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  1. 1. Introduction to Drug Utilization Research 2003 Introduction to Drug Utilization ResearchTittel: Introduction to Drug UtilizationResearchOpplag: 2 500Design: Grete SøimerFoto: Photo Alto/Laurent HamelsTrykk: Nordberg Aksidenstrykkeri ASISBN 82-8082-039-6IN 0000-2069 2003
  2. 2. Introduction toDrug Utilization ResearchWorld Health OrganizationWHO International Working Group for Drug Statistics MethodologyWHO Collaborating Centre for Drug Statistics MethodologyWHO Collaborating Centre for Drug Utilization Research and ClinicalPharmacological Services
  3. 3. WHO Library Cataloguing-in-Publication Data Introduction to drug utilization research / WHO International Working Group for Drug Statistics Methodology, WHO Collaborating Centre for Drug Statistics Methodology, WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Services. 1. Drug utilization 2. Research 3. Manuals I.WHO International Working Group for Drug Statistics Methodology II.WHO Collaborating Centre for Drug Statistics Methodology III.WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Services ISBN 92 4 156234 X (NLM classification: WB 330)2 © World Health Organization 2003 All rights reserved. Publications of the World Health Organization can be obtained from Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: bookorders@who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to Publications, at the above address (fax: +41 22 791 4806; email: permissions@who.int). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The World Health Organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. Printed in Oslo, Norway, 2003
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ContentsPreface: Drug utilization research - the early work ...........................................................................6Chapter 1: What is drug utilization research and why is it needed? ...............................................8 1.1 Definition and domains............................................................................................................8 1.2 Why drug utilization research? ................................................................................................9 1.2.1 Description of drug use patterns ....................................................................................9 1.2.2 Early signals of irrational use of drugs .......................................................................10 1.2.3 Interventions to improve drug use - follow-up ............................................................10 1.2.4 Quality control of drug use...........................................................................................10 1.3 Drug utilization studies and drug policy decisions................................................................11 1.4 General reading ......................................................................................................................12Chapter 2: Types of drug use information ........................................................................................13 2.1 Drug-based information .........................................................................................................13 2.1.1 Level of drug use aggregation .....................................................................................13 2.1.2 Indication .....................................................................................................................13 2.1.3 Prescribed daily doses .................................................................................................14 2.2 Problem or encounter-based information ..............................................................................15 2.3 Patient information.................................................................................................................16 2.4 Prescriber information ...........................................................................................................16 2.5 Types of drug utilization study ..............................................................................................17 2.6 Drug costs ..............................................................................................................................17 2.7 General reading ......................................................................................................................18 2.8 Exercises ................................................................................................................................19Chapter 3: Sources of data on drug utilization ................................................................................20 3.1 Large databases ......................................................................................................................20 3.2 Data from drug regulatory agencies ......................................................................................20 3.3 Supplier (distribution) data ....................................................................................................20 3.4 Practice setting data ...............................................................................................................21 3.4.1 Prescribing data ............................................................................................................21 3.4.2 Dispensing data ............................................................................................................22 3.4.3 Aggregate data .............................................................................................................22 3.4.4 Over-the-counter and pharmacist-prescribed drugs ....................................................22 3.4.5 Telephone and Internet prescribing .............................................................................22 3.5 Community setting data .........................................................................................................23 3.6 Drug use evaluation ...............................................................................................................23 3.7 General reading ......................................................................................................................24 3.8 Exercises ................................................................................................................................24Chapter 4: Economic aspects of drug use (pharmacoeconomy) ....................................................26 4.1 Introduction ............................................................................................................................26 4.2 Cost-minimization analysis....................................................................................................26 4.3 Cost-effectiveness analysis ....................................................................................................26 4.4 Cost-utility analysis ...............................................................................................................27 4.5 Cost-benefit analysis ..............................................................................................................27 4.6 General reading ......................................................................................................................28 4.7 Exercises ................................................................................................................................28
  6. 6. Chapter 5: Drug classification systems..............................................................................................33 5.1 Different classification systems .............................................................................................33 5.2 The ATC classification system...............................................................................................33 5.3 Ambivalence towards an international classification system ................................................35 5.4 Implementation of the ATC/DDD methodology ...................................................................36 5.5 General reading ......................................................................................................................36 5.6 Exercises ................................................................................................................................37Chapter 6: Drug utilization metrics and their applications ............................................................38 6.1 The concept of the defined daily dose (DDD).......................................................................38 6.2 Prescribed daily dose and consumed daily dose....................................................................39 6.3 Other units for presentation of volume..................................................................................39 6.4 Cost ......................................................................................................................................39 6.5 General reading .....................................................................................................................40 6.6 Exercises ...............................................................................................................................41Chapter 7: Solutions to the exercises .................................................................................................74Acknowledgements...............................................................................................................................84
  7. 7. Preface: Drug utilization research - the early work The development of drug utilization research became clear that we need to know the answers was sparked by initiatives taken in Northern to the following questions: Europe and the United Kingdom in the mid- • why drugs are prescribed; 1960s (1, 2). The pioneering work of Arthur • who the prescribers are; Engel in Sweden and Pieter Siderius in Holland • for whom the prescribers prescribe; (3) alerted many investigators to the importance • whether patients take their medicines correctly; of comparing drug use between different count- • what the benefits and risks of the drugs are. ries and regions. Their demonstration of the remarkable differences in the sales of antibiotics The ultimate goal of drug utilization research in six European countries between 1966 and must be to assess whether drug therapy is rational 1967 inspired WHO to organize its first meeting or not. To reach this goal, methods for auditing on «Drug consumption» in Oslo in 1969 (4). drug therapy towards rationality are necessary. This led to the constitution of the WHO The early work did not permit detailed compa- European Drug Utilization Research Group risons of the drug utilization data obtained from (DURG). different countries because the source and form The pioneers of this research understood that a of the information varied between them. To correct interpretation of data on drug utilization overcome this difficulty, researchers in Northern requires investigations at the patient level. It Ireland (United Kingdom), Norway and Sweden6 Figure 1 Utilization of insulin and oral antidiabetic drugs in seven European countries from 1971-1980 expressed in defined daily doses (DDDs) per 1000 inhabitants per day. For comparison the prescribed daily doses (PDD) per 1000 inhabitants per day of oral antidiabetic drugs are given for Northern Ireland (UK) and Sweden for 1980 (indicated with an asterisk).
