“A Tale of Two Worlds” .

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“A Tale of Two Worlds”

• http://news.bbc.co.uk/hi/english/health/

• http://bmj.com/cgi/content/full/324/7331/214

"We all have AIDS": case for reducing the cost of HIV drugs to zero

BMJ 2002;324:214-218 (26 January)

Now we all have AIDS. No other construction is any longer reasonable. The earth has AIDS; 36.1 million people at the end of the year 2000. In Botswana, 36 percent of adults are infected with HIV; in South Africa 20 percent. Three million humans died of AIDS in the year 2000, 2.4 million of them in sub-Saharan Africa. That is a Holocaust every two years; the entire population of Oregon, Iowa, Connecticut or Ireland dead last year, and next year, and next. More deaths since the AIDS epidemic began than in the Black Death of the Middle Ages. It is the most lethal epidemic in recorded history.

Berwick DM. We all have AIDS. Washington: Washington Post, Jun 26 2001:A17.

“A Tale of Two Worlds”

• http://news.bbc.co.uk/hi/english/health/

• http://bmj.com/cgi/content/full/324/7331/214• http://www.unaids.org/

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1 m i l l i o n1 m i l l i o n

S o u t h & S o u t h - E a s t A s i a

6 . 1 m i l l i o n6 . 1 m i l l i o n

A u s t r a l i a & N e w Z e a l a n d

1 5 0 0 01 5 0 0 0

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2 7 0 0 0 02 7 0 0 0 0S o u t h & S o u t h - E a s t A s i a

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A u s t r a l i a & N e w Z e a l a n d

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2 . 3 m i l l i o n2 . 3 m i l l i o n

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A u s t r a l i a & N e w Z e a l a n d

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L a t i n A m e r i c a

8 0 0 0 08 0 0 0 0

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0 0 0 0 2 - E - 4 – 1 D e c e m b e r 2 0 0 1

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3 3 6 m i l l i o n3 3 6 m i l l i o nS u b - S a h a r a n

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5 9 6 m i l l i o n5 9 6 m i l l i o n

E a s t e r n E u r o p e & C e n t r a l A s i a

3 9 2 m i l l i o n3 9 2 m i l l i o n

S o u t h & S o u t h - E a s t A s i a

1 9 2 0 m i l l i o n1 9 2 0 m i l l i o n

A u s t r a l i a & N e w Z e a l a n d

2 3 m i l l i o n2 3 m i l l i o n

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L a t i n A m e r i c a

4 7 3 m i l l i o n4 7 3 m i l l i o n

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E a s t A s i a & P a c i f i c

1 4 7 8 m i l l i o n1 4 7 8 m i l l i o n

0 0 0 0 2 - E - 4 – 1 D e c e m b e r 2 0 0 1

P r o p o r t i o nP r o p o r t i o n o f a d u l t s a n d c h i l d r e n e s t i m a t e d o f a d u l t s a n d c h i l d r e n e s t i m a t e d t o b e t o b e l i v i n g w i t h H I V / A I D Sl i v i n g w i t h H I V / A I D S a s o f e n d 2 0 0 1a s o f e n d 2 0 0 1

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1 . 4 p e r 1 , 0 0 01 . 4 p e r 1 , 0 0 0N o r t h A f r i c a

& M i d d l e E a s t

1 . 3 p e r 1 , 0 0 01 . 3 p e r 1 , 0 0 0

E a s t e r n E u r o p e & C e n t r a l A s i a

2 . 6 p e r 1 , 0 0 02 . 6 p e r 1 , 0 0 0

S o u t h & S o u t h - E a s t A s i a

3 . 2 p e r 1 , 0 0 03 . 2 p e r 1 , 0 0 0S u b - S a h a r a n A f r i c a

4 7 p e r 1 , 0 0 04 7 p e r 1 , 0 0 0 A u s t r a l i a & N e w Z e a l a n d

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1 5 0 / 1 01 5 0 / 1 0 66 p ap aC a r i b b e a n

1 8 8 0 / 1 01 8 8 0 / 1 0 66 p ap a

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2 7 0 / 1 02 7 0 / 1 0 66 p ap a

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0 0 0 0 2 - E - 6 – 1 D e c e m b e r 2 0 0 1

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1 7 / 1 01 7 / 1 0 66 p ap aN o r t h A f r i c a

