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Transcript of 1 Omeprazole Magnesium Keith C. Triebwasser, Ph.D. Senior Director Regulatory Affairs Procter &...
1
Omeprazole Omeprazole MagnesiumMagnesium
Keith C. Triebwasser, Ph.D.Keith C. Triebwasser, Ph.D.Senior DirectorSenior Director
Regulatory AffairsRegulatory AffairsProcter & GambleProcter & Gamble
2
Rx to OTC SwitchRx to OTC Switch
OmeprazoleOmeprazolefor the Prevention offor the Prevention of
Frequent Heartburn SymptomsFrequent Heartburn Symptoms
3Target Population: People withTarget Population: People withFrequent HeartburnFrequent Heartburn
Heartburn symptoms 2 or more days Heartburn symptoms 2 or more days per week (40 million people)per week (40 million people)
Affects their daily livesAffects their daily lives
Goal: to prevent vs. treat symptomsGoal: to prevent vs. treat symptoms
4Target Population Tries to Manage Target Population Tries to Manage Frequent HeartburnFrequent Heartburn
77% use OTC medications77% use OTC medications
OTC product useOTC product use
- 80% use antacids- 80% use antacids
- 48% use OTC H- 48% use OTC H22RAsRAs
- 38% use both- 38% use both
Only 19% report satisfactionOnly 19% report satisfaction
5Current OTC Therapies Not Well-SuitedCurrent OTC Therapies Not Well-Suitedfor People with Frequent Heartburnfor People with Frequent Heartburn
Pharmacology limits effectivenessPharmacology limits effectiveness– Short duration of actionShort duration of action
– Intended for episodic heartburnIntended for episodic heartburn
Current therapies lack all day efficacyCurrent therapies lack all day efficacy
6Omeprazole Ideally Suited for Target Omeprazole Ideally Suited for Target PopulationPopulation
Pharmacology provides forPharmacology provides for– Prolonged acid suppressionProlonged acid suppression
– 24 hour prevention of symptoms24 hour prevention of symptoms
– Once daily dosingOnce daily dosing
7Omeprazole Ideally Suited for Target Omeprazole Ideally Suited for Target PopulationPopulation
Omeprazole’s excellent safety profileOmeprazole’s excellent safety profile– 15 years15 years
– 125 countries125 countries
– 450 million patient treatments450 million patient treatments
8
OTC Label OTC Label
Label clearly directs consumers:Label clearly directs consumers:
How to select the productHow to select the product
How to use the productHow to use the product
What to do if symptoms continueWhat to do if symptoms continueor returnor return
9
OTC Label ElementsOTC Label Elements
Target populationTarget population– Frequent heartburn sufferers (2 or more days/week)Frequent heartburn sufferers (2 or more days/week)
Indication Indication – Prevention of the symptoms of frequent heartburn Prevention of the symptoms of frequent heartburn
for 24 hoursfor 24 hours
10
OTC Label ElementsOTC Label Elements
Target populationTarget population– Frequent heartburn sufferers (2 or more days/week)Frequent heartburn sufferers (2 or more days/week)
Indication Indication – Prevention of the symptoms of frequent heartburn Prevention of the symptoms of frequent heartburn
for 24 hoursfor 24 hours Dose Dose
– 20 mg of omeprazole as omeprazole magnesium20 mg of omeprazole as omeprazole magnesium
11
OTC Label ElementsOTC Label Elements
Target populationTarget population– Frequent heartburn sufferers (2 or more days/week)Frequent heartburn sufferers (2 or more days/week)
Indication Indication – Prevention of the symptoms of frequent heartburn Prevention of the symptoms of frequent heartburn
for 24 hoursfor 24 hours Dose Dose
– 20 mg of omeprazole as omeprazole magnesium20 mg of omeprazole as omeprazole magnesium Directions for useDirections for use
– Take 1 tablet in the morningTake 1 tablet in the morning
12
OTC Label ElementsOTC Label Elements
Target populationTarget population– Frequent heartburn sufferers (2 or more days/week)Frequent heartburn sufferers (2 or more days/week)
Indication Indication – Prevention of the symptoms of frequent heartburn Prevention of the symptoms of frequent heartburn
for 24 hoursfor 24 hours Dose Dose
– 20 mg of omeprazole as omeprazole magnesium20 mg of omeprazole as omeprazole magnesium Directions for useDirections for use
– Take 1 tablet in the morningTake 1 tablet in the morning– Take every day for 14 consecutive daysTake every day for 14 consecutive days
13
OTC Label ElementsOTC Label Elements
Target populationTarget population– Frequent heartburn sufferers (2 or more days/week)Frequent heartburn sufferers (2 or more days/week)
Indication Indication – Prevention of the symptoms of frequent heartburn Prevention of the symptoms of frequent heartburn
for 24 hoursfor 24 hours Dose Dose
– 20 mg of omeprazole as omeprazole magnesium20 mg of omeprazole as omeprazole magnesium Directions for useDirections for use
– Take 1 tablet in the morningTake 1 tablet in the morning– Take every day for 14 daysTake every day for 14 days
Instructions to see a doctorInstructions to see a doctor– If you have warning signsIf you have warning signs– If heartburn continues or returnsIf heartburn continues or returns
14
Omeprazole, properly labeled, can Omeprazole, properly labeled, can be safely and effectively used in be safely and effectively used in
an OTC settingan OTC setting
15
Presentation AgendaPresentation Agenda
OTC Omeprazole for Frequent Heartburn OTC Omeprazole for Frequent Heartburn David Peura, M.D.David Peura, M.D.
