Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders Proceedings of a Workshop (2017) / Chapter Skim
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6 Ethical Considerations
6 Ethical Considerations
Pages 45-54
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From page 45... ...
. • Natural history studies provide information about disease trajec tories across the life span and can inform decisions about how to ensure that clinical trials adhere to ethical guidelines, including 45
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From page 46... ...
The first relates to the identification of safeguards that may be needed before moving into human trials in the absence of predictive models of efficacy. The second is the need to ensure adequate capacity and consent from vulnerable populations, including children, individuals who may be compromised intellectually, as well as patients who are willing to subject themselves to considerable risks when therapeutic alternatives are not available.
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From page 47... ...
Nonetheless, preclinical evidence in support of a study may exist in the form of mechanistic research that examines fundamental aspects of pathophysiological processes. The important point to remember, said Kimmelman, is that a clinical trial should be initiated only when preclinical studies support a well-grounded hypothesis and when the trial has a high or reasonable probability of clinical application.
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From page 48... ...
Not going forward with research and thus not identifying beneficial therapies presents ethical concerns, added Farahany. The question about human protection regulations for early-phase trials leads to Kimmelman's fourth point, that the ethics of prelicensed drug trials involve factors beyond human protection.
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From page 49... ...
Todd Sherer raised more ethical questions related to the risks and benefits of clinical trials and disclosure. When a study establishes a subset of a population based on genetic or clinical characteristics so that a genetic or other risk factor may be uncovered, how much information -- such as individual research results, which some participants may want -- should be disclosed and how much should be added to the consent process to inform participants without adding substantial additional burden?
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From page 50... ...
they pose a minor increase over minimal risk, Dresser said.3 This latter category allows more leeway for children with preexisting health problems who face higher risks in their everyday life, and also includes research that does not offer direct benefit, but presents only a minor increase over minimal risk. Dresser said there is another important category in which studies that do not meet these requirements can be approved by the Secretary of the Department of Health and Human Services or the FDA Commissioner and Institutional Review Board after consultation with appropriate experts and a public comment period, if they advance important knowledge related to the condition and are conducted "in accordance with sound ethical principles." 3 For more information on ethical guidelines concerning clinical trials for children, including definitions of risk categories, go to https://www.hhs.gov/ohrp/regulations-andpolicy/guidance/special-protections-for-children/index.html (accessed February 1, 2017)
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From page 51... ...
INCLUDING PATIENT PERSPECTIVES AND NATURAL HISTORY OF DISEASE IN ETHICS DISCUSSIONS Bringing the patient perspective into ethics discussions early in the drug development process can be very valuable, both to educate investigators and to help avoid downstream consequences, said Bruijn. Dresser concurred, adding that, in her opinion, the experienced research subject is an underused resource.
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From page 52... ...
Even for conditions with less lethal consequences, natural history studies can be informative, added Steve Hyman. For example, he recalled a pharmacoepidemiologic study from decades ago that showed that one in a thousand children in America between the ages of 3 and 5 were getting Ritalin despite an absence of clinical trials data.
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From page 53... ...
ETHICAL CONSIDERATIONS 53 peration that some patients feel, the field needs to determine under what conditions this might be appropriate, she said.
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