by Dr Ray Greek
study in JAMA raises an interesting question about using animal models to
predict drug response. Taking the diabetes drug rosiglitazone has been linked
to an increased risk of heart attack. The study was a meta-analysis, which
is a fancy way of saying scientists analysed all the studies that have been
conducted on rosiglitazone and combined all the data in order to make a
judgement about the drug. The conclusion that rosiglitazone increases risk
for heart attack is controversial for reasons that do not have an impact
on this blog, hence we will ignore them.The question this study brings to
the fore is: What is the purpose of testing new drugs on animals?
are these tests to protect the patients taking them when the new drugs come
to the market? Or, are the animal tests supposed to protect the volunteers
and patients that take the drug in clinical trials?
reality is, the animal tests fail in both cases. But the question is valid
because the animal experimentation industry, via its spokespeople, tells
society that animal testing is performed to keep children and other patients
safe. They claim that every time a child takes a new drug, he would be at
risk of death and severe side effects were it not for animal testing.
the other hand, when new drugs kill people or cause liver failure or other
severe adverse reactions, the same people claim that the animal tests are
performed merely to decrease the risk of those in clinical trials and that
animal tests cannot predict what a drug will do to large numbers of genetically
diverse people. Like I said, animal tests fail on both accounts but I would
really like to know which position the industry affirms. If they admit the
tests are done in order to protect volunteers and patients in clinical trials
then it is disingenuous to sell animal testing to society on the basis of
protecting the general public after the drug goes to market. On the other
hand, if they maintain animal testing is necessary in order to protect society
after the drug goes to market, then they have to explain all the failures.
(Oraflex), Bextra (valdecoxib), Vioxx (Rofecoxib), Mibefradil (Posicor),
Astemizole (Hismanal), Baycol (Cerivastatin), Raplon (Rapacuronium), Phenylpropanolamine,
Propulsid (Cisapride), Rezulin (Troglitazone), Bromfenac (Xibrom), Seldane
(Terfenadine), Grepafloxacin (Raxar), Etretinate (Tegison), Levomethadyl
(Orlaam), Technetium (99mTc) fanolesomab (NeutroSpec), Pemoline (Cylert),
Pergolide (Permax), Tegaserod (Zelnorm), Practolol, Suprofen, Fenclozic
acid, Fenoterol, Dexfenfluramine. Zimeldine.
above is a partial list.Allow me a moment to anticipate the usual response
to this question. “Thousands of new drugs have been released and a
vast majority are safe and effective for humans. This fact refutes your
1, a vast majority of drugs have been approved for added uses or were me-too
drugs, which are drugs that were very similar to others already in distribution.
Many drugs were already known to be safe and were just reformulated to last
longer, or they were approved for different uses that came to light after
they had already been released in the market. According to the National
Institute for Health Care Management, of the 1035 New Drug Applications
between 1989 and 2000, only 155 were judged by the FDA to be new molecular
entities (NMEs). This means a vast majority were variations on a theme or
me-too drugs (1). These approvals are not new in the sense of animal models
predicting their safety or efficacy.
2, many drugs in use today were approved prior to animal testing. Included
in this category are morphine, nitrous oxide, and digitalis.
3, most drugs are not, in fact safe for everyone. Nor are they efficacious
for everyone. Think of the numerous drug-recalls reported in the news because
of previously unknown side effects. The animal models did not predict these
side effects. Also consider the following. More than 500,000 outpatient
children annually suffer adverse side effects from commonly prescribed medications.
Children under the age of 5 are often the victims (2). Approximately the
same numbers of children, already in the hospital, also suffer adverse effects.
Approximately 700,000 outpatients must visit the emergency room each year
due to adverse drug reactions (3). 15% of hospital admissions are caused
by adverse drug reactions (ADRs). Legal drugs kill approximately 100,000/yr,
more than all illegal drugs combined. This costs society over $136 billion
in health care expenses. Most drugs are effective in 30–60% of patients.
Adverse drug reactions are the fourth leading cause of death. 6.7% hospitalized
patients suffer severe ADRs. (4)
4, animals are not assessed to predict subjective reactions to drugs such
as nausea, headaches, dizziness, and so forth—which also happen to
be some of the most common side effects.Number 5, just because a drug was
tested on animals and did not harm humans does not mean that the test was
predictive for this. In other words, just because the test correlated with
the results from humans does not mean the test gives the right answers most
of the time much less enough times to qualify as a predictive test. This
particular correlation could have been a lucky guess or a random outcome.
This in fact is what most animal human correlations are, as even when the
outcomes are similar the mechanisms are not necessarily the same.I would
like an answer to my question so I could then challenge the nonsense based
on the best science we have available instead of being forced to address
two different answers simultaneously. By giving two different answers the
animal experimentation industry can change the parameters when they are
getting nailed on their nonsense. Then again, I would also like to live
in a world where giant corporations do not take shortcuts that result in
millions of gallons of oil spilling into the Gulf of Mexico.
Modern Drug Discovery, 7 (2002).
2. F. T. Bourgeois, K. D. Mandl, C. Valim, M. W. Shannon, Pediatrics 124,
e744 (Oct, 2009).
3. D. S. Budnitz et al., JAMA 296, 1858 (Oct 18, 2006).
4. J. Lazarou, B. H. Pomeranz, P. N. Corey, JAMA 279, 1200
(Apr 15, 1998).