1. 1 DRAFT SLIDES FOR NDA 21-198 ADVISORY COMMITTEE PRESENTATIONS

2. 2 Pravachol 10 Label Comprehension Study Karen Lechter, J.D., Ph.D. Division of Drug Marketing, Advertising, and Communications July 14, 2000

3. 3 Presentation Overview Purpose and Methodology of Label Comprehension Studies Pravachol Study Characteristics and Results Potential for Misuse Tested label vs. NDA label Conclusions

4. 4 Purpose and Methodology of Label Comprehension Studies

5. 5 Purpose of Label Comprehension Studies 21 CFR 330.10(a)(4)(v)…[OTC labels shall be written] in such terms as to render them likely to be read and understood by the ordinary individual, including individuals of low comprehension, under customary conditions of purchase and use Low comprehension= <8th grade reading

6. 6 Methodology of Label Comprehension Studies Malls, other public gathering places Special populations recruited from –phone lists – advertisements May or may be potential users

7. 7 Types of Questions Open-ended--no response suggested Closed-ended--possible responses given true/false, yes/no, multiple choice Levels of questions simple--identify if information is on label more difficult--regurgitate or recognize even more difficult--apply information

8. 8 Types of Questions to Avoid Leading questions--suggest response Questions assuming knowledge –Provide information participant may not know Series of questions, most answered the same way (e.g. “see a doctor”)

9. 9 Procedure Show outer carton –Usually leave in view Ask questions May show leaflet, brochure, etc. –Leave in view Ask questions

10. 10 Pravachol Study Characteristics and Results

11. 11 Pravachol Study Characteristics Open ended6 Multiple choice 16 Assume knowledge3 (must do something before and 1 yr; some diseases should not use) Confounded results2

12. 12 Pravachol Study Characteristics cont’d No hypotheticals--do not know if can apply information to variety of situations –Could have avoided leading questions –Could have produced more confidence in results

13. 13 Communication Objectives Communication objectives guide questionnaire development –Based on label information –Some may be designated key or primary

14. 14 Communication Objectives, cont’d Primary Objective Whether consumers understand they should see a doctor before using Pravachol 10

15. 15 Communication Objectives, cont’d Secondary Objectives Product purpose –lower cholest. if 200-240 mg/dL after diet & exercise Who should not use –diabetes or coronary heart disease –already taking Rx for cholesterol –liver disease or > 3 alcoholic drinks/day –taking erythromycin –pregnant

16. 16 Communication Objectives, cont’d Secondary Objectives, cont’d Who should use –non-pregnant females >55 –males >35 –people with total cholest. 200-240 mg/dL Need follow-up evaluations Report muscle pain to doctor

17. 17 Communication Objectives, cont’d Did not test simultaneous application of requirements for use Did not test about risk factors for heart disease

18. 18 Participants N=612 Age 25 and older Not necessarily concerned about cholesterol 163 Low Literate (below 9th grade reading) Quotas for sex, age

19. 19 Low Literate Results No differences in responses from low- literate, t-tests p<.05

20. 20 Results--Well Understood Purpose for using (90-95%) At least 1 disease precluding use (97%) –3 diseases precluding use (71%) Do not use if heart disease, diabetes, liver disease (88-90%) Do not use if pregnant, drink 3 alcohol (87%)

21. 21 Results--Well Understood, cont’d Not for normal cholesterol, pregnant, or hepatitis (87%) See doctor if unusual muscle pain or tenderness (93%)

22. 22 Results--Moderately Understood Age for men (77%) Age for women (80%) See doctor after 8 weeks (82%)

23. 23 Data Not Clear Must see Dr. before use (82-95%) Must see Dr. after 1 year (86%) Questions assumed participants knew they had to do something

24. 24 Where Tested Label Needs Work Don’t use if take erythromycin (65%) –Eliminated in latest label Don’t take if Rx cholest. meds. (73%) Appropriate cholesterol range (76%) –250-300 mg/dL OK to use (17%) –Tested label--range on own line –NDA label, range on line with LDL Age for men and women (77%-80%) –Age 18 for all on new label

25. 25 No Data Could participants use product themselves? (cross-checked with medical information) Need several criteria at once to use –New label--drops age/sex, adds LDL

26. 26 No Data, cont’d Special circumstances when consult Dr. –cholesterol above 240 mg/dL, HDL very low –have 1 risk factor for heart disease: smoking, hypertension family history of heart disease Understanding treatment failure, success, long-term benefits

27. 27 No Data, cont’d Importance of diet and exercise What healthy cholesterol is –Label says continue treatment if reach healthy cholesterol –Label says may need Rx if have not reached healthy level –“Healthy” not defined

28. 28 Potential for Misuse

29. 29 Potential for Misuse 17% said appropriate for 250-300 mg/dL –May signal potential for inappropriate use May use without combination of factors necessary--not tested –e.g., may use if in correct total range but may ignore LDL requirements

30. 30 Tested Label vs. NDA Label

31. 31 Tested vs. NDA Labels Tested Label At top: Before you start: SEE YOUR DR. to check cholest.levels and discuss risk factors for heart disease Pictogram of doctor and patient and statement “See Your Dr. Before Use on side of Use section NDA Label Nothing at top No pictogram or separate statement to see doctor before use

32. 32 Tested vs. NDA Labels, cont’d Tested Label Cholesterol 200-240 mg/dL Men >age 35; women >age 55 NDA Label Cholesterol 200-240 mg/dL LDL >130 mg/dL Do not use if under age 18

33. 33 Tested vs. NDA Labels, cont’d Tested Label Do not use if take erythromycin “Do not use” section with 6 bullets 1 “Ask a Dr. before use” section NDA Label Nothing about erythromycin “Do not use” section with 3 bullets Some “Do not use information” moved to 4 sections about asking a doctor, pharmacist, or health care professional before use

34. 34 Tested vs. NDA Labels, cont’d Tested Label Not Drug Facts Format NDA Label Drug Facts Format

35. 35 Conclusions

36. 36 Conclusions Label substantially modified in content and format after study –New Drug Facts format –New information added, some deleted Do not know how well new label works

37. 37 Conclusions Participants understand some important aspects of the label Some issues moderately or poorly understood, or results unclear Critical information not tested

38. 38 Conclusions For tested label, significant numbers may not understand – age/sex – when see Dr. based on time – erythromycin, other cholesterol medicines – total cholesterol Inadequate information on – simultaneous requirements for use – applying information – appropriate self-selection

39. 39 Conclusions, cont’d Questionable if results of label comprehension test applicable to NDA label due to major differences in format and content

40. 40 Conclusions, cont’d Evidence inadequate to conclude consumers can use safely and effectively in OTC setting