  8. 8. developed a new unit of measurement, initially Scandinavica, 1984, Suppl. 683:7-9.called the agreed daily dose (5) and later the 2. Dukes MNG. Development from Crooks to thedefined daily dose (DDD) (6). This unit was nineties. In: Auditing Drug Therapy.defined as the average maintenance dose of Approaches towards rationality at reasonablethe drug when used on its major indication in costs. Stockholm, Swedish Pharmaceuticaladults. The first study used antidiabetic drugs Press, 1992.as an example: it was found that the sum of the 3. Engel A, Siderius P. The consumption of drugs.DDDs of insulin and oral antidiabetic drugs Report on a study 1966-1967. Copenhagen,(about 20 DDDs per1000 inhabitants per day) WHO Regional Office for Europe, 1968 (EUROroughly corresponded to the morbidity due to 3101).diabetes after correction for the number of pati-ents treated with dietary regimens alone. Among 4. Consumption of drugs. Report on a symposium in Oslo 1969. Copenhagen, WHO Regionalthe first countries to adopt the DDD methodo- Office for Europe, 1970 (EURO 3102).logy was the former Czechoslovakia (7) and thefirst comprehensive national list of DDDs was 5. Bergman U, et al. The measurement of drugpublished in Norway in 1975 (8). Another consumption. Drugs for diabetes in Northernimportant methodological advance was the adop- Ireland, Norway, and Sweden. European Journal of Clinical Pharmacology, 1975,8:83-tion of the uniform anatomical therapeutic che- 89.mical (ATC) classification of drugs (see chapter 75.2). The use of standardized methodology allo- 6. Bergman U et al., eds. Studies in drug utilizati-wed meaningful comparisons of drug use in on. Methods and applications. Copenhagen,different countries to be made (Fig. 1). WHO Regional Office for Europe, 1979 (WHO Regional Publications, European Series No. 8). Drug utilization research developed quicklyduring the following 30 years and soon became a 7. Stika L et al. Organization of data collection inrespectable subject for consideration at inter- Czechoslovakia. In: Bergman U et al., eds.national congresses in pharmacology, pharmacy Studies in drug utilization. Methods and appli-and epidemiology. Particularly rapid develop- cations. WHO Regional Office for Europe, Copenhagen, 1979 (WHO Regional Publicationsments were seen in Australia (9) and Latin European Series No. 8) pp.125-136.America (10). The number of English-languagepapers on the subject listed in the Cumulative 8. Baksaas Aasen I et al. Drug dose statistics, listindex medicus rose from 20 in 1973 (when the of defined daily doses for drugs registered interm «drug utilization« first appeared) to 87 in Norway. Oslo, Norsk Medicinal Depot, 1975.1980, 167 in 1990, and 486 in 2000. 9. Hall RC. Drug use in Australia. In: Sjöqvist F, History has taught us that successful research Agenäs I, eds. Drug utilization studies:in drug utilization requires multidisciplinary col- Implications for medical care. Acta Medicalaboration between clinicians, clinical pharmaco- Scandinavica, 1983, Suppl. XXX:79-80.logists, pharmacists and epidemiologists. 10. Drug Utilization Research Group, LatinWithout the support of the prescribers, this rese- America. Multicenter study on self-medicationarch effort will fail to reach its goal of facilita- and self-prescription in six Latin Americanting the rational use of drugs. countries. Clinical Pharmacology and Therapeutics, 1997, 61:488-493.References 11. Bergman U, Sjöqvist F. Measurement of drug1. Wade O. Drug utilization studies - the first utilization in Sweden: methodological and clini- attempts. Plenary lecture. In: Sjöqvist F, cal implications. Acta Medica Scandinavica, Agenäs I. eds. Drug utilization studies: implica- 1984, Suppl 683:15-22. tions for medical care. Acta Medica
  9. 9. Chapter 1: What is drug utilization research and why is it needed? 1.1. Definition and domains not. Sophisticated utilization-oriented pharma- coepidemiology may focus on the drug (e.g. Drug utilization; pharmacoepidemiology; dose-effect and concentration-effect relationships), [ pharmacosurveillance; pharmacovigilance ] the prescriber (e.g. quality indices of the prescrip- tion), or the patient (e.g. selection of drug and • Drug utilization research was defined by dose, and comparisons of kidney function, drug WHO in 1977 as «the marketing, distribution, metabolic phenotype/genotype, age, etc.). prescription, and use of drugs in a society, with Drug utilization research is thus an essential special emphasis on the resulting medical, social part of pharmacoepidemiology as it describes the and economic consequences». Since then, a extent, nature and determinants of drug exposure. number of other terms have come into use and it Over time, the distinction between these two is important to understand the interrelationships terms has become less sharp, and they are some- of the different domains. times used interchangeably. However, while • Epidemiology has been defined as «the study drug utilization studies often employ various of the distribution and determinants of health- sources of information that focus on drugs (e.g. related states and events in the population, and aggregate data from wholesale and prescription the application of this study to control of health registers) the term epidemiology implies defined problems». populations in which drug use can be expressed8 • Pharmacoepidemiology applies epidemiologi- in terms of incidence and prevalence (see cal methods to studies of the clinical use of chapter 1.2.1). drugs in populations. A modern definition of Together, drug utilization research and pharma- pharmacoepidemiology is: «the study of the use coepidemiology may provide insights into the fol- and effects/side-effects of drugs in large numbers lowing aspects of drug use and drug prescribing. of people with the purpose of supporting the rational and cost-effective use of drugs in the • Pattern of use: This covers the extent and pro- population thereby improving health outcomes». files of drug use and the trends in drug use and • Pharmacosurveillance and pharmacovigi- costs over time. lance are terms used to refer to the monitoring • Quality of use: This is determined using audits of drug safety, for example, by means of spon- to compare actual use to national prescription taneous adverse-effect reporting systems, case- guidelines or local drug formularies.1 Indices of control and cohort studies. quality of drug use may include the choice of drug (compliance with recommended assort- Pharmacoepidemiology may be drug-oriented, ment), drug cost (compliance with budgetary emphasizing the safety and effectiveness of indi- recommendations), drug dosage (awareness of vidual drugs or groups of drugs, or utilization- inter-individual variations in dose requirements oriented aiming to improve the quality of drug and age-dependence), awareness of drug inter- therapy through pedagogic (educational) inter- actions and adverse drug reactions, and the pro- vention. Drug utilization research may also be portion of patients who are aware of or unaware divided into descriptive and analytical studies. of the costs and benefits of the treatment. The emphasis of the former has been to describe • Determinants of use: These include user cha- patterns of drug utilization and to identify pro- racteristics (e.g. sociodemographic parameters blems deserving more detailed studies. and attitudes towards drugs), prescriber characte- Analytical studies try to link data on drug utili- ristics (e.g. speciality, education and factors zation to figures on morbidity, outcome of treat- influencing therapeutic decisions) and drug cha- ment and quality of care with the ultimate goal racteristics (e.g. therapeutic properties and affor- of assessing whether drug therapy is rational or dability). 1 An audit in drug use was defined by Crooks (1979) as an examination of the way in which drugs are used in clinical practice carried out at intervals frequent enough to maintain a generally accepted standard of prescribing.
