Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices 75477 

1For prescription drugs and biologics, the FD&C 

Act requires advertisements to contain ‘‘information 

in brief summary relating to side effects, 

contraindications, and effectiveness’’ (21 U.S.C. 

352(n)). 

2See Schwartz, L., S. Woloshin, W. Black, et al., 

‘‘The Role of Numeracy in Understanding the 

Benefit of Screening Mammography,’’ Annals of 

Internal Medicine, 127(11), 966–72, 1997. 

3Woloshin, S. and L. Schwartz, ‘‘Direct to 

Consumer Advertisements for Prescription Drugs: 

What Are Americans Being Told,’’ Lancet, 358, 

1141–46, 2001. 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

21 CFR Section No. of 

recordkeepers 

Annual frequency per 

recordkeeper 

Total annual 

records 

Hours per 

recordkeeper Total hours 

516.141 ................................................................................ 30 2 60 0.5 30 

516.165 ................................................................................ 10 2 20 1 20 

Total .............................................................................. ........................ ........................ ........................ ........................ 50 

1 There are no capital costs or operating and maintenance costs associated with this collection of information. 

Dated: November 29, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–30316 Filed 12–2–10; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–N–0266] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Study of Clinical 

Efficacy Information in Professional 

Labeling and Direct-to-Consumer Print 

Advertisements for Prescription Drugs 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a proposed collection of 

information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Fax written comments on the 

collection of information by January 3, 

2011. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: FDA Desk Officer, FAX: 

202–395–7285, or e-mailed to 

oira_submission@omb.eop.gov. All 

comments should be identified with the 

OMB control number 0910-new and title 

‘‘Study of Clinical Efficacy Information 

in Professional Labeling and Direct-toConsumer (DTC) Print Advertisements 

for Prescription Drugs.’’ Also include the 

FDA docket number found in brackets 

in the heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Elizabeth Berbakos, Office of 

Information Management, Food and 

Drug Administration, 1350 Piccard Dr., 

PI50–400B, Rockville, MD 20850, 301– 

796–3792, 

Elizabeth.Berbakos@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. Study of Clinical 

Efficacy Information in Professional 

Labeling and Direct-to-Consumer (DTC) 

Print Advertisements for Prescription 

Drug—(OMB Control Number 0910– 

New) 

Section 1701(a)(4) of the Public 

Health Service Act (42 U.S.C. 

300u(a)(4)) authorizes FDA to conduct 

research relating to health information. 

Section 903(b)(2)(c) of the Federal Food, 

Drug, and Cosmetic Act (FD&C Act) (21 

U.S.C. 393(b)(2)(c)) authorizes FDA to 

conduct research relating to drugs and 

other FDA-regulated products in 

carrying out the provisions of the FD&C 

Act. 

FDA regulations require that an 

advertisement that makes claims about 

a prescription drug include a ‘‘fair 

balance’’ of information about the 

benefits and risks of the advertised 

product, in terms of both content and 

presentation (21 CFR 202.1(e)(5)(ii)). In 

past research FDA has focused primarily 

on the risk component of the riskbenefit ratio. In the interest of 

thoroughly exploring the issue of fair 

balance, however, the presentation of 

effectiveness, or benefit, information is 

equally important. 

The FD&C Act requires that 

manufacturers, packers, and distributors 

(sponsors) who advertise prescription 

human and animal drugs, including 

biological products for humans, disclose 

in advertisements certain information 

about the advertised product’s uses and 

risks.1 By its nature, the presentation of 

this risk information is likely to evoke 

active trade-offs by consumers, i.e., 

comparisons with the perceived risks of 

not taking treatment, and comparisons 

with the perceived benefits of taking a 

treatment.2 Since FDA has an interest in 

fostering safe and proper use of 

prescription drugs, an activity that 

engages both risks and benefits, an indepth understanding of consumers’ 

processing of this information is central 

to this regulatory task. 

Research and guidance to sponsors on 

how to present benefit and efficacy 

information in prescription drug 

advertisements is limited. For example, 

‘‘benefit claims,’’ broadly defined, 

appearing in advertisements are often 

presented in general language that does 

not inform patients of the likelihood of 

efficacy and are often simply variants of 

an ‘‘intended use’’ statement. In a 

content analysis of DTC advertising,3

the researchers classified the 

‘‘promotional techniques’’ used in the 

advertisements. Emotional appeals were 

observed in 67 percent of the ads while 

vague and qualitative benefit 

terminology was found in 87 percent of 

the ads. Only 9 percent contained data. 

