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1 Biostatistics Breakdown Common Statistical tests Special thanks to: Christyn Mullen, Pharm.D. Clinical Pharmacy Specialist John Peter Smith Hospital 2 Objectives • Briefly review important terms needed to understand common types of statistical analysis • Review the different types of data and how they determine what type of statistical analysis is appropriate to use • Explore real examples of common statistical analysis and their relevance to that particular study 3 Types of Variables • Independent ▫ Variables that occur regardless of other variables or factors Intervention in a trial • Dependent ▫ Variables that are dependent upon other variables or factors Outcome in a trial 4 Interval Arbitrary 0 Ex: Temperature (°F) Continuous Ratio Absolute 0 Ex: Blood glucose Types of Data Nominal Categories of data that do not have a rank Ordinal Data measured by a finite number of ranked categories Ex: Sex, Smoking Status, Race Categorical (Discrete) Ex: NYHA Classes I-IV 5 Central Tendency Continuous • Mean Ordinal • Median Nominal • Mode 6 Distribution Normal Distribution • Parametric Continuous Data Non-Normal Distribution Ordinal or Nominal Data • Nonparametric 7 Measures of Variability Range Interval between lowest and highest values within a data set Interquartile Range Describes interval between 25th and 75th percentile (middle 50% of measures) Standard Deviation Describes the distribution of values in a data set by comparing each measured value to the mean (continuous data only) Variance Deviation from the mean 8 Statistical Significance • P-Value – indicates statistical significance ▫ A p-value < 0.05 means that 5% of the time, the null could be rejected in error • Confidence Interval (typically 95%) ▫ The range in which sample values are likely representative of the true population • Power ▫ The ability of a study to detect specified differences between groups ▫ Increasing sample size can increase power 9 10 • Student t-test ▫ Compares means of 2 groups • ANOVA assumptions 1. Data have normal distribution 2. Each observation is independent of the others 3. The variances within the groups being compared are equal 11 • Mann-Whitney and Wilcoxan Rank ▫ Non-parametric equivalent to t-test • Kruskal- Wallis with multiple comparison correction • Wilcoxan signed-rank ▫ Alternative to log-rank analysis used in Kaplan Meier Regression 12 • Chi-square (X2) ▫ Compares categorical variables to see if there is a difference • Fisher’s exact test ▫ For a smaller sample size (n < 5) • Mantel – Haenszel ▫ Adjusts for confounding variables • McNemar ▫ Analyzes results from studies with related or dependent measures 13 Regression • Predicts the effect of independent variables on the outcome (Framingham Risk Score) • Multiple linear regression ▫ Used when outcome data is continuous • Logistic regression ▫ Used when outcome data is categorical (binary) 14 Relative Risk and Odds Ratio • Relative Risk ▫ Ratio of incidence of disease in exposed group divided by incidence in unexposed group Cohort Studies • Odds Ratio ▫ Odds of exposure in the group with the disease divided by odds in control group Case-Control Studies (approximates relative risk b/c patients already have the disease) If the Confidence Interval includes 1, there is NO statistical difference between groups 15 16 Survival Analysis • Kaplan- Meier Curve ▫ Assesses time to an event ▫ Log-Rank test will tell if differences between 2 groups are significant • Cox Proportional Hazard Model ▫ Assesses the effects of covariates (2 or more) on survival or time to an event (adjusts for confounders) ▫ Uses Hazard Ratio as a function of relative risk 17 Propensity Matching • Used to decrease selection bias by matching participants based on characteristics ▫ Matching can be done based on a score ▫ Can set number of significant digits depending on how precise you want to be • Allows for a more confident assessment of the intervention • Instrumental variable analysis ▫ Gives each participant a probability of receiving an intervention and then apply it to an entire group (grouped-treatment rate) ▫ Takes away selection bias based on prognosis or prescriber preference 18 19 References • • • • • • • • • • • Allen, J. Applying study results to patient care: Glossary of study design and statistical terms. Pharmacists Letter.. 2004;20:3-14. Gaddis, GM and Gaddis, ML. Introduction to biostatistics: Parts 1-6. Annals of Emergency Medicine. 1990; 19. Israni, RK. ‘Guide to Biostatistics.” MedPageToday. 2007. http://medpagetoday.com DeYoung GR. Understanding statistics: An approach for the clinician. Pharmacotherapy Self-Assessment Program, 5th Edition. Pg 1-15. Al-Qadheeb NS, et al. Impact of enteral methadone on the ability to wean off continuously infused opioids in critically ill, mechanically ventilated adults: A case control study. The Annals of Pharmacotherapy. 2012;46:11601166. Marcus M, et al. Kinematic shoulder MRI: The diagnostic value in acute shoulder dislocations. European Radiology. 2012;1-6. Stefan MS, Rothberg MB, Priyaa, et al. Association between B-blocker therapy and outcomes in patients hospitalized with acute exacerbations in chronic obstructive lung disease with underlying ishaemic heart disease, heart failure or hypertension. Thorax. (2012): DOI:10.1136/Thorax.JNL-2012-201945 http://stat.ethz.ch/education/semesters/ss2011/seminar/contents/presentation_2.pdf. Accessed 20 Sept 2012. http://www.gog.org/sdcstaff/MikeSill/Classes/STA575/Lectures/LectureNotesChp5.pdf. Accessed 25 Sept 2012. https://statistics.laerd.com/spss-tutorials/mann-whitney-u-test-using-spss-statistics.php. Accessed 24 Sept 2012. http://www.experiment-resources.com/mann-whitney-u-test.html. Accessed 26 Sept 2012.