Petition calls on FDA to amend informed consent requirements

The petition criticizes the use of animal models as a means of predicting the efficacy of drugs in humans

The Center for Responsible Science has asked the US FDA to adopt informed consent rules which ensure that trial participants know the experimental drugs they receive may be unsafe or ineffective.

The Center takes particular issue with the use of animal models as a means of predicting the efficacy of drugs in humans, though it does not suggest an alternative to animal research.

Despite scientific data demonstrating that preclinical animal models are poorly predictive of human response, animal models continue to be treated as the gold standard for preclinical testing under the current drug development paradigm,” the Center says in its petition. “This dichotomy illustrates that the alleged ‘gold standard’ title is meaningless. When the FDA informed consent regulations were enacted, it was not known that 92% of all drugs could fail human clinical testing.”

As far as compelling evidence suggesting that animal models are poor predictors of human response to a drug, the Center points to a 2007 systematic survey that found that 18 of 20 reviews published in peer-reviewed journals indicate animals are insufficiently predictive of human clinical or toxicological outcomes study, and showed limited concordance between treatment effects in animal experiments and subsequent clinical trials in humans. In studying adverse reactions, another study found that only 46% of visible human adverse reactions occurred in animals, “making the predictive likelihood of adverse reactions akin to the results of a coin toss,” the Center says.

In fact, for the vast majority of Phase I clinical trials no therapeutic benefit is expected, and in Phase II and III clinical trials such benefits are unlikely. The misconceptions that clinical trials subjects experience reflect a deficiency in the informed consent process,” the Center notes, adding, “Inter-species differences in drug pharmacodynamics and pharmacokinetics result in extrapolation issues. As a result, data from preclinical animal testing often does not translate to expected results in human clinical trials.”


The Center specifically requests that the agency amend its existing elements of informed consent to note: “The drug you will be given has been tested in animals and by other laboratory methods to determine whether it is likely to be safe and effective in humans. The decision to allow testing of this drug on humans relies heavily on the presumption that animal tests predict human response. Due to differences between animals and humans, animal tests may not predict whether a drug is safe and/or effective for use in humans.”

In addition, the Center calls for the FDA to note that the drug taken by a clinical trial participant “may later prove to be either unsafe for humans or ineffective in treating the condition for which it is being tested. You should not assume the drug will treat a medical condition you may have, because a determination of efficacy in an animal study does not necessarily predict efficacy in humans.”

The amendments, according to the Center, would help to ensure that trial subjects receive all information that a reasonable human subject participating in a clinical drug trial would find material. “Accordingly, the regulations must be updated to ensure that every prospective trial participant receives the information necessary to evaluate the real risks posed and to provide true informed consent,” the Center adds.

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