Jed Ervin, M.D. '70 would like to be retired. But he is not, and we should all be thankful. Jed, a three-time Bengal Bouts champ and one of Fr.Lange's boys (link) did retire from his Kansas City rheumatology practice a few years ago, but still runs the Center for Pharmaceutical Research (CPR). Jed and CPR are in the thick of the campaign to develop a COVID-19 vaccine. Jed took some time out from his busy work schedule to talk about his work.
Q. When and why did you start CPR?
A: Well, it just kind of happened. I did an Internal Medicine residency after med school, and during that time I was recruited to join an internal medicine group in town. I took a Rheumatology rotation, and just fell in love with the autoimmune diseases as a challenge in making the diagnosis of the 110 autoimmune diseases, and then the challenge of treating them. I did a fellowship in rheumatology and joined the group in 1977, but left to set up a solo practice in 1980. In 1986 a pharmaceutical company was developing Clinoril, a non-steroidal anti-inflammatory drug (similar to ibuprofen), and a drug representative asked me if I would be interested in conducting a phase III trial on the drug. It just so happened that I was going to fire my RN wife as my nurse, because when she put a patient in a room, she shot the breeze with them for five minutes, and so I was constantly behind. As my study coordinator, she could spend as much time with them as she wanted and then tell me what I was supposed to do for the visit.
So, we started Center for Pharmaceutical Research, and began doing research studies along with my practice. The research business grew and grew, and we began to do studies outside of the rheumatology arena (multispecialty), and hire more people…and we got up to 40 employees. In 2007 I was practicing rheumatology and running my research company, and was working up to 16 hours a day. I cut my practice hours back by 2 hours a day, but was still working 14 hours days. I made the very painful decision to quit my practice, which had 3 employees, but was my main job as far as hours spent, to do research only, where I had 40 employees. Jan 9, 2009 was my first day doing only research…and I thought to myself, “Wow!!! This is like a normal person.”
Q. Do you always do smaller, Phase I trials, or do you do larger trials as well?
A: We have done over 800 trials in all three phases, and over 110 vaccine trials, over 100 osteoarthritis trials, and other trials in just about every area of multi-specialty treatment. When a new drug or device or vaccine starts the process to becoming FDA approved, it has to go first through several research phases.
· Phase I are the first human trials. The I.P (investigational product, i.e. the medicine or vaccine being studied) may or may not have gone through animal studies first. Phase I trials are primarily aimed at proving safety. Usually the number of volunteer test subjects is small, and they typically will be given different doses of the I.P. to evaluate for safety and efficacy, in comparison with a placebo.
· Phase II: In these trials, the lowest dose that demonstrates efficacy, assuming it also appears to be safe, will be chosen (assuming FDA approval) to move on to Phase III. In phase II, more study subjects are recruited, and the doses further evaluated for safety and efficacy before moving on to the next phase.
· Phase III: This is the final phase, where a single dose, the one with the highest efficacy with matching safety, is selected. The numbers of test subjects in phase III trials are much larger in order to prove statistically significant effectiveness and safety compared to placebo.
The process for a drug to come to market takes an average of 8 years. We have primarily done phase III studies, but over the years we have done 20 or more phase I trials. In more than 10 of these, CPR has been the only site in the country to conduct the phase I trial. Typically, if we do the phase I trial, we will also be chosen to do the phase II and III trials for that I.P. Our largest trial to date involved about 300 study subjects. We were just approached about a COVID-19 trial for 1500 study subjects. I don’t think we can handle that. We’d have to hire more people and get more space. But I’d love to take up that challenge.
I feel privileged that we were selected to do COVID-19 trials for Moderna and Inovio, the first two companies in the U.S. to conduct these studies. We have started our third trial on a COVID-19 I.P., and are looking at others. Of the 800+ trials we have done, although many have been larger and more lucrative, these COVID-19 trials, for obvious reasons, are the most important. Because of these studies I have been interviewed 19 times by all three local television channels, the New Times (twice), the NY Post, AP, CNN, Fox News, NBC, and others. It is amazing how COVID-19 has affected our lives.
Q: How many COVID-19 vaccines are currently being developed in the US? Abroad? Which country is most likely to produce a safe, effective vaccine first?