For risk information, however, half the 

advertisements used data to describe 

side-effects, typically with lists of sideeffects that generally occurred 

infrequently. 

FDA regulations require that 

prescription drug advertisements that 

make (promotional) claims about a 

product also include risk information in 

a ‘‘balanced’’ manner (21 CFR 

202.1(e)(5)(ii)), both in terms of the 

content and presentation of the 

information. This balance applies to 

both the front (aka ‘‘display’’) page of an 

advertisement, as well as the brief 

summary page. However, beyond the 

‘‘balance’’ requirement limited guidance 

and research exists to direct or 

encourage sponsors to present benefit 

claims that are informative, specific, 

and reflect clinical effectiveness data. 

The purpose of this project is to: (1) 

Understand how physicians process 

clinical efficacy information and how 

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75478 Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices 

4As part of this effort, a qualitative mental 

models procedure was completed that helped us 

determine how physicians think about the efficacy 

of potential pharmaceutical options (OMB control 

no. 0910–0649). 

they interpret approved product label 

information,4 (2) determine physician 

preferences for alternative presentations 

of clinical efficacy information in DTC 

advertising, and (3) examine how 

different presentations of clinical 

efficacy information in DTC advertising 

affect consumers’ perceptions of efficacy 

and safety. Specifically, we are 

interested in how physicians and 

consumers make risk/benefit 

assessments and particularly, how 

consumers make such judgments in 

response to variations in the efficacy 

presentations in the ‘‘display’’ (first) 

page of a DTC print ad. A particular 

concern is whether certain presentations 

cause consumers to form skewed 

perceptions or unfounded risk/benefit 

tradeoffs. Therefore, we will investigate 

to what extent consumers, when 

provided with efficacy information, 

form perceptions that correspond with 

clinically-based physicians’ assessments 

of the benefits, risks, and benefit/risk 

tradeoffs of the same drugs. These 

studies will inform FDA’s thinking 

regarding how manufacturers may 

provide useful and non-misleading 

efficacy information in DTC print 

advertisements. 

Design Overview 

This study will be conducted in two 

concurrent, independent parts. The first 

part will involve 2,500 consumers in an 

experimental examination of variations 

of the display page of print DTC ads for 

two fictitious drugs, closely 

approximating existing drugs for 

overactive bladder (OAB) and benign 

prostatic hyperplasia (BPH). In the 

second part, 600 general practitioners 

will review and evaluate a fictitious 

‘‘approved’’ label for the same 

conditions. This design will allow us to 

compare consumers’ perceptions of 

efficacy with a more objective measure 

of the true efficacy of the drug as 

measured by physician perceptions of 

clinical efficacy from labeling. 

Consumer experiment. In this part of 

the study, women who have been 

diagnosed with or are at risk for OAB 

(self-designated based on relevant 

symptoms) will be recruited and will 

view one version of a DTC ad for a drug 

to treat OAB. Men who have been 

diagnosed with or are at risk for BPH 

(self-designated based on relevant 

symptoms) will be recruited and will 

view one version of a DTC ad for a drug 

to treat BPH. Although the two 

conditions are somewhat specific to 

gender (men can suffer from OAB but it 

is much more prevalent in women), they 

share many of the same symptoms and 

characteristics. These medical 

conditions afford us the ability to 

maintain various realistic manipulations 

of placebo level and type of claim, as 

explained below. The graphical 

elements and construction of the two 

ads will be comparable yet still realistic. 

Consumers will be randomly assigned 

to see 1 of 12 DTC print ads within their 

respective medical condition and will 

answer questions about the effectiveness 

and safety of the fictitious drug 

advertised in them. These twelve 

experimental conditions will be created 

by examining three independent 

variables in the following manner: Type 

of claim (2 levels: Treatment, 

prevention), placebo rate (3 levels: High, 

low, none), and framing (2 levels: 

Single, mixed). Please note that the 

numbers describing efficacy seen in the 

following table are for illustration only. 

Actual numbers used will be 

determined by pretesting. 

