Guidance for Industry 

Self-Selection Studies for 

Nonprescription Drug 

Products 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
April 2013 

OTC 

 
   
Guidance for Industry 

Self-Selection Studies for 

Nonprescription Drug 

Products 
 
 
 
 
Additional copies are available from: 

 
Office of Communications, Division  of Drug Information 
 
Center for Drug Evaluation  and Research 
 
Food and  Drug Administration 

10903 New Hampshire Ave., Bldg. 51, rm. 2201 
 
Silver Spring, MD   20993-0002 
 
Tel:  301-796-3400; Fax: 301-847-8714; E-mail:  druginfo@fda.hhs.gov 

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
April 2013 

OTC 

 
   
TABLE OF CONTENTS 

 
I.   INTRODUCTION............................................................................................................. 1 
 
II.   BACKGROUND ............................................................................................................... 2 
 
III.   STUDY DESIGN AND CONDUCT................................................................................ 2 
 
A.   Study Objectives ............................................................................................................................3
  
1.  Primary Objective............................................................................................................................3
  
2.  Secondary Objectives.......................................................................................................................3
  
B.   Study Population............................................................................................................................3
  
C.   Statistical Considerations and Data Analysis..............................................................................4
  
1.  Primary Endpoints, Success Criteria, and Mitigating Factors........................................................4
  
2.  Sample Size Considerations.............................................................................................................6
  
3.  Data Analysis...................................................................................................................................7
  
D.   Questionnaire Design.....................................................................................................................7
  
1.  Questions That Address the Study Objectives..................................................................................7
  
2.  General Questionnaire Design Concepts ........................................................................................8
  
E.   Study Conduct................................................................................................................................9
  
F.   Validating the Self-Selection Decision..........................................................................................9
  
G.   Data Collection and Recording.....................................................................................................9
  
IV.   FINAL REPORT ............................................................................................................ 10 
 
  Contains Nonbinding Recommendations 
1
 
Guidance for Industry  
Self-Selection Studies for 

Nonprescription Drug Products 

 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on this topic.  It 
does not create or confer any rights for or on any  person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance. 
 
 
 
 
I.  INTRODUCTION 
 
This guidance is intended to provide recommendations to industry involved in developing and 
conducting self-selection studies to support an application for nonprescription drug products.  A 
self-selection study assesses the ability of consumers to apply drug labeling information to their 
personal health situation to make correct decisions about whether or not it is appropriate for them  
to use a drug product. 
 
This guidance covers general principles related to the conduct of self-selection studies, including 
study design, methodology, and analyses, and should not be considered a substitute for an FDA 
review of specific protocols. We recognize that self-selection data can be obtained in a variety 
of different ways and that each development program raises distinct issues for which flexibility 
and creativity is important.  This guidance also incorporates advice obtained from the 
Nonprescription Drugs Advisory Committee at a meeting on September 25, 2006, at which the 
committee considered issues related to analysis and interpretation of consumer studies conducted 
to support marketing of nonprescription drug products.2  
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agencys current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited. The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required. 
 
                                                 
1  This guidance has been prepared  by  the Division  of Nonprescription Clinical  Evaluation and  the Office of  
Biostatistics in the Center for Drug Evaluation and Research (CDER) at the Food and Drug  Administration. 
 
2 The transcript  from the September 25, 2006, Nonprescription Drugs Advisory Committee meeting is available at 
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4230t.pdf. 
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  Contains Nonbinding Recommendations 
 
II.  BACKGROUND   

 
The development program for certain nonprescription drug products may include conducting 
consumer studies, in addition to the required safety and efficacy studies.  The consumer study 
process may include label comprehension studies, which assess consumer understanding of 
major communication elements,3 and self-selection studies, which test whether consumers can 
apply the label information to their personal medical situations and make correct decisions about 
whether it is appropriate for them to use or not use the drug product (self-selection decision).   
We recommend conducting a label comprehension study to optimize the label before conducting 
a self-selection study. 
 
A self-selection study may be needed to test whether consumers can make appropriate self-
selection decisions based on the information contained in the label.  Some of the circumstances 
under which we might recommend a self-selection study include:   
 
 	  The drug product is for a new nonprescription indication  
 
 	  The drug product is for a new nonprescription target population 
 
 	  There are specific populations who should not use the proposed nonprescription drug 
product (e.g., diabetics, transplant recipients)  
 
 	  A substantive labeling change has been proposed for an approved nonprescription drug 
product that may affect the appropriate nonprescription population (e.g., a change in the 
warnings, directions for use) 
 
We encourage sponsors to seek FDA consultation and advice on any protocol for a self-selection 
study. 
 
