possible - both of these vaccines are made from the coronavirus spike protein genetic sequence and our cells make a spike protein which stimulates our immune system.  Older vaccines were made with inactive viruses or proteins of the virus.

 

 

 

 

 

August 1, 2020

EUA! PROTESTERS! No Emergency Use Approval!

Three Vaccine developers began their Phase 3 Randomized Controlled Trials in the last several weeks.  Each of them must enroll 30,000 healthy volunteers.  Half of the group will receive vaccine injections and the other half will receive a saline (salt water) injection as placebo.  Each volunteer will then be monitored for adverse events, and Covid-19.  Subgroups will also be tested for efficacy -both development of antibody titers and neutralizing antibodies that block virus proliferation.  In addition cellular immunity will be assessed by T helper cell activity.  No one will know what shot they received until the end of the trial.

Continue Reading Below:

EUASIZE.jpg 

Evidence of prevention of Covid-19 will be monitored in the treatment and placebo groups and results may depend on the activity of the virus where they are enrolling volunteers.  New York tests 50,000+ individuals each day, but the incidence of positive virus tests is only 1-1.5%.  If volunteers are vaccinated in the states with increasing infectivity, enrollment and protection in the vaccinated vs the placebo group may be faster.  Recently developed FDA guidelines for vaccine approval set the minimum at 50% protection by each vaccine for FDA approval.

BUT there may be political pressure to give "EMERGENCY USE APPROVAL" ("Pre-election Surprise) and then the government would be shortening the observation time for "rare, but significant" adverse effects to be seen.  The FDA commissioner this week said that his decisions will only be based on SCIENCE - and we have to hope that he is a man of his word.

 

July 29, 2020

Masks, Masks, Wear Your Mask

We are going to have to learn how to live with this virus until the population is vaccinated, and natural infection increases herd immunity to more than 70%.  Until we can be vaccinated, we MUST practice social distancing, hand washing, and mask wearing.  There is data to suggest that masks keep us from spreading the virus, AND they also limit the amount of virus that we breathe in.  When populations have protected themselves with masks they tend to have mild symptoms or are asymptomatic! See article link below.

On my morning walk I saw two store windows filled with these head mannequins and they had many different types of masks, in many different colors.  There even was a black mask covered in Swarovski crystals! Why do you think that the masks on the left have a narrow sliver hole over the nose? The store was still closed early in the AM, or I would have asked them.  I made masks for my husband and I, and our kids and grandkids that live in NYC.  As my back continues to improve I will make more.  I think we are destined to be wearing masks until 2021.  I love the pattern I used, and will also include a link at the bottom of this post.  Read more below.

Masks%20MasksSIZE.jpg 

This week two companies began Phase 3 vaccine trials.  They each need 30,000 healthy volunteers to determine if the vaccinated and placebo groups have a significant difference in Covid-19infection. Research Labs will also be measuring antibody titers and T cell responses in a cohort of the subjects.  In order to have a definitive answer, infectivity in the geographic area must be high enough to make people sick - the FDA approval requires 50% protection in the vaccinated group - at a minimum.  .

The "In Press" paper re: Masks is embedded in this article.  This is not a clinical trial - just a collection of observations from the pandemic by a well trained infectious disease MD and public health expert.
 
I searched lots of mask patterns - and loved this video and pattern.  I insert the elastic so it goes around my neck and head.  Fits each of my family members better than other fabric masks they have - some like ear loops and some prefer the neck-head configuration.  Cut and paste the link into your browser.
https://www.youtube.com/watch?v=1V3SLUHIJ5A 

July 25, 2020

Can Antibodies Be Used to Treat Covid-19?

When you transfuse antibodies into patients, you develop "passive, instead of natural immunity."  During the 1918 flu pandemic, patients who recovered from influenza donated blood so their antibodies could be transfused into other critically ill patients.  More recently, "convalescent plasma" from recovered Ebola patients was given to other patients.  Randomized control trials (RCT) are being done to test "convalescent plasma" for Covid-19 patients, but in addition MONOCLONAL ANTIBODIES are being developed from blood obtained from recovered patients.   Read about them below the collage.

 MoAb%20InfusionSIZE.jpg

Patients who have recovered from Covid-19 have naturally occurring immunity against all parts of the SARS-CoV-2 virus.  Their antibodies and immune cells are being studied, and the strongest neutralizing antibodies (which stop viral replication), are used to develop monoclonal antibodies which can be produced in large quantities.  This technology was first developed in the 1970s and is now being used to create many types of therapy, including cancer drugs.  In the classic method, cells which are producing antibodies are fused with a specific clone of antibody producing cells that can be grown in culture.  This clone becomes a protein factory which makes just one potent neutralizing antibody.  There are many monoclonal antibodies being made to SARS-CoV-19 and at least 3 are in early clinical trials.  Passive immunity with monoclonal antibodies is only effective for weeks to a month+, but when administered they can change the course of critically ill patients.  You can usually recognize monoclonal antibodies that are FDA approved because their names end with "ab."

