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How to Search for Alternatives in a Research Protocol

Federal regulations require research investigators to search for alternatives to the use of animals when procedures causing more than momentary pain or distress will be used. Not only must investigators consider non-animal alternatives but also alternatives that may reduce the number of animals used, decrease animal pain or distress or replace the proposed animal species with a less sentient one.

The key to conducting an alternatives search is to focus on alternatives to the potentially painful or distressful procedures used in the study, not on alternatives to the topic or purpose of the research study. Alternatives for each potentially painful or distressing procedure used in the research study must be considered.

Investigators may use their own experience or consult with other professionals in the field as part of their search. However, many investigators rely on internet databases to conduct a comprehensive survey of their field of study. It takes thought and planning to conduct a good database search that yields beneficial information.

 Before beginning a literature search identify what experimental techniques or procedures used in the study have the potential to cause pain or distress in animals. Consider what the significance of these procedures is to the study and whether or not they can be refined or replaced. If painful or distressful procedures must be used, consider what endpoints will be chosen to determine when an animal will be removed from the study.

When conducting a literature search use descriptive search keywords specific for the techniques and procedures noted above. Include the animal species you wish to use and select a database appropriate for the area of study. Do not include search terms like the name of the gene you are studying or scientific keywords relating to your study. The use of the term “alternatives” in the search is usually not very productive.

For example, if the study proposes retro-orbital blood collection from mice search keywords could include: blood collection, method, and mouse. A search would provide alternative sites or methods for blood collection such as the tail artery, saphenous vein, and cardiac puncture. The investigator must then consider how much blood may be obtained with each method, whether or not repeated blood collection is required and the potential for pain and distress with each method.

For an experiment involving intra-cerebral injections in mice, the keywords could include: drug, administration, method, and mouse. A search will result in other potential administration routes such as: intravenous and subcutaneous injections, oral gavage and subcutaneous implants. The method the investigator selects will be dependent on the specific needs of the experiment. If the drug needs to cross the blood-brain barrier in a certain time frame, the intra-cerebral injection might be the only possible route.

Please refer to websites such as the UC Davis Center for Alternatives and the Fund for the Replacement of Animals in Medical Research for more information and examples when planning and conducting alternatives searches. PSU investigators may also contact an ARP veterinarian for assistance.