Chlamydia trachomatis (Ct) is the most commonly reported sexually transmitted infection in the United States.1 In 2015, there were approximately 63,000 reported cases in New York City (NYC) alone.2 Most Ct infections are asymptomatic; however, women with untreated or repeat Ct infections have an increased risk of developing pelvic inflammatory disease, with subsequent sequelae of chronic pelvic pain, ectopic pregnancies, and infertility.3 Therefore, it is vital that health care providers (HCP) not only treat infected (index) patients but also take measures to help protect their patients from repeat infections, which often result from resuming sexual activity with an untreated partner.4,5
There are several strategies HCPs can use to manage the sex partners of Ct-infected patients. The most commonly used method is patient referral, whereby an HCP treating an index patient asks the patient to advise their sex partners to seek treatment. Patient referral is probably sufficient in situations in which partners are likely to seek treatment. A more effective partner management strategy is provider referral, in which a healthcare or public health worker contacts an index patient's sex partners and encourages them to come in for presumptive treatment.6 Provider referral is a time-intensive approach and is less often used by providers.7 A third strategy is expedited partner therapy (EPT), whereby providers give index patients medication (“medication-EPT”) or prescription(s) (“prescription-EPT”) to deliver to their sex partners without first examining those partners. Prescription-EPT may be more time-intensive for the patients and partners than medication-EPT because it can require an additional visit to the pharmacy to fill the partners' prescriptions. Randomized controlled trials comparing medication-EPT to patient referral for Ct infection found that patients in the medication-EPT arm had lower rates of repeat infection.8–10 As a result of these studies, the Centers for Disease Control and Prevention (CDC) endorsed the general practice of EPT (2006 CDC White Paper), however, neither the efficacy nor the effectiveness of prescription-EPT has been studied independent of medication-EPT. Expedited partner therapy is now permissible in most of the United States and has been legal in New York State (NYS) for chlamydia since 2009.11,12
New York State regulations and provider guidelines specify how NYS providers should write EPT prescriptions.12,13 Law and regulations require that “EPT” be written in the body of the prescription and permit HCPs to give an EPT prescription, and pharmacies to fill such prescriptions, without any personal identifiers. Provider guidelines state that a unique prescription should be written for each sex partner and that a single prescription should not serve both the patient and the partner.14 Providers licensed in NYS are permitted to transmit EPT to pharmacies via electronic (electronic prescription) or conventional (paper prescription) means.
By 2014, NYC providers documented the use of EPT for more than a quarter of reported Ct cases with submitted provider case reports (Julia Schillinger, MD, written communication, 2015), and commonly do so by prescription.15 However, NYC pharmacists surveyed about EPT have reported infrequent receipt of EPT prescriptions.16 Two possible explanations for this discrepancy are that patients or partners are not filling EPT prescriptions given to them, or, that providers are not writing “EPT” in the body of the prescription (as required by state law) and pharmacists cannot, therefore, distinguish an EPT prescription from any other prescription for azithromycin. We conducted sentinel surveillance for EPT prescriptions in pharmacies located in 2 NYC neighborhoods where EPT prescriptions were known to be dispensed to assess the extent to which EPT prescriptions get filled.
MATERIALS AND METHODS
Selection of Neighborhoods
New York City providers are required to submit a case report to the NYC Department of Health and Mental Hygiene (DOHMH) each time they diagnose a patient with chlamydia; reports can be submitted via an online system, or mailed or faxed as paper reports. The case report form includes questions on the patient’s demographic characteristics, treatment regimen, and partner management. There is also a question about whether the provider gave EPT in the form of prescription or medication. We identified the 2 NYC facilities reporting the most frequent use of EPT prescriptions and selected the neighborhoods in which these 2 facilities were located. Both health care facilities were Federally Qualified Health Centers (FQHCs) in resource-poor, high Ct morbidity NYC neighborhoods outside of Manhattan. Facility 1 was a free-standing gynecology clinic belonging to an FQHC. Facility 2 was an FQHC health center offering a range of services, and included a gynecology clinic.
