Supporting Statement Part A Final 1-7-15

Disclosure Regarding Additional Risks in Direct-to-Consumer Prescription Drug Television Advertisements

0910-NEW

SUPPORTING STATEMENT

Terms of Clearance – None.

1. Justification

1. Circumstances Making the Collection of Information Necessary

Regulatory Background. Section 1701(a)(4) of the Public Health Service Act (42 USC 300u(a)(4)) authorizes the Food and Drug Administration (FDA) to conduct research relating to health information. Section 1003(d)(2)(C) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 USC 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 product claim ads for prescription drugs contain accurate information about the risks and benefits of the drug advertised (21 CFR 202.1(e)(5)). Specifically, the advertising must contain the FDA-approved indication for use of the drug for the purpose claimed in the ad (21 CFR 202.1(e)(3)(ii)), and must not be false or misleading with respect to the side effects, contraindications, and effectiveness of the drug (21 CFR 202.1(e)(5)(i)). Pertaining to drug risks, the ad must not contain a representation or suggestion that the drug is safer, has fewer, or less incidence of, or less serious side effects or contraindications than has been demonstrated by substantial evidence or substantial clinical experience (21 CFR 202.1(e)(6)(i).

Rationale. Prescription drug advertising regulations (21 CFR 202.1) require that broadcast (TV or radio) advertisements present the product’s major risks in either audio or audio and visual parts of the advertisement; this is often called the “major statement.” There is concern that as currently implemented in direct-to-consumer (DTC) ads, the major statement is often too long, which may result in reduced consumer comprehension, minimization of important risk information and, potentially, therapeutic non-compliance due to fear of side effects.¹ At the same time, there is concern that DTC TV ads do not include adequate risk information or leave out important information.^{2, 3} These are conflicting viewpoints. A possible resolution is to limit the risks in the major statement to those that are serious and actionable, and include a disclosure to alert consumers that there are other product risks not included in the ad. FDA plans to investigate the effectiveness of this “limited risks plus disclosure” strategy through empirical research.

2. Purpose and Use of the Information Collection

This research will investigate the impact of limiting the risks presented in DTC television ads to those that are serious and actionable, and including a disclosure to alert consumers that there are other product risks not disclosed in the ad. Part of FDA’s public health mission is to ensure the safe use of prescription drugs; therefore it is important to communicate the risks and benefits of prescription drugs to consumers in a way that is clear, useful and non-misleading. The results from this research will be used by FDA to inform its understanding of DTC advertising, inform regulatory policy, and may also help to identify areas for further research.

3. Use of Improved Information Technology and Burden Reduction

Automated information technology will be used in the collection of information for this study. The contracted research firm will collect data through Internet administration. Participants will self-administer the survey instrument via a computer, which will record responses and provide appropriate probes when needed. FDA estimates that 100% of the respondents will use electronic means to fulfill the agency’s request. In addition to its use in data collection, automated technology will be used in data reduction and analysis. Burden will be reduced by recording data on a one-time basis for each respondent, and by keeping surveys to 30 minutes or less.

4. Efforts to Identify Duplication and Use of Similar Information

We conducted a literature search to identify duplication and use of similar information. We conducted a systematic review of the scientific literature by locating relevant articles through keyword searches using four different databases, including PubMed and PsycInfo. We also identified relevant articles from the reference list of articles found through keyword searches. We did not find duplicative experimental work on the impact of limiting the risks presented in DTC television ads to those that are serious and actionable, and including a disclosure to alert consumers that there are other product risks not disclosed in the ad.

5. Impact on Small Businesses or Other Small Entities

No small businesses will be involved in this data collection.

6. Consequences of Collecting the Information Less Frequently

The proposed data collection is one-time only. There are no plans for successive data collections.

7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

There are no special circumstances for this collection of information.

8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency

In accordance with 5 CFR 1320.8(d), FDA published a 60 day notice for public comment in the FEDERAL REGISTER of February 18, 2014 (79 FR 9217). FDA received comments from 26 groups or individuals in response to our Federal Register notice. This amounted to 55 comments that specifically referenced the study and were PRA-related.

