Drug Utilization Studies - an Instrument in Drug Research

P.K.M.Lunde, M.Andrew, and I. Baksaas1

Introduction

The term drug utilization is formally defined in a technical report from the World Health Organization (1977) as follows:

The marketing, distribution, prescription and use of drugs in a society, with spe­cial emphasis on the resulting medical, social and economic consequences.

This comprehensive definition probably covers most, if not all, aspects of drug epidemiology, including methodological approaches as well as descriptive and ana­lytical evaluations. However, it might still have been desirable to include "drug development," which includes priorities in innovative drug research.

Accordingly, along with the fundamental misconception that clinical pharma­cology is a discipline merely reflecting interest in pharmacokinetics and plasma concentration monitoring, the notion should also be avoided that drug utilization research is, likewise, synonymous with drug statistics. However, this chapter will deal with ways in which various types of drug sales and prescription data can be used as a tool in more comprehensive drug evaluation and research, including some elements of drug regulation and information.

Types and General Use of Drug Statistics

Whenever drug statistics are to be established, a number of preambles have to be thoroughly considered. Above all, the purpose ought to be clearly defined, i. e., whether the use of the data relates to administrative, economical, commercial, phar­maceutical, or medical problems. Likewise, routine surveillances should not be designed unless appropriate criteria for interpretation (including limitation of data) and requirements for supplementary research are also included.

In order to enhance the validity, comparability, and relevance of the data, a suffi­ciently detailed drug classification system is necessary, along with appropriate units of measurement (cost or quantity). Needless to say, it is crucial to have open access to the relevant drug data sources (i. e., drug sales, prescriptions, etc.) according to

1 Department of Pharmacotherapeutics, University of Oslo, Norway

H. Kewitz et al. (eds.), Epidemiological Concepts in Clinical Pharmacology© Springer-Verlag Berlin, Heidelberg 1987

58 P. K. M. Lunde et a1.

drug class, geographical area, and various echelons of the health services, as well as to other relevant demographic and health statistics material. Unfortunately, restric­tions on the use of drug data, along with deficiences in various types of health statis­tics (morbidity, etc.), may greatly hamper the development of drug statistics as an instrument in these contexts.

However, with increasing awareness as to the usefulness of such data, consider­able progress has been made. Thus the Nordic countries, stimulated by WHO, have developed a more or less uniform system with adoption of a common drug classifi­cation as well as units of measurement (for details see Baksaas-Aasen 1975 a; WHO 1977; Westerholm 1979; Sakshaug et al. 1983; Lunde 1984; Sj6qvist and Agenas 1984; Tognoni 1984; The Nordic Council on Medicines 1985). This system has now been adopted by research groups and health authorities in most European coun­tries, and elsewhere.

When properly established and interpreted, drug statistics can be used to:

1. Describe patterns of drug use at various levels of the health care system, look at the development of therapeutic profiles over a period of time, and make rough estimates of the number of patients exposed to various drugs

2. Measure the effects of educational, informative, and regulatory efforts, price pol­icies, etc., and thus provide a basis for adjustments whenever necessary

3. Define areas for further investigations on the absolute and relative efficacy and safety of drug therapy

4. Aid in the determination ofbenefitlrisk and costleffectiveness 5. Indicate the overuse, underuse, or misuse of individual drugs or therapeutic

classes of drugs 6. Tentatively estimate drug needs in a society in relation to morbidity patterns,

thus aiding the planning of drug selection, supply, distribution, and use - as part of a drug and health policy

Tentative Calculation of "Morbidity"

The adoption of appropriate dose unit drug statistics makes it tempting, and some­times justified, to make rough estimates of detected morbidity. However, this only relates to well-defined diseases which distinctly indicate the prescription of specific drugs. Thus, it was originally thought that the use of insulin would broadly conform with the prevalence and incidence of type I Guvenile) diabetes. But insulin is also partly used for type II (adult onset) diabetes, thus making such estimates less pre­cise (see "Studies in Diabetes," p.65).

