Drug Prescribing in Hospitals: An International Comparison D. H. LAWSON, MD, MRCP,

AND

HERSHEL JICK, MD

Abstract: This paper presents a comparison of prescribing habits for patients hospitalized in medical wards of university hospitals in America and Scotland. American patients received almost twice as many drugs both during and prior to hospitalization than did comparable Scots. The differences between the countries were consistent for symptomatic and for more spe-

cific therapies. As compared to Scotland, drug therapy in America costs patients more in terms of financial outlay and adverse drug effects. The data do not permit evaluation of the relative benefits to the patients of the different quantities or types of drug used for similar circumstances in these countries. (Am. J. Public Health 66:644-648, 1976)

Intr-odluction1

medications they have consumed prior to hospitalization and their habits with respect to smoking and alcohol. In order to achieve standardized data collection, nurse monitors spend some four to six weeks training in Boston before commencing data collection in a new hospital. Where the new hospital is at a considerable distance from Boston, one nurse monitor is trained centrally and, after a trial period, may train subsequent monitors locally. A consistent finding of this international monitoring program has been that patients in North American hospitals receive more drugs during hospitalization than do those in Europe, the Middle East, or Australasia. On average, U.S. medical inpatients have received 9.1 drugs* per admission as compared with 7.1 drugs for Canadian, 6.3 for Israeli, 5.8 for New Zealand, and 4.6 for Scottish patients. In order to further explore these differences in prescribing habits, the countries with the highest (U.S.) and lowest (Scotland) drug use were compared. All participating hospitals in these two countries were university teaching hospitals and all monitored patients were hospitalized in general medical wards. Data were collected on patients from 12 wards in eight American hospitals and four wards in two Scottish hospitals. The American hospitals were located in Boston, MA, Providence, RI, Syracuse, NY, Tucson, AZ, and Richmond, VA, and the Scottish hospitals in Glasgow. Since drug use varies with the type of illness treated, those factors which reflect this, namely diagnosis, duration

In 1969, the Boston Collaborative Drug Surveillance Program (BCDSP) began collecting data from sources outside North America. In that year, two Israeli hospitals joined the program and, more recently, data have been collected from hospitals in New Zealand and Scotland. A consistent finding from this international drug monitoring has been widely differing patterns of drug usage by physicians in the different countries. The present report describes an evaluation of this finding.

Patients (and Methods The methods employed by the BCDSP have been described in detail elsewhere.' Nurse monitors are employed to collect data in a standardized fashion on consecutive patients admitted to certain medical wards. Included for each patient is a record of all drugs ordered while in hospital together with their starting indications and reasons for stopping. The starting indications for drug use include some 80 broad categories. I Patients are also questioned regarding the From The Boston Collaborative Drug Surveillance Program, Boston University Medical Center. Address reprint requests to Dr. H. Jick. Boston University Medical Center. Boston Collaborative Drug Surveillance Program, 400 Totten Pond Road, Waltham. MA 02154. Dr. Lawson is with the Royal Infirmary. Glasgow. Scotland. This paper, submitted to the Journal December 22, 1975, was revised and accepted for publication March 5. 1976. 644

*

All combination drug products are counted as one drug in this

study. AJPH, July, 1976, Vol. 66, No. 7

INTERNATIONAL DRUG PRESCRIBING TABLE 1-Per Cent of all Patients Receiving Treatment, for 10 Common Indications, in 721 Scottish and 1,442 American Patients.* Indication for therapy

SYMPTOMATIC Diarrhea Dehydration Constipation Anxiety Pain SPECIFIC Diabetes Hypertension Infection Congestive heart failure Anemia

America Number Per Cent

Scotland Per Cent Number

Ratio

America/Scotland

104 536 625 434 532

7 37 43 30 37

14 74 143 142 231

2 10 20 20 32

3.8 3.6 2.2 1.5 1.2

201 168 505 437 285

14 12 35 31 20

27 35 169 179 123

4 5 23 25 17

3.8 2.4 1.5 1.3 1.2

*Matched individually for age, sex, duration of admission, primary diagnosis, and survival.

