略過導覽連結
新藥查驗登記(NDA)
銜接性試驗評估申請案(BSE)
申請常見問題
國際醫藥法規協合會E5問答集
臨床試驗審查(IND)
原料藥主檔案(DMF)
申請及法規相關
ICH Topic E5 (R1)
Ethnic Factors in the Acceptability of Foreign Clinical Data
Questions and Answers
(September 2006)

http://www.emea.europa.eu/pdfs/human/ich/574603en.pdf
http://www.fda.gov/cder/guidance/7377fnl.htm

說明
國際法規協和會ICH E5 Q&A (問答集)於2006年9月有更新一次,該問答內容更有助於了解銜接性試驗全貌。中心為協助更多國內相關業者更清楚了解銜接性試驗及與藥物全球研發計畫關係特翻譯該問答集全文如下供參。

I am planning to develop my new drug globally. Does E5 provide guidance for this approach?
我正計畫研發一全球性新藥。E5能否針對這樣的計畫提供指引?

E5 does provide some guidance in this situation. E5 addresses primarily how development programs in one or two regions might support approval in another region. E5 says, in general, that if the data developed in one region satisfy the requirements for evidence in a new region, but there is a concern about possible intrinsic or extrinsic ethnic differences between the two regions, then it should be possible to extrapolate the data to the new region with a single bridging study. The bridging study could be a pharmacodynamic study or a full clinical trial, possibly a dose-response study. The bridging study would allow extrapolation of an adequate data base to the new region. It would seem possible, and efficient, to assess potential regional differences as part of a global development program, i.e. for development of data to occur simultaneously in various regions, rather than sequentially.

For example, if multi-regional trials had a sufficient number of trial subjects from the new region, it might be possible to analyze the impact of ethnic differences in those studied, to determine whether the entire data base is pertinent to the new region.

The basic issues to be considered in a global study design that could affect a region's willingness to rely on these data are: a) definition and diagnoses of disease condition and patient, b) choice of control group, c) regional target or objective of treatment with choice of efficacy variables, d) methods of assessment of safety, e) medical practice, f) duration of the trial, g) regional concomitant medications, h) severity distribution of eligible subjects, and i) similarity of dose and dose regimens. To determine whether your proposed global program will address the requirements of a specific region, it is recommended that early consultation and discussions be held with regulatory authorities in that region.
E5是可以提供一些指引的。E5主要指出如何於一或兩個區域執行之研發計畫可以作為其他區域獲得核准之支援。一般來說,如果在一個區域研發得到的數據資料及證據滿足在另一新地區的要求,但對在兩地區之間可能存在內因性或者是外因性的族群差異之疑慮時,即應實行銜接性試驗,將已有臨床數據資料外推至新區域。銜接性試驗可為一項藥效學試驗或完整的臨床試驗,最好可為一劑量療效反應試驗。銜接性試驗允許適當的臨床數據資料外推至新區域。評估區域間之潛在差異作為全球新藥研發計畫之一部分,似是可行且有效率方式,也就是說,可在多個區域同步進行臨床數據的開發,而非接續性的執行試驗來證實有無族群差異。

例如:如果在多區域臨床試驗中含有足夠新區域的試驗受試者,即可分析族群差異的影響,以確定整個臨床數據資料是否適用至新區域。設計全球性研究計畫需考慮幾項基本議題,其可影響一區域對此研究數據之信賴意願度︰a) 病患及疾病狀況之定義及診斷,b) 對照組的選擇,c) 區域性之藥物療效指標及療效選項變數,d) 安全性評估的方法,e) 醫療行為,f) 試驗期間,g) 區域性常被倂用之藥物,h) 受試者疾病嚴重度分佈,以及i) 劑量與用法的相似度。

建議即早與當地之法規機關諮詢與討論,以確定所提議的全球性試驗是否符合當地之要求。


I have developed my drug in one region, addressing safety, efficacy, dosing, etc., as well as use in special populations such as patients with renal/hepatic impairment, the elderly, children, and pregnant and lactating women. If I can successfully demonstrate (e.g. through a bridging study) that my safety, efficacy and dosing information in the general population are relevant to the new region, will I also need to further address the extrapolatability of the special population data?
我已經在某一地區針對某一藥品之安全、療效、劑量等等要求,以及使用於特殊族群,像是:腎/肝功能不全者、老年人、兒童和懷孕和授乳的婦女,完成研發。假如我可證實這些獲得自一般病人之安全、療效、劑量資訊(例如:透過一銜接性試驗),可成功的對應到新區域一般病人,是否另外還需要進一步探討特殊族群之臨床數據資料,於新區域之外推性?

