COVID Transmissions for 3-24-2021

More miscommunications from AstraZeneca

Mar 24, 2021

Greetings from an undisclosed location in my new apartment. Good morning and welcome to COVID Transmissions.

It has been 492 days since the first documented human case of COVID-19. In the year 492, the 48th Bishop of Rome (aka the Pope) died, shortly after starting a schism with the Patriarch of Constantinople over some rather esoteric matters of faith.

Today in 2021, and many Popes later, miscommunications still are a problem that plagues humanity. Today we’ll discuss one having to do with vaccines.

As usual, bolded terms are linked to the running newsletter glossary.

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AstraZeneca accused of various types of data misreporting

Over the course of the day, a story has evolved revealing that AstraZeneca appears to have released preliminary data regarding their vaccine candidate—which was very positive for the product—when they had available more complete data from later in their US trial.

When first released, these data were suggested to be the basis for an upcoming approval of the product in the US by the FDA. Now I am not so sure, because this is the latest in a series of bizarre problems with how the trials of that vaccine were conducted. First, there were issues with the reporting of safety data from the trial, which I found strange at the time. Then, there was a reagent quality error that led to a surprise result in terms of the vaccine dosing schedule. Now there is this strange reporting of “interim” data when final data were, apparently, already available, or at least in a state where they could have been analyzed.

What happened is this. AstraZeneca released its press announcement, and shortly thereafter a statement was put out by their study’s Data Safety Monitoring Board (DSMB) questioning if these data were the most accurate available. The DSMB felt that it could be misleading to use the interim data, which included only cases of COVID-19 that had occurred on-study through February 17th, when a dataset with longer followup was available.

In response, AstraZeneca promised to release a more up to date analysis within 48 hours. That clock has not yet run out.

I echo Tony Fauci in saying that this is really very unfortunate and amounts to an unforced error: https://abcnews.go.com/Politics/fauci-calls-outdated-data-astrazenecas-us-vaccine-trial/story?id=76629244

My career has been divided into two major eras: one where I was an active virology researcher in an academic lab, and another where I have been a communications and clinical trials expert within the pharmaceutical industry. I feel very qualified to say that this miscommunication of the results of a virus vaccine clinical trial was a serious amateur-hour situation, and I am at a loss to understand how it could have happened. AstraZeneca is an extremely well-established pharmaceutical company that really ought to know better. Perhaps their small portfolio of vaccines means they are inexperienced in vaccine communications; I am not sure.

Regardless, this is exactly the kind of problem that a good vaccine communications professional does everything in their power to avoid. There are enough people who assume that all communications from Pharma companies are given in bad faith as it stands. When those communications turn out to be wrong for completely avoidable reasons—such as not waiting two days for a more final analysis to be completed—it undermines public trust in vaccines and in pharmaceutical products in general. There is a reason that every pharmaceutical company I have ever worked with has emphasized integrity above all other principles, and unfortunately, it seems that AstraZeneca failed to live up to this principle in this case.

The saddest part is that I don’t think there is really any problem with the vaccine. It has undergone worldwide trials and we do have quite a lot of data about it. It appears to be relatively safe and acceptably effective, based on those data. For whatever reason, this particular dataset was rushed into public view, and I can’t imagine a good justification for doing that. I imagine that someone at the company—many someones, in fact, because such decisions are never made in isolation—simply wasn’t thinking about the consequences of speaking too soon.

I expect what we see from the vaccine in 48 hours will be in line with what we have seen from it already around the world. I do not think this will undo whatever damage has been done by this debacle, though, and I’m highly disappointed.

Still, do not let the incompetent miscommunication that happened here be the reason that you don’t get this, or any other vaccine. When all data are available, let the science be your guide instead.

This is still a vaccine manufactured and tested to a very high standard, and at the end of the day I think this incident is just a terrible communications blunder more than anything else. It is worthwhile to consider, perhaps, just how much worse things might be—as we’ll do in our next item.

DIY vaccines are NOT a solution

I have seen a lot of sketchy things in my career, particularly when I was a consultant for a small company and many other small companies wanted us to work with them. There is a world of small pharma out there, and small pharma is not always good pharma. Companies that are trying hard to survive, and that can’t attract the best talent, sometimes have problems in their product development, their communications, and their behaviors. While big companies also do bad things sometimes, the limited resources and often limited experience of small companies leads to things that go far beyond what would get you fired on the spot in a large, established pharma company.

I relate this experience because it is relevant to a story that I found courtesy of reader Carl Fink. As it turns out, there are some small manufacturers of vaccines as well as independent scientists who have been manufacturing untested “DIY” vaccines for COVID-19 and even administering them to actual patients without authorization. Some stories about this are related in this New York Times article, from back in fall 2020: https://www.nytimes.com/2020/09/01/science/covid-19-vaccine-diy.html

Look, there was a time when scientists making their own vaccines and testing them on themselves, their families, and their local communities was the norm. When this was the case, traveling by oxcart or horse carriage was also the norm, and clinical trial sciences were not nearly so well-developed. Furthermore, there was very little medical practice regulation and very little experience with bioethics as we have today.