July 22, 2020

Covid-19 Vaccine Development Update

There are 2 front runner vaccines being tested in the US - Moderna is a US Company based in Cambridge Mass and Oxford AstraZeneca is based in the UK, but has US financial support.  Both companies finally published their Phase 1 clinical trial results in the last week in peer-reviewed leading medical journals, and both are ready for Phase 3 "huge trials"  which will continue to test safety and will actually test effectiveness in preventing transmission of SARS-CoV-2 to vaccinated subjects.  These trials are prospective, randomized, placebo-controlled trials in not less than 30,000 volunteers per vaccine.  The trials will be "blinded" so neither the volunteers nor the MDs, Nurses, Trial Coordinators etc. will know what injection the volunteers receive.  The Phase 1 trials for both vaccines demonstrated antibody production, especially neutralizing antibodies which block virus replication.  And side effects were like the usual flu shot - mostly related to the injection site and some flu-like symptoms. 

The collage for my pandemic science series today is to celebrate the beginning of Phase 3 trials.  There are more than 140 vaccines being developed, that have not yet begun clinical trials.  As of today 19 vaccines are in Phase 1 and 13 in Phase 2.  Moderna will begin their Phase 3 trial on July 27th.  If you know the 3 phases of clinical trials, you are now better able to read and listen to the continual "chatter" about vaccines.  We aren't there yet!!  And may not be there until 2021.  But until then we will have to learn to live with the virus - and increasing deaths.  Stay home and stay healthy.

Continue reading below the collage: 

 

Phase3SIZE.jpg 

The Moderna-NIH Vaccine Research Center vaccine was made with the newest technology.  Instead of using the viruses themselves (usually dead or made ineffective), they made messenger RNA (mRNA) from the virus binding region of the spike protein of SARS-CoV-2 using the structure reported from China on January 10th. Most vaccines were created by making huge amounts of the antigenic proteins and injected them into us to stimulate the immune response.  Now the mRNA is stabilized and used as the ANTIGEN to stimulate our cells to begin the ANTIBODY immune response. 

The mRNA is transported into cells and acts as a blueprint for the cells to make the important part of the spike protein - the part that attaches to our cells and lets the virus in!  The spike protein then stimulates the immune response in the cells in our body and we make protective antibodies! This method cuts years out of the vaccine development process and has been tested in cell cultures, and various animal models- demonstrating that the immune response is able to then prevent the virus from replication in cells in our body.  Both vaccines completed Phase 2 Clinical Trials in hundreds of volunteers. 

This is complicated but very interesting and hopefully we will all get vaccinated, develop "herd immunity," and stop the pandemic.  The Oxford vaccine is using a similar, but not identical process. 

 

July 18, 2020

Will We Really Have a Vaccine for Covid-19 Soon?

I recently wrote about the 3 phases of Clinical Trials that must be completed to apply for FDA approval.  The mumps vaccine was created in 4 years - and set the record for vaccine development.  The average time is 7-10 years.  There are 150-160 vaccines being developed right now and 30 vaccines are in the pipeline. 

Read more below collage:

Phases1-3SIZE.jpg 

 

Phase 1 trials are small - to test different doses and assess the safety of the vaccine.  There are 15 vaccines in phase 1 trials.

Phase 2 trials have hundreds of volunteers and safety is still being assessed.  But vaccine effectiveness and antibody production is measured in the vaccinated vs placebo groups.  There are 11 vaccines in Phase 2 trials.   

Phase 3 trials still assess safety, but the effectiveness to prevent Covid-19 in 30,000 or more volunteers will be compared to a placebo group.  There are 4 vaccines in phase 3 trials: including one UK (Oxford), 2 Chinese, and 1 Australian  company (Data taken from NYT vaccine tracker).

The US front runner vaccine is from Moderna-NIAID/NIH and it will begin Phase 3 on July 27th.  The Oxford University/AstraZeneca vaccine is being supported in part by the US Gov't and both will be available in the US after approval. The number of Covid-19 cases and deaths are still in exponential growth in the US and companies are going to develop millions of doses for some of the vaccines, even before FDA approval is complete.   This is a huge financial risk for pharmaceutical companies and we can only hope that distribution will also be discussed and planned before approval is granted.  Until then we need to learn how to live safely with the virus. 

July 15, 2020

When Will the Pandemic End?

We either need a vaccine or miracle drugs to treat Covid-19.  All drugs must complete Phase 1, Phase 2, and Phase 3 Clinical Trials before applying for FDA Approval - just like vaccines which I wrote about several days ago.  These are also usually small, medium, and large trials. Phase 1 is to determine drug dose and SAFETY, Phase 2 determines drug dose, SAFETY, and efficacy.  The final big Phase 3 trial is a randomized controlled trial, double blind, with a placebo group or a group that is taking the current best drug for the disease for comparison.  This trial is primarily to study EFFICACY and safety. The major difference between the vaccine and drug trials is that volunteers who are testing a drug must have a firm diagnosis of Covid-19.

Continue reading below image. 