In general, if the studies of special populations are sufficient in design (e.g. include an appropriate range of severity of impairment) to address regulatory requirements of the new region, but are conducted in a foreign region, and if evidence supports the extrapolation of the data in the general population to the new region, you will probably not need to address the issue of special populations again in the new region. Note, however, that for a new indication in a special population (e.g. pediatric depression) a region might require a separate bridging study.
一般而言,如果其特殊族群之試驗在設計上(例如已涵蓋不同範圍之損傷程度)能充分符合新地區的法規要求,即使試驗是在國外地區執行,而且已有證據支持一般族群的資料可以對應外推到新地區,則在新地區你也許毋須再考量特殊族群的問題。然而,值得注意的是,對於特殊族群的新適應症(例如:小孩之憂鬱症),可能需要分別執行銜接性試驗。


I believe that my drug is sensitive to ethnic factors and that the medical settings in which it is used may vary among regions. Does this mean that my efficacy study in one region is of no value in support of my application in another?
我相信我的藥品對族群因子具敏感性,同時在不同用藥地區之醫療行為亦可能有所差異。這是否代表我在某一區域做的藥品臨床療效試驗研究,對支持不同地區的申請完全不具價值呢?

No. Assuming the new region finds the studies in the first region pertinent, the regulatory authority of the new region will likely require a controlled study in its own region to establish efficacy (and/or to address other issues). E5 indicates, however, that the second region would be likely to consider a single such study adequate if the data from the foreign region otherwise meet all the requirements of the new region. If the new study supports the same conclusions as the study(ies) in the original region, no further confirmation should be needed, as the data from the original region would likely be considered to confirm the finding in the new region. In that case, the study in the new region need not necessarily have the identical dose and treatment effect size to confirm the findings from the initial region.

There might also be situations in which the region would consider further safety data necessary. For example, if the new region considered a higher dose or more frequent dosing necessary and if this finding were not a pharmacokinetic effect, sponsors might need to provide additional safety data.
不盡然。假設新地區發現在第一個區域所作研究是適切的,新地區法規主管機關將很可能會要求在自己所在的地區執行一對照性研究以建立藥物之療效性(和/或解決其他的問題)。然而,E5指出,若國外的臨床數據資料除族群因子外都可符合新區域的要求,那麼在新的地區只考慮做單一的上述臨床試驗應是足夠的。若新試驗結果可以支持且該藥品在原區域的研究結論相同時,則來自原區域之數據就應可被用來確認在新地區的發現,不需再多做確認。在此情況下,新區域做的臨床試驗不一定須用與原區域相同的劑量和有效病人數目來確認既有的發現。
但在某些情況下,新區域仍會考量進一步安全性數據資料的必要性。例如:新區域認為更高的劑量或更頻繁的給藥頻率是必要時,且此現象又非屬於藥物動力學的影響時,廠商或許須提供額外的安全性數據資料。


I believe that my drug is insensitive to ethnic factors and that there are no significant relevant differences in extrinsic factors, including the practice of medicine, among the regions. The pharmacokinetics of the drug are insensitive to intrinsic and extrinsic factors. The diagnosis and therapy of the conditions in the indication do not significantly vary among regions. Nonetheless, the regulatory authority of the new region is requiring an additional study of safety and efficacy for bridging. Is this requirement inconsistent with E5?
我認為我的藥品不具族群因子敏感性,且無明顯之外因性族群因子差異(含區域間醫療行為)。藥品之藥物動力學特性不具內因性及外因性族群因子敏感性,對於該藥品之適應症的診斷與治療在區域間亦不具明顯的差異。然而,新區域的法規單位仍要求一個與安全性及療效相關之試驗以銜接數據。這要求是否與E5不一致呢?

