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There is considerable variability in the manner in which prescriptions are written by physicians and transcribed by pharmacists, resulting in patient misunderstanding of label instructions. A ‘universal medication schedule’ (UMS) was recently proposed for standardizing prescribing practices to four daily time intervals thereby helping patients simplify and safely use their medicine. We investigated whether patients consolidate their medications, or if there is evidence of unnecessary regimen complexity that would support standardization.
Structured interviews were conducted with 464 adults ages 55–74 who were receiving care at either an academic general medicine practice or one of three federally qualified health centers in Chicago, Illinois. Subjects were given a hypothetical, seven-drug medication regimen and asked to demonstrate how and when they would take all of the medicine in a 24-hour period. The regimen could be consolidated into four dosing episodes per day. The primary outcome was the number of times per day individuals would take medicine. Root causes for patients complicating the regimen (> four times a day) were examined.
Participants on average identified six times in 24 hours to take the seven drugs (SD=1.8; range 3 to 14). One third (29.3%) found seven or more times per day to take their medicine, while only 14.9% organized the regimen into four or fewer times a day. In multivariable analysis, low literacy was an independent predictor of more times per day for dosing out the regimen (β=0.67; 95% Confidence Interval 0.12 to 1.22, p=0.018). Instructions for two of the drugs were identical, yet 31% of patients did not dose these medicines at the same time. Another set of drugs had similar instructions with the primary exception of one having the added instruction to take “with food and water”. Half (49.5%) of participants dosed these medicines at different times. When medicines had variable expressions of the same dose frequency (“every 12 hours” vs. “twice daily”), 79.0% did not consolidate the medicines.
Many patients, especially those with limited literacy, do not consolidate prescription regimens in the most efficient manner, which could impede adherence. Standardized instructions proposed with the UMS and other task-centered strategies could potentially help patients routinely organize and take medication regimens.
Patients frequently misunderstand common instructions and warnings that accompany prescription drugs, resulting in unintentional misuse and potentially adverse drug events.1–6 This should not be surprising, as prescription labels may provide seemingly simple, but often unclear directions that are confusing to the majority of patients. In the United States, physician prescriptions and pharmacy labeling typically include vague information detailing recommended medication schedules described either in hourly intervals (i.e. every 4–6 hours) or times per day (i.e. twice daily). Davis and colleagues found that nearly half of patients misinterpreted common instructions such as these when attempting to dose out a single prescription medication.1
Yet the problem may be more serious than these findings suggest, as patients are increasingly managing multiple prescription and over-the-counter medicines. According to the Medical Expenditure Panel Survey (MEPS), the average adult in the U.S. fills nine prescriptions annually,7 while adults over 65 fill on average 20 prescriptions a year. Greater regimen complexity, based on multiple medications and/or multiple daily doses per drug may lead to poorer adherence, which in turn will lead to worse health outcomes.8–12 From a health system perspective, the known variability and poor quality in the manner in which prescription instructions are written by physicians and translated by pharmacies impedes an individual’s ability to organize and properly dose out multiple medications.13,14
The Institute of Medicine (IOM), in its 2008 report Standardizing Medication Labels, recognized the need for setting standards within prescribing and dispensing practices to promote safe and accurate medication use for patients.6 As approximately 90 percent of prescriptions are taken four times a day or less12, a universal medication schedule (UMS) was proposed in the IOM report specifying four standard time intervals (morning, noon, evening, bedtime) for the prescribing and dispensing of medicine.14 The UMS would describe when to take a medicine in the same manner on all prescription labels, removing the current variability often found in the manner in which prescriptions are written by physicians and transcribed by pharmacists.13–15 All prescriptions would instruct patients to take their medicines using these specified times, and this would be described in a single standardized fashion on the label. This standardization was viewed with both promise and controversy by the pharmacy and medical communities. While it might help patients organize and group increasingly complex medication regimens for daily use, it was concluded that further evidence would be needed to support the need for the UMS. In the present study, we sought to fill the gap of existing literature and investigate whether patients complicate multiple prescription regimens by taking medicines more than four times a day. Specifically, The accuracy and variability in the way patients implemented a typical seven-drug regimen was evaluated.
