Tag Archives: FDA

The Problem With Jane Goodall’s “Expert” Opinion

On September 7, 2017, Dr. Jane Goodall wrote a scathing letter to Dr. Scott Gottlieb, Commissioner of the U.S. Food & Drug Administration (FDA) denouncing what she called the “cruel and unnecessary nicotine addiction experiments on monkeys” occurring there. The letter, which relies on the repeated use of opinion versus fact-based arguments by Goodall, is not just problematic, it’s downright dangerous.

This is not Goodall’s first time lending her name to various efforts by animal rights activists opposed to federally-supported biomedical and behavioral research, despite her lack of expertise or relevant credentials. Goodall has often partnered with animal rights groups to attack life-saving science. In March 2016, she supported a campaign by the Animal Justice Project to stop preclinical trials of a new malaria vaccine. In September 2016, Goodall joined Cruelty Free International (CFI) to co-author a letter attacking the use of animals in neuroscience research (to which a counter-letter, signed by 400 prominent experts in the field, was published). In February 2017, Goodall worked with For Life on Earth to call out Prof. Roger Lemon, a notable Professor of Neurophysiology, to criticize his comparative work with both humans and non-human primates.

Squirrel monkey. Source: Wikimedia Commons.

As detailed here, her most recent letter to the FDA, in partnership with The White Coat Waste (WCW) Project, a conservative-leaning animal rights organization devoted to the elimination of animal research, relies on the repeated use of opinion rather than empirical observations or rigorous study to arrive at sweeping – and dangerous – conclusions.  

The problems

We’ll tackle this letter in particular, though past letters signed by Goodall and other notable figures like David Attenborough, are similarly flawed and should be similarly scrutinized.

  • No relevant credentials or expertise: This one bears repeating. Although this should be obvious, to many it is not. Though she possesses a PhD and is described as an expert on chimpanzees, Goodall’s “expertise” ends there. She does not possess an advanced degree pertinent to the field of addiction research, and moreover she has never conducted research in a biomedical research facility. Thus, her first-hand knowledge of the methodology and oversight in these types of studies is questionable at best. Would you consult a cardiologist for questions about your car’s transmission?  Or, conversely, consult an auto mechanic about your open heart surgery? In fact, Dr. Goodall appears to recognize this. For example, in her video targeting Prof. Roger Lemon, midway through the video Goodall notes: “I don’t have the scientific medical knowledge to take issue with Professor Lemon” before going on to demand he debate pseudoscientist, Dr. Ray Greek. The problem here is that the weight given to Goodall’s opinion is directly related to impressions of her expertise and credentials. This issue of ethics of expertise is an important one. Goodall herself may not be directly claiming to be a neuroscientist, or an addiction researcher, but one of the reasons that her opinion may be thought valuable in these campaigns is because she is a scientist. As as scientist, it is worth considering whether Goodall should be upfront about her lack of expertise in the topic at hand. In fact, Goodall’s conclusion that the research is “unnecessary” and that “the results of smoking are well-known in humans” are opinions, rather than statements based in evidence and expert analysis.

    “I don’t have the scientific
    medical knowledge…”
    – Jane Goodall

  • “I have been told that…”: This should immediately set off alarm bells to anyone reading Goodall’s letter. Forget what comes after that – who has told her what she describes? As we have noted in the past, it’s crucial to know the starting assumptions of those engaging in a conversation, and the assumptions must be spelled out. In this case, it is no secret that Goodall has worked with The White Coat Waste (WCW) Project, a conservative-leaning animal rights organization devoted to the elimination of animal research (this starting position itself is dangerous, as described below). The WCW’s site itself states, “On the heels of WCW’s new lawsuit against the Food and Drug Administration (FDA)…Dr. Jane Goodall has joined WCW’s campaign to expose and end this wasteful project.” Put simply: Goodall appears to rely only on information provided to her by animal rights groups to make the case in her letter.
  • Factual inaccuracies: Probably because she appears to rely on the distorted information from WCW, Goodall’s letter is full of multiple inaccurate statements. One example is when she writes, “Not only is it extremely cruel to restrain the monkeys.”  In reality, empirical evidence—that is data – show that restraint devices used in such studies do not cause severe stress to the animals, because they are slowly trained to be familiar with and calmly enter and remain in the restraint devices. Despite her scientific background—which should result in knowing that evidence and citations matter—Goodall cites no evidence for her claim that restraint is “extremely cruel.”
  • Sweeping assumptions: At least two glaring assumptions stand out in Goodall’s brief letter.
    1) Goodall writes, “To continue performing nicotine experiments on monkeys when the results of smoking are well-known in humans – whose smoking habits can still be studied directly – is shameful.” There are several problems with this statement. The first is that Goodall assumes that the monkey studies examining the neurobiology and physiology of nicotine addiction is the same thing as studying smoking habits in humans. Someone with expertise in this field should know these are false equivalencies. The only other plausible explanation is that she is choosing to ignore the fact that these two are not the same thing. The FDA describes on its webpage that nicotine research will inform about the toxicity of tobacco products as they continue to change by manufacturers, about how changes in tobacco product characteristics (e.g., aerosolized chemicals, often including nicotine, found in e-cigarettes) impact addiction, and about the changes in cell function/physiology after tobacco exposure. These types of findings are not readily available from studying humans’ smoking habits. 2) Near the end of her letter, Goodall writes, “I’m sure that most Americans would be horrified to learn that their tax dollars are paying for this abuse.” Again, Goodall makes major assumptions without citing any sources of data. We can just as confidently say that we’re sure most Americans would be glad to know their tax dollars are being used in highly-regulated research studies that address the health of current and future generations.

