“We live in an era of unprecedented innovation in pharmaceuticals, diagnostics, medical devices, and food and nutrition science. Such innovation offers unprecedented opportunities to advance and improve public health. It is essential that we at FDA keep pace with these changes, especially the evolving science that underpins them, in order to fulfill our regulatory responsibilities effectively and efficiently.” Stephen Ostroff, M.D. , Acting Commissioner of Food and Drugs, Remarks at 2015 FDLI Annual Conference Washington, D.C. April 20, 2015.
“Right now, we spend 15 years and half a million dollars or more in development, the drug gets tested in 10,000 patients and usually fails. You then do statistical number crunching to find the subpopulation that might respond, and if you’re lucky you find it, and then have to repeat the process. These (developments) allow you to take advantage of primary cells and stem cells from patients and you can do it for subpopulations.” Don Ingber, Keynote presentation at SLAS 2015.
“NCATS aims to get more treatments to more patients more efficiently,” said NCATS Director Christopher P. Austin. “That is exactly why we are supporting the development of human tissue chip technology, which could be revolutionary in providing a faster, more cost-effective way of predicting the failure or success of drugs prior to investing in human clinical trials.” Vanderbilt Research News, Vanderbilt’s neurovascular chip project moves into new phase by David Salisbury Nov. 18, 2014.
"If I did something in my academic lab that was wrong 50-60% of the time, even 30% of the time, people would think I was nuts, but thats how this industry works. We need to change how we approach this." Don Ingber, M.D., Ph.D, Wyss Institute at Harvard at Microphysiological Systems Program Workshop at the FDA , May 2013
"We have moved away from studying human disease in humans. We all drank the Kool-Aid on that one, me included." With the ability to knock in or knock out any gene in a mouse -- which "can't sue us," Zerhouni quipped -- researchers have over-relied on animal data. "The problem is that it hasn't worked, and it's time we stopped dancing around the problem...We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans." (Former NIH Director Dr. Elias Zerhouni, at NIH Record, Vol. LXV No. 13, June 21, 2013)
"A major problem in the pharmaceutical industry right now is that the drug development model is actually broken. It just does not work. It takes many, many years to get a drug to market, its incredibly expensive, innumerable animal lives are lost and then the results from animals usually don't predict what happens in humans. So this is a huge cost to the economy and to the pharmaceutical industry." Dr. Don Ingber, director of Harvard University's Wyss Institute of Biologically Inspired Engineering. Technology Review, July/August 2012
"The adoption of the precautionary principle by the regulatory authorities and the relative ease with which this burden of proof is accepted by the pharmaceutical industry without attempts to improve the current paradigm has created a stalemate in which animal studies, predictive or not, continue to exist with little room for innovation. Stakeholders in industry, academia, and regulatory agencies, need to critically assess animal studies and discuss their predictive value in all earnestness and with the scientific facts at hand. From this, possibilities based on scientific facts may develop which allow new technologies to be implemented that predict the safety and efficacy of therapeutics equal to or better than animal studies do. A way forward would be for the pharmaceutical industry to share clinical and laboratory data generated at all stages of product development with collaborating stakeholders, to enable a complete and transparent analysis of the predictive value of animal studies for drug development." Regulatory Toxicology and Pharmacology 64 (2012) 345349
"Testing the toxicity of pharmaceutical candidates in lab animals to support the safety for human clinical trials is notoriously unreliable. Often compounds that appear safe in rodents prove to be toxic in humans." Dr. Aaron Heifetz, Drug Discovery World, Fall 2011, p102011
"The use of small and large animals to predict safety in humans is a long-standing but not always reliable practice in translational science. New cell-based approaches have the potential to improve drug safety prediction before use in patients." Reengineering Translational Science: The Time is Right. Francis S. Collins, Director, National Institute of Health, Science Translational Medicine, July 6, 2011 Vol 3 Issue 90
"With earlier and more rigorous target validation in human tissues, it may be justifiable to skip the animal model assessment of efficacy altogether." Francis S.Collins, Director, National Institute of Health, Science Translational Medicine, July 6, 2011 Vol 3 Issue 90
"Indeed, because oncology drugs have a success rate of only 5%, it is clear that animal models are only marginally effective." M.B. Esch, T.L. King and M.L. Shuler, The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies, Annu. Rev. Biomed. Eng. 2011. 13:5572 (doi:10.1146/annurev-bioeng-071910-124629)2010
"Mice are mice, and people are people. If we look to the mouse to model every aspect of the disease for man, and to model cures, we're just wasting our time.... [The mouse] has cost us a new generation of medicines... The vast majority of the money that we spend in clinical trials based on mouse data is completely wasted... We keep getting led down the garden path. We've had thousands of mouse studies of tuberculosis, yet not one of them has ever been used to pick a new drug regimen that succeeded in clinical trials. This isn't just true for TB; it's true for virtually every disease. We're spending more and more money and we're not getting more and more drug candidates." Clif Barry, Chief of the Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, November, 2011 Read more.
