New lecture by Professor of finance, Lisa Kramer.

Posted by Alex

Human Stakeholders and the Use of Animals in Drug Development

Please watch the brilliant new lecture titled ‘Human Stakeholders and the Use of Animals in Drug Development’, delivered at Toronto University on March 4th, by Professor of finance, Lisa Kramer.

To watch the lecture please visit this link or click the image below:

This lecture shows that: constrained by regulations which date back to WWII, the pharmaceutical industry is being constrained to use animal models in the drug development initiative, which is stopping the development of harmful drugs from reaching the market place – and hindering the development of useful drugs.
 
If we were to revise the way we regulate the pharmaceutical industry and the entire drug development enterprise this could greatly benefit the human stakeholders – of which patients are those with the most at stake.
 
The lecture underlines that we have many viable human-based methods that are addressing the personal needs of each individual patient; but even if we had no viable human-based methods we would still have no grounds for continuing to employ animal models. We’d be better off literally tossing a coin to decide which drugs to use for humans, as animals correlate with human outcomes less than 50% of the time. Cherry picking data, after the event, ignores the fact that there’s no way you’re going to know which animals will be predictive for humans, and which won’t, in advance.  Anecdotes are not compelling, the proof is in the mathematics of predictive value.
 
And because we’re allocating all our resources to the status quo, we don’t know what we might be forgoing had we reallocated those resources to existing cutting edge human-based methods.
 
Drugs that have been ruled out after animal tests are later discovered accidentally to be useful for humans; for example Fleming discovered penicillin for humans after he saw it fail as an effective treatment of infections in animals. Fleming went on record stating that if animal testing had been required at the time he was developing penicillin, he fears that the “whole field of antibiotics might never have been realized”.
 
All of the above is underlined by the fact that the number of  effective and safe new drugs approved has slowed to a crawl, it’s ‘no greater than it was 50 years ago’, (Munos, 2009, page 259, Nature Reviews Drug Discovery) – and this, despite all the technological advances.
 
There are also huge financial costs 
 

Sepsis, for which animal models have yielded no effective treatment, costs US hospitals at least 14$billion annually (Mayr and Yende, 2014).

Cancer, coronary artery disease, congestive heart failure, stroke lung disease and other affliction which have been extensively explored with animal models also continue to be extremely costly to treat, with treatment outcomes nevertheless still extremely risky.

The costs of existing successful treatments are considerably inflated in order to underwrite the high costs of animal modeling, most of which fails.

Other stakeholders apart from patients are affected.
 
It is useful to examine the drug development industry’s costs relative to revenues:
 

The pharmaceutical industry spends more on R&D than any other industrial sector, (Pham 2010).

The majority of the costs to industry of developing drugs comes from human clinical trials.

The top reason for failure in human clinical trials are safety and efficacy (the very properties animal models are intended to asses)

Drug companies would actually prefer not to be required to do the animal tests. When Prof. Kramer presents her work at pharmaceutical scientists’ conferences they nod their heads “yes we need to bypass this costly and misleading aspect of the development process”.
 
Other Stakeholders
 

Clinical trial participants: these are among the first humans exposed to compounds that perhaps appeared safe in animal models, and they often aren’t informed of the significant risks they face based on the methodological problems with animal models.

New generations of scientists: those being trained to continue to employ animal models are missing the opportunity to advance scientific progress through use of better methods.

Tax payer and donors who fund these initiatives

Lower bound on annual cost to society: $10-12 billion of the annual NIH budget directly funds animal-based research at universities.

Non profit charities which use tax payers donations e.g. the for ice bucket challenge, lots of that money directly funded animal-based research.

Investors: constraining drug development firms to employ animal models prevents them from putting investment capital to its best use, and arbitrarily limits the firms’ financial returns.

Why does animal-based research continue?
 

Laws continue to codify animal models prior to human clinical trials.

The FDA and its counterparts around the world likely has the power to revise these laws but are unlikely to do so without action from legislative bodies.

Other obstacles include conflict of interest, status quo bias (including the 3Rs sector) and various other behavioral tendencies on the part of researchers and the public.

It often takes a better model to replace a model: in this case that effectively means 100% predictive value. Prof. Kramer argues these exist, so instead of looking where it’s easy to look – like the old drunk looking for his keys where the light happens to be, instead of somewhere else where he actually lost them – Prof. Kramer argues this is what we are doing by continuing to use animal models.

  • Instead we could be using the technology of personalized medicine:
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  • Examples of personalized medicine include genetically matched treatments where we can determine – based on your specific genetic makeup – whether you’re going to have the desired outcome from a drug or an adverse response. Immunotherapy: this is already being used in treating many forms of cancer where the treatment is targeted to the patient’s specific genetic makeup. Microdosing: where we can administer compounds to humans at doses far below therapeutic levels to determine safety and efficacy, at the cellular level. Personalized medicine is literally happening, it’s not some far fetched futuristic idea. At the University of Toronto there’s an example of personalized medicine in action: they’ve grown heart tissue from human stem cells and here you can see the tissue beating in the lab. Scientists can use this to study the effect of potential drug molecules on actual human heart tissue. This can help us determine safety and efficacy, particle implications that could never be possible by looking at animal tissue. This is human technology for human application for human benefit – which is the whole point.
 
CONCLUSION
 

Constrained by outdated standards, the pharmaceutical industry is effectively required to employ animal models in early stages of the drug development process.

The reliance on animal models is unable to prevent the development of harmful drugs and is hindering the development of useful drugs.

Humans are significantly harmed, including patients, clinical trial participants, researchers, tax payers and many others.

Elimination of policies and regulations that require the use of animal models will greatly benefit stakeholders of the pharmaceutical industry.

It’s time for the EDM 66 science debate – judged by independent experts from the relevant fields of science.

Human stakeholders – including patients – are being harmed by the claims of vested interest groups, which continue to make huge profits from animal modeling, at the expense of the rest of society.

Decision makers and the public need to be given the opportunity to make an informed decision about current scientific knowledge, and this can be achieved by our called-for medical debate, as outlined by Prof. Kramer and Dr. Ray Greek, in their new book chapter.

PLEASE TAKE ACTION TO HELP!

Please ask your MP to sign the current Parliamentary EDM 66, calling for our science hearing. Simply type in your postcode at this link to send your MP a letter now!

Thank you for your time and support.