말기 암 환자에 대한 임상시험과 피험자의 자기결정권의 본질

송영민 대한의료법학회 2014 의료법학 Vol.15 No.1

Because of unpredictability and high possibility of abnormal results by clinical trials compared to general medical behaviors, a procedure for ensuring with sufficient explanations by investigators must be secured. Therefore, in a sequence of clinical trials, what kinds of scope, stage, and method of explanations provided by investigators, including doctors or researchers, to trial subjects are closely related to the compensation for damages by violation of liability for explanation. In case of application of clinical trials to patients who have critical illness such as cancer, issues of 「Quality of Life」 regarding trial subjects, cancer patients, should be discussed. Especially, in case of clinical trials for terminal cancer patients, the right of subjects' self- determination, which is a fundamental principle in medical behaviors, should be discussed. The right of self- determination includes participation in clinical trials for the possibility of life-sustaining even a little bit, or no participation in clinical trials in order to have a time for completing the rest of his life. Like this, if the extent and scope of explanations related to the issues of 「Quality of Life」 are raised as main issues, the evaluation of 「Quality of Life」 , should be a prerequisite. In many occasions, realistically, despite bad results such as deaths or serious adverse drug reactions after clinical trials, it may not be easy for compensating to trial subjects or their survivors, who requested civil compensation for damage. Futhermore, in abnormal results after concealment of clinical trials or performance of clinical trials without permission, and in the case of trial subjects' failures of proving proximate cause between the clinical trials and abnormal results, problematic results such as no protection to the trial subjects could be occurred. In performing clinical trials, investigators should provide sufficient explanations for trial subjects and secure voluntary informed consents from the trial subjects. Therefore, clinical trials without trial subjects' permissions and the informed consent process violate trial subjects' rights of self-determination, and the investigators shall be liable for compensation for damages. Then, issues might be addressed are what are essential contents of patients' 「rights of self-determination」 infringed by clinical trials without subjects' permissions. Two perspectives about patients' rights of self-determination might be considered. One perspective regards physical distress of patients (subjects) from therapies without sufficient explanations as the crux of the matter. The other perspective regards infringement of human dignity caused by being subjects without permission as the crux of the matter irrespective of risks' big and small influences. This research follows perspective of the latter. Forming constant fiduciary relation between investigators (doctors) and subjects (patients) pursuant medical contracts, and in accordance with this fiduciary relation, subjects, who are patients, have expectations of explanations and treatments by the best ways. If doctors and patients set this forth as a premise, doctors should assume civil liability when doctors infringe patients' expectations.

네트워크 분석을 이용한 불면의 무작위임상시험 해외 연구 동향

백영화(Younghwa Baek),진희정(Hee-Jeong Jin) 한국콘텐츠학회 2013 한국콘텐츠학회논문지 Vol.13 No.12

본 연구는 불면과 관련된 무작위임상시험의 해외 연구 동향을 살펴보기 위하여 시계열적 키워드 비교분석 및 네트워크 분석을 실시하였다. 분석에 사용된 자료는 ‘Insomnia’와 ‘Randomized Clinical Trial’의 연관 키워드를 사용하여 ClinicalTrials의 379건, Web of Science의 132건을 선정하였다. 분석 결과, ClinicalTrials에서는 불면과 약물요법을 중심으로 인지행동요법, 우울 등의 키워드가 네트워크를 이루고 있었다. WOS에서는 ClinicalTrials의 결과에 멜라토닌 키워드가 추가적으로 나타났다. 또한, 연구 대상자 중 특징적으로 노인과 여성에 대한 연구가 꾸준히 진행되는 것으로 파악되었다. In this study, we applied the time series analysis to the randomized controlled trial (RCT) researches related to insomnia for finding international trends. The data used in the analysis of 379 of ClinicalTrials, Web of Science was the of 132 by several keyword related with ‘Insomnia’ and ‘Randomized Clinical Trial’. In ClinicalTials, RCT studies for insomnia, drug, cognitive behavioral therapy, depression were the key words make up the main network. In WOS, ‘melatonin’ key word was added in the main network. In addition to, we found the characteristic that the elderly and female subjects were steady studied.

여성의 갱년기 증상에 대한 석류농축액의 유효성 및 안전성을 평가하기 위한 단일기관, 무작위 배정, 이중맹검, 위약대조군 임상시험

안기훈 ( Ki Hoon Ahn ),김선미 ( Sun Mee Kim ),이경욱 ( Kyong Wook Yi ),박현태 ( Hyun Tae Park ),신정호 ( Jung Ho Shin ),김영태 ( Young Tae Kim ),허준용 ( Jun Young Hur ),김선행 ( Sun Haeng Kim ),이규완 ( Kyu Wan Lee ),김탁 ( Tak 대한폐경학회 2010 대한폐경학회지 Vol.16 No.2