& M i d d l e E a s t

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5 / 1 05 / 1 0 66 p ap a

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00001-E-37– 27 June 2000

Annual number of reported HIV infections in the Annual number of reported HIV infections in the UK, by mode of transmission, 1983 to 1999UK, by mode of transmission, 1983 to 1999

0

500

1000

1500

2000

2500

83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99

Nu

mb

er o

f d

iag

no

ses

Heterosexual MSM + MSM/IDU

Source: PHLS Communicable Disease Surveillance Centre UK, July 2000

00001-E-37– 27 June 2000

Annual number of reported HIV infections in the Annual number of reported HIV infections in the UK, by mode of transmission, 1983 to 1999UK, by mode of transmission, 1983 to 1999

0

500

1000

1500

2000

2500

83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99

Nu

mb

er o

f d

iag

no

ses

Heterosexual MSM + MSM/IDU

Source: PHLS Communicable Disease Surveillance Centre UK, July 2000

Leicester Warwick Medical School

Health and Disease in Populations

Measuring the Burden of Disease and

Comparing Groups

Ronald Hsu

Lecture objectives

You should be able to:

1. define and differentiate between ‘incidence’ and ‘prevalence’, and describe their inter-relationship

Lecture objectives

You should be able to:

2. describe the importance of systematic variation in risk of disease between groups:

a. as a useful source of information

b. as a nuisance which needs to be controlled for

3. explain the purpose of age/sex standardisation

4. interpret a Standardised Mortality (Morbidity) Ratio (SMR)

Objective 1 – Incidence & Prevalence

How much Disease is There?

The ‘amount’ of disease has two concepts:

1. The number of new cases that occurred– focuses on NEW EVENTS– useful when monitoring epidemics– e.g. the number of new cases of

meningitis in 1st year students

2. The number of people affected by the disease– counts PEOPLE with EXISTING DISEASE

(both OLD and NEW cases)– describes ‘burden of disease’– useful as a measure of need for services– e.g. cystic fibrosis in Warwickshire

Incidence Rate – measuring new cases

• 300 heart attacks in dye workers– is this a lot or a few?

• 300 heart attacks in 50,000 dye workers– considers population at risk

• 300 heart attacks in 50,000 dye workers between July ’94 & Dec ’95 (1½ years)– considers time dimension as well

300 heart attacks in 50,000 dye workers between July 94 & Dec 95 (1½ years)

– 300 = 0.006 heart attacks per worker in Jul ’94 - Dec ’95 50,000 (i.e. 6 heart attacks per 1,000 workers in 1½ years)

– 300 = 0.004 heart attacks per worker per year50,000 x 1.5

i.e. 4 heart attacks per 1,000 workers per year

Incidence rate = new events = events per persons per year

person x time (years)

Incidence Rate – measuring new cases

On 14th February 2002, 80 patients have cancer in a population of 1,500

(Point) prevalence = 80 1,500= 53 per 1,000= 5.3%

Prevalence is a proportion NOT a rate

Denominator is persons NOT person per time

Prevalence – measuring existing cases

Relationship between Incidence and Prevalence

Relationship between Incidence and Prevalence

• Increase incidence? – increase prevalence• Cure more patients? – lower prevalence• Kill more patients? – lower prevalence• Keep them alive longer? – increase prevalence

P (I x L)

P = Prevalence, I = Incidence, L = Length of disease

Incidence is a measure of the population’s average risk of diseasee.g. AIDS incidence 5 per 100,000 p-y

heart attack incidence 10 per 1,000 p-y.

But in a population not all people have the same ‘proneness’ or ‘risk’ of disease.

There are variations in risk of disease between groups of people.

Objective 2 – Systematic Variationa. as a useful source of information

• AIDS – variation in exposure to unsafe sex or infected blood products

• Heart attack – variation in exposure to cigarette smoking

Systematic (as opposed to random) variations in risk between people is of great interest because it can give us clues about the aetiology (cause) of disease.

Useful Variations in Risk of Disease

Aetiology (Cause) of Disease

We can look at the exposures in the two groups and try to identify the causal exposure.

Having identified the causal exposure, it may be possible to prevent exposure and thus reduce the incidence of the disease.

Useful Variations in Risk of Disease 1

Clues about the aetiology (cause) of disease:• we can compare incidence rates between

different groups:

Incidence Rate Ratio (IRR) = RateA

RateB

• if the rate in one group is higher than the rate in the other group, this implies that the two groups had different exposures which caused the difference in disease rates

Useful Variations in Risk of Disease 1

Efficacy of Treatment

Incidence rate ratios can also be used to compare the effects of two treatments and decide which is the best.

