Tag Archives: FDA

FDA response to Goodall letter found lacking

On September 25, 2017, Dr. Scott Gottlieb , Commissioner of the U.S. Food & Drug Administration (FDA) replied to a scathing letter from Dr. Jane Goodall, where Goodall denounced what she called the “cruel and unnecessary nicotine addiction experiments on monkeys”. We previously evaluated that letter from Goodall and now do the same with Commissioner Gottlieb’s letter.

The FDA Commissioner’s letter starts with an acknowledged appreciation of Goodall’s opinion and a re-statement of the FDA’s commitment to compliance with the rules and guidance governing the use of animals for research. It is indeed admirable that Commissioner Gottlieb places emphasis on compliance with the long-standing regulatory framework and guidance governing animal research in the US. What is unacknowledged in the letter is that all studies involving animals used in research, including the one that Goodall references, are continually monitored with respect to such compliance.

Gottlieb writes:

“After learning of concerns related to the study you referenced, I directed the Agency to place a hold on the research study earlier this month. Accordingly, at this time, all experimentation involving the monkeys in the study you referenced has been halted.”

Several things are surprising about this approach. Foremost, the vague reference to “concerns” when coupled with the failure to mention the review and oversight mechanisms in place, can give a public impression that is confusing. For example, is Gottlieb saying that his response is driven by Goodall and WCW? Speaking of Research, like the scientific community, supports an effective oversight system that has mechanisms for investigation and correction of animal welfare issues. In this letter, however, the Commissioner appears to bow to celebrity opinion, halting an ongoing experiment without providing evidence or acknowledgement of the continual monitoring that surrounds research. In fact, subsequent media coverage of Gottlieb’s response also conveys the impression that the decision was made directly in response to Goodall’s letter.

This is alarming on many levels. There is, for example, no acknowledgement of contact with the research institution’s federally-mandated review board (Institutional Animal Care and Use Committee, IACUC), no mention of the FDA’s process for review of research, or evaluation of records. Instead, the letter suggests that the federal agency’s decision is a bow to celebrity pressure from Goodall, who is acting on behalf of an anti-animal research organization (White Coat Waste, WCW).

Gottlieb continues:

“I asked for a medical team of primate experts to conduct a site visit to evaluate the safety and well-being of the monkeys and to understand whether there are additional precautions needed.”

This statement and the announcement of “halting” the study, absent any other information, imply that animal health and well-being are in immediate jeopardy. The evidence for that claim is not presented. If the animals were in immediate jeopardy, we would expect that the facility’s personnel would be taking action. Whether that is the case or not cannot be ascertained from Gottlieb’s letter. At the very least, the commissioner’s letter should acknowledge any ongoing efforts by his agency’s personnel—including those at National Center for Toxicological Research (NCTR).

Squirrel monkey. Source: Wikipedia Commons.

The letter can leave readers with the several wrong impressions by leaving out any information about the expertise of the existing veterinary, animal care, and scientific staff at the federal facility. Readers may be left with impression that primate experts—including scientists and veterinarians — are absent at the long-standing federal research facility, the NCTR. That is unlikely to be the case. Further, even when people with a high level of expertise and experience are present, adverse events that require thoughtful review and modifications in procedures sometimes occur. Animal research, like all human endeavors, has potential for error. Research teams, IACUCs, and regulatory bodies all play a role in making sure that those errors are addressed and corrected. Thus, in light of full transparency, actions taken by the institutional IACUC, the scientists, and the facility’s veterinarians, along with further information including the timing and venue for a public report of findings before decisions are taken need to be specified.

Gottlieb’s letter continues:

“I also appointed an independent FDA review team, led by senior career experts and with the guidance of primate veterinarians, to assess the science and integrity of the animal research process for this study. I also asked this team to evaluate whether the re-initiation of the study you referenced is necessary to fulfill FDA’s public health responsibilities, or if the study should be halted indefinitely.”

This is one of the more troubling aspects of the FDA commission’s letter as it is unclear whether he is aware that firstly, this study must have gone through rigorous review in terms of scientific merit, evaluation of the risks to the animals being used as well as the proposed benefit to humans, when it was funded. Secondly, the IACUC at this institution will have vetted all procedures being performed on these animals, including consideration of response and correction should an adverse situation occur.

Finally, separate to this letter, but parallel to this issue, an FDA spokeswoman is quoted as stating, “the agency is also considering creating a wider-ranging function that would provide for even greater oversight of the care of animals in the agency’s possession.”

