임상시험정보시스템 현황분석과 적용방안 모색

정순옥,권수경,최인영 대한임상약리학회 2008 Translational and Clinical Pharmacology Vol.16 No.2

Background: Over the past decade, pharmaceutical companies have introduced a number of initiatives to boost the productivity of clinical trials. In clinical trials, this can take to reduce costs and durations of that are being considered in applying information technology. One of these initiatives has been the rollout of electronic data capture (EDC) systems, which allow patients and researcher to enter their trial information directly, either in electronic diaries or online systems. The utilization rate of the EDC in the United States is 41.5%, and similar trends can be seen in 40.5% in Japan. Objectives: Currently, the adoption of EDC in Korea is also getting increased, so the current status of EDC application should be assessed in clinical trials. The aim of this study was identified in present status of EDC system and to improvements to develop it. Method: The survey of participants has been accomplishment in a clinical research coordinator workshop and e-CRF System workshop, which was held in a University Hospital, located in Seoul. The main questionnaire items were 14 including the career of EDC system. Totally, 109 responses were classified by fields of clinical trials study, and comparison analyzed each questionnaire items. Result: The survey of participants has been separated pharmaceutical company participants (39.4%), contract research organization or clinical research associate participants (26%), investigator (research coordinator) (24%), and other participants (10.6%). Current EDC System applied Phase III(40.0%) and will plan to use of system Phase I(34.5%), Phase II(16.7%) Conclusion: EDC systems are increasingly applied for clinical trials and current status of EDC system was assessed in this study. To increase the adoption of the EDCs, the related regulations should be developed, and also decision makers need to understand the importance of information technology in clinical trials. Background: Over the past decade, pharmaceutical companies have introduced a number of initiatives to boost the productivity of clinical trials. In clinical trials, this can take to reduce costs and durations of that are being considered in applying information technology. One of these initiatives has been the rollout of electronic data capture (EDC) systems, which allow patients and researcher to enter their trial information directly, either in electronic diaries or online systems. The utilization rate of the EDC in the United States is 41.5%, and similar trends can be seen in 40.5% in Japan. Objectives: Currently, the adoption of EDC in Korea is also getting increased, so the current status of EDC application should be assessed in clinical trials. The aim of this study was identified in present status of EDC system and to improvements to develop it. Method: The survey of participants has been accomplishment in a clinical research coordinator workshop and e-CRF System workshop, which was held in a University Hospital, located in Seoul. The main questionnaire items were 14 including the career of EDC system. Totally, 109 responses were classified by fields of clinical trials study, and comparison analyzed each questionnaire items. Result: The survey of participants has been separated pharmaceutical company participants (39.4%), contract research organization or clinical research associate participants (26%), investigator (research coordinator) (24%), and other participants (10.6%). Current EDC System applied Phase III(40.0%) and will plan to use of system Phase I(34.5%), Phase II(16.7%) Conclusion: EDC systems are increasingly applied for clinical trials and current status of EDC system was assessed in this study. To increase the adoption of the EDCs, the related regulations should be developed, and also decision makers need to understand the importance of information technology in clinical trials.

