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VINEIS__From Figures to Values the Implicit Ethical Judgements in Our Measures of Health

VINEIS__From Figures to Values the Implicit Ethical Judgements in Our Measures of Health

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From Figures to Values: The Implicit EthicalJudgements in our Measures of Health
Paolo Vineis
, School of Public Health, Imperial College LondonRoberto Satolli, Zadig, Milano Italy
Corresponding author: Paolo Vineis, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place W2 1PG London.Tel:
44 (0)20 75943372; Fax:
44 (0)20 75943196; Email: p.vineis@imperial.ac.uk 
The objective of the article is to examine the extensions of a clinical measure of efficacy, the Number Needed toTreat (NNT), in different settings including screening, scanning, genetic testing and primary prevention, and theassociated ethical implications. We examine several situations in which the use of the NNT or NNS (NumberNeeded to Screen) has been suggested, such as Prostate-Specific Antigen for prostate cancer, MagneticResonance Imaging scans, genetic testing and banning of smoking. For each application, we explore the ethicalimplications of the relevant measure. We have found that the different measures have different ethical impli-cations. For example, the Number Needed to Prevent is the only measure that can be lower than one, indicatingwith a numerical example that prevention is better than cure. Conversely, we raise questions about the accept-ability of genetic screening. In a realistic example, we show that primary prevention of the effects of arsenic indrinking water, targeted to the most susceptible, would require to genetically screen a large number of subjects,whereas giving rise to ethical concerns. We warn against the abuse of testing, in particular genetic testing, weshow that different measures are associated with different ethical issues and that prevention tends to be betterthan cure.
How the impact of medical and preventive activities ismeasured is one of the important issues that epidemi-ologists face, and it has moral implications. The purposeof this article is to show how different measures of treat-ment and prevention are associated with very differentimpacts for the populations involved, and entail differ-ent moral implications. For the aim of this analysis, any clinical or public health intervention can be consideredworthy on the basis of two ethical principles: (i) benefitsshouldexceedharm(beneficence)and(ii)thepriorityinthe use of public resources should be for interventionsthat produce more benefits for more people (utility).
Number Needed to Treat
The Number Needed to Treat (NNT) is probably themostusefulsinglefigurethatoneneedstoknowinorderto judge the efficacy of a therapy, and in fact of any medical intervention. Its properties have beendescribed—see (Schulzer and Mancini, 1996) and(Walter, 2001) for reviews and a discussion of statisticalaspects—and its use has thrived in the last decades—see(Zulman
, 2008) for an application to PublicHealth strategies. It is a summary measure that allowsthe physician to estimate how many patients need toreceive a treatment to have a benefit, it can be comparedwiththeexpected burden ofside-effects, withalternativecourses of action, and can lead to a cost–benefit analysis.However, its extensions to testing, screening, scanning(including incidental findings) and primary preventionhave not been fully explored and will be analysed herefrom a public health perspective.By examining different scenarios, we will address themoral implications involved in the use of the NNT andderived measures.
Scenario 1: Therapy and Tertiary Prevention
The NNT is the number of patients that is necessary totreat with a drug or any other medical intervention tosave one life, to avoid the loss of 1 year of life (or of oneQuality Adjusted Life Years (QALY)), or to reduce otherspecified adverse healthoutcomes.TheNNT(Box1)isafunction of the efficacy of the therapy and of the fre-quency of the outcome we want to avoid or prevent.