No, although you might want to discuss the issue with the regulatory authorities in the new region. E5 makes it clear that the need for a bridging study is always a matter of judgment and does not seek to discourage the new region’s asking for one. E5 specifically notes that familiarity with the other region is likely to be an important determinant of whether the new region asks for a bridging study. E5 does indicate the expectation that the regulatory authorities of new regions would request only those additional data necessary to assess the ability to extrapolate foreign data to the new region, but the amount of additional data called for is a matter of judgement on the part of the regulatory authority.
未必。你仍然可以與新地區的法規單位討論此問題。E5明確指出銜接性試驗執行與否需視當局判斷而定,且不會試圖阻擾新區域對此要求。E5特別提到對其他地區的認識及熟悉度,很可能是該局是否要求銜接性試驗的重要因素。E5的確有明確期望新地區的法規單位只額外要求必要的數據資料,以評估是否足以將國外資料外推至該區域,然而其額外需要的數據資料之多寡及程度,端賴該區法規單位之判斷。


My drug has been approved in two ICH regions and I am about to meet with regulatory authorities in the third region to discuss an application for marketing. I believe that the new regulatory authority should accept the present data, and that regulatory authority should require little or no additional data. What information should I submit to support my case that additional data are not needed?
我的藥物已經在兩個ICH區域被核准上市,而我將要和第三個區域的法規單位討論藥品上市的申請。我認為新區域的法規單位應該會接受目前的資料,且該法規單位應該不會要求太多或不要求額外的資料。我應該要提供什麼樣的資訊以支援我的案件是不需要額外的資料?

There are two distinct issues that need to be considered: 1) the adequacy of the data base and 2) the need for a bridging study. You will need to convince the regulatory authority that the available data are both adequate to meet the new region's requirements and that the data are applicable to the population of the new region. You should therefore indicate how your data address all the regulatory requirements of the new region. Where the choice of control groups, primary endpoints, or other key clinical trial design features are not those known to be considered acceptable to the new region, you should explain how and why they should be considered to meet the regulatory requirements of the new region. You should also indicate why the data and conclusions should be considered relevant to the new population. In doing this, you should identify the intrinsic factors (e.g. racial distribution) that differ between the regions and show that those factors do not substantially affect the drug effect (i.e. demonstrate that the drug is insensitive to any differences in ethnic factors). Data indicating that pharmacologically related compounds have similar effects in the two regions can be quite useful. You should also identify the extrinsic factors (e.g. diagnosis or management of the patient population studied) that you believe are generally similar to those in the intended population in the new region and explain why any significant differences would not alter conclusions to be drawn about the drug effect. Dose-response relationships should be evaluated to determine if these are sensitive to intrinsic or extrinsic factors, and whether the appropriate doses might vary markedly among individuals or ethnic groups.
這裡有兩個確切議題需要被考慮: (1)資料數據庫的足夠完整性和(2)銜接性試驗的需要性。您須讓新區域之法規單位確信你所提供的資料不但適切,且能符合當地法規單位的需求,且這些資料能適用於該區域的族群。因此,您須說明所提供的資料如何滿足新法規單位所有的法規需求。倘若對照組的選擇、主要療效指標或其他臨床試驗設計特性,不是普遍被新法規單位所認同接受,您應該解釋為什麼和為何可以符合這個新法規單位的需求。您也須表明為什麼這些資料和結論,可被認為可關聯至當地族群。此時,您應該要列出二區域族群其內因性族群因子(例如:種族分佈)的同異,及顯示這些因子並不顯著影響藥物的療效(例如:證明藥品對於族群性因子的差異是不具敏感性)。檢附資料能表明出藥理學相類似的化合物在兩個區域已有相似的療效,也是相當有用的資訊。
您也須要指出外因性族群因子,(例如:試驗收納的病患族群之診斷或處理方式),您必須確認其和將來預計要使用在新區域的病患族群有廣泛地相似性,並要能夠解釋若是有顯著差異時,為什麼不會改變對該藥品效果之結論。
劑量和療效間的反應關係應要被評估,以確定藥品是否對內因性或外因性族群因子具敏感性,及是否會因個體或族群不同而導致適當劑量的極大改變。


I believe that my drug is insensitive to ethnic factors and that drugs in its class have similar activity in all regions. However, the endpoints I studied and/or the control group I used were considered acceptable to the regions in which the studies were conducted but not to the new region. Does E5 indicate that the new region should accept those data as evidence of efficacy?
我相信我的藥物對於族群因素不具有敏感性,且該藥物類別在所有區域皆有類似的作用。我所執行之藥品臨床試驗使用的療效指標和/或使用的對照組在執行地區被認為是可接受的,但在新地區則否。E5是否有指出新地區需要接受這些臨床數據資料作為療效的證據呢?