A self-selection decision is not necessarily predictive of whether a consumer will actually use the 
drug product or whether he or she will use it correctly.  If information on consumer use is 
needed, an actual use study should be considered.  Actual use studies are outside the scope of 
this guidance. 
 
 
III.  STUDY DESIGN AND CONDUCT 
 
In general, self-selection studies can be open-label, uncontrolled studies.  The following are 
general recommendations for the design and conduct of a self-selection study.  Subsequent 
sections provide a more detailed discussion of each recommendation. 
 
                                                 
3 See the guidance for industry Label Comprehension Studies for Nonprescription Drug Products.  We update 
guidances  periodically.  To make sure you  have the most recent version of a guidance, check the FDA Drugs 
guidance Web page  at  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.   
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  Contains Nonbinding Recommendations 
   State the purpose and objectives of the study  
 
   Specify a study design that meets the study objectives and calculate the appropriate 
sample size 
 
   Use labeling that is as similar as possible to the final drug product label 
 
   Construct a questionnaire that targets the study objectives 
 
   Minimize factors that may contribute to a biased study (e.g., sampling, recruitment 
strategies, leading questions, interviews that bias the responses in a particular direction) 
 
   Enroll a population appropriate for the study objectives 
 
   Enroll subjects with low and normal literacy skills  
 
   When necessary, enrich the study with subjects who have relative or absolute 
contraindications to use of the drug product 
 
   Consider pilot testing before conducting a large self-selection study 
 
Self-selection can be studied in a variety of ways.  Sometimes it can be evaluated as part of an 
actual use study or sometimes in conjunction with a label comprehension study.  A separate 
study does not always need to be conducted to address self-selection. 
 
A.  Study Objectives 
 
1.  Primary Objective 
 
In general, the primary objective(s) of a self-selection study should be to assess if subjects, after 
reading the drug product label, can make a correct self-selection decision(s) based on their 
medical condition(s).  
 
2.  Secondary Objectives  
 
Secondary objectives may be included to assess self-selection  accuracy in specific 
subpopulations of interest and/or the reasons why subjects make incorrect self-selection 
decisions.  Thus, some of the data may come from questions asked to elicit reasons for incorrect 
self-selection.  It is important to determine why subjects make incorrect decisions to better 
understand what label revisions may need to be made to improve correct self-selection.   
 
B.  Study Population 
 
The study population should be defined based on the study objectives.  Some studies may 
include any subject who may have an interest in using the drug product, regardless of age, sex, 
underlying medical conditions, and use of concomitant medications.  Other studies may target a 
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  Contains Nonbinding Recommendations 
particular population of interest (e.g., subjects with a specific disease for whom use of the drug 
product may be contraindicated).  Because nonprescription drug products are available for 
purchase without the input of a health care professional and no drug product is administered in 
the study, exclusion criteria should be minimal (e.g., inability to speak, read, and understand 
English). 
 
Self-selection studies also should enroll an adequate number of subjects who have low literacy 
skills to examine the ability of this subgroup to make a correct self-selection decision.  Education 
level is not a reliable substitute for literacy testing.  At screening, the sponsor should assess 
literacy levels of the study subjects by administering a validated instrument such as the Rapid 
Estimate of Adult Literacy in Medicine (REALM) test,4 REALM-Teen for testing adolescents,5  
or the Test of Functional Health Literacy in Adults (TOFHLA or S-TOFHLA).6,7,8  Investigators 
should receive training to properly administer literacy tests. 
 
C.  Statistical Considerations and Data Analysis 
 
1.  Primary Endpoints, Success Criteria, and Mitigating Factors 
 
The primary endpoint for a self-selection study should be the proportion of the study subjects 
who make a correct self-selection decision.  A correct self-selection decision is based on the 
label element(s) that are needed to make an appropriate decision whether or not to use a drug 
product (self-selection decision).  A correct self-selection decision can be based on a single label 
element or a composite of several label elements depending on the drug product.   
 
For example, the drug product may have only one contraindication:  diabetics should not use the 
drug product. In this case, a correct self-selection decision for a diabetic (regardless of whether 
he or she has the condition for which the drug product is indicated) would be that the drug 
product is not appropriate for his or her use. In contrast, an incorrect self-selection decision 
would be a diabetic who selects to use the drug product.  An example of a composite of several 
label elements would be a drug product that is only for women between 18 and 65 years of age 
who do not have heart disease or hypertension.  A correct self-selection decision would be a 
woman between 18 and 65 years of age who has the labeled indication and does not have heart 
                                                 
4 REALM:   Davis, TC et al., 1993, Rapid Estimate of Adult Literacy in Medicine:   A Shortened Screening 
Instrument, Family Medicine, 25:391-395.   
 