연구목적: 석류농축액이 폐경여성의 갱년기 장애에 어떠한 영향을 미치는지 알아보고자 하였다. 연구재료 및 방법: 2008년 5월부터 2008년 9월까지 고려대학교 병원을 방문한 증상을 가진 폐경여성환자를 대상으로 무작위, 이중맹검, 시험-대조군 임상시험으로 진행되었다. 총 112명의 환자를 대상으로 55명의 시험군과 57명의 대조군이 포함되었으며 시험군은 석류 원액 20 ml가 포함된 100 ml의 시험약물을 대조군은 석류가 섞이지 않은 대조약물을 12주간 투여하여 연구시작시점과 마지막 시점의 결과를 비교하였다. 측정을 위한 일차지표는 쿠퍼만 지표로 계산된 폐경증상의 정도였고, 이차지표는 혈중 estradiol (E2, pg/ml) 수치였다. 결과: 쿠퍼만 지표로 측정한 폐경증상을 비교하였을 때 쿠퍼만 지표점수가 첫 방문시에는 석류농축액을 투여한 군과 위약을 투여한 군에서 유의한 차이가 없었으나 12주 뒤 (P<0.0001) 마지막 방문 시에는 석류를 투여한 군에서 유의하게 폐경증상이 좋아짐을 관찰할 수 있었다. 우울감의 경우 석류투여군에서 쿠퍼만 지표의 수치가 낮은 경향을 보였으나 통계학적으로 유의하지 않았다. 혈청 E2 농도는 첫 방문 시나 마지막 방문 시 두 군간에 차이가 없었다. 결론: 석류농축액은 증상을 지닌 폐경여성에서 안전하게 전반적인 개선을 나타냈다. 석류의 폐경여성에서의 효과가 에스트로겐에 의한 것인지는 이 연구로 결론 내리기 어려우며 향후 이에 대한 추가적인 연구가 필요할 것으로 보인다. Objectives: To investigate the safety and effect of pomegranate extract on postmenopausal syndrome. Methods: One hundred twelve women participated in a randomized, double-blind, placebo-controlled trial conducted in a tertiary university hospital in Korea. Women were treated with pomegranate extract or placebo for 12 weeks. The primary end point was menopausal symptoms, which were evaluated based on the Kupperman Index. The secondary end point was the serum estradiol (E2, pg/ml) level. Statistical analysis was performed. Results: Menopausal symptoms as the Kupperman Index were significantly improved in the pomegranate group compared to placebo during the 12 weeks of intervention (P<0.0001). Melancholia did not differ between the two groups. There was also no difference in serum E2 levels. There were no differences between the two groups in age, body weight, height, systolic and diastolic blood pressures, serum white and red blood cell counts, and fasting blood glucose, hemoglobin, aspartic transaminase, alanine transaminase, total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, creatinine, and E2 levels. The side effects of pomegranate extract were negligible. Conclusion: Pomegranate extract is safe and effective in the treatment of menopausal symptoms. Further studies on whether or not the beneficial effect of pomegranate extract is due to the estrogen component are needed.

무작위 임상시험의 윤리적,법적 문제

최경석 ( Kyung Suk Choi ) 한국의료윤리학회 2008 한국의료윤리학회지 Vol.11 No.1

Human experimentation can be ethically justified when subjects participate on a voluntary basis. Informed consent is required for clinical trials, including randomized clinical trials. Nevertheless, ethical issues arise when subjects are randomly distributed to experimental and control groups in randomized clinical trials. I argue that equipoise as well as informed consent is a condition of randomized clinical trials. Benjamin Freedman distinguishes theoretical equipoise from clinical equipoise. I call the former the "individual physician equipoise" and the latter the "clinical community equipoise". Under clinical community equipoise, randomized clinical trials are ethically justified because physicians may still provide the best treatment to their patients. The above ethical principle should be applied to placebo-controlled randomized clinical trials. When experimental drugs and placebos are in clinical community equipoise, a trial may be ethically justified. In addition, placebo-controlled randomized clinical trials should be designed with double-blinding. The reason for this requirement is that physicians would cheat their patients without doubleblinding. Current FDA regulations in Korea and the US do not sufficiently reflect the above ethical points. Institutional review boards should review their protocols in light of these ethical points. In particular, IRB regulations should reflect the basic ideas of equipoise in randomized clinical trials and double-blinding in placebo-controlled randomized clinical trials.

임상시험에서 비교군 설정 및 무작위 배정과 맹검

기모란 ( Mo Ran Ki ) 대한임상종양학회 2007 Korean Journal of Clinical Oncology Vol.3 No.1

일차의료에서 지질저하제 치료 후 외래방문율 개선효과에 대한 휴대폰 문자메시지와 편지 회상법간의 무작위배정 대조군 비교 임상시험

조성자,김영식,신호철,성은주,김대현,이상엽,전태희,양윤준,조충환,강희철,정유석 대한가정의학회 2010 Korean Journal of Family Medicine Vol.31 No.4

