# Presentation: 824706

## Orlistat 60 mg NDA 21-887Label Comprehension Study

- Joint Nonprescription Drugs Advisory Committee and Endocrine and Metabolic Drugs Advisory Committee Meeting
- Bethesda, Maryland / January 23, 2006
- Susanna Weiss, Ph.D., J.D.
- Division of Nonprescription Clinical Evaluation
- Office of Nonprescription Products

**Center for Drug Evaluation and Research**** **

## Overview of the Presentation

- Regulation concerning label comprehension
- The purpose of label comprehension studies
- The Orlistat label comprehension study:
- Design, population, questions and procedures
- Results concerning the Drug Facts label
- Results regarding materials included inside the package

## Regulation

**21 CFR 330.10(a)(4)(v) . . . **
- [Over-the-counter drug labels shall be written] in
- such terms as to render them likely to be read and
- understood by the ordinary individual, including
- individuals of low comprehension, under
- customary conditions of purchase and use.
- (Low comprehension  =  _<_ 8th grade reading level)

## The Purpose of 

**Label Comprehension Studies**

## Primary Objectives

_**Primary Objectives**_
- To measure consumers’ understanding of key label information:
** ****USE**
** ****WARNINGS**
** ****WHEN USING **
**  ****THIS PRODUCT**
** ****DIRECTIONS**
** ****OTHER **
**   ****INFORMATION**

## Primary Objectives

_**Primary Objectives**_
- To measure consumers’ understanding of where to locate additional information included in the package.

## The Orlistat 

**Label Comprehension Study**

## Study Design and Population

_**Inclusion/Exclusion Criteria**_
- Male/Female of any race/ethnicity.
- At least 18 years of age.
- Expressed an interest (“somewhat” or “very interested”) in weight loss.
_**Gender Breakdown**_
- General Population (GP) – 36% male and 64% female.
- Low Literacy (LL) – 39% male and 61% female.
_**Two cohorts of individuals**_
- General Population of 304 subjects, 18% of which qualified as Low Literate and were also counted in Cohort #2 (the low literacy group).
- Low Literacy group of 160 subjects, 54 of which were from the General Population group and 106 of which were specifically recruited as low literate subjects.

## Scenarios and Questions

**Diane and her friend Bev are both overweight**
**and started taking Orlistat at the same time.**
**After taking Orlistat for 4 weeks, Diane is**
**frustrated since she has not lost the same**
**amount of weight as Bev.**
- _Q42_:  Based on the package labeling, what, if
- anything, is the reason why Diane is not losing
- the same amount of weight as Bev?

## “When using this product” where it says: 

- The correct answer is contained in the section of the label sub-headed:
*“*_***When using this product***_*”* where it says:
- “How much weight you lose will depend on how closely you follow the recommended diet and the Orlistat program.”

## The Interviewing Script

**All of the study participants were told that . . . **
- This was a test of the package labeling.
- They would not be questioned about previous knowledge or commonsense but about what has been learned from reading the information in the package labeling.
- They should respond according to the information
-     in the label.
- They would be able to view and read all the package labeling throughout the test.

## The study participants’ responses were coded as:

**CORRECT **
- or
**ACCEPTABLE **
- or
**INCORRECT**

**Coding of Responses**

## Results 

## Breakdown of the Results

**27 scenarios and questions were used to test consumer**
**comprehension of information in the Drug Facts Label.  **
**The **_**General Population**_** group achieved the following**
**scores by answering questions correctly or acceptably:**
**95% to 100%  on 11 scenarios **
**90% to   94%  on   4 scenarios**
**82% to   89%  on   7 scenarios **
**72% to   79%  on   3 scenarios **
**69% on one scenario and question****	**
**48% on one scenario and question****	**

## Product Use and Target Population

|   Drug Facts Label Communication Objective – Results 
  Reported by % of Total Correct + Acceptable Responses  |  
 GP%     LL%  |  |
| --- | --- | --- |
|   Product Use   (“To promote weight loss in overweight adults
  when used along with a reduced calorie and low fat diet”) |  100 |  100 |
|   
  Not okay to take Orlistat if not overweight |   
   79 |   
  78 |