This statement is alarming in its lack of specificity and requires clarification. Does it mean that FDA is conducting a re-assessment of the existing federal structure for reviewing and conducting all animal research? If so, what is the impetus for the review? How is it different from existing policies? Who is involved in the review? What is the process by which public interests in scientific research that informs public health policy will be protected and scientific objectives balanced with animal welfare? How will the public be assured that the full range of relevant expertise is included in the review? There are many additional questions—all raised by the statement, none addressed, as far as we are aware, by any other materials provided by the FDA.

Finally, it is also important, in light of full transparency that the FDA provides an update about its ongoing lawsuit with WCW. The WCW suit appears to have arisen as a consequence of the FDA’s response to a WCW freedom of information (FOIA) request for records about the NCTR research. At this time, it is unclear whether the FDA’s decision to suspend this ongoing and already scientifically-justified funded research is related to this lawsuit. The Washington Post writes:

“Goodall was enlisted in the fight against the monkey tests by the White Coat Waste Project, an advocacy group that says its goal is to publicize and end taxpayer-funded animal experiments. In January, the organization obtained 64 pages of documents on the nicotine-addiction research from the FDA under the Freedom of Information Act. It is suing the agency to get more information on the research’s costs, as well as veterinary records and photographs and videos of the experiments.”

Speaking of Research is not the only organization concerned with the FDA response. The American Psychological Association (APA), the American College of Neuropsychopharmacology (ACNP), and the College on Problems of Drug Dependence (CPDD), have jointly penned their own letter to the FDA demanding a clear explanation for the suspension of the nicotine research project. Part of it is quoted below:

“As you may be aware, Dr. Goodall’s letter to you came at the behest of an organization, White Coat Waste Project (WCW), that is fundamentally opposed to all research with nonhuman animals. Your decision to suspend the research is extremely troubling because it appears to have occurred without any substantive input from experts in the scientific community who have deep knowledge and understanding of research on substance use disorders. Furthermore, the methods and technologies used in this study have been rigorously validated and commonly used in studies of substance use disorders, including research that is funded by other federal agencies, such as the National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA).”

Speaking of Research shares the APA, ACNP and CPDD’s concerns. We hope the FDA will be forthcoming with an explanation of the suspension of the research project in question. We also hope that they will be taking the evidence of experts over the opinions of prominent celebrity scientists and animal rights groups.

Speaking of Research

Speaking of Research response to FDA announcement regarding nicotine research

For immediate release

Speaking of Research response to FDA announcement regarding nicotine research

Late on September 25, as reported by the Washington Post, the US Food and Drug Administration (FDA) made the startling announcement that it has suspended a nicotine research project involving non-human primates; the goal of this research is to build a better scientific approach to preventing and treating smoking and its associated health complications. The FDA has not yet provided evidence or clear justification for why they took this action. This lack of transparency is concerning not only for halting an important research program that had the potential to improve human health, but also for the welfare of the animals involved.

The FDA yesterday began a review of animal welfare at the National Center for Toxicological Research (NCTR) where the research was conducted. The reason given for the review is four animal deaths that occurred over an unspecified time period. Whether the deaths were associated with the research procedures is also unspecified. While it is not clear when the deaths occurred, the article and timing of the announcement followed closely after publicity from a letter by celebrity primatologist Jane Goodall to the FDA Commissioner, stating her opinion that the research should be halted. Furthermore, Dr. Goodall has aligned herself with an anti-animal research group, The White Coat Waste Project, which perpetuates the notion that research addressing the health problems associated with substance use disorders, including problematic tobacco use, in animals is unethical. Together, these events raise the extremely disturbing possibility that the FDA may have relied on claims provided by individuals with no scientific background or expertise in addiction science to make their decision, rather than on sound scientific evidence.

In an open letter posted at Speaking of Research on September 22, dozens of scientific experts, including the many of the nation’s leading scientists conducting research into drug abuse and alcoholism, expressed deep concern over Dr. Goodall’s egregious and unscientific remarks.  Research into the biological effects of nicotine using primate models has, and continues to be, critical for understanding and development of medications for tobacco use, which is unquestionably a major public health problem worldwide.  That this research could be halted due to political reasons is outrageous, and speaks to the influence of a group opposed to animal research and their celebrity allies over science that impacts the health and care of our citizens.