Professor of MedicineProfessor of MedicineAssociate Chief of Gastroenterology, University of VirginiaAssociate Chief of Gastroenterology, University of Virginia
Efficacy and Consumer UseEfficacy and Consumer UseDouglas Bierer, Ph.D.Douglas Bierer, Ph.D.
Director, OTC Drug Development, The Procter & Gamble Co.Director, OTC Drug Development, The Procter & Gamble Co.
Safe Use in OTC SettingSafe Use in OTC SettingNora Zorich, M.D., Ph.D.Nora Zorich, M.D., Ph.D.
Vice President, Pharmaceuticals, The Procter & Gamble Co.Vice President, Pharmaceuticals, The Procter & Gamble Co.
SummarySummaryKeith Triebwasser, Ph.D.Keith Triebwasser, Ph.D.
Senior Director, Regulatory Affairs, The Procter & Gamble Co.Senior Director, Regulatory Affairs, The Procter & Gamble Co.
SafetySafetyDouglas Levine, M.D.Douglas Levine, M.D.
Chief Medical Officer, AstraZeneca LPChief Medical Officer, AstraZeneca LP
16
Proposed OmeprazoleRX to OTC Switch:
A Clinician’s Perspective
David Peura, M.D. FACP FACGProfessor of Medicine
Associate Chief of Gastroenterology and HepatologyUniversity of Virginia
17
Gap in OTC Therapy for Frequent Heartburn
Heartburn frequency variesHeartburn frequency varies
Current OTC meds are inadequate Current OTC meds are inadequate therapy for frequent HBtherapy for frequent HB
Condition does not require intensive Condition does not require intensive physician involvement physician involvement
Consumers could self-manage frequent Consumers could self-manage frequent HB with effective OTC therapyHB with effective OTC therapy
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More than 50% GI patients on PPIs
Primary care physicians comfortable prescribing PPIs for frequent heartburn
Endoscopy/diagnostic tests unnecessary for uncomplicated frequent heartburn
Symptom management/prevention is current practice
Current Physician ExperienceWith PPIs and Frequent Heartburn
19
OTC Omeprazole Consistent withCurrent Practice Guidelines
Therapy should be aimed at treating or preventing heartburn symptoms with
acid-reducing medications
20
Frequent Heartburn Can Be Self-Managed With OTC Omeprazole
Label encourages people to see their doctor
People will continue to see doctors
Low risk/high benefit to consumer
21
OTC Omeprazole Would Benefit Consumers
Symptom prevention is key
PPI best therapy to prevent frequent heartburn symptoms
Proposed dose and duration appropriate
Omeprazole safe and effective
22
Efficacy and Efficacy and Consumer UseConsumer Use
Douglas Ws. Bierer, Ph.D.Douglas Ws. Bierer, Ph.D.Director, OTC Drug DevelopmentDirector, OTC Drug Development
Procter & GambleProcter & Gamble
23Efficacy and ConsumerEfficacy and ConsumerBehavior ProgramBehavior Program
Pivotal efficacy studiesPivotal efficacy studies
Consumer understanding Consumer understanding and behavior studiesand behavior studies
– Label comprehensionLabel comprehension
– Appropriate OTC useAppropriate OTC use
24
Efficacy TrialsEfficacy Trials
Two efficacy trialsTwo efficacy trials
Study populationsStudy populations– Heartburn symptoms Heartburn symptoms >> 2 days a week 2 days a week
– No physician diagnosis of GERD or erosive No physician diagnosis of GERD or erosive esophagitisesophagitis
DosingDosing– One tablet in the morning forOne tablet in the morning for
14 consecutive days14 consecutive days
EndpointEndpoint– % subjects heartburn-free% subjects heartburn-free
– % days heartburn-free% days heartburn-free
25Percent of Subjects Heartburn Free ForPercent of Subjects Heartburn Free For24 Hours: Time Course Over 14 Days 24 Hours: Time Course Over 14 Days
00
1010
2020
3030
4040
5050
6060
7070
8080
9090
11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414
Time (days)Time (days)
% S
ub
ject
s W
ith
No
Hea
rtb
urn
% S
ub
ject
s W
ith
No
Hea
rtb
urn
Study 17120 mg OME
Study 171Placebo
Study 183 20 mg OME
Study 183Placebo
* p < .001 (day 1, day 14, across 14 days)* p < .001 (day 1, day 14, across 14 days)
26
Conclusion: Efficacy StudiesConclusion: Efficacy Studies
20 mg provides prevention of heartburn 20 mg provides prevention of heartburn symptoms for 24 hourssymptoms for 24 hours
