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 />
<str<strong>on</strong>g>animals</str<strong>on</strong>g> are useful models for humans in medical <str<strong>on</strong>g>research</str<strong>on</strong>g> in paragraphs 10.27–10.32).<br />
Systematic limitati<strong>on</strong>s faced by any modelling approach are addressed in paragraphs<br />
10.33–10.36), and the findings <str<strong>on</strong>g>of</str<strong>on</strong>g> scientific reviews <strong>on</strong> the critical evaluati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g><br />
<str<strong>on</strong>g>involving</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g> are discussed in paragraphs 10.37-10.43).<br />
8.39 We observe that claims that animal <str<strong>on</strong>g>research</str<strong>on</strong>g> is failing to protect people from adverse drug<br />
reacti<strong>on</strong>s (ADRs) need to be treated with some cauti<strong>on</strong>. ADRs 43 have a number <str<strong>on</strong>g>of</str<strong>on</strong>g> causes.<br />
Many <str<strong>on</strong>g>of</str<strong>on</strong>g> these are avoidable, for example where they arise from prescripti<strong>on</strong> errors, where<br />
people have been given or have taken the wr<strong>on</strong>g medicine, or from interacti<strong>on</strong>s between<br />
different medicines taken simultaneously. In 2004, <str<strong>on</strong>g>research</str<strong>on</strong>g>ers c<strong>on</strong>ducting the largest<br />
prospective analysis in the UK <str<strong>on</strong>g>of</str<strong>on</strong>g> ADRs as a cause <str<strong>on</strong>g>of</str<strong>on</strong>g> admissi<strong>on</strong> to hospital found that more<br />
than 70% were avoidable and could have been predicted by taking into account<br />
pharmacological properties <str<strong>on</strong>g>of</str<strong>on</strong>g> the medicines involved. 44 While ADRs may be the direct result<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> administrati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> <strong>on</strong>e specific medicine, the questi<strong>on</strong> remains whether this is pro<str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
the failure <str<strong>on</strong>g>of</str<strong>on</strong>g> the animal model (or any other model) involved in the development process,<br />
or a methodological problem. As we have said, phases I–II <str<strong>on</strong>g>of</str<strong>on</strong>g> human clinical trials in the<br />
development <str<strong>on</strong>g>of</str<strong>on</strong>g> a medicine include up to 5,000 patients to m<strong>on</strong>itor efficacy and safety. If<br />
severe ADRs occur during these trials, the development <str<strong>on</strong>g>of</str<strong>on</strong>g> the medicine is not usually taken<br />
further. However, ADRs may occur at very low statistical frequencies, for example 1 in<br />
10,000, and hence may not be revealed at this stage (see paragraphs 10.33 and 10.1). In<br />
making inferences about the occurrence <str<strong>on</strong>g>of</str<strong>on</strong>g> ADRs, and the role that animal <str<strong>on</strong>g>research</str<strong>on</strong>g> plays,<br />
it is therefore unhelpful to generalise. ADRs can occur for a number <str<strong>on</strong>g>of</str<strong>on</strong>g> reas<strong>on</strong>s and could,<br />
in principle, also be caused by a medicine that, hypothetically, had been developed without<br />
the use <str<strong>on</strong>g>of</str<strong>on</strong>g> <str<strong>on</strong>g>animals</str<strong>on</strong>g>.<br />
8.40 Some also argue that the withdrawal <str<strong>on</strong>g>of</str<strong>on</strong>g> medicines from the market is indicative <str<strong>on</strong>g>of</str<strong>on</strong>g> the<br />
fact that animal <str<strong>on</strong>g>research</str<strong>on</strong>g> does not help to prevent ineffective or harmful medicines being<br />
used by humans. 45 In the UK, the Medicines and Healthcare products Regulatory Agency<br />
(MHRA) m<strong>on</strong>itors whether medicines <strong>on</strong> the market meet the appropriate standards <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
safety, quality and effectiveness. When there is sufficient evidence to suggest that the risk<br />
<str<strong>on</strong>g>of</str<strong>on</strong>g> taking a medicine outweighs its benefit to patients, the Committee <strong>on</strong> Safety <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
