The contraceptive method that will be most effective for any couple is the one that they will use correctly and consistently. To that end, selection of a woman’s contraceptive method involves evaluation of a number of medical, psychosocial, lifestyle and economic factors. The prescription that is ultimately written by the clinician represents the thoughtful result of a discussion of those factors with the patient. Given the effort that is invested in this process, it is important to evaluat e how women continue to use the methods that they are prescribed.
Interruption of contraception use places women at risk for unintended pregnancy. The contrast between the pregnancy rates quoted with typical use of combined hormonal methods (8.7%)1 and those reported with correct and consistent use (less than 1%)2 has prompted examination of several real-world barriers that limit successful use of contraceptive methods. Another common reason volunteered by women for discontinuing their birth control methods is the difficulty they have obtaining a secure ongoing supply of contraceptive products. Recognizing that women can not use methods that they do not possess, the World Health Organization has recommended that women who elect to use oral contraception be provided a 1-year supply (13 cycles) all at once.3 However, the number of cycles dispensed in the United States is usually limited to one cycle.
Previous studies have demonstrated a positive association between providing more cycles of contraceptives and higher short term continuation rates.4,5 Those studies raised the possibility that formulations that provide potential long-acting contraception, such as 3-month extended-cycle oral contraceptives or 3-month injectables, might have higher continuation rates than single-cycle hormonal products dispensed on a monthly basis. Commercial databases have been suggested as sources of information about the behaviors of large numbers of women in the real world,6 but rarely have they been utilized.
Our study evaluates longitudinal refill patterns of prescription hormonal contraceptive products to estimate timely refill rates for a wide range of branded hormonal contraceptive products in a large, geographically diverse population of women.
MATERIALS AND METHODS
The Verispan database is compiled from information provided about 780,000 unique prescribers and more than 160 million unique patients. The combined sources of data represent 99% of retail pharmacies in the United States. In this database, information about prescription refills is collected for each individual patient. Each patient is tracked across time, pharmacies, data providers, prescribers and payers. For example, if a patient filled her first prescription at one pharmacy and refilled it at another, she is included in the database. Before the database is released for analysis, all the data are de-identified.
This study evaluated prescription refills by women who filled their first branded hormonal contraceptive prescriptions at any time during the period October 2003 through December 2004, meaning that women could enter this cohort over a 15 month period. The end of follow-up for all women in this analysis was August 2005; thus, women who filled their first prescriptions early in the study period were followed for longer periods of time. Women were included in the analysis if they were in the database and could be tracked for the entire study period. Women were excluded if they lost insurance coverage, left the country, died during follow-up, or changed their last names between refills. Analyses were organized to evaluate timely refills during follow-up periods from 240 days up to 600 days. Information collected included patient age, product prescribed, number of refills prescribed, date of first prescription filled, and the date of each refill of that product, if it occurred within 15 days of the expected time. If a woman had used one of the other products in the database at any time in the 6 months before filling her first prescription for one of these products, she was considered a “switcher.” If she had not filled a prescription for any of these products in the prior 6 months, she was classified as a “naive” user.
The hormonal products for which information was available for this analysis include the transdermal contraceptive patch (Ortho Evra; Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ); the vaginal contraceptive ring (NuvaRing; Organon Inc., a subsidiary of Schering-Plough, West Orange, NJ); five (proprietary) branded oral contraceptive pills available throughout the period of follow-up, including Ortho Tri-Cyclen and Ortho Tri-Cyclen Lo (Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ), Ovcon (Bristol-Myers Squibb Company, Princeton, NJ), Seasonale (Duramed Pharmaceuticals, Inc., a subsidiary of Barr Pharmaceuticals, Inc. Pomona, NY), and Yasmin (Bayer HealthCare Pharmaceuticals Inc., Wayne, NJ); and the 3-month contraceptive injection (Depo-Provera, Pfizer, Inc., New York, NY).
