Kathryn J. Aikin, Ph.D. Division of Drug Marketing, Advertising and Communications

1. Direct-to-Consumer Prescription Drug Advertising in the United States: Background, Research, and the Current Environment Kathryn J. Aikin, Ph.D. Division of Drug Marketing, Advertising and Communications US Food and Drug Administration International Seminar on Drug Advertising Brasilia, Brazil April 5, 2005

2. Overview of Talk • Legal Requirements • Types of DTC • Evolution of DTC • “Adequate Provision” in Broadcast Ads • General Considerations in DTC • Basis for Enforcement Actions • FDA Survey Research Findings • Current Environment and Recent Enforcement Actions

3. Jurisdiction/Legal Basics • No laws or regulations ever prohibited promoting prescription drugs to consumers (in general or for specific products or drug classes) • Regulatory focus is on the content of the materials NOT their general existence

4. Jurisdiction/Legal Basics • Law prohibits requiring preapproval of any ad except under “extraordinary circumstances” -- post hoc monitoring process -- still, many manufacturers voluntarily request our comments prior to use

5. Requirements for Ads Per FDA regulations issued in late 1960’s, ads: • Must not be false or misleading • Must present “fair balance” between benefits and risk information • Must disclose “material” facts in light of claims made about product

6. What Does this Mean? • Accurately communicate indication(s) including context for any claim • Communicate most important risks in a manner reasonably comparable to benefits (presentation and language) • Cannot omit important information • In plain language this means  Ads must communicate an accurate and balanced picture of the drug product

7. Some Sources of Product-Specific Health Information for Patients • Healthcare Provider • Patient Package Insert • Advertising • Brief Summary • Internet • Other Sources Disease Awareness Reminder Product Claim

8. How DTC Evolved • Up to 1980’s: consumer communications through “learned intermediary” • 1980’s: saw 1st DTC ads and fallout --1983-1985: FDA voluntary moratorium --1985: lifted, regulations provide “sufficient safeguards to protect consumers” • 1990’s: print ads proliferated • mid 1990’s: broadcast ads enters mix

9. Addressing “Adequate Provision” • Guidance (1997 draft; 1999 final) • no change to regulations • provided one possible interpretation of “adequate provision” given current technology and marketplace • Reinforces underlying requirements • Encourages consumer-friendly information

10. “Adequate Provision” • Assuming diverse audience, need multiple sources of product information • toll-free telephone contact number • website address • concurrently running print ads • reference to health care providers

11. Types of DTC Promotion • Disease Awareness • Reminder ads/labeling • Product claim

12. Types of DTC Promotion • Disease Awareness • disease discussion … “see your doctor”... consistently encouraged, important for under-diagnosed, under-treated health conditions • not drug ads, so not covered by FFD&CA • recent draft guidance clarifies FDA’s position on these types of ads

14. Types of DTC Promotion • Reminder ads/labeling • exempted from risk disclosure requirements • includes product name, but no representations beyond dosage form, packaging, price info • not for products with especially serious (boxed) warnings

15. Types of DTC Promotion • Product claim • claims or representations trigger disclosure requirements for accuracy and balance • risk disclosure requirement in regulations • “brief summary” for print ads • “adequate provision” for broadcast ads • full product labeling for promotional labeling

16. General Considerations in DTC Advertising • Accurate communication of indication(s) • Limitations on indication(s) • Relevant patient population • Concomitant therapies/treatments • Likelihood of benefit(s)

17. General Considerations in DTC Advertising • Disclose Most Important Risks • “In brief summary” for print ads • “Major” risks for broadcast ads + “adequate provision” • Boxed warnings • Bolded warnings • Significant precautions/drug interactions • Frequent & significant side effects • Contraindications (relevant to patients)

18. Risk Disclosure • Print ads need information “in brief summary” about risks and effectiveness • most important risks comparably prominent to effectiveness claims as “fair balance” • Regulations require that print ads must disclose all risks • February 2004 Draft Guidance provided alternatives to the current “brief summary” in effort to have information better conveyed to consumers

19. Risk Disclosure • Broadcast ads need: • most important risks disclosed in ad itself (in audio at least) “major statement” • access to either allrisks or “adequate provision” for disseminating product labeling (PI)

20. General Considerations in DTC Advertising • “Fair Balance” of Risks and Benefits • Prominence of the presentation • Amount of information • Language • Necessary context for benefit claims/risks • Should not undermine the role of the healthcare provider • Disclose prescription status

21. Additional Considerations in Product Claim Ads • Overstatement of efficacy, especially if relatively low • “freedom from,” “controls,” “proven protection,” graphics suggesting significant impact, other hyperbole • sometimes context can help, other times it can’t • Implied unsubstantiated outcome claims • “relaxed,” “confident,” “changed my life”

22. Additional Considerations in Reminder Ads • Avoid anything --verbal or visual -- that makes a claim about the product, e.g., • “why suffer through another day?” • “most prescribed of its kind” • implied fixing of something that is broken • clear suggestion of improved quality of life • clear suggestion of patient population (all children, all women, all people with some problem) • reference to particular type of specialist

23. Common Problems in Proposals and Final Submissions • Minimization or lack of risk information • missing content • presentation (minimization, comparability) • Misleading communication of the indication or overstatement of efficacy • Unsubstantiated comparative claims • Misleading visuals and graphics • Distracting modalities or illegible SUPERs • Rx status or role of healthcare provider minimized • Inadequate mechanism for ensuring dissemination of product labeling

24. Does DTC advertising... • Increase demand for advertised drugs? • Cause patients to pressure doctors for advertised drugs? • Cause inappropriate prescribing? • Increase the price of drugs or the cost of health care? • Harm the relationship between patients and doctors? • Is DTC advertising appropriate at all?

