Bridging studies play an important role in drug development, both in the clinical and preclinical stages. These studies provide important information that can circumvent the repetition of entire programs. Understanding the considerations and steps in switching rodent strains and the importance of bridging studies, is critical. In this post we outline the best practices on bridging studies.
Best practices on bridging studies
In the preclinical scenario, bridging studies are most commonly used in the context of safety evaluations to help establish relative comparability between different dosing regimens, analyze a change in formulation, or address a process change in the manufacture of a drug product. This framework can also be applied to efficacy assessments, wherein bridging studies can provide data to understand whether efficacy of the new molecular entity (NME) is consistent between two strains prior to conducting pivotal studies, such as those that may be used for regulatory submissions. Overall, bridging studies in the preclinical setting can help verify that the safety and/or efficacy of the drug product is consistent with what has been produced throughout the research and/or drug development program.
Bridging studies can be of great benefit when evaluating a new rodent strain to potentially replace an existing strain. In this situation, the key to effective bridging studies is the availability of robust data on the existing strain.
The underlying premise of the bridging concept is that the existing strain serves as the positive control and its data is then bridged to the data generated for the new strain.
Explore further best practices in this related post 'Best practices for bridging studies to generate data and validate a new strain'.
Bridging studies provide pharmacodynamic (PD) and efficacy data in the desired new rodent strain, using the same dose and dose regimen as in the existing strain. If possible, it is also desirable that pharmacokinetic (PK) behavior be assessed during the bridging study. Data from bridging studies in rodents can be valuable as a preliminary indicator as to whether full validation studies should be conducted using the new strain. In some cases, historical data from an existing strain can be extrapolated to the new strain and used for regulatory submission purposes, depending upon the bridging study results and other relevant similarities between the strains.
Overall, bridging studies provide a vital link in the transition to new rodent strains. Ideally, the goal is to generate similar data across strains to determine whether the strains correspond well with each other or whether the performance of one is superior to the other.
4 key steps to consider when switching rodent strains in oncology
1. Selection: Consider which strains might be viable candidates by consulting literature and vendor websites, in addition to vendor technical services.
2. Information gathering: Obtain as much information as possible on the new strain, especially by seeking any existing comparative data between the strains. Information sources can include publications; resources such as Envigo’s cell line tool; vendor documentation (which may provide information on survival, body weight, blood chemistry, hematology, radiation sensitivity, level of immunodeficiency, etc.); and genotype/phenotype databases.
3. Due diligence: Compare the characteristics of the existing and new strains to determine whether there are major differences that could impact the study. For oncology, specific characteristics to consider include tumor growth, such as uptake, growth, and time to reach desired size; radiation tolerance; life-span; estrogen tolerance; background incidence of lesions; immune phenotype and leakiness (i.e. tendency to produce some functional immune cells); tolerance to drug-induced DNA damage; metabolite screen (using liver microsomes and/or hepatocytes); ease of handling; and presence or absence of specific cell types, if these will be targeted or may interfere with assays.
4. Sampling programs: Some vendors offer sampling programs that can help develop very preliminary empirical data as to the performance of the new strain. If the sampling data are promising, moving to more rigorous bridging studies to fully validate the strain can be considered.
The importance of an integrated approach
Bridging studies play an important role in preclinical drug development, since they provide important information that can prevent the need to repeat entire study programs. The basis of these studies is that the existing strain serves as the positive control and its data is bridged to the data generated for the new strain.
Explore more about why researchers switch rodent strains when it comes to bridging studies.
By adhering to best-practices for general study design considerations and engaging in early discussions with experienced partners or collaborators, it is possible to enhance the potential success of the oncology preclinical program. From our comprehensive online resources, through to our model selection consultants and study directors- talk to us about your oncology portfolio needs from start to finish.
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