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“The FDA Almost Killed Me” – A True Story

“The FDA Almost Killed Me” – A True Story

Daniel C. Elton, Ph.D.


Author’s Note: This article is cross-posted from my Substack.

Preface: It’s well known that stories of people who suffer while waiting for drugs to be approved rarely get attention, while the stories of those who suffer from unexpected side effects often end up in the news and congressional hearings. There are many reasons for this. One of them is the act-omission distinction. Intuitively people tend to place much more blame on actions that result in harm rather than omissions that result in harm. Rationally though, the distinction doesn’t amount to much — a doctor that withholds a life-saving medicine, while processing knowledge that it is likely to help a patient, still commits a grave ethical injustice even if they didn’t directly cause harm. Another reason is that patients are often not aware of drugs in the pipeline that have a good chance of helping them.

It doesn’t have to be like this, though. I strongly believe those who have suffered under FDA regulatory delay should have their stories heard and appreciated. That’s why I’m so happy John Bennett attended my second #ApproveAstraZeneca #UnclogTheFDA protest outside the FDA. When I heard John’s story, I knew it deserved to be told to a wider audience. So, I had him retell the story to me so I could tell it to you here. I really appreciate John taking the time to tell me his story and proofread my writing.

 

John at a February 14th protest outside the FDA, organized in conjunction with the DC Transhumanist Party, where we protested the FDA’s failure to approve the AstraZeneca vaccine while millions of doses languished in a factory in Baltimore and thousands died daily from COVID-19.

When John was only around nine years old, he started experiencing joint pain. Initially his doctors thought he might have juvenile autoimmune arthritis. Around age ten, however, he was diagnosed with Crohn’s disease. Later his doctor would tell him that after that initial diagnosis he estimated his life expectancy was only nine more years.

Crohn’s disease is not just “digestive problems”. The disease affected all aspects of John’s life, and he spent much of middle and high school in and out of a wheelchair. In 2001 he started receiving infusions of the monoclonal antibody Remicade every six weeks. Due to Remicade, he started to be able to walk again and was able to live a mostly normal life. That all changed suddenly and unexpectedly in 2005 when his throat closed up after his injection. Unfortunately, as happens to many long-term Remicade patients, his body had developed an immune response to the drug. In response doctors switched him to a similar monoclonal antibody drug, Humira. However by 2013 his immune system had started rejecting the Humira as well. In response his gastroenterologist tried several general immune suppressors but at this point John was running out of good options.

Fortunately there was a new drug with a lot of clinical trials data to support it, Entyvio. Unlike Remicade and Humira, which are TNF-alpha antagonists developed for rheumatoid arthritis, Entyvio was developed specifically for Crohn’s disease and a similar disease called ulcerative colitis. Entyvio was specifically studied in Crohn’s disease patients like John who either could not tolerate or did not benefit from conventional therapy and TNF-alpha antagonists. A peer-reviewed Phase II study from 2008 showed a dose-dependent beneficial effect of Entyvio. Four Phase III studies followed. By February 2013 enough studies had been completed on Entyivio that a review article in Expert Opinion on Biological Therapy concluded the drug was “an effective and well-tolerated drug that is an important advance for the treatment of Crohn’s Disease.” Takeda Pharmaceuticals filed the paperwork for approval with the European Medicines Agency on March 7th, 2013 and filed with the FDA on June 21st, 2013.

This is where the story starts to get really dark. Throughout the summer and fall of 2013, John suffered from fatigue, joint pain, and stomach pain. His symptoms came and went in unpredictable waves, so he was never sure if he would be able to attend any social events or be able to go into work. He had to start taking a lot of leave from work, some donated from co-workers, and some unpaid.  Eventually the pain got so bad he started going to a pain clinic every two weeks, which started him on Vicodin and Percocet. His intestine was so inflamed it was shot through with holes. A persistent infection developed. His neck felt like it was in a vice and was so difficult to turn he had trouble driving.

Given John’s condition, his doctor knew he was in a race against time and that he needed Entyvio as soon as possible. As a member of the FDA’s Gastrointestinal Drugs Advisory Committee, John’s doctor had an inside view on the agency and predicted he should be able to get the drug by the end of the year. Indeed, on December 9th, 2013 the Committee voted 21-0 in favor of approving the drug for Crohn’s disease. Under normal circumstances, an approval would follow shortly thereafter. Unfortunately for John (as well as many other patients), this isn’t what happened.