  10. 10. • Outcomes of use: These are the health out price. Without a knowledge of how drugs arecomes (i.e. the benefits and adverse effects) and being prescribed and used, it is difficult to initiatethe economic consequences. a discussion on rational drug use or to suggest measures to improve prescribing habits.The initial focus of pharmacoepidemiology was Information on the past performance of prescri-on the safety of individual drug products (phar- bers is the linchpin of any auditing system.macosurveillance), but it now also includes stu- Drug utilization research in itself does notdies of their beneficial effects. The driving force necessarily provide answers, but it contributes tobehind this development was a growing awa- rational drug use in important ways as describedreness that the health outcomes of drug use in below.the rigorous setting of randomized clinical trialsare not necessarily the same as the health outco- 1.2.1 Description of drugmes of drug use in everyday practice. The clini- use patternscal trials needed to obtain marketing authori- Drug utilization research can increase our under-zation for new drugs involve limited numbers of standing of how drugs are being used as follows.carefully selected patients, who are treated andfollowed-up for a relatively short time in strictly • It can be used to estimate the numbers of pati-controlled conditions. As a result, such trials do ents exposed to specified drugs within a givennot accurately reflect how drug use will affect time period. Such estimates may either refer to 9health outcomes in everyday practice under every- all drug users, regardless of when they started today circumstances. Pharmacoepidemiological use the drug (prevalence), or focus on patientsstudies often make useful contributions to our who started to use the drug within the selectedknowledge about effectiveness and safety, because, period (incidence).unlike clinical trials, they assess drug effects in • It can describe the extent of use at a certainlarge, heterogeneous populations of patients over moment and/or in a certain area (e.g. in a coun-longer periods. try, region, community or hospital). Such des- Drug utilization research also provides insight criptions are most meaningful when they forminto the efficiency of drug use, i.e. whether a part of a continuous evaluation system, i.e. whencertain drug therapy provides value for money the patterns are followed over time and trends inand the results of such research can be used to drug use can be discerned.help to set priorities for the rational allocation of • Researchers can estimate (e.g. on the basis ofhealth care budgets. epidemiological data on a disease) to what extent drugs are properly used, overused or underused.1.2 Why drug utilization • It can determine the pattern or profile of drugresearch? use and the extent to which alternative drugs are Description of drug use pattern; early signals being used to treat particular conditions. of irrational use of drugs; interventions to • It can be used to compare the observed patterns improve drug use; quality control cycle; of drug use for the treatment of a certain disease continuous quality improvement with current recommendations or guidelines. • It can be used in the application of quality indi-The principal aim of drug utilization research is cators to patterns of drug utilization. An exam-to facilitate the rational use of drugs in popu- ple is the so-called DU90% (drug utilizationlations. For the individual patient, the rational 90%), a further development of the «top-ten»use of a drug implies the prescription of a well- list.documented drug at an optimal dose, together The DU90% segment reflects the number ofwith the correct information, at an affordable drugs that account for 90% of drug prescriptions
  11. 11. and the adherence to local or national prescrip- mal practice, whether pedagogic interventions tion guidelines in this segment. This general (education) are required or whether the guide- indicator can be applied at different levels (e.g. lines should be reviewed in the light of actual individual prescriber, group of prescribers, hos- practice. These hypotheses should apply to both pitals, region or county) to obtain a rough esti- under use and over use of drugs. mate of the quality of prescribing. • Drug utilization data can be fed back to pre- 1.2.3 Interventions to improve scribers. This is particularly useful when the drug use - follow-up drug prescribing by a particular individual can Drug utilization research undertaken in the follo- be compared with some form of «gold standard» wing ways may enable us to assess whether or best practice, and with the average prescrip- interventions intended to improve drug use have tions in the relevant country, region or area. had the desired impact. • The number of case reports about a drug pro- • The effects of measures taken to ameliorate blem or adverse effects can be related to the undesirable patterns of drug use (e.g. provision number of patients exposed to the drug to assess of regional or local formularies, information the potential magnitude of the problem. If it is campaigns and regulatory policies) should be possible to detect that the reaction is more com- monitored and evaluated. The researchers mon in a certain age group, in certain conditions should bear in mind that prescribers may have10 or at a given dose level, improving the informa- switched to other drugs that are equally undesi- tion on indications, contraindications and rable. These potential alternative drugs should appropriate dosages may be sufficient to ensure be included in the survey to assess the full safer use and avoid withdrawal of the drug from impact of the measure. the market. • The impact of regulatory changes or changes in insurance or reimbursement systems should 1.2.2 Early signals of irrational use be assessed using a broad survey. This is neces- of drugs sary because the total cost to society may remain Drug utilization research may generate hypothe- the same or may even increase if more expen- ses that set the agenda for further investigations sive drugs are used as alternatives. as outlined below, and thus avoid prolonged irra- • The extent to which the promotional activities tional use of drugs. of the pharmaceutical industry and the educatio- • Drug utilization patterns and costs between nal activities of the society affect the patterns of different regions or at different times may be drug use should be assessed. compared. Hypotheses can be generated to form the basis for investigations of the reasons for, 1.2.4 Quality control of drug use and health implications of, the differences Drug use should be controlled according to a found. Geographical differences and changes in quality control cycle that offers a systematic drug use over time may have medical, social and framework for continuous quality improve- economic implications both for the individual ment. The components of such a cycle are illu- patient and for society, and should therefore be strated on the next page. identified, explained and, when necessary cor- rected. After step 4, the cycle begins again with new • The observed patterns of drug use can be com- analyses, the setting of new targets, and so on. pared with the current recommendations and The quality control cycle can be applied at guidelines for the treatment of a certain disease. many levels, ranging from local or regional dis- Hypotheses can then be generated to determine cussion groups consisting of physicians, clinical whether discrepancies represent less than opti- pharmacologists or pharmacists to national and
  12. 12. Step 1. Plan. Analyse current situation to Step 2. Do. Implement the plan on a small establish a plan for improvment (e.g. analyse scale (e.g. provide feedback on possible current prescription patterns of individual overuse, underuse or drug misuse of prescribers, groups of prescribers, or health individual drugs or therapeutic groups). facilities). Step 4. Act Revise plan or implement plan Step 3. Check Check to see if expected on large scale (e.g. guide national imple- results are obtained (e.g. evaluate whether mentation of plan). prescription patterns really improve).international initiatives. An important technique and validated from 1992-1994. Since then,that can be used in conjunction with this cycle annual reviews of drug utilization have beenis benchmarking. By comparing drug utiliza- used to provide background information fortion data from different localities, it is often decisions on regulatory and reimbursement poli-possible to detect substantial differences that cies in Estonia; two examples are describedrequire further evaluation, which may then lead below.to the identification and promotion of best prac- If physicians have high rates of inappropriatetice. Such comparisons will be accurate and prescribing, drug regulatory authorities can 11truthful provided that the data are collected and require educational intervention or imposeaggregated in a standardized, uniform way (see restrictions on specific drugs or on practitioners.chapter 5). In Estonia, it was decided to stop the import and use of some hazardous products, such as phena-1.3 Drug utilization studies and cetine, older sulphonamides and