mevacor daily ® merck nda 21-213 nonprescription drugs advisory committee and endocrinologic and...

Mevacor DailyMevacor Daily®®

MerckMerckNDA 21-213NDA 21-213

Mevacor DailyMevacor Daily®®

MerckMerckNDA 21-213NDA 21-213

Nonprescription Drugs Advisory Committee andNonprescription Drugs Advisory Committee and

Endocrinologic and Metabolic Advisory Committee MeetingEndocrinologic and Metabolic Advisory Committee Meeting

Silver Spring, MarylandSilver Spring, MarylandDecember 13, 2007December 13, 2007

Linda Hu, M.D. Linda Hu, M.D.

Division of Nonprescription Clinical EvaluationDivision of Nonprescription Clinical Evaluation

Nonprescription Drugs Advisory Committee andNonprescription Drugs Advisory Committee and

Endocrinologic and Metabolic Advisory Committee MeetingEndocrinologic and Metabolic Advisory Committee Meeting

Silver Spring, MarylandSilver Spring, MarylandDecember 13, 2007December 13, 2007

Linda Hu, M.D. Linda Hu, M.D.

Division of Nonprescription Clinical EvaluationDivision of Nonprescription Clinical Evaluation

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research

NDAC NDAC December 13, 2007December 13, 2007

Self Evaluation of Lovastatin to Self Evaluation of Lovastatin to Enhance Cholesterol TreatmentEnhance Cholesterol TreatmentSelf Evaluation of Lovastatin to Self Evaluation of Lovastatin to Enhance Cholesterol TreatmentEnhance Cholesterol Treatment

(SELECT)(SELECT)

3NDAC NDAC December 13, 2007December 13, 2007

Overview Overview Overview Overview • Regulatory Background

• SELECT Labeling Paradigms

• SELECT Study Design

• SELECT Results

– Analyses of Mitigations

– Analysis Of Eligibility Criteria Subsets (Hierarchies)

– Analysis Of User Population

• Summary

• Regulatory Background

• SELECT Labeling Paradigms

• SELECT Study Design

• SELECT Results

– Analyses of Mitigations

– Analysis Of Eligibility Criteria Subsets (Hierarchies)

– Analysis Of User Population

• Summary


Regulatory Background Regulatory Background Regulatory Background Regulatory Background

• Initial submission 1999

• Response to October 2000 non-approval letter, which

included

– CUSTOM actual use study, “A Consumer Use Study of

Over-The-Counter MEVACOR”

– Label comprehension study

– Other efficacy data and safety data

• Led to non-approval letter in February, 2005

• Initial submission 1999

• Response to October 2000 non-approval letter, which

included

– CUSTOM actual use study, “A Consumer Use Study of

Over-The-Counter MEVACOR”

– Label comprehension study

– Other efficacy data and safety data

• Led to non-approval letter in February, 2005


CUSTOM Actual-Use StudyCUSTOM Actual-Use StudyCUSTOM Actual-Use StudyCUSTOM Actual-Use Study

• 10% of CUSTOM users correctly self-selected– Required criteria age, LDL-C, CHD risk factors, absence of

certain conditions (conditions = liver disease, high

triglycerides, history of statin-induced muscle pain)

• 54% (571/1059) of CUSTOM users considered

appropriate by sponsor– 416 said they talked to their doctor

• 10% of CUSTOM users correctly self-selected– Required criteria age, LDL-C, CHD risk factors, absence of

certain conditions (conditions = liver disease, high

triglycerides, history of statin-induced muscle pain)

• 54% (571/1059) of CUSTOM users considered

appropriate by sponsor– 416 said they talked to their doctor


Deficiencies in Feb 2005Deficiencies in Feb 2005Non Approval LetterNon Approval Letter

Deficiencies in Feb 2005Deficiencies in Feb 2005Non Approval LetterNon Approval Letter

• Concern about inability of consumers, on their own,

to make decisions on the appropriateness of statin

therapy for their own personal use

• Remaining safety concerns

– Use by pregnant women and women of

childbearing potential

– Compliance with muscle pain warning

– Use by patients with asymptomatic liver disease

• Concern about inability of consumers, on their own,

to make decisions on the appropriateness of statin

therapy for their own personal use

• Remaining safety concerns

– Use by pregnant women and women of


– Compliance with muscle pain warning

– Use by patients with asymptomatic liver disease


Recommendations from Feb Recommendations from Feb 2005 Non Approval Letter2005 Non Approval Letter