5 REALM-Teen:  Davis, TC et al., 2006, Development and Validation  of the Rapid Estimate of Adolescent Literacy 
in Medicine (REALM-Teen);  A Tool to  Screen Adolescents for Below-Grade Reading in Health Care Settings, 
Pediatrics, 118(6):e1707-1714. 
 
6 TOFHLA:  Parker, RM et al., 1995, The Test of Functional Health Literacy in Adults:  A New Instrument for 
Measuring Patients Literacy Skills, Journal  of General Internal Medicine, 10:537-541.   
 
7 Baker, DW et al., 1999, Development of a Brief Test to Measure Functional Health Literacy, Patient Education 
and Counseling, 38:33-42. 
 
8 The REALM  and TOFHLA  were designed as rapid screening tools that  were validated  against the Wide Range  
Achievement Test for literacy.  Therefore,  use of these instruments to screen literacy levels within the context of 
health is appropriate. 
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  Contains Nonbinding Recommendations 
disease or hypertension who selects to use the drug product.  An incorrect self-selection decision 
would be a 55-year-old woman with hypertension who selects to use the drug product (whether 
or not she has the indication). 
 
Several analyses to illustrate self-selection decision making may be of interest; usually one or 
two are chosen as primary endpoints, and the others may be used for exploratory analyses.  Table 
1 shows one way to consider choices for different endpoints, where A, B, C, and D represent the 
number of subjects in the cells. 
 
Table 1:   Two-by-Two Table Illustrating Possible Self-Selection Choices 
  Appropriate to  Not appropriate to   
select drug  select drug 
Self-selected to take  Correct  Incorrect   
drug  A  B  A+B 
Self-selected not to  Incorrect  Correct   
take drug  C  D  C+D 
A+C  B+D   
 
The analysis chosen for the primary endpoint depends on the study design and the issue(s) of 
greatest concern for nonprescription use.  For example, the primary endpoint might be correct 
self-selection for the entire population [(A+D)/(A+B+C+D)].  Alternatively, the primary 
endpoint might be the proportion who select correctly among those who select to take the drug 
([A/(A+B)]. As another example, the primary endpoint might be correct self-selection among 
those who cannot take the drug [D/(B+D)].  The primary endpoint and how it will be calculated 
should be defined in the protocol before the study starts, and discussed with the FDA.   
 
Success criteria should be related to the predefined target level for correct self-selection.  This 
target level should be justified based upon a clinical rationale.  Success criteria should be defined 
using the confidence interval approach:  the study can be claimed as a success only when the 
lower limit of a predefined two-sided 95 percent (or one-sided 97.5 percent) confidence interval 
for the correct self-selection rate is above the target level.  We recommend using a two-sided 95 
percent confidence interval to estimate the correct self-selection rate as well as to define the 
success criteria. This approach allows consideration of variability within the study data and sets 
the type I error rate for one-sided tests (2.5 percent) at half the conventional type I error rate (5 
percent) used in two-sided tests. 
 
Reasonable predefined mitigating factors may be acceptable in certain circumstances.  Mitigating  
factors are subject responses that would allow what appears to be an incorrect self-selection 
decision to be considered a correct self-selection decision.  Mitigations should be clinically 
reasonable.  The following is an example of a mitigating factor:  subjects who make an incorrect 
self-selection decision based on age, but who are within 1 year of the labeled age and verbalize 
an understanding of the correct age. For example, a subject who is 54 makes an incorrect self-
selection decision based on age for a drug product that is labeled for adults 55 and older.  After 
being asked a nonleading, open-ended question to elicit more information about his or her 
decision, the subject states that he or she knows the drug product is labeled for people aged 55 or 
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  Contains Nonbinding Recommendations 
older, but because he or she will be 55 within a month he or she feels it is okay to take the drug 
product. 
 
The definitions of a correct self-selection decision, mitigating factors, and the target success 
criteria for correct self-selection should be determined in advance of study enrollment and 
specified in the study protocol.  Mitigation decisions should be auditable, and subject level data 
should be presented so that the FDA can easily review and audit mitigating factors.  If a sponsor 
finds unexpected mitigating factors on post hoc analysis, the study report should explain why 
and how these other factors were used to mitigate the endpoint(s).   
 
With more complicated labels, such as those with multiple decision points, we recognize some  
label elements have greater clinical significance than others if not heeded.  Therefore, we 
recommend that sponsors discuss with the FDA the label elements to be used to define correct 
self-selection, the mitigating factors, and the predetermined success criteria before conducting 
the study. 
 
