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Understanding the concept of relative risk
Health Policy, 4 (1985) 241-246 0 Elsevier Science Publishers B.V. (Biomedical
241 Division)
A Second Opinion
Understanding
the concept of relative risk
The first problem which lies behind the discussion in this paper is that few people are able to understand the concept of relative risk. For example, many people have a vague subconscious fear of air travel and a few are pathologically nervous of flying. They fail to realise that they are several hundred times more likely to die of heart disease or cancer than they are to die in an aircraft crash - even if they are regular travellers. In order to try to make it easier to understand the principles of relative risk in relation to drug safety, Dr. Bill Inman of the Drug Surveillance Research Unit at the University of Southampton, has introduced the idea of “levels of risk” based on a logarithmic scale [l]. For example a risk of death of one in 50 would be a level 2 risk; a risk of death of one in 50 000 whould be a level 5 risk. The level in each case corresponds to the number of digits in the risk factor. A one in 5 000 000 risk would, therefore, be at level 7. This has the slight disadvantage, which Inman points out, that the higher the level of risk, the smaller the number attached to it. But it should be not impossible for people to recognise this fact. Figure 1 sets out the various levels of risk, and shows the
Fig. 1. A logarithmic
risk scale. Source:
Inman
[l].
242
position occupied on the scale by patients suffering from various diseases. Thus a patient with diabetes has between a 1 in 10 and 1 in 99 risk of dying from the disease in any given year. The figure also sets out the risks associated with the treatments for arthritis, whose use has been either prohibited or restricted in certain countries because of their supposedly “excessive” risks. At worst, the risks from treatment are two orders of magnitude (i.e., 2 risk levels) less than the risks from complications of the disease itself. This situation was never made explicit in the discussion which lead up to or which followed the withdrawal of benoxaprofen, for example. The second fact which has generally been ignored is that the “risk-benefit” equation cannot be stated precisely for a particular medicine. It varies according to the patient for whom it is being prescribed. Figure 2 shows what I have christened the “Teeling Smith Risk-Benefit Matrix” [2]. It shows the relative degrees of benefit along the bottom axis, and the relative degrees of risk on the vertical axis. Any medicine lying at the foor of the diagram (i.e., virtualy safe) is clearly acceptable. So is any medicine lying up against the right-hand vertical axis (i.e., a life-saving medicine). However, medicines in the top left-hand corner (dangerous remedies for trival conditions) are clearly unacceptable. But the important point is that a medicine does not have a fixed position within this matrix. For example chloramphenicol for a typhoid patient lies at the right hand side. The same medicine prescribed for a mild sore throat lies in the prohibited top left-hand corner. Similarly, benoxaprofen may have had negligable risks for younger patients, for some of whom it provided uniquely effective treatment. On the other hand, when it was prescribed for an elderly patient for whom some other therapy would have been equally effective, it moved towards the top left-hand corner.
Fig. 2. Risk-benefit
matrix. Source: Teeling-Smith
[2].
243
Third, clinicians and the drug regulatory authorities have so far given very little attention to the recently introduced principles of measurement of quality of life, using, for example, “health indicators”. The best known unit of benefit has perhaps become the “Quality Adjusted Life Year” or QALY. Without some such quantitative measurement of the benefits of medication, it is extremely hard to be rational about the relative risk. For years, health services in general have suffered from the corresponding problem in another area: costs are all too easily quantified; benefits have generally remained nebulous. Now the same applies to the question of risk. Even though the risks themselves are seen out of all proportion, they can fairly easily be quantified. On the other hand, we have generally had no offsetting measurement of the benefits. In this situation, it is not surprising that the attitudes of governments and the regulatory authorities have been irrational in respect of the risks of medication. At the time that a medicine is first licensed for use, it is extremely hard to guess at the ultimate assessment of either its risks or benefits. But when it has been used on a few hundred thousand patients, perhaps, its risks will have become apparent - if they exist - but little effort will have been made to evaluate its benefit in social and economic terms. It is at that stage that possibly irrational decisions have been taken in respect of medicines such as benoxaprofen over the last two or three years. If the process of pharmaceutical innovation is to continue, a more rational approach is needed in each of the three areas which I have mentioned. First, a proper understanding of relative risk; second, an appreciation that the risk-benefit equation may be different for different classes of patient; and third, that more quantitiative evidence is needed for the benefits. Van Andel’s paper suggests that at present we are far from achieving an academically sound basis for drug evaluation on any of these three counts. G. Teeling-Smith Director
Office of Health
Economics
London,
U.K.
References 1 2
Inman, W.H.W., (1984) Risks in Medical Intervention: in Prescription Event Monitoring News; University of Southhampton. Teeling-Smith, G., (1983) Measuring the Social Benefits of Medicine; Office of Health Economics.