의약품 임상시험에서 피험자 보호

위계찬 대한의료법학회 2012 의료법학 Vol.13 No.2

This study focuses on the protection of trial subjects, who participate in clinical trials for new drug. It takes long time to develop new drugs and the clinical trials are required. Usually, pharmaceutical company, which develop new drug, request a research institution(usually, hospital) to investigate the examination of security and side effects of new drug. The institution recruit trial subject to participate in the trials. The contract for clinical research of investigational new drug is concluded between the pharmaceutical company and the institution. This thesis studies the legal regulations for protection of participants of clinical research for new drug. In this respect the first matter of this study is to seek which relation between pharmaceutical firm and participants of clinical trials. Especially, there is a question which the trial subject is entitled to demand the pharmaceutical company which requested clinical trials the institution to supply the investigational new drug, after the contract for clinical trials had terminated or cancelled. This study take into account the liability of the pharmaceutical company to trial subject. Secondly, it is researched the roles and authority of Institutional Review Board(IRB). IRB is Research Ethics Committee of the institution, in which clinical trials for new drug are conducted. According to the rule of Korea good clinical practice(KGCP), IRB is the mandatory organization which is authorized to approve, secure approval or disapprove the clinical trials for investigational new drug in the institution. The important roles are the review of ethical perspective of trial research and the protection of trial subject. Thirdly, this paper focuses if the participants are to be paid for the participation for clinical research. This is ethical aspect of clinical trials. It is resonable that the participant is reimbursed for expenditure such as travels, and other expenses incurred in participation in trials. It is not allowed that the benefit of clinical trials is paid to trial subject. The payment should not function as financial inducements for participations of trials. Finally, the voluntary consent of the trial subject is required. The institution ought to inform the subject, who would like to participate in trials, and it ought to received informed consent in writing for subject. In this regard, it is matter that trial subject has ability of consent. It is principle that the subject as severely psychogeriatric patient has not ability of consent. However, it is required that not only healthy people but also patients are allowed to take part in clinical trials of new drug, in order to confirm which the investigation new drug is secure. Therefore there are cases, in which the legal representative of subject consent the participation of the trials. In addition, it is very important that the regulations concerning clinical trials of new drug is to be systematically well-modified. The approach of legal and political approach is needed to achieve this purpose.

Adaptive design clinical trials: current status by disease and trial phase in various perspectives

Hyunjoon Lee,Sejung Hwang,In-Jin Jang,Jae-Yong Chung,Jaeseong Oh 대한임상약리학회 2023 Translational and Clinical Pharmacology Vol.31 No.4

An adaptive design is a clinical trial design that allows for modification of a structured plan in a clinical trial based on data accumulated during pre-planned interim analyses. This flexible approach to clinical trial design improves the success rate of clinical trials while reducing time, cost, and sample size compared to conventional methods. The purpose of this study is to identify the current status of adaptive design and present key considerations for planning an appropriate adaptive design based on specific circumstances. We searched for clinical trials conducted between January 2006 to July 2021 in the Clinical Trials Registry (ClinicalTrials.gov) using keywords specified in the Food and Drug Administration Adaptive Design Clinical Trial Guidelines. In order to analyze the adaptive designs used in selected cases, we classified the results according to the phase of the clinical trial, type of indication, and the specific adaptation method employed. A total of 267 clinical trials were identified on ClinicalTrials.gov. Among them, 236 clinical trials actually applied adaptive designs and were classified according to phase, indication types, and adaptation methods. Adaptive designs were most frequently used in phase 2 clinical trials and oncology research. The most commonly used adaptation method was the adaptive treatment selection design. In the case of coronavirus disease 2019, the most frequently used designs were adaptive platform design and seamless design. Through this study, we expect to provide valuable insights and considerations for the implementation of adaptive design clinical trials in different diseases and stages.