pyrazolones,drug policy decisions after clarifying and explaining the reasons forMany of the questions asked in drug utilization this in the national Drug information bulletin,research and the answers obtained are important which is distributed free by the drug regulatoryfor initiating and modifying a rational drug poli- authority to all prescribers in Estonia.cy at both national and local levels. Two suc- In planning the reimbursement policies, thecessful examples of the use of such research are total volume of drug use in DDDs was monito-given below. red carefully. During the 1990s, the use of pre- scription-only medicines measured as number ofDrug use in Estonia DDDs per capita was less than one third of thatAn important reason for undertaking studies of reported from the Nordic countries. This proveddrug use in Estonia after its independence was to be the result of under-treatment of certainthe need to make decisions on drug policy. At chronic diseases (i.e. hypertension and schizo-the time, no information was available in the phrenia), and therefore the decision was to incre-country on which drugs were used (sold), or on ase the availability and use of cardiovascular andthe quantities and there was therefore no rationale neuroleptic drugs. Thus, the national drug usefor regulating the drug market. Moreover, in the surveys in Estonia have been used to monitor theabsence of any feedback system it was impos- impact of drug regulatory activities as well as tosible to gauge the impact of possible future follow the increase in drug expenditure.interventions. A national drug classification Because data on drug use are only part of thesystem was therefore developed for Estonia, and background material relevant to the discussionsa reporting system from wholesalers, based on and decisions on therapeutic strategies - at boththis classification, was implemented, checked the local and national levels - it is difficult to
  13. 13. evaluate the specific influence of drug utilization rent social-class districts in the catchment areas research on developments in drug policies. It is, of 11 health centres.1 however, reasonable to assume that such studies have contributed to a more rational use of drugs 1.4 General reading in Estonia.1 Bergman U et al. Drug utilization 90% - a sim- ple method for assessing the quality of drug pre- Drug use in Latin America scribing. European Journal of Clinical The second example is the successful work within Pharmacology, 1998, 54:113-118. the Latin American DURG, in association with Crooks J. Methods of audit in drug use. In: the WHO Collaborating Centre of Pharmaco- Duchene-Marulla ZP, ed. Advances in pharma- epidemiology in Barcelona, Spain. cology and therapeutics. Proceedings of 7th In September 1991, health professionals from International Congress of Pharmacology, Paris, Spain and eight Latin American countries met in 1978. Oxford, Pergamon Press, 1979:189-195. Barcelona for the «First Meeting of Latin Diogène E et al. The Cuban experience in American Groups for Drug Epidemiology». It focusing pharmaceuticals policy to health popu- was made clear that in most of the countries lation needs: initial results of the National taking part, data on drug utilization were scarce Pharmacoepidemiology Network (1996-2001). and fragmentary. Some national drug regulatory European Journal of Clinical Pharmacology,12 authorities had no access to either quantitative or 2002, in press. qualitative data on drug consumption and reali- Drug Utilization Research Group, Latin zed that information on patterns of drug utili- America. Multicenter study on self-medication zation would be useful for designing drug policy and self-prescription in six Latin American and educational programmes about drugs. countries. Clinical Pharmacology and It was agreed at this meeting to set up a Latin Therapeutics, 1997, 61:488-493. American network (later called DURG-LA), Dukes MNG, ed. Drug Utilization Studies: with the following aims: Methods and Uses. Copenhagen, WHO Regional – to promote drug utilization research in Latin Office for Europe, 1993 (WHO Regional American countries; Publications European Series No. 45) – to exchange experiences and information Einarson TR, Bergman U, Wiholm BE. between the participating groups; Principles and practice of pharmacoepidemiolo- – to use the knowledge generated to give techni- gy. In: Avery’s Drug Treatment, 4th ed. Adis cal advice to drug regulatory authorities and to International:371-392. guide teaching of pharmacology; Figueras A et al. Health need, drug registration – to write and disseminate information aimed at and control in less developed countries - the improving drug use, and Peruvian case. Pharmacoepidemiology and Drug – to participate in the training of health pro- Safety, 2001, 10:1-2. fessionals in pharmacoepidemiology and thera- Laporte JR, Porta M, Capella D. Drug utiliza- peutics. tion studies: a tool for determining the effecti- veness of drug use. British Journal of Clinical Seven further DURG-LA meetings have been Pharmacology, 1983, 16:301-304. held over the subsequent ten years to promote McGavock H. Handbook of drug use research drug utilization research. Part of the initial core methodology 1st ed. Newcastle upon Tyne, group participated in a first multicentre study in United Kingdom Drug Utilization Research six Latin American countries to examine self- Group, 2000. medication and self-prescription. The study was Strom BL. Pharmacoepidemiology, 3rd ed. carried out in a sample of pharmacies from diffe- New York, J Wiley, 2000. 1 The information about DURG-LA was provided in a personal communication by Dr Albert Figueras and Professor Joan-Ramon Laporte, Barcelona, Spain.
  14. 14. Chapter 2: Types of drug use informationDifferent types of drug use information are 2.1.2 Indicationrequired depending on the problem being exami- For drugs with multiple indications, it will usuallyned. These include information about the overall be important to divide data on use according touse of drugs, drug groups, individual generic indication to allow a correct interpretation of thecompounds or specific products. Often, infor- overall trends. An example is the relative use ofmation about the condition being treated, the drug groups in treating hypertension. The over-patient and the prescriber is also required. In all data might suggest that the relative use ofaddition, data on drug costs will be important in diuretics is comparable to that of ACE inhibitorsensuring that drugs are used efficiently and eco- and higher than the use of calcium channel bloc-nomically. These types of drug information are kers (column A in Table 1). However, analysisdescribed in detail below, together with exam- of the data according to indication may revealples to illustrate the ways in which the informa- that 75% of ACE inhibitors are used to treattion can be used to promote the rational use of hypertension whereas only 43% of diuretics aredrugs. used for this indication (most of the high-ceiling diuretics used are for treating heart failure). The2.1 Drug-based information picture that emerges of the use of the two drugKnowledge of the trends in total drug use may groups in the treatment of heart failure is mar-be useful, but more detailed information invol- kedly altered when use according to indication isving aggregation of data on drug use at various taken into account (column B of Table 1). 13levels, and information on indications, doses anddosage regimens is usually necessary to answer Table 1 Relative use of drug groups in the treatmentclinically important questions. of hypertension in Australia in 1998a2.1.1 Level of drug use aggregation Drug group Ab Bc CdThe level at which data on drug use are aggrega-ted will depend on the question being asked. ACE inhibitors (C09A) 31.80 36.6 34.8For example, the question might concern the Calcium channel blockersrelative use of drug groups in the treatment of (C08C) 24.50 28 26.7hypertension. It would then be appropriate to Diuretics (C03) 29.60 19.4 15.9aggregate data on diuretics, beta-blockers and Beta-blockersangiotensin-converting enzyme (ACE) inhibitors, (C07AA, C07AB) 11.20 11.5 15.7etc. If, however, the question concerns the rela-tive use of beta-blockers in hypertension, data at ATII antagoniststhe substance (generic drug) level would be nee- (C09CA) 3.00 4.6 6.9ded. Information on the relative scale of use ofindividual products will sometimes be required,for example to find the market leader or to Source: Australian Drug Utilizationassess the relative use of generic versus branded Subcommittee and BEACH Survey April-or innovator products. Information down to the December 1998, Sydney University, GPSCUlevel of dose strength will be necessary, for 1999.example, to determine whether there is a trend a Values are the use of the drug group expressed as a percentatowards use of higher strengths of antibiotics, or ge of the total use for these drug groups.to determine the relative use of strengths of anti- b Based on total use.depressants to assess whether they are being c Adjusted for the percentage of total use of each group for theused at effective doses. treatment of hypertension. d Relative prescribing of these drug groups in hypertension community practice patient encounters.
