Background: Polio, also known as infantile paralysis, is an infectious disease that strikes young children, often causing permanent paralysis. It spreads through person-to-person contact. In the 1950's, American scientist Jonas Salk developed a vaccine that protected monkeys from polio and was safe when injected into human subjects in the laboratory in the 1950's. By 1954, the vaccine was ready to be tested in the real world. In order to determine if the polio vaccine reduces the risk of polio infection, a cohort of children were invited to take part in a study. However, only some children had parental consent to receive the vaccine, which posed a problem for researchers. Two different study designs are conducted: First design: Children with parental consent were divided into two groups - treatment and control. The treatment group was vaccinated, and no placebo was given to the control group. All children without parental consent were placed in the control group as well, since they were not allowed to take the vaccine. This was known as the NFIP study (you may read up more on this if you wish). Second design: Only children with parental consent were considered in this study. Those without consent were excluded. Children with parental consent were assigned into the treatment and control groups based on a 50-50 randomised procedure. The control group received a placebo injection of salt dissolved in water. Doctors involved in the diagnosis were not told which group the children belonged to. The results of the two studies are tabulated as shown below. Sample NFIP study Polio +ve Polio -ve size Vaccinated (with parental consent) 225000 56 224944 Control (parental consent or no parental consent) 725000 391 724609 Sample Randomized controlled trial Polio +ve Polio -ve size Treatment 200000 56 199944 Control 200000 142 199858 Furthermore, some important characteristics of the different groups were discovered: Families who provided consent tended to be of a higher income group and as a result lived in more hygienic conditions. Children living in more hygienic conditions were more susceptible to polio as they were not exposed to the virus since young and lacked immunity to the virus.3a) Calculate the following for both study designs. For rates, leave your answers in percentages corrected to 3 5.f. (i) Find the conditional rate of getting polio given that they are vaccinated. (ii) Find the conditional rate of getting polio given that they are in control group. (iii) Comment on the appropriateness of using rates rather than absolute numbers for comparison in the NFIP study. 3b) Compare the two study designs by answering the questions below. (i) Were the children randomly assigned into treatment and control groups? NFIP study Randomized controlled trial (RCT) Random Assignment E.g. a random number generator was done to assigned children with parental consent into the treatment or control group. (ii) Discuss how the assignment in 3b(i) might affect the results of the studies NFIP study Randomized controlled trial (RCT) With large enough samples, all the important characteristics of both treatment and control group subjects will resemble each other very closely Allows for only the differences to be due to the response to the vaccine. (iii) Were the subjects/assessors blinded? NFIP study Randomized controlled trial (RCT) It was not stated if the doctors are blinded but the children knew if they were vaccinated or not as no placebo was given.(iv) Discuss how the blinding in b(iii) might affect the results of the studies NFIP study Randomized controlled trial (RCT) Double-blinding was not done for the NFIP study, which may lead to bias. For example, children in the control group who know that they are not getting the vaccine might result in them taking their own measures to reduce their risk of getting the disease. On the other hand, vaccinated individuals might think they now have full immunity and would be less stringent in health safety. Remark: In general, the importance of blinding depends on the context of the study. In some cases, whether subjects are blinded or not may not affect the results of the study. Nonetheless, blinding and the use of placebos act as important precautionary measures, especially in situations where it is difficult to tell if blinding can have an impact on the results or not. (v) According to the table of results, by how much does the vaccine reduce the polio rate? If we consider the discussions in b(i) to (iv), do you think the vaccine more or less effective than what is stated in the table of results? Consider each study separately. NFIP study Randomized controlled trial (RCT) The vaccine reduces the polio rate by 0.071% - 0.028% = 0.043% The actual effect is likely to be similar to 0.043% as the study was conducted with randomised assignment, double blinding and large sample size