Decision analysis in clinical medicine Clinical judgement, that major determinant of the quality of medical practice, is subject to a remarkable number of variables. Because the clinical judgement of a physician is, at the very least, related to his underlying intellectual ability, to the quality of his medical education and to the depth of his clinical experience, some are convinced that the generation of appropriate decisions in either simple or complex medical situations should not always depend solely upon clinical judgement. More scientific methods of making some medical decisions should be available methods primarily dependent upon facts and probabilities as opposed to the physician-to-physician variability of clinical judgement. In the search for such methods, techniques of decision analysis, long known and accepted in business and military circles, are beginning to be applied to medical problems. There are two general areas in which decision analysis is useful in medical decision-making: first, in medical decisions that can be clarified by straightforward "cost-benefit analysis" and, second, in more complex decisions of a recurrent nature that involve the advisability, in discrete populations, of tests or procedures with definite risks. Pauker and . reviewed the costbenefit type of decision-analysis problem; they constructed a formula integrating mathematical expressions of the costs and the benefits of investigation or therapy in a given disorder with the clinical probability of that disorder being present. Their formula states that: 1 T= B -+1 C where T = threshold probability (e.g., probability of a disease at which the expected value of each of the two principal alternative investigations or treatments are equal; B = benefit (e.g., percentage survival of individuals with disease after treatment minus percentage survival of individuals with dis-

ease without treatment); C = cost (e.g., percentage survival of individuals without disease without treatment minus percentage survival of individuals without disease with treatment). If the clinical probability of the disease exceeds T, then the test or treatment being considered is indicated; if T exceeds the clinical probability, the test or treatment should not be performed. The following hypothetical case history is an example of a medical problem that could be subjected to costbenefit analysis. A 60-year-old doctor's wife has a several-month history of depression, nonspecific malaise, ill-defined upper abdominal discomfort radiating to the back and weight loss of 2.7 kg. Physical examination is unremarkable. Erythrocyte sedimentation rate is 35 mm/h and hemoglobin value is 11.0 g/dl. Additional laboratory tests including intravenous pyelography and radiography of the gastrointestinal tract give normal results. In assessing this patient the family physician might argue, on the basis of his clinical judgement, that the most likely diagnosis is endogenous depression and that conservative and supportive therapy should be employed. Another physician might believe that these symptoms are caused by an occult neoplasm of the pancreas and, since the chance of survival in such cases is improved with early operation, he may suggest laparotomy and examination of the retroperitoneum. This situation outlines a patient problem with two different approaches dictated by the clinical judgement of two different physicians. Resolution of the differing medical opinions can be accomplished by costbenefit analysis or just a simple bedside calculation. For example, if the two clinicians agree that the probability of depression is 70% and of malignant disease, 30%; if operative mortality in depression is 2% and the 5-year survival in surgically treated malignant disease, 50%; and if the survival in conservatively treated depression is 100% while no patients with malignant disease survive if treated conservatively, then according to Pauker and Kassirer s formula:

B = 50% survival with disease with treatment - 0% survival without treatment = 50 C = 100% survival without disease without treatment - 98% survival without disease with treatment = 2 1 =0.038=T. B -+1 C The probability of malignant disease (0.30) is greater than T (0.038) and, therefore, surgery should be performed. It should be stressed that the probabilities used in this type of decision analysis are generated by the clinician at the bedside; the analytic process merely ensures that the decision that is made is appropriate to those probabilities. The second type of decision-analysis problem is more complex. For example, although there is abundant published information on the value of various approaches to the diagnosis and treatment of hypertension, full incorporation of all this data into the decision-making process is difficult, and clinical decisions related to aggressive or conservative therapy are generally made at the bedside. Schwartz and colleagues2 and others3'4 have described a decision-analysis model using a "decision tree" that can be constructed to portray the risks and advantages in any patient population of medical therapy for hypertension as opposed to initial renal arteriography and surgery for renal artery stenosis. The theoretical model proposed by Schwartz forces the clinician to consider all possible outcomes relevant to a particular decision (designing of a decision tree), demands that he rank these outcomes in order of personal preference (assigning of "values") and permits a full display of data pertaining to the probability of each of these outcomes (assigning of "probabilities"). By incorporating numerical values and probabilities into the decision tree the physician can determine mathematically the correct set of clinical decisions related to a particular problem. Use of the model leads