Even though the FDA had granted Enyvio Priority Review Status, for the next five months the FDA kept John (and undoubtedly many others) suffering as they debated the wording for the warning label. Since the approval of earlier monoclonal antibody drugs such as Remicade and Humira, scientists learned that in the long term some patients can develop allergic reactions to treatment. The FDA wanted to put a warning about the possibility of a severe allergic reaction on the label. The problem was that the drug had been designed specifically to avoid the allergic reaction rejection problems that occurred with Remicade and Humira, drugs which did not contain such a warning. A warning about allergic reactions would make Entyvio look less safe, something that the company rightly took objection to.

Another possible reason for the delay might be related to the fact that the FDA claimed that Entyvio put patients at risk for progressive multifocal leukoencephalopathy, (PML) an often fatal brain virus. In over a decade of trials however no patient who had taken Entyvio had ever developed PML. Still, the FDA pointed to a similar drug, Tysabri, which carries a “black box” label warning of the risk for PML. The company disputed this – pointing to established mechanistic differences in how the two drugs worked, but the FDA wasn’t convinced. In the end, the FDA decided to include a warning about PML on the label and require post-market surveillance.

By April 2014 John’s condition had gotten so bad that John’s doctor started filling out compassionate use paperwork. The FDA told him not to bother and to wait for the approval. In retrospect, he probably should have tried anyway. When the drug was finally approved on May 20th, 2014, the initial doses the drug company had made had expired. The company had to manufacture new doses, leading to a delay in commercial availability. It wasn’t until September 2014 that John got the drug. By that time John was in precarious health. Although he now had the drug in his system, it was too late to help. In January 2015 his doctor sent him to the ER where he stayed in an ICU for several days fighting an infection. John had to have two major surgeries that ultimately removed his large intestine altogether.

The story illuminates many areas for improvement in the FDA approval process. First, it took five and a half years after promising Phase II results for the drug to become available to patients. Other different regulatory approaches like Free to Choose medicine or adaptive licensing could have made Entyvio available to patients faster and at lower cost. But even if you remain convinced that pre-market Phase III trials are a necessity, there are still major areas for improvement highlighted by this case.

Ideally, after the company reached their endpoints in their Phase III trials the drug would be rapidly approved within a month or two. In reality, John suffered for well over a year waiting for Entyvio to be approved by the FDA. Even after the FDA’s board unanimously voted in favor of approval, John suffered for another five months waiting for approval (the FDA could have figured out the proper warning label much earlier, for instance in the five years during which the Phase III trial was running). Even after approval, John had to wait another four months before he finally got his first dose since the initial doses had expired.

As a result of over a year of completely unnecessary delays, John became dependent on opioids, ended up in the ICU with a major infection, and had to undergo several risky surgeries. In the end though, he was lucky to have survived the ordeal. One wonders how many patients like John there were who also suffered from the delay, and how many died as a result.

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack.

A Summary of the USTP’s FDA Reform Panel – Article by Dan Elton

A Summary of the USTP’s FDA Reform Panel – Article by Dan Elton

Daniel C. Elton, Ph.D.


The U.S. Transhumanist Party livestreams special Enlightenment Salon events every Sunday at 4 p.m. on YouTube. Two weeks ago, on April 4. 2021, the USTP organized a special Enlightenment Salon panel event on FDA reform. In addition to myself, the following people participated on the panel, which was moderated by USTP Chairman Gennady Stolyarov II:

  • Prof. Alex Tabarrok, Bartley J. Madden Chair in Economics, George Mason University
  • Dr. Max More, President Emeritus, Alcor Life Extension Foundation
  • Jim O’Neill, CEO, SENS Research Foundation
  • Dr. Edward Hudgins, Founder, Human Achievement Alliance
  • Prof. Garett Jones, Mercatus Center, George Mason University
  • Will C. , Medical Student and Blogger

The entire panel was probably the most information-dense event the USTP has done. I kicked things off by giving a short presentation, which I managed to blaze through in 15 minutes. (The slides can be viewed here.) The presentation set the stage for a very informative and productive discussion.

My only regret was that we didn’t have any women on the panel. However, during the course of researching my presentation, I found out about the work of Dr. Mary J. Ruwart. Dr. Ruwart estimated the number of people who die every year from FDA delays to be around 150,000 per year in her book Death by RegulationSo, I am happy to announce that Sunday, April 25th, from 4 – 6 p.m. Eastern Time, 1-3 p.m. Pacific Time, the USTP will be doing a special Virtual Enlightenment Salon with her.

