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ORIGINAL ARTICLES Patient Misunderstanding of Dosing Instructions Nicholas A. Hanchak, MD, Monica B. Pater Jesse A. Berlin, ScD, Brian L. Strom, MD, MPH

OBJECTIVE: To compare o u t p a t i e n t s ' understanding of medication dosing i n s t r u c t i o n s written in terms of daily freq u e n c y w i t h patients' understanding of i n s t r u c t i o n s specifyIng hourly intervals. DESIGN: Prospective cohort s t u d y involving patient inter-

views. SETTING: A u n i v e r s i t y hospital o u t p a t i e n t pharmacy. PATIENTS: Five hundred patients p r e s e n t i n g new and refill

prescriptions t o t h e hospital o u t p a t i e n t pharmacy. INTERVENTION: Patients were interviewed using a standard-

i z e d questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 71 p a t i e n t s wj'th prescriptions s p e c i f y i n g dosing i n s t r u c t i o n s in hourly intervals (e.g., q6h), 5 5 (77%) misinterpreted the recomm e n d e d frequency of dosage compared with only 4 (0.93%) of the 4 2 9 patients with dosing i n s t r u c t i o n s s p e c i f y i n g daily f r e q u e n c y (e.g., qid] (relative risk 83; 95% c o n f i d e n c e interval 31-200). This difference remained w h e n patient subgroups were evaluated by e d u c a t i o n level, n e w versus refill prescriptions, and analgesic versus n o n a n a l g e s i c medications. CONCLUSIONS: This s t u d y i n d i c a t e s that the i n t e n d e d dosing regimen is frequently m i s u n d e r s t o o d w h e n the p h y s i c i a n writes o u t p a t i e n t prescriptions in hourly intervals. To prom o t e optimal patient compliance, the o u t p a t i e n t prescription label should s t a t e the number of t i m e s a day a medicat i o n is t o be taken. K E Y W O R D S : prescription drugs; patient compliance; dosage. J GEN INTERN MED 1996; 1 1 : 3 2 5 - 3 2 8 ,

Received from the Hospital of the University of Pennsylvania, Philadelphia (NAH); University of Pennsylvania, Philadelphia (MBP); Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, and Division of General Internal Medicine of the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia (JAB, BUS). Dr. Hanchak is currently President, U.S. Quality Algorithms, Inc., Blue Bell, Pa. Presented as a poster at the 17th Annual National Meeting of the Society of General Internal Medicine, Washington, DC, April 29, 1994. Address correspondence and reprint requests to Dr. Strorrc Room 824 Blocktey Hall, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021.

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atient compliance is i m p o r t a n t in achieving optimal t r e a t m e n t outcomes. Poor compliance is frequently a c a u s e of s u b o p t i m a l t r e a t m e n t of medical illness a n d often results in adverse side effects and d a n g e r o u s toxicities. Among the m a n y i m p o r t a n t c o m p o n e n t s of patient compliance are unrealistic expectations by the physician, s u c h as asking a patient to take medication too frequently or in the middle of the night; a patient's lack of unders t a n d i n g of the importance of proper treatment; a n d a lack of reinforcement over time. The physician m u s t effectively and explicitly c o m m u n i c a t e the directions for drug t h e r a p y to the patient ff the patient is expected to follow the intended instructions. Haynes a n d coworkers defined compliance as "the extent to which a person's behavior (in t e r m s of taking medications, following diets, or executing lifestyle changes) coincides with medical or h e a l t h advice. "1 However, several s t u d i e s have suggested t h a t n o n c o m p l i a n c e often resuits from a lack of a g r e e m e n t between what the p a t i e n t thinks he or she is s u p p o s e d to do a n d w h a t the physician actually w a n t s the patient to do. 2-5 The timing of drug administration m a y be considered an i m p o r t a n t a s p e c t of drug therapy, especially w h e n multiple daily doses are required to m a i n t a i n a t h e r a p e u tic blood c o n c e n t r a t i o n of the drug. Critical to the adherence to an appropriate drug regimen is effective c o m m u nication of the dosage i n s t r u c t i o n s to the patient. W h e n the patient is taking multiple medicines, it is often difficult for the physician to state the exact time of day w h e n the patient should take each medication. Often the physician a s s u m e s patient u n d e r s t a n d i n g . However, a p a t i e n t who does not u n d e r s t a n d the correct dosage i n s t r u c t i o n s for a medication c a n n o t be expected to comply with those instructions. In an i n p a t i e n t setting, it is easy to a d m i n i s t e r medicines at specified hourly intervals, b u t s u c h a precise regimen is s o m e t i m e s impractical for patients to follow in their h o m e e n v i r o n m e n t s a n d usually u n n e c e s s a r y . Given that m o s t physicians have b e e n trained primarily in inpatient settings, this practice of giving dosages by hourly intervals m a y be c o m m o n and m a y often lead to m i s u n d e r s t a n d i n g a m o n g outpatients. W h e n a prescription is written for an hourly interval, the potential for confusion of interpretation is substantial. For exampte, a physician m a y write a prescription as q6h (every 6 hours), intending that the patient take the medication four times a day. 325

