Proceedings of the First Hong Kong (Asia PacFfic) Medical Informatics Conference

HK Proceedings of the First Hong Kong (Asia PacFfic) Medical Informatics Conference Hong Kong Polytechnid 6-18 November 1990 Edited by ANTHONY J HEDLEY Department of Community Medicine University of Hong Kong WONG CHUN POR Hong Kong Society of Medical Informatics Conference Organizing Committee Chairman: AJ Hediey Vice Chairman: CP Wong Secretary/Treasurer: YW Ho. Members; KK Cheng Wilson Chick-. William Chiu.. KJ Goulding - ' i :.,. ^ David Leung ; :.- :{ ' " Raymond Leung Debbie Shum Alfred Tang Douglas Tung CM Wong Published by the Hong Kong Society of Medicaf informatics and the Hong Kong Computer Society isbn:962-7545-01-5' ' '

"7 EProEIVnOLOGICAL AND RESOURCE DATA NEEDED FOR AN ECONOiVnC EVALUATION STUDY IN PATIENTS WITH GASTRIC ULCER ON NSAIDs RP Knill-Jones, HS Kohli Dept of Public Health, University of Glasgow, Scotland. MF Drummond, L Davies Centre for Health Economics, University of York, England. ABSTRACT Increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs) results in clinically significant complications, including gastric ulcers which may bleed or perforate. This study examines the information needed to undertake an economic evaluation of misoprostol in preventing gastric ulcers (GUs) in patients receiving NSAIDs. It also identifies the deficiencies in data available to the UK National Health Service (NHS) with respect to economic assessments, as existing large epidemiological data bases do not contain all the information needed for an economic evaluation. Costs of medical treatments and procedures are rarely available in the NHS and had to be measured in a special study. A detailed analysis of a sample of relevant admissions of patients with GI disease in Glasgow in 1987 was necessary to help in the interpretation of national epidemiological data, and to assess resources used in hospital. Structured telephone surveys of general practitioners in Glasgow and Birmingham were undertaken to provide estimates of the resources used in managing these patients in the community. 1. INTRODUCTION There is a worldwide use of non-steroidal anti-inflammatory agents (NSAIDs) in the elderly. 1

particularly in Europe. Over the past 8 years prescriptions for NSAIDs in the UK have increased by 64%, in 1986 reaching 23 million [1,2]. Concurrently there has been a rise in peptic ulcer perforation rates among women. This has occurred in spite of a fall in total hospital admissions for ulcer in both sexes, and a steady fall in ulcer perforations in males [3]. The rise in perforation rate in women has been accompanied by an increase in mortality for this complication of 18% in women aged over 75, compared with a fall of 23% in mortality for males over the same period [4]. Some, but not all, of these features have been noted in the USA [5]. A retrospective case-control study on bleeding peptic ulcers admitted to Nottingham hospitals showed a relative risk of 2.7 (95% confidence limits{cl} 1.7 to 4.4) for NSAID use in people over 60 [4]. The same community showed a similar relative risk for aspirin [8]. In contrast, a prospective study on ulcer perforation in the USA gave a relative risk of 1.6 (CL 0.7-3.7) suggesting no association [9]. Two others gave relative risks of 2.5 (CL 1.5-3.7) [10] and 4.7 (CL 3.1-7.2) [11] indicating, on balance, an association between NSAID use and ulcer. The precise extent of the risk of ulcer from NSAIDs is uncertain [6,7] and firm evidence that the observed association is a causal one is lacking. Ulcer-like symptoms occur in up to half the patients taking NSAIDs [12]. Over a three-month period of treatment, about one-third of patients on NSAIDs develop GI symptoms, and 1% may develop a major complication [13,14]. The situation is further complicated in that the use of NSAIDs amongst the over 75's seems to mask ulcer symptoms. This may lead to a late presentation of complicated peptic ulcer and a resulting poorer prognosis [15,16]. Drugs can be used to prevent GI complications from NSAIDs and several have been evaluated [1,17]. One of them is misoprostol, which is effective in preventing gastric mucosal lesions [18] and in reducing transfusion requirements in upper gastro-intestinal bleeding [19]. The prevalence of gastric mucosal erosions and ulcers (confirmed by endoscopy) is high following NSAID use. It was 22% in one clinical trial [18], 20% in asymptomatic patients with rheumatoid arthritis [20] and if anaemia was also present, higher at 37% [20]. Duodenal ulcer rates in the same studies are much lower, the correspondingfiguresranging between 2% and 4% [18,20], and up to 8% [1]. Ranitidine, an blocker, is effective in reducing 2

