DRAFT SLIDES FOR NDA 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 # OPTIONS, Protocol #
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 potential breast feeding females participation in a research study within the last 30 days
Study PREDICT Criteria for treatment on the label: Total cholesterol 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
PREDICTResults
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)
Treatment Guidelines Initiate Treatment/LDL-CGoal/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
PREDICTResults 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
PREDICTResults Compliance Assessed by pill count and self-report, and defined by %: 54% OTC vs. 65% RxCI -19%,-3.7% Mean duration of treatment: days OTC vs days RX
Are consumers able to self-diagnose hypercholesterolemia?
Knowledge about Cholesterol values Randomized Population (n=3,872) Healthy level TC: < 20074% Unknown21% Healthy level LDL-C: < 13012% Unknown80% 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 lactation participation 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 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
OPTIONSResults
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 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 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