FDA’s specific responses to the comments are divided into sections. The first section addresses pharmaceutical industry comments from PhRMA, Abbvie, Pfizer, and Eli Lilly and Company. The second section addresses comments from other organizations, including the Patient, Consumer, and Public Health Coalition, Washington Legal Foundation, Consumers Union, and Coalition for Healthcare Communication. The third section addresses comments from individuals (names indicated in-text when available). Many commenters indicated support for this research. We appreciate this support. Comments that are not PRA-relevant (e.g., “Ban DTC”) or do not relate to the proposed study are not included below or addressed in our responses. For brevity, all public comments are paraphrased and therefore may not reflect the exact language used by the commenter. We assure commenters that the entirety of their comments was considered even if not fully captured by our paraphrasing in this document.

Responses to Comments from the Pharmaceutical Industry

PhRMA

1. Use of an existing drug ad could have confounding results due to consumer familiarity with medicines and drug classes used to treat their existing condition.

Response: The decision to implement and modify existing ads was arrived at in an effort to balance the integrity of the research with cost considerations. It is significantly less expensive to implement and modify existing ads than it is to create and modify fictitious ads. Nonetheless, we appreciate this concern and in response, we have added questions to the survey to measure ad familiarity, which we can then control for in our analyses.

2. If FDA goes forward with the strategy to use existing ads, a) avoid using a drug ad that has aired within the past 12 months or that contains any iconic images or marks, b) alter the brand and established names of the drugs, c) record a new voiceover for the major statement using fictionalized risk information, and d) ensure that fictionalized risks are not similar to or associated with related drugs.

Response: We do not intend to fictionalize the risks and side effects or brand and established names. Our goal in using existing information is to ensure external validity of study findings when we draw comparisons between consumers who view existing versus modified risk statements. We intend to control for familiarity by measuring ad familiarity.

3. Participant sample should consist of consumers who self-identify as having the disease the drug featured in the ad treats.

Response: As stated in Federal Register Notice, “participants will be consumers who self-identify as having been diagnosed with one of three possible medical conditions.” The medical condition diagnosed will be consistent with the medical condition targeted by the advertising.

Abbvie

1. Ask participants to identify the name of the drug prior to asking about benefits and risks.

Response: Participants in this research will see only one drug ad and therefore perceptions will necessarily be associated with that one drug. It is outside the scope of this project to investigate drug name recall and/or recognition. Therefore, to avoid unnecessarily burdening participants, we do not intend to include these questions.

2. Include patients across a wider range of ages and with acute conditions.

Response: We proposed to recruit participants 18 years of age and older who self-identify as having been diagnosed with the medical condition being advertised. We considered many variables in choosing the conditions to test, including acute versus chronic conditions. We acknowledge that the type of condition (for example, acute, symptomatic, chronic, silent) may interact with the risk profile of the product (for example, very risky to less risky). With these variables in mind, we chose conditions that represent chronic and symptomatic diseases and a range of risk profiles.

3. Add a question to ascertain that participants can identify risks of the drug.

Response: Risk recall is currently assessed by Q6. Risk recognition is currently assessed by Q7.

4. Regarding Q8, if a fact-based statement was presented, it would be valuable to word the question to see if respondents comprehend the statement.

Response: Q8 (now Q9) reads, “In your opinion, if [DRUG] did help a person’s [condition], how much would it help?” The purpose of this question is to assess anticipated efficacy magnitude of the drug based on the advertising. This question has been subject to cognitive testing and refinement in other FDA research, confirming that respondents understand and are able to respond to this question.

5. Regarding Q18 and Q19 (Q23 and Q24 in revised questionnaire):

   1. These questions assume that participants are knowledgeable about alternative treatments; if they are knowledgeable, it is unclear what treatment participants might select as a comparator.

Response: We agree with this concern. In response, we have added language introducing these questions. The language reads, “Please think about other medicines you know of that treat [condition]. If you are not aware of other medicines that treat [condition], please choose the answer [Neither disagree nor agree].” Additionally, following Q23 and Q24, we intend to inquire which drug(s) participants had in mind with an open-ended question.

2. The focus of the questions should be on how to interpret the information when presented with all risks versus only major and most likely risks.