The institutional review board of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center approved this project as an exempt study because the database contained no personal identifiers. The main study endpoint was the proportion of women who continued to refill their prescriptions on a timely basis for selected branded hormonal contraceptive products included in the database. Timely refills were defined as those occurring within 15 days of the expected date based on the date of and the quantity provided at the prior fill/refill. Refill rates were calculated by product class and for individual branded oral hormonal contraceptive products at 30 days, 90 days, 180 days, 12 months, and 18 months. The refill rates of different products and groups of products were compared at 12 months. The refill rates among users in different age groups were compared at 6 months. That analysis included only newly starting (naive) users to eliminate influence that prior use might have on continuation rates, since older women were more likely than younger women to be prior users. Chi-square tests were used to test for statistical significance; P<.05 was selected to establish statistical significance.
For 28-day cycle methods, the most frequent prescription specified more than 7 refills. This suggests that clinicians are most frequently writing prescriptions that require monthly refills. We analyzed refill rates for three groups of women: those with 240 days, 420 days, and 600 days of follow-up. Women with the earliest initial prescription fill contributed data to all three follow-up endpoints; women who enrolled later had the shortest period of follow-up and thus contributed only to the 240-day population. The 240-day population included 1,689,385 women followed from January to September 2005; the 420-day population was composed of 980,625 women followed from July 2004 to September 2005; the 600-day population included 338,182 women followed from October 2003 to September 2005. The refill rate at each point in time (30 days to 18 months) is based on the women with follow-up to that end-point. For example, the 1.7 million women followed for at least 240 days provided information for the 30-, 90-, and 180-day refill rates, and data from the 980,625 women followed for at least 420 days was used to calculate 12-month refill rates.
Uninterrupted refill rates at 30, 90, and 180 days are listed in Table 1. Depending upon the product, up to 40.6% of women utilizing a 28-day method did not return on a timely basis to refill their prescriptions after their first unit. The first meaningful analysis of refill rates for the 3-month contraceptive injection (depot medroxyprogesterone acetate [DMPA]) and for the 91-pill packet for the extended-cycle oral contraceptive product available at the time (Seasonale) begins at the 90-day analysis. Overall, uninterrupted refill rates for all products at 90 days varied from 43.2% to 61.2%. By 6 months (180 days), only one contraceptive product had an uninterrupted refill rate in excess of 50%. By 12 months, refill rates varied from 16.3% to 34.5% (Table 2). After 365 days, the refill rates stabilized somewhat (Fig. 1).
At 12 months, two products—the drospirenone-containing pill and the extended-cycle (84/7) pill—had significantly higher refill rates than the other contraceptives. Compared with other branded 28-day pills, the drospirenone-containing pill had higher refill rates (34.5% compared with 29.0%; P<.001) as did the extended-cycle pill (31.0% compared with 29.0%; P<.001). Compared with all other hormonal methods, the drospirenone-containing pill had higher refill rates (34.5% compared with 24.8%; P<.001), as did the extended-cycle pill (31.0% compared with 24.8%; P<.001). The nonoral monthly hormonal delivery systems (vaginal ring and transdermal patch) had higher refill rates than monthly pills with 19-nortestosterone progestins (26.0% compared with 23.9%; P<.001). To test the hypothesis that products providing larger supplies might have higher continuation rates, the timely refill rate of the extended-cycle pill was compared with refill rates of all monthly methods; the extended-cycle pill had statistically significantly higher refill rates at 12 months (31.0% compared with 27.8%; P<.001). The high rate of interrupted DMPA use, however, drove down the timely refill rate of the 3-month products as a group compared with the monthly products (24.3% compared with 27.8%; P<.001).
Uninterrupted prescription refill rates of naive women were calculated for different age groups. Table 3 demonstrates that girls aged 14–16 had refill rates that were significantly higher (P<.05) than those of older women for branded monthly pills, for the extended-cycle pill, and for the 3-month injection (P<.05), but had lower refill rates than older women for the vaginal ring and the transdermal patch (P<.05). For both longer-acting combined hormonal methods, the youngest girls were less likely than older women to refill their prescriptions on a timely basis. They also had lower refill rates than same-aged pill users had.
In a Medline search using the query “(birth control OR contraceptive OR contraceptives OR contraception) AND (discontinuation OR continuation OR persistence) AND (refill OR refills OR prescription OR prescriptions)” for all years, only one related article was found, which reported 3-month continuation rates based on prescription refills for 225,000 women.7 Our study is the first to report uninterrupted prescription refill rates of hormonal contraceptives for at least 1 year based on longitudinal prescription data and, thus, provides a unique “high-altitude” overview from which potential uninterrupted continuation rates may be estimated.
