Where Is the Evidence That Animal Research Benefits Humans?

Sometimes-Ray Greek collaborator Pandora Pound was the lead author on a paper with that provocative title published by in the February 28th edition of the British Medical Journal. The correct answer, of course, is that it is all around us but that Pound, et al. choose to ignore it.

In the paper, Pound and her co-authors write,

We searched Medline to identify published systematic reviews of animal experiments (see bmj.com for the search strategy). The search identified 277 possible papers, of which 22 were reports of systematic reviews. We are also aware of one recently published study and two unpublished studies, bringing the total to 25. Three further studies are in progress (M Macleod, personal communication).

Seven of the 25 papers were systematic reviews of animal studies that had been conducted to find out how the animal research had informed the clinical research. Two of these reported on the same group of studies, giving six reviews in this category. A further 10 papers were systematic reviews of animal studies conducted to assess the evidence for proceeding to clinical trials or to establish an evidence base.w1-w10 Eight systematically reviewed both the animal and human studies in a particular field, again before clinical trials had taken place.w11-w18 We focus on the six studies in the first category because these shed the most light on the contribution that animal research makes to clinical medicine.

Each of the six studies is then examined and offered up as a criticism of animal research,

An unpublished study by Ciccone and Candelise systematically reviewed randomised controlled experiments of animal stroke models that compared the effects of thrombolytic drugs with placebo or open control.17 The background to the study was the finding that clinical trials of thrombolysis for acute stroke had found a substantial excess risk of intracranial haemorrhage that had not been predicted by individual animal studies. When the animal data were pooled, a significant difference was found in the rate of intracranial haemorrhage between animals in the control and treatment groups.

But, as Colin Blakemore and Tony Peatfield note in a letter to the BMJ, Pound, et al appear to have misinterpreted their own findings,

The authors identified 277 reviews of animal experiments but described just six systematic reviews, conducted to discover whether animal research had informed particular clinical studies. Far from providing evidence that animal research doesn’t work, five reviews showed that full analysis of the animal results predicted the ineffectiveness of the treatment being tested. But the clinical work was started before proper assessment of the animal studies.

It is imperative that animal research is properly evaluated before the results are transferred to medical practice. The relevant ethics committees and regulatory authorities should have identified that these clinical trials were based on inadequate analysis of animal experiments. The animal studies were not at fault.

Pound et al did not even consider the importance of animal studies for basic medical research. They ignored research on normal life processes and the natural history of disease, not to mention safety testing. All these make essential contributions to the development of new therapies for humans (and animals). Much of this work is required by law.

Some of the authors have called publicly for a “moratorium” on animal research.2 This is totally unjustified by their results.

In a comment on the paper posted on the BMJ’s web site, Blakemore put this more bluntly,

Pound et al. used a Medline search to identify 277 reviews of animal experiments but they chose to describe just six systematic reviews conducted to discover whether animal research had informed particular clinical studies. One pointed out that there is no simple animal analogue of the established relationship between social status and coronary heart disease in humans. This is hardly surprising in view of the complexities of human society, which have no clear parallel in animal hierarchies. The other five papers all described clinical trials that had apparently been started without full analysis of prior animal studies or even in parallel with animal work. In each case the putative therapy turned out to have no benefit and subsequent systematic review showed that animal research revealed exactly the same problems. Far from providing evidence that animal research doesn’t work, these studies revealed excellent agreement between animal results and clinical experience.

Unfortunately, as several posts to the BMJ site predicted would happen, mainstream news outlets picked up on Pound’s paper as suggesting a serious scientific controversy over whether animal research has benefited human health. The BBC, for example, ran coverage of the study on its website under the headline, “Scientists doubt animal research” and absurdly claimed that,

In reaching their conclusions, the London team [Pound, et al] carried out a systematic review of all animal experiments which purported to have clinical relevance to humans.

Even Pound, et al didn’t make that claim, which would be all but impossible to accomplish. Rather, they looked at the small number of studies that reviewed specific animal research, and then apparently cherry-picked just six of those studies to examine closer.

Sources:

Scientists doubt animal research. The BBC, February 27, 2004.

Where is the evidence that animal research benefits humans? Pandora Pound, Shah Ebrahim, Peter Sandercock, Michael B Bracken, and Ian Roberts. British Medical Journal, 2004;328:514-517 (28 February).

Missing evidence that animal research benefits humans. Colin Blakemore and Tony Peatfield, BMJ 2004;328:1017-1018 (24 April).

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