Response: The purpose of these questions is to assess anticipated efficacy and risk relative to other medicines that treat the condition. By drawing comparisons between the experimental conditions, we will be able to assess if anticipated efficacy and risk relative to other medicines differs due to exposure to the existing set of risks versus an abbreviated set (Condition 1) and whether or not a disclosure is presented (Condition 2).

3. A question should be added to ascertain if respondents can identify major risks of the drug.

Response: Risk recall is currently assessed by Q6. Risk recognition is currently assessed by Q7.

4. To assess participant ability to balance the risks of the drug with its benefits, respondent’s knowledge of the effectiveness of the drug should be queried using a 5 or 7 point scale anchored from Not Effective to Very Effective.

Response: The purpose of Q23 and Q24 is not to assess risk-benefit tradeoff. See response to comment 5b for the purpose of these questions. Note also that a number of questions already assess anticipated effectiveness of the drug (e.g., Q8 and Q9). Risk-benefit tradeoff is assessed by Q12 and Q13a-c.

6. Reword Q26 get the respondent to focus on the format of the information presentation versus how the study was executed.

Response: The language of this question (now Q28) has been reformatted to include the specific disclosure language. The purpose of this question is to assess noticeability and understanding of the concept that not all risks were presented. Later questions (e.g., Q29a) assess understanding of the specific statement wording.

7. Add questions to assess how informative and actionable participants found the list of risks and side effects.

Response: We agree with this suggestion and have now incorporated questions into the survey to assess these reactions.

Pfizer

1. It may prove difficult for respondents to quantify risk and benefit in Q7 and Q9 given that the ads will not explicitly quantify risk or benefit information; FDA should use these data only to assess relative differences across ad treatments.

Response: The purpose of these questions (now Q8 and Q10) is to assess perceived benefit and risk based on the advertising shown. We do not expect participants to quantify benefits and risks as they were empirically measured.

2. Avoid asking participants how other people will react.

Response: We agree with this suggestion and have revised the questionnaire accordingly.

3. Q18 and Q19 may prove difficult to interpret. Given that participants have not seen the revised major statements before, they may perceive drugs in the test ads to be more or less effective simply because other drugs advertised on TV are not using these formats. If implemented broadly, the comparative effect would likely go away.

Response: We appreciate the possibility that findings obtained in this study may differ from outcomes once implemented broadly. Still, it is important to measure these constructs. Findings from this study are one of a number of factors that would be considered prior to broad implementation in broadcast advertisements. These questions are reflected in Q23 and Q24 in the revised questionnaire.

4. Add questions to assess how clear, confusing, and important participants found the list of risks and side effects; also assess whether participants felt too much risk information and not enough risk information was presented.

Response: We agree with these suggestions and have incorporated questions into the survey that assess these constructs.

5. Delete Q11; the ads likely do not provide information about how easy or difficult it is to treat the condition with the drug.

Response: We agree with this suggestion and have modified the questionnaire accordingly.

6. Delete Q17; persuasiveness of the ad is subjective and difficult for respondents to assess.

Response: Our intention in asking this question (now Q26d) is to determine if displaying only serious and actionable risks along with a disclosure results in perceptions that the ad is more persuasive. We believe this is an important construct to measure and therefore will retain the question. Additionally, we have added Q17 (“I am interested in trying [DRUG]”) as an indirect measure of persuasion.

7. Delete Q23; it is not clear how respondents would be able to assess the quality of the drug.

Response: Our intention in asking this question (now Q25) is to determine if displaying only serious and actionable risks along with a disclosure results in perceptions that the drug is of high quality. This perception is based exclusively on the advertising and not on quality as it might be measured empirically. To clarify this intention, we have added instructions indicating that judgments should be reached based on the information in the prescription drug ad. We believe perceived drug quality an important construct to measure and therefore will retain the question.

8. Delete Q29a-d; it is not clear how assessing skepticism is relevant to the study objectives.

Response: Due to concerns about the length of the questionnaire, we have deleted these questions.

Eli Lilly and Company

1. Include a general population control group.

Response: The decision not to include a general population sample was arrived at in an effort to balance the integrity of the research with cost considerations. Each medical condition, or general population sample, comes at significant cost. The medical conditions we chose were selected because they represent conditions that are both chronic, symptomatic, and have a range of risk profiles (see response to Abbvie Comment 2 above). Although we appreciate the value of collecting data on a general population sample, we do not intend to adopt this suggestion in the present research based on cost considerations.

