A new 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? Specifically, 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?
The 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. On 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. Failures like:
Technetium (99mTc) fanolesomab (NeutroSpec)
The 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 argument.”
Number 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.
Number 2, many drugs in use today were approved prior to animal testing. Included in this category are morphine, nitrous oxide, and digitalis.
Number 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)
Number 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.
1. Editorial, 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).