Selection of Pharmacies
Pharmacies located within a half-mile walk from either facility were identified using 2013 New York State pharmacist licensing data, Google maps searches for “pharmacies” near the facility address, and the database of Big Apple Rx, a city-wide free prescription discount card program sponsored by the NYC DOHMH. Pharmacies near facility 1 were defined as neighborhood 1 pharmacies, and pharmacies near facility 2 were defined as neighborhood 2 pharmacies. All identified pharmacies were contacted between December 2015 and January 2016 and asked to participate in this sentinel surveillance project. Those who agreed to participate were visited during January and February, 2016.
Collection of Pharmacy Data
In NYS, pharmacies are required to keep a record of their prescriptions for at least 5 years. At each participating pharmacy, prescriptions filled in 2015 for azithromycin were examined using either the pharmacy's electronic software system or by manually reviewing stored paper prescriptions. Although a single 1-g dose of azithromycin can be used for the treatment of several sexually transmitted diseases, it is most commonly used to treat chlamydial infection. It is also an alternative treatment for traveler's diarrhea and dysentery. Prescriptions filled for one 1-g azithromycin dose, or two 1-g azithromycin doses were included in this analysis. Data on the prescription's written and fill date, number of days of treatment, dosage, prescribing provider and facility, patient’s gender and age, and prescribing instructions were extracted. A prescription was classified as an EPT prescription if: (a) “expedited partner therapy,” or “EPT” was written in the prescription, or, (b) a prescription indicated that azithromycin, 1 g was to be taken by “a partner.” The subset of EPT prescriptions that included treatment for both the patient and the partner on a single prescription were defined as “double-dose” prescriptions. We did not match individual Ct case reports to individual azithromycin prescriptions found at the pharmacies. At each pharmacy, the supervising pharmacist or pharmacy manager was also asked to estimate the number of prescriptions (of any kind) filled daily, with the expectation that we might find more EPT prescriptions at pharmacies that filled more prescriptions generally.
Collection of Contextual Data
After collecting data from several pharmacies, we contacted the clinical directors of the gynecology clinics at facility 1 and facility 2 and asked them to describe their clinic's standard practice for providing EPT.
Descriptive analyses on case reports and prescription data were conducted using SAS 9.4.
Human Subject Considerations
This project was determined to be public health surveillance, not subject to human subjects review.
Ct Provider Case Reports From Facilities 1 and 2
In 2015, providers at facility 1 submitted 229 (228 female, 1 unknown sex) Ct case reports to DOHMH through the online system (Table 1). In 51% (117/229) of these cases, the provider documented the use of EPT. Providers at facility 2 submitted 723 Ct case reports and 19% (20% [117/574] of the female cases and 14% [21/147] of the male cases) had documentation of EPT use. Facility 1 case reports indicated that 96% (112/117) of EPT was given in the form of prescription compared to 83% (114/138) at facility 2. The median age of patients at facility 1 was 22 years compared with 24 years at facility 2. In all cases in which there was documentation on the case report of the number of partners treated, the provider wrote an EPT prescription for only 1 sex partner.
EPT Practices at Facilities 1 and 2
At facility 1, the standard practice for providers caring for chlamydia-infected index patients who accepted EPT was to electronically transmit a single prescription to a particular local pharmacy; the prescription included medication for both the index patient and their partner(s). At facility 2, providers' standard practice was to transmit an electronic prescription as treatment for the index patient to either 1 of 2 of the local pharmacies, and to provide a separate, paper prescription to the index patient as EPT for the partner(s).
There were 26 pharmacies (22 independent, 4 chain) located within a half mile walking distance of either facility. All were invited to participate and 12, all independent, agreed to be involved in the project, including 7 of 13 pharmacies near facility 1 and 5 of 13 pharmacies near facility 2. There was little difference in average walking distance between the facility and the participating and nonparticipating pharmacies. The 12 pharmacies filled between 35 and 450 prescriptions daily (median, 200) (Table 2). The participating pharmacies in neighborhood 1 filled a median of 250 prescriptions daily compared to 150 prescriptions in neighborhood 2.
