# Presentation: 677763

## MevacorTM Daily 20 mg TabletsRx-to-OTC Switch 

- Daiva Shetty, M.D.
- Division of Over-the-Counter Drug Products

## Overview

- Important aspects of an actual use study
- Actual use issues to address for Mevacor OTC
- Actual Use Study # 084 (CUSTOM)
- Results of consumer behavior
- Differences in data analysis

## Important Aspects of an Actual Use Study

- Simulate OTC use
- Recruitment through mass media
- Site locations in pharmacies or grocery stores
- Have few exclusion criteria

## Important Aspects of an Actual Use Study

- Objectives depend on the specific product and concerns related to that product:
- Self-diagnosis
- Self-selection
- De-selection
- Compliance, dosing, duration of use
- Off-label use
- Safety and efficacy in OTC population

## Actual Use Issues to Address for Mevacor OTC

- Are consumers able to:
- Self-diagnose hypercholesterolemia
- Know their cholesterol values
- Understand serum cholesterol values
- Identify risk factors for CHD
- Self-select based on the label eligibility criteria and the contraindications for use

## Actual Use Issues to Address for Mevacor OTC

- Are consumers able to self-treat:
- Follow label directions
- for dosing and duration of use
- for follow-up cholesterol test
- when to see a physician
- Understand the treatment goal
- De-selection
- Identify risks during therapy with Mevacor

## Study #084 

Consumer Use Study of OTC MEVACORTM (CUSTOM)

- Consumer Use Study of OTC MEVACORTM (CUSTOM)

## Label Criteria

## CUSTOM: Decision to Purchase 

- Participated in purchase decision 		 	3316
- 							   No		Yes
- Purchased Mevacor OTC			2111		1205
- Needed more information			2101		 826
- To obtain cholesterol
- To talk to a doctor
- Personal health information
- Study related information

## Self-Selection of Users Based on the Label Criteria

- _Total Users_
- N=**1061**

- N=**206**

**(26%)**

## Self-Selection of UsersBased on the Label Criteria

- N=**206**

**(19%)**

## Self-Selection of UsersBased on the Label Criteria

**10% of all Users fit the label criteria**

- N=**185**

## Self-Selection Demographics

- 1061 Users

- 430 (40.5%) females

- 631 (59.5%) males

## Use of Mevacor in Women under 50  

- 21.5% of all women Users were < 50 years
- Many of these women are likely of child bearing potential
- Because during the first trimester of pregnancy women may not realize that they are pregnant, it is important to understand the risk to the fetus if women of child bearing potential are going to use the product in the OTC setting

## Did Users Know Their Cholesterol Values? 

| What did Consumers Think Their LDL-C Level Was | LDL-C (mg/dL) Measured at Purchase Visit |  |  |  | 

Total |
| --- | --- | --- | --- | --- | --- |
|  | Missing | <130 | 130 to 170 | >170 |  |
| Missing | 15 | 0 | 10 | 2 | 27 |
| Unknown | 66 | 55 | 103 | 94 | 318 |
| < 130 mg/dL | 10 | 87 | 16 | 9 | 122 |
| 130 -170 mg/dL | 19 | 54 | 250 | 44 | 367 |
| > 170 mg/dL | 18 | 13 | 26 | 168 | 225 |
| Total | 128 | 209 | 405 | 317 | 1059 |

## Did Users Know Their Cholesterol Values? 

| What did Consumers Think Their LDL-C Level Was | LDL-C (mg/dL) Measured at Purchase Visit |  |  |  | 

Total |
| --- | --- | --- | --- | --- | --- |
|  | Missing | <130 | 130 to 170 | >170 |  |
| Missing | 15 | 0 | 10 | 2 | 27 |
| Unknown | 66 | 55 | 103 | 94 | 318 |
| < 130 mg/dL | 10 | 87 | 16 | 9 | 122 |
| 130 -170 mg/dL | 19 | 54 | 250 | 44 | 367 |
| > 170 mg/dL | 18 | 13 | 26 | 168 | 225 |
| Total | 128 | 209 | 405 | 317 | 1059 |

**87**

**250**

**168**

**130 -170 mg/dL**

**27**

**318**

**122**

**Missing**

**Unknown**

**130 to 170**

**< 130 mg/dL**

**130 -170 mg/dL**

**265**

## Summary of the Users’ Knowledge of Their LDL-C Values at the Initial Visit

- 30% (318/1059) did not know their LDL-C
- 47.7% (505/1059) correctly identified their LDL-C value
- 71% of Users who correctly identified their LDL-C <130 mg/dL chose to use Mevacor OTC
- 75% of Users who correctly identified their LDL-C >170 mg/dL chose to use Mevacor OTC

## Did Users Meet the Label CHD Risk Factor Criteria?

- Risk Factors for CHD:
- Smoking
- Age
- _>_ 45 years men
- _>_ 55 years women
- Family history of CHD
- Hypertension
- Low HDL-C

