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Which Medical Condition Shall WeTreat First?

Laupacis, Sackett, and Roberts in Ontario, Canada,have lately written an article entitled "An assessmentof clinically useful measures of the consequences oftreatment". They started from the premise thatneither the time nor the resources are available to treatall the problems that a patient may have, or indeed toinstitute all the preventive measures known to beeffective. Most would agree with this concept, butsome may worry whether a single measure could beused to compare the treatment of different conditionsor different treatments for the same condition.

Laupacis and his colleagues suggest that a measurewith the greatest pay-off should be identified-

namely, the number of patients that have to be treatedto save one of them from an adverse consequence.They chose this yardstick on the following criteria:

(a) It gives some measure of the adverse

consequences of doing nothing.(b) It can be extended to give the number treated to

provide an adverse effect of the treatment or

preventive programme.(c) It can be applied to different groups, such as

those at high risk.(d) It can compare the benefits to be derived from

one treatment with those to be expected from adifferent treatment.The Canadian workers argue carefully that "the

numbers needed to be treated" is to be preferred to thereduction in relative risk achieved by treatment, or theratio of the odds of an event when treated comparedwith the odds when not treated. Both the relative riskreduction and the odds ratio do not give an absoluteestimate of gain, only a proportional measure. Forexample, a mildly hypertensive woman can expect a40% reduction in stroke incidence with active

treatment whether she is 20 or 70 years of age.However, the probability that the younger womanwill experience a stroke is much lower, and the youngpatient will be less interested in a 40% reduction in anear zero rate. Another measure, the reduction inabsolute risk, is not so affected, but Laupacis et alprefer numbers to be treated as a concept that is moreeasily understood.

Interesting examples are provided. 1592 womenhave to be screened by mammography to prevent 1death from breast cancer over the subsequent 7 years,and 1306 persons have to be exposed to the passivesmoke from 20 cigarettes a day for 14 years to have 1death from lung cancer. Nevertheless, there are

considerable disadvantages in relying solely on thenumbers to be treated as a measure of outcome, andmost are discussed by the Canadian group. First, the

1 Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures ofthe consequences of treatment. N Engl J Med 1988; 318: 1728-33.

numbers to be treated gives no indication of whathappens to the n - 1 who are treated but do notbenefit. We need to know how many will get an eventthat is not prevented. Moreover, the measure reliesentirely on the data from which it is derived and maybe based on observational information that includesa hidden bias; calculations based on randomisedcontrolled trials are less likely to be affected. Also, thenumber to be treated should be extended to cover total

mortality and serious morbidity. The patient will notbe grateful to be spared a myocardial infarction if he orshe sustains a cerebral haemorrhage due to thetreatment. Good compliance achieved during a

clinical trial, compared with general clinical practice,may give an inappropriately low number to be treated,as may any increased severity of illness in thoserecruited. A trial may also stop after, say, 3 years, witha proportion of high-risk patients surviving on aparticular treatment. Should this treatment then bediscontinued after 3 years when used in routine

medical care?-probably not. The number to betreated to save one life usually depends on the timeinterval considered, but may be identical for 1,3, and 5years of treatment.

Laupacis and his colleagues asked a most importantfeature for this measure of pay-off-that the measureshould be able to compare different therapies and indifferent conditions. Here the number to be treatedfalls short. First, one treatment may have to be givenfor a week and the second for 5 years. How may theybe compared? The Canadian researchers give a simplesolution for chronic treatments-standardising on 5years of follow-up-but they rightly worry about theassumption, for example, that a benefit observed for 1year will be increased five-fold if treatment iscontinued over 5 years. Second, how does onecompare death with, say, symptomatic improvement?Similarly, how does one take into account harm as wellas benefit? The latter problem is discussed byLaupacis et al, and the example given that, from datain the Medical Research Council hypertension trial 2107 men had to be treated for 5 years to prevent acardiovascular event. However, this figure has to beset against the fact that 4 of these men will be forced towithdraw because of impotence, 5 because of gout,and 1 because of lethargy.

Thus, the measure numbers to be treated is

obviously useful but cannot answer the question: shallthe clinician recommend first the treatment of

hypertension or a hip replacement; treatment fordepression or therapy for glaucoma? Elderly patientsmay have several such conditions. The only yardstickthat is claimed to compare these treatments is themeasurement of quality of life by use of a health index:combining this index with a measure of survival gives

2. Medical Research Council Workmg Party. MRC Trial of treatment of mildhypertension principal results Br Med J 1985; 291: 97-104.

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a well-year or a quality of life-adjusted year of survival(QAL Y).3-5A health index scores health on a continuum,

usually from 0 at death to 1 for perfect health, withvarious scores assigned to the states of disability inbetween these extremes. In the Rosser index,6 6

negative values are included--eg, when it is better tobe dead than in severe pain in an intensive care unit.These indexes have to be reviewed and their use is inits infancy. However, the concept may be useful forcomparing, say, a hip replacement with no change insurvival but an improvement in wellbeing, with thetreatment of hypertension where often wellbeing isimpaired but survival is prolonged.7,8 From theeconomic point of view, QALYS can also be costed,revealing that it is less expensive to provide 1 unit ofQALY by a hip replacement than by treatinghypertension.9 Such a measure may be important indeciding priorities between different treatments, butmany will wonder how well QALYS estimate clinicalurgency and the severity of the disease. Differentindexes and methods provide different scores for thesame states,10 and although such discrepancies will notdetract from their ability to detect improvement in acondition, they may make comparisons betweendifferent conditions difficult.

