Target Drug Programs and Medication Use Evaluation

Transcription

1 Target Drug Programs and Medication Use Evaluation Yechiel A. Hekster, Ph.D. Target drug programs and medication use evaluations are activities that are undertaken to improve the correct use of drugs. These programs should focus on inappropriate drug use, drug use problems, optimizing use of drugs, and improving the level of patient care. To monitor the effects of the programs, several types of outcomes have been evaluated, such as economic and financial, clinical quality, quality of life, patient satisfaction, and collaborative practice. The methodology to classify and monitor drug use incorporates the classification system developed by the World Health Organization, which takes into account each drug s anatomic, therapeutic, and chemical classification. In order to avoid focusing only on drugs and drug costs in these programs, and to allow for monitoring the impact of the programs on clinical practice, linking drug data to patient data is stressed. Target drug programs improve the appropriate use of drugs, and by doing so, contribute to safe and rational use of drugs in society. (Pharmacotherapy 2000;20(10 Pt 2):322S 326S) For many years, attention has been focused on the rational and optimal use of drugs in society. Currently, there are worldwide efforts to strengthen the attention on the appropriate use of drugs. Key factors for this attention have been the large numbers of patients in the community and in hospitals treated with drugs, the observation that these drugs are not used to their full potential, and the increasing cost of health care. In addition, potent drugs that require extra control measures have become available on the market. Several new drugs, such as biotechnology products and cytotoxic agents, are very expensive in relation to former drugs and often require special infusion techniques, devices, or pumps. Furthermore, many drugs can give rise to iatrogenic complications, resulting in hospital admissions or prolonged hospital stays. These accompanying costs far exceed the purchase cost of the drug. An evolution can be seen in the development From the Department of Clinical Pharmacy, University Hospital Nijmegen, St Radboud, Nijmegen, The Netherlands. Address reprint requests to Yechiel A. Hekster, Ph.D., Department of Clinical Pharmacy, KF-533, University Hospital Nijmegen, St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. of target drug programs, which is outlined in Table 1. In the first years, target drug programs addressed basic questions of drug use. Latergeneration programs focused on the consumer and outcomes by addressing questions about the health gains from drug therapy. A shift was made from looking at drugs in isolation to their role as part of overall health care management. Initiating a target drug program by the firstgeneration approach is easier. However, programs should shift from first- to thirdgeneration programs to be most meaningful for total health care issues; these advanced programs require more expertise. In recent years, programs have been developed to ensure the safe use of drugs in society. The programs include various aspects and objectives, such as continuous education to reduce inappropriate use of expensive therapeutic equivalents, intervention when inappropriate drug use is detected, attention on cost and acceptable level of care, assessment of the appropriateness of drug use, detection and quantification of drug use problems, evaluation of drug effectiveness, and promotion of drug utilization research. Target drug programs should focus on at least four different areas: (1) inappropriate drug use;

2 TARGET DRUG PROGRAMS Hekster 323S Table 1. Target Drug Programs First Generation Second Generation Third Generation Basic question What Why Wherefore Type Descriptive Intervention Outcome Focus Drug Information Health gain Orientation Logistic Service Client (2) drug use problems, taking detection, frequency, and severity into consideration; (3) improving use of drugs; and (4) improving the level of patient care. The activities in these areas should have clearly defined outcomes to measure the effects of the programs. Several types of outcomes have been described. Recently the American Pharmaceutical Association (APhA) and the National Wholesale Druggists Association (NWDA) published an annotated bibliography of studies on the benefits of pharmaceuticals and pharmacy services. 1 They classified outcomes into six different categories: (1) economic and financial, (2) clinical quality, (3) quality of life, (4) patient satisfaction, (5) collaborative practice, and (6) miscellaneous. The recent literature provides evidence on the need to improve drug use and management. For example, in the treatment of hypertension and elevated lipids, the majority of patients are not treated optimally. 2 5 One reason for suboptimal drug therapy is poor patient compliance. 6 Models have been developed for outcome studies with analysis by compliance stratification, which show that the degree of drug effects varied in relation to the average doses actually taken. In addition, meta-analyses have shown that inappropriate drug use has led to hospital admissions due to side effects. 