Medicines (CSM) and MHRA take appropriate regulatory acti<strong>on</strong> to protect the health <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
patients, and may initiate steps to withdraw medicines from use. Between 1995 and 2005,<br />
18 medicines were withdrawn from the UK market by companies or by the Licensing<br />
Authority <strong>on</strong> grounds <str<strong>on</strong>g>of</str<strong>on</strong>g> safety (see Box 8.6). A study c<strong>on</strong>ducted in 1994 <strong>on</strong> medicines<br />
withdrawn between 1961 and 1992 c<strong>on</strong>cluded that in the UK, 49 were taken <str<strong>on</strong>g>of</str<strong>on</strong>g>f the<br />
43 Edwards and Ar<strong>on</strong>s<strong>on</strong> define an ADR as ‘an appreciably harmful or unpleasant reacti<strong>on</strong>, resulting from an interventi<strong>on</strong><br />
related to the use <str<strong>on</strong>g>of</str<strong>on</strong>g> a medicinal product, which predicts hazard from future administrati<strong>on</strong> and warrants preventi<strong>on</strong> or<br />
specific treatment, or alterati<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> the dosage regimen, or withdrawal <str<strong>on</strong>g>of</str<strong>on</strong>g> the product.’ See Edwards IR and Ar<strong>on</strong>s<strong>on</strong> JK<br />
(2000) Adverse drug reacti<strong>on</strong>s: definiti<strong>on</strong>s, diagnosis, and management Lancet 356: 1255–9.<br />
44 <str<strong>on</strong>g>The</str<strong>on</strong>g> <str<strong>on</strong>g>research</str<strong>on</strong>g>ers, using Edwards and Ar<strong>on</strong>s<strong>on</strong>’s definiti<strong>on</strong> <str<strong>on</strong>g>of</str<strong>on</strong>g> ADRs (see previous footnote), sought to ascertain the burden <str<strong>on</strong>g>of</str<strong>on</strong>g><br />
ADRs though a prospective analysis <str<strong>on</strong>g>of</str<strong>on</strong>g> hospital admissi<strong>on</strong>s to two large general hospitals in the UK. Every patient aged over<br />
16 years who was admitted to these hospitals (18,820 patients) over a six m<strong>on</strong>th period was assessed to determine if the<br />
admissi<strong>on</strong> had been caused by an ADR. It was found that 1,225 admissi<strong>on</strong>s were related to ADRs (equalling 6.5%, which is<br />
c<strong>on</strong>sistent with an estimate <str<strong>on</strong>g>of</str<strong>on</strong>g> 5% based <strong>on</strong> pooled data from several studies worldwide). Three types <str<strong>on</strong>g>of</str<strong>on</strong>g> avoidability were<br />
assessed: definitely avoidable (7-10%: the ADR was due to treatment inc<strong>on</strong>sistent with present day knowledge <str<strong>on</strong>g>of</str<strong>on</strong>g> good<br />
medical practice), possibly avoidable (60-66%: the ADR could have been avoided by an effort exceeding the obligatory<br />
demands <str<strong>on</strong>g>of</str<strong>on</strong>g> present day knowledge <str<strong>on</strong>g>of</str<strong>on</strong>g> good medical practice) and unavoidable (25-30%: the could not have been avoided<br />
by any reas<strong>on</strong>able means). See Pirmohamed M, James S, Meakin S et al. (2004) Adverse drug reacti<strong>on</strong>s as cause <str<strong>on</strong>g>of</str<strong>on</strong>g> admissi<strong>on</strong><br />
to hospital: prospective analysis <str<strong>on</strong>g>of</str<strong>on</strong>g> 18 820 patients BMJl 329: 15–9. See also Waller P and Rawlins P A User’s Guide to the<br />
Safety <str<strong>on</strong>g>of</str<strong>on</strong>g> Medicines, available at: http://www.dsru.org/pat_guide_1.html. Accessed <strong>on</strong>: 2 May 2005; Kohn LT, Corrigan JM<br />
and D<strong>on</strong>alds<strong>on</strong> MS (Editors) (2000) To Err is Human: Building A Safer Health System, available at:<br />
http://www.iom.edu/report.asp?id=5575. Accessed <strong>on</strong>: 26 Apr 2005.<br />
45 See BUAV D<strong>on</strong>’t we need animal experiments to make sure drugs are safe for humans?, in Frequently asked questi<strong>on</strong>s<br />
about vivisecti<strong>on</strong>, available at: http://www.buav.org/faqs.html. Accessed <strong>on</strong>: 2 May 2005.<br />
CHAPTER 8 THE USE OF ANIMALS FOR RESEARCH IN THE PHARMACEUTICAL INDUSTRY<br />
147