Here is the recording of the FDA reform event. At 00:05:00 my presentation kicks off:

I’ve written a summary of the major points each of the panelists (and two others) made during approximately the first hour of the session. These are heavily paraphrased. (Instead of providing direct quotes, I shortened what was said in most cases while maintaining the core meaning of what was communicated.) I have put my own comments in italics.

Prof. Alex Tabarrok:

  • The FDA can approve a bad drug (Type I) or fail to approve a good drug (Type II). If they approve a bad drug, people who were affected will go on Oprah, and there will be huge backlash. If they don’t approve a good drug, there is no backlash. The invisible graveyard is a statistical reality, but it’s hard to see. This can be seen easily by asking people to name a time when the FDA approved a bad drug (or a drug with unexpected side effects). Lots of people can think of something. Many point to Thalidomide, which is actually a drug that was approved in Europe and caused birth defects. Thalidomide, incidentally, has many important applications but was not approved by the FDA until 1998.
  • When you have a Type I error, you learn something — we learn about the harms of a drug, and we change our behavior. With a Type II error we never learn anything. We can’t see the consequences of a failure to approve, and even worse, we can’t see the many drugs that never even made it to FDA-mandated trials in the first place because they were deemed too risky to justify the cost.
  • Reciprocity is a sensible reform that is one of the most feasible.
  • The FDA likes to think they are the “gold standard” for drug approval. Yet, people in other countries don’t worry about whether drugs are FDA-approved. For food safety we already have reciprocity with Canada.
  • The FDA has been working for 40 years on new standards for approving sunscreens. So Europeans have much more advanced sunscreen than the US.
  • If aspirin were invented today, it probably wouldn’t be approved.
  • One thing U.S. policymakers have done already, which is probably the smartest thing they have done in a while, is PEDUFA (Prescription Drug User Fee Act). The drug developers pay an extra tax as long as approvals are sped up. The FDA was happy because they got to expand their bureaucracy, and drug companies were happy because they could get to market faster.
  • In the EU the EMA “farms out” reviews to private companies. (So the EMA is more like “an approver of approvers”). Private companies can do a good job – for instance, look at Underwriters Laboratories in the realm of electrical devices. (If you look at many electrical devices, you may see a “UL” seal.) Many major companies like Amazon won’t carry devices unless they are UL-approved.
  • There is no formal process whereby where if a disease is more deadly, then the standards should be lowered to speed approvals. For instance, for pancreatic cancer, which often kills within 6 months, the standards should be lower (and more risk should be tolerated), since patients have less to lose. For something like acne treatment, the standards can be much higher. The FDA recognizes this to some extent in practice, but it’s totally informal – technically it’s not supposed to happen. However they could do this formally and adjust the required statistical significance levels. They could use Bayesian statistical techniques as well.
  • There’s no route to approve a drug for anti-aging. If a company wants to do R&D on anti-aging therapeutics, there is not a clear route for approval.

Dr. Max More:

  • We should keep in mind full abolition of the agency as a long-term goal. [My response: I am against full abolition, but I agree with this. Everyone should at least consider abolition, and if they are against it, explain in some detail why the government needs to be involved versus using private-sector companies and tort law. Going back to first principles regarding the role of government is healthy, especially in places like Washington, D.C., where government institutions are taken for granted and not questioned as much as they could be.]
  • We should keep in mind Milton Friedman’s statement that expecting the FDA to behave differently than it does is like expecting a cat to bark (Note: He said this in a 1973 Newsweek column.) We can’t just say, “We want the FDA to do X”; we have to make sure incentives are in place so people actually do the things we want. Legal mandates can help, but it’s easy for people to skirt around them if the proper incentives don’t exist.
  • We are facing an enormous cultural barrier when it comes to reforming the FDA and CDC. We don’t have a proactionary culture anymore; we have a very fear-based culture, and a simple solution to it does not exist. However, we have a good opportunity right now just like the AIDS activists had a good opportunity in the 1980s.
  • The proactionary principle is a “grab-bag” of tools based on a certain value perspective which basically says that progress is fundamentally good. We aren’t omniscient, so we have to learn by doing. As Alex Tabarrok said, you can’t really learn things without making mistakes. It’s impossible to make progress, like some rationalists believed, by just sitting in chairs and thinking carefully. We have to become empirical. You can “look before leaping”, but you also have “look while leaping” and adjust how you land, to use a crude metaphor.
  • Cost-benefit analysis is a basic approach that is used in many organizations but doesn’t seem to be used as much in government agencies. It shouldn’t be controversial. Mandating cost-benefit analyses would be a step towards using ideas from the proactionary principle.
  • We should institutionalize the Devil’s Advocate procedure and institutionalize respectful disagreement. Instead of having the most powerful person in the room getting what they want railroaded through, we should require debate and motivate decision makers to ponder both sides. Other approaches could help, such as reference class forecasting, structured argumentation techniques, auditing procedures, and auditing review panels.
  • Reciprocity seems like a no-brainer that is relatively easy to achieve, and would greatly reduce costs.
  • Besides getting out these great ideas, we need to figure out how to get people to follow those ideas. Laws can help, but people can choose to not follow them. How do we put “bite” into laws? I think an annual audit on the FDA’s decision making would be a good idea. Importantly, the auditor’s report should be made public. The auditors should come from a variety of institutions, for instance a variety of think tanks from different sides of the political spectrum.

