CLINICAL RESEARCH METHODS VISP356. MODULE LEADER: PROF A TOMLINSON B.Sc./B.Sc.(HONS) OPTOMETRY

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1 DIVISION OF VISION SCIENCES SESSION: 2005/2006 DIET: 1ST CLINICAL RESEARCH METHODS VISP356 LEVEL: MODULE LEADER: PROF A TOMLINSON B.Sc./B.Sc.(HONS) OPTOMETRY MAY 2006 DURATION: 2 HRS CANDIDATES SHOULD ATTEMPT FOUR QUESTIONS PLEASE READ THE QUESTIONS CAREFULLY MATERIALS TO Lined Examination Script Books BE SUPPLIED/ALLOWED: Unlined Examination Script Books Other Materials, e.g. Graph paper, statistical tables (please specify) formula sheets attached Page 1 of 8

2 1. a) Describe briefly each of the following concepts within the context of statistical data analysis: (i) statistical hypotheses. (2) (ii) test statistic. (3) (iii) p value. (3) b) A study was conducted into tear film osmolarity in patients with normal and dry eyes with a view to assessing its effectiveness as a diagnostic tool for detecting keratoconjunctivitis sicca (KCS). A random sample of patients in each category was obtained and had their tear film osmolarity (a measure of dissolved solute levels) measured. As part of the study, it was decided to investigate if tear film osmolarity would be higher for dry eye patients. The collected data were as follows: Normal: Dry Eye: The SPSS statistical software package was used to create exploratory and nonparametric inferential data analysis output for these data (see Appendix A). Use the output provided to answer the following. (i) (ii) Carry out an exploratory data analysis of the tear film osmolarity data with respect to the study objectives. (4) Test, at the 5% significance level, whether there is sufficient evidence to suggest that tear film osomlarity is higher for dry eye patients. State clearly the hypotheses being assessed and the practicality of the conclusion reached. (4) c) A paired samples study is planned to investigate how axial length of eyes in anisohypermetropic amblyopic patients without strabismus differ in order to assess if this difference could be used for clinical diagnosis. In the selected patients, the axial length of the healthy eye and the amblyopic eye are to be measured (in mm). The investigator is unsure of the number of patients to select for the study. A mean difference of 0.9mm is thought to be sufficient to indicate significant difference in axial length. Past studies suggest a standard deviation estimate of 1.13mm can be assumed for the axial length difference. The paired comparison t test is to be carried out at the 1% significance level with power approximately 90%. Estimate the number of patients necessary for this study. Comment on your answer. (4) Page 2 of 8

3 2. a) Linear regression is a statistical method designed to determine a linear model to describe the relationship between an independent variable X and a dependent variable Y. Its purpose is to find the best fitting linear model between Y and X. Explain the steps necessary to conduct an appropriate exploratory and inferential data analysis of a proposed linear regression model for two variables, X and Y. Comment on the purpose (or reason) for each step. (5) b) A study was conducted into tear physiology and its link to the phenol red thread test (PRT, mm). As part of this study, it was suggested that PRT could be modelled as a multiple linear function of the variables patient age (Age), tear meniscus height (TMH, mm) and tear turnover rate (TTR, %/min). The data related to this aspect were as follows: Age TMH TTR PRT Age TMH TTR PRT The SPSS statistical software package was used to create data analysis output for these data (see Appendix B). Use the output provided to help answer the following. (i) (ii) (iii) In the inferential part of the output provided, the numerical value of the relevant test statistic has been omitted. Show that the test statistic is F = (2) Using the test statistic calculated in (i), assess whether there is sufficient evidence, at the 1% significance level, to suggest that a multiple linear model for the phenol red thread test response as a function of patient age, tear meniscus height and tear turnover rate is valid. State clearly the hypotheses being assessed and the practicality of the conclusion reached. (4) State the adjusted coefficient of determination and comment on its practical meaning. (2) c) On next page. Page 3 of 8