7 Such costs are extremely high as was shown by Johnson and Bootman, based on calculations using a model of illness. 8 It is important that research be carried out on both adverse and beneficial effects of drugs. Jick et al reviewed the principles of epidemiological research in this respect. 9 Programs in the Hospital Setting The hospital environment provides a setting that facilitates assessment of costs and allows the implementation of activities such as target drug programs. Target drug programs are useful means to influence prescribing and costs in the hospital, not only in the inpatient area but also in the outpatient clinic or primary care setting without reducing quality of care. In addition to drugs, these programs can also optimize the use of blood and blood products and improve Table 2. Classification of the ATC Main Groups ATC ATC Main Group A Alimentary tract and metabolism B Blood and blood-forming organs C Cardiovascular system D Dermatologicals G Genitourinary system and sex hormones H Systemic hormonal preparations J General antiinfectives for systemic use L Antineoplastics and immunomodulating agents M Musculoskeletal system N Central nervous system P Antiparasitic products R Respiratory system S Sensory organs V Various X Raw materials/packaging Y Not yet classified Z No drug the process of diagnosis. A review of methods of cost management in hospitals was recently 10, 11 published. Programs to optimize drug use and patient care also exist for hospitals in developing countries. 12 Many of these programs focus on direct costs only. In such programs, measures are taken by a multidisciplinary approach to avoid excessive drug costs. Such measures are effective but have an intrinsic risk that pharmacists may be regarded primarily as budget holders and cost controllers. This risk occurs especially in the case of newer drugs, whose advantages may be more difficult to justify in view of their usually more expensive costs, especially when cost reductions are achieved in other medical areas. The Formulary As early as the 1970s in the United States, restrictions were initiated by formulary and therapeutics committees to reduce the assortment of drugs in hospitals and to promote rational drug use. The American Society of Health- System Pharmacists (ASHP) defines the formulary...to be an important tool, for assuring the quality of drug use and controlling its cost, not only as a means of cost containment Prior attention focused on reducing the

3 324S Supplement to PHARMACOTHERAPY Volume 20, Number 10, 2000 Table 3. ATC Classification of Diazepam as an Example ATC Level ATC Code ATC Name Anatomic main group N Central Nervous System Therapeutic main group N05 Psycholeptics Therapeutic subgroup NO5B Anxiolytics Chemical subgroup N05BA Benzodiazepine derivatives Drug substance N05BA01 Diazepam ATC = anatomic, therapeutic, chemical. assortment of drug products. Such an approach reduced costs in the logistic process but only to a limited level. More important is the need to influence the use of drugs. The development of pharmacoepidemiology has contributed greatly to a new understanding of the relationship between drug use and outcomes in patients through studies that assess drug utilization patterns and their impact on prescribing policies. Methodology for Data Collection A clear structure is necessary for the collection of data so the database can be used to identify signals for study areas and for feedback to the institute. In the 1980s, the Department of Clinical Pharmacy of the University Hospital Nijmegen implemented the methodology for pharmacoepidemiology and drug utilization research developed by the World Health Organization s (WHO) Drug Utilization Research Group (DURG). The DURG meets regularly to develop this area of research, and a report of their meeting held in 1997 was published. 14 This methodology allows for the analysis of drug use and the assessment of the effects of interventions over time. In this methodology, the classification of all drugs and the units of use have been standardized. Classification of drugs is based upon the anatomic, therapeutic, and chemical (ATC) classification of WHO. 15 Table 2 is a list of the 17 main groups of the ATC classification system used in our hospital. The main group categories are based on anatomy. Further classification is based upon therapeutic and chemical information. Table 3 gives an example of this ATC classification code system for diazepam. Using this classification scheme, a unique code consisting of seven numbers and characters is available for every drug. The WHO releases a new edition every year to include codes for new drugs. In addition to the drug classification system, a methodology has been developed to allow comparison of utilization data. The defined daily dose (DDD) is applied as the unit of comparison. The WHO DURG working group has given every drug a DDD, which is a technical value based on the dose for the main indication for adults. By grouping drugs in their therapeutic class (ATC) and by giving them a value of use based on a common unit, it becomes possible to describe the total use of drug groups such as antiepileptic drugs. 