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 Department of Health and Human Services Food and Drug Administration [Docket No. FDA-2008-N-0595]
 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 September 17, 2009.
 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: 202-395-6974, or e-mailed to 
                        *oira_submission@omb.eop.gov*. All comments should be identified with the OMB control number 0910—New and the title “Experimental Study: Toll-Free Number for Consumer Reporting of Drug Product Side Effects in Direct-to-Consumer Television 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 (HFA-710), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-796-3792.


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. Experimental Study: Toll-Free Number for Consumer Reporting of Drug Product Side Effects in Direct-to-Consumer Television Advertisements for Prescription Drugs—(OMB Control Number 0910—New) The Federal Food, Drug, and Cosmetic Act (the 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. For prescription drugs and biologics, the act requires advertisements to contain “information in brief summary relating to side effects, contraindications, and effectiveness” (21 U.S.C. 352(n)). FDA is responsible for enforcing the act and implementing regulations. On September 27, 2007, the President signed into law the Food and Drug Administration Amendments Act (FDAAA) (Public Law 110-85). Title IX of FDAAA amends section 502(n) of the act (21 U.S.C. 352) by requiring printed direct-to-consumer (DTC) advertisements for prescription drug products to include the following statement printed in conspicuous text: “You are encouraged to report negative side effects of prescription drugs to the FDA. Visit 
                    *www.fda.gov/​medwatch*, or call 1-800-FDA-1088.” Title IX of FDAAA also requires the Secretary of Health and Human Services (the Secretary), in consultation with the Risk Communication Advisory Committee (RCAC), to conduct a study not later than 6 months after the date of enactment of FDAAA to determine if this statement is appropriate for inclusion in DTC television advertisements for prescription drug products. As part of this study, the Secretary shall consider whether the information in the statement described previously in this paragraph would detract from the presentation of risk information in a DTC television advertisement. If the Secretary determines that the inclusion of such a statement would be appropriate for television advertisements, FDAAA mandates the issuance of regulations implementing this requirement, and for the regulations to reflect a reasonable length of time for displaying the statement in television advertisements. Finally, FDAAA requires the Secretary to report the study's findings and any subsequent plans to issue regulations to Congress. In accordance with the requirements of FDAAA, FDA convened a meeting of the RCAC on May 15 and 16, 2008. A draft design for studying this issue was proposed at that time and discussed by the advisory committee. Based on comments received at that meeting, changes were made to the proposed study design. The transcripts and materials from that meeting can be found at 
                    *http://www.fda.gov/​ohrms/​dockets/​ac/​oc08.html#RCAC*. I. Background Section 17 of the Best Pharmaceuticals for Children Act (the BPCA) (Public Law 107-109, January 4, 2002) required FDA to issue a final rule mandating the addition of a statement to the labeling of each drug product for which an application is approved under section 505 of the act (21 U.S.C. 355). Under the BPCA, the statements must include: (1) A toll-free number maintained by FDA for the purpose of receiving reports of adverse events regarding drugs, and (2) a statement that the number is to be used only for reporting purposes, and it should not be used to seek or obtain medical advice (the side effects statement). On April 22, 2004, FDA published a proposed rule with a proposed side effects statement for certain prescription drug product labeling and a proposed side effects statement for certain over-the-counter drug product labeling (69 FR 21778). In the proposed rule, FDA solicited comments on a proposed statement that FDA believed comported with the previously mentioned mandate in the BPCA. The agency received 12 comments suggesting changes to the specific wording proposed. The agency also received several comments suggesting that FDA engage in research to study the wording of the proposed side effects statement with consumers. Among the reasons cited for testing the statement were to: (1) Determine the best and most precise wording for the statement, (2) evaluate consumer comprehension of the proposed statement, and (3) address concerns that consumers who read the statement will mistakenly call FDA in search of medical advice rather than seeking appropriate medical treatment. In addition, during the clearance process for the proposed rule, both the Office of Information and Regulatory Affairs of OMB and the Office of the Assistant Secretary for Planning and Evaluation of the Department of Health and Human Services suggested that FDA conduct focus groups or other consumer studies to inform the wording of the side effects statement. During the spring of 2006, to assist in developing this study, FDA conducted two focus groups to gauge consumer understanding and preferences for a number of proposed side effects statements and to narrow the number of statements to be tested in subsequent experimental research. In addition to the information collected on which versions of the statements participants preferred, discussions showed that people varied in their understanding of when to call FDA or their health care 