Uses:Uses:For the prevention of the symptoms ofFor the prevention of the symptoms offrequent heartburn for 24 hoursfrequent heartburn for 24 hours
Dose:Dose:20 mg20 mg
Directions:Directions:1 tablet in the morning for 14 consecutive 1 tablet in the morning for 14 consecutive daysdays
27Consumer Understanding and Consumer Understanding and Behavior ProgramBehavior Program
ObjectivesObjectives– Correct self-selectionCorrect self-selection
– Understand how to use productUnderstand how to use product
– Understand and adhere to product Understand and adhere to product warningswarnings
StudiesStudies– Label comprehension Label comprehension
– Actual use Actual use
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Label Comprehension Study DesignLabel Comprehension Study Design
Subjects recruited from 12 sites across U.S.Subjects recruited from 12 sites across U.S.
n=684n=684
Study populationStudy population
– Infrequent or no heartburnInfrequent or no heartburn
– Frequent heartburnFrequent heartburn
– Low-literacy with frequent heartburnLow-literacy with frequent heartburn
– Potential drug-drug interactionsPotential drug-drug interactions
– Pregnant/nursing Pregnant/nursing
29Label Comprehension Study ResultsLabel Comprehension Study ResultsWho Should Use the ProductWho Should Use the Product
Infrequent/Infrequent/No HeartburnNo Heartburn
22%22%
78%78%Chose CorrectlyChose Correctly
n=229n=229
30Label Comprehension Study ResultsLabel Comprehension Study ResultsWho Should Use the ProductWho Should Use the Product
FrequentFrequentHeartburnHeartburn
1%1%
99%99%Chose CorrectlyChose Correctly
n=200n=200
31Label Comprehension of Low LiterateLabel Comprehension of Low LiteratePeople with Frequent HeartburnPeople with Frequent Heartburn
Frequent heartburn situationsFrequent heartburn situations79%79%
Infrequent heartburn situationsInfrequent heartburn situations49%49%
% Correct% Correct ResponseResponse
(n=162)(n=162)
32Subjects Understood How to UseSubjects Understood How to Usethe Productthe Product
1 tablet per day1 tablet per day 95%95%
Take for 14 consecutive daysTake for 14 consecutive days 91%91%
Contact healthcare professional Contact healthcare professional before using beyond 14 daysbefore using beyond 14 days 92%92%
33Subjects Understood When Not toSubjects Understood When Not toUse/Ask a Health ProfessionalUse/Ask a Health Professional
Drug-drug interactionsDrug-drug interactions
–Generic + brand namesGeneric + brand names
82%82%–Generic names aloneGeneric names alone
50%50% Pregnant/nursingPregnant/nursing
91%91%
General warning signsGeneral warning signs 81%81%
34
Actual Use Study: ObjectivesActual Use Study: Objectives
Evaluate consumer use in Evaluate consumer use in naturalistic OTC settingnaturalistic OTC setting
– Correct self-selectionCorrect self-selection
– Appropriate useAppropriate use
– Complied with label Complied with label instructionsinstructions
35
Actual Use Study DesignActual Use Study Design
Design mimicked consumer Design mimicked consumer purchase decisions:purchase decisions:– Mall kiosk site – not clinical siteMall kiosk site – not clinical site
– No health care professional on siteNo health care professional on site
– No subject contact in use phaseNo subject contact in use phase
– Purchase productPurchase product
– Product repurchase allowedProduct repurchase allowed
36
Follow-UpFollow-UpInterviewInterview
4 Weeks After Usage Period
Product Use/Product Use/RepurchaseRepurchase 8 Week Period
Study PhasesStudy Phases
Self Selection Self Selection DecisionDecision
At Mall Kiosk
37
Disposition of SubjectsDisposition of Subjects
Population Approached at MallPopulation Approached at Malln = 5060n = 5060
Population Approached at MallPopulation Approached at Malln = 5060n = 5060
No Heartburn/No Heartburn/Not InterestedNot Interested
Not Appropriate to useNot Appropriate to usen = 3809n = 3809
No Heartburn/No Heartburn/Not InterestedNot Interested
Not Appropriate to useNot Appropriate to usen = 3809n = 3809
Said They Could Said They Could Use ProductUse Product
n = 1251n = 1251
Said They Could Said They Could Use ProductUse Product
n = 1251n = 1251
Would Not Would Not PurchasePurchasen = 385n = 385
