Paper and Threads

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:

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. 

Posted by Shirley at 7:29 AM | Permalink | Comments (0)

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. 

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. 

Posted by Shirley at 7:26 AM | Permalink | Comments (1)

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)