and outcome of hospitalization, age and sex were taken into account in a detailed exploration of the difference in drug use between countries. In order to obtain comparability, each of the 773 Scottish patients was matched with two American patients, according to decade of age, sex, duration of hospitalization (< 10 days; 10+ days), survival and first discharge diagnosis (by 3 digit ICD code)2.** In addition, since data collection in Scottish hospitals commenced in 1972, only those American patients admitted since that date were included. Seven hundred twenty-one (93 per cent) Scottish patients were matched on all of the matching factors in this way. The remaining 52 -patients did not differ greatly from the original 773 with respect to number of drugs given during admission (average 5.7). Thus, 721 Scottish patients were successfully matched with 1,442 American patients. The mean age of both groups was 56 years, 51 per cent were male, 4.8 per cent died while in the hospital, and 47.5 per cent were hospitalized for ten days or less. The recorded discharge diagnoses in order of frequency were cardiovascular disease (36 per cent), gastrointestinal disease (12 per cent), respiratory disease (10 per cent), endocrine disease (8 per cent), cancer (7 per cent), blood disorders (3 per cent), musculoskeletal disorders (3 per cent), and others (20 per cent). The groups were comparable with respect to levels of blood pressure, blood urea nitrogen, and hemoglobin on admission, although not matched on these characteristics.

Results Drugs Administered in Hospital American patients received an average of 9.4 drugs per admission, whereas Scottish patients received only 4.5 drugs (p < 0.0001). A total of 603 American patients (42 per cent) The matching process was a direct one, 1-2, for each Scottish patient, two American patients with the same specified characteristics were sought and found. **

AJPH, July, 1976, Yol. 66, No. 7

received ten or more drugs during hospitalization, compared with only 63 Scottish patients (9 per cent). A review of the indications for prescribing medications revealed the differences to be present when the data were analyzed by selected symptom or by specific diagnosis. A comparison of the frequencies of medication use for ten representative indications is given in Table 14 For each indication, a greater proportion of American patients received therapy. The magnitude of the observed difference in frequency varied from about four-fold for diarrhea and diabetes mellitus to 16 per cent for pain and anemia. The data were also reviewed to assess differences in dosage of commonly prescribed drugs. The first daily dose of five commonly used drugs was assessed for each country. For furosemide, acetaminophen (paracetamol) and diazepam, starting doses were similar in the two countries. For oral ampicillin, there was a tendency for American physicians to prescribe higher doses-an initial daily dose of 4 G or more was given to 8 per cent of the Americans but only I per cent of the Scots who received this drug. By contrast, American physicians tended to prescribe lower doses of digoxin-a daily dose of 0.125 mg or less was given to 20 per cent of Americans but to only 6 per cent of the Scots. In addition to treating patients more frequently than did their Scottish counterparts, American physicians tended to use more drugs for each indication (Table 2). Thus, for diarrhea 15 per cent of those receiving any drug treatment in America received two or more drugs, whereas no Scottish patient did so. Similarly, 44 per cent of Americans who received treatment for hypertension were given two or more drugs compared with 23 per cent of Scots. Differences in the choice of drugs prescribed were noted for most indications. The information on drugs used to treat anxiety, hypertension and infection illustrate this point. Anxiety. In both American and Scottish hospitals, four t Information on "indication" is obtained routinely from the attending physician at the time a drug is prescribed. Discharge diagnosesper se are not included in Table I unless mentioned by the physician as a reason for prescribing. 645

LAWSON AND JICK

TABLE 2-Frequency of Use of Two or More Drugs in Those Receiving Treatment for Selected Indications among Matched Scottish and American Patients America Per Cent Frequency

Indication for Therapy

SYMPTOMATIC Diarrhea Dehydration Constipation Anxiety Pain SPECIFIC Diabetes Hypertension Infection Congestive heart failure Anemia