Would Not Would Not PurchasePurchasen = 385n = 385
Agreed to Purchase ProductAgreed to Purchase Product[Self-Selection Population][Self-Selection Population]
n = 866n = 866
Agreed to Purchase ProductAgreed to Purchase Product[Self-Selection Population][Self-Selection Population]
n = 866n = 866
38
Demographics of Self-Selection PopulationDemographics of Self-Selection Population
CharacteristicCharacteristic
Gender (% female) Gender (% female) 58%58%
Race Race
% Caucasian% Caucasian 68%68%
% African American% African American 16%16%
% Hispanic% Hispanic 11%11%
Mean age/rangeMean age/range 48/18-9148/18-91
Low reading ability (REALM Test)Low reading ability (REALM Test) 8% 8%
Heartburn symptoms Heartburn symptoms 2days/wk 2days/wk 90%90%
Use OTC heartburn medicationsUse OTC heartburn medications 90%90%
Use Rx heartburn medicationsUse Rx heartburn medications 40%40%
n=866n=866
39
Results of Self-Selection Results of Self-Selection
Correct self-selection ofCorrect self-selection ofall 6 selection criteriaall 6 selection criteria: : 81%81%
Heartburn Heartburn 2 days per week 2 days per week
18 years of age18 years of age
Not allergic to omeprazoleNot allergic to omeprazole
Not pregnant or nursingNot pregnant or nursing
No general warning signsNo general warning signs
No drug-drug interactionsNo drug-drug interactionsn=866n=866
40People Who Did Not CorrectlyPeople Who Did Not CorrectlySelf- SelectSelf- Select
< 18 years of age< 18 years of age 33
Pregnant/nursingPregnant/nursing 1 1
Allergic to omeprazoleAllergic to omeprazole 0 0
General warning signsGeneral warning signs 82 82
Drug-drug interactionsDrug-drug interactions 8 8
Infrequent heartburnInfrequent heartburn 86 86
NumberNumberof Subjectsof Subjects
n=866n=866
41Disposition of Subjects WhoDisposition of Subjects WhoPurchased ProductPurchased Product
Agreed to Purchase ProductAgreed to Purchase Product[Self-Selection Population][Self-Selection Population]
n = 866n = 866
Agreed to Purchase ProductAgreed to Purchase Product[Self-Selection Population][Self-Selection Population]
n = 866n = 866
WithdrewWithdrewConsentConsent n = 4n = 4Did Not MeetDid Not MeetStudy CriteriaStudy Criteria n = 8n = 8
WithdrewWithdrewConsentConsent n = 4n = 4Did Not MeetDid Not MeetStudy CriteriaStudy Criteria n = 8n = 8
No DiaryNo Diaryn = 96n = 96
No DiaryNo Diaryn = 96n = 96
Used Product and Used Product and Returned DiaryReturned Diary
[Use Population][Use Population]n = 758n = 758
Used Product and Used Product and Returned DiaryReturned Diary
[Use Population][Use Population]n = 758n = 758
42Subjects Are Compliant WithSubjects Are Compliant WithDosing DirectionsDosing Directions
No more than No more than 1 tablet per dose1 tablet per dose 96%96%
99% 99%
No more than No more than 1 tablet per day1 tablet per day 91%91%
98%98%
Per DosingPer Dosing Occasion OccasionPer SubjectPer Subject
43Compliance With the 14-DayCompliance With the 14-DayDosing RegimenDosing Regimen
Definition of complianceDefinition of compliance– 80-100% of the product within80-100% of the product within
14 14 ± 3 ± 3 daysdays
– Physician consultation if exceeded Physician consultation if exceeded 14 doses14 doses
(11-14 doses within 11-17 days)(11-14 doses within 11-17 days)
44Compliance With the 14-DayCompliance With the 14-DayDosing RegimenDosing Regimen
People achieved high People achieved high compliance withcompliance withdosing directionsdosing directions
79%79%AccordingAccording
to label to label directionsdirections
3% > 14 doses w/o 3% > 14 doses w/o doctor contactdoctor contact
9% 11-14 doses in > 17 days9% 11-14 doses in > 17 days
< 1% Multiple daily doses< 1% Multiple daily doses
9% < 11 doses9% < 11 doses
45
Rx Therapy15%
Return of Frequent HeartburnReturn of Frequent HeartburnFour Weeks After TrialFour Weeks After Trial
No Medication8%
Antacids 22%
H2RA
9%
Antacids + H2RAs3%
No FrequentHeartburn
43%
46
Actual Use Study: ConclusionsActual Use Study: Conclusions
Consumers appropriately self-selectConsumers appropriately self-select
Consumers understood the labelConsumers understood the label
Consumers used product for prevention of frequent Consumers used product for prevention of frequent heartburnheartburn
