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![Page 1: COMBINATION HORMONAL CONTRACEPTION: Translation of Clinical Trial Findings of Efficacy and Safety into “Real World” Effectiveness and Safety Paula J. Adams.](https://reader030.fdocuments.us/reader030/viewer/2022032600/56649dbb5503460f94aac8a2/html5/thumbnails/1.jpg)
COMBINATION HORMONAL CONTRACEPTION:
Translation of Clinical Trial Findings of Efficacy and Safety into “Real World”
Effectiveness and Safety
Paula J. Adams Hillard, M.D.Paula J. Adams Hillard, M.D.
University of CincinnatiUniversity of Cincinnati
Professor, Department of Obstetrics and Gynecology Professor, Department of Obstetrics and Gynecology andand
Department of PediatricsDepartment of Pediatrics
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Hatcher, R., J. Trussell, et al. (2004). Contraceptive Technology.18th ed. New York, NY, Ardent Media, Inc.
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Factors That Influence Efficacy Results in Practice &
in Research • Inherent method efficacy• User characteristics
• Consistency and correctness of method use
• Fecundity
• Frequency of Intercourse
• Age• Parity
• Influence of the Investigator
Design of the Study• Participation criteria• Methods for documenting
pregnancy outcomes• Use of additional
methods (EC, initial dual methods)
• Study duration
ARHP Slide Set 2000
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1315
13
10
67
64
<=19 20-24 25-29 >=300
5
10
15
20
Poor/Low Income
Higher Income
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Terminology
• Compliance• Paternalistic--Clinician centered
• “Cheerful obedience”--Westhof• Fails to acknowledge the therapeutic alliance
between clinician and patient
• Adherence (a part of “illness management”)• Re: Contraception
• “Successful Use”--Woman centered• Meeting her own family planning goals
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CONTRACEPTIVE COMPLIANCE
--Correct use
--Consistent use
--Continuing use
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Compliance with Contraceptives and Other
Treatments• “Contraceptive compliance can be placed in the
context of compliance with other medications.• The potential consequence of failing to comply with
contraception is pregnancy. • The literature on compliance suggests that there is
no consequence of failed compliance that is severe or onerous enough to assure complete compliance.”
Cramer, J.A.Obstet Gynecol, Vol. 88; 1989
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ADHERENCEADHERENCE
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Consequences of Inconsistent Use of Consequences of Inconsistent Use of Effective Contraceptives in U.S.Effective Contraceptives in U.S.Consequences of Inconsistent Use of Consequences of Inconsistent Use of Effective Contraceptives in U.S.Effective Contraceptives in U.S.
• Inconsistent/ improper OC usage or discontinuation of OCs results in ~1 million unintended pregnancies/year in the U.S.
.Rosenberg MJ, et al. Reprod Med. 1995;40:355-360.
Overview
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“The accurate measurement of
compliance is not easy; easy measurements of
compliance are not accurate."
Sackett,D in
Compliance in Health Care. R. B. Haynes, D. W. Taylor and D. L. Sackett. Johns Hopkins University Press; 1979
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MEASURING PILL-TAKING• Direct Methods
• Directly observed therapy• Measurement of blood levels• Measurement of biological marker in blood
• Indirect Methods• Self-reports• Pill counts• Rates of prescription refills• Assessment of clinical response• Electronic medication monitor• Measurement of physiologic markers• Patient diaries• When patient is a child, asking caregiver
Osterberg, L. and T. Blaschke (2005). "Adherence to Medication." N Engl J Med
353(5): 487-497.
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Oakley D et al. Oakley D et al. Fam Plann Perspect.Fam Plann Perspect. 1991;23:150-154. 1991;23:150-154.
Pill-Taking Behaviors by Age
0
10
20
30
40
50
60
70
80
90
100
Takes a pill qd Takes pillsame time qd
Takes pills insame order
Uses backup ifforgets
Takes onlyown pills
Perc
en
t'
<=14 15-17 18-19 20-24 25-29 >=30
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0
10
20
30
40
50
60
0 1 2 3 0 1 2 3 0 1 2 3
Diary
ElectronicDevice
Cycle 1Cycle 1 Cycle 3Cycle 3Cycle 2Cycle 2
Reported Pill Use vs Actual Pill UseReported Pill Use vs Actual Pill Use
Active Pills MissedActive Pills Missed
% o
f W
om
en%
of
Wo
men
(Ag
es 1
8 an
d o
lder
)(A
ges
18
and
old
er)
Potter L et al. Family Planning Perspectives. 1996. 2(4):154-158.