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However, the patient m a y interpret these instructions as every 6 h o u r s while awake a n d m a y take the medicine only three times a day, s u c h as on a 10:00 AM, 4:00 PM, and 10:00 PM schedule. This s t u d y c o m p a r e s patient und e r s t a n d i n g of dosage instructions, specifically how m a n y times a day a medication is to be taken, w h e n prescriptions are written in terms of hourly intervals between drug ingestion with t h a t w h e n prescriptions are written in terms of daily frequency.

METHODS This s t u d y was approved by the Hospital of the University of Pennsylvania O u t p a t i e n t P h a r m a c y a n d the Institutional Review Board of the University of Pennsylvania.

Patient Selection Five h u n d r e d patients presenting either n e w or refill p r e s c r i p t i o n s at the O u t p a t i e n t P h a r m a c y of the Hospital of the University of Pennsylvania were interviewed sequentially while they waited in line to fill their prescriptions. In general, persons using this p h a r m a c y are patients seen in the h o u s e s t a f f clinics or the faculty practices, b u t they also include some hospital employees. One nonphysician r e s e a r c h e r (MBP) interviewed all 500 patients. Interviews were collected over 7 m o n t h s , on weekdays only. The time of the day of the interviews was varied to e n s u r e a representative sampling of the patient population. A day w a s divided into m o r n i n g and a f t e r n o o n / e v e n i n g segm e n t s , with m o r n i n g including the h o u r s between 9:00 a n d 12:00 noon a n d a f t e r n o o n / e v e n i n g including the h o u r s between 12:00 noon a n d 7:00 PM. Interviews were collected during each period of each day of the week between Monday and Friday. All eligible patients who consented and spoke English were enrolled during a n y given period. Data collection began in A u g u s t 1993 and was completed in February 1994.

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tions written as prn (take as needed) and tad (take as directed) were excluded as well.

Study Questionnaire The s t u d y q u e s t i o n n a i r e first obtained demographic information. The m a i n outcome was b a s e d on the patient's response to the following question: "How m a n y times a day do you u n d e r s t a n d that your medication is to be taken?" Specifically, we were interested in w h e t h e r patients m i s u n d e r s t o o d the intended frequency of medication. Before asking the patient's u n d e r s t a n d i n g of frequency, the interviewer explained to the patient w h a t the instructions on the prescription specified. For example, if a prescription read "q6h," the interviewer would tell the patient that the instructions were to take the medication every 6 hours. Other information obtained from the patient included the total n u m b e r of prescriptions to be filled at that visit, the total n u m b e r of medications currently being taken (including those presented to the researcher), patient age, marital status, type of prescription insurance, level of education, gender, and race. Information obtained from the prescription label included the prescription type (new or refill), the dosage type (times a day or hourly intervals), the prescribed frequency of drug administration, the class of medication (analgesic, antibiotic, cardiovascular-renal, dermatologic, endocrinologic and metabolic, gastrointestinal, hematologic, respiratory and antihistamine, vitamin or nutritional supplement, or other), the presence or absence of the indication for the medication on the label or physician's prescription, and a g r e e m e n t of patient u n d e r s t a n d i n g of dosing instructions with instructions written on the label. For prescriptions written in hourly intervals, we a s s u m e d that the physician's intention was to be interpreted literally on the basis of a 2 4 - h o u r daily period: e.g., q6h was a s s u m e d to m e a n four times a day.

