Intentional Human Dosing Studies for EPA Regulatory Purposes Scientific and Ethical Issues (2004) / Chapter Skim
Currently Skimming:
Executive Summary and Recommendations
Executive Summary and Recommendations
Pages 1-20
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 1... ...
EPA commissioned The National Academies to provide advice on the vexing question of whether and, if so, under what circumstances EPA should accept and consider intentional human dosing studies conducted by companies or other sources outside the agency (so-called third parties) to gather evidence relating to the risks of a chemical or the conditions 1
|
From page 2... ...
; and (5) the extent to which, and how, the submitter of research with human subjects should be required to document or otherwise demonstrate compliance with appropriate standards for the protection of human research participants (see Chapters 3, 5, and 6)
|
From page 3... ...
Although it is not unusual or controversial for EPA to rely on human-derived data in its risk assessments, such data are typically derived from case reports, observational studies, or epidemiological studies that do not involve intentional dosing of humans. In part, the pesticide studies involving humans are controversial because they were conducted by economically interested third parties, whose motivation was to justify reducing the interspecies uncertainty factor, thereby increasing the acceptable or safe human exposure level and possibly permitting the continuation of certain pesticide uses that might otherwise have been precluded under FQPA's new safety standards.
|
From page 4... ...
and to broaden the issue to encompass third-party human dosing studies related not only to pesticides but also to EPA's other chemical regulatory programs, including those addressing toxic air pollutants and drinking water contaminants. EPA also asked the committee to consider the scientific basis that an otherwise ethically sound human study could rely on to alter the interspecies uncertainty factor.
|
From page 5... ...
· Intentional human dosing studies that are to be used only to improve the accuracy of an RfD, and that otherwise provide no health or environmental benefit, can be justified only when there is reasonable certainty that participants will experience no adverse effects. · All of the recognized ethical standards and procedures for protecting the interests of study participants are observed, including equitable selection and recruitment of participants, informed consent, and independent review of the scientific and ethical merits of the study by an Institutional Review Board (IRB)
|
From page 6... ...
, human dosing studies can generate different kinds of societal benefits as well, such as benefits to human health or the environment, depending on the nature of the scientific question a study seeks to answer, the uses to which the study results may be put, and the consequences that may flow from those uses. In cases in which such additional benefits are present, they can be considered in determining the extent of the potential risk to which participants may justifiably be exposed, and such additional health or environmental benefits are required to justify the consideration of a human dosing study that is not in the "no identifiable risk" or "reasonable certainty of no harm" categories.
|
From page 7... ...
Balancing Risks and Benefits Even if scientifically valid, an intentional human dosing study is not ethically acceptable unless the benefits it provides to the participants or to 3The order of the recommendations in this executive summary does not match the order in which they appear in the full report. For clarity, in this summary, the recommendations are provided in an order more conducive to a shorter format with abbreviated discussion.
|
From page 8... ...
In light of the nature and purpose of the human dosing studies that prompted this report, one of the critical questions the committee addressed was whether an intentional human dosing study anticipated to improve the scientific accuracy of EPA's decisions -- for example, by raising the RfD -- but not to directly enhance health or environmental protection confers a societal benefit. The committee carefully considered the congressional judgments and intent underlying EPA's chemical regulatory programs, including the requirement that EPA use the best available scientific evidence in making its regulatory decisions.
|
From page 9... ...
Recommendation 4-1: Value of Studies That Seek to Improve the Ac curacy of EPA's Decisions But Do Not Provide a Public Health or Environmental Benefit EPA should consider a human dosing study intended to reduce the interspecies uncertainty factor (for example, a study of a biomarker such as cholinesterase inhibition) as conferring a societal benefit only if it was designed and conducted in a manner that would im prove the scientific accuracy of EPA's extrapolation from animal to human data.
|
From page 10... ...
Necessary conditions for scientifi cally and ethically acceptable intentional human dosing studies in clude: a. prior animal studies and, if available, human observational studies; b.
|
From page 11... ...
Recommendation 5-2: Participant Selection Criteria IRBs reviewing intentional human dosing studies should ensure that the following conditions are met in selecting research partici pants: a. Selection should be equitable.
|
From page 12... ...
They should not be regarded as inflexible requirements that must be applied in every case. Recommendation 5-4: Best Practices in Informed Consent EPA should develop and disseminate to relevant IRBs, investiga tors, and sponsors a list of best practices regarding informed con sent in intentional human dosing studies.
|
From page 13... ...
Creation of a Comprehensive EPA Human Studies Review Process EPA is a signatory agency to the Common Rule, which requires, at a minimum, that human research protocols undergo review by an IRB and that participants provide voluntary informed consent. The Common Rule applies to human research sponsored by EPA as well as any research performed at an institution that has committed to have all research reviewed by an IRB as part of its assurance of compliance.
|
From page 14... ...
The committee concludes that another level of review is needed for intentional human dosing studies in order to add a supplementary layer of protection and to establish a body of knowledge and expertise with regard to these studies that can then be communicated to the public and the research community. Recommendation 6-2: Human Studies Review Board To ensure that intentional human dosing studies conducted for EPA regulatory purposes meet the highest scientific and ethical stan dards, EPA should establish a Human Studies Review Board to ad dress in an integrated way the scientific and ethical issues raised by such studies.
|
From page 15... ...
The proposed board supplements but does not replace the IRB. Its principal function would be to help assure that EPA considers only intentional human dosing studies that meet the rigorous scientific and ethical standards specified in this report.
|
From page 16... ...
It is the committee's view that the Human Studies Review Board is advisory only and is not a replacement for the scientific review EPA must perform in making regulatory decisions. EPA's Use of Data from Studies of Cholinesterase Inhibition The committee was asked to evaluate the use of data from intentional human dosing studies in EPA's risk-assessment process.
|
From page 17... ...
, in which proponents of intentional dosing studies in humans must document that the endpoints to be measured are the critical determinants of risk, represent a substantial hurdle. Recommendation 7-2: Use of Existing Cholinesterase Inhibition Studies The cholinesterase inhibition studies that already have been sub mitted to EPA, if determined to be scientifically valid and justified for EPA's regulatory purposes, may be considered for use in risk assessment and standard setting if they were not unethically con ducted (see Recommendation 5-7)
|
From page 18... ...
The committee concluded that, as a general rule, EPA should not use data from ethically problematic studies to inform its regulatory efforts. In an extraordinary case, when data from ethically problematic studies appear to warrant a regulatory standard that would provide better protection for public health, the Human Studies Review Board may recommend that EPA convene a special, outside panel, which should reach its judgment by considering:
|
From page 19... ...
In order to strongly deter sponsors and researchers from conducting unethical studies, data from such studies should not be used to favor the sponsor's interests in loosening regulatory standards. Recommendation 5-6: Studies Completed After Implementation of the New Standards EPA should operate on the strong presumption that data obtained in studies conducted after implementation of the new rules1 that do not meet the ethical standards described in this report will not be considered in its regulatory decisions.
|
From page 20... ...
Exceptional cases in which the Human Studies Review Board determines that unethically conducted studies may provide valid information to support a regulatory standard that would provide greater protec tion for public health should be presented to a special outside panel, described in Recommendation 5-6, for consideration. This special panel should consider recommending the use of such data only with the additional requirement that the ethical concerns raised by the study are documented and made publicly available.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.