16 To allow for comparisons among countries, the number of DDDs can be described in terms of 1000 patients per day. Examples of the application of this methodology can be found in Drug Consumption in Norway, describing the period of Within institutions and hospitals, the DDD is related to the number of bed-days to form a unit of comparison in terms of DDDs per 100 beddays. This unit gives an approximation of the percentage of patients who are treated with a particular medication or medication group. For several years, this methodology has been successfully applied in pharmacoepidemiological research and target drug programs in several therapeutic areas at the University Hospital of Nijmegen. The application of the ATC/DDD methodology to monitor antibiotic drug use was recently reported by Natsch et al. 18 Linkage of Drug Data with Patient Data These data, however, do not give information about the correct use of drugs. It is essential that drug use data be linked to patient data. For example, information about the use of antibiotics based upon drug data does not reveal whether the drugs were used according to protocols or standards of care. An example of patient carerelated drug use is a study recently published that looked at the timing of the first dose of antibiotics in patients admitted to the hospital. 19 The anticoagulation response would be important in studies on anticoagulant drug dosages. 20 Implementing Target Drug Programs During the workshops on target drug programs at the 1999 International Congress on Clinical

4 TARGET DRUG PROGRAMS Hekster 325S Table 4. Dos and Don ts for Implementing a Target Drug Program Dos Don ts Choose the right drugs (consider volume, Overload physicians with paperwork risks, costs and problems encountered) Fail to see the feasibility for all disciplines Identify the problems (baseline included) Make decisions in isolation Specify the criteria Try too much or too fast Benchmark Forget to follow-up Summarize the project for P & T committee Focus on costs only Estimate outcomes Forget to get baseline information Create incentives Neglect the impact Communicate about the project Get pressured Simplify the project Underestimate the workload Provide for exceptions (inclusion, exclusion) Reevaluate and update early in the program Be prepared (proactive) Be action oriented Pharmacy, discussions took place on how to make a program successful. The dos and don ts were discussed to help newcomers to this field avoid mistakes made in the past (Table 4). New Programs For newcomers to this field, an initial target drug program should contain several of the following elements to allow evaluation of its impact: it should be easy to perform, be drugoriented, be descriptive, include pre- and postprogram analysis, be based on a literature survey, have cost minimization as an outcome, deal with generic or therapeutic interchange, have a sufficient time frame to observe and evaluate the program, and lead to clear information that can be used for further studies. These programs could be evaluated independent of other health care workers or activities. Advanced Programs Advanced programs should focus on the correct use of drugs, be prospective in design, and search for health gain outcomes. Issues include methodology, targets, and the future role of pharmacists in these programs. The methodology should allow signal detection, preferably computerized, and include meaningful outcome parameters. For targets, the measurement of treatment effectiveness and health gain should receive high priority, as should the assessment of patients at risk. With so many information and automated tools, the question about the specific role of the pharmacist compared to other health care workers, such as pharmacologists, computer and information technologists, and administrators, should be raised. Pharmacists should be prepared to answer the question of their role and value in target drug-program activities. Program Orientation When initiating a target drug program, three different approaches can be taken: drugoriented, patient-oriented, or place-oriented. Drug Orientation These programs should focus on drugs with high costs, high volume, high risk, or that are overused under routine conditions. Examples are programs for antibiotics, albumin and blood products, histamine H 2 -receptor antagonists, and proton pump inhibitors. Patient Orientation These programs should focus on patient groups, such as neonates, pregnant women, the elderly, and patients at risk because of comorbidity. Examples are patients with high cholesterol or coronary heart disease, or patients who are anticoagulated or immunocompromised. Place Orientation Several units in the hospital are especially suited to carry out a program, such as the intensive care units. All health care workers realize the need for the correct use of medicines in such a unit. A place-oriented program might be the outpatient clinic, but it should not limit itself to a specialty clinic such as one for pregnant women or other special populations.