Recommendations from Feb Recommendations from Feb 2005 Non Approval Letter2005 Non Approval Letter

• A self-selection/use study or studies

• Label comprehension studies

• Address the risk in subjects with asymptomatic

liver disease

• A self-selection/use study or studies

• Label comprehension studies

• Address the risk in subjects with asymptomatic

liver disease


SELECT Study Label SELECT Study Label ParadigmsParadigms

SELECT Study Label SELECT Study Label ParadigmsParadigms

LDL-C Label LDL-C Label

Total-C LabelTotal-C Label

LDL-C Label LDL-C Label

Total-C LabelTotal-C Label


LDL-C Label Target LDL-C Label Target PopulationPopulation

LDL-C Label Target LDL-C Label Target PopulationPopulation

• Males ≥ 45 years; females ≥ 55 years

• LDL in range 130 - 170 mg/dL

• One or more additional cardiac risk factors

• Males ≥ 45 years; females ≥ 55 years

• LDL in range 130 - 170 mg/dL

• One or more additional cardiac risk factors


Cardiac Risk FactorsCardiac Risk FactorsCardiac Risk FactorsCardiac Risk Factors

• Cigarette smoking

• Hypertension or on BP medication

• Family history of premature CHD (below age of 55

years in a male parent or sibling or below 65 in

female relative)

• HDL-C < 40 mg/dL

• Age (men > 45 years, women > 55 years).

• Cigarette smoking

• Hypertension or on BP medication

• Family history of premature CHD (below age of 55

years in a male parent or sibling or below 65 in

female relative)

• HDL-C < 40 mg/dL

• Age (men > 45 years, women > 55 years).


Total-C Label Target Total-C Label Target PopulationPopulation

Total-C Label Target Total-C Label Target PopulationPopulation

• Total-C in range 200-240 mg/dL

• Males– > 45 years

• Females– HDL < 60 mg/dL

– > 55 years

– One or more additional cardiac risk factors

• Total-C in range 200-240 mg/dL

• Males– > 45 years

• Females– HDL < 60 mg/dL

– > 55 years

– One or more additional cardiac risk factors


SELECT Label ParadigmsSELECT Label ParadigmsSELECT Label ParadigmsSELECT Label Paradigms

• Label should be consistent with NCEP ATP III

guidelines

• LDL-C label conforms better to ATP III than

Total-C label

• Focus on results from LDL-C label arm

• Label should be consistent with NCEP ATP III

guidelines

• LDL-C label conforms better to ATP III than

Total-C label

• Focus on results from LDL-C label arm


NCEP ATP III GuidelinesNCEP ATP III GuidelinesNCEP ATP III GuidelinesNCEP ATP III Guidelines

<


(SELECT)(SELECT)(SELECT)(SELECT)

Self Evaluation of Lovastatin to Self Evaluation of Lovastatin to Enhance Cholesterol TreatmentEnhance Cholesterol TreatmentSelf Evaluation of Lovastatin to Self Evaluation of Lovastatin to Enhance Cholesterol TreatmentEnhance Cholesterol Treatment

Study Design and Study PopulationStudy Design and Study Population


SELECT Self-Selection SELECT Self-Selection StudyStudy


• How many consumers will decide correctly

that Mevacor is OK for them to use (“self-

selection”)?

• Study should be naturalistic

• How many consumers will decide correctly

that Mevacor is OK for them to use (“self-

selection”)?

• Study should be naturalistic

Self-selection: A decision by a consumer whether or not to choose a product for use based on two things: (1) his or her unique medical history and (2) the product labeling.




