6350 Lecture 3: Developing a Project with Hypotheses

1. 6350 Lecture 3: Developing a Project with Hypotheses • Key Concepts: How a question is developedProper Literature Citations (test)Hypothesis Writing (test)Clinical Grading (e.g., staining; test) Writing Questions and Hypotheses

2. Thought for the Day “To him/her whose elastic and vigorous thought keeps pace with the sun, the day is a perpetual morning” Henry David Thoreau

3. Student Research and the Research Question The Most Important Aspect of Research (according to JP) You want people to say: “What a neat idea!”when you describe your project

4. It’s Tough to Ask a Good Question! Writing Questions and Hypotheses

5. Dr. Paugh’s Example – The “Refresh Contacts” Study • Solution toxicities observed clinically with multi-purpose solutions (MPSs) • Carboxymethylcellulose (CMC): • Ubiquitous wood fiber; viscosifying agent in artificial tears and CL lubricants  The Question: Can a pre-application drop of CMC reduce solution toxicity? Writing Questions and Hypotheses

6. Grade 3.5 SPK “worst sector” on a 0-4 Scale; Grade 14.5 on a 0 – 20 Total Scale Writing Questions and Hypotheses

7. Dr. Paugh’s Example What does the literature say? • Solution reactions exist: • especially silicone-hydrogels & MPSs • Evidence that CMC can neutralize MPS actives (i.e., PHMB) • Vehige et al., Eye and CL, 2003: chemical availability of PHMB less in water and MPS when CMC present • Also, bacterial survival rates greater when CMC added  binding Writing Questions and Hypotheses

8. How Do We Reference the Literature? (especially in this increasingly electronic age?)

9. Literature Citations • Uniform Requirements for Manuscripts Submitted to Biomedical Journals • Used by many medical journals, including OVS, IOVS, etc. • International Committee of Medical Journal Editors (ICMJE); general medical journal editors who meet annually to develop uniform standards) • Consider reference software such as EndNote Writing Questions and Hypotheses

10. Citing Electronic Material: ICMJE* How To: SCCO Library: • Go to intranet, SCCO Library • Click on “How To” • Click on “ICMJE” • Go to specific chapter you need *Patrias K. Citing medicine: the NLM style guide for authors, editors, and publishers [Internet]. 2nd ed. Wendling DL, technical editor. Bethesda (MD): National Library of Medicine (US); 2007 [updated 2009 Oct 21; cited Year Month Day]. Available from: http://www.nlm.nih.gov/citingmedicine Writing Questions and Hypotheses

11. Citation-Journal (paper): • Use Index Medicus abbreviations for the journal (e.g., Optom Vis Sci) • List the first six authors followed by “et al.” • Example: • Halpern SD, Ubel PA, Caplan AL. Solid-organ transplantation in HIV-infected patients. N Engl J Med. 2002;347:284-7. Writing Questions and Hypotheses

12. Citation-Book (paper): • Personal Author: • Murray PR, Rosenthal KS, Kobayashi GS, Pfaller MA. Medical microbiology. 4th ed. St. Louis:Mosby;2002. + page numbers!!! Writing Questions and Hypotheses

13. Citation-CD-ROM(“electronic material”) e.g.: Anderson SC, Poulsen KB. Anderson’s electronic atlas of hematology [CD-ROM]. Philadelphia: Lippincott and Williams and Wilkins; 2002. e.g.: Writing Questions and Hypotheses

14. Citation-Internet Journal Article: e.g.: Writing Questions and Hypotheses

15. Citation-Homepage/Web Site • Cancer-Pain.org [homepage on internet]. New York: Association of Cancer Online Resources, Inc.; c2000-01 [updated 2002 May 16; cited 2002 Jul 9]. Available from http://www.cancer-pain.org/. Writing Questions and Hypotheses

16. Citation-SCCO Student Research Paper • Williams R. Strabismus and its therapies [student research paper]. Fullerton (CA): Southern California College of Optometry; 1980. • Note: could have a second author and faculty advisoras well Writing Questions and Hypotheses

17. FINER TEST (for student research) • F – feasible (adequate subjects, affordable?) • I – interesting (to investigator & profession) • N – novel (confirms or refutes prior work) • E - ethical • R – relevant? (to knowledge, clinical care?) (i.e., the So What? Test) Writing Questions and Hypotheses

18. Dr. Paugh’s Example (Refresh Contacts) • Poll Contact Lens Staff-What do you think? • So What? • Clinical care: • may corroborate in vitro findings • may develop a simple and cost effective solution to a given problem • Pre-application drop lubricates the lens-eye system-a benefit! • Feasibility! Writing Questions and Hypotheses

19. Dr. Paugh’s Example • Is there a difference between pre-instillation of a CMC vs. a non-CMC lubricant? • i.e., subjective? • Dryness, comfort etc. • i.e., objective? • Staining (overall and cumulative) • Bulbar injection • Limbal redness Writing Questions and Hypotheses