Adults between the ages of 55 and 74 who received care at either an academic general internal medicine ambulatory care clinic or one of three federally qualified health centers in Chicago, Illinois were recruited for a National Institute of Aging study, referred to as LitCog, that examined performance on everyday health tasks, including medication use (R01 AG030611).16 Subject enrollment took place between August 2008 and December 2009. Patients were ineligible if they had severe visual or hearing impairments, were too ill to participate, or were non-English speaking. The Northwestern University Institutional Review Board approved the study and all patients gave informed consent prior to participation. A total of 2168 patients were identified through electronic health record (EHR) systems at clinic sites as initially eligible to participate in LitCog by age. A random sample of 1012 eligible patients was selected to be contacted by research staff via phone and invited to participate in the study. Among those contacted, 479 patients refused, 12 were deceased, and 521 were ultimately consented to the study. Initial screening deemed 57 subjects as ineligible due to severe cognitive or hearing impairment (n=22), limited English proficiency (n=11), or not being connected to a clinic physician (defined as 2 or more visits in past two years; n=24). In all, 464 patients participated in the study, for a determined response rate of 52.1 percent following American Association for Public Opinion Research (AAPOR) guidelines.17
Subjects completed a two-hour, structured cognitive interview that included an assessment of their ability to perform everyday health tasks, including dosing out a seven-drug medication regimen over the course of a 24 hour period. A research assistant (RA) gave patients a hypothetical drug regimen, which consisted of seven actual prescription drug pill bottles with mock-up labels, each with a retired drug name no longer in use and different dosing instruction (see Table 1). The drug names that were chosen were specifically used to avoid the influence of participants’ potential current or prior experience with an actual drug.
The task presented to subjects was to demonstrate when they would take the entire regimen by dosing out fake pills contained with each prescription bottle at the times of day that they would take the medicine. The RA gave patients a ‘medication box’, which had 24 slots labeled with every hour of the day (12am–11pm) and instructed them to place the correct number of pills in the slots that identified the times when they would take a medicine. Unlike a pill organizer, the medication box was not meant to assist participants. Rather it allowed them to demonstrate precisely at what times during the course of a day they would take each drug. The scripted verbal instruction given to patients was, “Imagine that your doctor has prescribed you these medicines. I would like you to please show me when you would take these medicines over the course of 1 day.” Detailed guidance was then provided to patients on how to demonstrate, with the fake pills, how to dose out the regimen using the medication box.
In addition to completing this task, patients answered basic demographic questions and completed a literacy assessment known as the Newest Vital Sign (NVS).18 This is a six item measure that includes reading comprehension and numeracy items based on a nutritional facts label. The NVS is strongly correlated with the Short Test of Functional Health Literacy in Adults (STOFHLA).19
The outcome of interest was the number of times per day patients would propose to take the medicine, based on the manner in which they dosed out the seven-drug regimen throughout a 24 hour period as demonstrated using the medication box. Descriptive statistics were calculated for each variable. Student’s t-tests were used to evaluate the association between participant sociodemographic characteristics and the number of reported times per day subjects would take the seven-drug regimen. Multivariable linear regression analyses were then conducted to examine subject characteristics that independently predicted taking medicine at more times throughout a single day. Only variables that were found to be associated with the outcome with a set p value of <0.20 were included in the multivariable model. All statistical analyses were performed using STATA version 10 (College Station, TX).
The mean age of subjects was 63.3 years (SD=5.4); the majority were female (71.1%), white (60.8%), highly educated (61.4% college graduates), with a household income greater than $50,000 (61.9%). Nearly half of the sample, however, was identified as having either low (20.7%) or marginal (22.8%) health literacy skills. Eighty-four percent of subjects reported having one or more chronic health conditions (Table 2).