• Consumers were asked

– Self-assessment (SA) question

– Purchase decision (PD) question

– Reasons why, if incorrect

• Subjects randomized to two labels

– LDL-C

– Total-C

• Consumers were asked

– Self-assessment (SA) question

– Purchase decision (PD) question

– Reasons why, if incorrect

• Subjects randomized to two labels

– LDL-C

– Total-CFocus on LDL-C


Focus on Self-AssessmentFocus on Self-AssessmentFocus on Self-AssessmentFocus on Self-Assessment

• Purchase Decision is influenced by potentially

confounding economic and marketing issues

– cost

– consumer appeal of product

• Our interest is in whether the consumer

understands

– who should use

– why should one use

– how to use

• Purchase Decision is influenced by potentially

confounding economic and marketing issues

– cost

– consumer appeal of product

• Our interest is in whether the consumer

understands

– who should use

– why should one use

– how to use


Directions Prior toDirections Prior toSelf-Assessment QuestionSelf-Assessment Question

Directions Prior toDirections Prior toSelf-Assessment QuestionSelf-Assessment Question

• Participants were told

– The product is not appropriate for everyone

– You will be asked whether the product was

appropriate for you

– You will be asked whether you wish to purchase

– Concentrate and to take as much time as needed

• Participants were told

– The product is not appropriate for everyone

– You will be asked whether the product was

appropriate for you

– You will be asked whether you wish to purchase

– Concentrate and to take as much time as needed


Self-Assessment (SA) Self-Assessment (SA) Self-Assessment (SA) Self-Assessment (SA)

• “Based on this label, is this product

appropriate for you to use right now or not?”

– Yes

– No

– Other (unsure or wanted to ask a doctor)

• “Based on this label, is this product

appropriate for you to use right now or not?”

– Yes

– No

– Other (unsure or wanted to ask a doctor)


Purchase Decision (PD)Purchase Decision (PD)Purchase Decision (PD)Purchase Decision (PD)

• “Would you like to pay for this right now for

your own use or put it back in the display?”

• If the participant wants to purchase, then ask,

“Is there anything you plan to do before you

start using it?”

• “Would you like to pay for this right now for

your own use or put it back in the display?”

• If the participant wants to purchase, then ask,

“Is there anything you plan to do before you

start using it?”


RecruitmentRecruitmentRecruitmentRecruitment

• Recruitment by mass media advertising

• Ads told subjects to know:

– total cholesterol, LDL, HDL, and triglycerides

• Advertising may have recruited more

informed subjects who were better prepared

for self-selection

• Recruitment by mass media advertising

• Ads told subjects to know:

– total cholesterol, LDL, HDL, and triglycerides

• Advertising may have recruited more

informed subjects who were better prepared

for self-selection


SELECT: Self-Assessment SELECT: Self-Assessment PopulationPopulation

SELECT: Self-Assessment SELECT: Self-Assessment PopulationPopulation

Number of Number of Calls N=5107Calls N=5107

LDL-C LDL-C Paradigm Paradigm

N=767N=767

Number Number Randomized Randomized

N=1520N=1520

Total-C Total-C Paradigm Paradigm

N=753N=753

LDL-C Paradigm LDL-C Paradigm after exclusions after exclusions

N=662N=662

Total-C Paradigm Total-C Paradigm after exclusions after exclusions

N=664N=664


SELECT Study PopulationSELECT Study PopulationSELECT Study PopulationSELECT Study Population

• 1520 subjects randomized

– typically well educated, middle-class

– 90% high school graduates and 60% had some

college

– 70% had insurance

– 14% low literate

• 1520 subjects randomized

– typically well educated, middle-class

– 90% high school graduates and 60% had some

college

– 70% had insurance

– 14% low literate


Areas Targeted For Areas Targeted For Improvement in SELECTImprovement in SELECT

Areas Targeted For Areas Targeted For Improvement in SELECTImprovement in SELECT

• Decrease the proportion of women <55

• Decrease the proportion of women of


• Decrease the proportion of low CHD risk

(<5% risk of CHD in 10 years)

• Decrease the proportion of women <55

• Decrease the proportion of women of


• Decrease the proportion of low CHD risk

(<5% risk of CHD in 10 years)


SELECT RESULTSSELECT RESULTSSELECT RESULTSSELECT RESULTS


Eligibility Assessment Eligibility Assessment CriteriaCriteria


• Age

• Pregnant or breastfeeding

• May become pregnant

• Heart disease

• Stroke

• Diabetes

• Liver disease

• Listed risk factors

• Age



• Heart disease

• Stroke

• Diabetes

• Liver disease


• Allergy to drug

• Lipid-lowering

medications

• Interacting drugs

• LDL-C

• HDL-C

• Grapefruit juice

• Fasting lipid profile

• Allergy to drug

• Lipid-lowering

medications


• LDL-C

• HDL-C




Self-Assessment ResultsSelf-Assessment ResultsLDL-CLDL-C

Self-Assessment ResultsSelf-Assessment ResultsLDL-CLDL-C

Is it appropriate for Is it appropriate for you?you?