Dr. J. David Jentsch, a spokesperson for Speaking of Research said:

“Speaking of Research condemns the lack of transparency surrounding the decision to halt important research into understanding addiction.  We call on the FDA to provide much greater transparency on this issue, including a full explanation as to why they have cancelled the studies, and information on the findings of any and all inspections of the NCTR facility leading up to this decision.  

“We are gravely concerned over the influence that Jane Goodall and the animal rights organization The White Coat Waste Project appear to have over FDA research. Animal research remains a critical component of our understanding of disease and the development of new treatments to tackle them. The FDA must be led by the advice of the research community, not from those minimal understanding of key scientific issues.”

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Squirrel monkey.

Jane Goodall and White Coat Waste are wrong about nicotine addiction research

This open letter is from scientists and leaders in the addiction research community.  If you’d like to join the signatories listed below, please do in comments at the bottom of this article. Please also share with others with an interest in research on addiction.

Smoking – and nicotine addiction – are sometimes easy targets for criticism by many people. For others, addiction is a mental health issue of deep concern, affecting one in seven Americans during their lifetime, often resulting in immeasurable suffering and even death.  There are many reasons that addiction can be an easy target and perennial candidate for ridicule. One is that some believe addiction is “simply a matter of weak willpower,” evidence of a “moral failing,” or some other character flaw. In this, we see parallels to medieval beliefs that schizophrenia, bipolar disorder, and depression were due to witchcraft, demonic possession, wandering uteruses, and weak moral character.

Addiction is a brain disorder

Through decades of scientific study of the brain, behavior, genetics, and physiology, we now know that addiction is a complex disorder affected by neural function, genes, and the environment. We also know – at a specific level – about the brain chemistry and circuits that increase the risk for and play a role in addiction—including smoking. Unfortunately, there is still a lot we do not know, including questions such as: Why are some individuals vulnerable to addiction and others not? Why does relapse after any kind of treatment occur at such phenomenally high rates? Why do drug abusers persist in seeking and taking substances that so clearly will lead to incarceration, poverty, even death?

It is these gaps in knowledge – along with empathy for those suffering because of addiction—that lead the nation’s health research agencies to actively support addiction research. Yet, there are others who seek to end this lifesaving research. For example, a months-long campaign by the anti-animal research advocacy group White Coat Waste Project targeting nicotine addiction research recently got a boost from Jane Goodall, the celebrity primatologist known for research on chimpanzee behavior. This marks yet another high profile pairing of Goodall and groups fundamentally opposed to all nonhuman animal research. Here, Goodall wrote to the head of the US Food and Drug Administration (FDA) about research on nicotine addiction in monkeys conducted at the FDA’s National Center for Toxicological Research (NCTR).

Addiction costs the US billions each year

What Goodall claims is that the research is a misuse of taxpayer’s money because of her belief that ‘the results of smoking are well-known in humans’, and that the same research can be done in humans. Both statements are shocking, no less so because they come from a prominent scientist whose very profession is based on reporting facts.

Even a cursory glance at the state of tobacco use in the US gives some clues as to why statements like this are irresponsible: According to the National Institute on Drug Abuse (NIDA), tobacco use kills approximately 440,000 Americans each year. Given the White Coat Waste Project’s interest in saving the taxpayer’s money, the estimated economic impact of tobacco use, including everything from healthcare costs to cigarette-related fires, is almost $200 billion per year (see NIDA Research Report Series online, 2012). So, clearly nicotine addiction remains a significant public health problem and it is quite evident that we do not understand this disorder well enough to eradicate it—current treatments basically have just slowed it down. There is much work to do.

Outright wrong: the FDA nicotine research Goodall targets is not taxpayer funded

There is another blatant inaccuracy in Goodall’s letter to the FDA, namely, the very idea that this is a fraudulent waste of taxpayer’s money. In fact, the funding source for NCTR nicotine research is the Center for Tobacco Products (CTP), which was established to oversee implementation of the Family Smoking Prevention and Tobacco Control Act of 2009.

What is important here is that CTP funding comes from “tobacco user fees” charged to manufacturers of tobacco products. In other words, no taxpayer’s money is funding this research. How can the public trust any claim by Goodall and White Coat Waste if even this basic fact was ignored?