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to a set of clinical decisions internally consistent with both the preferred outcome of the clinician and the available data concerning the likelihood of such an outcome. As an extension of Schwartz's abstract decision-analysis model for the evaluation of hypertension, McNeil and Adelstein3 incorporated into the model actual values determined by a standard technique together with actual probability data related to both conservative and aggressive investigation and treatment of hypertension. They concluded that "the identification and surgical treatment of hypertensive renovascular disease resulted in an incremental benefit in morbidity over blind antihypertensive medical therapy only when compliance with the medical treatment was about 50% or less". In an independent study using a more detailed decision tree we confirmed these observations.4 We have provided further support for the decision-analysis concept by demonstrating, for the first time, that decisions made by such analysis frequently differ from those made by clinicians using clinical judgement in a tertiary referral centre. It is our belief that decision analysis will play an increasing role in clinical medicine. It is valuable in teaching us how to portray graphically, and therefore take full advantage of, our intuitive

judgement regarding the likelihood of certain diagnoses, and the probabilities of achieving advantageous or untoward therapeutic results. At a more sophisticated level decision-analysis models permit rational decisions based on optimal use of a sometimes dazzling array of data (see page 887 of this issue of CMAJ). These models should also find wide application in peer review programs and be useful to government agencies in determining medical costs, for example, related to the proper evaluation and therapy of hypertensive patients. Decision analysis should be viewed by the clinician not as an infringement upon, or indictment of, his time-honoured clinical approach, but as a refinement of the decision-making process so central to the practice of medicine. ROBERT BEAR, MD, FRCP[C] JACK SCHNEIDERMAN, MD Department of medicine St. Michael's Hospital Toronto, Ont.

References 1. PAUKER SG, KASsIRER JP: Therapeutic decision making: a cost-benefit analysis. N Engi J Med 293: 229, 1975 2. SCHWARTZ W'B, GORKY GA, KAssIRER JP, et al: Decision analysis and clinical judgement. Am I Med 55: 459, 1973 3. MCNEIL BJ, ADELSTEIN SJ: Measures of clinical efficacy: value of case finding in hypertensive renovascular disease. N Engi / Med 293: 221, 1975 4. SCHNEIDERMAN J, BEAR R: Decision analysis in evaluation of hypertension (abstr). Ann R Coil Phys S,.rg Can 9: 67, 1976

Sic transit non fumare Bill C-242, an act respecting relief to nonsmokers in transit, has been debated at length by the health, welfare and social affairs committee of the House of Commons. In its initial presentation to the House, it received support from all parties, as well as endorsement by the minister of national health and welfare, but it is still at the committee stage. Lewis Carroll would have found great pleasure in attending some of the discussions. For example, the official record of one evening's session contains the following statements made by the executive director of the Canadian Tobacco Manufacturers Council: It there are materials in smoke that can be identified by the industry as causing cancer, you can be bloody sure that the tobacco industry will start to work tomorrow morning to try to eliminate them. We have not been able to find them, nor has anyone come up with any evidence. There is statistical evidence that establishes an association or a clue.1 Forgotten in the emotionalism of statements like that is the fact that the inhalation of smoke is a health hazard,

regardless of whether cancer is the outcome. Obviously, the overriding concern is the financial benefit, and here is a little more "Alice": The Chairman: ... Would Canadian tobacco manufacturers consider in their advertising an appeal to smokers to be more considerate about the rights of nonsmokers? In short, would Canadian tobacco manufacturers contribute to an educational program on nonsmokers' rights? [Reply]: I have some doubt about why the hell we should contribute. I think that - and this is off the top of my head - depending on the province, governments collect 185 per cent to 265 per cent of the net value of cigarettes. You are getting quite a bit of money now. Please do not relate that to health. I am just talking in dollars.1 The health hazards of tobacco smoking have been well documented, as has the identification of a population at risk. Tobacco smoking is a contributing factor in some respiratory and cardiovascular diseases, but the effect of tobacco smoke on nonsmokers has received less scrutiny. The most harmful constituents of tobacco smoke are carbon monoxide,