2. Immediately following unaided recall (Q1b; now Q3) and category assignments (Q2 and Q3; Q2 now deleted, Q3 now Q4), it is advised that close-ended questions assessing respondents’ perception of whether the information in the ad is easily understood (similar to Q20 battery; now Q13) be added.

Response: We agree that these questions are important and central to the research objectives, and so we have placed these questions earlier in the revised questionnaire. However, we are unclear on the rationale for inquiring about these topics immediately following Q4. We plan to instead measure recall and recognition of benefits and risks before inquiring about the clarity in presentation of benefits and risks. We believe that involvement in answering recall and recognition questions first will allow consumers to provide a more accurate assessment of whether the information is easily understood.

3. Several questions (Q7, Q8, Q9, Q11, Q18, Q19, and Q23) appear to lack relevance to the research objectives and should be modified or deleted.

Response: The purpose of Q7, Q8, and Q9 (now Q8 through Q11) is to assess perceived benefit and risk of taking the drug. The purpose of Q18 and Q19 (now Q23 and Q24) is to assess anticipated efficacy and risk relative to other medicines that treat the condition. The purpose of Q23 (now Q25) is to assess perceived quality of the drug. We have modified these questions to communicate that perceptions should be based on the impression participants received from the advertising. By drawing comparisons between the experimental conditions, we may determine that the risk and disclosure statements alter the abovementioned perceptions. We agree that Q11 lacks direct relevance to the research objectives and therefore have deleted this item.

4. Q36 suggests that participants may be allowed to complete the study using a mobile device; pre-testing should be conducted to determine the appropriateness of this option.

Response: We intend to restrict participants to using devices that allow full functionality of study procedures. We will retain a modified version of Q36 (now Q39) to ascertain that this requirement was followed.

5. Provide instructions to respondents regarding ad downloading/buffering to ensure they can see and hear the stimuli.

Response: We agree with this suggestion and intend to implement it.

6. Maintain consistent scale parameters throughout the survey to avoid confusion by participants and reduce bias in analysis.

Response: We agree with this recommendation and have adopted it in cases where the specific scale has not been validated by prior research.

7. Terms in Q2 (e.g., over-the-counter drug) should be defined or presented in consumer friendly language.

Response: Due to concerns about the length of the questionnaire, we have deleted this question.

8. In Q3, the response option “High Blood Pressure” may confuse participants who are diagnosed with both high cholesterol and high blood pressure; consider an alternative condition for high blood pressure.

Response: We agree with this recommendation and have replaced “high blood pressure” with “seasonal allergies.” Q3 is reflected in Q4 in the revised questionnaire.

9. Q13, Q14, and Q15 (Q18 through Q22 battery in revised questionnaire) should be modified so that the respondent would indicate intention or likelihood for themselves, without asking them to project to others.

Response: We agree with this recommendation and have modified these questions accordingly.

10. Improve programming instructions to clarify which respondents are asked Q27 and Q28 versus those that are skipped to Q29.

Response: Participants in conditions in which the risk disclosure is not shown are skipped to Q30 in revised questionnaire. We have clarified this intention in the programming language.

Responses to Comments from Other Groups and Organizations

Patient, Consumer, and Public Health Coalition (PCPHC)

1. Define “serious and actionable.”

Response: We define “actionable” as something the patient would know (e.g., pre-existing condition or allergy) or recognize (e.g., observable physical or mental symptom) and can act upon to help mitigate (e.g., get immediate medical help to prevent a bad outcome). For example, “stop using the product and get immediate medical help if you have swelling of the face, lips, tongue, or throat.” Serious risks would include those that appear in the warnings and precautions section of labeling and results in any of the following outcomes: Death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed above.

2. Ensure a diverse participant sample: Internet recruitment may favor inclusion of younger, more affluent and Internet-adept populations; the medical conditions chosen may not adequately reflect the general U.S. consumer audience.