In fact, epilepsy turned out to be an even better example. Quite time-consuming epidemiological studies in the early 1970s had revealed that the total population with epilepsy in Norway was of the order of 20000-25000 patients. However, at least partly due to the deficient neurological services in Northern Norway, the pre­valence of epilepsy there was thought to be only about 70% of the country's average (de Graaf 1973). It is thought-provoking that a 3-h calculation exercise on the drug sales figures for anti epileptic drugs could easily confirm these results (Lunde et al. 1973). The fraction of patients receiving more than one drug (about 65%) was broadly known at that time from plasma concentration monitoring of antiepileptic drugs.

Drug Utilization Studies - an Instrument in Drug Research 59

Oral contraception is another probably quite valid example of the potential use­fulness nature of drug sales statistics whenever estimates of drug-exposed popula­tion fractions are desirable (Baksaas and Lund 1984).

It must be underlined that such estimates should generally be made with great caution, not least when drugs are used for several indications (most drugs!) and whenever they occur in a variety of fixed dose combinations (Baksaas-Aasen et al. 1975a; Laporte and Tognoni 1983).

"The Practolol Story"

Since 1971 practolol had, along with propranolol, become the most popular beta­adrenergic blocking agent in Norway, despite the fact that it was not approved for use in hypertension. Thus, late in 1974 when the alarming symptoms of ocular, der­matological, and other immunological adverse effects were recognized, it was esti­mated that about 10000-12000 patients could be on continuous treatment with this drug. This fact by itself made it quite difficult to withdraw practolol immediately from the Norwegian market, so a warning was forwarded to all Norwegian physi­cians by October/November 1974, telling them to avoid prescriptions of practolol to new patients, and gradually to transfer those already on treatment to an alterna­tive beta-blocker. These warnings were reinforced through local drug and therapeu­tic committees, and specific reports on suspected adverse reactions to practolol were also requested. Accordingly the sales of practolol went down by about 60% between November 1974 and June 1975 (Fig. 1), a decrease reflected in the increased sales of alternative drugs. However, this decline was slower in some outly­ing counties than in the most centrally located ones (Baksaas-Aasen et al. 1975b; Lunde 1976). After receiving about 80reports on adverse drug reactions (ADRs), several of which were severe and partly irreversible, the oral formulation of the drug was withdrawn from 1 September 1975. It should be stressed that nearly all these ADR reports referred to patients already on practolol treatment when the warnings were given.

Studies in Hypertension

The dilemmas of whether and how to treat various forms of hypertension according to severity, sex, and age remain broadly unsolved even after the publication of three major studies in 1985 (Amery et al. 1985; MRC trial 1985; IPPPSH trial 1985). Accordingly, major qualitative and quantitative differences in sales and prescrip­tion figures for antihypertensive drugs have repeatedly been demonstrated within as well as between countries (Lunde 1976; Baksaas-Aasen et al. 1977; Baksaas 1979, 1984). Depending on whether these disparities reflect real differences in the preva­lence of hypertension or in the rate of detection, demographic factors, therapeutic attitudes, and drug preferences, etc., they may have extensive medical and health economic consequences. Further analyses of these problems call for various approaches, including validation of the drug sales vs prescription statistics.

1. Norwegian Studies. Since drug dose statistics were adopted in Norway (Halse and Samseth 1971; Baksaas-Aaasen et al. 1975 a), persistent intercounty differences

60

.l: r: o o o ..... III

'" III o -0

>-

ns -0

-0

'" r:

12

10

8

6

'; I. o

2

_ Alprenolol

0-0 Oxprenolol _ Pindolol

_ Practolol

~ Propranolol

........ Timolol

..... Total

Sept Oct Nov. Des Jan. Febr Mar Apr May June

1971. 1975

P. K. M. Lunde et al.

Fig.1. Monthly sales figures of practolol and other beta-adrener­gic blockers in Norway, September 1974-June 1975. The gradual drop in the sales of practolol reflects the effect of warnings of adverse reac­tions forwarded by the health authorities, the pharmaceutical company, and local drug commit­tees in October/November 1974 to all Norwegian physicians. (Lunde 1976)

have been detected, although the amounts and types of drugs prescribed are chang­ing substantially with time (Fig.2 and 3). Another prominent feature is that most patients with hypertension are handled solely by general practitioners (GPs). Thus a prescription survey was undertaken in 1975, addressing 154 (54% of all) GPs in four Norwegian counties, two of which registered below and two above the country's average sales (Baksaas et al. 1978). A three-step approach was adopted;

a) Collection of prescription copies for one month, including all patients receiving antihypertensive treatment, supplemented by specific questions about the cur­rent and previous diagnostic and therapeutic situation of each patient

b) A follow-up enquiry asking each GP to make more general statements about his/her diagnostic, therapeutic, and control criteria

c) Apostproject discussion with the participating GPs of the results and their inter­pretation, including a brief teaching update on current antihypertensive treat­ment

Drug Utilization Studies - an Instrument in Drug Research 61

100% = MEAN

I 0stfold 120°1. •

2 Akcrshus 89 0/0

3 Oslo Jlll %

132 %

4 Hcdmark 95 0 /.

5 Oppland 129 oJ.

6 Buskcrud 84 0/.

7 Vtstfold 83 0 /0

8 Ttltmark 116 % •

9 Aust-Agdtr 103 %

10 Vtst-Agdtr 1OS0/0

II Rogaland 90 '/0

12 Hordaland 71 °/.

14 50gn og Fjordant 106 0/0

IS Mort og Romsdal 82 ,/, ••

16 50r-Trondtlag 90 0/0

17 Nord- Trondtlag 85 '/0

18 Nord land 113 0/.

19 Troms 114 ·/0

20 Finnmark 92 °1 • ••

Fig. 2. Sales of antihypertensive drugs in the 19 counties of N OTWay, 1974. Black and hatched areas indicate the two high- and the two low-consumption counties included in the prescription survey in October, 1975. (Baksaas et al. 1978)

A total of 4095 prescriptions for 3253 patients with mainly moderate to mild hyper­tension was collected. GPs alone treated 72% of the patients, 11 % had been referred to specialists, and the remaining also to hospitals. According to total sales figures (Table 1), this sample appeared quite representative. A clear female predominance among the patients was seen at all ages (Fig.4). At that time beta-blockers were already preferred for male patients below 50 years of age, while diuretics were pre­ferred for those above 50 years, and also especially for female patients. A quite satis­factory average blood pressure control could also be demonstrated (Fig.5). The most disturbing finding refers to the registration of ADRs (Table 2). This survey also included a validation of defined vs prescribed daily doses (DDDs vs PDDs). In gen­eral a good correspondence was found, although the PDDs for diuretics were about 20% lower than the DDDs. On the contrary, comparing the number of prescriptions only would often lead to more extensive skewnesses (Baksaas 1978).

More recent studies, based on a questionnaire survey of case histories, have revealed that Norwegian GPs are more prone to start treatment of nonsymptomatic mild to moderate hypertension than their specialist colleagues in internal medicine (Baksaas et al. 1986 b). Thus for younger patients, 71 % of a representative sample of 275 Norwegian physicians set a lower diastolic blood pressure limit than generally

62

140

120

~ 100 "C

.r:. c 80 0 0 0

60 Cl Cl Cl 40

20

o

140

120

~ 100 "C

.r:. c 80 0 0 0

60 Cl Cl Cl 40

20

o

NORTHERN IRELAND

"* other hypotensives

beta-blockers

~retics ------thiazides and comb.

1973 -75 -77 -79 -81

SWEDEN

other hypotensives

beta-blockers

other diuretics

thiazides and comb.

1973 -75 -77 -79 -81

P. K. M. Lunde et al.

NORWAY

other diuretics

-thiazides and comb.

