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DRAFT SLIDES FOR NDA 21-198 ADVISORY COMMITTEE PRESENATIONS
Pravachol 10 mg Tablets Rx to OTC Switch
Daiva Shetty, M.D.
Division of Over-the-Counter
Drug Products (HFD-560)
Food and Drug Administration
Friday, July 14, 2000
Actual Use Studies Background
Simulate OTC Use Have few exclusion criteria Objectives depend on the specific product
and concerns related to that product such as: compliance, dosing, duration of use off-label use safety and efficacy in OTC population
Actual Use Issues for Pravachol
Are consumers able to: self-diagnose
know their own cholesterol values understand serum cholesterol values
self-select identify risk factors for CHD
Actual Use Issues for Pravachol
Are consumers able to: self-treat hypercholesterolemia
when to start treatment are they able to follow label directions for
dosing and duration of use do they understand the treatment goal
Review of Pravachol Actual Use Trials
PREDICT, Protocol # 800-01-97 OPTIONS, Protocol # 800-03-97
Actual Use Trials
PREDICT
The Pravachol Experience Documented In a Consumer Trial
Study PREDICT
Study design: multi-center randomized parallel open-label 6 months duration
To test: behavior efficacy tolerability
Study PREDICT
Study design (cont.) recruitment done via advertising
(newspapers, radio, pharmacies) the call center directed interested subjects
to the enrollment site the call center also served as a screening
site for premenopausal or childbearing potential women
Study PREDICT
Study design (cont.)
Inclusion criteria:> 18 years
Study PREDICT
Study design (cont.)
Exclusion criteria: less than 18 years old females of childbearing potentialbreast feeding femalesparticipation in a research study
within the last 30 days
Study PREDICT
Criteria for treatment on the label: Total cholesterol 200-240 mg/dl LDL cholesterol > 130 mg/dl
Study PREDICT
Primary Objective:
Proportion of OTC randomized subjects, who having purchased OTC Pravachol 10 mg, consult a physician within two months of using medication
PREDICT Results
80%Learned throughadvertisem ents
20%W alk through
O TC1,924
Rx1,948
Random ized3,872
Screened at the Screening Site3,888
Called the Call Center11,065
PREDICT Results
119 subjects were ineligible to participate 61 (2%) women of childbearing age
Of the 11,065 who called, unknown how many were women of childbearing potential
Behavior of OTC Population(n=1,924)
720
553499
266
0
100
200
300
400
500
600
700
800
Purchased Consulted aphysician
Treated Did notqualify
Treatment Guidelines
Initiate Treatment/LDL-C Goal/LDL-C
No CHD or diabetes & 2 risk factors
>130 mg/dl, < 190 mg/dl < 130 mg/dl
No CHD or diabetes, <1 risk factor
>160 mg/dl, < 190 mg/dl < 160 mg/dl
PREDICT Results
• Lipid Profile at Baseline in Qualified and Treated Population
• LDL-C:• Mean 162 mg/dl + 17• Median 163 mg/dl
• TC:• Mean 245 mg/dl + 21• Median 245 mg/dl
Behavior of OTC Treated Population
290 (58%) withdrew from the study 123 were withdrawn from the study by a
physician Discontinuation due to adverse events
8% OTC vs. 5% Rx 53 subjects were titrated to a higher dose
PREDICT Results
Compliance Assessed by pill count and self-report, and
defined by 80-120%: 54% OTC vs. 65% Rx CI -19%,-3.7%
Mean duration of treatment: 109.4 days OTC vs. 152.5 days RX
Are consumers able to
self-diagnose hypercholesterolemia?
Knowledge about Cholesterol values Randomized Population (n=3,872)
• Healthy level TC:• < 200 74%• Unknown 21%
• Healthy level LDL-C:• < 130 12%• Unknown 80%
• Knowledge of HDL-C was not tested
Actual Use Trials
OPTIONS
OTC Pravachol Trial In an Observed Naturalistic Setting
Study OPTIONS
Study design: multi-center open-label pharmacy based 3 months duration
To assess: behavior compliance safety
Study OPTIONS
Study design (cont.)
Inclusion criteria: > 18 years member of a participating HMO for at least
6 months
Study OPTIONS
Study design (cont.)
Exclusion criteria:pregnancy or lactationparticipation in a research study
within the last 30 days less than 18 years old
Study OPTIONS
Study design (cont.)
Recruitment was done via: mailing the study brochure to the HMO
members walk through traffic in the participating
pharmacies radio newspaper
Study OPTIONS
Population was not representative of overall U.S. OTC population: restricted to certain geographical areas all participants had health care
insurance and prescription drug coverage
Study OPTIONS
Study design (cont.)
Criteria for treatment on the label Total serum cholesterol 200-240 mg/dl > 35 years for men > 55 years for women
Study OPTIONS
Primary Objective
To determine the proportion of subjects, who having purchased Pravachol 10 mg, contact their health care provider within 2 months of using the medication
OPTIONS Results
45% Responded to the m a ile r53% W alk through2% Responded to the new spaper or radio
782E nrol led
2 ,207Responded to the S tudy Recruitm ent M ate r ia l
161 ,322+T arge ted for enrol lm ent
OPTIONS Results
782
404321
178
0
100
200
300
400
500
600
700
Enrolled Purchased Treated Consulted
OPTIONS Results
Behavior of Treated Population
156 (49%)C ontinued on trea tm ent for > 56 days
165 (51%)W ithdrew from the s tudy
321T rea ted Popula tion
OPTIONS Results
95 (24%) purchase population were not recommended Pravachol by their health care provider
Median total-C level 235 mg/dl
Median LDL-C level 151 mg/dl
59.8% women were <55 years old
Proposed Label
• Total cholesterol 200-240 mg/dl
• “Bad” cholesterol (LDL) > 130 mg/dl
• Do not use• if you are under 18 years• if you have liver disease or drink >3 alcoholic
beverages daily• if you are allergic to pravastatin
Latest Proposed Label
• Total cholesterol 200-240 mg/dl
• “Bad” cholesterol (LDL) > 130 mg/dl
• For men over 35 years of age
• For women over 45 years of age
Overall Conclusions
Low consumer understanding of specific serum cholesterol values
Substantial number of self-selection errors
High withdrawal rate Poor adherence
Overall Conclusions
Behavior of childbearing age women was not addressed in these 2 trials
Consumer understanding was not assessed about: the goal (to lower cholesterol) the length of the therapy titration to a higher dose
Targeted OTC population on the current proposed label has not been studied
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