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The ethics of research involving animals - Nuffield Council on ...

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T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s<br />

Reducti<strong>on</strong> and Refinement<br />

Introducti<strong>on</strong><br />

12.1 In the previous chapter we discussed the opportunities and current limitati<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> the first <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

Russell and Burch’s Three Rs, the Replacement approach. We now turn to the remaining two<br />

c<strong>on</strong>cepts Refinement and Reducti<strong>on</strong>, which need to be c<strong>on</strong>sidered whenever the use <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

<str<strong>on</strong>g>animals</str<strong>on</strong>g> to achieve a scientific objective is deemed unavoidable. As we have said, the Three<br />

Rs are closely interrelated. 1 <str<strong>on</strong>g>The</str<strong>on</strong>g> relati<strong>on</strong>ship between Reducti<strong>on</strong> and Refinement is<br />

particularly evident when these principles are applied at the early stage <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> projects<br />

to improve <str<strong>on</strong>g>research</str<strong>on</strong>g> strategy as a whole. We first give brief c<strong>on</strong>siderati<strong>on</strong> to this relati<strong>on</strong>ship<br />

and then examine Reducti<strong>on</strong> and Refinement more closely as individual c<strong>on</strong>cepts. <str<strong>on</strong>g>The</str<strong>on</strong>g> role<br />

<str<strong>on</strong>g>of</str<strong>on</strong>g> harm<strong>on</strong>ising internati<strong>on</strong>al test guidelines for the purpose <str<strong>on</strong>g>of</str<strong>on</strong>g> reducing animal <str<strong>on</strong>g>research</str<strong>on</strong>g> is<br />

then explored before we focus <strong>on</strong> the potential <str<strong>on</strong>g>of</str<strong>on</strong>g> Refinements. We give examples <str<strong>on</strong>g>of</str<strong>on</strong>g> how<br />

to implement Refinements in specific areas <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g> and also c<strong>on</strong>sider possible barriers.<br />

Applying Reducti<strong>on</strong> and Refinement to <str<strong>on</strong>g>research</str<strong>on</strong>g> strategies<br />

12.2 Animals will suffer needlessly if they are used in <str<strong>on</strong>g>research</str<strong>on</strong>g> where scientific methodology is<br />

poor. In such cases, <str<strong>on</strong>g>research</str<strong>on</strong>g> does not achieve its scientific objectives, and fails to generate<br />

significant knowledge. It is for this reas<strong>on</strong> that the applicati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the Three Rs should begin<br />

with a careful assessment <str<strong>on</strong>g>of</str<strong>on</strong>g> the initial experimental design and be c<strong>on</strong>tinued throughout<br />

the durati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> each and every <str<strong>on</strong>g>research</str<strong>on</strong>g> project. This process requires a number <str<strong>on</strong>g>of</str<strong>on</strong>g> basic<br />

questi<strong>on</strong>s to be addressed at a very early stage. For example, is the chosen animal model<br />

sufficiently relevant to the scientific questi<strong>on</strong> being asked or health problem under study?<br />

Is there a genuine scientific basis for using a particular animal model? Could the scientific<br />

questi<strong>on</strong> itself be refined? Could the scientific objective <str<strong>on</strong>g>of</str<strong>on</strong>g> the work be modified to avoid<br />

the use <str<strong>on</strong>g>of</str<strong>on</strong>g> an animal model? <str<strong>on</strong>g>The</str<strong>on</strong>g> following three general approaches are relevant to the<br />

successful implementati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> Reducti<strong>on</strong> and Refinement at this stage <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g>.<br />

CHAPTER 12 REDUCTION AND REFINEMENT<br />

■ Background <str<strong>on</strong>g>research</str<strong>on</strong>g>: it is essential that a thorough search <str<strong>on</strong>g>of</str<strong>on</strong>g> the published literature is<br />

undertaken to ensure that the proposed experiments have not already been undertaken<br />

and the objectives <str<strong>on</strong>g>of</str<strong>on</strong>g> the <str<strong>on</strong>g>research</str<strong>on</strong>g> have not already been met by previous well-c<strong>on</strong>ducted<br />

experiments. Part <str<strong>on</strong>g>of</str<strong>on</strong>g> this survey <str<strong>on</strong>g>of</str<strong>on</strong>g> the literature should be an assessment <str<strong>on</strong>g>of</str<strong>on</strong>g> the validity<br />

<str<strong>on</strong>g>of</str<strong>on</strong>g> the c<strong>on</strong>clusi<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> previous studies. New experiments should not be based <strong>on</strong> unsound<br />

c<strong>on</strong>clusi<strong>on</strong>s drawn from poorly designed experiments.<br />

■ A staged approach: before embarking <strong>on</strong> large or complex experiments the project<br />

should be broken down into a series <str<strong>on</strong>g>of</str<strong>on</strong>g> pilot experiments, with defined decisi<strong>on</strong> points<br />

that inform the transiti<strong>on</strong> from <strong>on</strong>e stage to another. A small pilot experiment <strong>on</strong><br />

<str<strong>on</strong>g>animals</str<strong>on</strong>g> or in vitro <str<strong>on</strong>g>research</str<strong>on</strong>g> can be very useful in guiding the design <str<strong>on</strong>g>of</str<strong>on</strong>g> subsequent, larger<br />

experiments. For example, an initial pilot study might help define experimental<br />

parameters early <strong>on</strong>, so that fewer <str<strong>on</strong>g>animals</str<strong>on</strong>g> could be used later. It might also be possible<br />

to refine experiments so that suffering and the number <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> used is reduced by<br />

carrying out pilot experiments <strong>on</strong> anaesthetised <str<strong>on</strong>g>animals</str<strong>on</strong>g> that are not allowed to recover.<br />

■ Teamwork and resources: the successful completi<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> an experiment depends <strong>on</strong> many<br />

factors, including the skills and performance <str<strong>on</strong>g>of</str<strong>on</strong>g> the staff involved, and the availability <str<strong>on</strong>g>of</str<strong>on</strong>g><br />

suitable equipment and facilities. Optimal experimental design and successful applicati<strong>on</strong><br />

<str<strong>on</strong>g>of</str<strong>on</strong>g> the Three Rs requires a multidisciplinary approach with c<strong>on</strong>tributi<strong>on</strong>s from biomedical<br />

1 Russell and Burch themselves acknowledged that there was overlap between the Three Rs; see Russell WMS and Burch RL (1959)<br />

<str<strong>on</strong>g>The</str<strong>on</strong>g> Principles <str<strong>on</strong>g>of</str<strong>on</strong>g> Humane Experimental Technique (L<strong>on</strong>d<strong>on</strong>: Methuen).<br />

205

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