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Patterns of OC Pill-taking in Adults
50% of young women report imperfect pill use 50% of young women report imperfect pill use during a pill cycleduring a pill cycle• Potter L et al. Fam Plann Perspect 1996;28(4)154-8Potter L et al. Fam Plann Perspect 1996;28(4)154-8
• Oakley D et al. Fam Plann Perspect 1997;29(6)277-9, 287Oakley D et al. Fam Plann Perspect 1997;29(6)277-9, 287
Approximately 25% of OCP users miss 2 or more Approximately 25% of OCP users miss 2 or more pills during a pill cyclepills during a pill cycle• Oakley D et al. Fam Plann Perspect 1997;29(6)277-9, 287Oakley D et al. Fam Plann Perspect 1997;29(6)277-9, 287
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OC Continuation RatesOC Continuation Rates
50
55
60
65
70
75
80
85
90
95
100
0 1 2 3 4 5 6
OC switchersAll OC usersNew OC starts
Adapted from Rosenberg MJ et al. Adapted from Rosenberg MJ et al. Am J Obstet GynecolAm J Obstet Gynecol. 1998;179:577-582. 1998;179:577-582
Study MonthStudy Month
Co
nti
nu
atio
n R
ate
Co
nti
nu
atio
n R
ate
(( pe
r 1
00
Wo
me
n E
nro
lled
)p
er
10
0 W
om
en
En
rolle
d)
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INCONSISTENT PILL USE
0
5
10
15
20
25
30
All Pill Only Pill plus
15-1920-2425-44
NSFG 1995. Peterson et al. FP Persp.1998 30(1):19-23NSFG 1995. Peterson et al. FP Persp.1998 30(1):19-23
Inconsistent = Self-report of >= 2 missed pills in past 3 monthsInconsistent = Self-report of >= 2 missed pills in past 3 months
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ADOLESCENT PREGNANCYADOLESCENT PREGNANCYAn International PerspectiveAn International PerspectiveADOLESCENT PREGNANCYADOLESCENT PREGNANCYAn International PerspectiveAn International Perspective
0102030405060708090
United S
tate
s
Hunga
ry
New Z
eala
ndUK
Canad
a
Austral
ia
Slova
k Rep
Icela
nd
Czech
Rep
Norway
Sweden
Denm
ark
France
Finla
nd
Belgiu
m
Gre
eceIta
lySpai
n
Nether
lands
Japan
Births Abortions
UNICEF Innocenti Report Card #3, July 2001
Per
100
0 15
-19
year
old
s
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Patterns of OC Pill-taking in Adolescents
““Effective OCP use requires method commitment ( i.e., Effective OCP use requires method commitment ( i.e., considering one’s birth control method to be OCP) as well considering one’s birth control method to be OCP) as well as OCP use consistent with the method’s pharmacology as OCP use consistent with the method’s pharmacology and mechanism of action (i.e., method adherence).”and mechanism of action (i.e., method adherence).”
Many young women are at risk, especially during Many young women are at risk, especially during transitions into or out of periods of OCP usetransitions into or out of periods of OCP use
Even among young women with stable patterns of OCP Even among young women with stable patterns of OCP method choice, many have daily pill-taking patterns that method choice, many have daily pill-taking patterns that are sufficiently inconsistent to increase pregnancy riskare sufficiently inconsistent to increase pregnancy risk
Woods, JL et al JAH 2006; 29(3):381-7
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Patterns of OC Pill-taking in Adolescents
Categorized by pattern of useCategorized by pattern of use• Stable/3 monthsStable/3 months
• StartingStarting
• StoppingStopping
Daily DiariesDaily Diaries
Results:Results:• Mean days of consecutive OCP 20-32.5/ 3 mosMean days of consecutive OCP 20-32.5/ 3 mos
• Mean days of sequential missed OCP 17-31/ 3 mosMean days of sequential missed OCP 17-31/ 3 mos
• Episodes of 3 or > missed OCP 1.9-2.2 / 3 mosEpisodes of 3 or > missed OCP 1.9-2.2 / 3 mos
• 27% of coital events occurred during a period of 2 or more missed pills27% of coital events occurred during a period of 2 or more missed pills
Woods, JL et al JAH 2006; 29(3):381-7
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OC Continuation in Adolescents
18-57% of teenagers discontinued use of a 18-57% of teenagers discontinued use of a contraceptive within a yearcontraceptive within a year• Furstenberg et al. Contraceptive continuation among Furstenberg et al. Contraceptive continuation among
adolescents attending family planning clinics. Fam adolescents attending family planning clinics. Fam Plann Perspect 1983;15;211-7Plann Perspect 1983;15;211-7