                    ( print page 41704)
                    practitioners and that some people would not call FDA even if they experienced a serious side effect. Several people in the focus groups suggested the addition of a Web site to report adverse side effects. Based on the findings from the focus groups, nine statements were selected for quantitative testing. A labeling comprehension experiment was conducted with 1,674 men and women ranging in age from 21 to 95 with varying levels of education (OMB Control No. 0910-0497). The results from that quantitative test found that only one of the versions tested was rated as significantly less clear than the others, which were all rated as generally clear and understandable. The results also showed that participants reported they would not call FDA seeking medical advice. Further, among those participants who said they would call FDA, the majority indicated they would call their doctor for medical advice, rather than FDA, regardless of the severity of the side effect. Finally, participants indicated they could distinguish between serious and non-serious side effects, reporting that they would seek emergency medical care in the case of serious side effects. The report of the study is available in the docket for the final rule (Docket No. FDA-2003-N-0313). The final rule, Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug Products (TFNR) (73 FR 63886, October 28, 2008), is available at 
                    *http://www.fda.gov/​OHRMS/​DOCKETS/​98fr/​E8-25670.pdf*. In the 
                    **Federal Register**
                     of November 26, 2008 (73 FR 72058), FDA published a 60-day notice requesting public comment on the information collection provisions. FDA received six comments in response to our initial 
                    **Federal Register**
                     notice, published on November 26, 2008. One of these comments, from an anonymous citizen, did not require specific responses, as it was outside the scope of the project (e.g., FDA approves too many drugs; harmful drugs are “being foisted on the population”), although it could be viewed as a statement of support for conducting the research. II. Comments on the Information Collection In the following section, we outline the issues raised in the comments and provide our responses. (Comment 1) Do not place the toll-free statement in television ads because it is better placed within written materials that accompany prescription drugs. Some system for enforcing the legitimacy of calls is necessary, otherwise callers with an “agenda” or “the uninformed” could “doom medicines for no reason.” (Response) This comment mostly applies to MedWatch procedures that are outside the scope of the proposed research. This study is addressing the understanding of information in the ad. We have notified the appropriate parties in the agency of this comment. (Comment 2) The comment supports DTC advertising that is educational and “delayed until postmarketing surveillance data are collected and assessed.” DTC television ads should include a toll-free statement. Overall, this comment supports the proposed research, but includes the following specific suggestions: (1) The toll-free statement is best placed after the risk information and (2) it should be placed during the presentation of non-life-threatening or minor side effects. (Response) We agree that placement during non-life-threatening or minor side effects may be the best placement for the toll-free statement. In a television ad, however, that information is presented in a very short amount of time, sometimes only seconds (and this varies depending on the drug product). We have designed our study to allow the data to show for us the best placement of the statement. (Comment 3) Neither of the proposed toll-free statements addresses whether consumers can distinguish between serious and non-serious side effects. A simulation study should be used to assess this issue. (Response) We refer this comment to previous research conducted by FDA on this topic, described previously. This study found that participants were easily able to distinguish between serious and non-serious side effects and that they reported an ability to take the right action with regard to each one. (Comment 4) FDA should post the proposed questionnaire, the primary endpoint(s) of the study with action standards, and provide the mock advertisement to interested parties for use in their