2.  Sample Size Considerations 
 
The number of subjects in a self-selection study should be large enough to provide a reliable 
answer to the primary objective.  Sizing of such a study should be based on the success criteria in 
a hypothesis testing framework. This generally involves several elements:  the predefined target 
level for correct self-selection, the assumed percent of correct self-selection for the study 
population, the type I error rate, and the desired study power for testing the predefined 
hypothesis or hypotheses. 
 
Each of the different elements in the sample size calculation should be determined as follows:  
 
	   The predefined target level for correct self-selection should be based on a clinical 
rationale based upon the medical significance of incorrect self-selection, as discussed in 
the previous section. 
 
	   The assumed percent of correct self-selection should be the best guess of what the true 
self-selection rate is in the population of interest.  Ideally, it should be based on results 
from pilot studies on the same drug product or on self-selection studies for similar drug 
products in a similar population.  
 
	   The type I error rate should be set at 2.5 percent for a one-sided test corresponding to a 
one-sided 97.5 percent confidence interval, or 5 percent for a two-sided test 
corresponding to a two-sided 95 percent confidence interval. 
 
	   The study power typically should be decided by sponsors based on their resources.  We 
recommend that the study power be 80 percent or above.  
 
The number of subjects in a self-selection study should be large enough to evaluate the primary 
endpoint for important subgroups of interest.  Alternatively, a targeted self-selection study can be 
conducted to assess a specific subgroup. 
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  Contains Nonbinding Recommendations 
 
3.  Data Analysis 
 
The principal features of the planned analysis should be defined in the protocol.  The statistical 
methods and the analysis of the primary and secondary endpoints also should be specified in the 
protocol.  Methods for constructing a two-sided 95 percent confidence interval to estimate and 
define the success criteria for the correct self-selection rate should be described, including a 
detailed description of the numerators and denominators.  Methods for handling missing data 
should be specified. 
 
Typically, a comprehensive statistical analysis plan should be included in the protocol and 
address all the details of the data analysis.  In cases where the comprehensive statistical analysis 
plan is prepared as a separate document, it should be prepared before the results of the study are 
known and it should be submitted for FDA review.    
 
D.  Questionnaire Design 
 
Typically, a questionnaire is used to collect data in a self-selection study.  The questionnaire 
design should: (1) reflect the study objectives; and (2) optimize the validity and interpretability 
of the information collected.  Wording, question structure, and question sequences can 
significantly affect the validity and interpretability of the data collected.  A detailed discussion of 
questionnaire development is beyond the scope of  this guidance.  However, the following points 
merit particular consideration. 
 
1.  Questions That Address the Study Objectives  
 
The following are general recommendations about the types of questions that address the study 
objectives. 
 
	   The self-selection question: The first question asked should be an open-ended, self-
selection question (e.g., Is it okay for you to use this medication?) followed by an 
open-ended, nonleading probing question.  It is important to determine why subjects 
make incorrect decisions to better understand what label revisions may be needed to 
improve correct self-selection.   
 
	   Open-ended probing questions:  Open-ended questions that follow the self-selection 
question should be asked because they may help provide additional data for the analysis.  
Additional questions used to elicit more information should be nonleading and be used 
sparingly so as not to prompt the subject to provide a desired response.  An example of a 
nonleading question for subjects who say that it is okay for them to use the medication, 
would be to then ask, Why do you say that?  This question enables multiple possible 
responses including after I talked to my doctor.  By contrast, an example of a leading 
question, where the correct response is that a subject should talk to his or her doctor 
before using the drug product, would be to ask, Is there anything you would do before 
you start using the medication?  This question may direct subjects toward a correct 
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  Contains Nonbinding Recommendations 
answer. Additionally, subjects who feel obligated to provide an answer may respond 
with talk to my doctor as a logical default answer, which may introduce bias.    
 
 	  Medical history questions:  Medical history questions should be asked after the self-
selection question to prevent bias that can occur from prompting the subject to focus on 
specific label elements.  The medical history questions should be asked in consumer-
friendly language and be based on obtaining health information related to the drug 
products indications, warnings, and contraindications.   
 
Sponsors sometimes choose to add a question asking subjects whether or not they would 
purchase the drug product. We do not consider purchase decision data to be a reliable surrogate 
for self-selection data because a purchase decision may be influenced by factors other than 
personal health history, such as cost or the needs of someone else in the consumers home.  If a 
sponsor wishes to collect data on purchase decisions, these questions should be asked only 
following the completion of the self-selection portion of the assessment.   
 