Statistical Analysis Prescription Selection Data collection involved only one prescription per patient. In situations in w h i c h the p a t i e n t p r e s e n t e d more t h a n one prescription to be filled, a single prescription w a s selected by arranging the prescriptions t h a t specified hourly intervals in alphabetical order (according to their generic names) a n d identifying a single prescription at random, utilizing a table of r a n d o m n u m b e r s . If the patient p r e s e n t e d no prescriptions written in hourly intervals, t h e n the s a m e procedure was used to select a prescription written in terms of n u m b e r of times a day. B e c a u s e of an anticipated low frequency of m i s u n d e r standing, prescriptions written as qd (once a day) or q24h, qod (once every other day) or q48h, qhs (once at night) or q24h at night, and q a m (once in the morning) or q 2 4 h in the m o r n i n g were excluded from this study. Because of a lack of specific dosing instructions, prescrip-

The patients with prescriptions given in t e r m s of hourly intervals and those with prescriptions specifying n u m b e r of times a day were first c o m p a r e d with respect to demographic and other characteristics that might affect their level of u n d e r s t a n d i n g of prescriptions. For discrete variables ×2 tests were used. The m e a n age was compared between groups using the S t u d e n t ' s t test for i n d e p e n d e n t samples. The proportion of patients m i s u n d e r s t a n d i n g their dosing i n s t r u c t i o n s was compared between the two prescription groups using the ×2 test. The relative risk (RR) of m i s u n d e r s t a n d i n g a n d a 95% confidence interval (CI) were calculated u s i n g s t a n d a r d methods. 6 Stratified analyses and logistic regression were used to compare the two groups while controlling for potential confounding and to investigate the possibility that the differences were confined to particular s u b g r o u p s of patients. W h e n any ex-

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pected cell c o u n t s in 2 × 2 tables were less t h a n 5, Fisher's Exact Test and exact stratified analyses were used. 6

RESULTS Of the 500 patient prescriptions evaluated, 71 (14.2%) were written with i n s t r u c t i o n s specifying medication ingestion by hourly intervals while 429 (85.8%) were written specifying the n u m b e r of times a day the medication was to be taken. There were significant differences (p < .005) b e t w e e n the s t u d y groups in the distribution of analgesic v e r s u s nonanalgesic prescriptions and new vers u s refill prescriptions (Table 1). No significant differences were found b e t w e e n the two groups for a n y other characteristics studied. Overall, 59 (11.8%) of the 500 prescriptions were misinterpreted. Only 4 (0.93%) of the 429 prescriptions written in frequency of dosage were misinterpreted, w h e r e a s 55 (77%) of the 71 of those written in hourly intervals were misinterpreted (RR 83; 95% CI 31-200). Of the 59 patients who misinterpreted prescriptions, 40 h a d prescriptions written as q6h. Of those 40 patients, 31 (78%) interpreted q6h to m e a n three times per day and 9 (22%) t h o u g h t the medication was to be t a k e n twice per day. Although analgesic prescriptions m a y be written in hourly intervals, analgesic medications could be misinterpreted as having implicit p r n instructions. In this study, 83 (16.6%) of the 500 prescriptions were written for analgesics: 27 (87%) of the 31 analgesic prescriptions written in hourly intervals were misinterpreted, while 0 (0%) of the 52 analgesic prescriptions written in frequency per day were misinterpreted (p < .001). Nonanalgesic prescriptions showed similar results: 28 (70%) of the 40 prescriptions written in hourly intervals misinterpreted while only 4 (1.06%) of the 377 nonanalgesic prescriptions writt e n in frequency per day were misinterpreted (p < .001).

