Notice Number: NOT-OD-17-011

Key Dates
Release Date: November 8, 2016
Response Date: December 18, 2016

Issued by
Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)

Purpose

With this time-sensitive Request for Information (RFI), the Office of Research Infrastructure Programs (ORIP) solicits comments from the biomedical research community about the significance of standard environmental conditions in facilities and laboratories for the scientific rigor of animal model experiments and the effects of such conditions on the reproducibility of related experimental outcomes.

Background

ORIP, located in the NIH Office of the Director’s Division of Program Coordination Planning, and Strategic Initiatives, supports programs that enable the advancement of science and enhance research funded by all NIH Institutes and Centers. In particular, these programs include the development and modernization of research facilities, and support resources that create, maintain, and distribute models of human diseases using animals and cultured cells. ORIP is interested to learn from the research community about the impact of variations in standard environmental conditions in facilities and laboratories on the experimental reliability and reproducibility of research which uses animal models.

The Guide for the Care and Use of Laboratory Animals (hence forth referred to as the Guide) published by the National Research Council of the National Academies provides guidance to assist institutions in caring for and using animals in ways judged to be scientifically, technically, and humanely appropriate . The Guide sets general standards and recommendations to achieve a performance baseline for the best quality care and maintenance of laboratory animals. For the purpose of this RFI, we refer to the Guide’s recommendations as standard conditions or best practices. Details of the implementation of these standards at different institutions typically somewhat vary as the oversight at a local level is provided by the Institutional Animal Care and Use Committee.

NIH-funded investigators rely on many types of animal species as models for biomedical research; including, but not limited to roundworms, fruit flies, African clawed frogs, zebrafish, mice, rats, and rhesus macaques. Depending on a particular animal species and the scientific questions under considerations, details on how the animal is managed and maintained may be necessary to adequately describe the relevant experimental biological variables. Specific environmental conditions such as temperature, light on /off cycles, light color, noise level, humidity, feed type and feeding protocols - all within standards for animal research facilities as outlined in the Guide - may differently affect animal responses depending on what research protocols are undertaken. In some cases, these environmental conditions may need to be controlled for and become a part of an experimental design; in other situations, their influences on experimental outcomes may not be that critical. Each animal species requires a different housing environment and is maintained according to different protocols to ensure that the standards of best care practices are met. These best practices allow for a range of environmental conditions (e.g., temperature ranges, light or noise levels) and some variation in care protocols (e.g., feeding regimens, socializing, type of bedding); different animal models may respond differently to the same variations of environmental conditions in the course of similar scientific investigations.

The animal research community encompasses many investigators with different scientific interests and expertise: researchers who rely on animals, researchers who develop new animal models, and researchers who work in animal research facilities. This RFI seeks input from these diverse groups, as their experiences and professional interests in the design, conduct, and analysis of different animal experiments may be complementary and point to different pressing issues associated with the influences of environmental extrinsic factors, the ability to control them, and the reliability of experimental results.

In particular, different communities and different individuals might have different preferences on how to tackle the volume of issues addressed by this RFI. Of interest is the perceived relative importance of different animal species in the context of the scientific rigor of animal research as well as the relative impact of different extrinsic factors. Also, opinions about specific scientific areas or experimental approaches which would require special attention with regard to extrinsic factors, might vary among different experts. ORIP is interested to learn about a set of priorities which could direct ORIP’s efforts to further strengthen the rigor of animal research and to increase reproducibility of outcomes, by better monitoring of and accounting for standard environmental conditions.

The issues addressed in this RFI are directly related to NIH efforts to enhance scientific rigor and transparency, as outlined in the NIH Director’s Notice NOT-OD-16-011. The goals stated in this Notice include rigorous experimental design, leading to robust and unbiased results for all NIH-supported research.

This RFI DOES NOT seek information about responses to stress, drugs, microbiome, and other similar special causes. This RFI DOES NOT seek information about the value of or the rationale for to use animals in research. Responses addressing such issues won t be considered.