웹 기반 임상시험의 윤리적 고찰

김영옥(Kim, Young Ok),최병인(Choe, Byung In) 가톨릭생명윤리연구소 2018 인격주의 생명윤리 Vol.8 No.1

웹(web) 기반 임상시험은 임상시험 대상자가 임상시험 실시기관을 방문하지 않고 온라인으로 임상시험에 참여하는 것으로 임상시험의 전 과정이 모바일 기기, 컴퓨터 장치, 인터넷과 같은 전자 기술 (e-technology)을 최대한 활용하여 이루어진다. 이러한 방법은 최소한의 임상시험 기반시설을 바탕으로 대규모 잠재적 임상시험 대상자의 연구 참여를 간소화하고, 효율적인 데이터 수집과 분석을 통해 임상시험에 소요되는 시간을 단축시키며 비용을 절감하는 하나의 혁신적인 방법으로 평가된다. 그러나 웹 기반 임상시험은 우리 생활 속에 깊숙이 관여하고 있는 인터넷과 개인 기반의 전자 기술을 사용하는 고유한 특성 때문에 순기능(順機能)과 함께 기존의 임상시험 실시기관을 방문하는 임상시험에서는 볼 수 없었던 새로운 임상시험 관련 문제와 윤리적 문제들을 가지고 있을 수 있다. 2011년 미국의 제약회사 화이자(Pfizer)가 실시한 최초의 웹 기반 의약품 임상시험은 대상자 모집과 사전 선별과정, 대상자 전자동의, 대상자의 데이터 직접 보고 등 임상시험의 전 과정이 온라인으로 이루어져 전자 기술을 이용한 원격(remote) 임상시험의 응용과 발전에 도화선(導 火線)이 되었다. 하지만 웹 기반 임상시험은 임상시험 대상자의 웹 접근성과 기술 선호도 차이, 시험자와 임상시험 대상자의 상호작용이 부족한 전자동의 과정, 임상시험용 의약품 관리 및 이상반응 대응, 데이터의 신뢰성 보장 및 개인정보 보호 등 해결해야 할 과제를 가지고 있다고 하겠다. 따라서 모바일 기술과 컴퓨터 장치, 사물 인터넷(Internet of Things, IoT)과 같은 전자 기술은 계속해서 발전하고 이를 임상시험에 다양하게 적용하려는 시도가 이루어지고 있는 상황에서 웹 기반 임상시험에 대한 이해와 함께 해결해야 할 임상시험 관련 문제 및 윤리적인 문제를 깊이 있게 연구할 필요가 있다. Web-based or online clinical trials in which patients participate in clinical trials online without visiting clinical trial institutions take full advantage of information technologies, such as mobile devices, computer, internet of things(IOT) and etc. This new emerging methodology is applied from study start-up through execution to follow-up. The method is evaluated as one innovative way to reduce overall clinical trial costs through simplified procedures and to invite participation in larger and more geographically diversified prospective subjects. This also able to collect and analyze data with minimal trial infrastructure. Online clinical trials may have some positive effects but, at the same time, it brings new clinical trial-related and ethical issues that were not seen in the site-based clinical trials due to inherent characteristics of using internet and personal-based electronic technologies that are already integrated into our lives. In 2011, Pfizer conducted the first all-electronic, home-based clinical trial for a drug trial which performed pre-screening, recruiting participants, electronic informed consent, self-reported data by subjects through the study’s online website. It had introduced an opportunity to increase application and development of clinical trials to be done remotely. But there may be challenges at the same time, including the difference of accessibility to internet among the prospective subjects and technology preference between subjects, the process of electronic informed consent, lack of interaction between subjects and investigator, the management of investigational products and adverse event, the assurance for data reliability, privacy and confidentiality. Therefore, there is a need to study in depth for the ethical issues and clinical trial-related issues that need to be addressed as electronic technologies including mobile technology, computer devices, and internet of things(IOT) continue to grow and to apply them to clinical trials.

신약개발과 임상시험에 대한 미국 식품의약품청의 규제 법령에 관한 고찰

박수헌(Park, Soo-Hun) 한양법학회 2010 漢陽法學 Vol.30 No.-

Usually, it takes at least 8 years to develop new drugs. Especially, the clinical trials are required to spend about 5 years. In America, the whole steps for new drug development are provided thoroughly in statutes and regulations of FDA. Most of all, in this paper, I explored FDA’s regulations on the preclinical trials, Good Laboratory Practices, and FDA’s laws & regulations on the clinical trials that are the essential aspects in the new drug development. In order to protect the rights, safeties and welfares of the human research subjects in the clinical trials, FDA established very detailed provisions in the Code of Federal Regulations delegated by the relevant statutes. As mentioned earlier, FDA has exerted itself in recent years to ensure the safety as well as the speedy development of new drugs. The latter has been achieved by enacting PDUFA in 1992(now PDUFA IV from 2008 till 2012), the former is achieved by the thorough FDA regulations on the clinical trials. This paper consists of four chapters. Chapter Ⅰ describes the power of FDA on regulating the whole procedures of new drug development, the history of FDA’s laws and regulations on new drug development, and the purpose of this paper. Chapter Ⅱ examines the purpose, function, and contents of the preclinical trials and Good Laboratory Practices(GLPs). In addition, the methods of sanctions are explored when the clinical sponsor cannot comply with the GLPs. Chapter Ⅲ reveals the details relating to the clinical trials. It includes the contents of Investigational New Drug Application(IND), Informed Consent, IRB, the phases of the clinical trials, sponsor’s collaboration with FDA regarding clinical trials, obligations of clinical sponsors and investigators, expanded access to investigational drugs, clinical hold, IND termination and suspension. Chapter Ⅳ summaries the above mentioned contents in the first half. In the second half, I suggest that the status of KFDA’s guidances is required to be enhanced to the status of C.F.R. in America because they are related to the protection of the rights, safeties and welfares of the human research subjects in clinical trials.