The dangers

  • Calls for de-funding life-saving research: The most recent nicotine delivery methods, e-cigarettes, have not yet been well studied for their health effects, yet they represent a major public health concern. We do not yet know all the ways in which nicotine in e-cigarettes affects the brain. Studies such as those conducted by the FDA in animals, including monkeys, will teach us how these new delivery methods affect the brain and body, which will in turn lead to recommendations for regulation of these products and potential treatments for addiction. Despite these life-saving benefits, Goodall and WCW call for an end to this line of research in their letter. This explicit threat should ring alarm bells for any citizen concerned about public health. But this is not the first time animal research opponents have called for an end to beneficial research. Just a week ago, the Secretary of the Department of Veterans Affairs (VA), Dr. David Shulkin, had to make a plea to the United States Senate to not end life-saving canine research after a campaign by – you guessed it – WCW called for an end to this line of work. Think about that. The VA Secretary had to lobby the U.S. Senate to save a life-saving research program for veterans.

  • Threats to the advancement of scientific knowledge: As if threats to life-saving research weren’t enough, animal rights campaigns that rely on “experts” like Goodall are also threatening to end – or have already ended – scientific programs geared toward broadening and enhancing society’s basic knowledge of the way the world works, from the toxic effects of vapors in e-cigarettes to the safety of new vaccines to the communication between neurons to mechanisms of stress resilience to…the list goes on. This type of basic knowledge is crucial before life-saving treatments can be developed. This implicit threat should ring alarm bells for any citizen, period.

Nine out of ten Statistics are taken out of Context

This guest post is by Professor Robin Lovell-Badge, who is head of the division of Stem Cell Biology and Developmental Genetics at the Medical Research Council National Institute for Medical Research in London. This is a very clear and thorough debunking of a common animal rights myth where they suggest that because nine out of ten drugs that pass animal tests still fail to be approved, that animal tests must not work – In this post Prof Lovell-Badge explains the true meaning of these misused and misunderstood statistics. 

Facts without context

Those opposed to animal research often point out that most drugs that pass the legally required toxicology tests in animals go on to fail in human clinical trials. They then go on to suggest that this shows that animal research does not work, or that it is proof that animals are not accurate models for humans.

However, this is misleading without an understanding of the relevant context and the reasons for the animal safety tests. Ironically, the figures cited by many animal rights activists are actually drawn from industry and are intended to explain the expense of developing safe and useful medicines.

The most frequently used statistics are

  • 90% drugs tested on animals fail” – British Union for the Abolition of Vivisection
  • 92% of drugs fail in clinical trials, having successfully passed through animal studies” – Safer Medicines Trust
  • “In fact according to the FDA’s research, nine out of ten drugs deemed successful in animal tests fail in human clinical trials” – Humane Society International

The main sources of this information come from the US Food and Drug Administration (FDA). In 2006, Mike Leavitt said:

“Currently, nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies,” said Health and Human Services Secretary Mike Leavitt (alternative source).

The 92% statistic comes from an earlier report which showed only 8% of those drugs passing animal testing stages would go on successfully to be FDA approved.

“For example, a new medicinal compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market.” – Challenges and Opportunities Report, FDA, 2004

Are the figures right?

To help break down these statistics, it is useful to look at the success rates at each stage (source). In the diagram below the red percentages show the proportion of drugs that move from one stage to another – so 64% of New Molecular Entities (NMEs – essentially new drugs) will pass the animal tests (preclinical studies) and be moved into Phase 1 clinical trials in humans. Looked another way, animal experiments remove 36% of the potential drugs from moving onto the next stage. This is almost certainly a good thing as it avoids humans being given drugs which are likely to be toxic to them. The percentages at the bottom look at the percentage chance that a drug that has made it to that stage will make it all the way – so of all the drugs that make it to Phase 2 clinical trials, 12% will be approved by the FDA (and 88% will fail).

