# Presentation: 815661

## COMBINATION HORMONAL CONTRACEPTION:

**COMBINATION HORMONAL CONTRACEPTION:**

**Translation of Clinical Trial Findings of Efficacy and Safety into “Real World” Effectiveness and Safety**

**Paula J. Adams Hillard, M.D.**
**University of Cincinnati**
**Professor, Department of Obstetrics and Gynecology            and**
** ****Department of Pediatrics**

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

- 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

**Notes:**
In addition to math errors, the task of determining efficacy “fairly” is also complicated by the impact that many different factors have on method efficacy in practice or in a research study. These factors are especially important for methods that have lower inherent efficacy and/or require substantial ongoing user effort for correct use.
Methods that have high inherent efficacy (such as vasectomy, implants or IUD) have little variation in rates found in research.

## Slide 4

## 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**

## ADHERENCE

** **

**ADHERENCE**

## Consequences of Inconsistent Use of 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**

**Notes:**
A prospective, multicenter US study, was designed to evaluate poststerilization regret
It was found that among 11,232 women aged 18-44 years who underwent tubal sterilization, approximately 20% who were 30 years or younger later expressed regret
Using a decision tree to follow a cohort of OC users for one year, Rosenberg et al.,  estimate that over 1 million unintended pregnancies are related to OC use, misuse or discontinuation.  A staggering number considering that approximately 3.7 million women begin taking OCs in the US each year    

## “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.

## Pill-Taking Behaviors by Age

- Oakley D et al. *Fam Plann Perspect.* 1991;23:150-154.

**Pill-Taking Behaviors by Age**

**Notes:**
Pill-Taking Behaviors by Age
In a study examining behaviors related to effective contraceptive use, the authors found that, on average, only 42% of women took their pills every day. Only 19% of women took their pills at the same time every day; 88% reported using a backup method if  they forgot to take their pill; and 98% reported taking their pills in the same order.  When examining pill-taking behaviors by age, most behaviors were worse in the youngest adolescent age group. 

Reference:
Oakley D, Sereika S, Bogue EL.  Oral contraceptive pill use after an initial visit to a family planning clinic. Fam Plann Perspect. 1991;23:150-154.

## Reported Pill Use vs Actual Pill Use

****

****

****

**Active Pills Missed**

**% of Women**
**(Ages 18 and older)**

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

**Notes:**
Slide <number>
Reported Pill Use vs Actual Pill Use
Irregular use of an OC compromises its effectiveness. Patient reports of proper use are often unreliable, a finding that is typical of other groups of patients who take daily medication.
This 3-month study compared self-reported data (patient recall via diary) on OC-taking with data from an electronic device* among more than 100 women (ages 18 and older) who attended a university’s health service or a publicly funded family clinic in two states.†  Women returned each month for pills.
In each cycle, more women missed pills as recorded by the electronic device than as reported via the diary. For example, in cycle one, 58% of women reported that they had not missed taking any pills. However, the electronic device showed this percentage was much lower — 33%.
In all cycles, diary reporting was much less accurate than with the electronic device. The percentage of women who reported missing 3 or more active pills was considerably lower than what was recorded electronically (cycles 1 and 2, 10% vs 30-34%; cycle 3, 14% vs 51%).
In contrast to what might be expected (ie, proper pill use improving over time), the proportion of women who missed no active pills declined from cycle 1 to cycle 3 (33% to 19%) as recorded by the electronic device. This provides strong evidence that reinforcement of correct use must be ongoing.
* Medication Event Monitoring System (MEMS) was used to record presumptive taking of OC. With this device, a battery, clock and microchip were incorporated into a monitoring device attached via a thin casing to the bottom of a normal OC package. When a pill was removed, the microchip recorded the exact time and date of removal (presumed pill-taking time). Data were then analyzed by computer.
†There was no significant difference between data obtained from women attending the university health service and the family clinic.
Reproduced with the permission of The Alan Guttmacher Institute from: Potter L et al, Measuring compliance among oral contraceptive users, Family Planning Perspectives, 1996;28(4):154-158.
Guerrero D, Rudd P, Bryant-Kosling C, Middleton F. Antihypertensive medication-taking: investigation of a simple regimen. Am J Hypertens. 1993;6:586-592; Potter L, Oakley D, de Leon-Wong E, Cañamare R. Measuring compliance among oral contraceptive users. Fam Plann Perspect. 1996;28(4):154-158; Rudd P, Ramesh J, Bryant-Kosling C, Guerrero D. Gaps in cardiovascular medication taking: the tip of the iceberg. J Gen Intern Med. 1993;8:659-666.

