The results of this study show that a multistage intervention was effective at decreasing dispensing of medications that carry a risk of fetal harm. Pregnancy prescribing recommendations were developed and agreed on by researchers, physicians, and pharmacists. Coupling data from information systems with the knowledge and skills of physicians and pharmacists resulted in improved prescribing safety. However, the results of this study also show that the ability to link ambulatory clinical, laboratory, and pharmacy systems to provide safety alerts is not sufficient to ensure project success and sustainability. Systems limitations resulting in false-positive alerts and unacceptable human interactions contributed to stopping the project early. Two reasons were important contributors to the decision to end the intervention. First, due to limitations inherent to the pharmacy information system pregnancy software module, 2 of every 5 alerts were for drugs not contraindicated in pregnancy. Second, information about the end of pregnancy was not promptly available in the ambulatory clinical database that provided information to the pharmacy information system, resulting in pharmacists incorrectly being alerted that patients remained pregnant. Although incorrect patient status information did not cause difficulty in pharmacist-patient communication when a woman had delivered a healthy infant, when a woman’s pregnancy had ended in miscarriage or abortion at a hospital (or other location outside our health care system), extremely awkward and negative human interactions occurred between pharmacists and patients.
We believe the problem of noncontraindicated drugs being included in the intervention can be overcome in systems with more sophisticated software. For example, in the related area of ambulatory pharmacy drug-drug interactions software packages, false-positive alerts have been problematic, 34,35
but the performance of these systems has improved recently. 36
Unfortunately, because the problem of not promptly identifying the end of pregnancy relates to rate of transfer of coded diagnosis information between hospital and ambulatory medical care systems, relying on administrative data transfer is not likely to be timely enough for all pregnancy-drug interventions. Ideally, this time lag could be shortened by additionally linking hospital EMR data to ambulatory pharmacy information systems—a linkage that is not common when more than one health care system is involved. One alternative to avoid the need to identify the end of pregnancy promptly would be to redesign the intervention to be delivered later in the medication dispensing process via a warning label on the dispensed medication. However, to reduce these medication errors most effectively, error reduction strategies that address multiple points in the medication use process likely should be deployed. 37
Research is needed to evaluate the success of strategies that, for example, combine an intervention in the physician’s office at the point of CPOE with an intervention by the pharmacist at the point of dispensing.
The intervention medications dispensed most often to pregnant patients were products containing codeine or other narcotic analgesics, accounting for approximately 40% of category D and X dispensings to patients in each group. Dispensing these medication could be appropriate because they are considered risky only when used for prolonged periods and/or near term, largely due to the potential for respiratory depression in the newborn. 5
The NSAIDs and oral contraceptives each comprised about 10% of category D and X dispensings. NSAIDs inhibit prostaglandin synthesis; use during pregnancy has been associated with constriction and premature closure of the fetal ductus arteriosus, spontaneous abortion, and, particularly when indomethacin is used after 34 weeks’ gestation, reduced fetal urine output and oligohydramnios. 5
Prescriptions for oral contraceptives were expected among the women in this study because oral contraceptives are routinely prescribed at KPCO during the third trimester of pregnancy, with directions for use indicating that the oral contraceptive should be started after delivery. In this context, prescriptions for oral contraceptives could also be considered false-positive alerts.
The frequency of dispensing other targeted category D and X medications was very low in both groups (). Although beyond the scope of this study, for known teratogens such as warfarin and tretinoin, and for medications known to have other adverse effects on the fetus or newborn such as tetracyclines and β-blockers, it is important to understand the benefit to risk situation for each individual patient because the benefits of maternal therapy can sometimes outweigh the fetal risks. It is therefore inappropriate to state that these drugs should never be prescribed during pregnancy. For example, an intervention-group patient in our study was dispensed sulfamethoxazole-trimethoprim after the pharmacist documented that the prescriber confirmed the patient was <36 weeks gestation (and therefore, because the woman was not expected to deliver imminently, the prescriber was not concerned about the risk of kernicterus in her newborn). 5
A challenge with research that documents suboptimal medication use is in developing systems that are safe and effective at translating research results into improved practice. As we developed and implemented this intervention program we focused on getting institutional support, agreement, and stakeholder commitment, solving operational problems in a cooperative manner between physicians and pharmacists and seeking feedback. Other strengths of this study include that we randomized the entire health plan membership to intervention or usual care groups and that every potentially pregnant patient between the ages of 18 and 50 who was prescribed a targeted medication was included.
In addition to the systems’ limitations encountered in this project, there are other potential limitations to this work. Because we relied on health plan prescription data, we could not identify medication prescribing that occurred outside of our health care system. This probably occurred rarely, because 98% of KPCO members had a medication benefit during the study period. Also, the number of prescriptions for targeted medications that were written, but either modified or stopped altogether (not sold to the patient), was not available for either the intervention or the usual care group. Unfortunately, this information could not be extracted from the system electronically and pharmacists were not asked to manually track the number of alerts that resulted in modified or discontinued prescriptions.
This study was not designed to evaluate either the clinical or the economic outcomes associated with prescribing contraindicated medications during pregnancy. Research evaluating the effectiveness and the cost of this type of intervention in reducing adverse outcomes related to medication dispensing during pregnancy would be valuable. However, such prospective trials are unlikely to be conducted because of ethical concerns, the rare occurrence of most teratogenic effects, and the cost associated with trials requiring the huge sample sizes needed to study rare outcomes.