NME = New Molecular Entity. This means a possible drug that is going through trials.

NME = New Molecular Entity. This means a possible drug that is going through trials.

The first thing to note is of those drugs which pass animal tests, 94% will fail during human clinical trials stages (Phases 1 – 3)*.

* number of drugs which have passed Phase 3 clinical trials ÷ number of drugs which have passed just animal tests = 1.2 ÷ 19.4 = 6.2% of drugs which reach Phase 1 trials are eliminated by Phase 1-3 clinical trials. 100 – 6.2 = 93.8% fail.

 

So the failure rate is actually higher than even the animal rights organisations suggest (since they are using data from before 2006). Is this damning for animal research?

Consider that of all the drugs which pass Phase 1 clinical trials in humans, 86% will fail in later stage human trials**. Yet, we do not hear activists suggesting that humans are an entirely inappropriate model for drug development (though we should note that one human is not a perfect model for another).

** number of drugs which have passed Phase 3 clinical trials ÷ number of drugs which have passed Phase 1 trials = 1.2 ÷ / 8.6 = 14% of drugs which pass Phase 1 trials are eliminated by Phase 2-3 clinical trials. 100 – 14 = 86% fail.

Facts with context

Here is where it is important to understand a little about the drug development process.

Before the preclinical animal tests there are a large number of pre-preclinical non-animal tests done on all manner of research tools including computer models, automatic screening, cell cultures, microbial studies and more. These methods are used to (relatively) cheaply remove many potentially toxic, or obviously non-starting drugs from reaching the more expensive animal testing stage – greatly reducing the amount of animal research required for a drug to reach market.

So contrary to animal rights claims of alternative methods being better, the truth is that 94% of drugs that pass animal AND non-animal preclinical tests will fail in human tests.

So rather than damn just the animal tests, have animal rights activists managed to damn all of preclinical research? In short, no.

The role of preclinical animal tests is to check if the drug offers any potential therapeutic value and, importantly, if it is safe enough to move to Phase 1 trials in humans. This does not even mean free of all side effects, but to learn whether a drug can safely be given to humans and at what approximate dosage.

If you want to know how truly successful animal tests are, consider that in over 30 years there has not been a single death in a Phase 1 clinical trial in the UK. The last major incident was in 2006 in the Northwick Park trials where 6 people suffered extreme side effects in a Phase 1 clinical trial – though it should be noted that TGN1412 was a very novel type of molecule which was poorly understood. Considering that there are normally over 200 Phase I clinical trials each year in the UK (each involving multiple people), animal testing has been exceptionally effective at keeping dangerous drugs away from people.

Even Phase 1 clinical trials in humans are not intended to check for efficacy, but rather to assess whether a drug is safe enough to be tried in a larger number of patients (who are suffering from an illness the drug is intended to treat).

Furthermore, when a drug is licensed for use, it is on the basis of the clinical trials in humans, not the preclinical animal tests which exist to ensure that a drug is safe enough to move into Phase 1 trials. So when animal rights activists claim that adverse drug reactions can be blamed on animal tests approving the drug, remember that it is the clinical trials in thousands of people which provide the evidence of its safety.

Professor Robin Lovell-Badge

Head of the Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, London

A new era for embryonic stem cells

As the new president takes office and the scientific community eagerly awaits the announcement of the reversal of the ban on federal funding of most research involving human embryonic stem cells (hESC’s), there’s news that the FDA has approved the first ever trial of a treatment based on hESC’s for severe spinal cord injury.

This is a very welcome development; for a decade now hopes have been raised about the potential for hESC’s to treat a range of serious illnesses, particularly brain and spinal injuries,  but despite excellent work by organizations such as the Christopher and Dana Reeve Foundation no treatments have yet reached clinical trials in patients.  This is not a criticism of hESC’s, underneath the hype is the reality that hESC research is a very new science. After all the first hESC’s were produced by Professor James Thomson and colleagues at the University of Wisconsin-Madison a mere ten years ago, and a lot of work has been necessary to ensure that hESC therapies are safe and effective enough to justify human trials.

The treatment developed by Geron uses a type of cell known as an oligodendrocyte progenitor cell (OPC) that was derived by growing  hESC’s  under carefully controlled conditions. OPC’s  in their turn develop into oligodendrocytes, cells that forms a sheath around the nerve cells and are vital to the proper function of the nervous system.  In rat studies the scientists at Geron showed that OPC treatment could restore the ability to move after severe spinal injury.  Subsequent safety studies in rodents indicated that the injected cells remained within the nervous system and did not produce teratomas, a type of tumour produced by stem cells that have not been adequately processed to ensure they have differentiated into a more mature cell type suitable for transplantation. An important observation made during Geron’s animal studies of OPC therapy was that the therapy worked when the cells were injected 7 days after injury but not when treatment was delayed until 10 months after injury (1) indication that early treatment was vital, and leading to the decision to treat patients 7-14 days after injury in this phase I clinical trial.