No. E5 indicates clearly that it applies only when the foreign clinical data address all the regulatory requirements of the new region, but come from a different region. E5 does not address the regulatory requirements of individual regions. If your choice of clinical endpoints or control group is not considered acceptable to the new region, and if you cannot convince regulators in that region otherwise, then E5 does not apply to this situation.
Early discussion with regulators in regions where endpoints, control groups, inclusion criteria or diagnostic criteria might differ should be considered part of planning clinical studies to meet an individual region’s requirements. In this situation, the regulatory authority in the new region may require you to conduct a study using agreed-upon criteria in the new region.
否。E5清楚指出來自不同區域的外來臨床資料必須符合新地區法規單位需求時方為採用。E5不提出個別的地區之法規要求。當你選擇的臨床指標或者對照組不被新地區接受,且無法說服當地法規單位,則E5指引無法適用 。
在規劃符合個別區域要求之臨床試驗時,建議儘早與當地法規單位討論試驗指標、對照組、納入標準或者是診斷標準之不同處。在這種情況下,新地區的法規單位也許會要求你在新地區執行一項指標標準經雙方同意的臨床試驗。


I believe my drug is insensitive to ethnic factors. However, there is a clear difference in medical practice and the use and perceived need for certain drugs in the targeted therapeutic area. Does E5 indicate that the new region should accept those data as evidence of efficacy?
我的藥品應無族群敏感性問題存在。然而,於另一地區其醫療行為及在特定治療領域中對此類藥品使用上及需求性有明顯的不同。請問E5有指出如果在此情形下,新的區域應該要接受本品既有療效證據資料嗎?

No. As described, the data base might not be acceptable to the new region, apart from concerns about ethnic differences, because the data do not refer to a disease that the new region considers pertinent.
並非如此。 如上所述,如果不同地區有醫療行為及藥物使用上的差異,那原有的試驗數據的基礎可能是不被新的地區所接受,因為除了所關心的族群差異因子外,原有的試驗數據並未與新區域認為是恰當之疾病有關連。


My drug has been shown to be effective in preventing certain clinical events. However, the rate of these events is clearly different in the new region, even though the pathophysiology is the same. Does E5 indicate that the new region should accept those data as pivotal evidence of efficacy?
我的藥品顯示可有效預防某些臨床狀況。然而在新地區雖然此臨床狀況具相同病生理學特性,但是其發生率明顯不同。請問在E5是否指出新地區需要接受既有的數據資料作為支持療效之樞紐證據?

No. Certainly, in most cases where there is a definitive outcome study in another region, a region would probably not require that the study be repeated locally. There could, however, be exceptions; for example, if the event rate is indeed lower in the new region, and the risk reduction is the same in both regions, the actual number of patients benefited will be smaller and an adverse effect could become more important, affecting the benefit to risk relationship of the drug. A new region, in some cases, might need a clinical trial to assess the value of the drug.
並沒有。雖然絕大部分的情形是當於另一個區域已執行過有明確結果的試驗,就應該無須於當地再重複相同試驗。然而仍是有例外的; 舉例來說,假設某種臨床狀況於新區域之發生率顯然低於原區域,而新藥於此二區域所能降低之風險程度是相同的,則在此新區域能受益於此新藥的患者其實際數目會少很多,此時藥品的不良反應則相形更重要,影響到本藥品利益風險關係評估重點。在某些案例,若有此情形,新區域極可能會要求另外的臨床試驗以評估本藥品之價值。


My drug is approved for various indications in one region and it is shown in a bridging study in the primary indication that the data can be extrapolated. Does this mean that the new regions should accept all indications without further data?
我的藥物在一個區域已申請通過多個適應症,且由其原核准適應症之銜接性試驗結果顯示其相關數據可以外推至新地區。請問這是否表示在新的區域應該接受所有的適應症,而不再需要更多的數據資料嗎?


No. Whether or not the new region will require further data would be decided on a case-by-case basis, depending on whether the "bridged" indication was thought to satisfy all concerns about potential ethnic differences. For example, the additional indications might be extensions of the primary indication (perhaps not calling for an additional bridging study) or quite new uses (perhaps calling for bridging). It is recommended that early consultation and discussions be held with the authorities in the new region.