## Patterns of OC Pill-taking in Adults

**50% of young women report imperfect pill use during a pill cycle**
**Potter L et al. Fam Plann Perspect 1996;28(4)154-8**
**Oakley D et al. Fam Plann Perspect 1997;29(6)277-9, 287**
**Approximately 25% of OCP users miss 2 or more pills during a pill cycle**
**Oakley D et al. Fam Plann Perspect 1997;29(6)277-9, 287**

## Slide 15

## OC Continuation Rates

**Adapted from Rosenberg  MJ  et al.  *****Am J Obstet Gynecol*****. 1998;179:577-582**

**Study Month**

**Continuation Rate**
**(*****per 100 Women Enrolled)***

## INCONSISTENT PILL USE

**NSFG 1995. Peterson et al. FP Persp.1998 30(1):19-23**

**Inconsistent = Self-report of >= 2 missed pills in past 3 months**

## ADOLESCENT PREGNANCYAn International Perspective

**UNICEF Innocenti Report Card #3, July 2001**

**Per 1000 15-19 year olds**

## Patterns of OC Pill-taking in Adolescents

**“****Effective OCP use requires method commitment ( i.e., considering one’s birth control method to be OCP) as well as OCP use consistent with the method’s pharmacology and mechanism of action (i.e., method adherence).”**
**Many young women are at risk, especially during transitions into or out of periods of OCP use**
**Even among young women with stable patterns of OCP method choice, many have daily pill-taking patterns that are 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 use**
**Stable/3 months**
**Starting**
**Stopping**
**Daily Diaries**
**Results:**
**Mean days of consecutive OCP 20-32.5/ 3 mos**
**Mean days of sequential missed OCP 17-31/ 3 mos**
**Episodes of 3 or > missed OCP 1.9-2.2 / 3 mos**
**27% 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 contraceptive within a year**
**Furstenberg et al. Contraceptive continuation among adolescents attending family planning clinics. Fam Plann Perspect 1983;15;211-7**
**50% failed to return to clinic at 3 months--all of these had discontinued and 69% at risk for pregnancy**
**Balassone. Risk of contraceptive discontinuation among adolescents. J Adol Health Care.1989;10:527-33**

## OC Continuation in Adolescents

**Mean wait after coitarche before coming to clinic **
**1.4 years**
**“****inconsistent” (Discontinuing) users**
**Missed 3.4 pills/month**
**“****Consistent” (Continuing) users**
**Missed 2.7 pills/month**

**Balassone. Risk of contraceptive discontinuation among adolescents. J Adol Health Care.1989;10:527-33**

## FACTORS INFLUENCING SUCCESSFUL USE OF HORMONAL CONTRACEPTIVES

**Side Effects/Fear of Side Effects**
**Bleeding**
**Weight gain**
**Concerns about safety**
**Make you sick**
**Make you infertile**
**Cause cancer**
**Influences on use**
**Family members**
**Boyfriend**

## Slide 24

## OPTIONS AFTER DISCONTINUING OCs

**Continued sexual activity**
**With alternative method of contraception **
**Effective method--hormonal**
**Less effective method**
**Without contraception**
**Celibacy/Abstinence**

## OC Use in AdolescentsDecreased  Dysmenorrhea and Compliance

**Reduction of dysmenorrhea was the most statistically and clinically significant predictor  of consistent OC use **
**Adolescents with severe dysmenorrhea who experienced positive side effects (decreased cramping or flow) were 8 times more likely to   be consistent pill users (missed ********3 pills per month) than others**

- Robinson et al.  *Am J Obstet Gynecol.* 1992;166:578-583.

**Notes:**
Slide <number>
OC Use in AdolescentsDecreased  Dysmenorrhea and Compliance

Adolescents who experience reduced dysmenorrhea after taking an OC are more likely to continue taking the pill consistently. 
In one study of adolescents, those who experience improvement (decreased cramping or flow) of severe dysmenorrhea after OC use were 8 times more likely to be consistent pill users (missed 3 pills per month) than others who did not experience such positive effects.

Robinson JC, Plichta S, Weisman CS, et al.  Dysmenorrhea and use of oral contraceptives in adolescent women attending a family planning clinic.  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 FACTORSAffecting OC Continuation

**$/ Insurance/ HMO Coverage**
**One month at a time**
**Formulary**
**Generics**
**Office/ Clinic Hours**
**Sunday start**
**Extended cycle requirements for additional pills**

## OC Continuation:Access/Pill Packages Dispensed

**Women receiving 13 cycles of OCs were more likely to be continuing to get pills one year later than those receiving 1 or 3 cycles 49% vs 46% vs 42% (p< .001) **
**Continuous use at 15 months:**
**13 cycles  43%**
**3 cycles    22%**
**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.**

## Slide 30

## Slide 31