Scotland Per Cent Frequency

Ratio America/Scotland

16/104 255/536 292/625 51/434 199/532

15 48 47 12 37

0/14 55/74 40/143 20/142 83/231

0 74 28 14 36

0.6 1.7 0.8 1.1

112/201 74/168 225/505

56 44 45 59 49

7/27 8/35 50/169

26 23 30 22 33

2.2 1.9 1.5 2.7 1.5

257/437 140/285

39/179 40/123

emphasis. Firstly, the American physicians treated their patients for hypertension more often (Table 1) and with more drugs (Table 2) than did their Scottish counterparts despite the comparability of the patients with respect to mean blood pressure on admission to hospital. Secondly, the use of diuretics as hypotensive agents is much commoner in American than in Scottish hospitals. Thirdly, almost 15 per cent of Scots who received therapy for hypertension were given drugs which were not available to American physicians (bethanidine, debrisoquine, and clonidine). Finally, 15 per cent of Americans received drugs for hypertension which have all but been abandoned for this (or, indeed any) indication in Scotland (hydralazine and reserpine). Infection. In American hospitals, ten drugs and in Scottish hospitals. three drugs accounted for 75 per cent of those given for infection. The drugs given together with the frequency of their use for this indication are shown in Table 3. The differences between the countries were not due to variation in antibiotic use between American hospitals. The data indicate that American physicians treated infection more frequently (Table 1) and with more drugs (Table 2) than did their Scottish counterparts. In addition, Scottish physicians relied on a relatively small number of antibacterial agents, including one (trimethoprim-sulphamethoxazole) which has only recently been released to the American

drugs accounted for 90 per cent of those prescribed for the indication anxiety. In America. 63 per cent of such patients received diazepam compared with 43 per cent in Scotland. Comparable frequencies for phenobarbital were 8 per cent vs 20 per cent, for chlorpromazine 2 per cent vs 16 per cent and for chlordiazepoxide were 16 per cent vs 2 per cent. No American received promazine for anxiety whereas 13 per cent of Scots received this drug. Hvpertension. Eighty-four per cent of the drugs prescribed for hypertension was accounted for by eight drugs in American Hospitals as compared with six drugs in Scottish hospitals. In America, 27 per cent of those receiving a drug for hypertension received methyldopa, compared with 54 per cent in Scotland. Other drugs commonly used for this indication in America include hydrochlorothiazide (21 per cent), hydralazine ( I1 per cent), chlorothiazide (8 per cent), aldactazide (a mixture of spironolactone and hydrochlorothiazide) (5 per cent), furosemide (5 per cent), reserpine (4 per cent), propranolol (4 per cent), and spironolactone (4 per cent). The other drugs commonly used in Scotland for treatment of hypertension were bethanidine (12 per cent), propranolol (7 per cent), bendroflumethiazide (5 per cent), debrisoquine (5 per cent), and clonidine (5 per cent). Several differences between the two countries deserve

TABLE 3-Drugs Accounting for 75 Per Cent of Treatments for Infection Scotland

America

Drug Ampicillin Penicillin G

Cephalothin Gentamicin Phenoxymethyl-Penicillin G Tetracycline Sulphisoxazole Cephalexin Oxacillin

Erythromycin

Per Cent*

Drug

Per Cent*

24 11 6 6

Ampicillin TrimethoprimSulphamethoxazole Tetracycline

40 24 12

6 6 5 4 3

3

*Proportion receiving drug per 100 patients requiring treatment for infection. 646

AJPH, July, 1976, Vol. 66, No. 7

INTERNATIONAL DRUG PRESCRIBING

physician. Unfortunately, the data collected by the BCDSP do not include bacteriological information and so the comparability of the two groups with respect to type and antibiotic sensitivity of the infecting organism is unknown. New Drugs Several drugs in common use in Scotland are not available or only recently marketed in America. These include, "Slow K''-a slow release preparation of potassium chloride-given to 27 per cent of Scottish patients and consumed regularly prior to hospitalization by 9 per cent of them; "Septrin''-a fixed dose mixture of trimethoprim and sulphamethoxazole used to treat respiratory and renal infections-given to 8.3 per cent of Scottish inpatients; Salbutamol-a bronchodilator given to 5.5 per cent of Scottish patients and consumed regularly prior to hospitalization by 1.8 per cent of them; Practolol-a beta adrenergic blocking drug used for treatment of angina and arrhythmias-given to 2.2 per cent of Scottish patients and consumed by I per cent of them prior to hospitalization; Amoxycillin-a semisynthetic penicillin similar in action to ampicillin-given to 1 per cent of Scottish patients; and Nitrazepam-a benzodiazepine hypnotic-given to 33 per cent of Scottish inpatients. Of the drugs available in America which are unavailable or only recently marketed in Scotland, only flurazepam is prescribed in significant quantities. A total of 24 per cent of American patients received this drug in hospital. Adverse Effects of Drugs Where sufficient data were available for comparison purposes, as expected, the frequencies of adverse reactions attributed to specific drugs were similar in the two countries (Table 4). However, a total of 370 American patients were

