Post by sweetnessandlight on Dec 15, 2006 16:47:26 GMT
Found on another forum:
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A new review article due to appear in the British Medical Journal is out online:
"Comparison of treatment effects between animal experiments and clinical trials: systematic review"
www.bmj.com/cgi/rapidpdf/bmj.39048.407928.BEv1
I'm not sure if this is general access or not but I've read it. Here's what they did
Quote:
We identified six interventions for which there was evidence of a
treatment effect (benefit or harm) in systematic reviews of clinical
trials and we carried out a systematic review of the
corresponding animal experiments. We searched for all
published and unpublished controlled studies in animal models
for the following interventions: corticosteroids in traumatic head
injury,9–11 antifibrinolytics in haemorrhage,12 thrombolysis in
acute ischaemic stroke,13 14 tirilazad in acute ischaemic stroke,15
antenatal corticosteroids to prevent neonatal respiratory distress
syndrome,16 and bisphosphonates to prevent and treat
osteoporosis.17 We were unaware of the results of the animal
studies when selecting the six interventions. We carried out our
systematic review in accordance with the recommended
methods for health technology assessment, described
elsewhere.18–21 Briefly, we systematically searched for randomised
and non-randomised controlled studies of the six interventions
in animal models. To be eligible for inclusion the studies had to
report outcomes corresponding to those for which a treatment
effect had been shown in clinical trials.
Here's some relevant parts of the discussion:
Quote:
Concordance between animal studies and clinical studies varied
for six interventions: three had similar outcomes and three did
not. Thrombolysis with tissue plasminogen activator was effective
in animal models of acute ischaemic stroke and the results
agreed with the clinical trials. The animal studies were of poor
quality, however, with evidence of publication bias. Our evidence
for concordance may therefore be biased. We found over 100
experiments, totalling more than 3000 animals. The pooled
result was therefore precise although not necessarily valid. The
concordance may be explained by the large volume of evidence
and the replication of similar designs in different animals and
different laboratories. Furthermore, tissue plasminogen activator
was tested in older animals, in those with comorbidities, and at a
range of intervals after stroke onset, ensuring a reasonable match
with patients in clinical trials. The results for bisphosphonates to
treat osteoporosis agreed between animal studies and clinical trials.
We also found that antenatal corticosteroids reduced neonatal
respiratory distress syndrome in animal studies and in clinical
trials, although the data were sparse and we found no evidence of
agreement for mortality.
The four experiments in our meta-analysis of corticosteroids
in animal head injury models used the weight drop model.28 All
had good allocation concealment and blinded outcome
assessment. Taken together they showed benefit. The experiments
were, however, from one laboratory, had little evidence on
adverse effects, and did not examine the influence of comorbidities.
We also found a difference in results for tirilazad to treat
stroke. The data from the animal studies suggested a benefit but
the clinical trials showed no benefit and possible harm. It should
be noted that the interval between stroke onset and treatment
was longer in the clinical studies (median five hours) than in the
animal models (median 10 minutes). Some of the clinical trials
recruited patients up to 24 hours after stroke onset. For antifibrinolytics
in haemorrhage, clinical trials showed clear evidence of
benefit despite the lack of any reliable data from animal models.
Methodological strengths and weaknesses
It would be inappropriate to make general statements about the
utility of animal research on the basis of only six interventions.
Animal studies are often carried out to learn about biological
mechanisms and we cannot comment on the value of animal
research in these areas nor provide precise estimates of
agreement. Although we tried to contact the authors of
individual animal studies, we analysed what was reported and
cannot rule out that other relevant data were not published. Our
systematic review does, however, provide insights into the limitations
of animal models, including the extent to which they represent
disease in humans. As the number of systematic reviews of
animal experiments increases, a quantitative approach to determine
similarities between animal models and clinical trials
should be possible in the future.
Quote:
Research is needed on the aspects of study design that can
bias treatment effects in animal models. Empirical evidence of
bias from study design characteristics helped to improve the
quality of clinical trials and might do the same for animal experiments.
Standards for evidence based reporting, similar to the
consolidated standards of reporting trials statement for clinical
trials, might ensure that relevant aspects of experiment methodology
are reported.29
Quote:
That there is a gap between clinical research and clinical
practice is well established.30 Our work highlights another gap—
specifically the lack of communication between those involved in
animal research and clinical trialists. Systematic reviews of
animal experiments could promote closer collaboration between
the research communities and encourage an iterative approach
to improving the relevance of animal models to clinical trial
design. When models do not represent the clinical context they
could be adapted accordingly. Furthermore, as is the case for
human research, systematic reviews could help identify and
improve deficiencies in the conduct and reporting of animal
research.