duodenal inflammation when prescribed concomitantly with NSAIDs [1]. However, the same smdy failed to demonstrate a significant effect on gastric ulcers or erosions [1]. Medical decision analysis [21-23] can be used to elucidate the effectiveness of interventions in populations of patients. This allows an economic evaluation of the clinical decision to give prophylaxis or not. Economic evaluation has also been undertaken for treatment of Rheumatoid Arthritis [24], for maintenance therapy of duodenal ulceration using Ho antagonists [25-28], and for ulcer surgery [29]. Increasingly health care resources in the UK are stretched in the face of competing demands for their use. It is now necessary to show not only that therapies are effective, but also that they represent a good use of resources. Concerns about the value for money from prophylaxis of NSAID-associated ulcers were recently raised in two editorials [30,31]. For all these reasons it is becoming more important to use medical decision analysis and economic evaluation in health care. This paper draws attention to the lack of readily available data to enable an accurate economic evaluation to be carried out in the UK National Health Service (NHS). It also outlines the steps needed to complete a decision analysis of the prevention of NSAID - associated ulcers. 2. METHODS A decision tree demonstrating the process of care for a patient who developed symptoms while taking NSAIDs was drawn up and its structure agreed. Each circular node represents a chance node at which the probabilities of a patient following one or other branch need to be obtained. 3

Figure 1. Decision tree PATIENT WITH ABDOMINAL PAIN ON NSAIDs No Ulcer Ulcer Ambulatory care Hospital Admission 1 Medical Treatment Surgical Treatment 3 4 The numbers 1-4 at the bottom of the tree show that different costs had to be calculated for patients following each path. This process identified the two kinds of information that were needed to allow a full decision analysis to be performed. First the probabilities of certain events are required, for example: - the chance of developing a gastric ulcer, the subsequent chance of a severe bleed or perforation, and the probability that certain investigations would be arranged by the general practitioner. The second type of information needed was the cost of 4

attendance at a general practitioner's surgery, the cost of an endoscopy, and the cost of a stay in a hospital ward. 3. RESULTS 3.1 SOURCES OF PROBABILITIES The risk of developing a gastric ulcer in a patient with symptoms, if untreated, was about 22% [18]. The risk for a patient of a hospital admission with a complication (5.34%) was obtained from a large-scale study in general practice [32]. This provided approximate estimates because of differences in diagnostic classification which were broader than that of gastric ulcer. The tree shows that patients admitted to hospital could be kept in a medical ward, particularly if they had bled, or to a surgical ward if they had perforated. The relevant proportions were obtained from a Scottish data set covering all hospital discharges (680,000 annually), and from an equivalent data set in the West Midlands region in England (5(X),000 annually). There were 3867 discharges with gastric ulcer as a principal diagnosis in Scotland for the three years 1985-87. 43% of these cases, with an average age of 62.5 years, had operations and their mean length of stay was 9.5 days. The remainder, who were treated medically, were aged 65.3 and had a mean length of stay of 10.4 days. It was important to distinguish those receiving medical care from those having surgical care because of the differing costs. Special analyses had to be undertaken to provide information on type of care from the very large National or Regional data sets, which are readily available for this purpose and which also provided some data for the cost calculations. Another set of probabilities related to the investigation sti-ategy that general practitioners would adopt when faced with a patient with symptoms on NSAIDs. Ideally tiiis information might have been obtained by follow-up of a large number of patients on NSAIDs, some of whom could develop ulcer, but this would have been very expensive and time-consuming. Therefore telephone surveys with general practitioners in Glasgow and in Birmingham were conducted by one of the authors. Figure 2 on the next page gives an outline of the structure of the interview and also shows the items whosefrequencyof utilisation needed to be obtained. 5

Figure 2. GP telephone interviews. No ulcer Introduction Persistent / Symptomatic symptoms ( P?!' "t Investigate X Initsal actions Ulcer INFORMATION NEEDED Treatment Recall rate Endoscopy X-Ray Treatment Recall rate OP Appt. Biopsy Repeat endoscopy Recall rate The interviews provided estimates of the number of patients' attendances at a doctors' surgery, the probabilities of whether a directly referred investigation would first be by endoscopy or by X-Ray, or of a hospital appointment for a consultant opinion to obtain an endoscopy, the probability of which further investigations would be arranged should an ulcer be found, and the numbers of additional surgery visits during this period. Also needed for some patients, but not shown in figure 2, were the numbers of follow-up visits to hospital and to general practice after a hospital admission with a complication. 6