"In animal models of acute ischemic stroke, about 500 neuroprotective treatment strategies have been reported to improve outcome, but only aspirin and very early intravenous thrombolysis with alteplase (recombinant tissue-plasminogen activator) have proved effective in patients, despite numerous clinical trials of other treatment strategies." Van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, et al. (2010) Can Animal Models of Disease Reliably Inform Human Studies? PLoS Med 7(3): e1000245. doi:10.1371/journal.pmed.1000245 March 30, 2010
"We want to migrate away from animal testing. We also want to see drug development become more efficient so that fewer resources are wasted." David Jacobson-Kram, executive director for pharmacology and toxicology, FDA, Bloomberg News, 5 August 2010
"Along the path to marketing, the product is subjected to a series of evaluations to predict its safety and effectiveness and to enable its mass production. Despite extensive investment in basic biomedical science over the past three decades, there has been very little change in the science of the development process. The sophisticated scientific tools used in drug discovery and lead optimization are generally not utilized in the pre- clinical and clinical development stages. Instead, traditional empirical evaluation is used in both animal and human testing. We are using the tools of the last century to evaluate this centurys advances." The FDA Critical Path Initiative and Its Influence on New Drug Development, Janet Woodcock and Raymond Woosley Center for Drug Evaluation and Research, 2008
"Unfortunately, novelty does not easily penetrate into the pharmaceutical environment and, in particular, the very conservative world of safety sciences, which all too readily responds with the often heard boring refrain of 'the regulators won't accept these new approaches'! The safety science community should be reminded that regulators expect them to take the initiative to improve their sometimes catastrophic record in predicting clinical drug safety as a result of their investigational efforts." Dr. Icilio Cavero, reporting on a Safety Pharmacology Society workshop held at Pfizer, Kent, 13th February 2007. Expert Opinion Drug Safety, 6(4):465-471.
"We have learned well how to treat cancer in mice and rats but we still cant cure people." Professor Colin Garner, quoted in Accelerator MS Is a Powerful New Tool, Genetic Engineering & Biotechnology News, Vol. 27, No. 15. 2007
"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." Mike Leavitt, Secretary of Health and Human Services, U.S. Department of Health and Human Services (Food and Drug Administration press release, FDA Issues Advice to Make Earliest Stages of Clinical Drug Development More Efficient, January 12, 2006).
"Consider just one stark statistic: Today, nine out of 10 compounds developed in the lab fail in human studies. They fail, in large part because they behave differently in people than they did in animal or laboratory tests." Andrew C. von Eschenbach, M.D. then Acting Commissioner of the FDA (prepared statement for FDA Teleconference: Steps to Advance the Earliest Phases of Clinical Research in the Development of Innovative Medical Treatments, January 12, 2006).