The Author 2012. Published by Oxford University Press. Available online at www.phe.oxfordjournals.org
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When the therapy is very effective, like surgery forappendicitis, and the outcome is frequent in the absenceof intervention, then the NNT is very close to 1, i.e. wesave almost all patients who are treated. This is a very uncommon occurrence in medicine, and most NNTsfluctuate around 50–500. Notice that the NNT may behigh, even for a common adverse outcome, not only if the therapy is ineffective, but also if spontaneous recov-ery occurs, since the measure of efficacy is based on acomparison between treated and untreated patients(Box 1). Therefore, we may have a very high NNT inthe case of pancreatic cancer (frequency of death 100%,highly ineffective therapies), but also for the therapy of the common influenza, depending on the day of obser-vation (with very high rate of spontaneous recoveries afew days after treatment initiation).The NNT increases with a decreasing frequency of theoutcome, whereas in contrast adverse side-effects of therapies have the same occurrence rate, irrespectively ofthefrequency oftheoutcomethatwewanttoprevent.For example, there is a fixed proportion of subjects whowill undergo aplastic anaemia after treatment with ibu-profen, whether or not the drug is properly used in ser-iously sick patients who really need it or inappropriately used in subjects with a mild and self-containing disease.Thisrelationshipisrepresented inFigure1,which showsthat treatment should be initiated only when the advan-tages overcome the side-effects. This well-known Figureisusually applied to therapies, but common sense wouldsuggest to apply it to any medical act.Walter andSinclair (2009)have recently analysed the issue of the ‘minimum target event risk for treatment’, i.e. thethresholdto undertakeatreatment, and theynoticed thefrequent lack of information that may allow aninformed decision.The ‘first ethical implicationis that any benefitshould be compared with side-effects, and the two areasymmetric, because only benefits of treatment areinfluenced by the frequency of the outcome, so thatdamage without benefit can easily occur for rare out-comes. Benefit and harm are asymmetric also becausethey do not necessarily refer to the same persons, so thatan intervention can slightly harm a large number of people in order to benefit only one person. These twoasymmetries are in contrast with both the principles of beneficence and of utility.
Number Needed to Test
Suppose that a doctor wants to prescribe aComputerized Tomography (CT) for joint pain. If it ishighly likely that the CT will help her/him—to decidewhether to treat the patient or not, then the NNT fortherapy can be simply estimated for the treated subjects.But if any treatment is unlikely to be undertaken, why isthe test performed? Has the doctor considered the po-tential side-effects of the CT for the patient? In this cir-cumstance, it seems reasonable to estimate not actually the NNT, but the Number Needed to Test. In the case of Box 1. Example of a measure of treatment efficacy Let us consider a drug that is supposed to prevent heart disease (e.g. a statin). To express its efficacy, one cancalculate the frequency of deaths or of illnesses, after a sufficiently long time, in the treated group compared withthe control group. In a large study in healthy subjects with normal cholesterol, but with an altered level of aninflammation marker (CRP) (the Jupiter study), the deaths were
12.5 per year every 1000 people in the controlgroup, and 10 in those treated with the drug. The two frequencies can be compared by calculating the difference(i.e. the deaths decreased by 2.5 per 1000 per year). However, this measure is rarely used to communicate benefits.The authors of clinical trials prefer to calculate the percent of risk reduction in the treated arm compared withcontrols, in this case 20 per cent (i.e. 2.5 divided by 12.5). In this way, the apparently modest absolute result istransformed into a more attractive relative reduction. In other words, when the basal risk is low, even a modestabsolute benefit translates into an apparently large relative benefit. However, one of the most useful measures is theNNT in order to avoid one adverse event such as death. In our example, the drug benefits 12.5 patients out of 1000treated for 5 years (2.5 multiplied by 5 years). This means that (1000 divided by 12.5) subjects need to be treated toobtain one benefit, i.e. to avoid one death. The NNT is thus 80 subjects. Is it large or small? To give an idea,70 elderly patients with hypertension need to be treated for 5 years with anti-hypertensives, in order to avoid onedeath; or, 100 male adults with no sign of heart disease need to take aspirin for 5 years in order to avoid aninfarction. Not only is the NNT an easily interpretable measure, but also allows comparative analyses includingcosts. For example, if a year of therapy against cholesterol costs
1000 per patient; then approximately 
400,000are needed to prevent one death by treating 80 people for 5 years.