A: Over 80 COVID-19 vaccines are being developed world wide, 115 if you considering those under consideration for development. To date, 6 have reached clinical trials.
We have been selected for the first two out of the blocks, by Moderna and Inovio. 60 Minutes did an interesting cover of these two companies. It’s fascinating how quickly they created their vaccines after Hunan China posted the COVID-19 genome to the web on January 9. Inovio came up with the design of their DNA vaccine in 3 hours!
Oxford University, in England, may have the first available vaccine. They are working with Astra Zeneca. Most other countries have less stringent testing standards than the FDA, but we are hoping that, given the seriousness of the pandemic, the FDA will expedite the approval process for COVID-19 vaccines. We need to get that vaccine out there as quickly as possible.
I don’t think safety will be an issue. At least we haven’t seen any safety issues to date in the three COVID-19 trials we are conducting. We give our kids about 15 vaccines their first 16 months of life, and many 8th grade girls nowadays are taller than me (third grade girls are taller than Paul Partyka). Every NBA team has a 7 footer. All because we are planting our flowers in richly-fertilized soil. Our kids and grandkids aren’t getting all the illnesses we had growing up (we got planted in a bit more rocky soil).
Efficacy will be the issue. We won’t know if COVID-19 is a mutator like HIV or RSV (Respiratory Syncytial Virus), two viral diseases in which multiple attempts to develop vaccines have failed, or whether it will be like smallpox or polio, two of the greatest viral scourges in history. Smallpox has been eradicated, and polio was eliminated from the Western Hemisphere in 1994.
There are suggestions that the vaccines will be effective. Harvard researchers developed COVID-19 DNA vaccines and tested them in rhesus monkeys, whose DNA is 93% identical to humans (actually, 96% of Partyka’s). They exposed the monkeys to COVID-19 and then checked the level of neutralizing antibodies [antibodies that defend a cell from a pathogen or infectious particle by neutralizing any effect it has biologically] in the survivors. Then they vaccinated healthy monkeys, and found they developed the same level of neutralizing antibodies as those that had been infected with COVID-19. Thirty-five days later, they exposed the healthy, vaccinated monkeys to COVID-19, and and found that the vaccine protected them.
Although their results have not yet been published, clinicians have discovered that infusing plasma from previously-infected COVID-19 subjects into patients severely ill with COVID-19 has, in some cases, resulted in dramatic reversal of their downhill course. This is why Dr. Fauci and I are cautiously optimistic that the vaccines will stop this invisible invader that has altered all of our lives.
Q: How is Inovio's vaccine different from the others being tested? Is the DNA vaccine expected to be safer because it is synthetic?
A: Inovio’s DNA vaccine has several advantages:
* DNA vaccines can be designed and manufactured quickly.
* The DNA plasmid [an extra-chromasomal ring of DNA that replicates spontaneously] vaccine, is the only nucleic-acid based vaccine that is stable at room temperature for more than a year. This is an important advantage when implementing mass immunizations, especially in developing countries, where refrigeration might not be readily available.
* Inovio’s DNA vaccines deliver plasmids directly into cells intradermally [under the skin surface] or intramuscularly using a hand-held smart device called CELLECTRA®.
* The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and other nucleic acid approaches.
* The Inovio DNA vaccine's enhanced immune response, safety profile, and tolerability have been demonstrated in prior clinical trials.
Q: Will we be able to manufacture enough doses to conduct the Phase 3 trials early next year?
A: No single company will be able to manufacture enough for the needs of the U.S., with its 330 million people, so we need all of the companies that can manufacture safe and effective vaccines to do so as quickly as possible. This is one advantage of DNA vaccines. They can be churned out expeditiously by injecting the DNA plasmid into cells, which then reproduce themselves. This results in massive quantities of the self-replicating DNA plasmid, which serves as the vaccine, generating neutralizing antibodies by the thousands.
An un-solicited comment on “herd immunity”
To develop “herd immunity,” we will need either 70% of the population to be infected with the virus (with a mortality rate of 2%, that would result in around 6.4 million deaths), or we can vaccinate the populace to immunize the 70% required for herd immunity.
Q: How do you find volunteers? Are they paid? Do you test all age groups?
A: We have been conducting trials since 1986, and we have a database of nearly 30,000 study subjects, people who have either been in prior trials or expressed interest in participating in trials. We also use Facebook, other social media, and advertisements. We pay study subjects $50 when they send us a friend or family member who subsequently randomizes into a trial.