"Even when drugs with evidence of anticancer activity in preclinical in vivo models are given at their maximum tolerated doses, they frequently fail to produce useful activity in humans." Sausville & Burger, Cancer Research, 66, 3351-3354, April 1, 2006
"You really have to design the medicine for the species of interest ... You'll find it very rare to find a medicine that will work in both." Patrick M. O'Connor, head of oncology research for Pfizer, quoted in The New York Times, November 24, 2006
"Given that many of these investigational anticancer drugs eventually fail, the animal models on which clinical trials are predicated must at best be limited in power, and at worst wildly inaccurate." Dr Alexander Kamb, Global Head of the Oncology Disease Area at the Novartis Institutes for Biomedical Research, Nature Reviews Drug Discovery, 4, 161 - 165.
"The problem with animal carcinogenicity tests is not their lack of sensitivity for human carcinogens, but rather their lack of human specificity. A positive result has poor predictive value for humans." Knight, Bailey & Balcombe, British Medical Journal USA, Vol. 5, p477.
"Most of the animal tests we accept have never been validated. They evolved over the past 20 years, and the FDA is comfortable with them." Anita O'Connor, Office of Science, FDA 1998 (personal communication).
"It's been well known for maybe two decades that many of these preclinical human cancer models have very little predictive power in terms of how actual human beings — actual human tumours inside patients — will respond ... Preclinical models of human cancer, in large part, stink ... Hundreds of millions of dollars are being wasted every year by drug companies using these [animal] models ..." Prof. Robert Weinberg, Massachusetts Institute of Technology, Fortune, March 9, 2004
"The main causes of failure in the clinic include safety problems and lack of effectiveness: inability to predict these failures before human testing or early in clinical trials dramatically escalates costs. For example, for a pharmaceutical, a 10-percent improvement in predicting failures before clinical trials could save $100 million in development costs per drug." Innovation or Stagnation Challenge and Opportunity on the Critical Path to New Medical Products, FDA March, 2004
"The traditional tools used to assess product safety animal toxicology and outcomes from human studies have changed little over many decades and have largely not benefited from recent gains in scientific knowledge. The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, after marketing." Innovation or Stagnation Challenge and Opportunity on the Critical Path to New Medical Products, FDA March, 2004
"Despite some efforts to develop better methods, most of the tools used for toxicology and human safety testing are decades old." Innovation or Stagnation Challenge and Opportunity on the Critical Path to New Medical Products, FDA March, 2004
"In Tamoxifen's case, a drug first developed as a potential contraceptive languished for many years before its present application was found. Furthermore, its propensity to cause liver tumours in rats, a toxicity problem that thankfully does not carry over into humans, was not detected until after the drug had been on the market for many years. If it had been found in preclinical testing, the drug would almost certainly have been withdrawn from the pipeline." Nature Reviews Drug Discovery 2003; 2:167.
"In the face of these shortcomings, many experts believe the scientific value of the 2-year bioassay is highly limited—barely worth the investments in personnel, animals, money, and time." Charles W. Schmidt (Schmidt CW, 2002).
"HIV/AIDS [animal] models have not yielded a clear correlate of immunity nor given consistent results on the potential efficacy of various vaccine approaches." Johnston MI. The role of nonhuman primate models in AIDS vaccine development. Molecular Medicine Today 2000; 6: 267-270.
"The standard carcinogen tests that use rodents are an obsolescent relic of the ignorance of past decades." Philip Abelson, Editor of Science. Science (1990), Sep 21, p 1357.
"Ultimately, the answers to many of our questions regarding the underlying pathophysiology and treatment of stroke do not lie with continued attempts to model the human situation more perfectly in animals, but rather with the development of techniques to enable the study of more basic metabolism, pathophysiology and anatomical imaging detail in living humans." Wiebers DO, Adams HP, Whisnant JP. Animal models of stroke: Are they relevant to human disease? Stroke 1990; 21: 1-3.
"Candidate antivirals have been screened using in vitro systems and those with acceptable safety profiles have gone directly into humans with little supportive efficacy data in any in vivo [animal] system. The reasons for this are complex but certainly include the persistent view held by many that there is no predictive animal model for HIV infection in humans." Wyand MS. The use of SIV-infected rhesus monkeys for the preclinical evaluation of AIDS drugs and vaccines. AIDS Research and Human Retroviruses 1992; 8: 349-356.