SA population N=662 SA population N=662

Not appropriate for Not appropriate for me (SA =No)me (SA =No)

N=448 (68%) N=448 (68%)

Appropriate for me Appropriate for me (SA =Yes)(SA =Yes)

N=214 (32%)N=214 (32%)

Correct439 (98%)

Incorrect9 (2%)

Incorrect180 (84%)

Correct34 (16%)

Correct473 (71.5%)

Incorrect189 (28.5%)


Self-Assessment Results Self-Assessment Results Total-CTotal-C

Self-Assessment Results Self-Assessment Results Total-CTotal-C

Is it appropriate for Is it appropriate for you?you?

SA population N=664 SA population N=664

Not appropriate for Not appropriate for me (SA =No)me (SA =No)

N=422 (64%) N=422 (64%)

Appropriate for me Appropriate for me (SA =Yes)(SA =Yes)

N=242 (36%)N=242 (36%)

Correct414 (98%)

Incorrect176 (73%)

Correct66 (27%)

Incorrect8 (2%)

Correct480 (72%)

Incorrect184 (28%)


Mitigations for Incorrect Mitigations for Incorrect Self-AssessmentSelf-Assessment

Mitigations for Incorrect Mitigations for Incorrect Self-AssessmentSelf-Assessment

• Some subjects who incorrectly self-selected to

use gave open-ended responses that were

acceptable and could be “mitigated”

– Would talk to doctor

– Gave reasonable rationale for treatment

– Gave evidence of not understanding the self-

assessment question

• Some subjects who incorrectly self-selected to

use gave open-ended responses that were

acceptable and could be “mitigated”

– Would talk to doctor

– Gave reasonable rationale for treatment

– Gave evidence of not understanding the self-

assessment question


MitigationsMitigationsMitigationsMitigations

Label

(# Incorrect)

Talk to

Doctor

Did Not

Understand

SA

Other

Mitigations

Total

Mitigated

LDL (n=180) 46 16 23* 85

Total-C (n=176) 30 11 32* 73

• Almost half of incorrect subjects were mitigated– Talk to doctor was most common reason for mitigation

– Cannot verify whether subjects would actually talk to a doctor

• Other Mitigations– *Reviewers did not agree with 9 mitigations for LDL and 11

mitigations for Total-C

• Almost half of incorrect subjects were mitigated– Talk to doctor was most common reason for mitigation

– Cannot verify whether subjects would actually talk to a doctor

• Other Mitigations– *Reviewers did not agree with 9 mitigations for LDL and 11

mitigations for Total-C


Examples of Other Examples of Other MitigationsMitigations

Made by SponsorMade by Sponsor

Examples of Other Examples of Other MitigationsMitigations

Made by SponsorMade by Sponsor

• Substitution of Mevacor for current lipid

medication without talking to doctor

• High risk subject who self-selected to use

without talking to doctor

• Self-selected yes when had prior side effects

on statins

• Substitution of Mevacor for current lipid

medication without talking to doctor

• High risk subject who self-selected to use

without talking to doctor

• Self-selected yes when had prior side effects

on statins


Self-Selection Percent Self-Selection Percent Completely Correct, and Completely Correct, and Correct After MitigationsCorrect After Mitigations

Self-Selection Percent Self-Selection Percent Completely Correct, and Completely Correct, and Correct After MitigationsCorrect After Mitigations