  15. 15. Another example of a situation in which the when making such comparisons. The PDDs dif- indication is important is antibiotic utilization. fer between countries and ethnic groups, and In determining whether the use of a particular even between areas or health facilities within the antibiotic, for example, amoxicillin, is rational, it same country. The PDD will also often differ will usually be necessary to know what infecti- for different indications of the same drug, so it ons or problems it is being used to treat. It will sometimes be necessary to reach this level would therefore be necessary to break down data of detail to interpret overall use data. on amoxicillin use into indications and compare Data on the use of tricyclic antidepressants these uses with the appropriate guidelines. If it and selective serotonin reuptake inhibitors were found that there was substantial use of (SSRIs) in Australia are shown in Table 2 as amoxicillin to treat acute sore throat, for exam- both DDDs and prescription volumes. ple, this finding would indicate a problem that The two metrics give different results for the needed to be addressed. This is because a nar- relative use of the two groups of antidepressant row-spectrum agent (or no drug) would be a drugs because of the different relationship bet- more appropriate treatment for a sore throat, and ween the PDDs and the DDDs for the two drug if amoxicillin is used to treat mononucleosis, groups. On average, the PDD is lower than the which can present as a sore throat, there is a DDD for the tricyclics and higher for the SSRIs. high incidence of rash. In this case, knowledge of the PDDs is necessary14 for clinical interpretation of the data. 2.1.3 Prescribed daily doses The DDD per 1000 inhabitants per day is The prescribed daily dose (PDD) is the average often used to derive a rough estimate of the pre- daily dose prescribed, as obtained from a repre- valence of use in the population being studied, sentative sample of prescriptions. The use of and for chronic diseases it may even be used to DDD per 1000 inhabitants per day allows aggre- assess the prevalence of a disease when the drug gation of data across drug groups and compari- is prescribed for a single indication. Such esti- sons between countries, regions and health faci- mates are valid only if the DDDs and the PDDs lities. However, the DDD metric may not reflect are similar. the actual PDDs, and this needs to be considered Table 2 Relative use of antidepressants in Australia in 1998 Prescription % of total DDD/1000 % of total DDD/1000 volume prescription population/day population/day (millions)a volume Tricyclics (N06AA) 3.53 48.82 8.40 28.09 SSRI (N06AB) 3.09 42.74 17.20 57.53 Moclobemide (N06AG02) 0.61 8.44 4.30 14.38 Total 7.23 100.00 29.90 100.00 Source: Australian Drug Utilization Subcommittee, Department of Health & Aged Care, Commonwealth of Australia, http://www.health.gov.au:80/haf/docs/asm.htm
  16. 16. 2.2 Problem or encounter-based sistent. This consistency between data using twoinformation different approaches (i.e. drug and problem- based) gives confidence in the result. Reason for the encounter (the problem); Other questions that might be addressed using drug treatment versus non-drug treatment; a problem-based approach include the following: other problems managed; severity of the pro- blem managed; new or continuing presenta- • Does the severity of hypertension influence the tion; duration of consultation; medications choice of single or combination therapy? prescribed for the problem; how the medica- • Is the management of newly-presenting pati- tions were supplied; other medications pre- ents different to that of patients already receiving scribed treatment? • Are there likely to be any drug interactions with co-prescribed treatments?Rather than asking how a particular group of • Is the choice of drug influenced by evidence-drugs is used, it may be useful to address the based outcome data?question of how a particular problem (e.g. sorethroat, hypertension or gastric ulcer) is managed. For some diseases it may be important to studyThe different types of information that may be the relative use of drug treatment and other the-required are listed in the box above. As an example, consider how problem-based rapeutic approaches to map out and understand 15 pharmacotherapeutic traditions and other thera-information about the management of hyperten- peutic approaches. As an example, drug utiliza-sion might be used. Initially, concordance with tion research in Estonia has shown that there wasguidelines for drug treatment or non-drug mana- a reciprocal relationship between the use of hor-gement of blood pressure and other risk factors monal contraceptives and the abortion ratemight be assessed. Where drug treatment is from1989-1997 (Fig. 2).used, the proportion of patients treated with eachof the drug groups gives an overall picture of Another example was the excessive use of ulcermanagement (column C of Table 1). This is surgery in Estonia compared to Sweden duringmore direct information on how hypertension is the Soviet era. This was because of the difficul-managed than that provided by assessing the ties of obtaining modern anti-ulcer drugs inoverall use of the different drug groups as dis- Estonia at that time (Fig. 3).cussed above. In the example shown in Table 1,the data in columns B and C are reasonably con- (per 10 000 population Use of hormonal Nr of abortions contraceptives (DDD/1000/dayFigure 2 Abortion rate and use of hormonal contraceptives in Estonia in 1989-1997.Source: Kiivet R. Drug utilization studies as support to decisions in drug policy in Estonia. [MD Thesis]Stockholm, Karolinska Institutet, 1999.
  17. 17. 80 20 60 16 12 40 8 20 4 0 0 1993 1995 anti-ulcer drugs, Estonia surgery, Estonia anti-ulcer drugs, Stockholm surgery, Stockholm Figure 3 Treatment of ulcer disease in Estonia and in Stockholm County 1993-1995. Source: Kiivet R. Drug utilization studies as support to decisions in drug policy in Estonia. [MD Thesis] Stockholm, Karolinska Institutet, 1999. 2.3 Patient information 2.4 Prescriber information Age; gender; ethnicity; co-morbidities; Demographic information - age, gender,16 [ knowledge; beliefs and perceptions ] medical school, years in practice; type of practice (e.g. specialist or family, rural or Information on demographic factors and other urban); practice size; patient mix; knowledge details about the patient will often be useful. about drugs; factors driving prescribing For example, the age distribution of patients may behaviour be of critical importance, to assess the likelihood of severe adverse effects with nonsteroidal anti- The prescriber plays a critical role in determi- inflammatory drugs (NSAIDs), or whether the ning drug use. Claims have even been made that drug is being used to treat patients in an age the differences between doctors are greater than group different from that in which the clinical those between patients and that variations in trials were performed. The co-morbidities of the drug prescribing behaviour often lack rational patient group may be important in determining explanations. Dissecting the factors that deter- the choice of treatment and predicting possible mine prescribing behaviour is therefore often adverse effects. For instance, in the manage- central to understanding how and why drugs are ment of hypertension, beta-blockers should not prescribed. Some questions that might be be used to treat patients with asthma, and ACE addressed using prescriber information include inhibitors are the preferred treatment in patients the following: with heart failure. • Are prescribing profiles influenced by the Qualitative information relating to the know- prescriber’s medical education? ledge, beliefs and perceptions of patients and • Do the prescribing profiles of specialists differ their attitudes to drugs will be important in some from those of family practitioners? cases, for example in assessing the pressures put • Does the age or gender of the prescriber influ- by patients on their doctors to prescribe antibio- ence the prescribing profile? tics, or in designing consumer information and • Are there differences in prescribing behaviour education programmes. between urban and rural practices or between small and large practices? Do these variations indicate a need to target education to particular sectors?