As may be expected, continuation rates represented by timely refill rates in the Verispan database are much lower than the rates of continuation reported in the clinical trials for many of the products included in this study.8–11 Lower rates of continuation have been reported for clinical trials involving special groups of women.4,12–15
Our continuation rates are also lower than continuation rates derived from surveys. Rosenberg and Waugh16 reported that, at 6 months, 53.3% of women continued to use their initial methods. Based on the 1995 National Survey of Family Growth, Trussell et al2 estimated the percent of women continuing to use their method after one year to be 56% for DMPA users and 68% for all combined hormonal method users.
There may be many factors contributing to the low timely refill rates seen in the Verispan data. Some women may have stopped contraceptive use because they wanted to get pregnant. However, it is unlikely that a new desire for pregnancy contributed substantially to the high failure to refill rates seen at 1 month. Some women may have experienced side effects from their prescribed product and returned to their providers for a new prescription. Clearly this happens, but it does not account for a significant proportion of discontinuation.16
Some women may have switched to less-expensive generic products, which were not included in the Verispan database. However, at the time of the study, there were no generic equivalents for many of the products being studied, including the transdermal patch, the vaginal ring, the drospirenone-containing pill, or the extended-cycle pills. Refill rates for women using this group of methods as a whole at 90 days were roughly similar to the refill rates for products for which there were generic equivalents. The study by Murphy et al,7 which did include generic products, found continuation rates at 3 months that were similar to ours.
External factors may also have influenced continuation rates for individual products during this time period. Media reports of venous thromboembolism with the transdermal patch in April 2005 may have increased discontinuation rates for that product. Similarly, the black box warnings placed in November 2004 regarding bone mineral density loss with longer-term DMPA use may have prompted providers to switch their patients away from that method. The launch of Ortho Tri-Cyclen Lo may have resulted in lower continuation rates for Ortho Tri-Cyclen.
The disturbing conclusion from these observations is that a significant proportion of the observed failure to refill prescriptions on a timely basis rests with the users’ failure to return for those refills. Refilling prescriptions on a timely basis is clearly a necessary condition for successful contraceptive use. However, possession does not guarantee use. Hormonal contraceptive users themselves recognize that they often do not use their methods as prescribed.17 Potter et al18 reported that more than half of oral contraceptive users miss three or more pills by the third cycle.
Discontinuation may represent only a temporary interruption in use. However, with the rapid return to fertility seen with all the noninjectable contraceptive methods, even a 2-week interruption would place women at risk for pregnancy. Temporary discontinuation of oral contraceptive use was reported by Rosenberg and Waugh, 16 who found that 44.7% of women who discontinued pills restarted them within the 6-month study period. A common start-stop-restart pattern of use of DMPA has also been described.19 This restart pattern may explain why women do not perceive or report that they have discontinued their method.2
Uninterrupted continuation rates for hormonal contraceptive methods, as measured by timely refilling of prescriptions, are much lower than generally appreciated. The higher refill rates of the two new products may reflect some of the noncontraceptive benefits they provide, the impact of direct-to-consumer advertising, or professional enthusiasm for the novel properties of these products. Younger girls (14–16-year-olds) were at least as likely to refill their contraceptive methods as were older women, which conflicts with most perceptions about teen compliance patterns.5
Given these high discontinuation rates, it may be important for clinicians to reevaluate the parameters they consider when counseling women about their contraceptive options. Enhanced counseling has not been shown to improve contraceptive use.20 However, asking concrete questions about the impact of contraceptive cost and women’s commitment and ability to access refills on a timely basis may increase appropriate prescription of generic products, when indicated, or of products offering greater supplies. It may also prompt women to consider the benefits of the longer-term methods of birth control.
It is likely that a substantial percentage of women who delayed the refill of hormonal methods or who discontinued their use entirely engaged in inadequately protected intercourse. Therefore, clinicians need to provide education about back-up methods, such as male condoms, and to routinely prescribe emergency contraception in advance of need when starting any woman on a hormonal contraceptive method.
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