When dosing out the seven-drug regimen, participants on average identified six times in 24 hours to take medicine (SD=1.8); this ranged from as few as three to as many as 14 times a day. Approximately one third (29.3%) found seven or more times to dose out the regimen within 24 hours, while only 14.9% organized the medicine in four or fewer times a day as would be suggested through the proposed universal medication schedule. Examples of how patients actually dosed out the regimen are shown in Table 3.
In multivariable analysis that included the covariates of education, health literacy, and number of self-reported chronic conditions, low health literacy was found to be the sole independent predictor of a greater number of times per day for dosing out the seven-drug regimen (β=0.67; 95% Confidence Interval 0.12 to 1.22, p=0.018). Interactions between all patient characteristics were examined. Patients with low health literacy and no chronic conditions on average dosed out the regimen the most times daily compared to others (8.4 times a day vs. range of 5.6 to 6.3 times per day among other groups by literacy and chronic conditions, p=0.005). No other interactions by age, race, education, literacy, and chronic conditions were statistically significant.
To identify explanations for participants’ failure to consolidate the medicines into four or fewer times per day, we examined in detail how they handled three specific sets of medicines within the hypothetical regimen that could have been taken at the same time. Suspected root causes linked to each set were: overall difficulty taking multiple medications and coordinating doses (set 1), distraction of secondary, or ‘auxiliary’ instructions (set 2), and variability in language used to identify the time interval between doses (set 3). In the first set, the dosage instructions were exactly the same (Drugs E and F, Table 1). Nearly one third (30.8%) of subjects did not dose these drugs at the same hours of the day despite having identical label instructions.
In the second set, we investigated two drugs (F and G) that could have also be taken at the same daily intervals (3 times daily), yet one included the additional instruction to be taken “with food and water”. Half of participants (49.5%) did not take these medicines at the same time of day. In the final set, medications to be taken two times a day (A and B) were compared; Drug A expressed frequency as “twice daily” while Drug B stated the medicine was to be taken “every 12 hours”. Four out of five patients (79.0%) did not consolidate these variable expressions of dose frequency and took the two drugs at different times. Notably, Drug A instructions also included an auxiliary comment that the medicine should be taken for 10 days, and in both the second and third sets investigated, the dose (1 or 2 tablets) also varied.
Beyond examination of the above drug set scenarios, Table 4 details how long subjects demonstrated they would wait between doses for medications that were to be taken two times a day (Drugs A, B, D) and three times a day (Drugs E, F, G). Considerable variability was found among subjects with regard to how many hours they would allot between doses for both 2 and 3 times a day regimens. For drugs to be taken twice daily, subjects averaged 10.3 hours between doses (SD=3.0), with as small as one and as many as 18 hourly intervals (interquartile range= 10 – 12). For 3 times a day regimens, hourly intervals ranged from 1 to 13 hours, with the average between the first and second dose being 5.4 hours (SD=1.8; interquartile range = 4 – 7), and 6.5 hours between the second and third doses (SD=1.5; interquartile range = 6 – 8).
Our findings demonstrate that the majority of patients may self-administer multi-drug regimens more times a day than necessary, and those with limited literacy are at greater risk. This increased complexity at the very least translates to taking medicine too often each day, leading to substantial interference with patients’ lives. This could result in doses being frequently missed or incorrectly administered. Given the heightened concerns of medication safety and adherence, particularly among the elderly who take more medicine and are increasingly cognitively challenged20, we offer evidence that previously was unavailable. In particular strategies are needed to help patients not just understand how to take a particular medicine, but to consolidate and simplify how one takes an entire drug regimen.
