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

Hatcher, R., J. Trussell, et al. (2004). Contraceptive Technology.18th ed. New York, NY, Ardent Media, Inc.

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

1315

13

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64

<=19 20-24 25-29 >=300

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Poor/Low Income

Higher Income

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

CONTRACEPTIVE COMPLIANCE

--Correct use

--Consistent use

--Continuing use

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

ADHERENCEADHERENCE

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

“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

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.

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

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Takes a pill qd Takes pillsame time qd

Takes pills insame order

Uses backup ifforgets

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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

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Potter L et al. Family Planning Perspectives. 1996. 2(4):154-158.

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

OC Continuation RatesOC Continuation Rates

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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

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INCONSISTENT PILL USE

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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

ADOLESCENT PREGNANCYADOLESCENT PREGNANCYAn International PerspectiveAn International PerspectiveADOLESCENT PREGNANCYADOLESCENT PREGNANCYAn International PerspectiveAn International Perspective

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United S

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Births Abortions

UNICEF Innocenti Report Card #3, July 2001

Per

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-19

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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

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

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

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

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

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

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.

Barriers to Adherence

Osterberg, L. and T. Blaschke (2005).

"Adherence to Medication." N Engl J Med 353(5): 487-

497.

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

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.