BILLING CODE 4160–01–P 

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Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices 75479 

BILLING CODE 4160–01–C 

We will investigate variations of 

numerical presentation in two different 

types of claims: treatment and 

prevention. Treatment claims usually 

involve symptoms that may be 

alleviated by taking a given prescription 

drug. This type of claim is directly 

observable and somewhat testable by 

patients. If bothersome symptoms do 

not go away, a patient can return to the 

healthcare provider with this 

information and pursue additional 

options for treatment. In general, drugs 

that treat symptoms typically show 

substantial percentages of people who 

experience relief. 

Prevention claims are important but 

due to their long-term nature, 

potentially harder to communicate. A 

drug that prevents a negative future 

event may not alleviate any symptoms 


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75480 Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices 

5For a literature review, see Moxey, A., D. 

O’Connell, P. McGettigan, et al., ‘‘Describing 

Treatment Effects to Patients: How They Are 

Expressed Makes a Difference,’’ Journal of General 

Internal Medicine, 18, 948–959, 2003. 

6Fagerlin, A., P.A. Ubel, D.M. Smith, et al., 

‘‘Making Numbers Matter: Present and Future 

Research in Risk Communication,’’ American 

Journal of Health Behavior, 31, S47–S56, 2007; 

Schwartz, L.M., S. Woloshin, H.G. Welch, ‘‘Risk 

Communication in Clinical Practice: Putting Cancer 

in Context,’’ Monograph of the National Cancer 

Institute, 25, 124–133, 1999. 

7 Including internists, general practitioners, and 

family practitioners. 

8To reduce burden, the physician sample will be 

split in this task, so that half of the physicians see 

the four ad versions with treatment claims and the 

other half see the four ad versions with prevention 

claims. Type of claim is described in greater detail 

in the consumer experiment section. 

at all. Patients may feel no benefit from 

the drug and must trust their healthcare 

provider and the data, as much as they 

can process it, that the drug is providing 

a positive benefit for them. The nature 

of these claims is such that the event 

being prevented is relatively rare, and 

thus the numbers used to describe them 

are often very small. For example, a 

cholesterol drug that reduces the risk of 

heart attack from 3 out of 100 to 2 out 

of 100 may not seem objectively large, 

but has enormous consequences for 

millions of people and the healthcare 

system in general. We chose to test this 

type of claim to determine whether 

consumers are sensitive to the 

magnitude of the benefit in these 

clinically meaningful but objectively 

small and usually asymptomatic 

outcomes. While we will examine the 

current issues in both treatment and 

prevention claims, we do not intend to 

make comparisons between the two. 

The second variable of interest is 

communication of a placebo rate. Three 

levels will be examined. In addition to 

testing a control condition with no 

placebo information, we will utilize a 

high and low placebo rate to better 

understand if and how consumers use 

placebo information. We see three 

possibilities: (1) People use placebo 

numbers correctly, such that the low 

placebo group demonstrates higher 

perceived efficacy than the high placebo 

group; (2) people use the placebo 

numbers as a peripheral cue to mean 

‘‘science’’ so there are no differences 

between high and low placebo groups 

on perceived efficacy but both are 

higher than the no placebo group; and 

(3) people do not find the numbers 

meaningful or cannot process them, so 

the high and low groups do not differ 

from one another and they do not differ 

from the no placebo group. In an 

attempt to make our claims as realistic 

as possible, we will maintain fairly low 

rates of prevention in the prevention 

conditions. For this reason, in addition 

to the 12 cells in the table previously 

illustrated in this document, we will 

also have an additional control cell in 

which the effectiveness rates are quite 

high—higher than could reasonably be 

expected but high enough to be 

objectively noticeable (e.g., risk of 

bladder cancer on Drug X, 4/100; risk of 

bladder cancer on placebo, 15/100). 

This additional condition will provide 

confidence that our research 

manipulations are operating as we 

expect. 

Finally, we will examine the addition 

of mixed framing to the traditional use 

of a single positive frame in a DTC ad. 

