1. SELECT Label Comprehension Studies Mevacor™ Daily Capt. Laura Shay, RN, MS, C-ANP Division of Nonprescription Clinical Evaluation Center for Drug Evaluation and Research

2. 2 Joint NDAC/EMDAC Meeting December 13, 2007 Overview Label comprehension (LC) study OTC Mevacor Label Development CUSTOM LCS SELECT LCS Muscle Warning LCS Summary

3. 3 Joint NDAC/EMDAC Meeting December 13, 2007 Purpose of Label Comprehension Study OTC labels must: “...be likely to be read and understood by the ordinary individual, including individuals of low comprehension, under customary conditions of purchase and use.” 21 CFR 330.10 (a)(4)(v)

4. 4 Joint NDAC/EMDAC Meeting December 13, 2007 Purpose of Label Comprehension Study To evaluate whether or not consumers can comprehend important communication objectives on the label –Literate and low literate subjects –Diverse population: Representative of the U.S. population

5. 5 Joint NDAC/EMDAC Meeting December 13, 2007 Overview Label comprehension (LC) study OTC Mevacor Label Development CUSTOM LCS SELECT LCS Muscle Warning LCS Summary

6. 6 Joint NDAC/EMDAC Meeting December 13, 2007 OTC Mevacor Label Paradigms 2000: 10 mg Mevacor –Label: Total Chol. paradigm- Total Chol. follow-up 2005: 20 mg Mevacor OTC –Label: LDL paradigm-LDL follow-up 2007: 20 mg Mevacor Daily –Label 1: LDL paradigm-LDL follow-up –Label 2: Total Chol. paradigm-Total Chol. follow-up

7. 7 Joint NDAC/EMDAC Meeting December 13, 2007 OTC Mevacor Consumer Studies 2004: 20 mg Mevacor OTC (Custom Label) –CUSTOM actual use study A Consumer Use Study of OTC Mevacor (CUSTOM) –CUSTOM label comprehension study 2007: 20 mg Mevacor Daily (SELECT labels) –SELECT LCS –Muscle Warning LCS –SELECT self-selection study Self Evaluation of Lovastatin to Enhance Cholesterol Treatment (SELECT)

8. 8 Joint NDAC/EMDAC Meeting December 13, 2007 Overview Label comprehension (LC) study OTC Mevacor Label Development CUSTOM LCS SELECT LCS Muscle Warning LCS Summary

9. 9 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM Label 2004

10. 10 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM Label 2004

11. 11 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM Results: Selection Criteria Communication Objectives 0% 100% 20% 40% 80% 60% LDL/HDL (54-59%) Risk Factor: MI (37%) Correct Age (57%) Comprehension

12. 12 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM Results: Safety Communication Objectives Comprehension 0%100%20%40% 80% 60% breast feeding (77%) unexplained muscle pain (79%) allergy to lovastatin (72%) pregnant (74%) liver disease (69%) Woman <55 (55%)

13. 13 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM Results: Self-Selection Included a self-selection question Of 209 subjects who stated they “could start Mevacor OTC today” –1% were correct (n=3) on all the label criteria (age, LDL, risk factors, medical history, pregnancy status and medications)

14. 14 Joint NDAC/EMDAC Meeting December 13, 2007 Deficiencies Listed in the February 23, 2005 Not Approvable Letter Modify and retest the package label –pregnancy warning –unexplained muscle pain warning –liver disease warning Justification if deviate from Drug Facts format (21 CFR 201.66(d)) Demonstrate that consumers can make an appropriate self-selection decision based on the information contained on the label

15. 15 Joint NDAC/EMDAC Meeting December 13, 2007 Overview Label comprehension (LC) study OTC Mevacor Label Development CUSTOM LCS SELECT LCS Muscle Warning LCS Summary

16. 16 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT-LDL Label 2007

17. 17 Joint NDAC/EMDAC Meeting December 13, 2007 Back of the Box SELECT-LDL Label 2007

18. 18 Joint NDAC/EMDAC Meeting December 13, 2007 Inside Flap SELECT-LDL Label 2007

19. 19 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT-LDL Label 2007

20. 20 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT-LDL Label 2007 Bottom of Box

21. 21 Joint NDAC/EMDAC Meeting December 13, 2007 LDL-Label vs. Total Cholesterol-Label LDL-Label vs. Total Cholesterol-Label SELECT Label Paradigms

22. 22 Joint NDAC/EMDAC Meeting December 13, 2007 LDL  Women age 55 years or older  Man age 45 years or older  LDL between 130-170  Must have one or more risk factors (listed…) *including low HDL 1 to 39 (*not gender specific) Total Cholesterol  Women age 55 years or older  Man age 45 years or older  Total Chol. between 200-240  Men: No HDL requirement  Women: HDL between 1 and 59  Men : No risk factors require  Women: At least one or more risk factors (listed…) Selection Criteria

