The ethics of research involving animals - Nuffield Council on ...
The ethics of research involving animals - Nuffield Council on ...
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 />
macaques, but have not provided protecti<strong>on</strong> for humans. Fundamental differences between<br />
the HIV/AIDS disease processes in the macaque model and in humans need to be c<strong>on</strong>sidered<br />
carefully in making predicti<strong>on</strong>s from <strong>on</strong>e to the other (paragraphs 6.36–6.37).<br />
All modelling approaches face limitati<strong>on</strong>s c<strong>on</strong>cerning transferability and predictability<br />
10.33 Given the vast complexity and variability <str<strong>on</strong>g>of</str<strong>on</strong>g> biological systems, it is not surprising that<br />
there are sometimes problems in developing effective experimental approaches in<br />
biomedical <str<strong>on</strong>g>research</str<strong>on</strong>g> and in extrapolating from model systems to humans (see paragraph<br />
8.37–8.40). <str<strong>on</strong>g>The</str<strong>on</strong>g> difficulties, however, are an intrinsic part <str<strong>on</strong>g>of</str<strong>on</strong>g> any modelling approach that<br />
relies <strong>on</strong> surrogates for the range <str<strong>on</strong>g>of</str<strong>on</strong>g> organisms <str<strong>on</strong>g>of</str<strong>on</strong>g> interest. Nor are they c<strong>on</strong>fined to animal<br />
studies, but are also encountered in developing and applying other experimental<br />
approaches, such as in vitro and clinical studies. N<strong>on</strong>e <str<strong>on</strong>g>of</str<strong>on</strong>g> these methods can reproduce<br />
exhaustively all the features that characterise the wide diversity and variati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> genetic<br />
and biological processes that occur in a populati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> humans, as is clear from the<br />
following examples:<br />
i) Limitati<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> in vitro <str<strong>on</strong>g>research</str<strong>on</strong>g>: differences between human cells in vitro and in vivo can<br />
pose challenges in extrapolating findings from <str<strong>on</strong>g>research</str<strong>on</strong>g> <strong>on</strong> the functi<strong>on</strong>ing <str<strong>on</strong>g>of</str<strong>on</strong>g> human<br />
cells in culture to the functi<strong>on</strong>ing <str<strong>on</strong>g>of</str<strong>on</strong>g> human cells in vivo (see Chapter 11 for further<br />
discussi<strong>on</strong>). 9 Yet more acute challenges arise in using the findings from cell culture<br />
studies to make predicti<strong>on</strong>s relating to the integrated physiology <str<strong>on</strong>g>of</str<strong>on</strong>g> intact tissues, organs<br />
or the whole human body.<br />
CHAPTER 10 SUMMARY OF SECTION 2<br />
ii) Limitati<strong>on</strong>s <str<strong>on</strong>g>of</str<strong>on</strong>g> human clinical trials: even if the animal-<str<strong>on</strong>g>research</str<strong>on</strong>g> stage was omitted from<br />
the development <str<strong>on</strong>g>of</str<strong>on</strong>g> new medicines, intrinsic problems resulting from the way clinical<br />
trials are c<strong>on</strong>ducted remain. First, human clinical trials typically involve testing a drug <strong>on</strong><br />
1,000–5,000 human volunteers and patients. If a side effect occurs in 1 in 10,000 patients,<br />
it is likely to become apparent <strong>on</strong>ly after the product is marketed (see Boxes 8.6 and 8.7).<br />
Sec<strong>on</strong>dly, human trials usually involve a relatively homogeneous sample <str<strong>on</strong>g>of</str<strong>on</strong>g> patients in<br />
order to distinguish clearly between the effects <str<strong>on</strong>g>of</str<strong>on</strong>g> the therapy (the ‘signal’) against the<br />
background <str<strong>on</strong>g>of</str<strong>on</strong>g> variati<strong>on</strong> between different patient’ resp<strong>on</strong>ses (the ‘noise’). 10 Such trials,<br />
moreover, frequently provide little, if any, informati<strong>on</strong> about the effects <str<strong>on</strong>g>of</str<strong>on</strong>g> drug<br />
interacti<strong>on</strong>s, since they usually do not mimic the actual situati<strong>on</strong> in which patients may<br />
take several different medicines at the same time. 11 Uncertainties about the effects <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
treatments in the clinical setting are therefore inevitable, 12 and clinicians must exercise<br />
judgement in extrapolating the results <str<strong>on</strong>g>of</str<strong>on</strong>g> clinical trials to individual patients (see<br />
paragraph 11.21). 13<br />
9 This point draws <strong>on</strong> Horrobin’s provocative discussi<strong>on</strong> in a recent opini<strong>on</strong>: Horrobin DF (2003) Modern biomedical <str<strong>on</strong>g>research</str<strong>on</strong>g>:<br />
an internally self-c<strong>on</strong>sistent universe with little c<strong>on</strong>tact with medical reality? Nat Rev Drug Disc 2: 151–4.<br />
10 Fletcher RH (2002) Evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> interventi<strong>on</strong>s J Clin Epidemiol 55: 1183–90.<br />
11 Stricker BHCh and Psaty BM (2004) Educati<strong>on</strong> and debate article: detecti<strong>on</strong>, verificati<strong>on</strong> and quantificati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> adverse drug<br />
reacti<strong>on</strong>s BMJ 329: 44–7.<br />
12 Chalmers I (2004) Editorial: Well informed uncertainties about the effects <str<strong>on</strong>g>of</str<strong>on</strong>g> treatments: how should clinicians and patients<br />
resp<strong>on</strong>d? BMJ 328: 475–6.<br />
13 Fletcher RH (2002) Evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> interventi<strong>on</strong>s J Clin Epidemiol 55: 1183–90.<br />
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