A Vaccine's Effect Is In the Real World Is the True Measure Of Its Success

"No plan survives contact with the enemy." Helmuth von Moltke, creator of Germany's WWI strategy.  

"When you put a vaccine out in the real world, people may behave differently." Dr. Paul Offitt, Director of The Vaccination Center at Childrens' Hospital, Philadelphia. JL

Jaimy Lee reports in MarketWatch:

Clinical trials are conducted in controlled clinical settings that aren’t likely to be replicated in the real world. “In the clinical trial, you select the patients that you like, and you follow them very closely. In the real world, there’s all kinds of ages, and everyone has different underlying health conditions.” “When you put [a vaccine] out in the real world, people may behave differently. They think, ‘Great. I’m good. The vaccine works. It’s 90% effective. I can take off my mask.’”

BioNTech and Pfizer Inc.’s unexpectedly efficacious COVID-19 vaccine candidate caught Wall Street and the medical community by surprise this week, yet the same experts who are thrilled by the news caution that the effectiveness of the vaccine will likely be lower in the real world.

Shares of Pfizer PFE, +2.85%  were up 1.7% in trading on Friday, while BioNTech’s BNTX, +4.30%  stock had gained 3.9%.

The companies, which in March teamed up to develop a coronavirus vaccine, said Monday in a news release that an interim analysis from the Phase 3 clinical trial indicates BNT162b2, their investigational mRNA vaccine, has an efficacy rate that is higher than 90%. The study’s protocol calls for an efficacy rate of 60%.

“Given everything the world is going through and being humble enough to admit there’s a lot we are still learning about this virus, it was still a relief to see,” Raymond James analyst Steve Seedhouse wrote in an email.

But clinical trials are also conducted in controlled clinical settings that aren’t likely to be replicated in the real world.

“In the clinical trial, you select the patients that you like, and you follow them very closely,” said Mizuho Securities analyst Difei Yang. “In the real world, there’s all kinds of ages, and everyone has different underlying health conditions.”

In studies like the ones being conducted for the COVID-19 vaccines, this could include anything from how a vaccine is stored and handled by medical professionals to the types of people who volunteer to participate in a clinical study, who may be more likely to socially distance and wear a mask, especially if it’s unclear whether they received the investigational vaccine or the placebo.

“When you put [a vaccine] out in the real world, people may behave differently,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “They think, ‘Great. I’m good. The vaccine works. It’s 90% effective. I can take off my mask.’”

In addition, the data shared by BioNTech and Pfizer was gathered roughly two months after trial participants received the second and final dose of the vaccine candidate. There are still questions about how long immunity to the virus lasts, either by natural infection or vaccination, and differing lengths of durability could impact the effectiveness of a vaccine.

“As the vaccine is adopted in the real world, if durability of effectiveness wanes over months, then you would start to see a reduction of that 90% number over time,” Seedhouse wrote. “But while we don’t know a lot about [the] durability of immunity yet, the general lack of widespread reinfection a year or so into this pandemic suggests durability might be good enough to retain such a high efficacy even in the real world.”

There is still no detailed information about how the vaccine performed in different vulnerable patient populations, including the elderly and those with co-morbidities such as diabetes or hypertension that may make them more susceptible to infection and more severe forms of the disease. (BioNTech and Pfizer have not yet released the study in peer-reviewed or preprint format, which would provide more detailed findings from the late-stage trial, but have said they will do so.)

Knowing how the vaccine worked in older people or those with co-morbidities “will tell us truly how good the vaccine is,” Yang said. “One of the expectations that has been out there is that people were not sure that we are able to return to where we were, even with the vaccine.”

There are a handful of vaccines in late-stage development in the U.S., including one from Moderna Inc. MRNA, +1.79%, which is also developing a mRNA vaccine and is expected to soon release data from its Phase 3 clinical study.