並非如此。有關新的區域是否會要求更多的數據以核准其他適應症,依個案而定,端視其所申請的“被銜接的”適應症有無潛在族群差異之疑慮。例如:所申請的新適應症若屬原核准適應症之延伸,可能就不需要更多的銜接性試驗數據;但若是屬於完全新的用途(適應症),就會需要額外的銜接性試驗數據。建議即早與新地區相關法規單位作諮詢與討論。


E5 expresses the principle that, as experience with interregional acceptance of foreign clinical data increases, there will be a better understanding of situations in which bridging studies are needed and that it is hoped that, with these experiences, the need for bridging data will lessen. Is this principle still valid?
E5闡述以下這個原則:隨著區域間相互接受國外臨床試驗數據的經驗與日增加,將會更進一步的瞭解銜接性試驗的適用狀況,並且期待隨著這些經驗的增加,對銜接性數據資料需求會減少。這個原則是否仍然有效?

Yes, this is the expectation. The accumulation of experience by each region with implementation of the E5 guidance continues to add to our understanding of situations in which a bridging study would be considered necessary by a new region. The expectation continues to be that, with this experience, the need for a bridging study will lessen.
是的,這是可被預期的。藉由各區域執行E5準則之經驗累積,將會持續增加我們對在一個新的區域是否需要執行銜接性試驗的瞭解。隨著這種經驗累進,我們持續期望執行銜接性試驗的需求將會減少。


There seems to be an impression that the E5 bridging study would always be conducted after data in the original region is complete. Is this correct? It may be desirable in certain situations to achieve the goal of bridging by conducting a multi-regional trial under a common protocol that includes sufficient numbers of patients from each of multiple regions to reach a conclusion about the effect of the drug in all regions. Please provide points to consider in designing, analyzing and evaluating such a multi-regional trial.
似乎銜接性試驗總是於原開發地區試驗資料完成後才開始進行,這樣做對嗎?某些情形下為達到銜接性的目的,可於相同的試驗計畫書下進行全球多地區試驗,自各地區收納統計學上足夠之受試者數目,以對藥效做出結論。請提供針對該種多地區臨床試驗的設計、分析、評估考量重點。

Bridging data should allow for extrapolation of data from one region to another. Although E5 speaks generally to extrapolation of data to a new region, E5 was not intended to suggest that the bridging study should necessarily follow development in another region. In the answer to Q1, it is made clear that it is also possible to include earlier studies conducted in several regions in a global drug development program so that bridging data might become available sooner. This can expedite completion of a global clinical development program and facilitate registration in all regions. A bridging study therefore can be done at the beginning, during or at the end of a global development program. For a multi-regional trial to serve as a bridging study for a particular region, it would need to have persuasive results in that region, because it is these regional results that can convince the regulators in that region that the drug is effective, and can “bridge” the results of trials in other regions in the registration application.
A multi-regional trial for the purpose of bridging could be conducted in the context of a global development program designed for near simultaneous world-wide registration. The objectives of such a study would be: (1) to show that the drug is effective in the region and (2) to compare the results of the study between the regions with the intent of establishing that the drug is not sensitive to ethnic factors. The primary endpoint(s) of the study should be defined and acceptable to the individual regions and data on all primary endpoints should be collected in all regions under a common protocol. In instances where the primary endpoints to be used by the regions are different, data for comparison purposes on all primary endpoints should be collected in all regions.
For a study intended to serve as a bridging study, the following points should be considered:
Planning
The multi-regional trial would have to satisfy requirements of the region where the application is to be filed with respect to design and analysis (see answer to Q1). In general, a multi-regional study should be designed with sufficient numbers of subjects so that there is adequate power to have a reasonable likelihood of showing an effect in each region of interest. Minor differences in design (e.g., age inclusion criteria, concomitant medication, etc.) may be acceptable and prior discussion with regulatory agencies is encouraged. For safety evaluation, it is important to make as uniform as possible the method for collection and assessment of safety information among regions.
Analysis Given the goal of the multi-regional bridging study, it is critical to provide efficacy and safety results by region, with attention given to the usual analyses (e.g., demographic and baseline variables, patient disposition). It will be of interest also to examine consistency of effects across regions. In a dose response study, it will be especially important to analyze dose response relationships for efficacy and safety both within the regions and across the regions.
Evaluation
It is difficult to generalize about what study results would be judged persuasive, as this is clearly a regional determination, but a “hierarchy of persuasiveness” can be described.
  1. Stand Alone Regional Result
    The most persuasive would be demonstration of the effect in the entire study, with the results of each region of interest also demonstrating a statistically significant result. It will also be important to compare results across regions.

