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Editor's Notes |
alanjette{at}apta.org
Fifty years ago, on April 12, 1955, Dr Thomas Francis, an epidemiologist on faculty at the University of Michigan, announced to the world that he had just completed a study demonstrating that the Salk vaccine was "safe, effective, and potent" in preventing paralytic poliomyelitis. He released findings that showed convincing statistical evidence that the Salk virus preparation was 80% to 90% effective.1
In the decades before Francis' landmark announcement, physical therapist management of patients with polio brought our profession to the forefront of public attention. Polio was the catalyst for some of the skills that today we regard as fundamental to physical therapist practice: advanced muscle testing, gait training, and the teaching of functional activities. With subsequent extensive commercial production and widespread distribution of the Salk vaccine (and, eventually, the Sabin vaccine), Francis' feat ultimately led to the eradication of polio in the United States and, concomitantly, to a drastic change in the physical therapy profession. We began as a small cadre of physical therapists who tended primarily to wounded soldiers needing rehabilitation and to people who had polio. With the end of the polio epidemics, we applied foresight and courage both to bring our unique skills to many other types of patients who were in critical need of our interventions and to convince society of the value of our services. The process continues to this day.
Few today appreciate how remarkable the Francis field study was for its time, both in scope and in magnitude. As Dr Myron Wegman, Dean of the University of Michigan School of Public Health, noted at a dedication to Francis in 1970, "In an age of house-sized computers, IBM punch cards, propeller planes, and rotary telephones, the field trial that Thomas Francis proposed to test the safety and effectiveness of Jonas Salk's polio vaccine could have been seen as madness."2
The polio field trials involved approximately 1,830,000 children in 217 areas of the United States, Canada, and Finland. More than 300,000 individuals participated in the field trials—20,000 physicians and public heath officers, 40,000 registered nurses, 14,000 school principals, and 200,000 volunteer workers. A team of 100 individuals was responsible for tabulating the data received from the public health officials and health care professionals in the field who were participating in the study. Physical therapists were directly involved. During the trials, muscle testing was performed by 66 physical therapists in 44 states and 3 Canadian provinces as part of the follow-up phase.3
Until recently, I didn't realize how close the Salk vaccine study had come to being a scientific failure. The Francis announcement in 1955 actually was the culmination of 2 massive field trials of the Salk polio vaccine instead of the originally planned single trial. The original field trial, designed by a private foundation (the National Foundation for Infantile Paralysis), called for an experimental treatment arm involving the vaccination of second graders at selected schools in selected regions. The first and third graders at the same schools would not be given the vaccination and thus would form the control group. This design was called the observed control experiment. The study designers felt that use of a placebo control was too much of a risk—one that parents, teachers, and public health officials would reject. As Salk was quoted as saying about randomized controlled trial design, the original trial would have been "a ‘beautiful’...experiment over which the epidemiologist could become quite ecstatic but [which] would make the humanitarian shudder."4
The initial design was widely criticized by scientists and others because of 2 serious flaws: selection bias and diagnostic bias.3 Only second graders with parental consent could be vaccinated, and the consenting parents tended to have higher incomes than the non-consenting parents. Because the incidence of polio was related to parental income (those from lower-income families seem to have developed some early-life immunity that those from higher-income families did not), selection bias against the vaccine was a concern. Without blinding the parents and the health care professionals to the children who received the vaccination, diagnostic bias also was possible, because professionals might be a bit more likely to diagnose polio in an unvaccinated child. The dual effect of selection bias and diagnostic bias, therefore, would have made the results of the original trial difficult to interpret. Francis was brought in to salvage the study.
To overcome the deficiencies of the original design, Francis proposed using what is now regarded as the classic randomized, double-blinded controlled design in addition to the observed control experiment. In his design, a sample of children from participating states would be selected, all of whose parents would grant consent to participate in the trial. Following consent, the sample would be randomly assigned into a vaccination "experimental" group and a placebo "control" group, thus eliminating selection bias. All children and parents and the health care professionals doing follow-up diagnoses would be blinded to which children received the vaccine, thus eliminating diagnostic bias.1
In the end, 84 test areas in 11 states agreed to use Francis' randomized, double-blinded controlled design, whereas 127 test areas in 33 states opted for the observed control design. Francis decided to retain the original observed control design alongside his more internally valid design as a powerful means of maintaining public support for the vaccine. At the time of the trials, there was a climate of scientific doubt around Salk's killed-virus vaccine. Francis felt it was essential that the field trials offer public as well as scientific validation of effectiveness. He wanted the trials to be an enormous national event, enlisting thousands of volunteers across the country in a united effort to overcome this dreaded disease. In the end, 623,972 school children were injected with either vaccine or placebo, and more than 1 million others participated as observed controls. Analyses of data derived from both designs showed the vaccine to be safe and effective, and the vaccine became one of the greatest triumphs in public health science in the 20th century.
The Americas were judged polio free more than 10 years ago; however, worldwide, more than 1,200 polio cases were reported in 2004, with most concentrated in 6 countries that face the biggest threat.5 The World Health Organization has set a goal of eradicating poliomyelitis worldwide by the end of 2005.6 If this goal is achieved, polio will become the first disease eradicated in the 21st century.
Francis' successful conduct of the double-blinded randomized controlled polio vaccine trial—a trial in which physical therapists played a critical role—set the standard against which all efficacy designs are judged today. I often hear clinician colleagues voice Salk's initial ethical concerns as they talk about randomized controlled clinical trials that would withhold what they believe to be an efficacious physical therapy intervention for their patients. For me, the 50th anniversary of the polio trials is a dramatic reminder that these ethical concerns are not unique to physical therapy and that, with careful design, planning, and active clinical collaboration, these concerns can be overcome, just as Francis overcame them half a century ago.
References
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