Mixed framing provides the number of 

people who benefited and the number of 

people who did not benefit, whereas 

positive framing provides only the 

number of people who benefited. Only 

a few studies have actually measured 

this mixed approach 5 although risk 

communication guides recommend the 

use of mixed framing to create more 

accurate perceptions.6 Although a 

completely balanced design would also 

include a negative framing condition 

(which would provide only the number 

of people who did not benefit), we feel 

it is unrealistic to create an ad that 

would suggest, for example, that ‘‘Drug 

X did not work for 70 percent of people 

in clinical trials,’’ so we have chosen not 

to include negative framing in our 

investigation. 

In this part of the project, we are most 

interested in consumers’ perceived 

efficacy and safety, which we can then 

compare with ratings physicians will 

provide based on the prescribing 

information, described in the next 

section. We will also ask consumers 

questions to measure their accuracy 

with regard to claims, their recall of the 

information in the ad, and demographic 

questions that may influence their 

responses, such as knowledge about 

their medical condition and their level 

of numeracy. 

Physician Study. Six hundred general 

practitioners 7 will participate in an 

Internet survey lasting no longer than 20 

minutes. They will complete two tasks 

during this time. In the first task, they 

will evaluate a prescription drug label 

(also known as the prescribing 

information, written for healthcare 

practitioners) for one of the two 

fictitious drugs described in the 

consumer study below. To provide a 

match for the variations of information 

in the DTC ads the consumers will 

observe, physicians will be randomly 

assigned to see prescribing information 

that varies in terms of claim type, 

placebo rates in clinical trials, and the 

medical condition the drug treats (OAB 

or BPH). 

As part of this task, we will obtain 

timing and sequence information on 

which sections of the label physicians 

examine. This will enable us to have a 

deeper understanding of physicians’ 

processing of the prescribing 

information. We are not aware of 

existing literature on this topic. 

Additionally, physicians will answer 

questions about the efficacy and safety 

of the drug and quantitative questions 

about the benefit shown in the clinical 

studies (as described in the label). These 

questions have been designed such that 

they can be reasonably compared with 

the responses of consumers who will 

answer the same questions after viewing 

a corresponding DTC ad. 

In the second task, physicians will see 

four versions of a print DTC ad for a 

fictitious product for high cholesterol 

and will rank the ads in order of how 

representative of the clinical data as the 

physicians know it the ads are and how 

useful they believe the ads would be for 

their patients.8 The four versions will be 

selected to mirror the versions of the 

OAB/BPH drug that consumers will see 

in the consumer experiment (i.e., low 

placebo, frame). 

Thus, this research will provide us 

with a rich data set in order to address 

several questions: (1) How physicians 

process clinical efficacy information 

and how they use approved product 

label information, (2) how physicians’ 

interpretations of clinical efficacy 

information relate to their preferences 

for alternative DTC ad presentations, 

and (3) which variations of information 

in DTC ads bring consumers closer to or 

farther away from the conclusions of the 

physicians regarding the same drugs. 

FDA estimates the burden of this 

collection of information as follows: 

The total respondent sample for this 

data collection is 3,400. We estimate the 

response burden to be 20 minutes in the 

first part and 15 minutes in the second 

part, for a burden of 906 hours. 

In the Federal Register of June 16, 

2010 (75 FR 34142), FDA published a 

60-day notice requesting public 

comment on the proposed collection of 

information. No comments were 

received on the paperwork burden. 

FDA estimates the burden of this 

collection of information as follows: 

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Federal Register / Vol. 75, No. 232 / Friday, December 3, 2010 / Notices 75481 

TABLE 1—TOTAL ESTIMATED ANNUAL REPORTING BURDEN 1

21 CFR Section Number of 

respondents 

Annual 

frequency 

per response 

Total annual 

responses 

Hours per 

response Total hours 

Physician survey—pretest ................................................... 100 1 100 .33 33 

Physician survey—main study ............................................. 600 1 600 .33 198 

Consumer experiment—pretest ........................................... 200 1 200 .25 50 

Consumer experiment—main study .................................... 2,500 1 2,500 .25 625 

Total .............................................................................. 906 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

Dated: November 30, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–30385 Filed 12–2–10; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–N–0597] 

Agency Information Collection 

Activities; Proposed Collection; 

Comment Request; Index of Legally 

Marketed Unapproved New Animal 

Drugs for Minor Species 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing an 

opportunity for public comment on the 

proposed collection of certain 

information by the Agency. Under the 

Paperwork Reduction Act of 1995 (the 

PRA), Federal Agencies are required to 

publish notice in the Federal Register 

concerning each proposed collection of 

information, including each proposed 

extension of an existing collection of 

information, and to allow 60 days for 

public comment in response to the 

notice. This notice solicits comments on 

the burden hours associated with 

indexing of legally marketed 

unapproved new animal drugs for minor 

species. 