20. REFINING AND DEFINING:IMPORTANT!!!!!!!!! • Keep it small • Define the population rigorously • Focus on one thing - one relationship • Define the end-point in terms of primary outcome variable(s) and secondary outcome variable(s) • What exactly are you going to measure? Writing Questions and Hypotheses

21. Dr. Paugh’s example Population • Experienced soft lens wearers • NB: ideal would be identified solution responders • In reality, ANY soft lens wearers • > age 18 (expedited IRB review) • No torics • Fit with lens material that is likely to demonstrate the problem- Ethics??? Writing Questions and Hypotheses

22. Dr. Paugh’s example, cont’d Methods: • Fit all subjects with one lens material • All subjects disinfect with ReNu • During one 4-week period, use ReNu lubricant as pre-application drop • During 2nd 4-week period, use CMC lubricant as pre-application drop • Responses: subjective & biomicroscopy Writing Questions and Hypotheses

23. Variables – Definitions (textbook) • Independent variable or Predictor variable • The variable that is held constant; HOWEVER, the investigator controls it • A factor that is suspected to influence the outcome of an analytic study (e.g., a CL lubricant, or drug treatment, etc.) • Dependent variable or Outcome variable • Primary • Secondary • The response of interest (e.g., the development of staining, cure of disease etc.) Writing Questions and Hypotheses

24. Dr. Paugh’s Example • What is the independent / predictor variable? • e.g., disinfecting solution? • Lens material? • Length of wear? • Lubricant? • What is the dependent / outcome variable? • e.g., comfort? staining? refractive error? Writing Questions and Hypotheses

25. Research Questions: Summary • “Ask a Good Question!!!” • How? Discover an unanswered need: • Why does this happen clinically? What is known about this?, etc. Literature review; speak with experts Writing Questions and Hypotheses

26. Dr. Paugh’s Questions-Personal • How long does an ophthalmic solution last on the ocular surface? • Can a novel, more convenient method be developed to measure epithelial barrier function? • What are the factors that influence tear exchange beneath contact lenses? • Does ed peri-ocular humidity improve non-invasive tear parameters? • What is the in situ aqueous tear viscosity? Writing Questions and Hypotheses

27. Dr. Paugh’s Questions-Student • How much plus can be added to a rigid CL prior to optical distortion? • What is the prevalence of MGD? • Do warm compresses for MGD really provide benefit? • Do neophyte, latent hyperopes accept more plus with rigid contact lenses? Writing Questions and Hypotheses

28. List in Your Hands!!! Faculty to Contact: • Drs. Sendrowski, Comer, Tong: Ocular Disease • Drs. Barnhardt, Cotter, Borsting, Chu: • Pediatrics, VT, dyslexia, strabismus • Drs Jim Bailey, Stark • Accommodation, VT, Visual Optics • Drs. Edrington, Marsden, Lam et al. • Contact lenses, tear film, keratoconus • Dr. Ridder: Contrast threshold, ERG, aberrations • Dr. Paugh: Tears, CLs, dry eye Writing Questions and Hypotheses

29. GENERATING HYPOTHESES • Specify the end-point carefully: • e.g., IOP, TBUT, BI to break, etc. • What are you measuring exactly? • Is it best expressed as a mean? • e.g., average score, average difference, average visual acuity, average IOP • Is it best expressed as a proportion? • e.g., percentages, proportion with and without (a condition), categories (disease, no disease) Writing Questions and Hypotheses

30. HYPOTHESES: General • Null is always “no difference” • Alternative can be one-tailed or two-tailed • What is of interest to you? • What makes sense clinically? Writing Questions and Hypotheses

31. NULL HYPOTHESIS • There is no difference between... • ...Is not associated with... • ...Is not different... • Symbols: mu for means  pi for proportions  • Use equal sign = • E.g.: • Ho: 1 = 2 • Ho: 1 = 2 Writing Questions and Hypotheses

32. ALTERNATIVE HYPOTHESIS • One-tailed or two-tailed? • Not equal, greater than, less than • Symbols: (mu)  for means (pi)  for proportions • Use appropriate mathematical symbol for one-tailed or two-tailed ≠; >; < Writing Questions and Hypotheses

33. Dr. Paugh’s CMC Example • What exactly did we measure as the principal outcome measure? • Is this expressed as a proportion or a mean? Writing Questions and Hypotheses

34. Dr. Paugh’s Example • Should the alternative hypothesis be one-tailed or two-tailed? • Could SCL wearers have more or less staining when using lubricants? • Two-tailed makes it more difficult to demonstrate significance, but, more robust statistically  use 2-tailed approach if possible Writing Questions and Hypotheses

35. Examples: Writing Hypotheses • Null (no difference) Hypothesis: • E.g., There is no difference in the residence time, in minutes, between product 1 and product 2 • Ho: 1 = 2 • Alternative Hypothesis: • There is a difference in residence time, in minutes, between product 1 and product 2 • HA: 1 ≠ 2 • Two-tailed most robust (because covers all possible outcomes) Writing Questions and Hypotheses