Age, gender, race, insurance, education, marital status, and the a b s e n c e of m e d i c a t i o n indication showed no relation to patient u n d e r s t a n d i n g of dosage instructions. A d j u s t m e n t for any of the characteristics listed in Table 1, u s i n g either stratified analysis or logistic regression, also h a d no meaningful effect on o u r results.

DISCUSSION Several studies suggest that n o n c o m p l i a n c e may be c a u s e d by a m i s u n d e r s t a n d i n g of physicians' intentions regarding drug therapy. Ostrom et al. found disagreem e n t s between the patient's interpretation a n d the instructions on the prescription label for 51 (37%) of 138 patients interviewed who were using prescription drugs. 2 Zuccollo a n d Liddell found t h a t 37 (60%) of 60 elderly o u t p a t i e n t s did not have a clear u n d e r s t a n d i n g of prescription dosing instructions, 3 while Fletcher et al. reported t h a t only 77 {58%) of the 133 patients interviewed who received prescriptions knew the correct dosage for all of their medications. 4 Salako and Adadevoh interviewed patients to determine their r e a s o n s for not taking medications as they were prescribed, a A frequent c a u s e of n o n c o m p l i a n c e was m i s u n d e r s t a n d i n g of the prescription label, which included taking half or double the dosage or taking the medication in a m a n n e r u n r e l a t e d to the actual prescription instructions. Lack of p a t i e n t compliance often leads to t h e r a p e u t i c failure and consequently adverse side effects. Col et al. interviewed 315 elderly patients admitted to the hospital a n d found that 36 (11.4%) of those admissions were due to medication noncompliance. 7 O u r study d e m o n s t r a t e s t h a t an extremely large percentage of dosage instructions are misinterpreted w h e n they are written in hourly intervals. Other studies have

Table I. Distribution of Characteristics for Patients with Prescriptions Written in Terms of Frequency per Day Versus Those with Prescriptions Written in Terms of Hourly Intervals Frequency per Day (N = 429)

Hourly Intervals (N = 71 )

Characteristic

No.

(%)

No.

(%)

p Value

Mean age, years (SD) Male gender Black race Insured College education or higher Married Indication noted on prescription Analgesic No. of prescriptions being filled 1 2 3 New prescriptions

41.8 146 244 414 95 195 20 52

(16.4) (34.0) (56.9) (96.5) (22.1) (45.5) (4.7) (12.1)

39.7 23 48 68 13 28 9 31

{14.6) (32.4) (67.6) (95.8) ( 18.3} (39.4) (12.7) (43.7)

.31 .79 .09 .76 .47 .35 .007 <.001

205 122 102 352

(47.8) (28.4) (23.8) (82.1)

42 20 9 69

(59.1) (28.2) (12.7) (97.2)

