The Salk polio vaccine field trials constitute one of the most famous and one of the largest statistical studies ever conducted. The field trials are of particular value to students of statistics because two different experimental designs were used.
Background
The Salk vaccine, or inactivated poliovirus vaccine (IPV), is based on three wild, virulent reference strains:
- Mahoney (type 1 poliovirus),
- MEF-1 (type 2 poliovirus), and
- Saukett (type 3 poliovirus),
grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome.
The 1954 Field Trial
Statistical tests of new medical treatments almost always have the same basic format. The responses of a treatment group of subjects who are given the treatment are compared to the responses of a control group of subjects who are not given the treatment. The treatment groups and control groups should be as similar as possible.
Beginning February 23, 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania. Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis; the largest medical experiment in history. The test began with some 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and would eventually involve 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio.
The results of the field trial were announced April 12, 1955 (the 10th anniversary of the death of President Franklin D. Roosevelt, whose paralysis was generally believed to have been caused by polio). The Salk vaccine had been 60–70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. Soon after Salk's vaccine was licensed in 1955, children's vaccination campaigns were launched. In the U.S, following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States.
Experimental Design Issues
The original design of the experiment called for second graders (with parental consent) to form the treatment group and first and third graders to form the control group. This design was known as the observed control experiment.
Two serious issues arose in this design: selection bias and diagnostic bias. Because only second graders with permission from their parents were administered the treatment, this treatment group became self-selecting.
Thus, a randomized control design was implemented to overcome these apparent deficiencies. The key distinguishing feature of the randomized control design is that study subjects, after assessment of eligibility and recruitment, but before the intervention to be studied begins, are randomly allocated to receive one or the other of the alternative treatments under study. Therefore, randomized control tends to negate all effects (such as confounding variables) except for the treatment effect.
This design also had the characteristic of being double-blind. Double-blind describes an especially stringent way of conducting an experiment on human test subjects which attempts to eliminate subjective, unrecognized biases carried by an experiment's subjects and conductors. In a double-blind experiment, neither the participants nor the researchers know which participants belong to the control group, as opposed to the test group. Only after all data have been recorded (and in some cases, analyzed) do the researchers learn which participants were which.
This combination of randomized control and double-blind experimental factors has become the gold standard for a clinical trial.
The Salk Polio Vaccine Field Trial
Jonas Salk administers his polio vaccine on February 26, 1957 in the Commons Room of the Cathedral of Learning at the University of Pittsburgh where the vaccine was created by Salk and his team.