DrugTrialsSIZE.jpg

 

There are only two drugs which show efficacy against Covid-19 - dexamethasone and remdesivir  - and neither is a newly developed drug.  Dexamethasone decreases mortality by 1/3rd in patients on ventilators, and 1/5th in patients only on oxygen.  Dexamethasone, a powerful steroid, is directed at the inflammatory response to coronavirus in the lungs - called "cytokine storm."  Remdesivir, an anti-viral drug, shortens the length of the illness by several days. There are news articles about both drugs in the press and often in financial reports.  Both of these phase 3 drug trials are also now published as pre-prints.  Neither has yet been published as a peer-reviewed scientific journal publication.  Beware of the hydroxychloroquine press releases to date.  

Anyone who has read all the way to the end of this blog post may wonder why my blog posts now discuss science. I am a retired medical school professor of internal medicine and hematology (40 years) - and always enrolled patients on vaccine (pneumovax) and cancer drug trials for leukemia, lymphoma, and myeloma.  I'm not an epidemiologist or infectious disease specialist - and I rely on experts in these fields to lead the way through our SARS-Cov-2 pandemic.  We must learn to live with this virus until a vaccine is available for prevention or better drugs are developed for treatment. 

July 11, 2020

Roll Up Your Sleeve!

My healthy volunteer is enrolled in a vaccine trial which has 3 separate Clinical Phases before FDA approval.

Phase 1 usually has less than 50 healthy volunteers, in the age range of the proposed treatment group.  This phase is to test for SAFETY of the vaccine.  Several concentrations of the vaccine will be tested to determine the best dose(s) for Clinical Phase 2.   Antibody production after the vaccine may be assessed in a subgroup.  Subjects may be given 1 or 2 injections one month apart. Adverse effects are recorded and subjects followed for several months or a year.  Read Phase 2 and 3 below.

VaccineTrialsSIZE.jpg 

Phase 2 has many more healthy volunteers - usually in the hundreds.  Several concentrations of the vaccine may still be tested and 2 injections may be given 1 month apart.  The main goal of this phase is still assessing SAFETY, but some subjects will also be tested for the development of antibodies.  Subjects are usually randomized between treatment and placebo groups.

Phase 3 has thousands or tens of thousands of healthy volunteers randomized between the vaccine and placebo.  It may also be "double-blind" so neither the treated subjects nor the placebo group know what injection they received.  In this phase EFFICACY of the vaccine is assessed - usually by measuring antibody titers, the presence of neutralizing antibodies that prevent virus multiplication, and cases of Covid-19 in the vaccinated vs placebo groups. Safety is still assessed.  After the Phase 3 trial is analyzed, the data can be presented to the FDA for vaccine approval.  The FDA won't approve a vaccine unless it protects at least 50% of the treated group and would love to see even higher efficacy.

Only a few of the 150+ vaccines being developed will be in Phase 3 this Summer and Fall - and the leading vaccine trials will enroll at least 30,000 healthy volunteers randomized between vaccine and placebo.  The study sites selected must still have enough coronavirus virus transmission so the effectiveness of the vaccine can be measured. That shouldn't be a problem in the South or West in the US.

 

 

July 8, 2020

Weekly Tracker for Covid-19 Therapy

It is almost impossible to keep up with the number of vaccines, antiviral drugs, and treatments for Covid-19.  And it makes it more difficult because many haven't entered clinical trials.  Every vaccine and drug need to go through 3 clinical trials in the US in order to apply for FDA approval.  As someone in the most vulnerable age group for Covid-19, I started following vaccine development and as of Monday 11 vaccines have entered Phase 2 Trials and 2 have a Phase 3 Trial beginning now.  To give you pause, it is important to understand that these phase 3 trials will study a minimum of 30,000 volunteers (more below).

CovidTrackerSIZE.jpg 

Since I'm preparing a virtual seminar for later this month, I follow every article I can find on vaccine development and many of them are press releases, especially written for the business sites.  My main goal for my seminar is to review the clinical trial process, and the difference between news articles, pre-prints and full scientific articles.  I selected one vaccine (being developed by Moderna with NIH-NIAID), one repurposed drug (dexamethasone), and one new drug (a monoclonal antibody for treatment of Covid-19) as examples of the US testing process.   

The pie-chart is from Bio, one of many Covid-19 trackers - and the numbers are from June 6th.   

I think anyone who is concerned about their health, and will need to make decisions about a vaccine, or drug treatments, should understand the testing and approval process.  Last week there was yet one more report on hydroxychloroquine that appeared in newspapers and in news reports online and on TV.  This was a retrospective, chart review comparison of hydroxychloroquine and hospitalized patients who received usual care.  This is almost the worst type of clinical report that can be done, and consumers should require data from prospective, randomized clinical trials before information is ever published, even in a news flash. 

 

 

Shirley Parker Levine
New York City

August 2020

Sun Mon Tue Wed Thu Fri Sat
            1
2 3 4 5 6 7 8
9 10 11 12 13 14 15
16 17 18 19 20 21 22
23 24 25 26 27 28 29
30 31          

Archives

Powered by
Movable Type 3.38