research. (Response) The proposed questionnaire has been and continues to be available upon request. We agree that threshold levels and primary endpoints were not well explained in the 60-day notice and have worked to correct that in the 30-day notice. Please note the addition of specific hypotheses and the analysis plan. At the conclusion of our data collection, we will make the advertisement available to those who request it. (Comment 5) Adequate provision issues may not be considered or addressed. Multiple telephone numbers or Web sites may confuse consumers. Use alternate wording for the toll-free statement: “For information about PRODUCT X or to report side effects, see our ad in ___ magazine.” Include payment assistance information, as this is often currently included in television ads. (Response) We have designed the stimuli ad to closely approximate an actual DTC ad, including adequate provision measures and other supers. Division of Drug Marketing, Advertising, and Communications reviewers have examined the script and storyboard to ensure that the ad meets regulatory requirements. The contractor producing the ad has extensive experience with this type of production and provided additional quality control measures. In directing us to complete this research, Congress was likely concerned about the same issues expressed by this comment, i.e., that the toll-free statement may be confusing. That is one of the main research questions we will address. In terms of wording, Congress directed us to test specific language. In addition to this language, we propose to test another version that was found most acceptable in previous usability research conducted by the agency. Finally, because payment assistance information is relatively new, not universal, and not required by regulation, we have not included this statement in our stimuli ads. FDA has contracted with a professional multimedia company to create ad stimuli. In addition, FDA has instituted a procedure of extensive pretesting of the ad stimuli to be used. Our extensive experience with current and past DTC ads, pretesting, and collaboration with the contractor should ensure realistic ads that will enable us to successfully investigate our experimental variables. (Comment 6) Study multiple medical conditions, including symptomatic and asymptomatic conditions; diseases that affect different age groups; sufferers and non-sufferers; and consumers with varying degrees of knowledge about their medical conditions. (Response) We do not have the resources to create mock ads to test multiple medical conditions. We have no reason to suspect that the principles we study in this medical condition (e.g., placement, duration, wording, prominence) would be different when applied to an ad for another medical condition. We welcome other parties to extend the current research by applying it to other conditions. We will ask respondents about their knowledge of their medical conditions and will 
                    ( print page 41705)
                    conduct analyses to see if this variable plays a role in their responses. We have decided, however, to recruit for the study two distinct populations: Those who have been diagnosed with high blood pressure and a general population sample. This approach will allow us to determine whether diagnosed individuals and other people who may be exposed to such television advertising will differ in their responses to the ad. (Comment 7) Using the condition where the toll-free statement is present during the whole ad to control for novelty will increase rather than decrease the attention to the statement. (Response) We agree that the condition in which the toll-free statement appears during the entire ad may increase notice of it. We think there is also a good possibility that it might be ignored, in such a way that the statement might be more prominent in other conditions. To control for novelty, participants will see an unrelated DTC ad with the toll-free statement presented the same way as the test ad before they see the test ad. This may control for novelty in the test ad and may attenuate the belief that our test product has some unique quality that causes it to need a special toll-free statement. (Comment 8) This protocol will take much longer than 15 minutes. (Response) Because we are also concerned that this protocol will take longer than 15 minutes, we have revised our burden estimate to reflect a 20-minute protocol. Also, to ensure that all test parameters are met, including timing of experiment, we have budgeted for 2 pretests of 700 individuals each. (Comment 9) The placement and duration variables should be removed from study because regardless of placement, the statement may interrupt the flow of the most important information. (Response) These are empirical questions. We will not know the answer to either of these questions until we collect data. (Comment 10) Remove the audio-only condition because this eliminates the hearing-impaired population. Include visually and hearing-impaired persons to more accurately represent the population. (Response) Even in our