Gennady Stolyarov II:

  • The USTP agrees that abolishing the FDA should not be out of the question. In our Platform, Section CXVIII states:

Section CXVIII [Adopted by a vote of the members during March 25-28, 2020]: Given the extreme delays, bottlenecks, and expenses created by the mandatory approval processes on the Food and Drug Administration (FDA), the United States Transhumanist Party supports abolishing the FDA and replacing it with a Radical Life Extension Administration (RLEA), whose mandate would be to prioritize the rapid development of potential disease cures, treatments, and vaccines – including any possible cures or vaccines for COVID-19, as well as treatments to mitigate and reverse the disease of biological aging, the major risk factor for COVID-19. The RLEA would allow the marketing and collection of patient data on any potential cure, treatment, or vaccine which has passed affordable safety testing at a reasonably acceptable threshold.

Jim O’Neil:

  • I’ve had the pleasure of working with the FDA quite a bit, and in my experience most of the people there are very smart, and they actually believe in approving things, contrary to what it may look like from the outside.
  • The problem is that incentives matter, and the FDA is a central point of failure.
  • When someone has a severe side effect from a drug, the FDA Commissioner gets hauled in front of several Congressional Committees and is interrogated. When someone dies because something wasn’t approved, there’s total silence in Washington. We should blame Congress, not the FDA, for that incentive being in place.
  • Individuals respond to the institutional incentives, but they also have personal incentives. A lot of people want to be the next whistle-blower who finds the next thalidomide and calls a halt to it. Both of these are pretty severe and would affect even the most principled person in ways they couldn’t even detect.
  • I disagree with Alex that “FDA not recognizing aging as a disease is a major problem.” In order for the FDA to reasonably measure success of any therapy, there must be metrics and biomarkers. It’s not the FDA’s job to do all the scientific work to develop biomarkers for aging. That’s the job of the science community and the NIH to some extent. There are epigenetic clocks, but we need a lot more work on those. Those clocks can then be run through the FDA’s biomarker approval program.
  • The second thing I disagree with is Dan’s idea of making the FDA independent from HHS. I think that would make things worse.
  • My favorite approval ideas fall under the category of “progressive approval” or what Dan calls “tiered approval”. Contrary to what the FDA often thinks, doctors and patients are capable of processing information and making risk-benefit calculations using their knowledge about the specific situation they are in. The more information provided and the more transparency, the better. The FDA should focus back on their original mission of safety and purity. I absolutely support repealing the 1962 Kefauver-Harris Amendments.

Prof. Garett Jones:

  • I come at this as an macroeconomist. I think we can learn from what economists have learned about central banks around the world. The FDA should be as independent of congress and the president as central banks are or as judges are.
  • The Federal Reserve is a panel. That’s how we run the SEC, the FEC, the Federal Reserve, and the Supreme Court. There seems to be some magic to having a panel — it’s probably giving us a bit of the Law of Large Numbers in decision-making.
  • Another aspect of these panels is they have long terms. They are probably going to be serving under a few different Presidents. As I say in my book 10% Less Democracy, “short terms make short-term thinking”. Political independence can lead to decision-making independence, and we have evidence that’s a good thing.
  • Discussions in institutional reform have “high marginal product” right now, as an economist would say. Congress moves slowly, but Congresspersons tend to look for big opportunities for reform a couple years after a crisis. The Federal Reserve was established in 1913 but was born out of the Panic of 1907. Six years was how long it took between a huge financial crisis and Congress getting around to making some reforms. We saw something similar after the global financial crisis – it took about 2-3 years. The ideas that people are discussing now will be part of the information ecology of the next few years in Washington, D.C.
  • These ideas of long terms, independence, and panels are a good path for decision making. I am an unreformed Tabarrokian, so I agree with everything Alex Tabarrok has written about FDA reform (chuckle). What I want to push here is institutional reforms that seem to work in a wide variety of settings. A little more financial and legal independence will lead to a situation where Congress is less of a source of fear for FDA officials.
  • A lot of people on social media have told me that the President is in charge of the FDA. These people have never actually talked to anyone who worked on Capitol Hill — agencies live in fear of their Congressional overlords. They live in fear of the Senate Majority Leader and the Speaker of the House, who have power over their budgets. They also know that if they make a mistake, they can be hauled up before Congress and fired ignominiously.
  • There is a risk that a more independent agency may misuse its freedom. However, in practice, if we look at the data, independent agencies with long terms have high benefits and low costs.
  • It’s fun to complain about the FDA, but it’s wise to complain about Congress.