Finally, here's the Guradian article that informed [the original poster] of the existence of the BMJ review:
www.guardian.co.uk/animalrights/story/0,,1972659,00.html
Full report at:
www.pcpoh.bham.ac.uk/publichealth/nccrm/PDFs%20and%20documents/Publications/JH18_Final_Report_May_2006.pdf
--------------------------------------------------------------------------------
A new review article due to appear in the British Medical Journal is out online:
"Comparison of treatment effects between animal experiments and clinical trials: systematic review"
www.bmj.com/cgi/rapidpdf/bmj.39048.407928.BEv1
I'm not sure if this is general access or not but I've read it. Here's what they did
Quote:
We identified six interventions for which there was evidence of a
treatment effect (benefit or harm) in systematic reviews of clinical
trials and we carried out a systematic review of the
corresponding animal experiments. We searched for all
published and unpublished controlled studies in animal models
for the following interventions: corticosteroids in traumatic head
injury,9–11 antifibrinolytics in haemorrhage,12 thrombolysis in
acute ischaemic stroke,13 14 tirilazad in acute ischaemic stroke,15
antenatal corticosteroids to prevent neonatal respiratory distress
syndrome,16 and bisphosphonates to prevent and treat
osteoporosis.17 We were unaware of the results of the animal
studies when selecting the six interventions. We carried out our
systematic review in accordance with the recommended
methods for health technology assessment, described
elsewhere.18–21 Briefly, we systematically searched for randomised
and non-randomised controlled studies of the six interventions
in animal models. To be eligible for inclusion the studies had to
report outcomes corresponding to those for which a treatment
effect had been shown in clinical trials.
Here's some relevant parts of the discussion:
Quote:
Concordance between animal studies and clinical studies varied
for six interventions: three had similar outcomes and three did
not. Thrombolysis with tissue plasminogen activator was effective
in animal models of acute ischaemic stroke and the results
agreed with the clinical trials. The animal studies were of poor
quality, however, with evidence of publication bias. Our evidence
for concordance may therefore be biased. We found over 100
experiments, totalling more than 3000 animals. The pooled
result was therefore precise although not necessarily valid. The
concordance may be explained by the large volume of evidence
and the replication of similar designs in different animals and
different laboratories. Furthermore, tissue plasminogen activator
was tested in older animals, in those with comorbidities, and at a
range of intervals after stroke onset, ensuring a reasonable match
with patients in clinical trials. The results for bisphosphonates to
treat osteoporosis agreed between animal studies and clinical trials.
We also found that antenatal corticosteroids reduced neonatal
respiratory distress syndrome in animal studies and in clinical
trials, although the data were sparse and we found no evidence of
agreement for mortality.
The four experiments in our meta-analysis of corticosteroids
in animal head injury models used the weight drop model.28 All
had good allocation concealment and blinded outcome
assessment. Taken together they showed benefit. The experiments
were, however, from one laboratory, had little evidence on
adverse effects, and did not examine the influence of comorbidities.
We also found a difference in results for tirilazad to treat
stroke. The data from the animal studies suggested a benefit but
the clinical trials showed no benefit and possible harm. It should
be noted that the interval between stroke onset and treatment
was longer in the clinical studies (median five hours) than in the
animal models (median 10 minutes). Some of the clinical trials
recruited patients up to 24 hours after stroke onset. For antifibrinolytics
in haemorrhage, clinical trials showed clear evidence of
benefit despite the lack of any reliable data from animal models.
Methodological strengths and weaknesses
It would be inappropriate to make general statements about the
utility of animal research on the basis of only six interventions.
Animal studies are often carried out to learn about biological
mechanisms and we cannot comment on the value of animal
research in these areas nor provide precise estimates of
agreement. Although we tried to contact the authors of
individual animal studies, we analysed what was reported and
cannot rule out that other relevant data were not published. Our
systematic review does, however, provide insights into the limitations
of animal models, including the extent to which they represent
disease in humans. As the number of systematic reviews of
animal experiments increases, a quantitative approach to determine
similarities between animal models and clinical trials
should be possible in the future.
Quote:
Research is needed on the aspects of study design that can
bias treatment effects in animal models. Empirical evidence of
bias from study design characteristics helped to improve the
quality of clinical trials and might do the same for animal experiments.
Standards for evidence based reporting, similar to the
consolidated standards of reporting trials statement for clinical
trials, might ensure that relevant aspects of experiment methodology
are reported.29
Quote:
That there is a gap between clinical research and clinical
practice is well established.30 Our work highlights another gap—
specifically the lack of communication between those involved in
animal research and clinical trialists. Systematic reviews of
animal experiments could promote closer collaboration between
the research communities and encourage an iterative approach
to improving the relevance of animal models to clinical trial
design. When models do not represent the clinical context they
could be adapted accordingly. Furthermore, as is the case for
human research, systematic reviews could help identify and
improve deficiencies in the conduct and reporting of animal
research.
Finally, here's the Guradian article that informed [the original poster] of the existence of the BMJ review:
www.guardian.co.uk/animalrights/story/0,,1972659,00.html
Full report at:
www.pcpoh.bham.ac.uk/publichealth/nccrm/PDFs%20and%20documents/Publications/JH18_Final_Report_May_2006.pdf