audio-only condition as originally proposed, the Web site and phone numbers were placed on screen. Current requirements for the most important risk information (i.e., the major statement) are that it be placed in the audio portion of the ad. Thus, this is a reasonable condition to test. Upon further discussion, however, we agree that we do not need two distinct extra-prominent conditions, and will test only one. We do not plan to actively exclude people with audio or visual impairments from the study but we do not have the resources to actively recruit them. (Comment 11) High blood pressure may not be the most representative condition for a general sample of consumers “over the age of 18.” The tested sample population should be representative of actual sufferers of the condition being advertised. (Response) We agree that this is an important consideration. Upon further discussion, we have decided to recruit for the study two distinct populations: Those who have been diagnosed with high blood pressure and a general population sample. This approach will allow us to determine whether diagnosed individuals and other people who may be exposed to such television advertising will differ in their responses to the ad. (Comment 12) Remove the fourth commercial for an unrelated medical condition because it does not contribute to the study and may confound results. (Response) Study participants will see four ads—the second ad will be an unrelated DTC ad and the fourth ad will be the test ad. We propose to include the other DTC ad with the matching toll-free statement parameters so that consumers do not think that our test ad reflects a special product that needs a special warning. It also may attenuate the effect of novelty. (Comment 13) Because the toll-free statement may artificially increase impact of risk information, FDA should test information gleaned from the presence of the toll-free statement in print ads first. (Response) FDA has not collected any information on the presence of the statement in print ads, although we agree this would be valuable information. Moreover, Congress has instructed us specifically to test the toll-free statement in television ads. (Comment 14) Including the manufacturer's toll-free number instead of the FDA contact number may help to mitigate the possibility that the toll-free statement artificially increases the impact of risk information. (Response) Sponsors already include the manufacturer's telephone number in all ads as a way to fulfill one part of the adequate provision requirement. The current study does not examine the replacement of that number with the toll-free statement, but instead the statement's inclusion above and beyond current requirements. (Comment 15) The agency's expectation of yielding a sample of 2,000 people from a total of 2,400 is unrealistic based on a typical response rate of 5 percent. (Response) We do not expect to yield a sample of 2,000 people from a total of 2,400. As shown in Table 1 of this document, we have revised our sample numbers. (Comment 16) How well can an Internet study simulate a television environment? (Response) We agree that simulating an everyday television-watching environment would increase the realism of the study. Participation in an experiment in any context, however, is unlikely to perfectly do so. We do not believe that a mall-intercept administration would increase the realism of the study and a phone-based survey is not feasible, given the modality of the advertisement in question. Moreover, an Internet study may be as close to the television-watching environment as any other method because participants will be in their own homes and some participants already watch streaming video on their computers. (Comment 17) What are the thresholds for interference (“detraction”) in this study? Specifically, will the statement be included only if it does not affect risk comprehension at all, or if it does not affect risk comprehension “much”—and if this is the case, what is too much? (Response) If the study demonstrates that the inclusion of the toll-free statement does not interfere with the processing of the risk information, then Congress is likely to mandate its inclusion. If the data demonstrate some detraction from risk information, then the decision becomes more complicated. As the interference between the toll-free statement and the risk information increases, the less likely it is that it will be mandated. A tradeoff analysis will have to be conducted and this study will be only one part of the determination. That is, the amount of detraction will have to be weighed against the benefit of including the statement and this benefit will be determined in part by public health concerns and analysis of MedWatch data. (Comment 18) Participants will see the test ad three times and this may cause problems. (Response) Participants will see the test ad only once after seeing three other filler ads, one of which will be an unrelated DTC ad. (Comment 19) The current proposed study is comprehensive and appropriate to address the primary research questions under consideration.