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241 Division)
A Second Opinion
Understanding
the concept of relative risk
The first problem which lies behind the discussion in this paper is that few people are able to understand the concept of relative risk. For example, many people have a vague subconscious fear of air travel and a few are pathologically nervous of flying. They fail to realise that they are several hundred times more likely to die of heart disease or cancer than they are to die in an aircraft crash - even if they are regular travellers. In order to try to make it easier to understand the principles of relative risk in relation to drug safety, Dr. Bill Inman of the Drug Surveillance Research Unit at the University of Southampton, has introduced the idea of “levels of risk” based on a logarithmic scale [l]. For example a risk of death of one in 50 would be a level 2 risk; a risk of death of one in 50 000 whould be a level 5 risk. The level in each case corresponds to the number of digits in the risk factor. A one in 5 000 000 risk would, therefore, be at level 7. This has the slight disadvantage, which Inman points out, that the higher the level of risk, the smaller the number attached to it. But it should be not impossible for people to recognise this fact. Figure 1 sets out the various levels of risk, and shows the
Fig. 1. A logarithmic
risk scale. Source:
Inman
[l].
242
position occupied on the scale by patients suffering from various diseases. Thus a patient with diabetes has between a 1 in 10 and 1 in 99 risk of dying from the disease in any given year. The figure also sets out the risks associated with the treatments for arthritis, whose use has been either prohibited or restricted in certain countries because of their supposedly “excessive” risks. At worst, the risks from treatment are two orders of magnitude (i.e., 2 risk levels) less than the risks from complications of the disease itself. This situation was never made explicit in the discussion which lead up to or which followed the withdrawal of benoxaprofen, for example. The second fact which has generally been ignored is that the “risk-benefit” equation cannot be stated precisely for a particular medicine. It varies according to the patient for whom it is being prescribed. Figure 2 shows what I have christened the “Teeling Smith Risk-Benefit Matrix” [2]. It shows the relative degrees of benefit along the bottom axis, and the relative degrees of risk on the vertical axis. Any medicine lying at the foor of the diagram (i.e., virtualy safe) is clearly acceptable. So is any medicine lying up against the right-hand vertical axis (i.e., a life-saving medicine). However, medicines in the top left-hand corner (dangerous remedies for trival conditions) are clearly unacceptable. But the important point is that a medicine does not have a fixed position within this matrix. For example chloramphenicol for a typhoid patient lies at the right hand side. The same medicine prescribed for a mild sore throat lies in the prohibited top left-hand corner. Similarly, benoxaprofen may have had negligable risks for younger patients, for some of whom it provided uniquely effective treatment. On the other hand, when it was prescribed for an elderly patient for whom some other therapy would have been equally effective, it moved towards the top left-hand corner.
Fig. 2. Risk-benefit
matrix. Source: Teeling-Smith
[2].
243
Third, clinicians and the drug regulatory authorities have so far given very little attention to the recently introduced principles of measurement of quality of life, using, for example, “health indicators”. The best known unit of benefit has perhaps become the “Quality Adjusted Life Year” or QALY. Without some such quantitative measurement of the benefits of medication, it is extremely hard to be rational about the relative risk. For years, health services in general have suffered from the corresponding problem in another area: costs are all too easily quantified; benefits have generally remained nebulous. Now the same applies to the question of risk. Even though the risks themselves are seen out of all proportion, they can fairly easily be quantified. On the other hand, we have generally had no offsetting measurement of the benefits. In this situation, it is not surprising that the attitudes of governments and the regulatory authorities have been irrational in respect of the risks of medication. At the time that a medicine is first licensed for use, it is extremely hard to guess at the ultimate assessment of either its risks or benefits. But when it has been used on a few hundred thousand patients, perhaps, its risks will have become apparent - if they exist - but little effort will have been made to evaluate its benefit in social and economic terms. It is at that stage that possibly irrational decisions have been taken in respect of medicines such as benoxaprofen over the last two or three years. If the process of pharmaceutical innovation is to continue, a more rational approach is needed in each of the three areas which I have mentioned. First, a proper understanding of relative risk; second, an appreciation that the risk-benefit equation may be different for different classes of patient; and third, that more quantitiative evidence is needed for the benefits. Van Andel’s paper suggests that at present we are far from achieving an academically sound basis for drug evaluation on any of these three counts. G. Teeling-Smith Director
Office of Health
Economics
London,
U.K.
References 1 2
Inman, W.H.W., (1984) Risks in Medical Intervention: in Prescription Event Monitoring News; University of Southhampton. Teeling-Smith, G., (1983) Measuring the Social Benefits of Medicine; Office of Health Economics.
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