Label Self

Assessment

% Completely

Correct

% Correct After

Mitigations

LDL Yes 16% ~50%

Total-C Yes 27% ~50%


SELECT RESULTS:SELECT RESULTS:ANALYSIS OF ELIGIBILITY ANALYSIS OF ELIGIBILITY

CRITERIA SUBSETSCRITERIA SUBSETSHIERARCHIESHIERARCHIES

SELECT RESULTS:SELECT RESULTS:ANALYSIS OF ELIGIBILITY ANALYSIS OF ELIGIBILITY

CRITERIA SUBSETSCRITERIA SUBSETSHIERARCHIESHIERARCHIES


HierarchiesHierarchiesHierarchiesHierarchies

• Many eligibility criteria– Difficult to get all eligibility criteria correct– Some criteria of more clinical importance then

others

• New analyses where % correct was calculated for subsets of eligibility criteria (“hierarchies”)

• Self-assessment hierarchies will be presented

• Many eligibility criteria– Difficult to get all eligibility criteria correct– Some criteria of more clinical importance then

others

• New analyses where % correct was calculated for subsets of eligibility criteria (“hierarchies”)

• Self-assessment hierarchies will be presented


Hierarchies for LDL-C ArmHierarchies for LDL-C ArmHierarchies for LDL-C ArmHierarchies for LDL-C Arm

• Self-Selection Results Using ALL Label Criteria

– % entirely correct (16%)

– % correct after mitigation (~50%)

• Using “hierarchies” or subsets of label criteria

– % correct before mitigation

– % correct after mitigation

• % correct depends on which criteria are used in

hierarchy

• Self-Selection Results Using ALL Label Criteria

– % entirely correct (16%)

– % correct after mitigation (~50%)

• Using “hierarchies” or subsets of label criteria

– % correct before mitigation

– % correct after mitigation

• % correct depends on which criteria are used in

hierarchy


Sponsor Safety HierarchySponsor Safety HierarchySponsor Safety HierarchySponsor Safety Hierarchy

• Pregnant/breast feeding


• Allergy to lovastatin

• On interacting medications

• On lipid-lowering medications

• Liver problem

• Pregnant/breast feeding


• Allergy to lovastatin

• On interacting medications

• On lipid-lowering medications

• Liver problem


SAFETY Hierarchy SA=Yes (LDL arm)

SAFETY Hierarchy SA=Yes (LDL arm)

N=214

Of 2 Pregnant/breastfeedingCorrect

NoN=0

N=214

Of 12 may become pregnantCorrect

NoN=1

N=213

Of 4 allergy to lovastatinCorrect

NoN=0

N=213

Of 12 on interacting medicineCorrect

NoN=3

N=210


SAFETY Hierarchy SA=YesSAFETY Hierarchy SA=Yes

N=210

Of 140 on lipid lowering medicineCorrect

NoN=36

N=174

Of 23 liver problemCorrect

NoN=0

N=174

Percent Correct 81.3%


Sponsor Safety HierarchySponsor Safety HierarchySponsor Safety HierarchySponsor Safety Hierarchy

Hierarchy

LDL (N=214) Total-C (N=242)

% Correct Before

Mitigation

% Correct After

Mitigation

% Correct Before

Mitigation

% Correct After

Mitigation

Sponsor Safety* 81.3% 89.3% 83.1% 90.1%

For all eligibility criteria 16% correct

Sponsor Safety: Pregnant/breast-feeding, may become pregnant, allergy to lovastatin, interacting medications, lipid lowering medications, and liver problems




• Age



• Heart disease

• Stroke

• Diabetes

• Liver disease


• Age



• Heart disease

• Stroke

• Diabetes

• Liver disease


• Allergy to drug

• Lipid-lowering

medications


• LDL-C

• HDL-C



• Allergy to drug

• Lipid-lowering

medications


• LDL-C

• HDL-C




Sponsor HierarchiesSponsor HierarchiesSponsor HierarchiesSponsor Hierarchies

Hierarchy


% Correct Before

Mitigation

% Correct After

Mitigation

% Correct Before

Mitigation

% Correct After

Mitigation

Safety* 81.3% 89.3% 83.1% 90.1%

Benefit** 25.7% 57.0% 41.7% 62.4%

Safety & Benefit 21.0% 52.8% 35.1% 58.3%

* Pregnant/breast-feeding, may become pregnant,

allergy to lovastatin, interacting medications, lipid

lowering medications, liver problems

** Age, lipid values (LDL-C or Total-C), and risk factors


Other Sponsor HierarchiesOther Sponsor HierarchiesOther Sponsor HierarchiesOther Sponsor Hierarchies