.03 (trend) .001

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also shown that the patient misunderstands instructions w h e n a p r e s c r i p t i o n d o e s n o t specify t h e n u m b e r of t i m e s a d a y a m e d i c a t i o n is to b e t a k e n . W h e n K e n d r i c k a n d B a y n e a s k e d 3 7 n u r s i n g h o m e r e s i d e n t s to i n t e r p r e t a prescription written as "take one tablet every 6 hours," o n l y 8 (22%) i n d i c a t e d t l l a t t h e y w o u l d t a k e f o u r t a b l e t s a day, t h e c o r r e c t d o s a g e for t h i s m e d i c a t i o n . 8 M a z z u l l o e t at. f o u n d t h a t 17 (25%) of 6 7 p a t i e n t s i n t e r p r e t i n g a p r e scription written as "tetracycline, 250 mg every 6 hours" indicated that they would take the medication only three t i m e s a day. 9 T h e m a i n r e a s o n for e x c l u d i n g t h e f o u r t h d o s e w a s t h a t t h e p a t i e n t s h a d i n t e r p r e t e d a "day" to ind i c a t e 18 h o u r s or o n l y h o u r s w h i l e a w a k e . 9 K i m m i n a u and Wright suggest that prescriptions written as "take at 7 : 0 0 AM, 12 n o o n , 6 : 0 0 PM, a n d 1 1 : 0 0 PM" a r e b e t t e r t h a n " t a k e e v e r y 6 h o u r s . "1° H o w e v e r , t h e s e s t u d i e s o b s e r v e d m i s u n d e r s t a n d i n g of p r e s c r i p t i o n l a b e l s of m e d i c a t i o n s t h a t w e r e n o t specifically p r e s c r i b e d to t h e p a t i e n t i n t e r viewed. Wootton interviewed patients about their prescription instructions and concluded from her data that informat i o n o n p r e s c r i p t i o n l a b e l s is o f t e n p o o r l y w r i t t e n . 11 In a d d i t i o n , Morrell e t al, f o u n d t h a t p r e s c r i p t i o n s w r i t t e n a s " t a k e a t 8 : 0 0 AM a n d 8 : 0 0 PM" w e r e m o r e o f t e n c o r r e c t l y u n d e r s t o o d t h a n p r e s c r i p t i o n s w r i t t e n a s " t a k e e v e r y 12 h o u r s . "12 T h e s e s t u d i e s s t r e s s t h e n e e d for a c l e a r definit i o n of w h a t c o n s t i t u t e s a "day." T h e s t r e n g t h s of t h i s s t u d y i n c l u d e its p r o s p e c t i v e nature, rigorous study design, and unambiguous results. W e a n a l y z e d s e v e r a l i m p o r t a n t p a t i e n t c h a r a c t e r i s t i c s inc l u d i n g e d u c a t i o n level a n d i n s u r a n c e t y p e a s p o s s i b l e c o n f o u n d e r s a n d p o s s i b l e s o u r c e s of i n t e r a c t i o n a n d f o u n d n o c h a n g e i n o u r c o n c l u s i o n s , Also, all i n t e r v i e w s were conducted using a standardized questionnaire des i g n e d to a n a l y z e a c l e a r l y d e f i n e d s t u d y o u t c o m e . However, t h i s d e s i g n h a s a few p o t e n t i a l l i m i t a t i o n s . The study measured patient compliance by evaluating only one prescription per patient. Patient understanding of i n s t r u c t i o n s m a y n o t b e a c c u r a t e l y a s s e s s e d f r o m o n e p a r t i c u l a r p r e s c r i p t i o n label, a l t h o u g h t h e r e s u l t s w e r e c l e a r l y n o t d u e to r a n d o m error. We also assumed that prescriptions written as hourly i n t e r v a l s r e q u i r e a n explicit d r u g a d m i n i s t r a t i o n p e r i o d of 2 4 h o u r s . A l t h o u g h it s e e m s u n l i k e l y , p e r h a p s p h y s i c i a n s who write prescriptions as q6h actually intend drug adm i n i s t r a t i o n 3 t i m e s a d a y r a t h e r t h a n 4 t i m e s a day. If so, w e m i s i n t e r p r e t e d p h y s i c i a n s ' i n s t r u c t i o n s , b u t p a t i e n t s w h o i n t e r p r e t q 6 h a s f o u r t i m e s a day, a s we did, would then be taking more medication than their physic i a n s i n t e n d e d . W h a t is i m p o r t a n t is n o t t h e p h y s i c i a n ' s i n t e n t , p e r se, b u t t h a t t h e p a t i e n t ' s u n d e r s t a n d i n g m a t c h e s t h a t i n t e n t . E v e n if t h e p h y s i c i a n e x p l a i n s h i s or h e r i n t e n t to t h e p a t i e n t , it w o u l d s e e m c r u c i a l to r e i n f o r c e t h a t

