Flu Vaccine Study: ‘Two for One’ Design

A recent study by Bloomberg School researchers has provided data beyond its original scope, answering unintended questions. Senior author Mark Steinhoff, MD, often uses the term "two for one" when referring to the data on flu shots for pregnant women.

The first "two for one" refers to the study's original design. Steinhoff and colleagues were funded to conduct a randomized controlled trial to evaluate the effects of pneumococcal (not influenza) vaccine on mothers and infants. Instead of using a placebo with the control group of pregnant women, these researchers gave flu shots. "Ethically," says Steinhoff, a pediatrician and professor of International Health, "we wanted to give them something with a potential benefit." But because the study was randomized and controlled—the gold standard—there was an opportunity to use the control group data to answer a separate question.

"It's a rare concept" for randomized controlled trials, says Steinhoff, "answering two completely separate questions with one study. This, in fact, was the second vaccine study where two vaccine questions were answered in one trial, both done by Hopkins researchers and [International Centre for Diarrhoeal Research, Bangladesh]." (The first study was of cholera vaccine; Robert Black, chair of International Health, and colleagues analyzed the control group of non-pregnant women who received tetanus vaccine and showed that their children subsequently born were protected from neonatal tetanus.)

The second two-for-one finding concerns protection against flu. Since 1997, influenza immunization has been recommended in the U.S. for pregnant women as a means of protecting them against the virus. Because we know that mothers transfer influenza antibodies to their infants, it's been assumed that the antibodies stimulated by a flu shot would transfer as well, protecting mother and infant. But there have been no studies proving the benefit for the infant, and despite the recommendation, only about 15 percent of pregnant women in the U.S. receive the vaccine.

This study, however, provides the proof that immunization confers two-for-one protection for both mother and infant, reducing proven influenza illness by 63 percent in newborns. This finding addresses an important limbo period for infants, who, in their first six months, cannot receive flu vaccine or antivirals and are therefore especially vulnerable to influenza. Steinhoff hopes that this data will increase immunizations of pregnant women.

The third two-for-one is the study's contribution to the body of knowledge about the natural history of influenza in Bangladesh. Researchers were able to verify that in tropical Dhaka, near the Tropic of Cancer, flu presents a year-round challenge. (By contrast, in the U.S. and other regions, flu is seasonal.)

When he submitted the paper to the New England Journal of Medicine, Steinhoff used the word "serendipity" to refer to the unexpected but favorable findings about flu in the tropics. The Journal'seditor questioned the use of the word in a scientific journal, but Steinhoff prevailed. He argued, If this study isn't a perfect example of serendipity, what is?