Response: The rapid expansion of Internet access across the US population has made panel participation feasible for an increasingly broader range of respondents. Still, there are some demographic groups that are more responsive than others; but that can be found across all research methodologies. For example, there is a natural skew on those that will take a research phone call, and those that will attend a focus group.  The same can be said for Internet research as well. To rectify those skews, we utilize the Research Now panel, which is recruited to match a natural distribution of all demographic groups. Research Now works with clients to set fixed quota expectations in the survey instrument itself to enforce the final distribution and work with the invitation mix to balance the outcome as needed during the field period. Research Now’s panels are recruited through a partner network of ubiquitous brands utilizing a "By-Invitation-Only" approach and through tailored online marketing with over 300 diverse online affiliate partners and targeted website advertising. Specifically, Research Now uses e-Rewards® "By-Invitation-Only" recruitment methodology to invite pre-validated individuals to participate in their Consumer and Business Panels. Their recruitment methods provide a sample mix representative of the general population and also provide access to hard-to-reach business professionals and low-incidence consumers who are typically less likely to join panels.  Research Now controls and manages the demographic make-up of their panels and enrolls individuals who share known characteristics – ensuring access to populations of interest to the study. Their panels also comply with, or exceed, all applicable industry standards published by: ESOMAR, the MRS, the AMSRS (Australia), BVM (Germany), CASRO (US), MRS (US), MRIA (Canada).

Regarding choice of medical conditions, we considered many variables in choosing the conditions to test, including acute versus chronic conditions. We acknowledge that the type of condition (for example, acute, symptomatic, chronic, silent) may interact with the risk profile of the product (for example, very risky to less risky). With these variables in mind, we chose conditions that represent chronic and symptomatic diseases and a range of risk profiles.

3. Study conditions must be as similar to real life situations as possible.

Response: Because this is the first test of abbreviated risk statements with disclosures, our primary goal is to closely examine the cognitive effects of exposure to the test ads in a controlled experiment. As such, internal validity is a greater priority than external validity. We considered presenting test ads within a clutter reel to help mimic real world conditions, but worry that this approach may introduce unwanted bias (e.g., how attention-getting the test ad is compared to the filler ads). To increase study realism without sacrificing internal validity, we have chosen a sample that would potentially be interested in the drug. In addition, modified ads will be professionally developed and appear realistic.

4. Examine presentation of major statement earlier in the advertisement, when a greater proportion of consumers may be paying attention.

Response: We recognize the value of asking this question; consumers may respond differently if the major statement was to be presented earlier in an advertisement. However, this is a different research question than proposed by the present study and so we do not intend to address it in this research. We encourage other researchers to pursue this unique empirical question.

Washington Legal Foundation (WLF)

1. Supports the proposed collection and requests that it be expanded to test an alternative hypothesis that the average consumer is very unlikely to be “misled into believing that the drug poses no significant health risks for him” if a broadcast DTC advertisement for the drug “alerts consumers to its potential benefits, states generally that taking the drug poses significant potential health risks, lists any types of individuals who are categorically contra-indicated for the drug, and then asks the consumer to consult with his doctor for a more detailed explanation of risks,” and to include a First Amendment analysis.

Response: FDA appreciates the support for the proposed collection. However, FDA declines to expand the scope of this proposed information collection as suggested. The primary objective of the proposed study is to assess whether consumer perception and understanding of serious and actionable drug risks is improved if DTC television ads for prescription drugs present limited information focused on those serious and actionable risks together with a disclosure that there are additional risks, as compared to a broader presentation of risk information without disclosure that there are additional risks, like that commonly used in TV ads today. The presentation of risk information about prescription drugs to consumers implicates multiple important public health concerns, including how the presentation of both risk and benefit influences consumer judgments about the risk-benefit trade-off of advertised drugs, and how it impacts consumer decisions about whether or not to approach a healthcare provider about advertised drugs.

In considering how to allocate its limited resources for research, FDA must make choices and has identified its initial hypothesis as a useful one to help improve understanding of how different approaches in DTC television advertisements can impact consumer perception and understanding of drug risks. Once this proposed research is complete and published, the results will facilitate further consideration and analysis, including by outside entities, and may suggest additional topics for research.

A First Amendment analysis is likewise outside the scope of the current proposed research and FDA therefore declines to redesign the study along the lines suggested by the comment.⁴ Of course, when FDA implements its regulatory program, it does so in a manner that seeks to promote and protect the public health, consistent with its statutory authorities and mandate, while harmonizing this goal with First Amendment interests.