The inherent complexity of the task of organizing multiple medicines into as few times per day may be an apparent reason for so many patients not utilizing more efficient consolidation strategies. This is evident in our finding that one in three older adults did not take two medicines (Drugs E and F) that had the exact same dosage instruction at the same time. Variability in how prescriptions are written, both in describing the timing of doses and expression of auxiliary instructions further distract individuals from this goal. Yet many patients may not explicitly perceive finding the most efficient medication-taking strategy to be the objective. It is also possible that patients might not understand that they can take different medicines at the same time, especially when the instructions are not identical.
We investigated older adults’ dosing of a hypothetical medication regimen and not their actual medicine. Therefore, the context and task of demonstrating use via the medication box might not directly reflect the way participants would self-administer prescribed drugs in their daily life. Further research is needed to investigate in-depth patient dosing strategies and beliefs about their own regimens. Second, our study was limited to the outcome of demonstration of medication use for a multi-drug regimen, and not adherence. While prior studies support the premise that taking medicine at more times daily could negatively impact long-term regimen adherence, our findings do not directly offer evidence to that association. Third, our analysis of root causes of overcomplicating regimens was post hoc and exploratory, and other aspects of the instruction for sets 2 and 3, such as different doses (one vs. two tablets) could have contributed to patient confusion. Fourth, our sample was representative of older adults of higher socioeconomic strata, as indicated by education attainment and household income. However, our findings should be viewed as the ‘best case’ scenario, as more socioeconomically disadvantaged patients are more likely to have limited health literacy and face even greater difficulty in organizing and dosing out complex medication regimens.21,22 Finally, we only provided participants with the task of demonstrating how and when they would take a seven-drug regimen; a large proportion of chronically ill and elderly patients take far more medicines daily. This also suggests our findings provide a conservative estimate of the potential confusion older adults face when attempting to consolidate and manage all of their prescribed medications.
The UMS was not directly evaluated, but our study highlights patient confusion surrounding medication use. Standardized instructions could be one of many remedies to aid patients and families. Of note, an efficacy trial of the UMS to improve patient comprehension was also conducted recently; findings show patients are better able to dose out medicines safely with UMS versus current standard instructions.23 With these findings and the IOM report, legislation has already been approved and passed by the State Board of Pharmacy in California requiring pharmacies to use these UMS instructions when applicable.24 Further study of the possible benefits, as well as risks of the UMS strategy is warranted, and evidence will soon be available from ongoing National Institutes of Health (NIH) and Agency for Healthcare Research and Quality (AHRQ) studies that are currently testing the UMS in actual use.25–27
If standardizing prescription instructions does aid patients in consolidating and taking their medication regimens, the UMS could further unite medical and pharmacy practice. Beyond pharmacy labeling, physicians could write the instructions with the more explicit UMS times to help patients have an adequate understanding of when to take not just newly prescribed medicines, but their entire regimen at the point of prescribing. Opportunities now exist with medical practices increasingly adopting EHR systems to leverage these tools and standardize prescribing practices following the UMS concept.28,29 By working across the medication prescribing and dispensing continuum, the previously noted variability within and between physician prescription writing and pharmacist transcribing can be reduced, and patient understanding and adherence to medication regimens improved.14–16
We offer compelling, preliminary evidence of the need to help all patients more clearly understand, organize, and simplify their medication regimens. While providing standard, explicit instructions is one possible response, other interventions will likely be necessary. For instance, drug labeling is meant to support and not replace prescriber and pharmacist spoken communication with patients. Educational and health system strategies that target provider communication skills and screening methods for identifying those at risk for complicating regimens and poor adherence are warranted. Similarly, prescribing one-a-day regimens, and bundling medications by times per day at the pharmacy might also be possible solutions. Ultimately, public health initiatives should help patients acquire a fundamental understanding of prescription medication use and when it would be safe and appropriate to take medications together.
Funding: This project was supported by the following: National Institute on Aging (R01 AG030611; PI: Wolf), National Cancer Institute (R21CA132771; PI: Wolf), and Agency for Healthcare Research and Quality (R01 HS017687, R01 HS019435; PI: Wolf)