Consumers used omeprazole according to label Consumers used omeprazole according to label directionsdirections
47
SummarySummary
Indication Indication – Prevention of the symptoms of frequent Prevention of the symptoms of frequent
heartburn for 24 hoursheartburn for 24 hours
Dose Dose – 20 mg of omeprazole as omeprazole 20 mg of omeprazole as omeprazole
magnesiummagnesium
Directions for useDirections for use– Take 1 tablet in the morningTake 1 tablet in the morning
– Take every day for 14 daysTake every day for 14 days
48
Our proposed label, the efficacy data Our proposed label, the efficacy data and the consumer’s abilityand the consumer’s ability
to understand and use this product to understand and use this product safely and appropriately are congruentsafely and appropriately are congruent
49
OTC OmeprazoleOTC OmeprazoleUpdate on SafetyUpdate on Safety
Doug Levine, M.D.Doug Levine, M.D.
Chief Medical OfficerChief Medical OfficerAstraZeneca LPAstraZeneca LP
50
OTC Omeprazole Product SafetyOTC Omeprazole Product Safety
Product safety is defined as adverse Product safety is defined as adverse events occurring in relation to product events occurring in relation to product use during short or long termuse during short or long term
Safety of omeprazole is established Safety of omeprazole is established based on:based on:
Clinical trials with Rx productClinical trials with Rx product Rx post-marketing surveillance Rx post-marketing surveillance OTC clinical trialsOTC clinical trials
Adverse event profile of omeprazole is Adverse event profile of omeprazole is established, and is acceptable for OTCestablished, and is acceptable for OTC
51
OTC Omeprazole Product SafetyOTC Omeprazole Product Safety
Sponsor intent = short term useSponsor intent = short term use
If unintended long-term use occurs If unintended long-term use occurs without medical supervision, product without medical supervision, product adverse event profile is acceptable adverse event profile is acceptable (based on Rx product experience)(based on Rx product experience)
52Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the Product Related to the Product
Potential consequences of consumer Potential consequences of consumer behavior without medically behavior without medically supervised usesupervised use
Involves medical diseases other than Involves medical diseases other than acid reflux diseaseacid reflux disease
Involves the natural history of acid reflux Involves the natural history of acid reflux induced damage to the esophagusinduced damage to the esophagus
Not directly linked to omeprazoleNot directly linked to omeprazole
53Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the ProductRelated to the Product
Not likely with alarm symptoms (labeled)Not likely with alarm symptoms (labeled)– Dysphagia (trouble swallowing food)Dysphagia (trouble swallowing food)
– Frequent chest painFrequent chest pain
– Unexplained weight lossUnexplained weight loss
– Frequent wheezing, chronic coughFrequent wheezing, chronic cough
– Chest pain with shortness of breath; sweating; Chest pain with shortness of breath; sweating; pain spreading to arm, neck or shoulders; or pain spreading to arm, neck or shoulders; or lightheadednesslightheadedness
54Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the ProductRelated to the Product
Possible with responders who do not seek Possible with responders who do not seek medical advice (despite label instructions):medical advice (despite label instructions):
Non-neoplastic upper GI conditionNon-neoplastic upper GI condition
– Esophageal erosionsEsophageal erosions
– Gastric/duodenal ulcersGastric/duodenal ulcers
Upper GI malignanciesUpper GI malignancies
Upper GI conditions with risk of malignancyUpper GI conditions with risk of malignancy
55Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the ProductRelated to the Product
Unlikely with upper GI malignancy Unlikely with upper GI malignancy (esophagus, stomach)(esophagus, stomach)