Consumers Union (CU)

1. Define “serious and actionable.”

Response: Please see our response to PCPHC Comment 1.

2. The proposed study could lead to replacing the current requirement to reference where to get full drug/device information with a mere mention that there are more side effects.

Response: Adequate provision refers to elements in a broadcast ad describing ways viewers can get the full product labeling, such as through the manufacturer’s website, through a print ad, by calling the manufacturer’s toll-free number, and by asking their healthcare provider. The proposed research was not designed to inform whether adequate provision should or should not remain in direct-to-consumer advertising, and therefore the study results should not be used for such purposes.

3. The study procedures should reflect the way an average consumer would see or hear an ad (e.g., when the consumer’s focus is not necessarily on the ad).

Response: Please see our response to PCPHC Comment 3.

Coalition for Healthcare Communication (CHC)

1. Include a qualitative leg to the study.

Response: Although adding a qualitative leg to the study would likely generate interesting and insightful outcomes, cost considerations restrict us from doing so. Note however that we do intend to conduct cognitive interviews prior to administration of the main study. Cognitive interviews involve a trained interviewer who will sit with participants as they view the stimuli, complete the questionnaire, and discuss their thought processes out loud, prompting participants to explain why they answered certain questions as they did. Findings from the cognitive interviews will then inform development of the final stimuli and questionnaire.

2. Include physicians in the study.

Response: We agree that physician perspectives about prescription drug advertising are important and interesting. However, as their perspective is outside the scope of the current research, we do not intend to adopt this suggestion. Note that we recently completed a separate study examining this topic, entitled “Healthcare Professional Survey of Prescription Drug Promotion.” Results from this study will be made available in the peer-reviewed literature.

3. Recruit respondents and analyze results by age cohort.

Response: We agree that recruiting participants across a wide range of ages is important and our sample will reflect this shared perspective.

4. Consider including communication media beyond television.

Response: We understand that it is important to understand effects of prescription drug advertising across mediums. Commonalities exist across multiple communication mediums, but also differences that may impact consumer perception of drug benefits and risks. Consequently, our research program has investigated various topics across these mediums. We intend to focus on television advertising in this study because it is most closely related to the research objectives, and due to cost considerations.

5. Reconsider using existing DTC ads in the proposed study.

Response: Please refer to our response to PhRMA comments 1 and 2.

6. Clearly define what “serious and actionable” risks are.

Response: Please refer to our response to PCPHC comment 1.

Responses to Comments from Individuals

Mel Sokotch

1. To ensure ad presentation is consistent with real world viewing conditions, the test ad should be presented as part of a clutter reel.

Response: Please refer to our response to PCPHC comment 3.

2. Immediately following the clutter reel with test ad inserted, initial survey questions should include open-ended assessment of issues such as recall, communication, and motivation. The ad should then be presented again and followed by additional questions designed to assess the impact of the ad.

Response: Our current procedures involve two presentations of the ad: once prior to administering the questionnaire and once during the questionnaire immediately preceding specific questions about the risk disclosure statement. To avoid unnecessarily burdening participants, we do not intend to show the ad a third time, per this recommendation.

Anonymous

1. As an end consumer, the side effects listed give us information to research further to determine the severity of the side effects.

Response: We address this concern by asking participants, in open-ended fashion, to list the thoughts that were going through their mind as they viewed the ad. In doing so, we hope to learn whether this is a broad concern among consumers. We are also assessing perceptions of risk.

2. Prescription drug commercials seek to persuade consumers, and healthcare providers have little time to discuss these risks and side effects with patients; thus, providing this information in television advertisements is important and necessary.

Response: Current regulations (21 CFR 202.1(e)(1)) require that prescription drug broadcast advertisements present the major risks of the drug as well as provide adequate provision, or mention of where the patient can obtain additional information about risks and side effects of the drug (e.g., websites, magazines). We recognize that providing risk information is an important and necessary component. As stated in the Federal Register, however, there is also concern that the length and content of some major statements is not adequately communicating this important information. Thus, we are conducting empirical research to test this question. This study does not address the question of adequate provision.