2.  General Questionnaire Design Concepts 
 
The following are general recommendations about the design of questionnaires. 
 
	   Simple vocabulary should be used, and questions should be pretested to ensure the 
questions elicit the intended information.  
 
	   Some questions should be direct, specific, and unambiguous, and should address a single 
item or issue.  
 
	   Some questions should involve a higher level of understanding where subjects may need 
to put together several pieces of label information to arrive at the correct response.  
 
	   Questions should be ordered so that information contained in a question does not bias a 
subjects ability to answer subsequent questions.  
 
	   Response choices in multiple-choice questions should be independent and contain only 
one correct answer. 
 
	   When listing response categories for multiple-choice questions (e.g., to assess the 
medical history), I dont know should be included as one of the response categories to 
give subjects permission to admit that they do not know so they avoid guessing.  The 
category other also should be included to allow subjects to add something that may not 
be listed as a choice. 
 
	   Questions intended to measure the behavioral intent of the subject should not be used.  
Testing behavior is outside the scope of a self-selection study.  If information about how 
subjects would behave under real-world conditions is needed, an actual use study should 
be conducted. 
 
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  Contains Nonbinding Recommendations 
The questionnaire can be pretested with a sample of respondents similar to the target population 
to ascertain that the questionnaire is eliciting the intended information. 
 
E.  Study Conduct 
 
Advertisements for the study should not contain any information about the proposed drug 
product. If there is initial telephone contact, subjects should receive only information on how 
and where to participate in the study.  Occasionally, it may be necessary to use a clinical setting 
for the study site so a specific population can be accessed.  The study setting should be 
comfortable and well lit for reading.  Subjects should have adequate time to read the label and be 
able to refer to it throughout the testing period.  However, subjects should not be prompted to 
refer to the label during testing. 
 
Subjects should receive sufficient instruction on the format and conduct of the study and the 
expected length of time it will take to participate.  Two general approaches to administering the 
questionnaire that can be considered include self-administration or asking the questions using a 
trained interviewer.  Using an interviewer may lessen the chance that low literate subjects will 
respond incorrectly because they cannot comprehend the written question when, in fact, they 
comprehend the label.  Using an interviewer, however, may lead to interviewer bias, particularly 
if the interviewer leads the subject to elicit a response.  Therefore, interviewers should be 
adequately trained and should adhere to established protocols and/or scripts.  Inherent bias can 
occur with any data collection method.  Therefore, sponsors should provide a rationale for why a 
particular method was chosen and should address any potential bias. 
 
F.  Validating the Self-Selection Decision 
 
Answers to the self-selection question can be validated in a variety of ways.  Sometimes this can 
be accomplished by asking medical history questions, but other times collecting laboratory data 
or conducting a physical examination also may be needed.  Not all of these methods of validation 
will be needed for every study. 
 
G.  Data Collection and Recording 
 
Verbatim responses to all open-ended questions should be recorded.  The procedure for coding, 
categorizing, and analyzing verbatim responses to open-ended questions should be specified in 
advance and described in the protocol. In addition, all correct and incorrect answers to closed-
ended questions should be prespecified. Any post-hoc coding for open-ended questions should 
be documented.   
 
Methods for verification of complete and accurate recording of study data should be described in 
the protocol or the statistical analysis plan (i.e., subjects responses, data entry, missing data, and 
data coding). 
 
 
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IV.  FINAL REPORT   

 
The final report should summarize the study design, study conduct, and interpretation of the 
study results. The report should assess whether the appropriate population has been enrolled to 
adequately assess self-selection decision making.  It also should describe the nature of the 
recruitment effort and the response rate (i.e., the proportion of screened subjects who were 
actually enrolled in the study). If possible, potential subjects who were excluded, or who chose 
not to enroll in the study, should be characterized by demographic factors and the reasons for 
nonparticipation. Enrolled subjects should be characterized as to relevant demographic factors 
(including literacy) and whether or not they completed the entire study.  Reasons why subjects 
failed to complete the study should be provided in the final report.  
 
The presentation of the study results should include both the overall correct self-selection rates 
and correct self-selection rates in appropriate subsets (e.g., literacy level, sex, age, race, and 
presence of high risk factors). 
 
The acceptable success criteria for correct self-selection should be based on meeting the success 
criteria that were established before the study began and were documented in the protocol and/or 
the statistical analysis plan.  The interpretation of the quantitative data should be augmented by 
the verbatim responses collected from open-ended, nonleading questions used to assess the self-
selection. Thus, an analysis of both quantitative and qualitative data types should be provided to 
support and interpret the study findings. 
 
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