Dr. Ed Hudgins

  • We’ve been talking about how FDA regulators are always in fear of Congress. What I want to see are FDA regulators in fear of patients who want to get access to medications at less cost and quicker.
  • One of the most egregious examples of defining efficacy was when the FDA decided that 23andme could not offer advice on whether someone was prone to breast cancer. Essentially they thought that women were too stupid to understand the information and would rush out to get a double mastectomy without getting a second opinion.
  • Another example is in 1989-1990 when they wanted to classify a urine sample cup as a “class A medical device”, in the same category as a heart valve.
  • In April 2019, the FDA stated that it wants to regulate artificial intelligence as a medical device.
  • There are many consultants now, whose entire job is to help companies get through the FDA bureaucracy. So there’s a whole industry now just to help people get through the FDA — and that’s part of the problem now, too.
  • The “Free to Choose Medicine” idea should be at the top. Something like this was created around 1992 during AIDS crisis. Congress stepped in and put pressure on the FDA to do something. What they did was create a parallel track where sufferers could access a particular medication for AIDS during the three years it was being tested. 12,000 people took advantage of that, so there are 12,000 people who are not in the invisible graveyard as a result.
  • The idea of a parallel track has been put forward by Bart Madden. Data from people on that track would be put into a public real-world database.
  • There are alternatives to randomized controlled trials (RCTs). If observational data is put into a public database, then doctors can look at that data and make informed recommendations. Drugs would be able to fail quicker, too.
  • In the case of AIDS, it was patient groups that besieged the FDA’s buildings. In light of COVID-19, and people seeing that the system isn’t working for them, we have an opportunity now to push for change.
  • There’s momentum for FDA reform building off of the right-to-try legislation that has been passed in many states. In Texas and North Carolina there are strong pushes to broaden right-to-try to people like patients with Alzheimer’s Disease.

Will C.

  • The AIDS-FDA story is a little more nuanced than was described by Ed Hudgins and Max More. We all know about the militant groups like ACT-UP which pressured the FDA in the 1980s. However in the mid-1990s there developed a few counter-movements against that. One group was called Treatment Action Group, and they pressured the FDA to move slower because they felt the FDA was approving HIV/AIDS treatments that didn’t actually have much benefit.
  • A good book is Malignant by Vinay Prasad. It documents how, over the last twenty years or so, the FDA has lowered the standards for many cancer drugs. They often are approving drugs based on surrogate endpoints and biomarkers, and then the drugs don’t go through follow-up studies to show if they have actual clinical benefit. So there has been a natural experiment where we tried to lower the standards for cancer drugs, and it doesn’t seem to have worked very well. Of course, I’m not an economist, so there might be a way of adding up the costs and benefits where the marginal benefits have outweighed the costs.
  • The FDA had many failures during COVID-19. The first big one was with testing, both with the FDA and the CDC. Others were the decision to delay the approval of Pfizer and Moderna vaccines (by about 4-6 weeks), and the decision not to approve the AstraZeneca vaccine, which hasn’t had any transparency. Finally, there was a complete lack of experimentation with human challenge trials. What all of these share is there has been very little transparency and not much good reporting on these issues. There have not been any thorough investigations from journalists, and we don’t really know what’s going on. Before attempting reform we need to first go and find out what went wrong during COVID-19. We need a non-partisan investigation of all of these issues. We need to utilize Freedom of Information Act requests. We need to find out how Trump was involved, why approvals took the amount of time they did, etc.

Dr. Natasha Vita-More

  • Cosmetics does not need FDA approval pre-marketing. It only needs post-market approval if the company says something in their marketing materials that could be misleading. There are many doctors pushing crack cosmetic treatments and behaving in a very “loosey goose-y”. I have a hard time understanding how they get away with these things, unless there are big-monied interests behind them.
  • We all know about Theranos. In 2015 they got FDA approval for one of their tests. There’s clearly an imbalance here – many life-saving treatments struggle to get approval, but a company which is completely fraudulent like Theranos was able to get approval. [My response: This is a great point! Theranos did receive approval, but only for their Herpes test. If I recall correctly, this test was done with conventional laboratory equipment rather then their special “minilab” device, a fact which Theranos hid from investors. Theranos also utilized a loophole to sell tests without FDA approval.]