Background: In the primary care setting, compliance with lipid lowering therapy was relatively low. In order to compare the efficacy of a short messaging service (SMS) text messaging and postal reminder as means of improving attendance rates during the first 24 weeks of lipid-lowering therapy, a randomized controlled trial of 918 patients from 19 family practice clinics was conducted between February 2003 and June 2006. Methods: Patients were randomly assigned into 3 groups: SMS (327), postal (294),and control (297) group. To ascertain attendance rates, patients were followed up at 24 weeks after their treatment. Reminders were sent at 16 weeks from the coordinating center. Results: Overall attendance rate was 74.1%. This differed between groups, with 76.1% attendance for the SMS group,73.5% for the postal group, and 72.4% for the control group. According to a multivariate analysis, the SMS group had a significantly higher attendance rate (Odds ratios [OR] 1.48; 95% confidence interval [CI], 1.01 to 2.16) than the control group, but the postal group (OR, 1.15; 95% CI, 0.79 to 1.69) did not. Moreover, the cost per attendance for the SMS reminder (155 Korean Won [KRW]) was much lower than that for the postal reminder (722 KRW). Conclusion: SMS reminder may be more cost saving method to improve the attendance rate compared with the postal reminder.

임상예방의료에 필요한 과학적 증거의 평가방법

이중엽,박병주 대한의사협회 2011 대한의사협회지 Vol.54 No.10

Evaluation of scientific evidence in the medical literature is based on the research methodology, which can be the fundamental tool for medical professionals to improve their practice. Since analytic studies usually provide evidence for generating hypotheses and selecting appropriate research designs, this article aims to review the methods for evaluating the study quality in randomized controlled trials (RCTs), cohort studies, and case-control studies. Critical appraisal of systematic errors including selection bias, performance bias, attrition bias, detection bias, and publication bias are the essential elements of the evaluation. Clinical trials need to have an adequate description of sequence generation and allocation concealment, blin-ding for exposure measurement, completeness of follow-up and intention to treat analysis, and blinding for outcome evaluation. For cohort studies, like RCTs, appropriate control of confoun-ding variables is needed to prevent selection bias, and blinding and completeness of follow-up are also very important. Matching of the case group to the control group, blinding of interviewers, and proper definition of the cases and controls are important to prevent bias in a case-control study. Since the process of critical appraisal depends on the quality of reporting, there have been efforts to improve the reporting quality of the medical literature. However, reporting all of the elements necessary to avoid bias does not automatically guarantee an exclusion of bias or the quality of a study; instead, what is important is the logical connection of the elements of a study and the eventual lucid expression of the elements.

위암의 선행화학 요법

홍영선,박조현,Hong, Young-Seon,Park, Cho-Hyun 대한위암학회 2005 대한위암학회지 Vol.5 No.3

위암은 한국에서 가장 발생빈도가 높은 암이며 암 사망원인의 2위를 차지하고 있다. 치료법 중에서 수술이 유일하게 완치의 기회를 제공하나, 진행 암에서는 근치적 절제(R0 resection, R0 절제)수술 후에도 약 50%의 환자에서 재발을 보여, 보다 효과적인 치료법의 개발이 필요하다. 선행화학요법은 병소가 급격하게 성장, 팽창하는 것을 막고 내성을 지닌 세포의 출현을 예방하며 그렇게 함으로써 완치의 기회를 늘리고, 암의 국소 조절을 더 잘 함으로서 수술의 범위를 줄여 수술로 인한 부담을 줄이며, 절제 불가능한 암을 절제 가능한 암으로 만드는 것이 목표이다. 따라서 치유절제가 불가능할 것으로 판단되었던 위암의 병기를 낮추어 R0 절제 후 완치율을 높일 것으로 기대되고 있으며 계속되는 연구에서 수술로 인한 이환율과 사망률을 높이지 않는 것으로 나타나고 있다. 선행 화학요법에 사용할 수 있는 항암제는 여러 가지이나 가장 높은 효과를 보이는 항암제가 결정되지 않았고 또 항암제를 투여하는 시기, 선행 화학요법 후에 재발을 방지하기 위한 항암제의 복강 내 투여나 방사선 치료의 병용 등이 복막 전이와 국소재발을 줄이는 데 도움이 되는지 등이 향후 시행될 연구에서 규명되어야 하겠고, 또 적절한 수술방법에 관하여도 합의가 이루어져야 하겠다. 선행 화학요법과 관련된 여러 가지 의문들을 해결하기 위한 노력은 다기관이 참여하는 전향적 무작위 3상 임상연구를 통하여 이루어져야 할 것으로 생각된다. Gastric cancer is the most prevalent cancer in Korea and comprises the second cause of cancer death. Surgery only can provide chance of cure, but most locally advanced cancers recur after a curative resection, even though important advances in the surgical and nonsurgical treatments of gastric cancer have taken place. Preoperative chemotherapy theoretically can provide the advantages of reducing the bulk of tumor, which might improve the R0 resection rate, and of treating micrometastases early. Also, preoperative chemotherapy is expected to render unresectable tumors resectable without increasing postoperative morbidity and mortality. There are many new chemo-therapeutic agents available for the treatment of advanced gastric cancer, but still the most effective agent, the optimal time and number of cycle for administration are still not known. The addition of postoperative chemotherapy through an intraperitoneal route and/or radiotherapy might affect the outcome of surgery favorably, but that hasn't been proved yet. A multicenter prospective randomized phase III trial should be peformed to answer for those questions and to improve the curability of gastric cancer treatment.