DATES: Submit either electronic or 

written comments on the collection of 

information by February 1, 2011. 

ADDRESSES: Submit electronic 

comments on the collection of 

information to http:// 

www.regulations.gov. Submit written 

comments on the collection of 

information to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852. All 

comments should be identified with the 

docket number found in brackets in the 

heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Johnny Vilela, Office of Information 

Management, Food and Drug 

Administration, 1350 Piccard Dr., PI50– 

400B, Rockville, MD 20850, 301–796– 

7651, juanmanuel.vilela@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: Under the 

PRA (44 U.S.C. 3501–3520), Federal 

Agencies must obtain approval from the 

Office of Management and Budget 

(OMB) for each collection of 

information they conduct or sponsor. 

‘‘Collection of information’’ is defined in 

44 U.S.C. 3502(3) and 5 CFR 1320.3(c) 

and includes Agency requests or 

requirements that members of the public 

submit reports, keep records, or provide 

information to a third party. Section 

3506(c)(2)(A) of the PRA (44 U.S.C. 

3506(c)(2)(A)) requires Federal Agencies 

to provide a 60-day notice in the 

Federal Register concerning each 

proposed collection of information, 

including each proposed extension of an 

existing collection of information, 

before submitting the collection to OMB 

for approval. To comply with this 

requirement, FDA is publishing notice 

of the proposed collection of 

information set forth in this document. 

With respect to the following 

collection of information, FDA invites 

comments on these topics: (1) Whether 

the proposed collection of information 

is necessary for the proper performance 

of FDA’s functions, including whether 

the information will have practical 

utility; (2) the accuracy of FDA’s 

estimate of the burden of the proposed 

collection of information, including the 

validity of the methodology and 

assumptions used; (3) ways to enhance 

the quality, utility, and clarity of the 

information to be collected; and (4) 

ways to minimize the burden of the 

collection of information on 

respondents, including through the use 

of automated collection techniques, 

when appropriate, and other forms of 

information technology. 

Index of Legally Marketed Unapproved 

New Animal Drugs for Minor Species— 

21 CFR Part 516 (OMB Control Number 

0910–0620)—Extension 

The Minor Use and Minor Species 

Animal Health Act of 2004 (MUMS Act) 

amended the Federal Food, Drug, and 

Cosmetic Act (the FD&C Act) to 

authorize FDA to establish new 

regulatory procedures intended to make 

more medications legally available to 

veterinarians and animal owners for the 

treatment of minor animal species 

(species other than cattle, horses, swine, 

chickens, turkeys, dogs, and cats), as 

well as uncommon diseases in major 

animal species. 

The MUMS Act added three new 

sections to the FD&C Act (sections 571, 

572, and 573 (21 U.S.C. 360ccc, 360ccc– 

1, and 360ccc–2, respectively)). The 

final rule (72 FR 69108, December 6, 

2007) implements section 572 of the 

FD&C Act, which provides for an index 

of legally marketed unapproved new 

animal drugs for minor species. 

Participation in any part of the MUMS 

program is optional so the associated 

paperwork only applies to those who 

choose to participate. The final rule 

specifies, among other things, the 

criteria and procedures for requesting 

eligibility for indexing and for 

requesting addition to the index as well 

as the annual reporting requirements for 

index holders. 

Under the new subpart C of part 516 

(21 CFR part 516, subpart C), § 516.119 

provides requirements for naming a 

permanent-resident U.S. agent by 

foreign drug companies, and § 516.121 

provides for informational meetings 

with FDA. Section 516.123 provides 

requirements for requesting informal 

conferences regarding agency 

administrative actions and § 516.125 

provides for investigational use of new 

animal drugs intended for indexing. 

Provisions for requesting a 

determination of eligibility for indexing 

can be found under § 516.129 and 

provisions for subsequent requests for 

addition to the index can be found 

under § 516.145. A description of the 

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