1973 -75 -77 -79 -81

Fig. 3. Sales/prescription figures for anti­hypertensives in Northern Ireland, Norway, and Sweden, 1973-1981, according to the Anatomical Therapeutical Chemical classi­fication system, as given in defined daily doses (D D D) per 1000 inhabitants per day. (Griffiths et al. 1985)

Drug Utilization Studies - an Instrument in Drug Research

oil 800 e---. Females C -- Males " dI .. ~ . 0 700 . 0- . . . . '0

. . . . . . 0 600 . . . z . .

; . · ~

500 · · · · · · · · · · · · · · · · 400 · · · · · · · · 30 · · · · · · · · · · 200 · · · • . . 100 . , . . ,

< 30 3~9 40-49 50-59 60-69 70-79 > 79

Age groups (years)

Table 1. Distribution of 4083 prescriptions for antihyperten­sive drugs by 154GPs in four Norwegian countries in October 1975 as compared to total sales figures, according to defined daily doses (DDD) (Baksaas et al. 1978)

ATC1 class

Thiazides Other diuretics Synthetic hypotensives Beta-blockers

%DDDs

Prescriptions (n=4083)

37 30 20 13

Total sales

34 35 15 16

a Anatomical Therapeutic Chemical Classification System

63

Fig. 4. Age and sex distribution of 3253 patients included in the pre­scription survey on antihyperten­sives in four Norwegian counties in October 1975. (Baksaas et al. 1978)

recommended in the tentative guidelines given in the Norwegian Drugs and Thera­peutics Formulary (Vennemd 1984) and elsewhere. Systolic blood pressure limits conformed well with the guidelines in this category of patients, whereas elderly pat­ients tended to be somewhat less intensively treated. The poor correlation between claimed intention to treat and the regional differences in total sales may indicate apparent or real differences in morbidity.

2. International Studies. Based on DDDs per 1000 inhabitants per day, the sale or prescription of antihypertensive (and antidiabetic, see p.65) drugs has persistently varied two- to threefold between Northern Ireland, Norway, and Sweden (Fig.3). Even larger differences have been detected when other European countries have

64

120 ~

-c::

- S BP 01 slorl r- of treolmenl

110 <::

CI ::>:: E E

~100 .!::! C5 Vi .!:? o

90

,:=...

r- - r-- BP at losl control

<30 30 -49 50 -69 >69 Age groups (years)

P. K. M. Lunde et al.

Fig.5. Mean diastolic blood pressure at the com­mencement of treatment (open bars) and at the exami­nation in October 1975 (hatched bars) in 1885 patients of different sex (not shown) and age classes. (Baksaas et al. 1978)

Table 2. Relative registration of potential ADRs in 3253 patients receiving antihypertensive treatment, by 154 Norwegian GPs in October 1975 (Baksaas et al. 1978)

Patients Registered by Registered by with adverse reactionsa (%) (%)GPs (%) Patients

0 32 26 1-10 30 37

11-20 23 25 >20 14 13

a Registered as percentage of each GP's number of patients.

been included (Baksaas 1979, 1984). When adopting PDDs for antihypertensive drugs, the Northern Irish and Norwegian consumption figures were respectively 40% and 21 % lower than the Swedish ones, compared to 38% and 25% when using DDDs as unit of comparison (Griffiths et al. 1985). However, further methodologi­cal validation according to age and sex differences indicated that antihypertensive drug use might be 21 % rather than 38% lower in Northern Ireland and 18% rather than 25% lower in Norway, when adjusted to Swedish age- sex-specific sales ·data. When also including the PDD adjustment, an unexplained difference of 23% remained between Sweden and Northern Ireland as compared to 14% between Sweden and Norway. It should be stressed that these tentative adjustments may also be subject to considerable uncertainties.