5 326S Supplement to PHARMACOTHERAPY Volume 20, Number 10, 2000 Outpatient clinic-oriented programs could address areas such as ulcer disease in patients using nonsteroidal antiinflammatory drugs or needing pain relief medications. Cohorts of patients can serve as comparisons. Potential Risk of Target Drug Programs One of the major risks of target drug programs is the focusing on drugs or drug costs only. Drugs are part of a disease treatment process, and the correct use of drugs can reduce overall health costs in society. The discussions about the use of lipid-lowering drugs in relation to cerebral accidents underlines this aspect. In many countries, health authorities blame prescribers for overprescribing such drugs based on the current registration files. It should be kept in mind that postinnovation innovation is a slow but continuous process. 21 Drugs that were approved for use in one indication may gradually become recognized as beneficial in other indications. In our current pharmacotherapeutic approaches, a shift from treatment to prevention is noticeable. Disease management is a comprehensive approach to preventing and treating disease. Emphasis is placed not only on patients with specific diseases but also on those with risk factors for drug-related problems, a history of nonadherence, or frequent changes in medication regimens. 22 Conclusion Target drug programs have seen rapid development in the last several years and have proven to be effective for rationalization of drug use. It should be kept in mind, however, that changes in drug utilization also change other aspects of the health care system. Drugs should be regarded as a part of a total treatment approach, and not as an isolated subject. Several points should be considered when carrying out programs. The program should be part of a structure and not be person dependent, not be an isolated process, and not be single-drug oriented but examine the impact on use of other drugs and drug classes. Furthermore, the time required to implement such programs should not be underestimated; drug programs are time consuming and follow-up is essential. When the setting is suitable, target drug programs are able to improve the correct use of drugs and by doing so contribute to the safe and rational use of drugs in society. References 1. Anonymous. Pharmacy services: improving patient outcomes and reducing costs. An annotated bibliography of studies on the benefits of pharmaceuticals and pharmacy services. Reston, VA: APhA and NWDA, Berlowitz DR, Ash AS, Hickey EA, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med 1998;339: Klungel OH, Boer A de, Paes AHP, Seidell JC, Nagelkerke NJD, Bakker A. Undertreatment of hypertension in a population-based study in The Netherlands. J Hypertens 1998;16: Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-densitylipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol 1998; 32(3): Cleeman JI, Lenfant C. The National Cholesterol Education Program: progress and prospects. JAMA 1998;280; Urquhart J, De Klerk E. Contending paradigms for the interpretation of data on patient compliance with therapeutic drug regimens. Stat Med 1998;17(3):251 67, Lazarou J, Pommeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279: Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost-of-illness model. Arch Int Med 1995; 155: Jick H, Garcia Rodriguez LA, Perez-Gutthan S. Principles of epidemiological research on adverse and beneficial drug effects. Lancet 1998;352: Pacey S, Li Wan Po A. A review of methods of drug cost management in hospitals. J Clin Pharm Ther 1998;23: Pacey S, Warner J, Li Wan Po A. A multidisciplinary approach to hospital -based drug cost containment J Clin Pharm Ther 1998;23: Thamlikitkul V, Danchaivijitr S, Kongpattanakul S, Ckokloikaew S. Impact of an educational program on antibiotic use in a tertiary care hospital in a developing country. J Clin Epidemiol 1998;51(9): Anonymous. ASHP statement on the formulary system. Am J Hosp Pharm 1986;43: Schubert J. Drug utilization in Europe. Report of the EURO- DURG Workshop and Joint Symposium with the EACPT. Int J Clin Pharm Ther 1998;36: World Health Organization. Guidelines for ATC classification and DDD assignment, 2nd ed. Oslo, Norway: Norsk Medicinaldepot, Lammers MW, Hekster YA, Keyser A, Meinardi H, Renier WO, Herings RM. Use of antiepileptic drugs in a communitydwelling Dutch population. Neurology 1996;46(1): Anonymous. Drug Consumption in Norway Oslo, Norway: Norsk Medicinaldepot, Natsch S, Hekster YA, de Jong R, Heerdink ER, Herings RM, van der Meer JW. Application of the ATC/DDD methodology to monitor antibiotic drug use. Eur J Clin Microbiol Infect Dis 1998;17(1): Natsch S, Kullberg BJ, van der Meer JW, Meis JF. Delay in administering the first dose of antibiotics in patients admitted to hospital with serious infections. Eur J Clin Microbiol Infect Dis 1998;17(10): Poller L, Shiach CR, MacCallum PK, et al. Multicentre randomised study of computerised anticoagulant dosage. European concerted action on anticoagulation. Lancet 1998;352(9139): Gelijns AC, Rosenberg N, Moskowitz AJ. Capturing the unexpected benefits of medical research. N Engl J Med 1998;339(10): Holdford D, Kennedy DT, Bernadella P, Small RE. Implementing disease management in community pharmacy practice. Clin Ther 1998;20(2):