Study subjects receive a “travel and inconvenience” stipend of $100-$150 per visit, less for studies in which the subject receives a “treatment,” more for healthy volunteers.
We test all age groups, from 6-month-olds (pediatric vaccines) to the elderly. We ran trials for Merck’s shingles vaccine for the over 65 age group, which was effective for about 70% of the elderly population, and then brought GlaxoSmithKline’s shingles vaccine to market. Their's was effective in 96% of the populace, and Merck’s product disappeared.
The COVID-19 vaccine is considered a “healthy volunteer” trial, as are all the vaccine trials, but for this one we had 90 people vying for the 20 slots for the phase I trial. We probably could have charged them to participate.
Q: Did you ever envision yourself doing this kind of research as a ND student, or as a medical student or resident?
A: No.
As I said, it all just fell into my lap. I will say, however, that it’s been very satisfying. I still miss my practice, my patients, the challenge of making a diagnosis, the satisfaction of effecting a cure, and the bonds that develop with my patients. But, I don’t miss the 14-16 hour days, the call, the stress of having to be perfect. What caused me to choose between giving up research or quitting my practice to get back to more reasonable hours was the fact that I had 3 employees in my practice, the far harder job, and had 40 employees in CPR, including my wife and daughter.
The satisfaction has been in the important treatments and vaccines, and even devices, that we have brought to market, giving my employees good jobs with good benefits, and even watching them get hired away for supervisory jobs at competing sites – jobs they would have never been qualified for before they spent years with us.
We have developed a reputation as one of the premier sites in the country, of which I’m also proud, but as a fellow dotard to the rest of the class of ’70, I’m ready for retirement, if I ever am able to do so.
Q: Do you speak to Tony Fauci about the trial? (He said yesterday that he is optimistic about the results so far. Is he referring to the safety aspect of the vaccine? Efficacy has not been tested yet, correct?)
A: I last spoke with Tony Fauci in 1977, when I was a rheumatology rheumatology fellow at the University of Kansas Medical Center, and he was an NIH (National Institutes of Health) vasculitis specialist. He did grand rounds, and then did patient rounds with us. We were both much younger then, but he already was considered a whiz kid. He later moved into infectious disease. I have a tremendous amount of admiration for him as a physician. He clearly does what he does because he loves it, although maybe not so much recently. Tony is “cautiously optimistic." So am I.
Q: What was your inspiration for becoming a physician? Did you have role models growing up? Were there any ND professors who you took inspiration from?
A: I’m not sure what first interested me in becoming a physician. I have asked myself that question and I honestly can’t pin it say when that first hit me. The idea started in late grade school or early high school, and just stayed as my goal. I think I could have been an architect, which my dad was, but I just always felt I wanted to be a surgeon.
When I started med school the surgeon idea kind of changed. The biggest challenge I found, after taking Physical Diagnosis, and then going from the classroom to the hospital in my third year, was evaluating the patient, taking a history, doing the physical exam, and formulating a differential diagnosis. Reading about and eliminating the possibilities one by one to arrive at the correct diagnosis; the satisfaction of dealing with patients; and the challenge and satisfaction of making them better, turned me toward internal medicine. When I took a rotation in rheumatology my last year of residency, I found autoimmune diseases fascinating. The additional challenge of puzzling out which one the patient was suffering from pushed me toward that subspecialty.
Regarding influential Notre Dame professors, I can’t think of any single one who really inspired me. I thought most of them were good. Fr. Lange, of course, as you know, was a significant inspiration to me, as he was to you.
I was a Kansas City, Missouri boy all my life, so I applied to the University of Missouri Medical School. However, my folks moved to Leawood, Kansas, a suburb of Kansas City on the Kansas side by about a block, and this entitled me to also apply to Kansas University Medical School. It was in Kansas City, Kansas, just a few blocks on the Kansas side of the state line, and close to where I grew up on the Missouri side. So, I’ve been back in the KC area since.
Now I’m just a 72 year old dotard, waiting to retire before I end up in a nursing home. Still bench pressed 295 earlier this year, so I’m old and fat….but still strong!
Leawood, Missouri
A.B. Pre-Professionial
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