**Product Use and Target Population**

**GP = General Population group**
**LL =  Low Literacy group**

## Warnings

| Drug Facts Label Communication Objective – Results Reported by 
% of Total Correct + Acceptable Responses  |       
 GP%   LL%    |  |
| --- | --- | --- |
| Not okay to use Orlistat if having gallbladder problem |   99 |  97 |
| Not okay to use Orlistat if had kidney stones in the past |   97 |  97 |
| Not okay to use Orlistat if currently taking medicine for diabetes |   97 |  97 |
| Okay to use Orlistat if experiencing problems sleeping |   97 |  94 |
| Not okay to use Orlistat if allergic |   97 |  94 |
| Not okay to use Orlistat if under 18 years old. |   96 |  95 |
| Okay to take Orlistat if not currently taking any other medication for weight loss |   96 |  94 |
| Not okay to use Orlistat while taking cyclosporine |   96 |  90 |
| Not okay to use while breastfeeding |   95 |  92 |
| Not okay to use Orlistat while taking Warfarin |   94 |  93 |
| Okay to use Orlistat if experiencing a headache |   92 |  80 |
| Not okay to use Orlistat if diagnosed with problems absorbing food |   90 |  86 |
| Okay to continue using Orlistat if experiencing loose stool and bowel changes |   86 |  74 |

**Warnings**

## Warnings

| Warnings  | Cyclosporine |  |    Warfarin |  | Kidney Stones |  |  Gallbladder |  |   Diabetes |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Responses | GP
% | LL
% | GP
% | LL
% | GP
% | LL
% | GP
% | LL
% | GP
% | LL
% |
| Correct Exactly Per
Label Instruction | 91 | 89 | 29 | 22 | 59 | 50 | 61 | 47 | 45 | 39 |
| Acceptable Alternative:
“Not okay to use” or
“Ask Dr /HC Professional” |   5 |   1 | 65 | 71 | 38 | 47 | 38 | 50 | 52 | 58 |
| Total correct and acceptable responses | 96 | 90 | 94 | 93 | 97 | 97 | 99 | 97 | 97 | 97 |

**Warnings**

**  ****The GP group achieved excellent scores on almost all label warnings.**
**  ****The LL  group achieved excellent scores on almost all label warnings.**
**  ****For example, comprehension of warnings for cyclosporine, warfarin, **
**    ****kidney stones, gallbladder problems, and diabetes were as follows:**

## When Using This Product

| Drug Facts Label Communication Objective – Results Reported by % of Total Correct + Acceptable Responses |          
 GP%    LL% |  |
| --- | --- | --- |
| Change your eating patterns before starting Orlistat |    95 |   86 |
| How Orlistat works to promote weight loss |    85 |   64 |
| Timeframe of when to expect results when taking Orlistat |    82 |   69 |
| Why weight loss may vary between people taking Orlistat |    82 |   62 |
| How to decrease the likelihood of loose stool and bowel changes |    72 |   48 |

**When Using This Product**

## Directions

| 
  Drug Facts Label Communication Objective – Results
  Reported by % of Total Correct + Acceptable Responses |          
 GP%   LL%
     |  |
| --- | --- | --- |
|   Recommended dosage to start taking Orlistat
 |   93 |   90 |
|   When to increase dose from 1 capsule to 2 capsules with each meal |   89 |   81 |
|   Where to find information on using Orlistat |   88 |  85 |
|   Maximum capsules of Orlistat in one day |   86 |   67 |
|   Weight loss goal not met after 6 months |   78 |   74 |

**Directions**

## Directions

| Drug Facts Label Communication Objective
Results Reflect Total of Correct + Acceptable Responses |   Sponsor
GP%   LL%     |  |  Reviewer
GP%  LL% |  |
| --- | --- | --- | --- | --- |
| Q27 – Concern about vitamin absorption |   93 |  88 |  69 |  50 |
| Q28 – Recommended timing for taking a multivitamin |   79 |  66 |  48 |  34 |

**Directions**

**The need to take a daily multivitamin and the timing for taking the multivitamin**

## Concern About Vitamin Absorption

## Directions

***Directions***
-  to ensure adequate
- vitamin absorption,
- you should take a
- multivitamin once a
- day, 2 hours before or after taking orlistat
- capsules

## Concern About Vitamin Absorption

_**Q 27  Scenario **_
**Terry is overweight and would like to use Orlistat**
**for weight loss.  She is concerned that she will not**
**be able to absorb the vitamins in the food if she**
**starts taking Orlistat.**
- _Q 27_: Based on the package labeling, what, if
- anything, should Terry do about this concern?