"We always have a battle on the issue of what to do with the animal data." Dr. Edward Stein, Health Scientist, US Occupational Safety and Health Administration (Brinkley, 1993).
"So much evidence has accumulated that chemicals frequently have wholly different effects in animals and humans that officials throughout government and industry often do not act on the studies findings." Brinkley, Joel, New York Times, Many say lab-animal tests fail to measure human risk, March 23, 1993, p A1.
"The US National Cancer Institute tested 40,000 plant species on animals for anti-tumor activity. From all this, all positive animal results were useless for humans. A lab handbook concluded, despite 25 years of intensive work and positive results in animals not a single anti-tumor drug emerged from this work." JCW Salen Animal Models Principles and Problems in Handbook of Laboratory Animal Science Sevendsen and Hau (eds) 1994, p4
"We have relied too heavily on animal testing, and we believed in it too strongly. Now, I think we are commencing to realize that what goes on in an animal may not necessarily be applicable to humans." Marvin Pollard, former president of the American Cancer Society. Expressions 2 (1994) New England Anti-Vivisection Society, p4. (Available from New England Anti-Vivisection Society)
"The US National Cancer Institute treated mice growing 48 different human cancer with which they had been implanted. They used 12 different drugs which were proven successful in humans, and in 30 cases the drugs were useless in mice." Science vol 278 7th Nov 1997, p1041
"The history of cancer research has been a history of curing cancer in the mouse," said Dr. Richard Klausner, director of the National Cancer Institute. "We have cured mice of cancer for decades--and it simply didn't work in humans." Dr. Richard Klausner, director of the National Cancer Institute, Los Angeles Times article Cancer Drugs Face Long Road From Mice to Men May 6, 1998.
"The extensive animal reproductive studies to which all new drugs are now subjected are more in ...the nature of a public relations exercise than a serious contribution to drug safety." Prof R W Smithells, Monitoring for Drug Safety, ed. Inman, p 306-313. 1980
"The methods of assessing toxicity in animals are largely empirical and unvalidated...It is urgently necessary to know whether the tests as in fact conducted have sufficient predictive value to be justifiable, or whether they are a colossal waste of resources to no good purpose." Professors Laurence, McLean and Weatherall, writing in the introduction to their book, Safety Testing of New Drugs - Laboratory Predictions and Clinical Performance, ed. DR Laurence, AEM McLean & M Weatherall, publ. Academic Press, 1984.
"Drugs known to damage the human fetus are found to be safe in 70% of cases when tried on primates." Developmental Toxicology: Mechanisms and Risk, p313, McLachlan, Pratt, and Markert (Eds). 1987
"...there is no ideal animal model to extrapolate teratogenicity results to human exposure because of species sensitivity and species difference." Dr. Lin, In Vitro Toxicology, vol 1. 1987
"Extrapolating from one species to another is fraught with uncertainty...For almost all of the chemicals tested to date, rodent bioassays have not been cost- effective. They give limited and uncertain information on carcinogenicity, generally give no indication of mechanism of action, and require years to complete. [They are] rarely the best approach for deciding whether to classify a chemical as a human carcinogen." Dr. Lester Lave, of Carnegie Mellon Univ., and Drs. Ennever, Rosenkrantz and Omenn, writing in Nature, Vol 336, p 631, 1988.
"Surely not even the most zealous toxicologist would deny that epidemiology, and epidemiology alone, has indicted and incriminated the cigarette as a potent carcinogenic agent, or would claim that experimental animal toxicology could ever have done the job with the same definition." Dr. Michael Utidjian, writing in Perspectives in Basic and Applied Toxicology, p 309-329, ed. Bryan Ballantyne, publ. Butterworth, 1988.
"As a cancer specialist engaged in clinical practice, I can't agree with the researchers who believe that results obtained with laboratory animals are applicable to human beings." Dr Heinz Oeser, Quick, March 15, 1979
"Animal studies are done for legal reasons and not for scientific reasons. The predictive value for such studies for man is meaningless which means our research may be meaningless." Dr.James D. Gallagher, Director of Research of Lederle Laboratories in the Journal of the American Medical Association, March 14, 1964