  18. 18. • Who are those prescribers who rapidly adopt often obtained from repeated cross-sectional sur-recently released drugs? veys (e.g. IMS (Intercontinental Medical• In assessing rational use of medicines by a Statistics) practice-based data are of this type).practitioner, has the practice mix been taken into Data collection is continuous, but the practitio-account? ners surveyed, and therefore the patients, are• Can the factors that determine and change pre- continually changing. Such data give informa-scribing behaviour be identified? tion about overall trends, but not about prescri- bing trends for individual practitioners or practices.2.5 Types of drug utilizationstudy Continuous longitudinal studiesDrug utilization studies can be targeted towards In some cases continuous longitudinal data at theany of the following links in the drug-use chain: individual practitioner and patient level can be obtained. Claims databases are often able to – the systems and structures surrounding drug follow individual patients using a unique (but use (e.g. how drugs are ordered, delivered and anonymous) identifier. These data can provide administered in a hospital or health care facility); information about concordance with treatment – the processes of drug use (e.g. what based on the period between prescriptions, co- drugs are used and how they are used and prescribing, duration of treatment, PDDs and so does their use comply with the relevant on. As electronic prescribing becomes more 17 criteria, guidelines or restrictions); and common, databases are being developed to pro- – the outcomes of drug use (e.g. efficacy, vide continuous longitudinal data comprising adverse drug reactions and the use of resour- full medical and prescribing information at the ces such as drugs, laboratory tests, hospital individual patient level. Such databases are very beds or procedures). powerful, and can address a range of issues including reasons for changes in therapy, adverseCross-sectional studies effects and health outcomes.Cross-sectional data provide a «snapshot» ofdrug use at a particular time (e.g. over a year, amonth or a day). Such studies might be used for 2.6 Drug costsmaking comparisons with similar data collectedover the same period in a different country, Total drug costs; cost per prescription; costhealth facility or ward, and could be drug-, pro- per treatment day, month or year; cost perblem-, indication, prescriber- or patient-based. defined daily dose (DDD); cost per prescri-Alternatively, a cross-sectional study can be car- bed daily dose (PDD); cost as a proportionried out before and after an educational or other of gross national product; cost as a propor-intervention. Studies can simply measure drug tion of total health costs; cost as a propor-use, or can be criterion-based to assess drug use tion of average income; net cost per healthin relation to guidelines or restrictions. outcome (cost-effectiveness ratio); net cost per quality adjusted life-year (cost-utility-Longitudinal studies ratio)Public health authorities are often interested intrends in drug use, and longitudinal data are Data on drug costs will always be important inrequired for this purpose. Drug-based longi- managing policy related to drug supply, pricingtudinal data can be on total drug use as obtained and use. Numerous cost metrics can be used andthrough a claims database, or the data may be some of these are shown in the box above. Forbased on a statistically valid sample of pharma- example, the cost per DDD can usually be usedcies or medical practices. Longitudinal data are to compare the costs of two formulations of the
  19. 19. same drug. However, it is usually inappropriate ced a marked increase in the cost of anti-psycho- to use this metric to compare the costs of diffe- tic drugs over the last 5-10 years; the data on use rent drugs or drug groups as the relationship bet- and cost for these drugs in Australia are illustra- ween DDD and PDD may vary. ted in Fig. 4. Estimates of the costs at various levels and using data aggregated in various ways will be In Australia, there has been little increase in the required, depending on the circumstances and overall volume of use of antipsychotic drugs, the perspective taken. A government perspective and the cost increase has been driven by the might require information on drug costs and cost transfer from the cheap ‘classical’ agents to the offsets to government to be collected, whereas a much more expensive ‘atypical’ drugs such as societal perspective would require both govern- clozapine, olanzapine and risperidone resulting ment and non-government (private sector) costs in an increase in the average cost per prescrip- and cost offsets to be determined. A patient per- tion. In contrast, both the prescription volume of spective will be appropriate if questions about antidepressant drugs and the average cost per affordability and accessibility are being asked. prescription have increased over the same period, Costs may be determined at government, health due to an ‘add-on’ prescribing effect of the more facility, hospital, health maintenance organiza- expensive SSRIs. tion or other levels within the health sector.18 Costs will often need to be broken down 2.7 General reading according to drug group or therapeutic area to Einarsson TR, Bergman U, Wiholm BE. determine, for example, the reason for an increase Principles and practice of pharmacoepidemiology. in drug costs. For instance, the introduction of In: Speight TM, Holford NH, eds. Avery’s Drug new, expensive anti-cancer agents may be found Treatment. Place, Adis International, 1999:371- to be driving the increases in drug costs in a hos- 392. pital. Changes in drug costs can result from changes in prescription volumes, quantity per Lee D, Bergman U. Studies of drug utilization. prescription or in the average cost per prescripti- In: Strom B. ed. Pharmacoepidemiology, 3rd ed. on. For example, most countries have experien- Chichester, J Wiley, 2000:463-481. 10 100 community use govt cost with clozapine 8 80 DDs/1000/Day $ million 6 60 use 4 40 2 20 cost 0 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 Figure 4 Antipsychotic drugs - use and cost trends in Australia
  20. 20. 2.8 Exercises 4. Antidepressant use3. Amoxicillin The use of antidepressant drugs (in DDDs per You note that amoxicillin use expressed as 1000 population per day) and their costs have DDDs per1000 population per day has been increasing for at least the last five years. increased over the last two years. What types What types of data would you need to deter- of drug utilization data would you need to mine the reasons for the change and whether it evaluate the possible reasons for this? has resulted in positive or negative health out- comes? 19
  21. 21. Chapter 3: Sources of data on drug utilization Drug-use chain; large databases; other sour- drug distribution chain, pharmaceutical and [ ces; drug use evaluation; pharmacoeconomics ] medical billing or samples of prescriptions. The databases may be international, national or local The drug-use chain includes the processes of in scope. They may be diagnosis-linked or non- drug acquisition, storage, distribution, prescri- diagnosis-linked. Diagnosis-linked data enable bing, patient compliance and the review of out- drug use to be analysed according to patient cha- come of treatment. Each of these events is an racteristics, therapeutic groups, diseases or con- important aspect of drug utilization, and most ditions and, in the best of cases, clinical out- countries have regulations to cover these aspects. come. A useful analysis requires an understand- Data are collected, or are available, at national, ing of the sources and organization of the data. regional and local health facility or household level and may be derived from quantitative or 3.2 Data from drug regulatory qualitative studies. Quantitative data may be agencies used to describe the present situation and the Drug registration; drug importation trends in drug prescribing and drug use at vari- [ ] ous levels of the health care system. Drug regulatory agencies have the legal respon- Quantitative data may be routinely collected data sibility of ensuring the availability of safe, effi- or obtained from surveys. Qualitative studies20 assess the appropriateness of drug utilization and cacious and good-quality drugs in their country. They are thus the repositories of data on which generally link prescribing data to reasons (indi- drugs have been registered for use, withdrawn or cations) for prescribing. Such studies have been banned within a country. Regulatory agencies referred to as «drug utilization review» or «drug also have inspection and enforcement functions, utilization evaluation». The process is one of a and are responsible for supervising the importa- «therapeutic audit» based on defined criteria and tion of drugs and for the issuance of permits for is intended to improve the quality of therapeutic drug registration. care. There is an increasing interest in the evalu- It is possible, therefore, to obtain data on the ation of the economic impact of clinical care and number of drugs registered in a country from medical technology. This has evolved into a dis- such agencies. Where the agency issues import cipline dedicated to the study of how pharma- permits and supervises drug importation, data on cotherapeutic methods influence resource utili- product type (i.e. generic or branded), volume, zation in health care known as pharmacoeco- port of origin, country of manufacture, batch nomics (see chapter 4). number and expiry date may be collected. The sources of drug utilization data vary from Where the data reflect total national imports, country to country depending on the level of estimates of quantities of drugs in circulation sophistication of record keeping, data collection, can be obtained for defined periods and for analysis and reporting and the operational consi- various therapeutic groups derations of the health care system. It may be difficult to obtain true estimates if documentation is incomplete and not all trans- 3.1 Large databases actions are recorded. Information on smuggled The increasing interest in efficient use of health goods or goods entering the country through ille- care resources has resulted in the establishment gal routes will not be captured by these data. of computer databases for studies on drug utili- zation. Some of the databases can generate sta- tistics for patterns of drug utilization and adverse 3.3 Supplier (distribution) data drug reactions. Data may be collected on drug Drug importation; local manufacture; cus- sales, drug movement at various levels of the [ toms service ]
