Peer Review Process
July 13, 2007 - EPA announced in a July 2007 Federal Register Notice (PDF) (4 pp, 67K, About PDF) the approach it intends to take for conducting peer reviews of the Tier 1 screening assays and Tier 2 testing assays that are being validated. The Federal Register notice also announced EPA's approach for conducting the peer review of the Tier 1 battery.
- EDSP Work Products for Peer Review
- Peer Review Process for Tier 1 Assays
- Peer Review Process for Tier 1 Battery
- Peer Review Process for Tier 2 Assays
EPA is validating assays that are candidates for inclusion in the Tier 1 screening battery, selecting the appropriate screening assays for the screening battery based on the validation data, and developing and validating Tier 2 tests. Validation is defined as the process by which the reliability and relevance of test methods are evaluated for a specific use. EPA has implemented the validation process in several phases:
- Preparing detailed review papers (DRPs) that involve a search of the relevant scientific literature and development of a document that discusses the scientific basis of each assay and critically evaluates candidate protocols.
- Conducting pre-validation studies that demonstrate and optimize the assay, with the end result being a standardized protocol for use in the multi-laboratory validation phase.
- Conducting validation studies in multiple laboratories. The purpose of this phase is to demonstrate the transferability of the protocol, measure lab-to-lab variability, and help establish final performance characteristics for the assay.
- Peer reviewing the data to determine strengths and weaknesses of the assays. Peer review is the critical evaluation of scientific and technical work products by independent experts. Its purpose is to improve the quality, credibility, and acceptability of regulatory decisions.
Review the assay status table for information on the stage of the validation process of each assay.
EPA plans to peer review the following EDSP work products. Review assays under consideration for a brief description of each assay. Links to each assay will be activated as peer review materials become available.
* The Hershberger assay has been peer reviewed by the Organization for Economic Cooperation and Development (OECD). EPA will not conduct a separate peer review of this assay.
** The uterotrophic assay has been peer reviewed by OECD. EPA will not conduct a separate peer review of this assay.
The primary product to be peer reviewed for each assay will be an Integrated Summary Report (ISR) that summarizes and synthesizes the information compiled from the validation process (i.e., DRPs, pre-validation studies, and inter-lab validation studies, with a major focus on inter-laboratory validation results).
The mechanism that will be used to peer review Tier 1 assays will be an external letter review organized under an EPA peer review contract. The procedures used for peer review of the Tier 1 assays will be in accordance with EPA's Peer Review Handbook (PDF) (190 pp, 1.15M, About PDF). For each assay, a balanced peer review panel consisting of three to ten peer reviewers will be selected from a pool of qualified peer review candidates identified from academia, government, and the private sector, based on their subject matter expertise, availability, and lack of conflict of interest or past involvement in the project. A charge will be issued to the peer reviewers to address the following types of issues:
- Clarity of the stated purpose of the assay.
- Clarity, comprehensiveness, and consistency of the data interpretation with the stated purpose of the assay.
- Biological and toxicological relevance of the assay as related to its stated purpose.
- Clarity and conciseness of the protocol in describing the methodology of the assay such that the laboratory can:
- Comprehend the objective;
- Conduct the assay;
- Observe and measure prescribed endpoints;
- Compile and prepare data for statistical analyses; and
- Report the results.
- Strengths and/or limitations of the assay.
- Impacts of the choice of (a) test substances, (b) analytical methods, and (c) statistical methods in terms of demonstrating the performance of the assay.
- Repeatability and reproducibility of the results obtained with the assay, considering the variability inherent in biological and chemical test methods.
The peer review panel's comments will be compiled and presented to EPA in a peer review record. EPA will use the peer review record to make a final determination as to a Tier 1 assay's suitability for use in the screening program, and finalize the assay for consideration for inclusion in the Tier 1 battery. EPA plans to begin peer reviewing Tier 1 assays by mid-2007 assuming the studies that are currently underway are successfully completed.
As recommended by the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA's EDSP testing strategy will consist of a battery of Tier 1 assays. The battery is expected to be comprised of screening assays that, when used in combination, will identify substances that have the potential to interact with the estrogen, androgen, and thyroid hormone systems.
Prior to initiating testing, EPA intends to propose a battery of Tier 1 screening assays. The battery will be peer reviewed by the Scientific Advisory Panel (SAP) established under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). The proposed battery, along with the materials supporting its composition, will be provided to a panel of approximately 15 to 20 SAP reviewers.
Some of the panel members may be individuals who participated in review of one or more Tier 1 assays, and some individuals will be new to the EDSP peer review process. Use of some of the same reviewers for both the Tier 1 assays and the Tier 1 battery is intended to ensure that individuals familiar with the individual assays are represented when the battery is discussed. This should not present a conflict of interest because the context of the review and the questions being asked of the battery reviewers will differ from what is asked of the reviewers for the individual Tier 1 assays (e.g., questions posed to the SAP reviewers would pertain to whether the proposed battery adequately covers the endpoints of interest for estrogen, androgen, and thyroid while questions posed to the Tier 1 assay reviewers would focus on the strengths and weaknesses of individual assays).
The peer review strategy for the Tier 2 assays will follow a pattern similar to that used for Tier 1 battery. These assays will be peer reviewed by the FIFRA SAP.
EPA created a listserver (Listserv) or "mailing group" to communicate information about EDSP peer reviews.
This Federal Register notice serves as an announcement. The formal peer review process described above is intended to ensure a systematic and unbiased review of the scientific basis for including an assay in the EDSP. EPA is not currently soliciting public comment. The Agency recognizes that the public may wish to offer opinions on the merits of the assays, however, and will accept comments on the overall Tier 1 battery from the public when the composition of the Tier 1 battery is being peer reviewed by the SAP. A separate Federal Register notice will announce the SAP review of the Tier 1 battery and provide information on opportunities for public comment.