836 CMA JOURNAL/NOVEMBER 6, 1976/VOL. 115

Aldactazidd Summary of prescribing information: Pharmacology: Spironolactone effects diuresis by blocking through competitive inhibition, the sodium snd water retaining snd potassium excreting effects of sldosterone on the distal rensl tubule. Hydrochlorothiazide promotes excretion of sodium and wster primarily by inhibiting their resbsorption by the corticsl diluting segment of the rensl tubule. Thus the components of Aldactazide hsve different and complementary modes of action. In addition, spironolactone minimizes potassium loss characteristically induced by hydrochlorothiazide, thereby reducing the possible serious consequences of potassium depletion. Indications: The treatment of essential hypertension; the edema and ascites of congestive heart failure, cirrhosis of the liver, the nephrotic syndrome and idiopathic edema. Contraindications: Acute renal insufficiency; rapidly progressing impairment of renal function; anuria; hyperkalemia; patients known to be sensitive to thiazides or other sulfonamide-derived drugs; patients with severe or progressive liver disease at the discretion of the physician; nursing mothers; sensitivity to spironolactone. Warnings: Concurrent potassium supplementation is not indicated unless a glucocorticoid is also given. Aldactazide should not be used in conjunction with other potassium conserving agents. Precautions: The most potentially serious electrolyte disturbance is hyperkalemia which is more likely to occur in severely ill patients. If hyperkalemia occurs, discontinue Aldactazide. Hypokalemia may develop. Use cautiously in patients with sodium depletion. Check for signs of fluid or electrolyte imbalance. The most frequent electrolyte disturbance encountered is dilutional hyponatremia. Rarely a true low-salt syndrome may develop. Decrease dosage before diuresis is complete to avoid dehydration. Thiazide diuretics may precipitate hepatic coma. Use with caution in patients subjected to regional or general anesthesia. Discontinue 48 hours prior to elective surgery as both hydrochlorothiazide and spironolactone reduce vascular responsiveness to norepinephrine. Orthostatic hypotension may occur. Thiazides may increase responsiveness to tubocurarine. Pathological changes in the parathyroid glands have been observed. Consider the possibilities of sensitivity reactions in patients with a history of allergy or asthma as well as exacerbation of systemic lupus erythematosus. Thiazides may cause elevation of BUN. Aldactazide may potentiate the effect of other antihypertensives especially the ganglionic blocking agents. The dosage of such drugs should be reduced at least 50% when Aldactazide is added to the regimen. Spironolactone interferes with the assay of plasma cortisol but not the Ertel method. ASA may interfere with the action of spironolactone. Use with caution in patients with hyperuricemia or history of gout. Insulin requirements may be increased, decreased or unchanged in diabetics. Hyperglycemia and glycosuria may be manifested in latent diabetics. Use with caution in women of childbearing age and weigh benefits against the possible hazards to the fetus. Adverse Effects: Nausea or other gastrointestinal disturbances, gynecomastia or mild androgenic manifestations have been reported in some patients. Other side effects including those of hydrochlorothiazide occur less frequently. Overdose: Symptoms of Overdosage: Acute overdosage may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness or diarrhea. Rare instances of hypokalemia, hyponatremia, hyperkalemia or hepatic coma may occur. Thrombocytopenic purpura and granulocytopenia have occurred with thiazide therapy. No specific antidote. Treat fluid depletion and electrolyte imbalances as indicated. Dosage: In essential hypertension, a daily dosage of 2 to 4 tables, in divided doses, will be adequate for most patients, provided the treatment is continued for 2 weeks or longer. Dosage may range from 2 to 8 tablets daily. Dosage should be adjusted according to the response of the patient. In endematous states, a daily dosage of 2 to 4 tablets, in divided doses, will be adequate for most patients but may range from 2 to 8 tablets daily. Dosage should be adjusted according to the response of the patient. Supply: Each round, ivory-coloured tablet contains, spironolactone, 25 mg and hydrochlorothiazide, 25 mg. Available in bottles of 100, 1,000 and 2,500 tablets. Complete prescribing information available on request.

Searle Pharmaceuticals Oakville, Ontario L6H 1M5

## Decision analysis in clinical medicine.

Decision analysis in clinical medicine Clinical judgement, that major determinant of the quality of medical practice, is subject to a remarkable numbe...