Azithromycin Prescriptions at Participating Pharmacies
We found a total of 505 azithromycin prescriptions for one 1-g dose (n = 387) or two 1-g doses of azithromycin (n = 118) (Table 2). The median number of prescriptions found at each pharmacy was 20 (range 0 to 189). Fifty-seven percent (286/505) of these prescriptions were found in neighborhood 1, and of these, 47% (134/286) were written by providers at facility 1 (Fig. 1). Of the 219 prescriptions found in neighborhood 2 pharmacies, 30% (65/219) were written by providers at facility 2. There were 2 facility 2 prescriptions found in neighborhood 1, but no facility 1 prescriptions found in neighborhood 2.
A total of 102 of the 505 found azithromycin prescriptions (102/505; 20%) met the case definition for an EPT prescription. Fifty-six percent (57/102) of EPT prescriptions had “EPT” written in the prescription, and 44% (45/102) specified that the prescription was intended for partner therapy (and did not write “EPT” in the body of the prescription). Overall, 86% (88/102) of all EPT prescriptions were double-dose and 89% (91/102) were written for female patients (Table 3). A median of 2 EPT prescriptions were filled at the participating pharmacies; five pharmacies had none. Almost all (96%; 98/102) EPT prescriptions found were filled in neighborhood 1, of which 62% (61/98) had been written by providers facility 1 (Fig. 1); the remaining EPT prescriptions were written primarily at nearby clinics that belonged to the same FQHC as facility 1. The majority of these EPT prescriptions (83%; 81/98) were filled at one pharmacy. Even after excluding that pharmacy, significantly more EPT prescriptions were found in neighborhood 1 pharmacies than in neighborhood 2 pharmacies (17 in neighborhood 1 vs 4 in neighborhood 2; (P < 0.001)). Of the 4 EPT prescriptions found in neighborhood 2, only 1 was written by providers at facility 2.
Assuming that provider case reports for Ct indicated all instances in which EPT prescriptions were given, 52% (61/112) of the EPT prescriptions reported by facility 1 providers and 0.9% (1/114) of prescriptions reported by facility 2 providers were found at the participating pharmacies. There were 373 non-EPT, single-dose azithromycin prescriptions. If we assume all of these were index-patient treatments, and include the 88 double-dose prescriptions, we found the treatments for 52% (120/229) of Ct cases reported by facility 1 providers and 9% (66/723) of Ct cases reported by facility 2 providers. We found 0.2 (102/461) partner treatments per index patient. After excluding pharmacy 1, there were 0.07 (21/288) partner treatments per index-patient.
The EPT prescriptions were received in NYC pharmacies near to EPT-prescribing facilities, but at a lower frequency than expected. The EPT prescriptions were unevenly distributed, both between and within neighborhoods, with 1 pharmacy accounting for the majority of the EPT prescriptions we found. In addition, the EPT prescriptions we found were mostly double-dose prescriptions, allowing treatment for both patient and partner on the same prescription.
In total, we found one quarter of the number of EPT prescriptions reported in the provider Ct case reports, indicating that at least some EPT prescriptions were being filled. The primary intent of this project was to determine whether EPT prescriptions were filled. However, the notable difference in the number of EPT prescriptions found in the 2 neighborhoods compelled us to consider how the different EPT prescribing practices used at facility 1 and facility 2 may have influenced the extent to which EPT prescriptions were filled. Facility 1's standard practice was to electronically prescribe treatment for index patients, and, if they accepted EPT, to include partner treatment on the same prescription. This practice allowed treatments for the patient and partner to be filled at the same time by the index patient. At facility 2, index patients were electronically prescribed treatment, and separate paper prescriptions were given for EPT. In order for facility 2 EPT prescriptions to be filled, they needed to be either: (a) delivered to the partner who could then fill the prescription, or (b) filled at the expense of the index patient.