John Bonanno; Aaron Heyman; Thomas Klugh (similar comment)

1. All warnings should be clearly stated.

Response: Per 21 CFR 202.1, current regulations require that broadcast ads disclose the product’s major risks; these are typically the most common and the most serious risks described in labeling. At the same time the full product labeling should be made available through other means (see Guidance for Industry: Consumer-Directed Broadcast Advertisements⁵). With this in mind, the current study is addressing the impact of the current major statement risk format versus an abbreviated format, along with a disclosure indicating that not all risk information was presented.

John Sovitsky

1. Existing regulations do not go far enough; warnings should be described in text as large as benefits, and spoken at a slower, more intelligible speed.

Response: Although interesting, this comment is outside the scope of the present research.

Duane De Vries; Gary Graham (similar comment)

1. Consumers need all of the information that they can get to protect them against unscrupulous drug companies.

Response: Please see response to comment above.

Nila Jamerson; Charles McCloud (similar comment)

1. Risk disclosures in drug ads are tedious and unneeded; they should be provided by healthcare providers.

Response: Communication between healthcare providers and patients about drug risks is an important component of the healthcare decision making process. Nonetheless, the regulations require that benefit information in prescription drug ads should be balanced with presentation of risk information so that consumers can adequately consider both benefits and risks (i.e., the risk-benefit trade off) before approaching a healthcare provider about the drug.

Janessa

1. Additional risks should remain in TV ads; otherwise, advertised drugs sound like cure-all miracles.

Response: Note that we do not propose studying whether all risk information should be eliminated from broadcast ads. In both the current major statement condition and the experimental condition with abbreviated major statement plus disclosure, significant risks associated with the drug are presented in broadcast advertisements. . Thus, we do not agree that the presentation would imply a cure-all miracle.

Patricia Simon

1. The number of participants is far too few.

Response: Sample size per experimental condition in the main study is 125. This sample size is based on a statistical power analysis with power set at .90 and alpha equal to .05 assuming a small to medium effect size. Thus, power analyses support that our sample size is adequate.

External Reviewers

In addition to the comments above, the following experts reviewed the study design, methodology, and questionnaires:

• Craig Andrews, Ph.D., Professor, Marquette University.

• Anthony Cox, PhD, Professor, Indiana University.

• Joel J. Davis, PhD, Professor, San Diego State University.

9. Explanation of Any Payment or Gift to Respondents

Internet panel participants receive points for completing a survey. The incentive options allow panelists to redeem from a large range of gift cards, points programs, and partner products or services. Internet panel participants are enrolled into a points program that is analogous to a ‘frequent flyer’ card: respondents are credited with bonus points in proportion to their regular participation in surveys. Traditionally, panelists earn bonus points for surveys that are longer or require special tasks by the panel member. When a panelist’s point balance is equivalent to $10, panelists may elect to redeem the points for vouchers to a variety of national retailers. Participants who complete the 30 minute survey will receive an estimated $7.50 in e-Rewards currency, redeemable towards partner network vouchers.

10. Assurance of Confidentiality Provided to Respondents

No personally identifiable information will be sent to FDA. All information that can identify individual respondents will be maintained by the independent contractor in a form that is separate from the data provided to FDA. The information will be kept in a secured fashion that will not permit unauthorized access. Confidentiality of the information submitted is protected from disclosure under the Freedom of Information Act (FOIA) under sections 552(a) and (b) (5 U.S.C. 552(a) and (b)), and by part 20 of the agency’s regulations (21 CFR part 20). These methods will all be approved by FDA’s Institutional Review Board (Research Involving Human Subjects Committee, RIHSC) prior to collecting any information.

All respondents will be provided with an assurance of privacy to the extent allowable by law. The Internet panel includes a privacy policy that is easily accessible from any page on the site. A link to the privacy policy will be included on all survey invitations. The panel complies with established industry guidelines and states that members’ personally identifiable information will never be rented, sold, or revealed to third parties except in cases where required by law. These standards and codes of conduct comply with those set forth by American Marketing Association, the Council of American Survey Research Organizations, and others.