23. 23 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT Label Comprehension Study Design Primary objective: To measure consumer comprehension of key communication messages on the label Secondary objective: To test comprehension of two different usage paradigms based on LDL-C and Total-C

24. 24 Joint NDAC/EMDAC Meeting December 13, 2007 Study Design Parallel two group design Random assignment –LDL label (LDL-C) –T. Chol. label (Total-C)

25. 25 Joint NDAC/EMDAC Meeting December 13, 2007 Sample Cholesterol concerned individuals 20 geographically dispersed malls Inclusion/Exclusion criteria –18 years or older, –speak/read English, –have not participated in a market research survey in the mall in the past 3 months –Not a healthcare provider –Not employed by advertising/marketing/healthcare product company

26. 26 Joint NDAC/EMDAC Meeting December 13, 2007 Sample Size LDL Label Rep. Sample=307 Total Chol. Label Rep. Sample=303 Sample Total n=816 * Augmented Low Literate=155* Low Literate=160*

27. 27 Joint NDAC/EMDAC Meeting December 13, 2007 Data Collection Trained interviewer/scripted questionnaire Open-ended –Example: “What is Mevacor Daily used to treat?” Scenario questions –Example: Diane has been taking Mevacor Daily for several weeks. She now is feeling muscle pain that she can not explain. Is it ok or not ok for her to continue using Mevacor daily? –“Why did you say that?”

28. 28 Joint NDAC/EMDAC Meeting December 13, 2007 Data Analysis Step 1: Analysis of initial response to “ok or not ok” question: –Correct –Incorrect Step 2: Analysis of follow-up question (“Why did you say that?”): –Correct (“truly” correct-eliminated “guessers”) –Acceptable (“talk to a doctor”) –Correct + Acceptable

29. 29 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT Labels Results: Selection Criteria Communication Objectives Comprehension 0% 100% 20% 40% 80% 60% LDL/HDL (64%-78%) T.Chol/HDL (70%-86%) Correct Age: both labels (86-92%) Risk Factor MI: (29%-44%) Overall Scores T. chol

30. 30 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT Results (Both Labels): Safety Communication Objectives Comprehension 0% 100% 20% 40%80% 60% Liver Disease (84-94%) Allergy to lovastatin (91-99%) Pregnant (94-98%) Unexplained Muscle Pain (96-98%) Breast Feeding (94-97%) Woman <55/Female Subjects (92%)

31. 31 Joint NDAC/EMDAC Meeting December 13, 2007 Key Communication Objectives CUSTOM LCS VS. SELECT LCS

32. 32 Joint NDAC/EMDAC Meeting December 13, 2007 Results CUSTOM vs. SELECT Selection Criteria Communication Objectives 0% 100% 20% 40% 80% 60% Age LDL/HDL T. Cholesterol/HDL SELECT CUSTOM 54-59% 64-92% ~80%

33. 33 Joint NDAC/EMDAC Meeting December 13, 2007 Results CUSTOM vs. SELECT Selection Criteria Communication Objectives 0% 100% 20% 40% 80% 60% 29-44% Risk Factor (MI)

34. 34 Joint NDAC/EMDAC Meeting December 13, 2007 Results CUSTOM vs. SELECT Safety Communication Objectives 0% 100% 20% 40%80% 60% SELECT CUSTOM Liver Disease Woman <55/Female Subjects Pregnant/Breast Feeding Unexplained Muscle Pain Allergy to lovastatin 55-79% 84-99%

35. 35 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM vs. SELECT Follow-Up Lipid Testing What to do if LDL has not reached goal

36. 36 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM : When to Retest Lipids

37. 37 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT: When to Retest Lipids

38. 38 Joint NDAC/EMDAC Meeting December 13, 2007 Question: When to Retest Lipids CUSTOM LCS: 71-87% correct* SELECT LCS: 45-62% correct *In the CUSTOM actual use study, ~70% of the subjects obtained a follow-up cholesterol test

39. 39 Joint NDAC/EMDAC Meeting December 13, 2007 CUSTOM: What to do if LDL has not reached goal

40. 40 Joint NDAC/EMDAC Meeting December 13, 2007 SELECT: What to do if LDL/T.C. has not reached goal Bottom of Box

41. 41 Joint NDAC/EMDAC Meeting December 13, 2007 Question: What to do if LDL has not reached goal CUSTOM LCS: 54-68% correct* SELECT LCS: 59-69% correct *In the CUSTOM actual use study, ~75% of the subjects made a correct decision on whether to continue to use Mevacor Daily based on their LDL results

42. 42 Joint NDAC/EMDAC Meeting December 13, 2007 Overview Label comprehension (LC) study OTC Mevacor Label Development CUSTOM LCS SELECT LCS Muscle Warning LCS Summary