Why research with humans cannot answer the full range of questions

What is lost in the simple formulation that Goodall uses is the fact that research with humans cannot answer fundamentally important questions that are basic to progress in understanding, preventing, and treating addiction. Species other than humans take drugs. The fact that monkeys and rodents “self-administer” drugs in a manner similar to humans provides scientists with an extremely valuable model of drug addiction. The discovery of the “reward center” in the brain, the role of the chemical dopamine, even the basic principles of many behavioral therapies for addiction—all of these basic findings come from studies with monkeys and/or rodents self-administering drugs. In fact, the discovery that nicotine is the primary ingredient of tobacco products that contributes to their addictive properties, as well as the designation of nicotine as a drug of abuse, relied on self-administration studies. And yet, we are just at the beginning of understanding addiction as a brain disorder (rather than a simple moral failure or a series of bad decisions).

Instead of using monkeys in nicotine addiction research, Goodall suggests that ‘smoking habits’ can be studied ‘directly’ in humans. These two scenarios are entirely different—you don’t study ‘smoking habits’ in monkeys (who generally don’t go to the local gas station for some smokes). Smoking habits are an incredibly important part of nicotine addiction, but studying nicotine self-administration has entirely different goals. For example, the NCTR researchers are interested in brain changes following nicotine taking in adults and adolescents. What the monkey experiments allow them to do is isolate just nicotine (burning tobacco creates approximately 7000 chemicals)

and study its effects in a highly controlled environment. This approach allows the researchers to draw much firmer conclusions about effects on brain function than could ever be obtained in people smoking cigarettes. To treat nicotine addiction, we have to know precisely what nicotine does to the brain, and we need to do this in a systematic, carefully controlled manner.  We also need to know, however, what all the other chemicals are doing in order to understand the “real life” situation.  Studying nicotine alone provides a platform for going about doing those types of studies, eventually recreating the real life experiences of the tobacco abuser.

Absolutism is different from consideration of animal welfare

Research in laboratories with animals is conducted humanely, ethically, and under careful oversight guided by federal and state laws, regulations, guidelines, and by institutional policy.  Importantly, it is unclear what evidence Goodall and White Coat Waste have for any serious violations of regulations at the FDA facility. It may be the case that Jane Goodall and White Coat Waste are opposed to animal research that is conducted in order to benefit human health. That is a different argument, however, than saying that addiction research is unnecessary, that human studies are all that is needed, or that the animals are abused. We in the scientific community wholeheartedly support ethical, humanely-conducted research on addiction to nicotine and other drugs of abuse, which is in the public’s interest. At the same time, we condemn this irresponsible and factually-challenged assault on research at the NCTR.

Conclusion

We, the undersigned, support the careful, considered and regulated use of primates in addiction research. While respecting Dr. Jane Goodall as an eminent primatologist—known for her knowledge of chimpanzee behavior in the wild—we do not believe she has the necessary expertise to intervene into the scientific questions of addiction research and neuroscience. Addiction is a major public health issue worldwide, and requires and deserves close scientific scrutiny, some of which will require the use of animals.

James K. Rowlett, Ph.D., Professor and Vice Chair for Research, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Jack E. Henningfield, Ph.D., Vice President, Research, Health Policy, and Abuse Liability, Pinney Associates, Inc. and Professor, Department of Psychiatry, Johns Hopkins University School of Medicine

Marina Picciotto, Ph.D., Charles B.G. Murphy Professor of Psychiatry and Professor in the Child Study Center, of Neuroscience and of Pharmacology, Deputy Chair for Basic Science Research, Dept. of Psychiatry, Deputy Director, Kavli Institute for Neuroscience, Yale University

Travis Thompson, Ph.D., L.P., Professor, University of Minnesota; Past President of American Psychological Association Division of Psychopharmacology and Substance Abuse; Past Member, College on Problems of Drug Dependence Executive Committee

Charles P. France, Ph.D., Robert A. Welch Distinguished University Chair in Chemistry, Professor of Pharmacology and Psychiatry, University of Texas Health Science Center- San Antonio

Michael A. Nader, Ph.D., Professor of Physiology, Pharmacology, and Radiology and Director, Center for the Neurobiology of Addiction Treatment; Co-Director, Center for Research on Substance Use and Addiction, Wake Forest School of Medicine

Thomas Eissenberg, Ph.D., Professor of Psychology (Health Program) and
Director, Center for the Study of Tobacco Products, Virginia Commonwealth University

Nancy A. Ator, Ph.D., Professor of Behavioral Biology, Johns Hopkins School of Medicine

