problems basing human studies on animal

Problems Basing Human Studies on Animal Studies

A few days ago I was listening to BBC World Service on my computer,

when I caught just the end of a news report. What caught my attention

was a statement from a British medical researcher that went something

like this: "We base our medical studies on humans on our studies on

animals. But, if the studies on animals don't follow the same

standards, don't have the same quality, then how can we trust the

results? Is this what we're basing our human subject research on?"

Well, I went digging, but I couldn't find the news report. (If someone

out there can, I'll be happy to give a more accurate quote and

appropriate credit.) However, I did find this. This is a study by

Luciano E Mignini, MD and Khalid S Khan, M.Sc. and a Member of the

Royal College of Obstetrics and Gyenecology, titled, "Methodological

quality of systematic reviews of animal studies: a survey of reviews

of basic research." The article was published at BMC Medical Research

Methodology, an online journal.

You can get a sense of the concern the researchers were addressing

from their "Backgrounds" section:

In the development of new health technologies, it is widely held

that drugs or procedures should first be assessed in animal models

before proceeding to clinical trials in humans. High quality

systematic reviews provide unbiased overviews of the available

evidence. There have been calls for application of this approach in

basic research, particularly in animal research, to better

understand biological plausibility and to translate findings of

basic research to the bedside. Cumulative assessment of emerging

evidence in animal research can help rationalize human clinical

trials. The idea that these experiments impact future human studies

is well recognised, but lack of systematic review of this evidence

can lead to a sort of research bias that has seldom been previously

considered explicitly. The link (or lack of appreciation of a link)

between animal and human studies is illustrated by the case of

nimodipine in focal cerebral ischemia; it has become clear from

systematic review of animal experiments that there was no

convincing evidence to substantiate the decision to perform trials

with nimodipine in humans Because the initial animal studies were

not evaluated systematically; human trials of nimodipine proceeded

at significant cost and potential human risk despite a lack of

clear scientific rationale. The extent and the quality of

systematic reviews of animal studies is unknown. The aim of this

study was to assess the methodological features of such systematic

reviews.

To translate: when preparing to do medical research involving human

subjects, scientists review the literature for reports of relevant

research on animal subjects. Part of what they look for is reviews of

research on animal subjects. However, research studies on animals

haven't been subject to the same qualitative review that is common in

studies on human subjects; and, as a result, decisions can be made

based on animal studies that aren't in fact well done. Therefore, they

decided to review a large group of animal studies for standards of

good research practice that they felt would be necessary for good

human subject research. In describing their own methodology, they list

the standards and procedures they're looking for.

The results of their review?

From 4749 citations initially identified, 1517 were considered

potentially relevant and their full manuscripts were evaluated.

Among these, there were only 30 (1.9% of 1517) reviews of animal

studies that met our selection criteria. The reviews summarised

studies of animals including cat, cow, horse, dog, mouse, nonhuman

primate, rabbit, rat, sheep and swine amongst others. The ranges of

topics included cardiology, dentistry, gynaecology, immunology,

neonatology, obstetrics, oncology, toxicology and urology amongst

others....

There next paragraph goes on to detail the standards by which

significant portions of those 1517 studies fell short.

Now, this is an important issue in medical ethics. As the authors

note, studies involving human subjects are determined to worth

pursuing, both in terms of results and in terms of benefits

outweighing risks, based largely on studies in animals. However, the

assumption is that those animal studies are well done, and meet

sufficient standards for quality. If those studies do not meet

sufficient standards, they mislead researchers, wasting money and time

with no benefit to patients. The authors citation of the nimodipine

studies is a case in point.

Moreover, not only are such poor studies not sufficient grounds for

moving forward to human studies, they are not adequate justification

for any risks and suffering for the animals. After all, it is a

recognized principle in human subject research that a study that will

not produce usable results by definition places those human subjects

at inappropriate risk. If these animal studies are not producing

usable results, they put the animals at a risk that is at least

wasteful, and is demonstrably immoral.

I am also concerned about this study because it brings me back to a

favorite soapbox: the tendency for any research study that shows

progress in a disease that we fear to show up in the evening news.

There is always the caveat that "it will be years before we know

whether this will result in a new treatment;" but by that point the

damage is done. The public has been told of a study result, and told

that the result was hopeful. If the study is good, that may well be in

question: it is a long way from an animal study to a useful treatment

for humans. If, on the other hand, the study is poor it is indeed

false hope, perpetrated by haste. Particularly where there are people

suffering with diseases for which we currently have little to offer,

bad studies are mercy delayed and distracted; and indiscriminate

publication in the broadcast media is little better.

I'm sure others will be looking at this article with their own reviews

and arguments. I think that will be good, and will move medical

research forward. However, in the meantime we need to take animal

studies with a grain of salt, both those in research and we in the

larger community. We trust - we can only trust - that researchers will

carefully evaluate animal studies when they seek justification to move

forward with human subjects. We need whenever we can to express our

own concerns that those studies be done according to the highest

research standards.