i n f o r m a t i o n b y h a v i n g explicit i n s t r u c t i o n s

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w r i t t e n di-

r e c t l y o n t h e label. W e c a n n o t r u l e o u t t h e p o s s i b i l i t y t h a t , i n fact, t h e i n d i v i d u a l p h y s i c i a n s w h o w r o t e p r e s c r i p t i o n s i n h o u r l y int e r v a l s a l s o t o o k l e s s t i m e to e x p l a i n t h e p r e s c r i p t i o n s to p a t i e n t s . E v e n if t h i s w e r e t r u e , t h a t l a c k of t i m e s p e n t w i t h p a t i e n t s m a k e s it still m o r e i m p o r t a n t for l a b e l i n g to b e e x t r e m e l y explicit. A n o t h e r p o t e n t i a l l i m i t a t i o n is t h a t r e s u l t s f r o m t h i s single university hospital may have limited generalizability to o t h e r s e t t i n g s . F o r e x a m p l e , t h e p r o p o r t i o n of p r e scriptions already being written in terms of frequency was q u i t e h i g h (85.8%). If t h i s p r o p o r t i o n w e r e still h i g h e r a t o t h e r t y p e s of h o s p i t a l s , t h e a b s o l u t e n u m b e r of m i s u n derstood prescriptions would be smaller than expected on t h e b a s i s of o u r r e s u l t s . N e v e r t h e l e s s , a m o n g p a t i e n t s with prescriptions written in hourly intervals, there was a h i g h level of m i s u n d e r s t a n d i n g of daily f r e q u e n c y . In c o n c l u s i o n , i n o r d e r to e n s u r e c o m p l e t e p a t i e n t u n d e r s t a n d i n g of o u t p a t i e n t p r e s c r i p t i o n d o s i n g i n s t r u c t i o n s , we r e c o m m e n d t h a t : (1) t h e p r e s c r i p t i o n l a b e l s h o u l d s t a t e t h e n u m b e r of t i m e s a d a y a m e d i c a t i o n s h o u l d b e t a k e n , r a t h e r t h a n t h e h o u r l y i n t e r v a l s , a n d (2) if a r o u n d - t h e - c l o c k a d m i n i s t r a t i o n or t h e h o u r l y i n t e r v a l o r b o t h a r e clinically i m p o r t a n t , a m b i g u i t y s h o u l d b e a v o i d e d , p e r h a p s b y s p e c i f y i n g t h e a c t u a l t i m e s of d a y when medications should be taken.

REFERENCES 1. Haynes RB, Taylor DW, Sackett DL. Introduction. In: Compliance in Health Care. Baltimore, Md: Johns Hopkins University Press; 1979. 2. Ostrom JR. Hammarlund ER, Christensen DB, Plein JB, Kethley AJ. Medication usage in an elderly population. Med Care. 1985; 23:157-64. 3. Zuccollo G, Liddell H. The elderly and the medication label: doing it better. Age Ageing. 1985;14:371-6. 4. Fletcher SW, Fletcher RH, Thomas DC, et al. Patients' understanding of prescribed drugs. J Community Health. 1979;4:183-9. 5. Salako LA. Adadevoh BK. Patient attitudes, understanding and consumption of prescribed drugs. West Air J Med. 1972; 140-3. 6. Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic Research: Principles and Quantitative Methods. Belmont, Calif: Lifetime Learning Publications; 1982. 7. Col N, Fanale JE, Kronholm P. The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. Arch Intern Med. 1990; 150:841-5. 8. Kendrick R, Bayne JRD. Compliance with prescribed medication by elderly patients. CMA J. 1982; 127:961-2. 9. Mazzullo JM, Lasagna L, Griner PF. Variations in interpretation of prescription instructions. JAMA. 1974;227:929-31. 10. Kimminau MD. Wright RJ. The pride and perfection of the prescription label. Am Pharm. 1981;NS21:46-9. 11. Wootton J. Prescription for error. Nurs Times. 1975;884-6. 12. Morrell RW. Park DC, Poon LW. Quality of instructions on prescription drug labels: effects on memory and comprehension in young and old adults. Gerontologist. 1989;29:345-54.