All electronic data will be maintained in a manner consistent with the Department of Health and Human Services’ ADP Systems Security Policy as described in the DHHS ADP Systems Manual, Part 6, chapters 6-30 and 6-35. All data will also be maintained in consistency with the FDA Privacy Act System of Records #09-10-0009 (Special Studies and Surveys on FDA Regulated Products).

11. Justification for Sensitive Questions

This data collection will not include sensitive questions. The questionnaire is available upon request. .

12. Estimates of Annualized Burden Hours and Costs

12a. Annualized Hour Burden Estimate

The total annual estimated burden imposed by this collection of information is 1,631 hours for this one-time collection.

FDA estimates the burden of this collection of information as follows:

Table 1.--Estimated Annual Reporting Burden
Disclosure Regarding Additional Risks in DTC Prescription Drug TV Ads	No. of Respondents	No. of Responses per Respondent	Total Annual Responses	Average Burden per Response	Total Hours
Pilot Study Screener	1700 (insomnia) 539 (high cholesterol) 3774 (depression)	1	6013	0.03 (2 minutes)	180
Main Study Screener	4252 (insomnia) 1347 (high cholesterol) 9433 (depression)	1	15,032	0.03 (2 minutes)	451
Pilot Study	600 (200 for each medical condition)	1	600	0.50 (30 minutes)	300
Main Study	1500 (500 for each medical condition)	1	1500	0.50 (30 minutes)	750
Total					1,681

12b. Annualized Cost Burden Estimate

Type of Respondent	Total Burden Hours	Hourly Wage Rate	Total Respondent Costs
General public	1,631	$19.50a	$31,805

^a Based on the 2014 median weekly income of $780 for both sexes, as reported by the Department of Labor, http://www.bls.gov/news.release/pdf/wkyeng.pdf.

13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs

There are no capital, start-up, operating or maintenance costs associated with this information collection.

14. Annualized Cost to the Federal Government

The total estimated cost to the Federal Government for the data collection is $608,730. This includes the costs paid to the contractor to perform a literature review, design a study, create and test measures and experimental stimuli, recruit a consumer sample, collect and analyze data, write reports of work completed, and present findings. The task order was awarded as a result of competition. Specific cost information other than the award amount is proprietary to the contractor and is not public information. The cost also includes FDA staff time to design and manage the study, to analyze the resultant data, and to draft a report.

15. Explanation for Programs Changes or Adjustments

This is a new data collection.

16. Plans for Tabulation and Publication and Project Time Schedule

Conventional statistical techniques for experimental data, such as descriptive statistics, analysis of variance, and regression models, will be used to analyze the data. See part B for detailed information on the design, hypotheses, and analysis plan. The Agency anticipates disseminating the results of the study after the final analyses of the data are completed, reviewed, and cleared. The exact timing and nature of any such dissemination has not been determined, but may include presentations at trade and academic conferences, publications, articles, and posting on FDA’s website.

Estimated Project Timetable

Task	Estimated Completion Date
60-day FRN publication	February, 2014
External peer review	December, 2014
RIHSC review	January, 2015
30-day FRN publication	January, 2015
OMB Review of PRA package	January, 2015
Cognitive testing	June, 2015
Pretesting	September, 2015
Main Study Data Collection	December, 2015
Data Analysis	March, 2016
Final Draft of Manuscript	July, 2016

17. Reason(s) Display of OMB Expiration Date is Inappropriate

No exemption is requested.

18. Exceptions to Certification for Paperwork Reduction Act Submissions

There are no exceptions to the certification.

1 Delbaere, M., & Smith, M. (2006). Health care knowledge and consumer learning: the case of direct-to-consumer drug advertising. Health Mark Quarterly, 23(3), 9-29.

2 Friedman, M., & Gould, J. (2007). Consumer attitudes and behaviors associated with direct-to-consumer prescription drug marketing. Journal of Consumer Marketing, 24(2), 100-109.

3 Frosch, D. L., Krueger, P. M., Hornik, R. C., Cronholm, P. F., & Barg, F. K. (2007). Creating demand for prescription drugs: A content analysis of television direct-to-consumer advertising. The Annals of Family Medicine, 5(1), 6-13.

4 We also note that we disagree with several aspects of the comment’s assertions related to First Amendment law, but we do not believe it is necessary or appropriate to address those arguments here.

5 http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm125064.pdf

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