                    ( print page 41706) (Response) Thank you. (Comment 20) The toll-free statement in the unrelated DTC ad should be presented in the same way as in the test ad. (Response) We had planned to do so. (Comment 21) The questionnaire does not specifically address the risk of nontreatment of the disease condition. (Response) FDA acknowledges that this study does not address this risk. Nevertheless, this is outside the scope of the current investigation. (Comment 22) Ask if respondents suffer from diabetes, high cholesterol, obesity, or the condition treated in the unrelated DTC ad. (Response) We plan to ask about the state of respondent's health. In considering this comment, we have added additional questions to the questionnaire. Please see the revised questionnaire for details. (Comment 23) Question 7 in the questionnaire is vague and should be placed earlier in the questionnaire. (Response) Question 7, which originally asked participants in an open-ended fashion to report on “some information written on the screen” has been changed. We now ask participants which of several options they saw and follow that up with an open-ended question about what the statement means to them. We do not wish to move this question series earlier in the questionnaire because it is not one of our main dependent measures. (Comment 24) It is unclear how FDA plans to analyze results from this research, particularly what action consumers are expected to take after they have heard and understood the toll-free statement. (Response) The purpose of this research is not to determine what action consumers will take after seeing the ad. We addressed these issues in the labeling comprehension study described at the beginning of this notice (Docket No. FDA-2003-N-0313). The purpose of the current proposed study is to determine whether the risk information is adequately comprehended and whether the toll-free statement is noticeable and recalled. III. Revised Study Experimental Study: Toll-Free Number for Consumer Reporting of Drug Product Side Effects in Direct-to-Consumer Television Advertisements for Prescription Drugs—(OMB Control Number 0910—New) Based in part on these comments, further research discussions, and the input of the RCAC on May 16, 2008, we propose the following revised design, hypotheses, and analysis plan. A. Overview This study will examine the placement of the toll-free statement and the length of time the statement is presented on screen in a DTC television advertisement for a prescription drug. The primary dependent measure of interest is consumer comprehension of the important risk information in the advertisement. This study will also examine potential differences in comprehension based on the wording of the toll-free statement and the prominence of the statement. The application of a new piece of information for viewers of DTC ads presents logistical challenges. From a research perspective, the primary issue under investigation is how to impart additional information without increasing “cognitive load,” thus leading to information overload. Cognitive load is an index of the memory demands necessary to process a set of information (Ref. 1). As cognitive load increases, more mental resources are necessary to process and understand the information. DTC ads are already quite dense when compared to ads for other products. The risk information in the major statement of the ad should not be compromised by the addition of the toll-free statement. At the same time, it is preferable that the risk information and the toll-free statement information are presented in such a way that both are understandable. We have chosen a set of variables in the current study to investigate issues of cognitive load. They are described briefly below before examining the details of the research design. 1. Placement The location of the toll-free statement may facilitate or detract from the risk information in the major statement. We have chosen three locations for this information to test which location results in the greatest communication of the risks of the drug and the concept that side effects can be reported. It is possible that locating the toll-free statement before the major statement provides a “prime” for the risk information that follows; that is, the mention of side effects in the toll-free statement will cause consumers to start thinking about side effect-related information, which facilitates comprehension of the risk information that follows. In this case, the two conceptual pieces of information may flow together easily. Conversely, it is possible that the toll-free statement confuses consumers or provides no information for them because they have not yet heard any risk information. Thus, without context, the statement lacks applicability. Placing the toll-free statement during the major statement likely reduces the comprehension of the risk information for the drug because it divides viewer's attention between two competing pieces of information. It is possible, however, that the juxtaposition of these two informational concepts are complimentary and therefore do not conflict. The toll-free statement may serve the best role after the risk information has been presented. In this case, participants have been told about the risks and side effects of the drug before they are told they may report this information. This essentially primes the toll-free statement with the major statement. We do not expect this placement to interfere with the comprehension of risk information, as it is not present during the voicing of risks and has not been introduced to viewers at this point. In addition, the usefulness of the toll-free statement may improve in this condition relative to those discussed in the previous paragraphs because viewers have been provided with context. Over time, it is likely that the toll-free statement will become part