Hierarchy


% Correct Before

Mitigation

% Correct After

Mitigation

% Correct Before

Mitigation

% Correct After

Mitigation

Benefits w/o Lipid* 65.4% 77.1% 77.3% 88.4%

Expanded Benefit** 40.7% 65.9% 57.4% 77.3%

* Age and risk factors** Age, risk factors, heart disease, stroke, and diabetes,

lipid lowering medications


FDA Review Team FDA Review Team HierarchiesHierarchies

FDA Review Team FDA Review Team HierarchiesHierarchies

Hierarchy


% Correct Before

Mitigation

% Correct After

Mitigation

% Correct Before

Mitigation

% Correct After

Mitigation

#1* 21.0% 52.8% 35.1% 58.3%

#2** 17.8% 50.9% 31.4% 57.0%

* Age, lipid lowering medications, lipid values, interacting medications, risk factors

** Age, lipid lowering medications, lipid values, interacting medications, heart disease, stroke, diabetes, risk factors


HierarchiesHierarchiesHierarchiesHierarchies

• None of the hierarchies was defined a

priori in the study protocol

• Depending on which criteria are

included, the percent correct in the

hierarchies before mitigations ranged

from 20-80%

• None of the hierarchies was defined a

priori in the study protocol

• Depending on which criteria are

included, the percent correct in the

hierarchies before mitigations ranged

from 20-80%


SELECT RESULTS:SELECT RESULTS:Profiles of User Profiles of User

PopulationPopulation

SELECT RESULTS:SELECT RESULTS:Profiles of User Profiles of User

PopulationPopulation


CHD Risk Profiles SA=Yes LDL-CCHD Risk Profiles SA=Yes LDL-CCHD Risk Profiles SA=Yes LDL-CCHD Risk Profiles SA=Yes LDL-C

10-Year CHD Risk

Men WomenTotal

Men + Women

n % n % n %

unknown 4 3.2% 1 1.1% 5 2.4%

<5% 13 10.5% 42 46.7% 55 25.7%

5-20% 51 41.1% 22 24.4% 73 34.1%

>20% 13 10.4% 1 1.1% 14 6.6%

CHD/DM/Stroke 16 12.9% 12 13.3% 28 13.1%

Rx Chol. Med. 27 21.8% 12 13.3% 39 18.2%


Women Too Young (<55 yo) LDL Women Too Young (<55 yo) LDL armarm

Women Too Young (<55 yo) LDL Women Too Young (<55 yo) LDL armarm

• 391 women were asked the self-assessment question in

the LDL arm, 220 (56.3%) were too young.

– 13.2% (29/220) self-selected to use

• Of 391 women asked the SA question, 101 women of all

ages self-selected to use

– Of these 101 women, ~ 29% were < 55 years old

• Reasons for their decision were: age is close, lower my

cholesterol, family history

• 391 women were asked the self-assessment question in

the LDL arm, 220 (56.3%) were too young.

– 13.2% (29/220) self-selected to use

• Of 391 women asked the SA question, 101 women of all

ages self-selected to use

– Of these 101 women, ~ 29% were < 55 years old

• Reasons for their decision were: age is close, lower my

cholesterol, family history


Pregnant/May Become Pregnant/May Become PregnantPregnant

Pregnant/May Become Pregnant/May Become PregnantPregnant

• Pregnant (n=4)– 1 out of 4: SA=Yes,

– sponsor mitigated

– reviewers agreed

• May become pregnant (n=22)– 9% (2/22) chose SA=Yes,


– reviewers did not agree

• Pregnant (n=4)– 1 out of 4: SA=Yes,


– reviewers agreed

• May become pregnant (n=22)– 9% (2/22) chose SA=Yes,


– reviewers did not agree


Heart Disease (LDL Arm)Heart Disease (LDL Arm)Heart Disease (LDL Arm)Heart Disease (LDL Arm)

• 48.5% (33/68) with heart disease

self-selected yes

• Subjects at high CHD risk might be

undertreated by 20 mg of lovastatin

• 48.5% (33/68) with heart disease

self-selected yes

• Subjects at high CHD risk might be

undertreated by 20 mg of lovastatin


Already on Lipid Medications Already on Lipid Medications

(LDL arm)(LDL arm)

