Article & Final Reviews Session 7 Article & Final Reviews Youngju Pak, Ph.D. (ypak@labiomed.org)

McCann, et al., Lancet 2007 Nov 3;370(9598):1560-7 Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Target population: 3-4, 8-9 years old children Study design: randomized, double-blinded, controlled, crossover trial Sample size: 153 (3 years), 144(8-9 years) in Southampton UK Objective: test whether intake of artificial food color and additive (AFCA) affects childhood behavior

Case Study: Participant Selection It may be that only a few schools are needed to get sufficient individuals. If, among all possible schools, there are few that are lower SES, none of these schools may be chosen. So, a random sample of schools is chosen from the lower SES schools, and another random sample from the higher SES schools.

Why Randomize? So that groups will be similar except for the intervention. So that, when enrolling, we will not unconsciously choose an “appropriate” treatment for a particular subject. Minimizes the chances of introducing bias when attempting to systematically remove it, as in plant yield example.

Case Study: Crossover Design Each child is studied on 3 occasions under different diets. Is this better than three separate groups of children? Why, intuitively? How could you scientifically prove your intuition?

McCann, et al., Lancet 2007 Nov 3;370(9598):1560-7 Sampling: Stratified sampling based on SES in Southampton, UK Baseline measure: 24h recall by the parent of the child’s pretrial diet Group: Three groups, for 3 years old mix A : 20 mg of food colorings + 45 mg sodium benzoate, which is a widely used food preservative, and mix A was used at the previous study. mix B : 30mg of food coloring + 45 mg sodium benzoate(current average daily consumption for 3 and 8-9 years old children in UK) Placebo Mix A for 8/9 years old: multiply these by 1.25 Cross-over Design A participants receive one of 6 possible random sequences. In a separate study with N=20, no significant difference in looks and taste of drinks among three groups was found even though people ask about which diet type they got when they received placebo (65%) > mix B (52%) > mix A (40%) Typical Diet Randomize Washout Randomize Washout Randomize T0 (baseline) Week 1 Week 2 Week 3 Week 4 Week 5 Week 6

McCann, et al., Lancet 2007 Nov 3;370(9598):1560-7 Outcomes: Global Hyper Activity(GHA) Score Attention-Deficit Hyperactivity Disorder(ADHD) rating scale IV by teachers, scaled 1 – 5, higher number means more hyperactive Weiss-Werry-Peters(WWP) hyperactivity scale by parents, Classroom observation code, Conners continuous performance test II (CPTII)  GHA to be aggregated from these four scores

Why standardized outcome measure? Biostatistics in Practice Fall 2015/Session2 7/6/2018 Why standardized outcome measure? GHA = Global Hyperactivity Aggregate , where a higher value ↔ more hyperactive For each child at each time: Z1 = Z-Score for ADHD from Teachers Z2 = Z-Score for WWP from Parents Z3 = Z-Score for ADHD in Classroom Z4 = Z-Score for Conner on Computer , where Z-score= (Score-Score at T0)/SD to make each measure scaled similarly. GHA= Mean of Z1, Z2, Z3, Z4. When comparing two groups(group1-group2), a positive difference means that the group1 increase GHA more than group2. Thus, we expect positive mean differences for mix A or B – Placebo

We have learned .. 1. Study designs 2. Descriptive vs. Inferential statistics 3. Hypothesis testing and a p-value 4. Five elements to determine a sample size 5. Covariates and multivarite regression models 6. Bonferroni’s correction

What are left in your statistical brain?

Where we started will be where we end! How to describe the results from statistical inferences. If two psychiatrists agrees no better than random chance (H0), the probability of observing sample kappa statistics of 0.5 or higher is __, which is contradictive to the H0. Thus, we will reject H0 favoring that two psychiatrists agrees better than random chance (Ha). There is still a certain chance that our conclusion might be wrong because there is ?? chance observing k^ > 0.5 under H0 but we believe that is very rare since that chance is substantially low, and below the threshold value of 5%(type I error rate). Therefore, we will reject H0 (p-value = ___ )favoring that two psychiatrists agrees better than random chance (p-value = __ ) with a risk of 5% making a wrong conclusion(Type I error rate ).

Biostatistics in Practice: Session 6 EPILOGUE GIVE A BIG CLAP TO YOURSELF SINCE YOU ‘VE MADE THIS FAR ! CONGRATULATION !!!