TABLE 4-Adverse Reactions Rates Attributed to Selected Drugs in America and Scotland Drug

Heparin Furosemide Digoxin Ampicillin Diazepam

America Per Cent Frequency

29/188 34/280 46/415 24/223 22/420

15.4 12.2 11.1 10.8 5.2

Scotland Frequency Per Cent

2/14 19/155 12/111 11/107 1/91

14.3 12.3 10.8 10.3 1.1

recorded as experiencing one or more adverse effects of therapy (26 per cent) as compared with 107 Scottish patients (15 per cent) (p < 0.001). This suggests that the greater frequency of adverse reactions in American patients was due to greater drug use rather than to a greater proportion suffering toxicity to individual drugs. Drugs Prescribed on Discharge The average number of drugs American patients were advised to take following discharge from hospital was 2.1, compared with 1.3 for the Scots patients (p < 0.001). AJPH, July, 1976, Vol. 66, No. 7

Drugs Consumed Prior to Hospitalization A medication history was obtained from 1,360 Americans (94 per cent) and 672 Scots (93 per cent). Of these, 959 Americans (70 per cent) and 376 Scots (56 per cent) stated that they had consumed medications on a regular basis prior to hospitalization; 283 Americans (21 per cent) and 52 Scots (7.7 per cent) reported consuming four or more drugs regularly before admission. The average number of drugs consumed regularly by Americans prior to admission was 2.0 and by Scots was 1.2 (p < 0.001).3 Twenty-six per cent of American patients received cardiac drugs (including digoxin, quinidine, procainamide, and propanolol) compared with 11 per cent of Scots patients. The frequency of diuretic use was 23 per cent in U.S. and 12 per cent in Scotland; of antidiabetic agents was 13 per cent and 3 per cent; of vitamins, 10 per cent and I per cent; and of analgesics 10 per cent and 5 per cent respectively. Although there was a significantly greater proportion of American patients consuming medications prior to hospitalization, the proportion of smokers (53 per cent) was similar to that in Scotland (55 per cent), and the proportion who consumed alcohol was lower-63 per cent in America and 74 per cent in Scotland.

Discussion This paper provides a comparison of drug use in patients admitted to two Scottish and eight American university hospitals. The patients were all hospitalized in general medical wards during 1972-1974 and were matched for age, sex, survival, primary discharge diagnosis, and duration of hospitalization. American patients received over twice as many drugs during hospitalization as did their Scottish counterparts. In general, therapy was ordered more often for all common indications in America. Moreover, American physicians tended to order more drugs for each indication than did the Scottish physicians. This difference in drug use was noted both during hospitalization and following discharge from the monitored wards. In addition, the history of medication consumption prior to hospitalization showed similar differences between the countries. Several explanations for those differences must be considered. They were not due to inter-hospital variations within the countries, nor, in the case of medication histories, were they likely to be due to major differences in history taking since, in both countries, the information was collected by trained nurses in a standardized fashion. For specific indications, such as hypertension and diabetes, the decreased use of drugs in Scotland could be due to decreased prevalence of the diseases in the Scottish patients as compared to the matched American patients, less frequent diagnosis in Scottish patients who are otherwise comparable to their American counterparts in this study, less frequent drug treatment of diagnosed patients in Scotland, or some combination of the three. The current data are 647

LAWSON AND JICK

not complete enough to evaluate how much each of these factors may have contributed to the results. For most other indications, the differences were not likely to be due to substantial differences in severity of illness, reason for admission, or length of hospital stay, since the patients were matched on factors which tend to reflect these. In addition, they were unlikely to arise as a result of wide variations in criteria for making second or subsequent diagnoses, since all patients were from university teaching hospitals. Even if there were some differences in criteria for diagnosis, such differences are not likely to explain the very large disparity in prescribing habits. In addition, where objective data were available, such as admission blood pressures, hemoglobin and blood urea nitrogen levels, the patients were comparable in these respects. It seems unlikely, therefore, that differences in patient attributes or criteria of diagnosis are large enough to fully explain the extraordinary difference in prescribing habits between American and Scottish physicians. Thus, a major proportion of the difference appears likely to be due to physician prescribing habits rather than