Already on Lipid Medications Already on Lipid Medications

(LDL arm)(LDL arm)

• 140/750 (18.7%) in the self-selection

population were already taking lipid-

lowering medication

• 44/140 (31.4%) of these participants

self-selected yes

• 140/750 (18.7%) in the self-selection

population were already taking lipid-

lowering medication

• 44/140 (31.4%) of these participants

self-selected yes


Reasons Why Subjects on Reasons Why Subjects on Rx Selected IncorrectlyRx Selected Incorrectly

Reasons Why Subjects on Reasons Why Subjects on Rx Selected IncorrectlyRx Selected Incorrectly

• The most frequent reasons for choosing to

use or purchasing, when the subject was

already taking lipid-lowering medication

– to replace the prescription medication

– specifically to replace it because of lower cost

• The most frequent reasons for choosing to

use or purchasing, when the subject was

already taking lipid-lowering medication

– to replace the prescription medication

– specifically to replace it because of lower cost


Substitution Rate of OTC for Rx Substitution Rate of OTC for Rx Medications CHDMedications CHD

Substitution Rate of OTC for Rx Substitution Rate of OTC for Rx Medications CHDMedications CHD

Reported Action

LDL-C(N=27)N(%)

Take along with it 8 (29.6%)

Take in place 14 (51.9%)

Don’t know 1 (3.7%)

Other 3 (11.1%)

Missing 1 (3.7%)


Reasons for Preferring OTC Reasons for Preferring OTC Med Rather than Rx Med for Med Rather than Rx Med for

CholesterolCholesterol

Reasons for Preferring OTC Reasons for Preferring OTC Med Rather than Rx Med for Med Rather than Rx Med for

CholesterolCholesterol• The most frequent reasons for preferring OTC

medications, for those who self-selected yes : – less expensive (50%)

– convenience (29%)

– don’t have to see the doctor (15%)

– feels safer/less side effects (11.3%)

• The most frequent reasons for preferring OTC

medications, for those who self-selected yes : – less expensive (50%)

– convenience (29%)

– don’t have to see the doctor (15%)

– feels safer/less side effects (11.3%)


High Risk, CHD, Diabetes, High Risk, CHD, Diabetes, Stroke: LDL-C armStroke: LDL-C arm

High Risk, CHD, Diabetes, High Risk, CHD, Diabetes, Stroke: LDL-C armStroke: LDL-C arm

• On average, ~30% of subjects with CHD,

DM or stroke wanted to buy

• 2/3 of these subjects were not on any lipid-

lowering medications

• On average, ~30% of subjects with CHD,

DM or stroke wanted to buy

• 2/3 of these subjects were not on any lipid-

lowering medications


What Medications Would Be What Medications Would Be Substituted: LDL armSubstituted: LDL arm

What Medications Would Be What Medications Would Be Substituted: LDL armSubstituted: LDL arm


Knowing LDL-C versus Knowing LDL-C versus Total-CTotal-C

Knowing LDL-C versus Knowing LDL-C versus Total-CTotal-C

• In the LDL-C arm, 37.5% (268/714) did not know their

LDL-C, whereas in the Total-C arm, 21% (149/708)

did not know their Total-C.

• Of those who did not know their cholesterol numbers– LDL-C: 22.4% ( 60/268) self-selected yes

– Total-C: 17.4% (26/149) self- selected yes

• In the LDL-C arm, 37.5% (268/714) did not know their

LDL-C, whereas in the Total-C arm, 21% (149/708)

did not know their Total-C.