종이기반 임상시험의 문제와 개선을 위한 정보기술

김옥구,김선하,김주한,배균섭,김화정,박병주,Kim, Ok-Gu,Kim, Seon-Ha,Kim, Ju-Han,Bae, Kyun-Seop,Kim, Hwa-Jung,Park, Byung-Joo 대한임상약리학회 2003 Translational and Clinical Pharmacology Vol.11 No.2

Despite the importance of clinical trials in developing a new drug, paper based clinical trial is still costly and time-consuming. The process of a clinical trial has not kept up with available information technologies. We identify two major problems in paper based clinical trial. They are time delay and poor error control. To solve the problems information technologies are used in certain areas of clinical trial, but it is still restricted and partially helpful. This paper first explains the two problems in the process of paper based clinical trial and introduces four available information technologies that can help clinical trial in implementing electronic clinical trial (ECT), where information technologies are used in the whole process of clinical trial.

Current Status and Challenges of Cancer Clinical Trials in Korea

심병용,박세훈,이순일,김진수,이경은,강윤구,안명주 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Purpose Cancer clinical trials in Korea have rapidly progressed in terms of quantity and quality during the last decade. This study evaluates the current status of cancer clinical trials in Korea and their associated problems. Materials and Methods We analyzed the clinical trials approved by the Korea Food and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey containing 22 questions was also performed with several cooperative study groups and individual researchers in 56 academic hospitals. Results The number of cancer clinical trials approved by the KFDA increased almost twofold from 2007 to 2013. The number of sponsor-initiated clinical trials (SITs) increased by 50% and investigator-initiated clinical trials (IITs) increased by almost 640%. Three hundred and forty- four clinical trials were approved by the KFDA between 2012 and 2013. At the time of the on-line survey (August 2013), 646 SITs and 519 IITs were ongoing in all hospitals. Six high volume hospitals were each conducting more than 50 clinical trials, including both SITs and IITs. Fifty-six investigators (31%) complained of the difficulties in raising funds to conduct clinical trials. Conclusion The number of cancer clinical trials in Korea rapidly increased from 2007 to 2013, as has the number of multicenter clinical trials and IITs run by cooperative study groups. Limited funding for IIT is a serious problem, and more financial support is needed both from government agencies and public donations from non-profit organizations.

의약품 임상시험 및 피험자 동의서에 대한 인식도

이성희,최병인,김철민,김경수 대한임상약리학회 2009 Translational and Clinical Pharmacology Vol.17 No.1

