3 reasons why Pfizer and BioNTech’s coronavirus vaccine could fail even if it works

Pfizer (NYSE: PFE) and BioNTech (NASDAQ: BNTX) are set to produce Phase 3 data that could show their coronavirus vaccine, BNT162, protects participants from the development of COVID-19 better than placebo. But investors should be aware that certain caveats could result in a negative clinical trial even if the vaccine actually helps patients.

1. Early infection

The clinical trial begins classifying patients as positive for COVID-19 if the test takes place seven days after the second and last dose of the vaccine. Pfizer and BioNTech set the measure based on antibody formation in participants enrolled in early stage studies, but if it takes longer to fully protect participants, some of the participants who received the vaccine could be infected. between day 7 and when the participant is truly protected, which would reduce the perceived effectiveness of the vaccine.

2. Viruses in the nose

The vaccine is designed to create antibodies that can bind to and inhibit the coronavirus once it enters the bloodstream. But COVID-19 tests look for the virus in patients’ noses.

Study participants could be protected from the coronavirus, but still test positive for COVID-19 because the immune system does not clear the virus in the nose and upper respiratory tract where the test sample is taken.

It is possible that a participant will end up being exposed to the virus, not end up developing COVID-19, but still be considered a positive case based on detection of the virus in the patient’s nose.

Image source: Getty Images.

3. False positive test

COVID-19 tests are not 100% accurate. A study of 90 patients tested with a COVID-19 test developed by Danaherof (NYSE: DHR) The Cepheid unit, which is used in the Pfizer and BioNTech study, produced two false positives.

The Pfizer and BioNTech study also requires patients to have at least one symptom within four days before or after testing positive to be counted as a positive COVID-19 case, but many symptoms, including fever, cough. , throat, diarrhea and others, are associated with other milder illnesses.

With 21,000 volunteers in the study receiving the vaccine, it’s easy to imagine that there might be a few participants who get a false positive test and also have one of these rather mild symptoms.

Difficult to handicap

While all three problems are theoretically possible, it is difficult to determine to what extent they will end up affecting the patients who received the vaccine in the clinical trial. Unfortunately, even a small effect could influence the results, since the first results of the study depend on very small numbers.

The first interim analysis, for example, comes after only 32 people in the study developed COVID-19. If six or fewer cases are from the group that received the vaccine, the study will be considered a success, but a single false-positive person in the group could push the analysis beyond the criteria for success.

Of course, it’s just as likely that all three issues would result in a false positive in the placebo group, but a false negative in each group could still skew the results compared to a statistically significant result. Consider the possibility that a real result would be that six participants who received the vaccine received COVID-19, while 26 participants who received a placebo developed COVID-19. Add only one more false positive to each group before the true reading, and now the ratio could be 7:25 after 32 cases, which would result in a negative intermediate result.

There are several interim analyzes in the study, so failure isn’t necessarily the end of the world, but a cumulative addition of false positive patients could potentially negate the final action, which will be taken after 164 positive COVID-19 cases. .