  22. 22. Data on suppliers may be obtained from drug motivate health care providers to adhere to esta-importers, wholesalers or local manufacturers. blished health care standards.In countries where permits or licences arerequired from drug regulatory authorities and 3.4.1 Prescribing dataministries of health before importation of drugs, Prescribing data are usually extracted from out-data may be available from such sources. patient and inpatient prescription forms. SuchCustoms services, in the process of clearing data may be easily retrieved where records areimports from the ports of entry, may collect data computerized and computerized data also facili-on drugs. However, the codes used by customs tate trend analysis. In the absence of electronicservices are not detailed enough to capture all databases, prescribing data are usually extractedrelevant information. National agencies respon- from patient records or from patient interceptsible for the collection of excise duty can also studies or retrieved at dispensing points.provide information on the volume of production Information that may be obtained from pre-and on distribution of drugs from local manufac- scriptions includes patient demography, drugturers. name, dosage form, strength, dose, frequency of Data from these sources can generally be used administration and duration of treatment. Whereto describe total quantities of specific drugs or diagnoses are noted on prescriptions, and parti-drug groups, origins of supplies and type (i.e. cularly for inpatient prescription, it is possible tobranded or generic). link drug use to indications. Trends in utilization 21 In the absence of a national mechanism for the for specific drugs and diseases can also be esta-direct capture of data on drug production or blished. As an example, inpatient data may pro-importation, wholesalers become an important vide a link to empirical treatment of infections assource of information on drug acquisition. Such opposed to treatment based on microbiologicaldata are reliable insofar as wholesalers are the assessment. This may be achieved by extractingonly legal entity able to import drugs. In some relevant data from the patient records, but requi-countries, medical, dental and veterinary practiti- res that the records be of good quality.oners, as well as pharmacists, can import phar- Prescriptions are a good source of informationmaceutical products. It is usually very difficult for determining some of the indicators of drugto collect comprehensive data from such sources use recommended by WHO including the:even if there are regulatory requirements aboutsubmitting reports. Public sector procurement – average number of drugs per prescriptionpractices, however, have reasonable documen- (encounter);tation but provide data only on that sector. – percentage of drugs prescribed by generic name;Practice setting data – percentage of encounters resulting in prescrip- tion of an antibiotic; Prescribing data; dispensing data; drug use – percentage of encounters resulting in prescrip-[ indicators; facility data (aggregate) ] tion of an injection; – percentage of drugs prescribed from essentialData from health facilities may be used to evalu- drugs list or formulary, andate specific aspects of health provision and drug – average drug cost per encounter.use and to generate indicators that provide infor- Prescribing data allow the determination of themation on prescribing habits and aspects of pati- PDD which may differ from the DDD. Whileent care. These indicators can be used to deter- the DDD is based on the dosages approved inmine where drug use problems exist, provide a standard product characteristics with clinical out-mechanism for monitoring and supervision and come data from controlled clinical trials, the
  23. 23. PDD is variable and dependent on factors such can be used to obtain information on various as severity of illness, body weight, interethnic aspects of drug use including: differences in drug metabolism and the prescri- – the cost of individual drugs and classes of bing culture of the health provider. Using DDDs drug; enables comparison to be made between drug – the most frequently or infrequently used drugs; groups as the influences of prescribing culture – the most expensive drugs; and available dosage strengths are eliminated. – the per capita consumption of specific pro- In some countries, it is a legal requirement ducts; that prescriptions dispensed by pharmacies and – comparisons of two or more drugs used for the drug outlets are kept for a minimum period before same indication; disposal. Where these regulations are adhered – the prevalence of adverse drug reactions; to, prescription data may be obtainable from – the prevalence of medication errors; and pharmacies. However, in many developing – the percentage of the budget spent on specific countries the rule is not generally followed. In drugs or classes of drug. countries where computerized records of prescri- bing data are kept, they may be readily retriev- Aggregate data are often useful for comparing able depending on the depth of the database. the utilization of a particular drug to that of other drugs and to utilization in other hospitals,22 3.4.2 Dispensing data regions or countries. Drug dispensing is a process that ends with a client leaving a drug outlet with a defined quan- 3.4.4 Over-the-counter and tity of medication(s) and instructions on how to pharmacist-prescribed drugs use it (them). The quantity of drugs dispensed Pharmacists and other drug outlet managers may depends on their availability. Thus information prescribe over-the-counter preparations or phar- available from dispensers may include: macist-prepared drugs that do not require pre- – drug(s) prescribed; scription by a physician. Data on such medica- – dose(s) prescribed; tions may be difficult to obtain especially in – average number of items per prescription; environments with weak drug regulation and – percentage of items prescribed that were actu - poor record keeping, but when such information ally supplied (an indicator of availability); is available from stock or dispensing records, it – percentage of drugs adequately labelled; broadens the understanding of drug utilization – quantity of medications dispensed; and patterns. – cost of each item or prescription. 3.4.5. Telephone and Internet These data may be obtained from records kept at prescribing the drug outlet either in electronic or manual Physicians in certain countries may prescribe form. over the telephone. Prescribing and dispensing using the Internet also occurs, especially in deve- 3.4.3 Aggregate data loped countries. Most Internet prescriptions are A number of data sources within the health faci- for nutritional supplements and herbal preparati- lity or hospital setting can provide aggregate ons. However, as exemplified by sildenafil data on drug utilization. These sources include (Viagra®), other medicines are also increasingly procurement records, warehouse drug records, being sold on the Internet. Innovative ways have pharmacy stock and dispensing records, medica- to be devised to collect information on this type tion error records, adverse drug reaction records of transaction. and patient medical records. These data sources
  24. 24. 3.5 Community setting data Drug use evaluation can assess the actual pro- cess of administration or dispensing of a medica- Household survey; compliance (adherence tion (including appropriate indications, drug[ to treatment); drug utilization ] selection, dose, route of administration, duration of treatment and drug interactions) and also theThe drugs available in households have either outcomes of treatment (e.g. cured disease condi-been prescribed or dispensed at health facilities, tions or decreased levels of a clinical parameter).purchased at a pharmacy (with or without a pre- The objectives of drug use evaluation include:scription) or are over-the-counter medications.The drugs may be for the treatment of a current – ensuring that drug therapy meets current stan--illness or are left over from a previous illness. It dards of careis not uncommon for patients to adhere poorly to – controlling drug cost;the instructions given for taking their dispensed – preventing problems related to medication;medicines. Thus dispensing data and utilization – evaluating the effectiveness of drug therapy; anddata may not be equivalent because they have – identification of areas of practice that requirenot been corrected for non-compliance. further education of practitioners. Drug utilization by outpatients is best assessedby performing household surveys, counting left- The problems to be addressed by drug use evalu- ation may be identified from any of the data des-over pills or using special devices that allow cribed in section 3.4 (including prescription indi- 23electronic counting of the number of times a par-ticular drug is administered. Drug utilization by cators, dispensing data and aggregate data). Theinpatients can be determined by reviewing treat- main source of data for drug use evaluation isment sheets or orders. the patient records. An identifiable authoritative For both outpatients and inpatients, the data group, such as the drugs and therapeutic com-on the utilization of a particular drug can be mittee, usually carries out reviews of drug use inaggregated for a defined population in DDDs. a hospital or health facility. This group has theUsing DDDs has the advantage of allowing com- responsibility for drawing up the guidelines, cri-parison for example between inpatients and out- teria, indicators and thresholds for the evaluati-patients. Data on various dosage forms and on. Drug use evaluation may be based on datageneric equivalents of the same medication can collected prospectively (as the drug is being dis-also be aggregated. pensed or administered) or retrospectively (based on chart reviews or other data sources).3.6 Drug use evaluation • Typical criteria reviewed in prospective studies Drugs and therapeutic committee; prospec- include the following tive evaluation; retrospective evaluation; – indications; criteria setting – drug selection; – doses prescribed;Drug use evaluation, sometimes referred to as – dosage form and route of administration;drug utilization review, is a system of continu- – duration of therapy;ous, systematic, criteria-based drug evaluation – costs;that ensures the appropriate use of drugs. It is a – therapeutic duplication;method of obtaining information to identify pro- – quantity dispensed;blems related to drug use and if properly develo- – contraindications;ped, it also provides a means of correcting the – therapeutic outcomeproblem and thereby contributes to rational drug – adverse drug reactions; andtherapy. – drug interactions.