Different symptoms (e.g., dysphagia, Different symptoms (e.g., dysphagia, nausea, vomiting, early satiety, weight nausea, vomiting, early satiety, weight loss) do not respond to omeprazoleloss) do not respond to omeprazole
Malignancy usually present at first Malignancy usually present at first presentation for medical care, without presentation for medical care, without antecedent heartburn, other symptomsantecedent heartburn, other symptoms
Malignancy is unusual in endoscoped Malignancy is unusual in endoscoped populations with frequent heartburnpopulations with frequent heartburn
56Long-term Safety Issues Not Directly Long-term Safety Issues Not Directly Related to the ProductRelated to the Product
Possible with upper GI conditions with risk Possible with upper GI conditions with risk of malignancyof malignancy
Barrett’s esophagus (complication of acid reflux Barrett’s esophagus (complication of acid reflux induced esophageal damage)induced esophageal damage)
Common, but rare progression to malignancyCommon, but rare progression to malignancy
Difficult to effectively manage cancer riskDifficult to effectively manage cancer risk
Omeprazole does not increase cancer riskOmeprazole does not increase cancer risk
Omeprazole does not induce regression Omeprazole does not induce regression
57
Heartburn and Esophageal CancerHeartburn and Esophageal Cancer
Increasing incidence of esophageal Increasing incidence of esophageal adenocarcinoma is not related toadenocarcinoma is not related toacid reducersacid reducers
Afflicted patients generally present without Afflicted patients generally present without heartburn or Barrett’s esophagusheartburn or Barrett’s esophagus
Presently, incidence rate approximately Presently, incidence rate approximately equals mortality rate for this cancer, equals mortality rate for this cancer, suggesting lack of clinical “signal” to draw suggesting lack of clinical “signal” to draw medical attentionmedical attention
No evidence that acid reducers mask such No evidence that acid reducers mask such “signals”“signals”
Cancer development is rareCancer development is rare Omeprazole does not increase cancer riskOmeprazole does not increase cancer risk
58
ConclusionsConclusions
Product-related safety profile of Product-related safety profile of omeprazole is acceptableomeprazole is acceptable
The natural history of esophageal acid The natural history of esophageal acid reflux damage can involve rare, serious reflux damage can involve rare, serious consequencesconsequences
Omeprazole does not directly increase the Omeprazole does not directly increase the risk of esophageal adenocarcinomarisk of esophageal adenocarcinoma
Based on overall safety considerations, Based on overall safety considerations, omeprazole is acceptable for OTC useomeprazole is acceptable for OTC use
59
Benefit/Risk Assessment Benefit/Risk Assessment of Omeprazole in the of Omeprazole in the
OTC MarketOTC Market
Nora Zorich, M.D., Ph.D.Nora Zorich, M.D., Ph.D.Vice President Pharmaceuticals Vice President Pharmaceuticals
Procter & GambleProcter & Gamble
60Considerations of Chronic Use of Considerations of Chronic Use of Omeprazole Without Physician Involvement Omeprazole Without Physician Involvement
1.1. What proportion of consumers may use What proportion of consumers may use OTC omeprazole on a regular basis?OTC omeprazole on a regular basis?
2.2. Do consumers with FHB go to their Do consumers with FHB go to their physicians? Will OTC omeprazole physicians? Will OTC omeprazole change that?change that?
3.3. What benefits and risks might result What benefits and risks might result from use without physician from use without physician involvement?involvement?
61
NDC Prescription Database: PPI UseNDC Prescription Database: PPI Use
1.1. What Proportion of Consumers May Use What Proportion of Consumers May Use OTC Omeprazole on a Regular Basis?OTC Omeprazole on a Regular Basis?
20.720.76+6+
4.44.455
6.26.244
9.09.033
15.415.422
44.344.311
Patients (%)Patients (%)Rx Dispensed/YearRx Dispensed/Year
62
Bardhan Study DesignBardhan Study Design
1.1. What Proportion of Consumers May Use What Proportion of Consumers May Use OTC Omeprazole on a Regular Basis?OTC Omeprazole on a Regular Basis?