Accordingly, it was decided to explore more thoroughly the potential reasons for these differences, on the basis of the hypothesis that different diagnostic and thera­peutic attitudes among the prescribing physicians in the three countries might be of significance. Thus a study, designed as a questionnaire survey of case histories, was conducted in 1983, addressing a representative sample of 300-400 GPs and hospital

Drug Utilization Studies - an Instrument in Drug Research 65

doctors in internal medicine in each country (diabetes, see below). For hypertension this study confirmed the previously documented differences between the three countries in terms of drug preferences among the prescribers (Baksaas et al. 1986a). Somewhat unexpectedly, however, the doctors in Northern Ireland showed a greater tendency to start antihypertensive drug treatment at lower diastolic and sys­tolic blood pressures than their colleagues in Norway and Sweden. Quite tenta­tively, this may indicate real or apparent morbidity differences, thus calling for fur­ther epidemiological studies. It should be added that great concern has· repeatedly been expressed in the United Kingdom that hypertension remains broadly under­detected (Coope 1984). According to an ongoing survey in the Norwegian county of Northern Trondelag, the fraction of undetected patients with hypertension appears quite small (Holmen, personal communication 1985).

Studies in Diabetes

Whereas type I ("juvenile") diabetes represents an absolute indication to prescribe insulin along with some dietary restrictions, type II ("adult onset") diabetes leaves room for considerable variation in judgement. Thus some of the latter patients might be well-treated with dietary measures alone, while others are also given oral hypoglycemics or even insulin. Whenever drug treatment is given, especially in type II diabetes, the positive symptomatic effects have to be weighed against the risk of serious hypoglycemia as well as the potential long term cardiovascular com­plications claimed, but not conclusively proven, to be related to lifelong use of anti­diabetic drugs (UGDP 1970).

Again, wide and persistent intra- and intercountry differences have been demon­strated in the sale and prescription of insulin as well as of oral antidiabetic drugs (Wade et al. 1973; Bergman et al. 1975; Andrew and Jerve1l1984; Griffiths et al. 1985; Staff and Baksaas 1985). The time trends for insulin and oral antidiabetics (Fig.6) show that insulin is increasingly used in Norway, whereas the use of oral

6

>- 5 <X: 0 '- 4 a:i <X: ::r: z 3 0 0

~ 2 "-

0 0 0

o INSULIN ORAL AGENTS

1973 -75 -77 -79 -61 -63 -84

Fig. 6. Sales of insulin and oral antidiabetic drugs in Norway 1973-1984, given in DDDs per 1000 inhabitants per day. (Staff and Baksaas 1985) YEAR

66 P. K. M. Lunde et al.

agents has remained more or less stable since the mid-1970s, probably reflecting intensive discussions as to their justification. Thus the increased use of insulin may partly refer to type II diabetes and partly to increasing prevalence of type I diabetes, i. e., enhanced life expectancy rather than increased incidence of the latter. The intercounty differences have remained impressive for the last 15 years (Fig. 7). This also refers to the countries most intensively studied and compared (Fig. 8).

I. Norwegian Studies. In contrast to Sweden (Westerholm 1979), no general pre­scription analyses are run routinely in Norway, except for narcotics. Therefore, age­and sex-related figures on insulin and oral anti diabetics were not available until a recent ad hoc study was performed (Staff and Baksaas 1985). Figure 9 shows a bimodal tendency in the prescription of insulin versus age in both sexes, which may reflect its use in type I and type II diabetes respectively. This is in clear contrast to the increasing use of oral antidiabetics at the age levels when type II diabetes becomes manifest (Fig. 10). The dominant oral drugs are the sulfonamides (gliben­clamide 85%, chlorpropamide 11 %, tolbutamide 0,4%), whereas the share of bigua­nides (metformin only) is only about 4%. The PDD: DDD ratio for the dominant sulfonylureas was 0.9, as compared to 0.5 for metformin. Thus, tentative prevalence estimates based on DDDs seem reasonably valid for most practical purposes. Adjusting for age and sex distribution in the Norwegian population, the total preva­lence pattern can be calculated (Fig. 11). A female predominance is seen among pat­ients receiving antidiabetic drugs, but only from the age of 60 years and upward. These calculations further indicate that about 1 % of the Norwegian population may