Background: The questionnaires were answered by the patients and their family members who visited the hospitals, the staffs in the hospitals, and the personnels who are involved with clinical trials such as the physicians, pharmacists and nurses for the purpose of surveying the cognition on clinical trial and informed consent. This study was performed in order to provide with the basic information and/or data for supporting to motivate the clinical trials by analyzing the factors affecting the difference of the cognition on each item. Method: The number of whom responded to the questionnaires was 310 in total, which was composed with 137 patients and their family members, 109 staffs in the hospitals, and 64 personnels involved with clinical trials. Result: Most of them were well acquainted with clinical trial, and knew that it is the processes to identify the safety and efficacy with the patients and it has been done in the big hospitals like university hospitals. As the results of surveying the cognition on the processes of clinical trials, most of them were known well but something was not recognized like the patients’ right to see their medical history records. While the expectation which can be obtained by participating in clinical trials was not so big, the biggest one was to get more advantageous benefits (efficacy) from clinical trial. With regard to the cognition on the informed consent, it was well understood its basic concept and procedures. The responders who participated in clinical trials before answered they regard that to conduct the clinical trial is more ethic and the mandatory process to develop the new drugs rather than what those that did not participated in the clinical trials, by 2.0 and 2.7 times, respectively. From the points of general relations considering the participation in clinical trials, the persons with diseases show more experience to participate in it, by 5.8 times, rather than those without diseases, and the persons with medication have 4.8 times more experience in participate in clinical trials than those who do not take the drugs. In addition, the persons who have participated in clinical trials showed more willingness to participate in clinical trials than those who have not participated in it. Conclusion: From the survey results by the questionnaire, considering the current circumstances that the numbers of clinical trials has been rapidly increasing, it was found and is recommended that the persons participating in clinical trials should continuously give the patients and their family members more correct and useful knowledge and information on clinical trials and at the same time that the patients should make their efforts to acquire the adequate information and their duties on clinical trials and make decision of their participation in clinical trials by themselves. Background: The questionnaires were answered by the patients and their family members who visited the hospitals, the staffs in the hospitals, and the personnels who are involved with clinical trials such as the physicians, pharmacists and nurses for the purpose of surveying the cognition on clinical trial and informed consent. This study was performed in order to provide with the basic information and/or data for supporting to motivate the clinical trials by analyzing the factors affecting the difference of the cognition on each item. Method: The number of whom responded to the questionnaires was 310 in total, which was composed with 137 patients and their family members, 109 staffs in the hospitals, and 64 personnels involved with clinical trials. Result: Most of them were well acquainted with clinical trial, and knew that it is the processes to identify the safety and efficacy with the patients and it has been done in the big hospitals like university hospitals. As the results of surveying the cognition on the processes of clinical trials, most of them were known well but something was not recognized like the patients’ right to see their medical history records. While the expectation which can be obtained by participating in clinical trials was not so big, the biggest one was to get more advantageous benefits (efficacy) from clinical trial. With regard to the cognition on the informed consent, it was well understood its basic concept and procedures. The responders who participated in clinical trials before answered they regard that to conduct the clinical trial is more ethic and the mandatory process to develop the new drugs rather than what those that did not participated in the clinical trials, by 2.0 and 2.7 times, respectively. From the points of general relations considering the participation in clinical trials, the persons with diseases show more experience to participate in it, by 5.8 times, rather than those without diseases, and the persons with medication have 4.8 times more experience in participate in clinical trials than those who do not take the drugs. In addition, the persons who have participated in clinical trials showed more willingness to participate in clinical trials than those who have not participated in it. Conclusion: From the survey results by the questionnaire, considering the current circumstances that the numbers of clinical trials has been rapidly increasing, it was found and is recommended that the persons participating in clinical trials should continuously give the patients and their family members more correct and useful knowledge and information on clinical trials and at the same time that the patients should make their efforts to acquire the adequate information and their duties on clinical trials and make decision of their participation in clinical trials by themselves.

