One in a Million

Dear Members of the Baylor College of Medicine Community,

The news of the day is the CDC/FDA recommended “pause” in the use of the Johnson & Johnson vaccine until the Advisory Committee on Immunization Practices (ACIP) has an opportunity to review the data related to recent complications and make recommendations on the future use of the vaccine.

I am writing this on the morning of the ACIP meeting, so I cannot predict what they will recommend, but based on the limited facts we have available, we can start to get a sense of where this is headed. I want to spend today reviewing what we know. A takeaway: Our safety monitoring system is working as intended, assessing potential risks of vaccines on a continual and systematic basis. A prediction: The J&J vaccine will continue to be used as a safe and effective vaccination option.

As I am sure most of you have already read the details, I will review them only briefly. Six people, all women between the ages of 18 and 48, developed a relatively unusual blood clot (cerebral venous sinus thrombosis or CVST). These were six events in 6.8 million vaccinations – almost literally a “one-in-a-million” event.

One question the ACIP will consider: Is this is truly a vaccine complication or just a background level of disease. When you follow 6.8 million people for a period of time, you will see a lot of heart attacks, strokes, and new cancer diagnoses that are entirely unrelated to their vaccination and would have occurred anyway. Part of the challenge in safety monitoring is figuring out if the occurrence of any event is a real signal of a complication or just background noise.

I have no inside knowledge that is not available to all of you reading this, but I suspect this “pause” was called due to a couple of concerns.

First, because of some of the specifics around this particular condition, CVST. This is a relatively rare condition, occurring with an annual incidence of 3-4 cases per million people. On first blush, this is comforting, as CVST related to J&J only seems to be occurring in one out of a million, but that is not an annual incidence – it is the incidence calculated over a few weeks following vaccination.

As a very rough, back-of-the-envelope calculation, we have been using the J&J vaccine since mid-January. If we assume the reported events were based on an eight-week period, and convert that to an annual rate, the incidence of CVST would be between 6-7 cases per million vaccinated individuals. Again, these are my casually derived estimates based on very limited and incomplete data. I suspect part of the reason for regulatory concern was the suggestion the incidence seemed to be higher than would be expected in the general population. I would point out, six in a million is still an extremely rare event.

Second, there was a relatively unusual presenting factor in the six cases, which were associated with thrombocytopenia (low platelet count). Normally, platelets help your blood to clot, so it seems paradoxical to have low platelets and an increased risk of developing blood clots. In fact, this combination occurs clinically and is often associated with an underlying immune mechanism. In this case, we have a condition (thrombosis associated with thrombocytopenia) that is known to have an immunologic basis. In the context of providing an intervention that promotes an immune response (vaccination), it is easy to see why the experts who monitor safety would want to evaluate this risk more carefully.

Our battle against COVID-19 has always felt like we take two steps forward and one step back. The J&J vaccine pause is clearly a step back, but I think a relatively small one. The greatest risk is the impact this will have on the “vaccine-hesitants” who are on the fence and will delay vaccination.

However, I think the news is more good than bad – our safety monitoring system is working as intended. During Phase 3 clinical trials, when treatments are tested with thousands of patients, pausing enrollment to look carefully at possible adverse events is common. After review, the trials usually resume. Instead of thousands of people in a trial, we are now treating millions in real life. If you add up all our vaccines, we have delivered nation-wide over 175 million total injections to date. With that many interventions, I would be suspicious of our safety monitoring efforts if we were not identifying potential issues.

As has become our pandemic habit, elements of the media and political opportunists are racing to catastrophize this event: “The FDA/CDC should have been more aggressive;” “the FDA/CDC is being overly cautious;” “they are hiding something from us.”

I think FDA/CDC got this exactly right. We have identified a potential problem. Let us pause, convene a broad coalition of experts to look carefully at the available data, and adjust our approach if necessary. Do this in a highly transparent fashion. This is what “following the science” looks like.

I would like to finish by addressing two questions. First: “If I recently received the J&J vaccine, should I be concerned.” Answer: No. With almost seven million doses of the J&J vaccine administered, even if there is a link to this blood-clotting issue, your risk of being personally impacted is vanishingly small (and after about three weeks, probably close to zero). Obviously, if you develop symptoms (severe headache, blurred vision, new onset weakness, chest pain, shortness of breath, leg pain or swelling, unusual bleeding,) please seek medical attention.

Second: “Assuming FDA/CDC recommend reintroducing the J&J vaccine to our national efforts, would you recommend it to a friend or family member?” Answer: I will wait for the official recommendation, but yes. Your chance of contracting COVID-19, becoming ill and dying far, far exceeds the risk of vaccination. To put this in perspective, we are talking about a potential – to re-emphasize, potential, not proven – thromboembolic risk that is very low. Thromboembolism is also a known complication of COVID-19. That rate is not one-in-a-million. In hospitalized COVID-19 patients, it likely occurs in one-quarter to one-third cases.

More to come.

Stay well.

James T McDeavitt, M.D.
Senior Vice President and Dean of Clinical Affairs

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