of the background of the ads as people become accustomed to seeing this statement in all DTC ads. In this respect, people will have the statement as an option if needed but may be able to disregard it to focus on the risk information otherwise. Thus, we are testing a condition in which the toll-free statement will be present during the entire ad. This test condition will control for the effect of novelty arising from the fact that consumers have not previously seen this type of statement in TV ads. Presence of the statement during the entire ad may increase noticeability of the toll-free statement initially, but will be unlikely to interfere with risk information over time. 2. Statement Type The second variable, statement type, will have two executions of statement language: The language from the FDAAA versus the language used in the final rule, Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug Products Rule (TFNR; Public Law 107-109, January 4, 2002), and previously tested by FDA. The wording from these two statements is as follows: “You are encouraged to report negative side effects of prescription drugs to the FDA. Visit*www.fda.gov/​
                        ( print page 41707)
                        medwatch*, or call 1-800-FDA-1088.” (FDAAA)
                “Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 orwww.fda.gov/​medwatch.” (TFNR) We think it is important to test both the toll-free statement version in FDAAA and the version that we have previously tested with actual consumers. The most obvious reason for this is to make sure that the statement is maximally readable and understandable. It may be valuable, however, to test two statements for another reason. If the toll-free statement is enacted in broadcast ads, it is possible that because of the boilerplate language, some amount of habituation will occur. That is, after viewers have seen the same language in multiple ads for multiple products, they may “tune out” and not pay attention to the toll-free statement at all. If we test two versions of the statement and find both acceptable, it would be possible to either allow sponsors to choose one statement versus another or to suggest some alternating of the two statements. This is a long-term idea, however, and finding appropriate wording is the primary goal of investigating this variable. 3. Duration Congress specifically mandates that we investigate the duration of the display of the toll-free statement. As with placement, the length of time the toll-free statement is presented on screen may influence the cognitive load in the ad. For experimental control, we will look at the duration of the statement while holding placement in the ad (after the major statement of risks) constant. Although this placement should not interfere with the processing of the risk information, it is possible that the duration influences the take-away message from the ad. For example, having the statement on screen for a short amount of time may not give consumers enough time to read and process the toll-free message. This may result in lower comprehension of the message but may have no impact on the comprehension of the risk information. Alternatively, displaying the toll-free statement for a longer period of time may remove memory traces of the risks from the major statement, resulting in lower risk comprehension. To determine whether this longer duration increases the usefulness of the toll-free statement itself, we will compare these short and long durations to instances where the toll-free statement is present during the entire ad and where there is no toll-free statement at all. 4. Prominence In addition to superimposing the toll-free statement on the screen during the ad, there are other methods available to increase the prominence of the statement. In particular, having the statement read aloud in the ad voiceover while the statement is on the screen may be considered particularly prominent. Does the additional prominence of the statement compromise the comprehension of the risk information in the major statement? If not, does the additional prominence result in a greater understanding of the toll-free statement itself? It is likely that there is a tradeoff between the gains of emphasizing the toll-free statement and the comprehension of the risk information. In examining this variable, we are exploring the parameters of this tradeoff. B. Design The design will consist of three parts. Part one will be a between-subjects factorial design examining the placement of the toll-free statement by the type of statement. The first variable, placement, will have four levels: Before the major statement of risks, during the major statement of risks, after the major statement of risks, or continuously throughout the whole ad. In each condition the toll-free statement will appear in the ad as superimposed text at the bottom of the screen. We will also include a control condition in which the statement does not appear. **Part One: Placement by Statement Type**
4 x 2 + 1
Statement TypePlacement
FDAAA
TFNRBefore major statement of risksDuring major statement of risksAfter major statement of risksDuring the whole ad
 Plus: Control (no toll-free statement)
 Part two of the study will examine four variations in the duration of the toll-free statement using the language from FDAAA: Short (on screen for approximately 3 seconds after the major statement), long (on screen for approximately 6 seconds after the major statement), on screen during the whole ad, and the control condition of no toll-free statement included. These times were adopted by calculating how long it would take a person reading at an average reading speed to read the statement. As in the first part of this study series, the toll-free statement will appear as superimposed text and a control condition in which the toll-free statement does not appear will be included.
