1

FDA Regulation of Advertising and Promotion of Prescription Drugs

Carol H. Barstow, J.D.Special Assistant to the DirectorDivision of Drug Marketing, Advertising, and CommunicationsFood and Drug AdministrationNovember 9-10, 2004

What is DDMAC?

Food and Drug Administration (FDA)’sDivision of Drug Marketing, Advertising, and CommunicationsDDMAC’s Mission: To protect the public health by assuring prescription drug promotion is truthful, balanced, and accurately communicated

DDMAC’s Role

Education and advice to industry and within FDAGuidances and policy developmentSurveillance and enforcement

2

Advice to Industry

FDA does not review or “pre-clear” all ads and other promotionPromotion may be submitted voluntarily for advisory comments

Types of Promotion

Help seeking/Disease awarenessReminderProduct claim

Federal Food, Drug and Cosmetic Act (F D & C Act), 21 U.S.C. 301

FDA regulates promotional activities done by or on behalf of sponsorFalse or misleading promotion “misbrands” the drug21 Code of Federal Regulations (CFR)– §201 - Prescription Drug Labeling– §202 - Prescription Drug Advertising

3

Code of Federal Regulations (CFR)

– Not be false or misleading– Have fair balance and include material

facts– Consistent with the approved product

labeling or package insert (PI)– Claims must be substantiated by adequate

and well-controlled clinical studies– Not promote uses not in product labeling

Enforcement Options

Untitled letters (notice of violation or NOV)Warning LettersInjunctions/consent decreesSeizuresCriminal actions

Help-Seeking Draft Guidance

Characteristics of help-seeking/disease awareness promotion– Discusses/raises awareness about a

disease/health condition– Advises consumers to see their doctor– Encourages diagnosis and treatment– Should be a responsible public health message– Does not mention a particular drug or device– Does not include any representation or suggestion

relating to a particular drug or device

4

Types of Promotion

Reminder -- includes brand and established name of product – Optional info: dosage form, packaging, price – MAY NOT contain any representation or suggestion re:

the drug– Exempt from risk disclosure, balance, etc., requirements– Not permitted for products with especially serious (“boxed”)

warnings in Prescribing Information

Types of PromotionPromotion with Product Claims– Must include indication (i.e., approved use)– Must not suggest unapproved uses– Must include risk information (“fair balance”)– Must include facts that are material in light of representations

made in the promotion– May not be false or misleading– Claims must be supported by “substantial evidence”– Must include PI (for promotional labeling) or “brief summary”

(for advertising) or “adequate provision for PI” (for broadcast ads)

– Other requirements

Prescription Drug Promotion

Advertising– E.g., journal ads, magazine ads, TV

commercials, telephone communicationsPromotional Labeling– E.g., sales aids, file cards, brochures,

mailers, mugs, pens, sell sheets

5

Enforcement

Common Violations Omission of riskMinimization of risk (in content or prominence)Promotion of unapproved uses or “broadening the indication”Unsubstantiated effectiveness or safety claimsUnsubstantiated comparative claims

OxyContin Warning Letter

Professional journal advertisementsOmission of risk information – Boxed warning information related to

abuse liability and potentially fatal risks associated with OxyContin due to formulation and dosage

Broadening of indication– Omission of important limitations on

appropriate indicated use

6

Pravachol Warning Letter

Pravachol not indicated to reduce risk of stroke in patients who do not have clinically evident coronary heart disease (CHD) Zocor has such an indication

7

Xeloda Warning Letter

“Mechanism of Action” professional sales aid– Failed to provide any risk information (including boxed warning)– Suggested efficacy against a wide range of cancer tumors (beyond

limited indications in colorectal and breast cancer)Patient video– Claims that Xeloda, unlike other chemo drugs, does not make you

feel too tired or too sick to do your daily activities -- No data and contrary to reported adverse events (“AEs”)

– Claims that Xeloda is safer and has fewer toxicities than IV chemo drugs

– Minimized risk of serious AEs including severe diarrhea (“some looseness of bowels”) and hand-and-foot syndrome (“dryness of the palms of your hands and bottoms of the feet”)

Taxotere Warning Letter

DTC print adsOverstated 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

– Are other drugs with proven survival benefitsUnsupported outcomes claims– Stay involved in important aspects of your life

Taxotere WL (cont.)

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– Risk information lacked visual prominence– Began “Like all anticancer agents, there are side

effects…”

8

Lamisil Untitled Letter

DTC TV ad (“Digger”)Overstatement of efficacy– Showed complete “mycological cure” (all dermatophytes

gone) and “clinical cure” (pink healthy toenails) – only seen in 38% of patients

– Qualification on expected timeframe for efficacy (10-12 mos) not presented with claims

Minimization of risk– “Competing modalities” during risk info: compelling visuals

(e.g., giant tablet attacking and defeating Digger), sound effects, efficacy super

9

Paxil CR Untitled Letter

DTC TV ad (“Hello, My Name Is…”)Misleading communication of indication– Indication: Social anxiety disorder– Name tags suggested drug is appropriate for

lesser degrees of performance anxiety or shyness (e.g. “NERVOUS” “SELF-CONSCIOUS”)

Minimization of risk– Multiple scene changes, distracting visuals (e.g.,

“strobe-light” white out effect), competing/difficult to read supers, music

Zelnorm Untitled Letter

Product ad, not “help seeking”Failed to include risk information, indication and limitations, and brief summaryOverstated efficacy– Not a cure– Doesn’t work for all patients– Short-term treatment and symptoms can return– No data on complete relief in 3 days

10

Kaletra Untitled Letter

DTC ad in POZ magazine and restroom posterGraphics and text ( e.g., “Where do you see yourself in 5 years? Talk to your doctor about Kaletra.”) implied survival and good health for five years– Not “reminder”; therefore failed to comply with

requirements for full product claim promotion– No substantial evidence to support 5 year claims

Claritin Untitled Letter

“Reminder” and “Help-Seeking” ads appeared as front and back cover wrap to magazinesBecame a full product ad for ClaritinNo risk information/fair balance or brief summaryUnsubstantiated implied claims re: impact on school attendance and children’s attention spans

11

12

DDMAC Information

Web address:– http://www.fda.gov/cder/ddmac– Warning and untitled letters : Posted on

www.fda.gov/cder/warn– Guidances: www.fda.gov/cder/guidance

Phone number:– (301) 827-2828

Fax number:– (301) 594-6771