##    Q27 Concern About Vitamin Absorption

|    Responses Coded by Sponsor as Correct / Acceptable  | GP
%  (N=304) | LL
%  (N=160) |
| --- | --- | --- |
|    GSK’s Total of Correct + Acceptable Responses | 93% | 88% |
|    Correct | 69% | 50% |
|    Take a multivitamin once a day, 2 hours before or after taking 
   Orlistat     | 47%  | 36% |
|    Take a multivitamin | 21% | 14% |
|    Take a multivitamin once daily/ Take a multivitamin |   1% |   0 |
|    Acceptable  | 24% | 38% |
|     Ask a doctor |  |  |
|     Ask a doctor / pharmacist |  |  |
|     Eat better foods / More balanced diet / Watch diet |  |  |
|     Call 1-800# |  |  |
|     Look in User’s Guide / Manual / Directions on label / Reference card  |  |  |

-    **Q27 Concern About Vitamin Absorption**

**Partially**
**correct**

**COMPLETELY CORRECT RESPONSE**

## Recommended Timing for Taking a Multivitamin

_**Q 28  Scenario**__** **_
**Terry is overweight and would like to use Orlistat**
**for weight loss.  She is concerned that she will**
**not be able to absorb the vitamins in the food if**
**she starts taking Orlistat.**
- _Q28_:  Based on the package labeling, what is the
- recommended timing for taking a multivitamin to
- ensure adequate vitamin absorption?

## Due to rounding, percentages may not sum. 

|     Q28 . . . What is the recommended timing for taking a
    multivitamin to ensure adequate vitamin absorption? | General Population
%   N= 160 | Low 
Literacy
%   N=102 |
| --- | --- | --- |
|      GSK’s Total of Correct + Acceptable Responses | 79% | 66% |
|      Correct | 48% | 34% |
|      2 hours before or 2 hours after taking capsule  Correct | 48% | 34% |
|      One to two hours before meals |   1%  |   0% |
|      Acceptable | 31% | 31% |
|      2 hours before [incomplete answer]  |  |  |
|      2 hours after [incomplete answer] |  |  |
|      Six months; Once a day; Once a day for six months  |  |  |
|      Before a meal; After you eat |  |  |
|      Ask a doctor or pharmacist; Call 1-800#  |  |  |
|      Once a day 2 hours before [incomplete answer] |  |  |

**Due to rounding, percentages may not sum.**

**Q28  Recommended Timing for Taking a Multivitamin**

## Timing for Taking a Multivitamin

| 
Question 27 | GP
n=304 | LL
n=160  |
| --- | --- | --- |
| “Take a multivitamin once a day, 2 hours before or after taking Orlistat capsules” | (144)
  47% | (58)
36%
 |

| 
Question 28 | GP
n=160 | LL
n=102 |
| --- | --- | --- |
| "2 hours before or 2 hours after taking capsule” |  (76)
 48%
 | (35)
34% |

**(220)**

**(93)**

**Total number of subjects who responded correctly on Q27 and Q28**

**73% **

**58%**

**Timing for Taking a Multivitamin**

## Target Population:

**Orlistat is for Overweight Adults**

## Jane is 25 years old and not overweight. Jane is considering using Orlistat.

- _Q15/Q16_: Based on the package labeling, is it okay or not okay for Jane to use Orlistat?

## Orlistat is for Overweight Adults

**Jane is 25 years old and not overweight. Jane is considering using Orlistat**

_**Q15/Q16**_**: Based on the package labeling, is it okay or not okay for Jane to use Orlistat?**

-   78% of the GP group responded _correctly_ according to the label that
-     it is “Not okay.”
-   74% of the LL  group responded _correctly_ according to the label that
-     it is “Not okay.”
-   21% of the GP group responded _incorrectly_ that it would be okay.
-   23% of the LL  group responded _incorrectl_y that it would be okay.
-   The remaining small percentage in each group said “Jane” should
-     ask her doctor or healthcare professional.

## Possible Use by Non-Overweight Adults

_**Verbatim Responses**_
- Over 20% of the respondents from each cohort (GP & LL) rationalized
- that, since “Jane” in the scenario was over 18 and healthy, and since
- there was no specific warning on the box stating that non-overweight
- people should _not_ take Orlistat, it would be okay for “Jane” to take Orlistat.** **
*Is not contraindicated*
*Package / label does not mention *
*Don’t have to be overweight to use *
*Over 18 years old / old enough *
*Healthy / isn’t sick*
*Safe to use*

## Possible Use by Non-Overweight Adults

- Another set of responses reflected the idea that Orlistat
- would be good for _*maintaining*_ desired weight.  Here are
- some examples:
**“****It could help her not to be overweight.”**
**“****If she wants to maintain her weight. It’s fine to use.”**
**“****If she uses it moderately, it will help her maintain her weight.”**
**“****It could help her stay thin.”**
**“****She just might want to keep her weight the way it is.”**
**“****It’s only a fat reducer and it would keep her thin.”**
**“****Helps block fat so you don’t gain weight.” **

