The following are general instructions for sponsors preparing documents for sponsors preparing documents for TERA Peer Reviews and Consultations. Particular reviews or consultations may differ somewhat to meet the needs of the documentation to be reviewed and the sponsors. These are meant as general guidance. More specific guidance is provided by TERA staff in consultation with sponsors.
A documentation package should be prepared by the sponsors to provide a comprehensive review of the data and analyses used to support the conclusions. For a chemical assessment the sponsor would prepare of package to document and support the risk value and scientific rationale behind it. TERA staff will work with the sponsor to suggest appropriate documentation and format. The documentation package should be submitted to TERA 8 weeks prior to the review meeting (usually a draft document is provided to TERA at least 12 weeks prior to the meeting dates for a screening). The following is an example documentation package for a review of a risk assessment value such as a reference dose.
1. A supporting risk assessment document that provides a discussion of all relevant literature and the rationale for the risk values. Tables summarizing studies and pertinent details are very helpful. A suggested format for document is as follows.
- Executive Summary
- Hazard Characterization discussion of human and animal data, including mode of
- Discussion of critical endpoint and study
- Discussion of dose/concentration (and human equivalent calculations), and
- Discussion of uncertainty factors or extrapolation method/models
- Discussion of the confidence in the overall assessment
2. A brief 3-5 page summary of the derivation of the toxicity value, following the format of an ITER Level 3 summary
3. A copy of the literature search strategy indicating the databases and years searched.
4. Copies of the critical study(ies), supporting studies and other significant data.
5. Results from model runs (e.g., benchmark dose modeling).
6. Results of any previous peer reviews and other organizations' risk values
7. Discussion of any outstanding issues and/or ongoing studies.
8. Identification of important issues or questions for the panel to discuss.
TERA staff will screen the draft package to ensure it is complete and that the review will be effective. A Charge for Peer Reviewers/Consultants will be prepared by TERA which will outline the issues and questions to guide the review. Panel members will be sent the complete package of materials and Charge one month prior to the meeting and will have reviewed it carefully before the meeting. Panel members are asked to provide preliminary comments prior to the meeting to assist the sponsor/authors in identifying additional issues to be addressed.
Presentation and Discussion
At the meeting, the sponsors/authors will briefly present their assessment and answer questions from the panel. Depending on the complexity of the review, the sponsors/authors may be asked to make more than one presentation (e.g., a presentation on hazard characterization and another on dose-response). Powerpoint slides, overheads and/or handouts are encouraged. Because the reviewers have read the materials before the meeting, this presentation should briefly cover the highlights and emphasize the issues in about 15-30 minutes total. The following is a suggested outline for the author's presentation for a chemical assessment with risk values.
1. A brief overview of the available toxicity literature and gaps
2. Hazard Characterization
- mode of action
- choice of critical study and rationale
- choice of critical effect and rationale
- other issues as needed
3. Dose Response
- availability of pharmacokinetic data/models
- choice of dose response model and rationale
- other issues as needed
The panel members may then ask clarifying questions, followed by a systematic discussion of the key data and decisions. The panel members will be asked to make recommendations and identify outstanding issues.
Reviews of chemical specific assessments are conducted on the basis of the methodology identified by the sponsor/authors, and reviewers will be provided with documentation of the chosen methodology (e.g. U.S. EPA Risk Assessment Guidelines). Discussions on the risk assessment methods are not generally pursued, unless the sponsor requests such discussion.
If a panel member finds the assessment unacceptable, he or she will be asked to explicitly state what additional work would be needed to make the assessment acceptable. The panel member may be asked to work with the sponsoring group to resolve the issues prior to submittal for a subsequent review. For peer reviews where the goal is to reach consensus, there are four possible outcomes:
1. the assessment is endorsed as written,
2. the assessment is endorsed after some items are revised,
3. the assessment has major problems that precludes consensus, or
4. the assessment is rejected.
If there are major problems that preclude consensus, the sponsor/authors may revise and resubmit the assessment for a future review.
A TERA scientist takes notes of discussions and conclusions, and provides a draft meeting report to the panel members for comment and concurrence. The final approved draft report is made available to the public on the Meeting Reports webpage.
Inclusion of Chemical Assessments on ITER Database
A peer review panel can recommend an approved assessment or risk value for inclusion on the ITER database if the sponsor desires. The ITER Program Manager will review the request and recommendation to insure that the assessment or value meets the following criteria:
1. Independent peer review with documentation of process and results.
2. Assessment follows an identified, commonly used methodology (e.g., U.S. EPA, IPCS, Health Canada ).
3. Significant recommendations of the peer review panel for revisions have been followed.
4. Potential and real conflicts of interest are clearly identified, real conflicts of interest are avoided, and the process for managing these issues is clearly described.
5. Final meeting summary, assessment summary and supporting documents are made available to anyone upon request.