                    ( print page 41708) **Part Two: Duration***
4 x 1
Short (on screeen for approximately 
                             3 seconds after major statement)Long (on screen for approximately 
                             6 seconds after major statement)During the whole adControl (no toll-free statement)*
                        Using FDAAA statement
 Part three of the study will examine two variations in the prominence of the toll-free statement using the language from the FDAAA: Spoken after the major statement with only the Web site and phone number in superimposed text, and a control condition where the toll-free statement is presented visually after the major statement. **Part Three: Prominence***
2 x 1
Extra Prominent (spoken after major statement of risks, Web site and phone number on screen)Control (after major statement of risks)*
                        Using FDAAA statement
 We will investigate these issues in one disease condition, high blood pressure, because high blood pressure has a high incidence rate in the population, is a public health concern, and is likely to occur in both males and females. Further, because there is little broadcast promotion for prescription treatment of high blood pressure at this time, participants should be less familiar with DTC television ads for this type of drug, reducing the potential influence of prior experience. Our primary dependent variable is comprehension of the risk information mentioned in the major statement. In addition to this variable, we will also examine comprehension of benefit information. We will also examine the noticeability and comprehension of the toll-free statement. C. Procedure Participants will see a cluster of four ads: Two 15-second non-DTC ads (fillers), an approximately 60-second DTC ad for a fictitious high blood pressure medication, and a 30-second DTC ad for an unrelated medical condition with the same toll-free statement included. We include two DTC ads with the toll-free statement in our protocol because this better approximates what will happen if this statement is enacted. That is, viewers will see the statement in all DTC ads for all products. In this study, we want to avoid the suggestion that there is something particular about the high blood pressure drug class that causes the statement to be mandated. Thus, we will show multiple DTC ads but ask questions regarding only the ad which has been manipulated to test our hypotheses. To maximize response information, the test ad will always be the last ad they see. After viewing the ads, a structured interview will be conducted. Participants will answer questions about the high blood pressure DTC test ad they have seen. Questions will examine a number of important perceptions about the advertised product, including risk comprehension, risk recall, benefit comprehension, benefit recall, behavioral intention, noticeability of the toll-free statement, and recall of the toll-free statement. Finally, demographic and health care utilization information will be collected. The entire procedure is expected to last approximately 20 minutes. A total of 6,000 interviews will be completed. This will be a one-time (rather than annual) information collection. D. Participants Data will be collected using an Internet protocol. Two samples of consumers will be recruited: One sample of individuals diagnosed with high blood pressure and another sample of consumers over the age of 21. Both groups will represent a range of education levels. Because the task presumes basic reading abilities, all selected participants must speak English as their primary language. FDA proposes to conduct two rounds of pretesting with 700 consumers in each round to refine the questionnaire and the stimuli before collecting data for the main study. Hypotheses Overall, we expect effects to be stronger in the high blood pressure sample than in the general population sample, as high blood pressure sufferers will likely have higher involvement with the medical condition. 1. Risk Comprehension This section explains the following: Any inclusion of the toll-free statement will reduce the comprehension of risk information. (Risk comprehension will be highest in control condition for all analyses) Placement: Conditions in which the statement is presented after the major statement and the statement is present for the whole ad will reduce comprehension least. (After control condition, risk comprehension will be highest in conditions where statement is present for whole ad or after the major statement; risk comprehension will be lowest when statement is presented during or before the major statement). 
 
 Wording: Type of statement will not influence risk comprehension.
                Placement x Wording: This analysis is exploratory
                Duration: Statement will interfere with risk comprehension less when presented in the whole ad than when presented for briefer periods. Short duration will result in lower risk comprehension than long duration because it will be displayed for a short time, causing attention to shift twice in quick succession (Risk comprehension highest in control condition, followed by whole ad condition followed by long duration, and, finally, short duration) Prominence: Prominence of statement will not affect risk comprehension. 2. Benefit Comprehension This section explains the following: Any inclusion of the toll-free statement will reduce the comprehension of benefit information. (Benefit comprehension will be highest in control condition for all analyses) Placement: Conditions in which the statement is presented after the major statement and the statement is present for the whole ad will reduce comprehension least. (After control condition, benefit comprehension will be highest in conditions where statement is present for whole ad or after the major statement; benefit comprehension will be lowest when statement is presented during or before the major statement). Wording: Type of statement will not influence benefit comprehension.
                Placement x Wording: This analysis is exploratory
                Duration: Statement will interfere with benefit comprehension most when presented in the whole ad than when presented for briefer periods after the major statement. No prediction of differences between short and long duration of statement on benefit comprehension. (Benefit comprehension highest in control condition, followed short and long duration conditions together, followed by condition where statement is present in whole ad) Prominence: Prominence of statement will not affect benefit comprehension. 3.Toll-Free Statement Recall This section explains the following: Toll-free statement recall will be higher in any condition where it is included in the ad.