50% failed to return to clinic at 3 months--all of 50% failed to return to clinic at 3 months--all of these had discontinued and 69% at risk for these had discontinued and 69% at risk for pregnancypregnancy• Balassone. Risk of contraceptive discontinuation Balassone. Risk of contraceptive discontinuation
among adolescents. J Adol Health Care.1989;10:527-among adolescents. J Adol Health Care.1989;10:527-3333
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OC Continuation in Adolescents
Mean wait after coitarche before coming to clinic Mean wait after coitarche before coming to clinic • 1.4 years1.4 years
““inconsistent” (Discontinuing) usersinconsistent” (Discontinuing) users• Missed 3.4 pills/monthMissed 3.4 pills/month
““Consistent” (Continuing) usersConsistent” (Continuing) users• Missed 2.7 pills/monthMissed 2.7 pills/month
Balassone. Risk of contraceptive discontinuation among Balassone. Risk of contraceptive discontinuation among adolescents. J Adol Health Care.1989;10:527-33adolescents. J Adol Health Care.1989;10:527-33
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FACTORS INFLUENCING SUCCESSFUL USE OF
HORMONAL CONTRACEPTIVES Side Effects/Fear of Side EffectsSide Effects/Fear of Side Effects
• BleedingBleeding
• Weight gainWeight gain
Concerns about safetyConcerns about safety• Make you sickMake you sick
• Make you infertileMake you infertile
• Cause cancerCause cancer
Influences on useInfluences on use• Family membersFamily members
• BoyfriendBoyfriend
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OPTIONS AFTER OPTIONS AFTER DISCONTINUING OCsDISCONTINUING OCs
Continued sexual activityContinued sexual activity• With alternative method of contraception With alternative method of contraception
• Effective method--hormonalEffective method--hormonal
• Less effective methodLess effective method
• Without contraceptionWithout contraception
Celibacy/AbstinenceCelibacy/Abstinence
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OC Use in AdolescentsOC Use in AdolescentsDecreased Dysmenorrhea and ComplianceDecreased Dysmenorrhea and Compliance
Reduction of dysmenorrhea was the most Reduction of dysmenorrhea was the most statistically and clinically significant predictor statistically and clinically significant predictor of consistent OC use of consistent OC use
Adolescents with severe dysmenorrhea who Adolescents with severe dysmenorrhea who experienced positive side effects (decreased experienced positive side effects (decreased cramping or flow) were 8 times more likely to cramping or flow) were 8 times more likely to be consistent pill users (missed be consistent pill users (missed 3 pills per 3 pills per month) than othersmonth) than others
Robinson et al. Am J Obstet Gynecol. 1992;166:578-583.
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Barriers to Adherence
Osterberg, L. and T. Blaschke (2005).
"Adherence to Medication." N Engl J Med 353(5): 487-
497.
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LOGISTICAL FACTORSLOGISTICAL FACTORSAffecting OC ContinuationAffecting OC Continuation
$/ Insurance/ HMO Coverage$/ Insurance/ HMO Coverage• One month at a timeOne month at a time
• FormularyFormulary
• GenericsGenerics
Office/ Clinic HoursOffice/ Clinic Hours
Sunday startSunday start
Extended cycle requirements for additional Extended cycle requirements for additional pillspills
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OC Continuation:OC Continuation:Access/Pill Packages DispensedAccess/Pill Packages Dispensed
Women receiving 13 cycles of OCs were Women receiving 13 cycles of OCs were more likely to be continuing to get pills one more likely to be continuing to get pills one year later than those receiving 1 or 3 cycles year later than those receiving 1 or 3 cycles 49% vs 46% vs 42% (p< .001) 49% vs 46% vs 42% (p< .001)
Continuous use at 15 months:Continuous use at 15 months:• 13 cycles 43%13 cycles 43%
• 3 cycles 22%3 cycles 22%
• 1 cycle 20% (p< .001)1 cycle 20% (p< .001)
Foster, D. G., R. Parvataneni, et al. (2006). "Number of Oral Contraceptive Pill Packages Dispensed, Method
Continuation, and Costs." Obstet Gynecol 108(5): 1107-1114.
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