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack. 

To Maryland Governor Larry Hogan: Liberate Vaccine Doses from the FDA! – Article by Dan Elton and Edward Hudgins

To Maryland Governor Larry Hogan: Liberate Vaccine Doses from the FDA! – Article by Dan Elton and Edward Hudgins

Daniel C. Elton, Ph.D.
Edward Hudgins, Ph.D.


Note from the Authors: This was an op-ed we wrote in the first week of February 2021. Unfortunately, no newspaper wanted to publish it. We first submitted it to the Baltimore Sun, which promptly turned it down. We then submitted it to the Capitol Gazette, The Washington Times, and The Washington Examiner but never heard back from any of them. Sadly, this op-ed is just as relevant today as when we first wrote it almost two months ago. Since it was written, the evidence for the safety and efficacy of the AstraZeneca vaccine has only gotten stronger. An observational study of millions of people in Scotland published in early March found that a single dose of the AstraZeneca vaccine offers ~94% protection against hospitalization, outperforming Pfizer’s vaccine, which offered ~85% protection. Last week AstraZeneca reached an endpoint in the Phase III trial in the United States that the FDA requested, finding an efficacy of 76%, very similar to the previous Phase III trial result (70%). Despite all this, there has been no action from the FDA,and millions of AstraZeneca doses remain languishing in factories in Baltimore, Maryland and West Chester, Ohio as thousands of American taxpayers that are desperate for them die every day.

~ Daniel C. Elton and Edward Hudgins, March 31, 2021


If Maryland Governor Larry Hogan acts immediately and decisively, he can save thousands of Marylanders from suffering and death from COVID-19. A facility in Baltimore produces the very effective AstraZeneca vaccine and has stockpiled millions of doses. But the U.S. Food and Drug Administration, headquartered in suburban Maryland, which must certify all vaccines and medical treatments before patients can reap their benefits, is holding those doses hostage to its antiquated, bureaucratic red tape. Hogan should act now to liberate the vaccine to save the lives of Marylanders.

Over a year into the pandemic, over 8,200 Marylanders have died, and some 410,000 have suffered from COVID-19. Marylanders have suffered from a chronic shortage of the FDA-approved Pfizer and Moderna vaccines. AstraZeneca is approved in the E.U. and 19 other countries. So as our morgues fill up, what’s the FDA’s excuse for delay?

The AstraZeneca vaccine has passed Phase I and Phase II efficacy trials, which were published in the medical journal The Lancet in July and November 2020. A Phase III peer-reviewed study that was conducted in three other countries indicates the vaccine has an efficacy of 70 percent, ranging from 62 percent to 90 percent with different dosages. Most importantly, the vaccine showed a 100-percent efficacy at preventing COVID-19 hospitalizations and deaths. The AstraZeneca vaccine was also the first shown in a scientific study to reduce transmission. And unlike the two already-approved vaccines, it requires only regular rather than ultra-cold refrigeration. It has been given to over one million people in the U.K. without safety issues detected, yet FDA has requested that AstraZeneca redo most of their Phase III trials using patients from the U.S.

Some media outlets have reported that AstraZeneca’s vaccine “may not work” in the elderly. Unfortunately, AstraZeneca’s Phase III data published so far does not allow for efficacy to be determined for those older than 65. However, Phase I & II trials showed a similar immune response after the second dose across all age groups, including those over 65, so there are good reasons to believe the efficacy should be similar for the elderly. Even if the efficacy is much lower, because the elderly are at such high risk it still makes sense to give them the vaccine in order to save lives. This was shown clearly by Oxford bioethicists Jonathan Pugh and Julian Savulescu, who ran some numbers to show the grave consequences of denying the vaccine to the elderly. It is also true that recent results show the AstraZeneca vaccine is not very effective against the South African variant at preventing mild forms of COVID-19. However, the current study only addressed mild illness and AstraZeneca’s vaccine gives a similar immune response to Pfizer’s vaccine, which has been shown to protect strongly against hospitalization from the South African variant. The World Health Organization recently released guidance recommending the rollout of the vaccine not be halted due to this finding and that the vaccine be given to all age groups. 