patient attributes. While these data on inhospital drug use cannot be assumed to apply to non-teaching hospitals in the two countries, the fact that the magnitude of the differences in drug use was similar both within hospital and prior to hospitalization strengthens the view that the data are applicable more generally. Unfortunately, the data cannot be of assistance in deciding whether American patients benefited from the greater drug use in their country, but they raise this important question since it is certain that drug treatment in America costs more both in terms of financial outlay and adverse drug effects. It should be noted, however, that the greater incidence of adverse reactions in the American patients included in this study did not reflect itself in longer hospitalizations. Recently. considerable interest has been expressed concerning possible delays in introducing new drugs to America as compared to other countries.47 In this study of patients in medical wards of teaching hospitals, only six drugs were commonly used in Scotland which were unavailable in America. Since completing the study, two of these drugs have been released for use in America. In addition, one drug used

in Scotland (nitrazepam) has a therapeutically identical counterpart in everyday use in America (flurazepam). In this study the greatest difference in prescribing habits was in the treatment of hypertension, where Scottish physicians often used drugs unavailable in America. The information available does not permit comparison of the relative benefits or hazards of these drugs as opposed to those used in America.

REFERENCES 1. Jick, H., Miettinen, 0. S., Shapiro, S., Lewis, G. P., Siskind, V., and Slone, D. Comprehensive drug surveillance. JAMA 213:1455-1460, 1970. 2. U. S. Department of Health, Education, and Welfare. International Classification of Diseases (8th Revision), Vol. 1, 1968. 3. Snedecor, G. W., and Cochrane, W. G. Statistical Methods. 6th Edition. Iowa, Iowa State University Press, 1967. 4. Wardell, W. M. British usage and American awareness of some new therapeutic drugs. Clin. Pharmacol. Ther. 14:1022-1034, 1973. 5. Wardell, W. M. Therapeutic implications of the drug lag. Clin. Pharmacol. Ther. 15:73-96, 1974. 6. Wardell, W. M. Drug development, regulation and the practice of medicine. JAMA 229: 1457-1461, 1974.

ACKNOWLEDGMENTS Hospitals which have participated in the Boston Collaborative Drug Surveillance Program are: Boston, Massachusetts: Lemuel Shattuck Hospital, Peter Bent Brigham Hospital, Boston City Hospital, Veterans Administration Hospital, Massachusetts General Hospital, and University Hospital; Providence, Rhode Island: Roger Williams General Hospital; Syracuse, New York: State University Hospital of the Upstate Medical Center; Tucson, Arizona: Arizona Medical Center; Richmond, Virginia: Virginia Commonwealth University Hospital; Canada: St. Joseph's Hospital, London, Ontario; Israel: Hadassah-Hebrew University Hospital, Jerusalem, Beilinson Medical Center, Petah Tiqva, and Asaf-Harofe Hospital, Zerifin; New Zealand: Auckland Hospital, Auckland, and Hutt Hospital, Wellington; Scotland: Western Infirmary and Stobhill General Hospital, Glasgow; Italy: Desio Hospital, Milan. The Boston Collaborative Drug Surveillance Program has been supported by Public Health Service Contract No. NOI-GM-4-2148 from the National Institute of General Medical Sciences (NIGMS); and in part by grants from the United States Food and Drug Administration; the Canadian Health Protection Branch; the Israeli Ministry of Health; the Hadassah Medical Organization; the Kupat-Holim; Auckland Hospital, Auckland, New Zealand; the Roger Williams General Hospital (Brown University NIGMS Grant No. GM165-38-02); and the Scottish Home and Health Department.

SEMINAR ON DISEASES COMMON TO ANIMALS AND MAN SET FOR SEPTEMBER The Eighteenth Annual Midwest Interprofessional Seminar on "Diseases Common to Animals and Man" will be held on Tuesday and Wednesday, September 21-22, 1976 at the University of Missouri, Columbia, MO 65201. For information contact Dr. Don Blenden or Ms. Carol J. McAllister, Continuing Education in Veterinary Medicine, University of Missouri, 23 Veterinary Sciences, Columbia, MO 65201.

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AJPH, July, 1976, Vol. 66, No. 7

Drug prescribing in hospitals: an international comparison.

Drug Prescribing in Hospitals: An International Comparison D. H. LAWSON, MD, MRCP, AND HERSHEL JICK, MD Abstract: This paper presents a comparison...
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