• 한국임상약학회지
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• 제28권2호
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• pp.146-153
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• 2018

Objective: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. Methods: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. Results: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. Conclusion: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.

• Translational and Clinical Pharmacology
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• 제26권3호
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• pp.101-102
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• 2018

• Communications for Statistical Applications and Methods
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• 제25권4호
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• pp.341-354
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• 2018

The one of the principles described in ICH E9 is that only results obtained from pre-specified statistical methods in a protocol are regarded as confirmatory evidence. However, in multi-regional clinical trials, even when results obtained from pre-specified statistical methods in protocol are significant, it does not guarantee that the test treatment is approved by regional regulatory agencies. In other words, there is no so-called global approval, and each regional regulatory agency makes its own decision in the face of the same set of data from a multi-regional clinical trial. Under this situation, there are two natural methods a regional regulatory agency can use to estimate the treatment effect in a particular region. The first method is to use the overall treatment estimate, which is to extrapolate the overall result to the region of interest. The second method is to use regional treatment estimate. If the treatment effect is completely identical across all regions, it is obvious that the overall treatment estimator is more efficient than the regional treatment estimator. However, it is not possible to confirm statistically that the treatment effect is completely identical in all regions. Furthermore, some magnitude of regional differences within the range of clinical relevance may naturally exist for various reasons due to, for instance, intrinsic and extrinsic factors. Nevertheless, if the magnitude of regional differences is relatively small, a conventional method to estimate the treatment effect in the region of interest is to extrapolate the overall result to that region. The purpose of this paper is to investigate the effects produced by this type of extrapolation via estimations, followed by hypothesis testing of the treatment effect in the region of interest. This paper is written from the viewpoint of regional regulatory agencies.

• 한국임상약학회지
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• 제29권4호
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• pp.267-277
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• 2019

Backgrounds: With the globalization of drug development, multi-regional clinical trials (MRCTs) have emerged to facilitate rapid availability of medicines to patients worldwide. The present study aimed to has explored attitudes and perceptions towards adopting the Korean MRCT guideline. Methods: An online survey, consisting of 16 questions, classified into two subjects, was administered to stakeholders in Korea. Most quantitative components were measured using the Likert scales. A content analysis of the qualitative components was carried out to identify the keywords in open-ended responses. Results: A total of 94 survey responses were analyzed: 51 participants from pharmaceutical companies, 11 from clinical research organizations, and 21 from clinical trial centers. The content of the guideline was rated as appropriate for clarity, acceptability, and applicability (96.8, 96.8, and 93.6%, respectively). The local environmental impact of the systemic/political, academic/technical, and industrial/economical aspects of the guideline was rated as appropriate at 95.7, 97.9, and 91.5%, respectively. The suggested adoption period was 1~2 years (40, 42.6%). The concept and individuals' domestic circumstances were the key problems affecting the clarity, applicability, and local environmental impact of the guideline. Conclusion: The Korean MRCT guideline was well-developed. Their overall impact on the local environmental impact of MRCTs in Korea was expected to be beneficial, but methods are needed to minimize the negative impacts. The findings of this study can inform the priorities for the future adoption of the guideline in Korea.

• Clinical and Experimental Pediatrics
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• 제49권4호
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• pp.424-430
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• 2006

목 적 : JRA는 소아에서 가장 흔한 결체 조직 질환 중의 하나이고 장, 단기적인 신체장애를 유발하는 중요한 원인이 된다. 저자들은 JRA 환아들의 질병 양상과 경과를 알아보기 위하여 본 연구를 시행하였다. 방 법 : 1990년 8월부터 2004년 11월까지 서울아산병원 소아과를 내원한 59명의 JRA 환아를 대상으로 하였다. 성별, 연령, 유형, 침범 관절, 관절 외 소견, 검사 및 방사선 소견, 치료, 경과 등에 대하여 후향적으로 고찰하였다. 결 과 : 소수 관절형은 32.2%, 다수 관절형은 30.5%, 전신형은 37.3%였다. 남녀비는 1.7 : 1이었으며 평균 발병 연령은 $9.3{\pm}3.7$(1.3-15.9)세이었다. 가장 흔히 침범된 관절은 무릎과 발목, 팔목이었다. 관절 외 소견을 살펴보면 발열, 발진, 근육통, 림프절 비대 등이 있었다. 검사 소견을 살펴보면 백혈구증가증, 빈혈, 혈소판증가증, ESR 상승, CRP 상승 등의 소견을 보였다. 류마토이드 인자, 항핵항체 양성률은 각각 5.3%, 18.0%이었다. 비스테로이드성 소염제(NSAID)가 가장 많이 투여되었으며, 메토트렉세이트 또는 스테로이드를 함께 투여했던 경우가 27.1%였다. 88.1%의 환아에서 장애 후유증 없이 완치되었으며 한 명의 환아에서만 기능성 상태 IV의 장애가 있었다. 폐침범이 동반되었던 한 명의 환아가 사망하였다. 결 론 : 본 연구에서는 균등한 유형별 분포, 남아에서 호발하는 양상, 늦은 발병 연령, 낮은 홍채모양체염 발병률, 그리고 낮은 ANA 양성률을 보였는데 이러한 소견들은 한국에서의 JRA의 소견이며 서양에서의 보고와는 상이한 결과들이다. JRA가 민족과 지역에 따라서 서로 다른 발병양상을 보인다는 점을 시사한다고 생각된다. 앞으로 더 많은 수의 환자들을 대상으로 하는 다기관 협동 연구 및 역학조사가 필요할 것으로 생각된다.