Explorations in regime change: -Thalassaemia and the interplay of technological change & social norms.

Zosia Bornik & Hadi DowlatabadiUniversity of British Columbia

with thanks to:Sue Cox, Peter Danielson, Ed Levy and Bernadette Modell

2: Regime Change 14/01/04

Overview

• Objective of this research• Definitional issues. • Domain information.• Findings.• Conclusions/more

3: Regime Change 14/01/04

Objective

• At UBC:– Study democratic issues related to applied

genomics.

• At CMU:– To explore features of regime change.

• Synthesis:– What might drive shifts in social norms?

4: Regime Change 14/01/04

Social Norms

• As a noun:– It describes how a peer group shares specific values

and hence chooses among a set of options.

• As a verb:– It is used as an approach to risk communication and

intervention. It has been successfully employed to address excessive drinking among college students…

• Recent History:– Based on research by Alan Berkowitz and H. Wesley

Perkins working at Hobart and William Smith Colleges.

5: Regime Change 14/01/04

A two-level model of behaviour

• Norm based heuristics:– “There are the values we hold”

• Deliberated decision:– “I know what is valued and estimate the

benefits of this to outweigh its costs …”

6: Regime Change 14/01/04

The question:

• What makes the higher level of decision-making be revised?

• Changing circumstance:– Social– Economic– Technologic– …

7: Regime Change 14/01/04

An example:Thalassaemia

• Thalassaemia, is an inherited condition where the genes controlling haemoglobin production are affected.

• Each hemoglobin molecule contains four subunit proteins (2x and 2x). – Hemoglobin properly binds and releases oxygen only

when two alpha subunits are connected to two beta subunits.

– A pair of genes located on chromosome #16 controls the production of the alpha subunits of hemoglobin.

– A single gene located on chromosome #11 controls the production of the hemoglobin beta subunit.

8: Regime Change 14/01/04

Its in the genes

-globin genes -globin genes

Chromosome 11 Chromosome 16

Hemoglobin Protein

b1

b2

a1

a3

a2

a4

9: Regime Change 14/01/04

-Thalassaemia

• When the -globulin genes (or their neighbours) are defective or absent, the patient suffers from -Thalassaemia of different severities. – Minor: where haemoglobin production is slightly

affected – Intermedia: …– Major: where both genes are affected leading to

severe anaemia.

• Patients with -Thalassaemia major need:– chronic blood transfusions

• AND– Chelation therapy (to address iron over-load)

10: Regime Change

14/01/04

Clinical intervention

1. Diagnose anaemia2. Test for -trait using haemoglobin

electrophoresis3. Blood transfusions4. Iron-Chelation therapy

• ≥2 units of blood/mo.• Liver, heart & other medical problems

• ≥15 days/mo. of Chelation therapy

• Life expectancy: ~ 60yrs • Cost: CDN$1-2 M

Source: Zeuner et al, 1999

11: Regime Change

14/01/04

Social intervention

1. Identify potential carriers2. Give them genetic counselling3. Bring pressure to avoid pregnancy

• Revised norms on procreation• Cost: CDN$ 6-100/cap

Source: Zeuner et al, 1999

12: Regime Change

14/01/04

Genomic interventions

1. Test the genes:• Pre-natal

2. Give genetic counselling

3. Offer termination of pregnancy

• Revised norms on abortion

• Cost: CDN$ 150-1000/test

1. Test the genes:• Pre-implantation

2. Give genetic counselling3. Try in-vitro fertilization

again

• Revised norms on eugenics

• Cost: CDN$ 4000-5000/test

Sources: Verma 2003, Karczeksi 2003

13: Regime Change

14/01/04

The Thalassaemia Belt

• 2-18% of the population consists of carriers (WHO, 1994)– includes Mediterranean Region, Middle East, Indian Subcontinent,

and Far East• Population movements have led to dissemination of the

gene…– ß-Thal now widespread in Europe, Americas and Australia. In 2002:– ~ 240 million healthy carriers worldwide.– ~ 200,000 ß-Thal major births per year (Cao et al, 2002).

14: Regime Change

14/01/04

Fall in Thalassaemia Major with screening

Source: Modell

15: Regime Change

14/01/04

The choices made in Cyprus

• 4% chose a different marriage partner.• 20% chose a smaller final family size.• 76% had selective abortion.

Source: Modell

16: Regime Change

14/01/04

Fall in Thalassaemia Major Births

Source: Modell

17: Regime Change

14/01/04

Uptake of pre-natal diagnosis by ethnic group (UK)

0%

20%

40%

60%

80%

100%

Cypriot Indian Pakistani Other

1st Trimester 2nd Trimester

Source: Modell

18: Regime Change

14/01/04

High infant mortality

DiagnosisTransfusio

nservices

TechnologicalChange

Desferri-oxamine

Genetic screening

Improve infants

survival

Improve child

survival

Some get blood transfusions

Control health

spending

Some get Iron Chelation therapy

Revise social norms

Most are not born

SocialChange

Typically 150/1000 IM drops to ~

40/1000 of which 17% are ß-Thal major!

IM drops by another ~7/1000

19: Regime Change

14/01/04

Why was Cyprus so successful?

Cyprus:• Genetically

homogeneous population 2-3 mutations.

• High prevalence rate 14% carrier rate.

• Broad public engagement through church, schools and community.

Elsewhere:• Genetically heterogeneous

(e.g., >23 mutations in Iran).

• Lower prevalence rate (and priority).

• Dominated by other concerns/norms.

20: Regime Change

14/01/04

Conclusions

• When pressure is sufficiently high norms can shift (i.e., Cyprus, Italy, Iran).– Perhaps such shifts are more readily

accepted because they also address other objectives.

• Pressure to “preserve norms” (itself a norm at a higher level) trumps where population is heterogeneous(i.e., UK).

21: Regime Change

14/01/04

Clinical Intervention costsfrom Zeuner et al, 1999Average life expectancy = 63 yearsTotal lifetime treatment costs for B-thal major = 490,000 British pounds

= 123,000 at a 6% discount rate (includes diagnosis, blood transfusion, outpatient visits, costs assoc w/ complications)

For costs incurred over different life stages, see Table 33, p.68

Social Intervention costsfrom Zeuner et al, 1999Total antenatal screening programme costs per 10,000 population group

= 33,869 – 800,060 British pounds(see CB analysis and Table 55, p. 90)

(includes carrier screening, counseling, pre-natal Diagnosis, and abortion)

Genomic Intervention costsCost for Pre-natal Diagnosis depends on countryIndia = 150$ Canadian per case (Verma, 2003) USA = 1000$ Canadian per case (Karczeksi, 2003)

Predicted costs for Pre-implantation Genetic DiagnosisUSA = at least 4000-5000$ Canadian per case (Karczeksi, 2003)