4 Question 2 (continued) c) A repeated measures study was conducted into the growth of various strains of Pseudomonas aeruginosa on different hydrogel contact lenses. The study was set up to assess if different bacterial strains adhere in different ways to certain types of contact lens. It is known this bacterium can cause inflammation of the cornea. Three strains of Pseudomonas aeruginosa were tested, labelled as A, B and C (PsStrain). Four types of contact lens were tested: silicone hydrogel (control), and three hydroxyethyl methacrylate (HEMA) lenses whose water content increased from HEMA-A to HEMA-C. Counts of relative primary adhesion were made and were reported in CFU/mm 2 (Colony Forming Units). The investigator was unsure of whether the reported response data would conform to the normality assumption and so elected to transform the data by taking logarithms before conducting the analysis. The SPSS statistical software package was used to create statistical output for the transformed adhesion data (see Appendix C). Use the output provided to help answer the following. (i) (ii) Interpret the ANOVA output to decide whether there is sufficient evidence, at the 5% significance level, to suggest that the Pseudomonas aeruginosa strain and type of contact lens interact in their effect on adhesion. State clearly the hypotheses being assessed and the practicality of the conclusion reached. (4) Use the Pseudomonas aeruginosa strain type of contact lens interaction plot to assess and evaluate the interaction effect. (3) 3. a) Briefly describe the seven differences between a Clinical Trial and other designs employed in clinical research (e.g. prospective cohort studies). (9) b) What are the technical and ethical issues which may be barriers to conducting Clinical Trials? (4) c) In analysing Clinical Trials data what approaches are taken and which is the most commonly applied technique. (7) Page 4 of 8

5 4. Describe the following, as used in epidemiology: a) An epidemic and an endemic disease. (2) b) Prevalence of a disease. (2) c) General mortality and infant mortality and their uses. (8) d) Years of potential life lost, and its importance. (4) e) Survival time, and the problems of its definition. (4) 5. You are measuring visual acuity. Your patient can read every letter correctly on the 6/12 line (and all letters above this). He correctly reads five out of six letters on the 6/9 line, four out of eight letters on the 6/6 line, one out of eight letters on the 6/5 line and no letters on the 6/4 line. a) Sketch a psychometric function of letter size versus percent correct letter identification for this patient. (8) b) How do you define this patient s visual acuity? Justify your answer and link it to the graph. (3) c) Indicate, with the aid of the psychometric function, what specific property this point (threshold for visual acuity) has. (3) d) What drop in visual acuity at the next visit would you consider significant and why? (6) END OF PAPER Page 5 of 8

6 Appendix A [Question 1(b)] Osmolarity Normal Dry eye Case Summaries N Mean Median Std. Deviation OsmoNormal OsmoDryEye Ranks Test Statistics b Osmo EyeCode 1 2 Total 1 = Normal, 2 = Dry eye N Mean Rank Sum of Ranks Mann-Whitney U Wilcoxon W Z Asymp. Sig. (2-tailed) Exact Sig. [2*(1-tailed Sig.)] a. Not corrected for ties. b. Grouping Variable: EyeCode Osmo a Appendix B / Page 6 of 8

7 Appendix B [Question 2(b)] Model 1 Regression Residual Total b. Dependent Variable: PRT ANOVA b Sum of Squares df Mean Square Model 1 R Model Summary b R Square Adjusted R Square.786 a a. Predictors: (Constant), TTR, TMH, Age b. Dependent Variable: PRT Std. Error of the Estimate Appendix C/ Page 7 of 8

8 Appendix C [Question 2(c)] Dependent Variable: LogAdh Source Model PsStrain LensType PsStrain * LensType Error Total Tests of Between-Subjects Effects Type III Sum of Squares df Mean Square F Sig a a. R Squared = (Adjusted R Squared = 1.000) Interaction plot Pseudomonas strain Strain A Strain B Strain C log(adhesion) Silcone hydrogel HEMA-A HEMA-B Type of contact lens HEMA-C Page 8 of 8