75

70

65

>- 60 « 58 0 "- 5 5 III « 53 I Z 50 0 0

~ 45 "-0 0 0 40

3 5

------- -- -------

- I- r--

I • t:

'" '" E E ~ E >-LL

Mean Insulin

Mean oral agents

Fig. 7. Sales of insulin (open bars) and oral antidiabetic drugs (filled bars) by county in Norway 1983, given in ODDs per 1000 inhabitants per day. (Staff and Baksaas 1985)

Drug Utilization Studies - an Instrument in Drug Research 67

25

20

=--.. " "-.c: ~ 0 0 0 ... ..... 0 0 0

=-­..

15

10

5

o

25

20

~ 15 .c: ~ o o o ... o 10 o o

5

o

NORTHERN IRELAND

1973 -75 -77 -79 -81

SWEDEN

91ibenclamide

chlorpropamide

:==::::~anides

1973 -75 -77 -79 -81

NORWAY

~9 ~c

1973 -75 -77 -79 -81

Fig.S. Sales/prescription figures for insulin and oral antidiabetic drugs in Northern Ire­land, Norway, and Sweden during 1973-1981, according to the Anatomical Therapeutical Chemical classification sys­tem, given in DDDs per 1000 inhabitants per day. (Griffiths et al. 1985)

68

VI ..... z w ..... «

20

Q. 10 -;;e.

,A, " \ , , , ,

" '", .. ''0',,,, " __ ... _-t:r- .. - --6... ... .. ~'

..... -(y"

.-4 \

\ , , , \ , \ , ,

Q ' , ' , , , , \ ' \ lI9 , ,

'bo'

0-9 10-1 9 20-29 30-39 40-49 50-59 60-69 70-79 :>80

AG E [Y EARS)

P. K. M. Lunde et al.

Fig. 9. Age and sex distribution of patients using insulin in Norway based on 2485 prescriptions from a survey of 61 % of Norwegian pharmacies in October 1984. (Staff and Baksaas 1985)

VI ..... z w

49

30

..... 20 rf. -;;e.

10

0- 9 10-19 20-29 30-39 40-49 50-59 60-09 70-79 :> 80 AGE [Y EARS )

Fig.tO. Age and sex distribution of patients using oral antidiabetic drugs in Norway based on 4292 prescriptions from a survey of 61 % of Norwegian pharmacies in October 1984. (Staff and Bak­saas 1985)

receive treatment with one antidiabetic drug. However, no precise data are currently available either with regard to the frequency of drug combination treatment in type II diabetes nor to the fraction of patients who may be well-regulated on diet alone. It is also worth noting that the present survey demonstrated reduced doses of oral antidiabetic drugs with increasing age, especially in patients above 80 years as compared to those of middle-age.

Drug Utilization Studies - an Instrument in Drug Research 69

Po , , ,

36 '09

32 cf

VI

~ 26 ~ iIi ~ 24 ~

g 20 C> , ~ 16 z UJ -' ;;: 12 UJ ~ Q.

6

4

0- 9 10-19 20-2930-3940-49 50-5960-69 70-79 ~60

AGE (Y EARS)

Fig.11. Prevalence according to sex and age for antidiabetic drug use in Norway calculated from 6777 prescriptions from a survey of 61 % of Norwegian pharmacies in October 1984, as adjusted for age and sex distribution in the Norwegian population. (Staff and Baksaas 1985)

More recent studies based on a questionnaire survey of case histories have revealed that Norwegian GPs prescribe insulin to their patients with type II diabe­tes less frequently than their colleagues in internal medicine and diabetology (Bak­saas et al. 1986b). Diabetologists were also more prone to treat milder cases with dietary measures alone than the remaining doctors. The study explained neither the quantitative nor the qualitative regional differences previously detected from the drug sales statistics. This may reflect either that the three model cases presented were not sufficiently representative of the population of type II diabetics, or that the historical therapy traditions differ from those more recently adopted. Morbidity dif­ferences in type I diabetes have, however, recently been demonstrated between Southern and Northern Norway (Joner and S"lVik 1981). In general, the results were in quite good agreement with guidelines currently given in the Norwegian Drugs and Therapeutics Formulary (Vennemd 1984) and elsewhere.