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appendicitis, diagnosis is very simple, and in most casesall patients undergoing the relevant tests will have thecorrect diagnosis and will be saved by surgery. But this isclearly an exception. The doctor may decide to performa CT scan in 1000 patients with joint pain to identify the10 who can theoretically benefit from a specific therapy.The NNT for those 10 patients may be, say, 10 (to beoptimistic), i.e. out of the 10 patients with that condi-tion who are treated, only 1 will recover, thanks to thetreatment. The other nine will get the drug (with itsside-effects) with no benefit. But we also have to includein the equation the 990 patients who underwent a CTscan with no gain. Therefore, the Number Needed toTestisinfact999,andamongtheside-effects, wehavetocount also those of the diagnostic test. Again, the fre-quency of the side-effects is independent of the efficacy (or lack of) of the treatment and of the frequency of theoutcome.The ‘second moral implication’ is that testing itself (not only treatment) can lead to a large number of use-less interventions, and the related discomfort. In fact,the ratio between useful and useless interventions can bemuch higher than for the NNT. Therefore, the calcula-tion of the Number Needed to Test is more useful thanthe NNT in evaluating the beneficence and utility of any medical intervention.
Scenario 2: Secondary Prevention—theExample of PSA Testing
The 1000 hypothetical patients above were all affectedby joint pain. What about a screening scenario, such asProstate-Specific Antigen (PSA) for prostate cancer?This situation is similar to the estimation of NumberNeeded to Test, but the computation needs to incorp-orate the prevalence of the condition in asymptomaticsubjects. It is like the Number Needed to Test but in theabsence of signs and symptoms, and therefore with ausually much lower disease prevalence. In fact, theNumber Needed to Screen (NNS) for breast cancerscreening, e.g. is around 2500–20,000, depending onthe age bands. This means that at least 2500 womenwill undergo the screening test to identify a fractionwho have a potentially malignant lesion, among whomthere is one who will be saved by the screening activity.This leads to a ‘third moral implication’, i.e. the over-all effect of a screening test in asymptomatic subjectsdepends on the prevalence of the asymptomatic condi-tion, so that a test has completely different effectiveness,e.g. in different age groups, and in accord to the prin-ciples of beneficence and utility should not be offered toa population with a low prevalence of the condition,when the expected benefits are likely to be exceeded by the harm.According to one study,
3 million American menaged 40–74 years would show abnormal PSA levels if screened (
4.0 nanograms per millilitre; with a pro-posed threshold of 2.5 nanograms per millilitre, an add-itional 3 million men would be abnormal). However,only 0.4 per cent of men in the age range 40–74 yearsare expected to die every year from prostate cancer. Letus suppose that screening reduces the risk of dying by 20per cent, probably an optimistic estimate [this is theestimate found in the European ERSPC trial, not inthe American PLCO (Andriole
, 2009)]. With the figures given in the recentERSPC report (Schroder
, 2009), the
risk reduction is 0.7 per 1000 in 10 years, which gives a NNSto save a life of 1400 (1/0.0007), a rather high value.Another way to estimate the impact is to say that 48additional tumours need to be treated to prevent onedeath (Schroder
, 2009). This means that approxi-mately 1399 subjects will undergo screening with nobenefit, and 47/48 will suffer from all the complicationsrelated to prostatectomy with no real gain in survival.If we consider the different life expectations, the NNS toavoid the loss of 1 year (or a QALY) would probably behigher for older people (
70 years), in spite of thehigher prevalence of the cancer.
Scenario 3: Disease Prediction—the Exampleof Genetic Testing
One can argue that breast cancer screening is usefulindeed, at least over the age of 50 years; and perhaps,
Figure 1.
The Figure shows that with an increasingfrequency of health effects (outcomes) the NNT is lower,i.e. the benefits of treatment are higher, whereas harm isindependent of the frequency of outcomes (see also Box 1).
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