Paper and Threads

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.

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.

Posted by Shirley at 7:33 AM | Permalink | Comments (0)

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).

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. 

Posted by Shirley at 8:36 AM | Permalink | Comments (1)

We are all hoping, not so patiently, for a vaccine against coronavirus. Each day new companies or research groups begin another vaccine development project and over the last few months 120 became 140, and now as many as 150 developers are on the list.  The average vaccine takes 7-10 years to develop, test in clinical trials, and get government approval.  The record for completing this process is 4 years.  But there are many groups who are moving much faster and could break the record - safely. 

In the US every vaccine, drug, or medical device must go through preclinical studies, and phase 1, 2, and 3 clinical trials before applying for FDA approval. 

I am giving a virtual seminar as part of a series on Covid-19 for woman students in STEM at my undergraduate college.  As a hematologist I'm very familiar with the development process for cancer drugs, and regularly had patients enrolled in one of these types of clinical drug trials.  When there are headlines everywhere about a newly repurposed drug being amazing for Covid-19, I would like the students to understand the quality of the research required in the 3 phases of clinical trials and the qualities of scientifically-based research studies. 

Posted by Shirley at 8:44 AM | Permalink | Comments (0)

I wanted to review and document our life in NYC in a collage - since the pandemic spread to the US. 

New York City had its first documented China travel Covid-19 case on March 1st.  On March 2nd a patient was reported in the county next to NYC, and he had no travel or known exposures.  But he worked in Manhattan.  This was the first sign that we had community spread in our area.   This 2nd patient infected many people - most who attended two big social events with him as he was becoming symptomatic.  This cluster in Westchester County was contained quickly by limiting travel in or out of the community.  They set up testing, isolated positive cases, and traced and tested their contacts.  Meanwhile testing kits were so limited that only people who traveled to China, or had contact with someone who did, could be tested here.  It was many weeks later that the genome of our coronavirus proved that our early infections came from Europe - not China - so the City was already infected in the beginning of March.

The surge of new cases began full force on March  14th and by the apex of new cases on April 15 there were over 8000 new cases per day.  On March 20th the Gov. instituted a strict "stay at home" mandate, and a daily morning briefing with lots of cheerleading by Governor Cuomo was able to slow the virus spread.  Only when NYC met preset criteria for the number of new cases, and hospitalizations, did NYC begin a 4 phase reopening schedule on June 8th.  The graph in my collage shows how long that took! 

We are now in Phase 2, behind all of the other regions in our state.  Yesterday we only had 189 new cases and for several days there were only 30 or less deaths.  thousands of virus tests are done daily and only  1-1.2% of the tests are positive.  The graph in the collage below is an actual copy of the statistics for NYC.  When I walk in my neighborhood in the morning there are no groups of people congregating,80-90% of people are wearing masks, and we go out of out way to stay 6' away from others even with our masks on. 

I don't think New Yorkers want to go back to our surge and consequent "stay at home" restrictions that lasted from March 20th to June 8th.  There is an early warning "dashboard" on our state website for people to follow, and at the first sign that more cases or hospitalizations are occurring, Gov. Cuomo will dial back the "faucet and pipes" as he says continually.   We currently have 1-1.2% positive tests per day (~30,000 tests per day) and less than 30 deaths per day. 

This is the graph for the daily death counts in NYC over the same time period.  There was surge and very slow gradual decline as New Yorkers worked hard to contain the virus. 

 If you want to hear an example of good leadership, here is the 30 min briefing on the day he told the 3million people in this City that we were closing down.

Governor Cuomo had a televised briefing every morning and I understand my friends from around the country listened like the New Yorkers did.  If you want to listen to "good leadership"   

Posted by Shirley at 9:01 AM | Permalink | Comments (0)

Make America Great Again (MAGA) Red Hats were seen all over Trump Rallies in Tulsa and Phoenix.  He is a president who doesn't believe in science, and he has been a horrific President as a leader during the worst pandemic since 1918.  If you listen to dozens and dozens of epidemiologists and public health scientists, we need to control the coronavirus and "Stay at Home" until you can limit the  number of new cases and hospitalizations.  Then, and only then, should there be a carefully planned reopening - occurring in phases and monitored by "testing - isolating - tracing contacts". 

Our population should wear masks, wash their hands frequently, and socially distance, perhaps even until a vaccine is available. 

The above two rallies were held in cities with increasing Covid-19 case numbers, and there was no social distancing or masks required.  Because our anti-science President, who never understood the basis of containment and refused to wear a mask, these cities might have a significant increase in new cases and deaths in the next 2-3 weeks.  He is directly responsible for the increased number of deaths.  This will not "Make America Great Again."

New York State was the epicenter for Covid-19 in the US, and there were more than 11,000 new cases per day at the peak.  Now, under the guidance of Gov. Cuomo and a population that was willing to work together to "flatten the curve" daily testing of more than 50,000 people/day shows that only slightly more than 1% of the population has Covid-19. And a phased reopening will depend on keeping that percentage and the number of hospitalizations steady. 

Posted by Shirley at 8:12 AM | Permalink | Comments (1)