Laupacis, Sackett, and Roberts have brought backto the notice of clinicians methods of measurement ofbenefit useful for clinical decision making. Numbersto be treated is undoubtedly useful; it has limitations,but so does the well-year or QALY. The QALY is aconcept difficult to grasp, buffeted by disagreementson how to compute it, often lacking reliable data for itscalculation, and perhaps it is attempting the

impossible. The measure of benefit should considerall areas of benefit and harm, yet we wish to

summarise the concept of quality of life and survivalinto one simple statistic. As long ago as 1936 Stoumanand Falk pointed out that such an approach leads to aserious loss of information.ll A loss of information,maybe, but useful until we have something better.

3. Williams A. The economic role of "Health Indications" In. Teeling-Smith G, ed.Measuring the social benefits of medicine. London. Office of Health Economics,1983: 63-67.

4 Office of Technology Assessment. A review of selected Federal vaccine andimmunization policies. Washington, DC: United States Congress, 1979

5. Fanshel S, Bush JW. A health status index and its application to health servicesoutcomes. Oper Res 1970; 18: 1021-66.

6. Rosser RM, Kind P. A scale of valuations of states of illness-is there a socialconsensus? Int J Epidemiol 1987; 7: 347-58

7 Bulpitt CJ, Quality of life in hypertensive patients. In: Amery A, Fagard R, Lijnen P,Staessen J, eds. Hypertensive cardiovascular disease The Hague: MartinusNijhoff, 1982. 929-48.

8. Fletcher AE, Hunt BM, Bulpitt CJ. Evaluation of quality of life in clinical trials ofcardiovascular disease. J Chron Dis 1987, 40: 557-66.

9. Maynard A. Logic in medicine: an economic perspective. Br Med J 1987; 295:1537-41.

10. Fletcher AE. Measurement of quality of life in clinical trials of therapy. In: Recentresults in cancer research, vol III. Berlin. Spnnger-Verlag, 1988. 216-30

11. Stoutman K, Falk IS. Health indexes. a study of objective indexes of health in relationto environment and sanitation Bull Health Org League of Nations, 1936; 5:901-96

DO PATIENTS WITH MILD ANGINANEED SURGERY?

IT IS generally accepted that coronary artery bypassgrafting (CABG) is effective in relieving severe angina.However, CABG cannot be regarded as curative, anginatends to recur with time, and the procedure is not free fromrisk. Even so, the improvement in quality of life for thoseseverely incapacitated by pain is ample justification forsurgery. But what of the patient with mild or moderateangina well controlled by drugs? Is it safe to manage suchpatients conservatively even when angiograms show

extensive arterial disease? Two formal randomised trials

designed to evaluate the life-saving potential of CABGamong such patients have produced conflicting results. TheCoronary Artery Surgery Study (CASS) involved a highlyselected group of angina patients under the age of 65 years inwhom coronary angiography had been carried out. Patientswith minimal arterial disease, no operable vessels, or severeangina and those with 70% or more narrowing of the leftmain coronary artery were excluded. The study was notstrictly a comparison of medical and surgical treatment, buta policy of early elective CABG with expectant medicalmanagement during which increasing severity of angina wasregarded as an indication for operation. As it happened,nearly a quarter of all patients initially randomised to themedical group had an operation within 5 years. The mostimportant and reassuring finding of CASS was the high5-year survival in the medical group analysed on anintention-to-treat basis-92% vs 95% in the early surgerygroup. A suggestion that patients with impaired left-ventricular function fared better when operated upon earlywas confirmed by a 7-year follow-up.2 This high survivalrate among patients initially randomised to medicaltreatment was supported by a further CASS study ofpatients suitable for randomisation3 who had refused to takepart in the study but had opted instead for elective medicalor surgical treatment. However, the results did not accordwith those of a similar European study" which showed a92% survival at 5 years among patients receiving earlyCABG vs only 84% among the medical group; a smaller butdetectable benefit from surgery was still present 12 yearspostoperatively. Again, surgery was permitted amongpatients randomised to medical treatment in the event ofworsening angina. At particular risk of dying were patientswith left main coronary artery disease, three-vessel disease,and certain combinations of two-vessel disease involvingproximal stenosis of the left-anterior descending artery.Only patients with good left-ventricular function were

included. More recently published experience from

1. CASS principal investigators and their associates. Coronary artery surgery study(CASS) a randomized trial of coronary artery by-pass surgery: survival data.Circulation 1983; 68: 939-50

2 Passamani E, Davis KB, Gillespie MJ, Killip T A randomized trial of coronary arterybypass surgery. Survival of patients with a low ejection fraction. N Engl J Med1985, 312: 1665-71.

3 CASS principal investigators and their associates Coronary artery surgery study(CASS): a randomized trial of coronary artery bypass surgery comparability ofearly entry characteristics and survival in randomized patients and non randomizedpatients meeting randomization criteria JACC 1984, 3: 114-28.

4 European Coronary Surgery Study Group Long-term results of prospectiverandomised study of coronary artery bypass surgery in stable angina patienttsLancet 1982; ii 1173-80

5. Varnauskas E and the European Coronary Surgery Study Group Twelve year followup of survival in the randomized European Coronary Surgery Study N Engl J Med1988; 319: 332-37