Bridging Study in Clinical Trials: Definition, History, and Importance
In today’s economic environment, it is near impossible for drug makers to evolve their businesses unless they sell their products globally. Investors of newer drugs are thus requiring to do more in quick time but at less cost. So, they are facing newer challenges, as well.
One of the biggest challenges, nowadays, to globalize a product is the ethnic factor.
Since the pharmacodynamic or clinical data in the original patient population can greatly differ with the population in the new region, regulatory authorities across the globe are now less willing to rely on foreign clinical data to approve a new compound.
To overcome this issue, in recent years bridging studies are becoming more and more popular among drug makers developing a potential new drug.
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.
Put simply, a bridging study is a faster and cheaper means of doing a clinical trial in a new region. It saves drug makers from having to start a new study from the ground up.
In the new country, a bridging trial simply builds a bridge to extrapolate data from prior studies.
The aim of a such trial is usually twofold:
- to fill the knowledge gap
- to deal with the local regulatory authority's concerns about ethnicity
Sometimes, a pharmacokinetic study may also serve as a bridging study. This happens if the regulatory authority in the respective region requires no bridging trial for efficacy.
Note: bridging studies done to assess the efficacy of new drugs could provide additional drug response data in the population of the new region.
History of Bridging Study
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| Clinical Study Source: Shelah, CC-BY-2.0, via Flickr |
In the early 90s, global development of drugs became an important concern for pharmaceutical sponsors to success in the international market. The ethnic sensitivity of a newly developed drug in different regions was therefore getting much attention from the sponsors as well as regulatory authorities. As the ethnic factors could affect the medicine's efficacy, safety, and dose response, the executed clinical trial data in original region required extrapolation and/or bridging for the new region.
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 local population where the original study is done. However, there is no guarantee that it will have the same effect in a different region with a different ethnic population. Its efficacy may differ due to genetic, environmental, and cultural differences. For example, the effectiveness of different classes of penicillins may vary between ethnicities. Several factors may play a role such as genetic predispositions to antibiotic resistance or variations in drug metabolism rates across different populations.
Therefore, before considering an application for registration, the regulatory authority in a new area must review all the foreign clinical data of the medicine. To fulfill the regulatory requirements for a new region, sponsors or manufacturers often duplicate all or much of the foreign clinical data in support of registration. In many occasions, they are requested to perform additional studies to fulfill the regulatory requirements of 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 was 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 suggests that there is no need to run a full clinical evaluation from scratch for a new region. Sponsors can use previous test results by conducting a bridging study. They will only conduct a few additional tests to account for any challenges that may arise due to ethnic differences between the original population and the new group.
Bridging studies should also be 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.
A Bridging Study Example: Botox Use Across Ethnicities
When considering Botox for cosmetic use, it is important to know that people from different backgrounds may react differently. This shows the role bridging studies play in clinical research. Just like how a drug's effectiveness varies across different groups due to genetics, environment, and culture, the amount of Botox needed to achieve desired outcomes can also vary widely among individuals from different ethnic groups. Doctors must consider several facial features like skin type, muscle strength, and face shape. These differences emphasize the need for a personalized treatment plan, informed by detailed medical history and clinical data. This approach highlights the broader implications of ethnic sensitivity in medical practices.
Evaluation Process in a Bridging Study
Endnotes
Ethnic FactorsEthnicity 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 DataThe 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 DataA 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 PackageA 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.
Pharmacokinetic DataA 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.
Pharmacodynamic DataA 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.
Medical Reference
- Liu JP, & Chow SC (2002). Bridging studies in clinical development. Journal of biopharmaceutical statistics, 12(3), 359-67.
- Naito C (2000). Necessity and requirements of bridging studies and their present status in Japan. International journal of clinical pharmacology and therapeutics, 38(2), 80-6.
- Berelowitz, K., & Taubel, J. (2012). Early phase Japanese bridging studies. Int Pharma Ind, 3, 64-72.
- Gupta, S. K. (2011). Implications of ICH-E5: assessment of drug's sensitivity to ethnic factors and necessity of a bridging study for global drug development. Perspectives in Clinical Research, 2(4), 121-123.