While the global pandemic may feel like a pressing emergency, there are ways to speed up vaccine development that preserve the scientific integrity of the process, and there are ways that do not. The approaches described in that article do not preserve scientific integrity. There is little possibility for a consistent quality standard to be applied in small-scale lab batches of experimental vaccines, and without a quality standard being met it becomes nearly impossible to rely on the outcome of small experiments with small numbers of patients. Even AstraZeneca, which has a massive international operation, had a small dosing mistake that impacted its vaccine clinical trials; I do not understand, therefore, why any scientist thinks they could do better, working on their own, without oversight, quality control, or a team to check their work.

I share this story partly to warn you about potentially dangerous products, but also to contrast how I know the authorized vaccines are made with these more fly-by-night operations. The authorized, FDA-reviewed vaccines are all created at facilities that use the “GxP” suite of pharmaceutical industry standards. “G” and “P” stand for “good” and “practices.” “x” is a placeholder for several sets of processes that can have good practice. L (good laboratory practices), C (good clinical practices), M (good manufacturing practices), and P (good publications practices) are all some examples of specific GxPs in common use in the industry. The GxP processes are used to ensure a quality output of scientific data and of the product itself from the very beginning of development. They call for consistent and transparent documentation, availability of records to regulators, and multiple redundant process controls that allow oversight, error detection, and error correction. There are widely-established norms for how errors are handled through these processes. At most pharmaceutical companies, every employee must take a full suite of GxP trainings and is aware of the consequences of a “QE”—a “quality event,” where the standards are not upheld.

A company like AstraZeneca, even with the mistakes it has made, has GxPs implemented throughout its organization. These practices take a lot of resources to implement, but without them, regulators will put you out of business. You can rest assured that each and every mistake made by AZ in their COVID-19 development will trigger some kind of QE investigation, and I think quite a few of these QEs will lead to what we call a “CAPA”—a corrective and protective action.

For the smaller DIY operations, I do not think we can be confident that there is a robust GxP system in place. In several cases I think it’s very clear there is not. Like I mentioned, it’s expensive to implement GxPs and they require a lot of training. They are also essential to making a safe product.

It is very easy for medicine to become poison. There was an era in the world when it was impossible for the consumer to tell the difference most of the time. While there are still sporadic—but well-publicized—examples of missteps, for the most part the existence of accepted industry GxP standards has made these examples more exceptions than the rule. Through regulation, both self-imposed and government-imposed, the pharmaceutical industry has moved on from the days of snake oil, by and large.

In times of emergency, though, people’s desperation can cause them to turn to less reputable providers. Please don’t let yourselves get so desperate as to turn to unreliable products billing themselves as “cures,” “treatments,” or “vaccines” that do not have reputable data to back up their claims. My sentiment here is echoed within this piece from Science magazine: https://science.sciencemag.org/content/369/6511/1570

While these links are all from the early fall of last year, I think with the national vaccine rollout there is still a chance for unwise or unscrupulous actors to take advantage. Be aware of what you are getting, and trust the vaccines that have been through the rigorous and robust FDA review process. Other options from less reputable sources need not apply.

What am I doing to cope with the pandemic? This:

Scheduling a vaccine appointment

I have, for some time, been qualified to receive the vaccine in New York State. There are a variety of ways I could qualify, but the one that most distinctly works for me is obesity as defined by body mass index. In 2020, as I’ve documented here, I lost almost 40 pounds. I have made back some of that weight loss in muscle gain, and so my BMI is again past the threshold. It’s not as though I have a perfect body fat percentage here at this point, though, but it remains that BMI is not a terribly good measurement of someone’s metabolic health. Still, I don’t make the rules, and the rules say a BMI of 30 or above qualifies for vaccination.

When comorbidities were first added as a reason to qualify for vaccination, I did not pursue it because vaccine supplies were still relatively low and I felt I could let others take my place in line. I had little reason to go out in public so the need did not feel very urgent.

However, I have recently changed my mind, based mostly on two factors: (1), vaccine availability has essentially more than tripled in a very short time and (2) I get a lot of questions about vaccination and I would like to say with confidence that I went ahead, got a vaccine, and really put my money where my mask is.

Since I communicate publicly about the COVID-19 pandemic and the importance of vaccination, I think it’s important that I communicate about my willingness—and enthusiasm—to get the vaccine. You’ll hear more about this here, in about a week, after I’ve had my first dose.

I owe a number of you comment replies, email replies, or coverage of specific news stories—I have not forgotten these! Give me a few days to get back into the swing of things after my brief hiatus.

You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

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