The final set of probabilities that were required related to the investigations completed and to the use of hospital-based resources, for example the proportion of patients having blood transfusions, the average number of bed-days in intensive care and the average mix of tests done. Such information is not routinely available in the NHS for different diagnoses, neither for'clinical specialty or diagnosis-related groups, nor even for an entire hospital. Identification of these probabilities was done by case review. A random sample of 778 patients admitted to Glasgow hospitals was identified from all admissions (4355) in 1987 with gastrointestinal diagnoses. These represented 3586 individuals from which the sample was drawn. Case notes in the 5 main Glasgow hospitals were examined to assess the resources used, only 17 (2.2%) being unavailable during the three months needed to complete the review. Analysis of this data demonstrated that 53% of patients over 60 years of age in a surgical ward received a blood transfusion, 91 % an endoscopy, 18% a Barium meal and that patients spent an average of 0.6 days in intensive care. 3.2 COSTS NHS routine data sources provided costs of only a few items needed for the study. The cost of all investigations (endoscopies, X-Rays, etc.) had to be estimated by a special survey as these individual items are not costed separately in the NHS. This involved an assessment of the staff time, drugs and other items needed for an X-Ray, which in turn were costed and the figure of 37 calculated (Table 1). The cost of a bed-day in intensive care was not available fi-om the NHS at the time and a private sector charge had to be used as an estimate. 7

TABLE 1 ^ Item Source of Cost to Source of valuation nearest utilisation estimate Attendance at CP's surgery NHS 6 GP survey Attendance at Out Patient Dept NHS 14 GP survey Endoscopy Special survey 84 GP survey Biopsy Special survey 44 GP survey/ consultant opinion X-Ray Barium meal Special survey 37 GP survey/ case review X-Ray Barium enema Special survey 56 GP survey/ case review Ambulance journey (Emergency) NHS 17 Case review Hospital 'hotel' cost per day NHS 51 NHS/ National data bed-days Intensive care per day Private sector 330 NHS/ Case review bed-days Surgery* Special survey 352 NHS/ National data bed-days Medical care* Special survey 52 NHS/ National data bed-days Blood transfusion (average ulcer) Special survey 89 Case review Drug cost - H2 antagonist 6 weeks NHS 45 Consultant Drug cost - misoprostol 400jig/day NHS (3 months) 39 Consultant^ Study design. *in addition to investigations, day cost and follow-up costs Cost data were combined with the utilisation data to give the cost of the four different paths through the decision tree for Scotland. The results of the full decision analysis, including the data from the West Midlands, are presented in detail elsewhere [33]. Misoprostol will prevent 75% of the ulcers when given in a 400 jig daily dose [18]. The decision analysis shows (summarised over the page in Table 2) that under this set of assumptions the reduction in the numbers of ulcers and their associated high costs is greater than the additional cost of treating 8

patients with misoprostol. On balance there are cost savings that will arise from the use of this drug to prevent ulcer as shown by the average cost per case in Table 2. In other words the additional cost of misoprostol is more than balanced by the expected savings from the substantial reduction in the number of ulcers. TABLE 2 Tree branch Cost per case for 3 months (Scotland) (nearest ) (Figurel) No misoprostol misoprostol 1 No ulcer 42 80 2 Ambulatory ulcer care 315 334 3 Medical admission 1308 1328 4 Surgical admission 1527 1546 Average cost per case 114 98 4. DISCUSSION This study underlines the difficulty in obtaining cost and other data from existing NHS sources to provide the information needed for decision analysis. Ideally all the information should be readily available from the NHS. This is not so now, though may improve as reforms to the NHS become effective. At present most effort is being directed towards preparing contacts between the purchasers of health care (the NHS health boards) and the providers (hospitals, some general practitioners). In the absence of detailed cost data these 9

contracts can only be given in the most general of terms. Tfte easy availability of the data needed to undertake the many necessary economic evaluations of activities in the NHS remains an objective for the future. 5. ^ REFERENCES 1. EhsanuUah RSB, Page MC, Toldesley G, Wood JR. Prevention of gastro-duodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. Br Med J 1988; 297: 1017-21. 2. Walt R, Katchinski B, Logan R, Ashley J, Langman M. Rising frequency of ulcer perforation in elderly people in the United Kingdom. Lancet 1986; 1:489-92. 3. Coggon D, Lambert P, Langman MJS. 20 years of hospital admissions for peptic ulcer in England and Wales. Lancet 1981; 1: 1302-4. 4. Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet 1986; 1:462-4. 5. Kurata JH, Haile BM. Epidemiology of peptic ulcer disease. Clin Gastro 1984; 13: 289-307. 6. Doherty M. Non-steroidal anti-inflammatory drugs in patients with peptic ulcer disease: to be considered in certain circumstances. Br Med J 1989; 298: 176-9. 7. Hawkey C. Non-steroidal anti-inflammatory drugs in patients with peptic ulcer disease: rarely justified in terms of cost or patient benefit. Br Med J 1989; 298:177-8. 8. Faulkner G, Prichard P, Somerville K, Langman MJS. Aspirin and bleeding ulcers in the elderly. Br Med J 1988; 297: 1311-3. 10