- Users with _>_ 2 risk factors
- (Age + _>_ 1 risk factor)
- 		57.3%
- Users with < 2 risk factors
- 		42.7%

## Sponsor’s Definitions of Correct Self-Selection

- _Original Definitions_
**AL**: According to Label
- entirely consistent with label
**NAL-MASM**: Not According to Label, Medically Acceptable for Self-Management; i.e., a favorable benefit to risk ratio (achieve LDL-C goal at 6 weeks)
- _Modified Definition_ (a physician override)
**AL-MASM**: According to Label, Medically Acceptable for Self-Management
- AL and
- not AL but consulted with a doctor

## Sponsor’s Additional Analyses of Correct Self-Selection 

- _Closely adhered to the label (post-hoc definition)_
- Outside age criteria
- Absence of label risk factors
- LDL-C < 130 mg/dL
- LDL-C > 170 mg/dL
- HDL-C _>_ 60 mg/dL
- But:
- Knew their lipid profile
- Did not have elevated triglycerides
- Did not substitute Mevacor OTC for a prescription lipid lowering medication, and
- Did not have diabetes, heart disease or stroke

## Sponsor’s Additional Analyses of Correct Self-Selection (cont.)

- _Failed to Closely Adhere to Label Benefit Criteria But Eligible for Statin Therapy_ _(post-hoc definition)_
- Did not know their lipid profile
- Had elevated triglycerides > 200 mg/dL
- Substituted Mevacor OTC for their Rx medication
- Had diabetes, heart disease, or stroke
- _But_:
- were eligible for statin therapy by ATP III based on calculated > 10% 10-year risk for myocardial infarction or coronary death

## Sponsor’s Results: Correct Self-Selection 

- Self-selected AL-MASM					484
- Without physician override (AL)  	  	 68
- With physician override (MASM)		 416
- Closely adhered to label					202
- Did not adhere to label benefit criteria	  357
- Eligible for statin therapy					258
- 							Total		944

## Users with Relative Contraindications for Using Mevacor OTC According to Label

**No risk conditions**
**(42.3%)**

_**>**_** 1 risk condition**
**(55.5%)**

** ****Not known**
**(2.2%)**

## Users with Relative Contraindications Who Did Not Consult a Physician

_**Condition**_

_**Total Users**_

_**Did Not**_
_**Consult Doctor**_

## Decisions Regarding Continuation of Therapy

- _Total Users_
- N=**1059**

- No

- Follow-up LDL-C test?

- N=**393**

- N=**666**

- Continued treatment?

- Yes

- No

- Yes

- N=**277**

- N=**116**

## Decisions Regarding Continuation of Therapy

- _Total Users_
- N=**1059**

- N=**666**

- Yes

- Discontinued

- Continued

- N**=7**

- N**=659**

- Follow-up LDL-C test?

**375** LDL-C <130 mg/dL

**60** LDL-C unknown;
-      continued w/physician advice

**30** LDL-C _>_130 mg/dL;
-      continued w/physician advice

**34** LDL-C _>_130 mg/dL; discontinued

**160** LDL-C unknown or
-        _>_130 mg/dL; continued

**160 LDL-C unknown or**
**        **_**>**_**130 mg/dL; continued**

## Achievement of the LDL-C Goal at the End of the Study

- 548 of 878 Users with known LDL-C value had LDL-C < 130 mg/dL at the end of the study
- 160 with LDL-C < 130 mg/dL at baseline
- 39 LDL-C level at baseline unknown
- 349 with LDL-C > 130 mg/dL at baseline

## Safety Data 

- 17% of Users had drug-related adverse events
- 1 serious allergic reaction to lovastatin
-  no other serious drug-related adverse events

## Summary (Cholesterol Knowledge)

- 69% of Purchasers needed more information to make a purchase or use decision
- 47.7% correctly identified their LDL-C
- 33% of Users did not know their LDL-C at the initial visit

## Summary (Self-Selection)

- 37% of women Users were < 55 years of age
- 26% of Users met the age and baseline LDL-C level 130-170 mg/dL
- 19% of Users met the age, LDL-C and risk factor for CHD criteria
- 10% of Users met all label eligibility criteria without a physician override

## Summary (CHD risks and contraindications)

- 42.7% of Users had <2 CHD risk factors
- 55.5% of Users had _>_1 relative contraindication according to the label for the use of Mevacor

## Summary (Follow-up LDL-C)

- 63% of Users had a follow-up cholesterol test
- 35.6% of Users achieved the LDL-C goal on their follow-up testing
- Median reduction in LDL-C in the User
- 	population was 21%
- 548 (62%) of Users with known LDL-C value at the end of 6 months had an LDL-C <130 mg/dL
- 199 Users started at an LDL-C <130 mg/dL or had missing baseline LDL-C

## Summary

- No new serious safety signals during the study
- Based on the CUSTOM results, it is likely to be used by:
- Women of childbearing age
- Consumers with contraindicated conditions
- Consumers with no risk or low risk for CHD
- Consumers at high risk for CHD