Patients with frequent heartburnPatients with frequent heartburn
Controlled study to assess omeprazole Controlled study to assess omeprazole usage pattern over 1 year periodusage pattern over 1 year period
Omeprazole 20mg daily for 14 daysOmeprazole 20mg daily for 14 days
If FHB returned (in 1 year) patients selfIf FHB returned (in 1 year) patients selfmanaged additional courses of therapy managed additional courses of therapy
Bardhan et al., BMJ, 1999, 18:502-507Bardhan et al., BMJ, 1999, 18:502-507
63
Bardhan Study ResultsBardhan Study Results
1.1. What Proportion of Consumers May Use What Proportion of Consumers May Use OTC Omeprazole on a Regular Basis?OTC Omeprazole on a Regular Basis?
72% used intermittent 14-day regimens72% used intermittent 14-day regimens
– Of these, 68% requested 3 or fewer Of these, 68% requested 3 or fewer treatment courses over the yeartreatment courses over the year
– Symptom control after 2 weeks was a Symptom control after 2 weeks was a strong predictor of outcomestrong predictor of outcome
28% required maintenance therapy at 28% required maintenance therapy at some point during the yearsome point during the year
Bardhan et al., BMJ, 1999, 18:502-507Bardhan et al., BMJ, 1999, 18:502-507
64
Actual Use Trial ResultsActual Use Trial Results
No Frequent Heartburn
43%
Antacids/H2RAs/No Medicine
42%
1.1. What Proportion of Consumers May Use What Proportion of Consumers May Use OTC Omeprazole on a Regular Basis?OTC Omeprazole on a Regular Basis?
Rx Therapy15%
651.1. What Proportion of Consumers May Use What Proportion of Consumers May Use OTC Omeprazole on a Regular Basis?OTC Omeprazole on a Regular Basis?
Administrative claims databaseAdministrative claims database– 21% used chronically21% used chronically
Published literaturePublished literature– 28% required maintenance therapy28% required maintenance therapy
Actual Use TrialActual Use Trial– 15% returned to prescription PPI15% returned to prescription PPI– An additional 4% took two or moreAn additional 4% took two or more
14 day regimens14 day regimensMost of the people who use Most of the people who use
omeprazole don’t use it chronicallyomeprazole don’t use it chronically
66
1.1. What proportion of consumers may use What proportion of consumers may use OTC omeprazole on a regular basis??OTC omeprazole on a regular basis??
2.2. Do consumers with FHB go to their Do consumers with FHB go to their physicians? Will OTC omeprazole physicians? Will OTC omeprazole change that?change that?
3.3. What benefits and risks might result What benefits and risks might result from use without physician from use without physician involvement?involvement?
Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement
67
Oliveria Study DesignOliveria Study Design
2.2. Do Consumers With FHB Go toDo Consumers With FHB Go toTheir Physicians?Their Physicians?
Survey of 2000 people with heartburnSurvey of 2000 people with heartburn
How they understand their heartburnHow they understand their heartburn
How they manage their symptomsHow they manage their symptoms
How often they have physician How often they have physician contactcontact
Oliveria et al., Arch Intern Med. 1999;159:1592-1598Oliveria et al., Arch Intern Med. 1999;159:1592-1598
68
Oliveria Study ResultsOliveria Study Results
2.2. Do Consumers With FHB Go toDo Consumers With FHB Go toTheir Physicians? Their Physicians?
Over 90% were taking therapy for Over 90% were taking therapy for symptomssymptoms
Physician contact directly correlates Physician contact directly correlates to the frequency of symptomsto the frequency of symptoms– People with frequent HB were 4 times People with frequent HB were 4 times
more likely to see their physicianmore likely to see their physician
– 78% of people with most frequent HB 78% of people with most frequent HB had physician contacthad physician contact
Oliveria et al., Arch Intern Med. 1999;159:1592-1598Oliveria et al., Arch Intern Med. 1999;159:1592-1598
69
OTC HOTC H22RA’s Effect on Physician VisitsRA’s Effect on Physician Visits
2.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That? Physicians? Will OME Change That?
Fallon Community Healthcare SystemFallon Community Healthcare System– 2000 patients with acid-related diseases2000 patients with acid-related diseases
Minneapolis Cross-Sectional Survey Minneapolis Cross-Sectional Survey (1993-1997)(1993-1997)– 3400 consumers3400 consumers
MEDSTAT Marketscan data base MEDSTAT Marketscan data base (1995-1998)(1995-1998)– Database of >7 million peopleDatabase of >7 million people
70
Fallon Community Healthcare SystemFallon Community Healthcare SystemPre & Post OTC HPre & Post OTC H22RARA
2.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That?Physicians? Will OME Change That?