43. 43 Joint NDAC/EMDAC Meeting December 13, 2007 Purpose To measure in-depth consumer comprehension of the warning about unexplained muscle pain, tenderness or weakness after starting Mevacor™ Daily contained in the Drug Facts and the internal package materials

44. 44 Joint NDAC/EMDAC Meeting December 13, 2007 Muscle LCS Label 2007

45. 45 Joint NDAC/EMDAC Meeting December 13, 2007 Muscle LCS Label 2007

46. 46 Joint NDAC/EMDAC Meeting December 13, 2007 Quick Start Guide Muscle LCS Label 2007

47. 47 Joint NDAC/EMDAC Meeting December 13, 2007 Package Insert/Brochure Muscle LCS Label 2007

48. 48 Joint NDAC/EMDAC Meeting December 13, 2007 Magnet Muscle LCS Label 2007

49. 49 Joint NDAC/EMDAC Meeting December 13, 2007 Study Design One group (LDL label) Sample Size: –Rep. Sample=316 –Low literacy=104 Cholesterol interested individuals/malls Inclusion/Exclusion

50. 50 Joint NDAC/EMDAC Meeting December 13, 2007 Data Collection Trained interviewer/scripted questionnaire Questionnaire –Scenario –Open-ended –Closed-ended –All questions not focused on muscle warning

51. 51 Joint NDAC/EMDAC Meeting December 13, 2007 Muscle LCS Results Correct responses to questions related to: –the side effect of muscle pain –stop using Mevacor if develop muscle pain 97-98% Correct responses to questions related to: –What happens if someone who develops muscle pain continues using Mevacor 75-85%

52. 52 Joint NDAC/EMDAC Meeting December 13, 2007 Muscle LCS Results cont. Responses to question : “how likely would he/she contact a doctor if he/she developed muscle pain while taking Mevacor Daily?” –Extremely –Very likely –Somewhat likely –Not at all likely –Not too likely Unknown whether or not respondents understood if they should talk to a ‘doctor’

53. 53 Joint NDAC/EMDAC Meeting December 13, 2007 Muscle Results cont. Most respondents understood that muscle pain is a side effect of lovastatin and a person who develops unexplained muscle pain should stop taking Mevacor™ Daily (96-98%). *In the CUSTOM actual use study, 60% of the subjects who developed unexplained muscle pain (38 out of 63 subjects), stopped using lovastatin. (CUSTOM LCS: 79% correct comprehension )

54. 54 Joint NDAC/EMDAC Meeting December 13, 2007 Overview Label comprehension (LC) study OTC Mevacor Label Development CUSTOM LCS SELECT LCS Muscle Warning LCS Summary

55. 55 Joint NDAC/EMDAC Meeting December 13, 2007 Summary Well designed studies –A lot of useful qualitative data –Validation of correct responses The major communication elements on the label were tested with one exception: –The part of the pregnancy warning that describes women who may become pregnant Areas of improved comprehension from CUSTOM label

56. 56 Joint NDAC/EMDAC Meeting December 13, 2007 Safety Correct Responses (~ >90%) –Muscle warning (need to stop taking) (96-98%) –Correct age (86-92%) –Pregnancy* (94-98%) –Breast feeding* (94-97%) –Liver disease (84-94%) –Muscle warning (continue using) (75-85%) *Of those who were incorrect on the pregnancy and breast feeding questions –Unable to find the pregnancy warning on the label

57. 57 Joint NDAC/EMDAC Meeting December 13, 2007 Selection Criteria –Age/LDL/T. Chol/HDL (64-92%) (~80%) –Risk factor MI (29-44%)

58. 58 Joint NDAC/EMDAC Meeting December 13, 2007 Lipid Testing/Follow-up When to retest (45-62%) What to do if have not reached goal (59-69%)

59. 59 Joint NDAC/EMDAC Meeting December 13, 2007 Summary The pregnancy/breastfeeding, liver, and muscle warnings were better understood There was improved comprehension of the selection criteria (esp. T. Chol) with the exception of the one risk factor tested (MI) There was a decrease in comprehension that lipids should be retested in 6 weeks There was no improvement in comprehension what to do if have not reached goal Overall comprehension levels were similar for the low literate study population

60. 60 Joint NDAC/EMDAC Meeting December 13, 2007 Self-Selection SELECT Self-Selection Study Linda Hu, Medical Officer Division of Nonprescription Clinical Evaluation

61. 61 Joint NDAC/EMDAC Meeting December 13, 2007 Acknowledgements Review Team –Andrea Leonard Segal, M.D. –Joel Schiffenbauer, M.D. –Daiva Shetty, M.D. –Linda Hu, M.D. –Stan Lin, Ph.D. –Michael Koenig, Ph.D. –Matthew Holman, Ph.D. –Mary Lewis, RN