## Possible Use by Non-Overweight Adults

**A variety of other interesting verbatim responses referred to whether or not**
**25-year-old, non-overweight “Jane” in the scenario could take Orlistat:**
**“****If she really wants to go for that ***[famous actress]*** look, she can.  It doesn’t say specifically not to, and it probably won’t be any worse for her than if she just goes bulimic.”**
**“****If she wants to, it could help to lose cellulite but she really doesn’t need it but she has no health problems to keep her from using the product.”**
**“****Some people may want to lose weight no matter what they weigh.  Nowhere on this box does it say for those that are overweight only.”**
**“****She can see if it will cut down her appetite.”**
**“****It just says a well-balanced diet and I don’t think it says you can’t use it unless you are overweight.”**
**“****She doesn’t need to take it, but it doesn’t say not to take it if not overweight.”**

## Additional Information 

**Included in the Package**

## Slide 35

## Slide 36

## Slide 37

##                                                           Q19 Based on the package labeling, 

**                                                          ****Q19 Based on the package labeling,**
-                                                                    **where could Steve find information?**

_**Information on what to order when dining out**_**.**
**Steve is overweight.  He has been using Orlistat.  Steve is going out **
**to dinner tonight but is not sure what would be best for him to order.**

_**The accurate response is**_**: **
**“****Away from Home Guide” which clearly states that it covers “Dining Out” issues.  **
_**Some variations are acceptable**_**:**
** ****Dining Out Guide.**
** ****In the little restaurant guide.**
** ****Calorie/fat counter/diet cards.**

## Additional Information Included in the Package

| Where to Find Information in the Educational Materials | GP %   LL % |  |
| --- | --- | --- |
| Q48  Information on fast food restaurants | 90 | 90 |
| Q49  Information on setting realistic goals | 90 | 86 |
| Q51  Information on understanding personal eating habits | 82 | 76 |
| Q47  Information on snacking tips | 77 | 69 |
| Q50  Information on learning to navigate the grocery store | 66 | 65 |
| Q52  Information on the food and activity tracker | 43 | 41 |
| Q35  Information on fat and calories | 42 | 26 |
| Q26  Information on preparing meals | 42 | 24 |
| Q19  Information on what to order when dining out | 37 | 23 |

**Additional Information Included in the Package**

## Where to Find Information on What to Order When Dining Out

** “****Ask a doctor/pharmacist” is not an acceptable answer, nor are a number of**
**    ****other responses that were coded as “acceptable.” The following are so**
**    ****general as to be no better than default answers:**
**	****In the booklet**
**	****In the packet**
**	****Inside the box**
** **_**As many as 42 respondents gave completely inaccurate answers such as**_**: **
**    “****Back of package / on back in drug facts; Directions on box / label; **
**     ****Directions; On the label / box”**
** **_**4 respondents said**_**:**
**    “****From restaurant / ask the waiter / restaurant / consult the restaurant”**
** ****Other respondents said look in the “When using this product” section of **
**    ****the Drug Facts label; or “In the inactive ingredients” section of the**
**    ****label; or in the “Activity Tracker;” or simply at “The bottom of the label.” **

**Where to Find Information on What to Order When Dining Out**

## Summary and Observations

- There was very high comprehension of the label Warnings.
- Correct response rates concerning cyclosporine were in the 90th percentile for both the General Population and   Low Literacy cohorts.
- Almost all the label Directions were well understood by the General Population group and the Low Literacy group.
- Only the directions concerning multivitamin use were not particularly well understood by either group.
- This indicates that some modification of the Drug Facts label is needed to clarify and emphasize the instructions concerning taking multivitamins.

## The lack of a warning on the Drug Facts label specifically  telling consumers “Do not use if you are not overweight,” confused some participants and led them to think that use by non-overweight individuals would be acceptable. 

After the completion of the label comprehension study, the Sponsor amended the Drug Facts label to include a specific Warning that states: “Do not use if you are not overweight.”  This may help to alleviate the misunderstanding. 

It may help consumers to make a more informed self-selection and purchase decision if there were some indication on the external packaging as to what constitutes being overweight.  From the label comprehension study it seems that many people have a variety of subjective opinions about this. 

- After the completion of the label comprehension study, the Sponsor amended the Drug Facts label to include a specific Warning that states: “Do not use if you are not overweight.”  This may help to alleviate the misunderstanding.
- It may help consumers to make a more informed self-selection and purchase decision if there were some indication on the external packaging as to what constitutes being overweight.  From the label comprehension study it seems that many people have a variety of subjective opinions about this.

**Summary and Observations**