9. Jick SS, Perera DR, Walker AM, Tick H. Non-steroidal anti-inflammatory drugs and hospital admissions for perforated peptic ulcer. Lancet 1987; ii: 380-2. 10. Hillman AL, Bloom BS. Economic effects of prophylactic use of misoprostol to prevent gastric ulcer in patients taking non-steroidal anti-inflammatory drugs. Arch Int Med 1989 ;149:2061-65. 11. Giffin MR, Ray WA, Shaffner W. Non-steroidal anti-inflammatory drug use and deaths ii-om peptic ulcer in elderly persons. Ann Int Med 1988; 109: 359-63. 12. Coles LS, Fries JF, Kraines RG, Roth SH. From experiment to experience: side effects of non-steroidal anti-inflammatory drugs. Am J Med 1983; 120:- 820-8. 13. Husby G, Holme I, Rugstad HE, Herland OB, Giercksky K-E. A double-blind multicentre trial of peroxicam and naproxin in osteoarthritis. Clin Rheumatol 1986; 5: 84-91. 14. Giercksky K-E, Husby G, Rugstad HE, Revhaug A. Epidemiology of NSAIDinduced GI problems and the role of cimetidine in their prevention. Aliment Pharmacol Therap 1988; 2 (suppl 1): 33-41. 15. Skander MP, Ryan FP. Non-steroidal anti-inflammatory drugs and pain free peptic ulceration in the elderly. Br Med J 1988; 297: 833-4. 16. Armsti-ong CP, Blower AL. Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut 1987; 28:527-32. 17. Watkinson G, Hopkins A, Akbar FA. The therapeutic efficacy of misoprostol in peptic ulcer disease. Postgrad Med J 1988;64: Suppl 1,60-73. 18. Graham DY, Agrawal NW, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind placebo-controlled trial. Lancet 1988; 2: 1277-80. 11

19. Birnie GD. Akbar FA. Shroff NE, Shelton JR, Watkinson G. A double blind comparative study of misoprostol with placebo in acute upper GI bleeding. Int Gastroent 1988; Vol 1: 110. 20r" Upadhyay R, Taha AS, Sturrock RD, Russell RI. Misoprostol and ulcer prophylaxis. Lancet 1989; i: 212-3. 21. Weinstein MC, Fineberg HV. Clinical Decision Analysis. Philadelphia: WB Saunders, 1980. 22. Carrin G. Economic evaluation of health care interventions: a review of alternative methods. Soc Sci Med 1984; 19: 1015-30. 23. Macartney FJ. Diagnostic logic. Br Med J 1987; 295:1325-31. 24. Thompson MS, Read JL, Hutchings CH, Paterson M, Harris ED. The cost effectiveness of Auranofm: results of a randomised clinical trial. J Rheumatol 1988; 15:35-42. 25. Fox N, Morton RE, Jacobs J. The cost-effectiveness of maintenance therapy for duodenal ulceration with an H2 antagonist. Aliment Pharmacol Therap 1988; 2:297-309. 26. Sitonen H, Alander V. Estimating the cost-effectiveness of three drugs in the treatment of duodenal ulcers. 4th annual meeting of the International Society of Technology Assessment in Health Care. Boston 1988. 27. Navarro RP, Blissenbach HP. Using H2 antagonist "cost of therapy" data to make formulary decisions within a managed health care system. Medical Interface 1988; March: 14-19. 28. Weisbrod BA. Economic approaches to evaluating a new medical technology: the drug cimetidine. In AJ Culyer and B Horisberger. Economic and medical evaluation of health care technologies. Berlin: Springer-Verlag, 1983. 12

29. Culyer AJ, Maynard AK. Cost-effectiveness of duodenal ulcer treatment. Soc Sci Med 1981; 15C: 3-11. 30. Editorial. Lancet 1988; 2: 1293-4. 31. Roth SH. Non-steroidal anti-inflammatory drugs: Gastropathy, deaths and medical practice. Ann Int Med 1988; 109: 353-4. 32. Royal College of General Practitioners, OPCS, DHSS. Morbidity Statistics from General Practice 1981-82. HMSG Series MB5 No. 1, London, 1986. 33. Knill-Jones RP, Drumm^ond M, Kohli H, Davies L. Economic evaluation of gastric ulcer prophylaxis in patients with arthritis receiving non-steroidal anti-inflammatory drugs. Postgrad Med J 1990; 66: 639-646. 6. ACKNOWLEDGEMENTS We are grateful to the Information and Statistics Division of the Common Services Agency of the Scottish Health Services, the Information Services Department of the Greater Glasgow Health Board, and the Statistics Department of the West Midlands Regional Health Authority for supplying data. We are also grateful to GPs in Glasgow and in Birmingham for their opinions on management and to G.D.Searle, UK, forfinancialsupport. 13 i