Roger D. Spealman, Ph.D., Professor of Psychobiology, Department of Psychiatry, Harvard Medical School

Kathleen A. Grant, Ph.D., Chief and Senior Scientist, Division of Neuroscience, Professor, Dept. Behavioral Neuroscience, Oregon National Primate Research Center

Alan J. Budney, Ph.D., President, College on Problems of Drug Dependence, Past President, Division of Psychopharmacology and Substance Abuse (28) and the Division on Addictions (50) – American Psychological Association, Professor, Geisel School of Medicine at Dartmouth

Peter W. Kalivas, Ph.D., Professor and Chair, Department of Neuroscience, Medical University of South Carolina

Marilyn E. Carroll, Ph.D., Professor of Psychiatry and Neuroscience, Department of Psychiatry, University of Minnesota

Craig A. Stockmeier, Ph.D., Professor, Dept Psychiatry & Human Behavior, University of Mississippi Medical Center

Janet Neisewander, Ph.D., Professor, School of Life Sciences, Arizona State University

Mary E Cain, PhD, Professor of Psychological Sciences, Past President for Behavioral Neuroscience and Comparative Psychology, Kansas State University

Wei-Dong Yao, PhD, Professor, SUNY Upstate Medical University

Lance R. McMahon, PhD, Chair and Professor of Pharmacodynamics, College of Pharmacy, University of Florida

Michael N. Lehman, Ph.D., Professor and Chair, Department of Neurobiology and Anatomical Sciences, Chairman of the Board, UMMC Neuro Institute, University of Mississippi Medical Center

Donna M. Platt, Ph.D., Associate Professor, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Michael A. Taffe, Ph.D., Associate Professor, The Scripps Research Institute

Linda J. Porrino, PhD, Professor and Chair, Wake Forest School of Medicine

Kevin B. Freeman, Ph.D., Associate Professor, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Mei-Chuan Ko, Ph.D., Professor, Wake Forest School of Medicine

Sally L. Huskinson, Ph.D., Instructor, Department of Psychiatry & Human Behavior, University of Mississippi Medical Center

Mark Smith, PhD, Professor, Department of Psychology and Program in Neuroscience, Davidson College

Daniel C. Williams, Ph.D., Associate Professor, Director, Division of Psychology, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center

Eric J. Vallender, PhD, Associate Professor, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center

Matthew Banks, PharmD, PhD, Assistant Professor of Pharmacology and Toxicology, Virginia Commonwealth University

Paul May, Ph.D., Department of Neurobiology & Anatomical Sciences, University of Mississippi Medical Center

Juan Carlos Marvizon, Ph.D., Adjunct Professor, UCLA, VA Greater Los Angeles Healthcare System

Catherine M. Davis, PhD, Assistant Professor, Division of Behavioral Biology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine

Klaus A. Miczek, Ph.D., Moses Hunt Professor of Psychology, Psychiatry, Pharmacology, & Neuroscience, Tufts University, Department of Psychology

Wendy J. Lynch, Ph.D., Associate Professor of Psychiatry and Neurobehavioral Sciences, University of Virginia

Michael T. Bardo, Professor of Psychology, Director, Center for Drug Abuse Research Translation (CDART), University of Kentucky

Xiu Liu, MD, PhD, Professor, Department of Pathology, Associate Director, Graduate Program in Pathology, University of Mississippi Medical Center

Katherine Serafine, PhD, Assistant Professor of Behavioral Neuroscience University of Texas at El Paso, Department of Psychology

Robert L. Balster, PhD,  Butler Professor of Pharmacology and Toxicology, Research Professor of Psychology and Psychiatry, former CoDirector of the Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, VA

David Jentsch, Ph.D., Professor of Psychology, Binghamton University

William W. Stoops, Ph.D., Professor, University of Kentucky College of Medicine

Jack Bergman, Ph.D., McLean Hospital / Harvard Medical School

Barry Setlow, PhD, Professor, Department of Psychiatry, University of Florida College of Medicine

Doris J. Doudet, PhD, Professor, Dept. Medicine/Neurology, University of British Columbia

Leonard L. Howell, PhD, Professor of Psychiatry and Behavioral Sciences, Emory University

S. Stevens Negus, PhD, Dept. of Pharmacology and Toxicology, Virginia Commonwealth University

Carrie K. Jones, Ph.D., Director, In Vivo and Translational Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University

 

 

 

 

 

 

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