2. International Studies. Similarly to antihypertensives, the differences for antidia­betic drugs between Northern Ireland, Norway, and Sweden (Fig.8) have also recently been validated (Griffiths et al. 1985; Staff and Baksaas 1985). Unfortu­nately, the doses of insulin are often not given routinely on the prescriptions. There­fore a PDD : DDD ratio could not be established for comparative purposes. According to DDDs, the use of in sui ins is 39% and 42% lower in Northern Ireland

70 P. K. M. Lunde et al.

and Norway respectively, as compared to Sweden. When adopting PDDs for oral antidiabetics, the Northern Irish and Norwegian consumption figures were respec­tively 62% and 54% lower than the Swedish ones, compared to 67% and 56% when using DDDs as a unit of comparison. Adjustment according to age and sex differ­ences indicated that insulin use might be 30% rather than 39% lower in Northern Ireland and 40% rather than 42% lower in Norway, when based on Swedish age­sex-specific sales data. For oral agents the corresponding figures might be 57% rather than 67% lower in Northern Ireland and 52% rather than 56% lower in Nor­way, as co.mpared to Sweden. Accordingly, much larger differences apparently per­sisted for antidiabetic drugs than for antihypertensives, judging by these tentative adjustments. .

These differences have therefore been subject to a similar questionnaire survey of case histories as briefly described above for antihypertensives (Bergman et al. 1986). In general, the current opinions among GPs, diabetologists, and specialists in inter­nal medicine agreed with qualitative, but not with quantitative, intercountry differ­ences. However, significant differences were detected between countries as well as between doctors with regard to the relative role of diet, oral antidiabetics, and insu­lin in type II diabetes. As stated above for Norway, there was a greater trend among GPs to start oral drug treatment than among their hospital colleagues. Again, the study supports the hypothesis that true or apparent morbidity differences between and within countries may be of greater explanatory power than hitherto assumed.

Comments and Conclusions

1. Precise drug utilization statistics have been demonstrated to represent a most useful tool in description, problem identification, and analysis as regards drug regulation, information, prescription, and use (i. e., the "pharmacokinetics" and "pharmacodynamics" in our communities). However, the implementation of complete drug and therapeutic audits still belongs to the future.

2. Pronounced qualitative and quantitative differences in drug utilization have been unmasked; between and within countries, between and within health insti­tutions, and between physicians - and patients.

3. The explanations of these differences are insufficiently known, but they are most likely to be complex (Lunde 1984). Above all they may reflect widely varying diagnostic criteria and attitudes as to the usefulness of drugs in precisely and less precisely defined diseases and disorders. Thus the differences between prescrib­ers may often be greater than the objective differences between patients. This phenomenon is medically rather unsound and also has economic implications. However, there is some preliminary evidence that the differences in prevalence and incidence of a number of diseases may be more pronounced than hitherto recognized. Population age, other demographic and cultural factors, regulatory and economic diversities, etc. may also, to varying degrees, explain the observed differences.

4. Further analysis to outline the explanatory potential of these and other factors and to explore the medical and other consequences is one of the most important

Drug Utilization Studies - an Instrument in Drug Research 71

tasks for modem medicine. This is necessary in order to make the best possible use of drugs vs alternative measures in the prevention, symptomatic alleviation, and cure of diseases and disorders.

5. Finally, it is a matter of establishing the best possible criteria for the prescription and use of drugs, and of implementing these through appropriate teaching, training, and information for health workers, patients, and the pUblic.

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