Our ability to infer a causal relationship between EPT prescribing practices and the number of EPT prescriptions found in each neighborhood is limited, for several reasons. First, double-dose EPT prescriptions (from facility 1) were easy to identify because double-dose prescriptions included instructions stating that the patient should take only one dose, and the other dose be given to a partner. In contrast, single EPT prescriptions (such as those from facility 2) could only be distinguished from other azithromycin 1 gram prescriptions if “EPT” was written on the prescription, or if there were directions on the prescription that indicated that it was for partner therapy, so it is likely that we did not identify all the single gram azithromycin prescriptions intended as EPT. Second, because double-dose prescriptions (from facility 1) were electronic and single-dose prescriptions (from facility 2) were paper, it was not possible to disentangle the effect of prescribing method (electronic versus paper), from the effect of double (versus single) dosing on whether a prescription gets filled. There may well have been other confounding factors related to providers' or pharmacists' interaction with the index patients that we could not observe. Third, anecdotally, some pharmacists do not fill double-dose prescriptions because they consider this practice to be insurance fraud, so it is likely that facility 1’s double-dose EPT prescriptions were purposefully sent to a local pharmacy known to fill double-dose prescriptions, which kept facility 1 EPT prescriptions in neighborhood 1. We do not know if the reported chlamydia case-patients and their partners lived close to the facilities or if they lived in other neighborhoods, and if facility 2's paper EPT prescriptions were taken to pharmacies outside neighborhoods 1 and 2, we would have underestimated the number of these prescriptions filled. Finally, it is possible that the very pharmacies in neighborhood 2 that declined to participate in this sentinel surveillance project were those filling EPT prescriptions.
Accounting for pharmacy participation rates in neighborhood 1, we found the expected number of facility 1 EPT prescriptions. Almost all of these prescriptions were at 1 pharmacy. Prior research has found that almost 40% of Ct-infected patients at California Title X clinics did not fill prescriptions for their own treatment and, that in Scotland, 60% of vouchers for EPT medication were not redeemed.17,18 If we assume that the Ct-infected patients treated at facility 1 had similar rates of noncompliance, then we may have found almost all the EPT prescriptions that were filled.
Even when accounting for pharmacy participation rates and patient noncompliance, we did not find the expected number of facility 2 EPT prescriptions. The low number of EPT prescriptions could have resulted from patients not filling their prescriptions or from filling a large number of them at nonparticipating pharmacies and/or pharmacies outside neighborhoods 1 or 2. However, there is no reason to assume that facility 2 EPT prescriptions were clustered at the neighborhood 2 nonparticipating pharmacies because facility 2 EPT prescriptions were paper and could have been filled at any pharmacy. Facility 2's share of found 1-g azithromycin prescriptions was much higher than its' share of found EPT prescriptions, consistent with the hypothesis that facility 2 EPT prescriptions were not being filled.
The results of this sentinel surveillance analysis may not be generalizable. We conducted sentinel surveillance in neighborhoods where we knew prescription EPT was occurring and sought to enroll nearby pharmacies, and it is possible that these neighborhoods are not representative of NYC neighborhoods. It is also possible that the pharmacies that decided to participate in this project were not representative of all pharmacies in their neighborhood. We know that nonparticipating pharmacies and participating pharmacies were equidistant from the facility in question, and that none of the 4 chain pharmacies we approached agreed to participate, but we do not have any other data with which to assess for bias in participating pharmacies. Also, we cannot comment on the differing rates at which men and women fill EPT prescriptions. The majority of EPT prescriptions found were written by providers at facility 1, a women's clinic. Providers at facility 2 reported the use of prescription-EPT for both men and women but very few prescriptions from that facility were found.
Prescription-EPT is commonly practiced in NYC, yet the efficacy and effectiveness of this mode of EPT has never been established. The effectiveness of prescription EPT will hinge on whether EPT prescriptions are filled; our findings point to potential problems with this process. Future studies should establish the frequency with which EPT is given by prescription in different jurisdictions, and surveillance for filled EPT prescriptions should be conducted. Investigators should seek to explore whether index patient sex affects whether EPT prescriptions are filled, and examine the independent effect of prescribing method (electronic versus paper prescribing) on filled EPT prescriptions to determine whether double-dosed EPT prescriptions are more likely to be filled than single-dosed prescriptions. In NY, patient and partner receipt of EPT could be better monitored if providers adhered to EPT regulations stipulating that “EPT” be written in the body of EPT prescriptions; efforts to educate NY providers about this requirement could improve the accuracy of local measures of EPT use. Other jurisdictions should consider ways to monitor prescription EPT in order to accrue data to examine the effectiveness of this form of EPT.
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