  2. No Significant Regional Result But Similar Results Across Regions
    With an effect demonstrated in the entire study, an analysis of results by region might not show a significant result in a region of interest but the data might nonetheless be persuasive to regulators in that region. Consistent trends in endpoint(s) intended for comparison across the regions or, in the case of a dose-response study, similar dose-response relationships across regions, might support an argument that the drug is not sensitive to intrinsic or extrinsic ethnic factors. Other data, for example, from approved drugs in the same class within region(s) could support such a bridging conclusion.
Other consideration
This Q&A discusses use of multi-regional studies as bridging studies. There are other possible uses of multi-regional studies. For example, at an early stage of development, such studies could compare various endpoints in an exploratory setting in different regions to guide a synchronized global development plan.
雖然E5說明銜接性資料可提供將一地區的試驗結果外推至新地區,但E5並沒有建議銜接性試驗必須接著原開發地區試驗完成後再執行。在上述Q1的回答中已經清楚說明,在全球藥物開發計畫的早期試驗,即可考慮於不同的地區執行,如此銜接性資料可能於開發早期即可獲得,可以加速完成藥品全球性開發及促進全球的登記上市。因此銜接性試驗是可於全球藥品開發計畫之初期、中期或末期來執行。如以一項多地區臨床試驗來做為某一地區之銜接性試驗,則該臨床試驗必須有對該地區具說服力之結果,且可使該地區法規單位信服試驗藥品的療效,進而可以“銜接”至其他地區的資料,用來申請核准上市。 執行銜接為目的之多地區臨床試驗可為全球藥物開發計畫中一環,為了全球同步上市申請而設計,這樣的試驗其目標包括(1)顯示試驗藥物於該區具療效(2)比較不同地區試驗結果,以顯示該試驗藥物不具族群敏感性。關於試驗主要療效指標(primary endpoint)應明確在計畫書定義並可為各地區接受的指標,而在各地區都必須在同一個試驗計畫書下,收集所有主要療效指標數據資料。 若遇到地區間使用不同主要療效指標時,則須於所有地區收集可供比較此不同的數據資料。
臨床試驗是否可以被認可為一個銜接性試驗,下列需納入考量:
設計:
多地區試驗之試驗設計及分析方法等,應必須要能滿足你提出申請地區之法規要求(見Q1) 。一般而言,多地區試驗應設計出適切檢定力(power)來收納足夠的受試者人數,以顯示在各試驗地區的藥效,然而各地區間次要的試驗設計不同(例如收納的年齡層、可併服藥物等)是可以接受的,且可盡量即早與各國法規單位討論。另外,針對藥物的安全性評估,於各試驗執行地區採統一的資料收集及評估方式是重要的。
分析:
為了多地區試驗之銜接性目的,應提供各地區的療效及安全性的試驗結果,並重視一般性分析(包括人口學、基期變數、病人分佈比例等)。亦可嘗試檢視藥效跨地區間一致性情形等。就劑量反應試驗(dose-response study)而言,分析各地區內及跨地區間之藥品療效與安全性之劑量反應關係,是非常重要的 。
評估:
試驗結果是否具信服力須由各地區做判斷,並不易做一般論述,不過這裡提供一“信服層級”描述供參。
  1. 完整地區性結果
    最具信服力者應該是整體試驗結果都顯示藥效,而於各地區都能顯示具統計學上有意義的結果。對各地區間比較其結果亦是非常重要。
  2. 地區試驗無顯著結果,但跨地區間有類似的結果
    整體試驗結果顯示藥效,就算各別地區性分析無法得到顯著結果,然其數據資料仍可為各區法規單位接受。例如欲相互比較之各地區療效指標的趨勢結果具一致性,或是在劑量反應試驗(dose-response study)中,跨地區間有類似的劑量反應結果等,皆可能被視為支持該藥物沒有內因性或外因性族群因子的考量。另外,亦可由已被核准的同治療類藥物的資料特性,支持此銜接性評估的結論。
其他考量:
此問答集討論到使用多地區性臨床試驗作為銜接性試驗。當然多地區臨床試驗亦有其他用處,例如,於早期研發階段,這樣的試驗可用於探索階段來比較不同的試驗指標,為往後全球同步發展計畫提供指引。