Since the pharmacodynamic or clinical data in the original population can significantly vary with the population in the new region, many regulatory authorities have limited the willingness to rely on foreign clinical data to approve a new compound. To overcome the issue, in recent years the bridging studies have been a matter of critical importance for drug manufacturers developing a potential new drug.
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What is a Bridging Study?
According to ICH E5 guideline, a bridging study on a medicine can be defined as an additional study executed in the new region to "build a bridge" with the foreign clinical data on safety, efficacy, and dose response. This bridging of clinical studies is usually made by allowing extrapolation of the foreign clinical trial data to the population in the new region.
In other words, a bridging study is a supplemental study on a medicine that is performed in the new region to build a bridge between the information available from the tests already done and the questions arising from the regulatory authority due to ethnic factors. Bridging studies done to assess the efficacy of new drugs could provide additional drug response data in the population of the new region. A pharmacokinetic study may be accepted as a bridging study too, if the regulatory authority in the new region requires no bridging study to provide clinical data for efficacy.
History of Bridging Study
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To solve the issue, in 1998, the International Conference on Harmonization (ICH) introduced a guideline (ICH E5) entitled "Ethnic Factors in the Acceptability of Foreign Clinical Data". The ICH E5 guideline proposes a general outline for assessing the impact of ethnic factors upon a medicine’s efficacy, safety, and dose response. A complete clinical data package and a bridging study in the new region are included as the mainstays of the harmonized final document.
The objectives of the ICH E5 guideline are to:
- Evaluate the influence of extrinsic and intrinsic ethnic factors
- Minimize duplication of clinical data
- Facilitate acceptance of foreign clinical data
- Describe the use of bridging studies
Intrinsic and Extrinsic Ethnic Factors
Importance of Bridging Studies
A drug or vaccine may work well in the population of the region where the clinical study is done. However, questions can arise about how it will perform in the different region on a dissimilar ethnic population. The regulatory authority in the new region is therefore required reviewing all the foreign clinical data of the medicine to consider the application for registration. To fulfill the regulatory requirements in the new region, sponsors have often duplicated all or much of the foreign clinical data in support of registration. Moreover, sponsors are requested to perform more clinical studies to satisfy the regulatory authority in the new region.
Although ethnic variations among populations may alter a pharmaceutical compound’s safety, efficacy, or dose response, but many drugs have similar characteristics and effects across regions. Regulatory requirements for duplication of clinical evaluation for every new drug or vaccine can delay the accessibility to new therapies; the requirements can unnecessarily waste resources of drug development, as well. Thus, the concept of bridging studies has brought up to solve the issues inherent to extrinsic factors caused by different ethnicity.
A bridging study saves duplication of effort by using the complete clinical data package and performing only the additional tests, which are necessary to assess the efficacy and safety of the compound. The ICH E5 guidance proposes that there is no need to run a clinical evaluation from the beginning for a new region. By conducting a bridging study, the sponsor can use the previous test results with the addition of new tests, which covers the difficulties that could arise because of ethnic differences between the original population and the new group. Bridging studies are also performed when a modification in the manufacturing level -- preparation, packaging, storage, or dosage -- or other changes done that might affect the safety, efficacy, or dose response of the medication.
Properly executed bridging studies provide crucial early insights for a recent developed drug, which can help govern the future clinical development. By conducting a bridging study, pharmaceutical sponsors are therefore able to reach critical “go/no-go” decisions faster now.
Briefly, a bridging study helps to:
- Verify safety and efficacy of a new compound.
- Extrapolate the foreign efficacy data and/or safety data to the new region.
- Meet the requirements for registration by the regional regulatory authority.
- Determine the ethnic sensitivity of a drug in a new region.
- Make new therapies available by minimizing the extensive duplication of clinical data.
- Reduce needless waste of drug development resources.
Evaluation Process in a Bridging Study
Ethnicity is an important term, which is derived from the Greek word “ethnos”, meaning people or nation. The term ethnicity is often used to identify a larger group of people in a region. Accordingly, ethnic factors can be defined as factors linking to populations or races grouped in a region with shared traits and customs.
Foreign Clinical Data
The foreign clinical data is the clinical data of test results, which is performed in a foreign region -- i.e., outside of the new region.
Extrapolation of Foreign Clinical Data
A bridging process of the pharmacokinetic and pharmacodynamic data executed in the population of a foreign region to the population of a new region.
Complete Clinical Data Package
A clinical data package proposed for registration in a new region containing clinical data that meet the regional regulatory requirements and containing efficacy and/or safety data suitable for the population in that new region.
A clinical data that provides information about how a drug is handled by the body, meaning absorption, distribution, metabolism, and excretion of a drug. Usually, a pharmacokinetic data includes measurement of blood concentrations of drug and its metabolite at regular intervals after ingestion.
A pharmacological or clinical data that gives information on what the drug does to the body. A pharmacodynamic data includes the dose-response relationship, describes the physiological effect of the drug at different dose or concentration.
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