0.670.670.720.72GERD-related GERD-related clinic visits/yr clinic visits/yr (mean)(mean)
7/95-7/967/95-7/967/94-7/957/94-7/95
33SE Andrade et al, Med Care; 1999; 37:424-430SE Andrade et al, Med Care; 1999; 37:424-430
71
Minneapolis Cross-Sectional Survey:Minneapolis Cross-Sectional Survey:Physician Visits in Past YearPhysician Visits in Past Year
2.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That?Physicians? Will OME Change That?
23.523.522.022.0DyspepsiaDyspepsia
21.921.923.623.6HeartburnHeartburn
19971997(n=1238)(n=1238)
%%
19931993(n=1141)(n=1141)
%%
MJ. Shaw et al, Am J Gastroenterol 2001, 96(3):673-6MJ. Shaw et al, Am J Gastroenterol 2001, 96(3):673-6
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MEDSTAT Marketscan Data BaseMEDSTAT Marketscan Data Base1995-19981995-1998
2.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That?Physicians? Will OME Change That?
2.122.122.002.002.042.04
0.160.160.180.180.160.160.140.14
UGIUGIEndoscopyEndoscopy(% of pop)(% of pop)
19981998199719971996199619951995
2.092.09
Visits/UGIVisits/UGIDx Code (mean)Dx Code (mean)
732.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That?Physicians? Will OME Change That?
Rate of physician consultation for Rate of physician consultation for heartburn doubled during the studyheartburn doubled during the study
20% contacted a doctor for the first 20% contacted a doctor for the first time about their heartburn duringtime about their heartburn duringthe study the study
53% of people taking more than53% of people taking more than14 doses, talked to their physician 14 doses, talked to their physician during or just after the studyduring or just after the study
Actual Use Trial ResultsActual Use Trial Results
742.2. Do Consumers With FHB Go to Their Do Consumers With FHB Go to Their Physicians? Will OME Change That?Physicians? Will OME Change That?
The majority of people with FHB The majority of people with FHB see a doctor for their symptomssee a doctor for their symptoms
Physician visits stayed the same Physician visits stayed the same after Hafter H22RA’s were available OTCRA’s were available OTC
The Actual Use Trial suggests The Actual Use Trial suggests that physician visits will not that physician visits will not decrease and may increasedecrease and may increasewith OTC omeprazolewith OTC omeprazole
75
1.1. What proportion of consumers may use What proportion of consumers may use OTC omeprazole on a regular basis?OTC omeprazole on a regular basis?
2.2. Do consumers with FHB go to their Do consumers with FHB go to their physicians? Will OTC omeprazolephysicians? Will OTC omeprazolechange that?change that?
3.3. What benefits and risks might result from What benefits and risks might result from use without physician involvement?use without physician involvement?
Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement
763.3. Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement
The label is clear - see physician if The label is clear - see physician if FHB returnsFHB returns
OTC omeprazole a better option than OTC omeprazole a better option than current OTC therapiescurrent OTC therapies
Benefit to UserBenefit to User
77Short-term PPI Superior to Long-Term Short-term PPI Superior to Long-Term HH22RA for Healing of EsophagitisRA for Healing of Esophagitis
Chiba et al., Gastroenterology 1997, 112:1798-1810Chiba et al., Gastroenterology 1997, 112:1798-1810
783.3. Considerations of OTC Chronic Use of Considerations of OTC Chronic Use of Omeprazole Without Physician InvolvementOmeprazole Without Physician Involvement
The majority of consumers won’t The majority of consumers won’t use chronicallyuse chronically
Consumers who use chronically Consumers who use chronically will involve their physicianwill involve their physician
The risks of use without physician The risks of use without physician involvement are minimal and the involvement are minimal and the benefits are substantialbenefits are substantial
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SummarySummary
Omeprazole will fill a critical gap in OTC Omeprazole will fill a critical gap in OTC for frequent heartburnfor frequent heartburn
The target population is those people with The target population is those people with frequent heartburnfrequent heartburn
The label is understood and it is congruent The label is understood and it is congruent with OTC omeprazole usewith OTC omeprazole use
The label should specify a 14-day regimenThe label should specify a 14-day regimen
Omeprazole is acceptable for use OTCOmeprazole is acceptable for use OTC
80
ConclusionConclusion
Omeprazole can be safely Omeprazole can be safely and effectively used OTCand effectively used OTC
81