25. FDA Surveys • Look more closely at impact of DTC advertising on doctor-patient relationship • Two consumer surveys (1999 and 2002) • One physician survey (2002)

26. 1999 National probability sample conducted by telephone interview 1,081 respondents, 960 who had visited a doctor in the last three months for a problem of their own 2002 National probability sample conducted by telephone interview 943 respondents who had visited a doctor in the last three months for a problem of their own 1999 and 2002 Consumer Surveys: Methodology

27. 2002 Physician Survey: Methodology • Random Sample from American Medical Association Physician Masterfile • 250 General Practitioners • 250 Specialists in areas targeted by DTC • Dermatology • Allergy/Pulmonology • Endocrinology • Psychiatry

28. Does DTC advertising increase demand for advertised drugs? • DTC not primary driver of visits to doctor • DTC plays a role in generating questions for doctor • Patients still use their doctors as #1 information source when looking for more information about a drug or treatment • Pharmacists, nurses also highly ranked as sources

29. Does DTC advertising cause patients to pressure doctors for advertised drugs? • Some patients do expect a prescription because of a DTC ad • Asking about prescription drugs constant across time • Brand-specific requests are likely to be accommodated • Patients who ask about a brand are more likely to be prescribed that brand than patients who ask in general • General Practitioners are more likely to prescribe a requested brand than Specialists • General Practitioners report feeling more pressured to prescribe

30. Does DTC advertising cause inappropriate prescribing? • Vast majority of patients who ask about a brand have the condition that drug treats • Among physicians who did not prescribe requested drug, most common reasons were: • drug not right for patient • different drug more appropriate

31. Does DTC advertising increase the price of drugs or the cost of healthcare? • Patients rarely discuss cost of drugs with doctor • Certain groups are more likely to discuss cost: • Women • Patients in poor health • Patient taking one or more prescription drugs • Patients without prescription drug payment plan

32. Does DTC advertising harm the relationship between patients and doctors? • Patients report their doctors generally respond positively to questions • Greater percentage of doctors say patient having seen a DTC ad had positive impact on interaction, as opposed to negative impact • General Practitioners report more negative beliefs about potential negative effects of DTC ads than Specialists • Physicians are evenly divided in opinions about overall impact of DTC ads on patients and practice- 1/3 positive, 1/3 no effect, 1/3 negative • General Practitioners report a more negative overall impact of DTC ads on patients and practice than Specialists

33. Is DTC advertising appropriate at all? • DTC ads increase awareness of possible treatments • DTC ads do not convey information about risks and benefits equally well • Physicians believe patients understand benefits much better than risks • Physicians believe DTC ads confuse patients about relative risks and benefits of drugs • Patient attitudes about many aspects of DTC advertising have become less positive over time

34. Current Environment • Continued increase in DTC promotion spending • Concern about changing tone in ads • Concern about presentation of risks Are the winds of change on the way?

35. Number of Disseminated Promotional Pieces Submitted 2003 and 2004

36. Number of Broadcast Ads Submitted1999-2004

37. Draft Brief Summary Guidance • Regulations require that the “brief summary” include “each specific side effect and contraindication” (i.e., all risk concepts) • Manufacturers historically complied by reprinting risk-related sections of product labeling • Verbatim reprinting is not required • Draft guidance describes consumer-friendly options for brief summary in DTC ads

42. Enforcement Actions • Kaletra Untitled Letter • Taxotere Warning Letter • Seasonale Untitled Letter

43. Kaletra Untitled Letter • Print ad and restroom poster • Indicated for use in combination with other antiretroviral agents for the treatment of HIV-infection • Contraindications • Warnings

44. Kaletra Print Ad

45. Kaletra Untitled Letter • Ad and poster did not contain the indication or risk information • Not aware of substantial evidence to support 5-year claims for: • survival • good health • undetectable HIV RNA levels • disease control

46. Taxotere Warning Letter • Three DTC print ads • Limited indications for certain types of breast and lung cancer • Boxed warning for severe and potentially life-threatening adverse reaction

47. Taxotere Warning Letter • Overstated survival benefits: Headline: “The next move may be the key to survival” • Proven survival differences were at best several months and were only observed in specific populations • Other drugs with proven survival benefits • Unsupported outcomes claims • Stay involved in important aspects of your life

48. Taxotere Warning Letter • Omission of risk information • Boxed warning information on risk of life-threatening infections, severe allergic reactions, and severe fluid retention • Certain common side effects • Minimization of risk information • Risk info lacked visual prominence • Disclosure began “Like all anticancer agents, there are side effects…”

50. Seasonale Untitled Letter • Product claim TV ad • Indicated as an extended-cycle OC • 91 days: 84 active tablets and 7 inert • Warnings • The usual OC warnings plus • Bleeding irregularities: “the convenience of fewer planned menses (4 per year instead of 13) should be weighed against the inconvenience of increased intermenstrual bleeding and/or spotting” • Warning also contained in patient labeling