The U.S. government has already contracted for 300 million doses of the vaccine, costing taxpayers over $1 billion. Yet with thousands dying daily and many more suffering from COVID-19 across the county, the FDA projects they won’t approve the vaccine until late April.  

Since FDA won’t certify the AstraZeneca vaccine immediately, Governor Hogan should act. He might invoke emergency authority to simply take possession of enough of the AstraZeneca vaccine supply in the Baltimore factory producing it to meet Maryland’s needs. But this would likely be unnecessary. He should request that the facility release the vaccine and inform them that the state will likely be able to guarantee no adverse repercussions from the FDA. After all, during the past decade over 40 states passed “Right To Try” laws that allowed terminally ill patients to access safe treatments not certified by FDA for efficacy. The only “repercussion”: in 2018 Congress passed bipartisan legislation, signed by President Trump, recognizing the state’s authority to do so. 

But in parallel, Hogan should call on President Biden to issue an executive order suspending the need for final FDA certification in this exceptional case.

Or Biden, backed strongly by the Maryland Congressional delegation, could request Congress pass emergency legislation creating a Free To Choose Medicine track parallel to FDA’s normal, slow certification process, on which COVID vaccines, tested safe and promising in Phase II or III trials, could be accessed by individuals, with informed consent. Such a track was created in 1992 for AIDS treatments, saving the lives of thousands of sufferers.

Or Biden could request Congress pass a reciprocity law certifying for the use of Americans any COVID treatment approved  in other advanced countries. Rep. Chip Roy (TX-21) and Sen. Ted Cruz, (R-TX) have introduced legislation allowing for reciprocal approval of drugs approved in other trusted countries. This proposal could be focused to allow access to COVID vaccines.

Since AstraZeneca is produced in Maryland and the FDA headquarters is also in Maryland, Hogan is in an ideal position to be the hero, shake things up, and break the bureaucratic walls separating citizens from a lifesaving medication.

If you agree that Hogan should act now, please sign this petition on Change.org:
Larry Hogan : Liberate the AstraZeneca vaccine from the FDA!

Ed Hudgins is founder of the Human Achievement Alliance and a science policy researcher.  He can be reached at ehudgins@humanachievementalliance.org. Dan Elton is  Director of Scholarship at the US Transhumanist Party.  You can reach him via direct message on Twitter (@moreisdifferent).

A List of Possible FDA Reforms – Compilation by Dan Elton

A List of Possible FDA Reforms – Compilation by Dan Elton

Daniel C. Elton, Ph.D.


I have ranked these according to my own perception of which have the most support among DC bureaucrats and members of congress.