                Placement: Recall of statement will be highest in conditions where it is on screen for the whole ad and where it is placed after the major statement. Wording: This analysis is exploratory.
                Placement x Wording: This analysis is exploratory
                Duration: Recall of the statement will be greatest in the condition where it is present for the whole ad, followed by the condition in which it is located after the major statement. Prominence: Recall of the statement will be higher in the Extra Prominent condition than in the condition in which it is only in super form after the major statement. 4. Behavioral Intention This section explains the following: This analysis is exploratory and for completeness. Analysis Plan We will conduct the following analyses separately for the general population sample and the high blood pressure sufferers sample. Once these separate analyses are completed, we will conduct the analyses with the samples combined, using the type of sample as a moderator variable to determine whether any effects differed significantly between the groups. Part 1: We will test whether there is a main effect of placement on our main dependent variables (i.e., risk comprehension, benefit comprehension, and behavioral intention) using one-way Analysis of Variants (ANOVAs) (four placement conditions, plus control condition). We will conduct ANOVAs that assess the main effect of placement (four placement conditions), the main effect of statement type, and the interaction between placement and statement type on our main dependent variables. We will examine logistic regression models predicting toll-free statement recall from placement (four placement conditions, plus control condition), and from placement, statement type, and the interaction between placement and statement type. We will conduct these analyses both with and without covariates (e.g., demographic and health characteristics) included in the model. In addition, we will test whether any main effects are moderated by other measured variables (e.g., time spent viewing the ad, demographic and health characteristics). If any main effects are significant, we will conduct pairwise-comparisons to determine which conditions are significantly different from one another. We will also conduct planned comparisons in line with our hypotheses (see 
                    *Hypotheses*
                     in this document). Part 2: We will test whether there is a main effect of duration on our main dependent variables using one-way ANOVAs and logistic regression models. We will examine these analyses both with and without covariates (e.g., demographic and health characteristics) included in the model. In addition, we will test whether the main effect is moderated by other measured variables (e.g., time spent viewing the ad, demographic and health characteristics). If the main effect is significant, we will conduct pairwise-comparisons to determine which conditions are significantly different from one another. We will also conduct planned comparisons in line with our hypotheses (see 
                    *Hypotheses*
                     in this document). Part 3: We will test whether there is a main effect of prominence on our main dependent variables using one-way ANOVAs and logistic regression models. We will examine these analyses both with and without covariates (e.g., demographic and health characteristics) included in the model. In addition, we will test whether the main effect is moderated by other measured variables (e.g., time spent viewing the ad, demographic and health characteristics). 5. Pretesting of Stimuli The key to our study is the reasonableness and appropriateness of the stimuli we use to approximate television DTC prescription drug ads. Because the particular images are subjective, we will conduct extensive pretesting with consumers similar to our main target audience. This pretesting will involve 700 individuals in 2 waves. The purpose of the pretesting is to ensure that the stimuli are perceived as realistic. During the pretesting stage, the primary dependent variable will be the success of the particular manipulation. The pretesting will allow us to make changes in the ad stimuli before the actual study commences, thus making participants' time more valuable.
                    ( print page 41710) **Table 1.—Estimated Annual Reporting Burden**1
21 CFR Section
No. of Respondents
Annual Frequency 
                             per Response
Total Annual 
                             Responses
Hours per Response
Total HoursScreener, pretesting
2,800
1
2,800
.03
84Questionnaire, pretesting
1,400
1
1,400
.25
350Screener, study
12,000
1
12,000
.03
360Questionnaire, study
6,000
1
6,000
.33
1,980Total




2,7741
                         There are no capital costs or operating and maintenance costs associated with this collection of information.
 IV. References 1. Chandler, P. and J. Sweller, “Cognitive Load Theory and the Format of Instruction,” 
                        *Cognition and Instruction*, 8(4), 293-332, 1991. Dated: August 11, 2009. Jeffrey Shuren, Associate Commissioner for Policy and Planning.


[FR Doc. E9-19782 Filed 8-17-09; 8:45 am] BILLING CODE 4160-01-S