DOI: 10.5061/dryad.k2ff3
title: Data from: Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

description: Background: The harm benefit analysis (HBA) is the cornerstone of animal
 research regulation and is considered to be a key ethical safeguard for
 animals. The HBA involves weighing the anticipated benefits of animal
 research against its predicted harms to animals but there are doubts about
 how objective and accountable this process is. Objectives: i. To explore
 the harms to animals involved in pre-clinical animal studies and to assess
 these against the benefits for humans accruing from these studies; ii. To
 test the feasibility of conducting this type of retrospective HBA.
 Methods: Data on harms were systematically extracted from a sample of
 pre-clinical animal studies whose clinical relevance had already been
 investigated by comparing systematic reviews of the animal studies with
 systematic reviews of human studies for the same interventions
 (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis,
 corticosteroids for brain injury, Tirilazad for stroke, antenatal
 corticosteroids for neonatal respiratory distress and thrombolytics for
 stroke). Clinical relevance was also explored in terms of current clinical
 practice. Harms were categorised for severity using an expert panel. The
 quality of the research and its impact were considered. Bateson's
 Cube was used to conduct the HBA. Results: The most common assessment of
 animal harms by the expert panel was 'severe'. Reported use of
 analgesia was rare and some animals (including most neonates) endured
 significant procedures with no, or only light, anaesthesia reported. Some
 animals suffered iatrogenic harms. Many were kept alive for long periods
 post-experimentally but only 1% of studies reported post-operative care. A
 third of studies reported that some animals died prior to endpoints. All
 the studies were of poor quality. Having weighed the actual harms to
 animals against the actual clinical benefits accruing from these studies,
 and taking into account the quality of the research and its impact, less
 than 7% of the studies were permissible according to Bateson's Cube:
 only the moderate bisphosphonate studies appeared to minimise harms to
 animals whilst being associated with benefit for humans. Conclusions: This
 is the first time the accountability of the HBA has been systematically
 explored across a range of pre-clinical animal studies. The regulatory
 systems in place when these studies were conducted failed to safeguard
 animals from severe suffering or to ensure that only beneficial,
 scientifically rigorous research was conducted. Our findings indicate a
 pressing need to: i. review regulations, particularly those that permit
 animals to suffer severe harms; ii. reform the processes of prospectively
 assessing pre-clinical animal studies to make them fit for purpose; and
 iii. systematically evaluate the benefits of pre-clinical animal research
 to permit a more realistic assessment of its likely future benefits.
description: Antenatal
 corticosteroids data extractionData extraction from
 antenatal corticosteroid studiesAntifibrinolytics data
 extractionData extraction from
 antifibrinolytics studiesBiphosphonates data
 extractionData extraction from
 bisphosphonate studiesCorticosteroids data
 extractionData extraction from
 corticosteroid studiesThrombolytics data
 extractionData extraction from
 thrombolytic studiesTirilazad data
 extractionData extraction from
 Tirilazad studiesSummary antenatal
 corticosteroidsSummary tables
 (antenatal corticosteroids)Summary
 antifibrinolyticsSummary tables
 (antifibrinolytics)Summary
 bisphosphonatesSummary tables
 (bisphosphonates)Summary
 corticosteroidsSummary tables
 (corticosteroids)Summary
 thrombolyticsSummary tables
 (thrombolytics)Summary
 TirilazadSummary tables
 (Tirilazad)