  • Improving transparency. During the COVID-19 pandemic the public has been kept in the dark regarding how key decisions were made, such as the decision to issue an EUA for hydroxychloroquine, the decisions that pushed Pfizer’s EUA from early November to late December, and the decision to require additional Phase III data from AstraZeneca which delayed their EUA by at least 3-4 months. Currently the FDA keeps much of the information relevant to decision making confidential. In theory Freedom of Information Act (FOIA) requests can be used to obtain some information, but in practice FOIAs are slow-walked, may require litigation, and take years to resolve. There are many possible ways to increase transparency at the FDA, some of which are outlined in this recent article in STAT News. 18 specific recommendations can be found in this journal article from 2018. One of people referenced as a top candidate for FDA Commissioner, Joshua M. Sharfstein, is a poor choice when it comes to implementing other reforms but has been a leading voice calling for more transparency.
  • Reciprocity. If a drug/medication is approved by a regulatory agency in a different country which has equivalent standards to the FDA (for instance agencies in the UK or Japan, the European Medicines Agency (EMA), or Health Canada), it should automatically be approved by the FDA (and vice versa). Reciprocity would save both taxpayers and companies a lot of time and money. Imagine if the AstraZeneca vaccine had been approved on January 1st, a few days after the UK approved it. It’s easy to see that tens of thousands of lives would have been saved, especially when you consider it would have been given to the most at-risk first!  In 2015 Senators Mike Lee and Ted Cruz introduced the RESULT Act, which is primarily focused on implementing reciprocity.
  • Making the agency independent from the executive branch. It’s hard to insulate the FDA from political concerns as long as Congress controls the FDA’s purse, but it could at least be removed from direct interference from the executive branch by making it an independent agency like the FCC or Federal Reserve. There seems to be wide support behind this idea right now and recently four former FDA commissioners all endorsed this idea in an interview.
  • Rolling reviews. It should not take 3-4 weeks from the submission of an EUA application until a decision is made, especially when thousands are dying every day while waiting for vaccines. According to Dr. Marty Makary, a professor of public health policy at the Johns Hopkins Bloomberg School of Public Health who has conducted over a hundred clinical studies, the FDA “could have done the approval in 24-48 hours without cutting any corners”. Likewise, the approval of drugs and therapies after Phase III trials have reached an endpoint should not take 6 – 18 months. While the FDA does engage in a back and forth with companies prior to when they submit their paperwork for an EUA or approval, they do not use rolling reviews. Due to their rolling review systems other countries like the UK were able issue EUAs for COVID-19 vaccines faster than the FDA. Rolling reviews should be the norm, and the submission and analysis of trial data should made as streamlined and as efficient as possible without compromising the integrity of the analysis.
  • Tiered approvals. Doctors who want to provide new drugs to at-risk patients currently have to wait 5-10 years for lengthy Phase III trials to conclude and then another 6 – 18 months for the FDA to carry out their review of the trial data. Tiered approvals would allow a lower level of approval after just Phases I and II, freeing up treatments to those who need them most. The centrist Niskanen center has a white paper which suggests four levels of approval (see also their op-ed in The Hill).
  • Expansion of Right-to-Try. Federal right-to-try legislation was passed in 2018. However, it is very restrictive, and patients need to have met a number of strict requirements before they can try new medications and treatments, greatly limiting its utility.
  • Treating aging as a disease. Currently it is illegal to market an FDA-approved product as a treatment for aging. Even though aging is a harmful biological process, it is not considered a legitimate “indication” for a drug or therapy by the FDA. In other words, the FDA doesn’t view aging as a “disease” and therefore anti-aging treatments fall outside their mandate. Some specific aspects of aging are also not considered as legitimate indications. The FDA is currently operating in an inconsistent way as some conditions which are due to the aging process can are considered legitimate targets, such as osteoporosis and menopause, but others, like sarcopenia (age-related muscle loss /frailty), are not.  Many experts, including David Sinclair, have spoken out about this issue. Some companies have found ways to get around the FDA’s restrictions, such as by using certain metabolic markers to track the degree of damage from aging. However, the impossibility of getting FDA approval for therapies that directly slow down or repair the damages from aging greatly dis-incentivizes industry R&D investment in this area.  Fortunately, with advanced gene and stem-cell therapies on the horizon, the Congress and the FDA have already taken a few steps towards being able to review and approve anti-aging drugs and therapies. The 21st-Century CURES Act, for instance, mandated the creation of the Regenerative Medicine Advanced Therapy designation at the FDA.
  • Challenge trials in emergency situations. Many people, including a group of legislators, lobbied the FDA to give companies the go-ahead to do challenge trials, but there was no action. Thousands of volunteers for COVID-19 challenge trials signed up with 1daysooner.org but were unable to participate as they had wished to. As a result, data on vaccine efficacy was obtained much slower than it could have been.
  • Use of the proactionary principle for all drug & therapy approvals. The FDA should publish a transparent, quantitative, scientifically informed, and structured cost-benefit analysis for each regulatory action performed, which estimates the expected quality-adjusted life years (QALYs) saved versus risk of QALYs lost for both the action and inaction. The analysis should be made public, ideally sometime before the decision goes into effect. Crucially, the analysis should enumerate the risks and benefits of granting an approval and the risks and benefits of not granting it. See Max More’s overview of the proactionary principle and his chapter in The Transhumanist Reader, where he presents not just a principle but an entire framework for rational decision making. The key reform here is to make it mandatory that decision making at the FDA be highly structured and quantitative so it under less sway from political concerns and cognitive biases. If such a framework for rational decision making was in place it’s unlikely the FDA would have decided to delay Pfizer’s Emergency Use Authorization (EUA) from early November to December 11th, a decision which cost tens of thousands of American lives.
  • Free to Choose Medicine with a Trade-off Evaluation Database.  In brief, Free to Choose Medicine would create an additional track after Phases I and II to allow doctors to prescribe new therapies to at-risk patients who are unable or unwilling to participate in a Phase III trial. Patients in the Free-to-Choose Track would be mandated to submit data to a trade-off evaluation database, creating a trove of valuable real-world data (this could be genetic, biomarker, and adverse events data, for instance).  See this excellent podcast interview with Bart Madden for more information. 

Figure from Bart Madden, “Free to Choose Medicine“, The Heartland Institute

 

Dan Elton, Ph. D., is Director of Scholarship for the U.S. Transhumanist Party.  You can find him on Twitter at @moreisdifferent, where he accepts direct messages. If you like his content, check out his website and subscribe to his newsletter on Substack.