  25. 25. • In retrospective studies, the criteria source that could help you understand the situa- reviewed include: tion, and (2) some possible advantages and/or – evaluation of indications; limitations of each of the sources of data you – monitoring use of high-cost medicines; have listed. – comparison of prescribing between physicians; – cost to patient; When evaluating the advantages and – adverse drug reactions; and limitations of the data, consider the ans- – drug interactions. wers to the following questions: • How relevant are the data for It is possible to incorporate some of the above learning about antibiotics? criteria into databases thus allowing drug experts • How easy is it to collect these to evaluate any items that do not meet establis- types of data in your country? hed criteria. For meaningful results to be obtai- • How much will it cost to collect ned from drug use evaluation a reasonable num- and process the data and how ber of records need to be assessed. A minimum long will it take? of 50 to 75 records per health care facility is • How reliable are these data? considered adequate. However, the number of records sampled would depend on the size of the For example, from data from previous24 facility and the number of prescribers. surveys, we might obtain the following useful information: historical utilization 3.7 General reading rates by facility or geographical area, and How to investigate drug use in health facilities: possibly utilization by type of antibiotic, Selected drug use indicators. Geneva,World health problem or age. The advantages Health Organization, 1993 (unpublished docu- of using historical survey data are that ment WHO/DAP/93.1; available on request from they have already been collected and Department of Essential Drugs and Medicines carry no additional cost. However, their Policy, World Health Organization, 1211 limitations include not being able to con- Geneva, 27, Switzerland). trol exactly which data have been collec- ted or from where, not knowing whether 3.8 Exercises current practices reflect those of the past, Examine the sources of data listed in the and having no patient-specific or provi- Worksheet. Imagine that you want to learn der-specific information. It would also about the utilization of antibiotics in your coun- usually not be possible to find informa- try. In the spaces provided in the right-hand tion on dosing of antibiotics. columns of the worksheet, write down (1) what kinds of useful data you might gather from each
  26. 26. Worksheet for section 3.8 Sources of data on drug utilizationData source Type of information available Advantages and limitationsDrug import recordsDrug supply to healthfacilityOrders and/ordelivery receiptsPrevious reports ofsurveys 25Pharmacy stock cards/pharmacy ledger bookPharmacy salesreceiptsLarge hospital orinsurance databasesPrivatedrug outlet salesrecordsCommunityor household surveysDrug manufacturingrecordsOther sources
  27. 27. Chapter 4: Economic aspects of drug use (pharmacoeconomy) Pharmacoeconomics; types of cost; cost-mini- 4.2 Cost-minimization analysis mization analysis; cost-effectivness analysis; Cost-minimization analysis is a method of calcu- cost-benefit analysis; cost-utility analysis lating drug costs to project the least costly drug or therapeutic modality. Cost minimization also 4.1 Introduction reflects the cost of preparing and administering a Drug costs per se are important, as they account for dose. This method of cost evaluation is the one a substantial part of the total cost of health care - used most often in evaluating the cost of a speci- typically 10-15% in developed countries and up to fic drug. Cost minimization can only be used to 30-40% in some developing countries. However, compare two products that have been shown to drug costs usually need to be interpreted in the con- be equivalent in dose and therapeutic effect. text of the overall (net) costs to the health system. Therefore, this method is most useful for compa- Drugs cost money to buy, but their use may also ring generic and therapeutic equivalents or «me save costs in other areas. For example, the purchase too» drugs. In many cases, there is no reliable of one specific type of drug may lead to reductions equivalence between two products and if thera- in the following: peutic equivalence cannot be demonstrated, then – use of other drugs; cost-minimization analysis is inappropriate. – the number of patients requiring hospitalization If a new therapy were no safer or more effecti- or in the length of stay in hospital; ve than an existing therapy (i.e. there is no incre-26 – the number of doctor visits required; mental benefit), it would normally justify the – administration and laboratory costs compared same price as the existing therapy. An example with those incurred by using another drug to treat would be the introduction of a new ACE inhibi- the same condition. tor with essentially the same properties as exis- Assessing the true cost to a health system of ting members of the class; the price would be using a specific drug will therefore require the cost equivalent to that of the existing drug(s). This is of acquisition of the drug to be balanced against often not as simple as it may seem, as it requires both any cost savings resulting from the use of that sound trial-based information on the doses of the drug and the extra health benefits it may produce. two drugs required for equivalent efficacy. An On the other hand, costs may arise from adverse alternative is to use the PDDs for the two drugs drug reactions both in the short- and particularly the in the marketplace to determine the relative pri- long-term. ces. This is a pragmatic approach, but assumes Assessing the value for money of using a drug that the two drugs are actually used at equiva- requires the extra health benefits achieved to be lently effective doses, and this may not always weighed against the extra net cost. This compari- be the case. son is usually expressed as an incremental cost- effectiveness ratio (ICER) which is the net incre- 4.1 Cost-effectiveness analysis mental cost (costs minus cost offsets) of gaining an Cost-effectiveness analysis involves a more com- incremental health benefit over another therapy. prehensive look at drug costs. While cost is Concerns about the cost of medical care in gene- measured in monetary terms, effectiveness is ral, and pharmaceuticals in particular, are currently determined independently and may be measured being expressed by all health systems. There is a in terms of a clinical outcome such as number of general focus on providing quality care within limi- lives saved, complications prevented or diseases ted financial resources. Decision-makers are increa- cured. singly dependent on clinical economic data to guide Cost-effectiveness analysis thus measures the policy formulation and implementation. Some of incremental cost of achieving an incremental the concepts used in making such decisions include: health benefit expressed as a particular health cost-minimization, cost-effectiveness, outcome that varies according to the indication cost-benefit, and cost-utility. for the drug. Examples of ICERs using this

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