Ethical evaluation

Timo Nevalainen

University of Eastern Finland

Ethics?

to do good

not to do bad

Is it worth it?

Does it hurt?

Interests groups

Abolition No restrictions

Scientists

Animal welfare Patient groups

Tools for assessment?

Science community well meaning ethical purpose how to balance purpose with cost

Philosophies animal rights, utilitarism at project level of little help

Law

Law, science & ethics

excellence

Harmonization

Council of Europe (CoE) Convention

Revision of Appendix A CoE working groups species specific documents

general, rodents, rabbit, dogs, cats, primates, fish and farm animals

enrichment and group housingmandatory unless there is a veterinary or scientific reason not to

European Science Foundation

Use of Animals in Research (2001) ..animal use should be subjected to independent

expert review .. both scientific and animal welfare considerations .. weighing of the likely benefit and likely animal

suffering …an essential part of the review process

www.esf.org

Report on Directive 86/609 … s (2001/2259(INI))

by Committee on the Environment, Public Health and Consumer Policy

must be able clearly to substantiate and justify the purpose … the experiments will be of benefit to animals or humans

an ethical and animal-welfare assessment must be carried setting limits to the level of stress to which the animals may be subjected

should include a cost/benefit analysis

Revision of the Directive

Experts meet in Brussels

Four groups Scope, the 3Rs, Central Database Authorisation Ethical review Cost-benefit analysis and severity

classification

Cost-benefit

Benefit

CostBenefit

Cost

Can a proper cost-benefit analysis be made?

A cost-benefit analysis = An ethical judgement

Basis: weight suffering of the experimental animals against fulfilling human needs

Why is Cost-Benefit difficult?

1. Different scientific viewpoints2. Conflicting daily experiences3. Different (moral) viewpoints4. Considerable political charge

Practical Ethics

Ethics Committees Do we have to know ?

basic research

applied research Project review

cost-benefit analysis

probability to get valid, reliable results

Breakdown of costs and benefits

Both should be assessedRelative weight of elements?How to use?

Scoring systems

Identification of problem areas Item(s) to be improved Thought assistance

Porter’s scoring

A. Purpose of study

B. Probability for reaching the purpose

C. Species

D. Anticipated pain

E. Duration of pain

F. Duration of exp

G. Number of animals

H. Animal care

Scoring 1-5

Points C-H max 30 limit 15

Points A-H max 40 limit 22

Ref: Nature 356: 101-102, 1992

Porter / Research

A. Aim of the experiment 1 = alleviation of substantial human ior

animal pain 3 = clear benefit to human or non-human

health or welfare 5 = advancement of knowledge

B. Realistic potential to achieve goals 1 = excellent 5 = very limited or cannot be assessed

Porter / Animals I

C. Species 5 = NHP, 4 = other mammals….

D. Likely pain 5 = Severe..1 = None

E. Duration of pain 5 = very long..1 = none or very short

Porter / Animals II

F. Duration of experiment in relation to life span

(LS) 5 = > 0.2 x LS

(mouse – 110 days) 4 = 0.02 x LS 3 = 0.002 x LS 2 = 0.0002 x LS 1 = 0.00001 x LS

(mouse – 10 min)

G. Number of animals 5 =>100 4 = 20-100 3 = 10-20 2 = 5-10 1 = 1-5 or lowest score for

appropriate no of animals?

An example of possible cost

Quality of animal care (New App A) Excellent

space above minimum / group housing / enrichment / bedding Very good

one of the criteria above missing Good

two of the criteria above missing Satisfactory

three of the criteria above missing Poor

minimum space, alone and no enrichment

Concluding Remarks

Unfair for fundamental research ? 57 Nobel prizes in medicine

Problems with GM-animals ? life time studies, high number of animals

Expects major advances with minor cost yet, ideal worth thriving for

Limits set too low?

Breakdown clarifies thinking

Example:Xylitol and dogs

Man commonly used

sweetener positive effects on

caries and on ear infections

excessive use may induce laxative effects

Dogs 2-year toxicity study

at 2 g/kg daily in diet resulted in minor liver changes

accidental consumption of xylitol: mortality with seizures clinically

Formulating hypothesis

Kuzuya et al. 1966: Xylitol in dogs produces much stronger insulin release than glucose

Hypothesis: Ingested xylitol causes insulin secretion, which results in hypoglycemia

BUT: Was this tested in the 2-year toxicity study ?

Hypoglycemia only in fasted dogs ?

What about home-made first aid ?

Scoring xylitol study

A. Purpose of study

B. Probability for reaching the purpose

C. Species

D. Anticipated pain

E. Duration of pain

F. Duration of exp

G. Number of animals

H. Animal care

A3=clear health benefit

B3=moderate

C4=sentient, conscious

D3=moderate

E2=short

F1=very short

G2= 5-10

H1= excellentC-H= 13, A-H=19

Insuliini ja glukoosi vasteet ksylitolille (1.5 g/kg po)

020406080

100120140160180200

0 100 200 300 400

Time (min)

Insu

lin

(mU

/L)

0

1

2

3

4

5

Glu

cose

(m

mol

/L)

InsulinGlucose

A Dutch system to support decision-making

In 1999 Frans Stafleu, Ronno Tramper, Jan Vorstenbosch and Jaap Joles have developed a system to support decision-making.

In order to compare the apples with the oranges they quantified the different aspects.

Cost – Means - Benefit principleBenefitCost

Means

Facilities, transportTraining and competenceVeterinary careExperimental design - species, number - end points - alternativesAnimal sourceNegative results

Pain, distress, discomfort, sufferingDuration, frequency, severity of thoseDeath

Human healthAnimal healthSafety (toxicity studies)Increasing knowledgeEcologyEconomy (macro)

Nordic Forum 2003:Cost - Benefit - Means

COST

BENEFIT

Low High

High

Low

Means

Quality of care

Pain

Quality

Likelihood

Purpose no and species

Retro perspective ethics evaluation?

Cost benefit primer

Four short study protocols

Read through and discuss in groups identify both benefits and costs weigh them against each other consider means to

increase the benefits

decrease the costs