임상시험 관련 법제의 문제점과 개선방안

이은영 전북대학교 동북아법연구소 2020 동북아법연구 Vol.13 No.3

Today, formal and informal clinical trials have become part of our lives. Aside from the underlying questions and concerns about the nature of clinical trials that test drugs or devices for which human safety has not been confirmed, it is doubtful whether the various clinical trials that are widely conducted today are fair and transparent. Recently, KolonTissuegean's Invossa, which received a license from the Food and Drug Administration due to the submission of false data in Korea, clearly proves this. However, in Japan, a medically advanced country, the inadequacy of clinical trials of Novartis's anti-hypertensive drug Diovan was debated many years ago. Representative laws governing clinical trials include the Bioethics and Safety Act and the Pharmacy Act. Because both laws contain individual content about clinical research, a wide range of legal gaps arise in the area of ​​legal system governing clinical research. In the case of clinical trials involving economic interests with pharmaceutical companies, there is an urgent need to improve the legal system. Regarding the legal rules for clinical trials, a clinical research method to prevent cheating in clinical trials has recently been enacted in Japan, which is considered more passive than Korea, and has been in effect since April 1, 2018. The medical incidents related to clinical trials over the past several years have shifted to active institutional interventions in the medical and pharmaceutical fields, which were previously recognized as the autonomous domain of experts and had minimal restrictions. In Korea, it is time to deepen the concern about improving the overall legal system for clinical trials. Korea's current legislation on clinical trials, referred to as the “gold standard” of medical health research, is not systematic and decentralized. Unnecessary and inefficient related systems need to be drastically abolished or revised. However, the question of how to obtain results that are beneficial to patients and society while securing the safety of participants or patients in clinical trials is an issue that should be constantly considered when seeking ways to improve legislation on clinical trials. 오늘날 임상시험의 일상화, 나아가 임상시험의 국제화 및 산업화로 인하여 파생되는 각종 문제에 대응하기 위한 법제도의 정비는 비단 우리만의 문제는 아닐 것이다. 우리나라에서는 이제 첨단재생의료법의 시행과 맞물려 임상시험에 관한 전반적인 법제도의 정비에 대한 고민이 깊어지는 시점이다. 임상시험에 대한 법적 규율과 관련해서는 우리나라보다 소극적이라고 평가받는 일본에서도 최근 임상시험의 부정행위를 방지하기 위한 임상연구법이 제정되어 이미 2018년 4월 1일 부터 시행되고 있다. 지난 수년간 임상시험과 관련한 사회적인 사건들이 잇따르면서 기존에 전문가의 자율영역으로 인정되어 최소한의 규제만 가해졌던 의·약학 분야에 적극적인 제도적 개입으로 방향이 전환된 것이다. 우리나라에서 임상시험을 규율하는 대표적인 법률로는 생명윤리 및 안전에 관한 법률과 약사법이 있다. 두 법률 모두 임상연구에 관해 개별적인 내용만을 담고 있기 때문에 임상연구를 규율하는 전체 법제도의 영역에서는 광범위한 법적 공백이 발생한다. 특히 제약회사와의 경제적 이해관계가 얽혀 있는 임상시험의 경우 이를 규율할 법적 장치가 없다는 점에서 법제도의 개선이 시급하다. 의학보건 연구의 ‘최적표준(gold standard)’으로 일컬어지는 임상시험에 관한 우리나라의 현행 법제는 체계적이지 못하고 분산되어 있다. 물론 임상시험에 관한 법제도를 정비한다고 하여 모든 문제가 해결되는 것은 아닐 것이다. 병원이나 제약회사에서 관련 법령에서 규정하는 방법과 절차에 따라 공정하고 투명하게 임상시험을 진행하는 것이 중요하다. 잘 설계되고 수행되는 임상시험은 연구 참여자의 복지를 침해하지 않고 보건의료의 문제에 대한 해답을 제시할 수 있다. 그럼에도 불구하고 임상시험에 대한 체계적인 규제를 통하여 임상시험의 공정성 및 투명성을 제고할 수 있는 기초를 마련한다는 점을 감안하면 임상시험에 대한 법제의 정비는 더 이상 미룰 수 없는 시급한 과제가 아닐 수 없다.

임상시험 재 참여에 대한 임상시험 피험자의 이해도 및 만족도의 영향

최선,최유리,류병은,한옥연,나현오 한국병원약사회 2011 병원약사회지 Vol.28 No.4

This research was conducted to identify the influence of trial participants’general knowledge and satisfaction in a clinical trial on re-participation. From September 2008 to October 2008, a survey questionnaire was distributed to 108 new clinical trial participants in ongoing clinical trials at the investigated Hospital. The participants’general knowledge and satisfaction were measured using a 5-point Likert scale (from 0 to 4) for general attitude towards clinical trials, information source and motive for clinical trial participation,general knowledge of clinical trials, and satisfaction towards one’s own clinical trial. The response rate was 83.3% and 63.3% of respondents agreed with re-participation. We grouped respondents as ‘re-participation acceptor’and ‘re-participation decliner’based on respondents’intent of re-participation. Most re-participation acceptors had more positive attitude towards clinical trial (p<0.05). Similarly, more re-participation acceptors evaluated their general knowledge level positively, especially for‘ background and objective’,‘ frequency of visit and test’and investigational drug dosing’(p<0.05). Among the investigated items, “interest in trials in general”was the most important factor, while “needs for clinical trial into some area”,and“ subjective satisfaction level”were significant effect factors (p<0.05). According to the results, clinical trial staff should make an effort to interest possible participants by providing proper information, and help them recognize the need for clinical trials and the benefits of clinical trials through consistent communication.