If you take a look through the Geron and Christopher and Dana Reeve Foundation websites you will see that there are many other hESC based treatments under development, and appreciate the undeniable importance of animal research to this work. With a new president who appreciates the importance of hESC research we will no doubt see more announcements of this sort, but it’s also worth remembering that animal research is crucial to other types of stem cell research, including the iPS approach we’ve discussed here and other methods we discussed earlier this week on our sister blog in the UK.

Could this be the dawn of a new era in medicine?

Update 21 February 2011: After being put on hold for over a year due to potential problems with cyst formation identified in an animal study, additional animal studies have proved reassuring and the FDA gave its approval for the trial to go ahead. Geron recently announced the enrollment of  the first patient into their phase I study of hESC based therapy for spinal injury.

Regards

Paul Browne

1) Keirstead H.S. et al. “Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury” J Neurosci., Volume 25(19), Pages 4694-4705 (2005) doi:10.1523/JNEUROSCI.0311-05.

2005

92% of statistics are taken out of context…

A better response to the “92%…” argument has been written by Robin Lovell-Badge and can be found on our website here.

I thought I’d dedicate an entire post to a certain statistic which has been repeatedly misused and misunderstood by animal rights groups.

92% of drugs that test successfully in animals fail during human trials

You will find animal rights organizations, such as PETA and PCRM, all using this statistic. Often claiming that this shows that “animal research doesn’t work”.

The statistic is from the FDA (Food and Drug Administration), used to illustrate inefficiencies in drug development. However the actual statistic is much broader, it should be:

92% of drugs fail during human trials

The original quote was:

A new medicinal compound entering Phase 1 testing, often representing the culmination of upwards of a decade of preclinical screening and evaluation, is estimated to have only an 8 percent chance of reaching the market

Now it is true that they have passed animal testing to get to human (clinical) trials, but it also means that they have passed non-animal pre-clinical tests, such as in vitro. Consider:

92% of drugs that have successfully passed in vitro tests, fail during human trials

Misleading? Yes. So the next obvious question:

Why do drugs fail at the clinical stage?

Drugs fail clinical trials for two reasons – they don’t work well (lacking efficacy) or they are potentially dangerous. Drugs may fail at different stages of clinical trials – so sometimes a relatively rare, but potentially dangerous side effect turns up late into human trials when many thousands of humans are being used (late in clinical stages many more humans than other animals may have tested the drug – as more people/animals are tested, more side effects are discovered); equally some drugs may simply be ineffective in humans, or ineffective in enough humans (no one wants to release a drug that only works in, say, 30% of people – unless that 30% is a particular and selectable demographic e.g. children), this is bound to be the case since animals are not perfect models for humans, just as humans are not perfect models for other humans (thus why some people get adverse drug reactions and not others).

According to the FDA report, which suggests various improvements to the drug development process, the top area where improvements could be made is to improve the animal models (not remove, but use and improve – they also accept the good track record of animals for finding dangerous chemicals in toxicology tests), with the increase in genetically modified animals allowing us to create better animal models, hopefully we will see that 92% statistic drop.

It is worth highlighting that the FDA says many drugs are failing clinical trials at late stages, meaning that problems with drugs are not becoming clear until they are tested in many people – so it is a mystery as to why the animal rights groups try and put the blame solely on the shoulders of animal research.

What about the benefits of animal safety tests?

Well why DO we use animal safety tests? The 92% statistic ignores all the benefits of safety tests, so:
You have 1000 drugs entering animal safety tests
900 of them fail, of which, say, 20 might actually be safe in humans (false positive).
Of the remaining 100, 92 fail human tests

[The above stats are made up for illustration purposes. Approx 90% of drugs fail at the animal testing stage, and false positives aren’t (cannot legally or safely be) measured]

Therefore:

90.5% of dangerous drugs have been kept out of clinical trials thanks to animal safety tests**

(However 92%of drugs have still failed clinical trials)

**[[Dangerous Drugs removed by animal safety tests]] / [[Total number of dangerous drugs]] = [[880/972]]

We can see that the lower statistic makes no mention of the benefits of animal safety tests made clear by the top statistic.

It is worth noting that around 90% of drugs are removed at every stage of safety tests, i.e. 90% are removed at non-animal pre-clinical safety tests, 90% at animal stages, and 90% during human clinical trials.

Check back on the website for more AR debunking!

Cheers

Tom