• Of those who did not know their cholesterol numbers– LDL-C: 22.4% ( 60/268) self-selected yes

– Total-C: 17.4% (26/149) self- selected yes


Ineligible Subjects for Lipid Ineligible Subjects for Lipid ValuesValues

Ineligible Subjects for Lipid Ineligible Subjects for Lipid ValuesValues

• Many of the subjects who had LDL outside

the eligible range nevertheless selected yes

in the LDL-C arm – 43% (52/122) of subjects w/ LDL-C too high

(above 170) self-selected yes

– 17% (26/153) of subject whose LDL-C too low

(below 130) self-selected yes

• Many of the subjects who had LDL outside

the eligible range nevertheless selected yes

in the LDL-C arm – 43% (52/122) of subjects w/ LDL-C too high

(above 170) self-selected yes

– 17% (26/153) of subject whose LDL-C too low

(below 130) self-selected yes


SELECT Summary SELECT Summary SELECT Summary SELECT Summary

• ~20% self-selected yes entirely correctly

– With mitigations, % correct ~ 50%

• Only 4 pregnant women in the study

• Of those who may become pregnant

– 2/22 (9%) were incorrect (SA=Yes)

• ~ 30% of participants with CHD, diabetes mellitus, or

stroke wanted to buy

– 2/3 were not on cholesterol medications

• ~20% self-selected yes entirely correctly

– With mitigations, % correct ~ 50%

• Only 4 pregnant women in the study

• Of those who may become pregnant

– 2/22 (9%) were incorrect (SA=Yes)

• ~ 30% of participants with CHD, diabetes mellitus, or

stroke wanted to buy

– 2/3 were not on cholesterol medications


SELECT Summary (LDL SELECT Summary (LDL paradigm)paradigm)


• ~ 30% of subjects on lipid-lowering medication self-

selected to use

• Of those who would purchase and were on lipid-lowering

medication

– 50% would take Mevacor “in place of” Rx med

– 30% would take Mevacor along with their Rx Med

– The most commonly taken lipid-lowering medications

were atorvastatin, simvastatin, rosuvastatin, and

lovastatin

• ~ 30% of subjects on lipid-lowering medication self-

selected to use

• Of those who would purchase and were on lipid-lowering

medication

– 50% would take Mevacor “in place of” Rx med

– 30% would take Mevacor along with their Rx Med

– The most commonly taken lipid-lowering medications

were atorvastatin, simvastatin, rosuvastatin, and

lovastatin




Those who self-selected to use in the LDL arm included:

• 101 of 391 women who were asked the SA question

– 29% were < 55 years old

• 13.2% of women < 55 years old

• 22% of the participants who did not know their LDL-C

value

• 43% of subjects who had LDL too high (above 170)

• 17% of subject whose LDL was too low (below 130)

Those who self-selected to use in the LDL arm included:

• 101 of 391 women who were asked the SA question

– 29% were < 55 years old

• 13.2% of women < 55 years old

• 22% of the participants who did not know their LDL-C

value

• 43% of subjects who had LDL too high (above 170)

• 17% of subject whose LDL was too low (below 130)


SELECT SummarySELECT SummarySELECT SummarySELECT Summary

10 -Year CHD risk: LDL-C Label (SA=Yes)

• 41.1% men were in the targeted CHD risk range – Most men outside the target range were of high risk, CHD

equivalent or on lipid lowering meds

• 24.4% of women were in the targeted range– Most women outside this range were low risk

• ~11% of men and over 45% of women were of low

CHD risk (<5% risk of CHD in 10 years)

10 -Year CHD risk: LDL-C Label (SA=Yes)

• 41.1% men were in the targeted CHD risk range – Most men outside the target range were of high risk, CHD

equivalent or on lipid lowering meds

• 24.4% of women were in the targeted range– Most women outside this range were low risk

• ~11% of men and over 45% of women were of low

CHD risk (<5% risk of CHD in 10 years)


AcknowledgementsAcknowledgementsAcknowledgementsAcknowledgements

• Division of Nonprescription Clinical Evaluation Review Team

– Daiva Shetty, M.D.

– Joel Schiffenbauer, M.D.

– Andrea Leonard Segal, M.D.

– Laura Shay, CNP

– Stan Lin, Ph.D.

– Michael Koenig, Ph.D.

– Matthew Holman, Ph.D.

– Mary Lewis, PM

• Division of Nonprescription Clinical Evaluation Review Team

– Daiva Shetty, M.D.

– Joel Schiffenbauer, M.D.

– Andrea Leonard Segal, M.D.

– Laura Shay, CNP

– Stan Lin, Ph.D.

– Michael Koenig, Ph.D.

– Matthew Holman, Ph.D.

– Mary Lewis, PM

mevacor daily ® merck nda 21-213 nonprescription drugs advisory committee and endocrinologic and...

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