Exposure is therefore treatment A or B. (where A is the old treatment and B is the new treatment)

Useful Variations in Risk of Disease 2

Drug A (old): 8 deaths in 800 p-y

Drug B (new): 5 deaths in 1,000 p-y

RateA = 8/ 800 = 10 per 1,000 p-y

RateB = 5/1,000 = 5 per 1,000 p-y

Mortality rate ratio = RateA = 10 per 1,000 RateB 5 per 1,000

= 2.0

Useful Variations in Risk of Disease 2

Mortality rate ratio = RateA (old) = 2.0 RateB (new)

(N.B. – rate ratio has no units)

‘Twice as likely to die on the old treatment compared with the new treatment’

OR

‘New treatment halves the risk of death compared to the old treatment’

Useful Variations in Risk of Disease 2

The previous examples show how systematic variations in risk between groups can give us pointers to possible causes of disease and can be used to compare the effects of treatment.

However, other types of systematic variation can still be IMPORTANT but not at all useful – in fact they are a nuisance.

Objective 2 – Systematic Variationb. as a nuisance to be controlled for

For example:• Age and sex are strong determinants of health

and ill health• Rate ratios for most diseases comparing

Rateold are usually > 1.0Rateyoung

• Not particularly useful for prevention: whilst it may be possible to target prevention at particular age (sex) groups, age and sex are not modifiable factors

So, should we worry about these sorts of factors?

Nuisance Variations in Risk of Disease

An illustration:

Skin cancer mortality rate in Bournemouth vs. rest of UK: Incidence Rate Ratio (IRR) = 5.0, i.e.‘mortality rate 5 times as high in Bournemouth than the rest of the UK’

Is sunbathing the cause?

BUT• people retire to the coast, so Bournemouth

has on average an older population than UK• old people are prone to skin cancer

Nuisance Variations in Risk of Disease

?Place Skin cancer

(Exposure) (Disease)

Confounding as a Nuisance

?Place Skin cancer

(Exposure) (Disease)

associated

Age

Confounding as a Nuisance

?Place Skin cancer

(Exposure) (Disease)

associated

Age

Confounding as a Nuisance

?Place Skin cancer

(Exposure) (Disease)

associated associated

Age(Confounder)

Age in this situation is a CONFOUNDER

Confounding as a Nuisance

Confounding can explain ALL or PART of an apparent association between an exposure and a disease.

So in the illustration, the difference in age distribution between Bournemouth and the rest of the UK, gives a SPURIOUS association between living in Bournemouth and a high risk of skin cancer.

Confounding as a Nuisance

In the illustration, (Crude) IRR = 5.0

BUT once age was ‘adjusted’ for,

(Adjusted) IRR = 1.2

i.e. now Bournemouth seems a much safer place!

Age was a CONFOUNDER in this situation.

Age in this situation was a nuisance, which was getting in the way of the search for modifiable causes of disease.

Confounding as a Nuisance

So how can we deal with confounding by age?Could use age-specific rate ratios,• compare within each age band, e.g.

are 20-24 year olds in Bournemouth at higher risk than 20-24 year olds in the UK?

• continue for all age groups…With narrow age bands, little confounding occurs

– so any differences are real.BUT the results are difficult to interpret as you get

too many answers: one for each age-band!

Confounding as a Nuisance

Get around the problem of age/sex confounding by asking:

What would the rate ratio for the two populations be IF the age/sex structure of the

two populations were the same?

Calculate a Standardised Mortality Ratio (SMR) – see small group session.

3 & 4 – Age/Sex Standardisation & Standardised Mortality Ratio (SMR)

• SMR is a summary (single) figure which describes the mortality (morbidity) experience of a local population compared to a standard population’s experience, which takes account of age-sex confounding (indirect standardisation)

• Usually expressed as a percentage: 100 = same risk in local population as in the

standard population>100 = higher risk in local population(sometimes expressed as being relative to 1.0)

Standardised Mortality Ratio (SMR)

• Incidence rate of disease• Prevalence (proportion) of people affected• Incidence rate ratio (IRR) comparisons• Systematic variations in IRR can be:

– useful in searching for• causes of disease (c.f. cohort studies)• treatment effects (c.f. clinical trials)

– can also be a nuisance (c.f. confounding)

• SMRs give a single summary measure of disease corrected for age-sex confounding

Summary