Information Requested

ORIP is interested to learn from the research community who uses or relies on animals, about the current knowledge and practices regarding monitoring of extrinsic environmental conditions, accounting for them in the experimental design, identifying their influences on experimental results, and sharing such information with other researchers. ORIP is also interested to learn from the members of the community about their views on priorities on addressing these issues; in particular, with regard to specific animal species, scientific thematic areas, experimental approaches, and the most dominant extrinsic environmental factors. The focus of this RFI is on standard environmental conditions and best care practices - as outlined in the Guide - for specific animal species, in the context of biomedical research. Any comments will be helpful and may include the following areas:

1. Current knowledge about the effects of standard environmental conditions (e.g., temperature, humidity, noise level, type of feed, feeding protocols, cycles of lights on/off, color of light, quarantine procedures) on the design and conduct of experiments using specific animal species as models for biomedical research (e.g., roundworms, fruit flies, African clawed frogs, zebrafish, mice, rats, and rhesus macaques), and on the reproducibility of experimental outcomes



a) Correlations between specific extrinsic environmental conditions and experimental outcomes
b) Biological mechanisms affected by standard environmental conditions in specific animal models as relevant to specific research areas (e.g., genomics, metabolomics, neuroscience, immunology, cancer research)

2. Missing knowledge about the effects of environmental conditions (e.g., temperature, humidity, noise level, type of feed, feeding protocols, cycles of lights on/off, color of light, quarantine procedures) on outcomes of specific experiments (e.g., gene expression investigations, cell-cycle regulation studies, measurements of drug responses, memory retention testing) using different animal species (e.g., roundworms, fruit flies, African clawed frogs, zebrafish, mice, rats, and rhesus macaques)


3. Current practices regarding monitoring, accounting for, and reporting influences of particular environmental conditions (e.g., temperature, humidity, noise level, type of feed, feeding protocols, cycles of lights on/off, color of light, quarantine procedures) on outcomes of specific experiments (e.g., gene expression investigations, cell-cycle regulation studies, measurements of drug responses, cell-cycle regulation studies, memory retention testing) in different scientific areas (e.g., genomics, metabolomics, neuroscience, immunology, cancer research) using specific animal species (e.g., roundworms, fruit flies, African clawed frogs, zebrafish, mice, rats, and rhesus macaques); strengths and deficiencies of these practices
   


4. Priorities for ORIP's decision making on how to proceed to strengthen the scientific rigor and to improve reproducibility of animal research experiments in the context of monitoring of and accounting for external standard environmental conditions, for the benefit of the animal research community; comment on priorities regarding animal species, scientific areas, experimental approaches, and extrinsic environmental factors
   


5. Effective approaches to disseminate to the broad research community, knowledge and practices about environmental factors which contribute to the rigor of experimental design and reproducibility of experimental outcomes of animal model research


6. Any comments about animal research, related to extrinsic environmental factors contributing to the rigor of experimental protocols and reproducibility of experimental outcomes

All interested parties are invited to respond and all responses are voluntary. It is optional for the responders to provide their professional position, expertise, and experiences. Similarly, it is optional for the responders to state types animals they are commenting about.

How to Respond

All responses to this RFI must be submitted on the website https://dpcpsi.nih.gov/FactorsRFI by December 18, 2016.

Responses to this RFI are voluntary. This RFI is for planning purposes only and should not be construed as a solicitation for applications or an obligation on the part of the Federal Government, the National Institutes of Health, or individual NIH Institutes or Centers. The government will not pay for the preparation of any information submitted or for the government’s use of that information.
The information provided will not be considered confidential. The NIH will use the information submitted in response to this RFI at its discretion; the submitted information will be reviewed by the NIH and shared with the NIH Institutes and Centers that have an interest in this matter. The NIH will not acknowledge receipt of information submitted or provide comments to any responder. No proprietary, classified, confidential, or sensitive information should be included in your response. The government reserves the right to use any non-proprietary technical information in any resultant solicitation(s), policies or procedures; responses to the RFI may be reflected in future funding opportunity announcements. The information provided will be analyzed, may appear in reports, and may be publicly shared on an NIH website.

Inquiries

Please direct all inquiries to:
Office of Research Infrastructure Programs
Email: [email protected]