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.

불면증 무작위배정 임상시험에 대한 문헌 고찰

박혜주 ( Hye Joo Park ),유종향 ( Jong Hyang Yoo ),권지혜 ( Ji Hye Kwon ),이시우 ( Si Woo Lee ) 대한한방신경정신과학회 2013 동의신경정신과학회지 Vol.24 No.3

Objectives : To review the recent trend of randomized controlled clinical trials on insomnia and to provide information for future clinical trials. Methods : A total of 667 pieces of literature were searched using the key words ‘insomnia’ and ‘randomized controlled trial’ and using the title ‘insomnia’ with the topic ‘trial or trials’, published from 2008 to 2012 through Web of Science. Studies including randomized controlled clinical trials were sorted from the search result and finally 104 pieces of the literature were selected and examined. Results : Besides 104 clinical trials, 14 trials related to CAM (Complementary and Alternative Medicine) were also reviewed. On average, 20 trials were annually conducted and they showed a growing trend. Participants were between 31 and 90 (34.6%), and were observed for less than 30 days (28.8%) in most trials. As intervention methods for clinical trials, non-pharmaceutical methods were used in 59 studies (56.7%), pharmaceutical drug in 43 studies (41.3%) and combinations in 2 studies (1.9%). In 60 studies, only insomnia without any underlying diseases was examined and other 44 studies involved other diseases. As diagnosis assessment tools, Sleep diary and Polysomnography were used. Conclusions : Randomized controlled trials relevant to insomnia were on the increase, but only a small number of clinical trials on Oriental Medicine have been performed. Larger scientific and well-founded randomized controlled trials are required for developing Oriental Medicine and establishing high-quality guideline going forward.

한국 침 임상시험의 질 평가 및 분석

박지은,강경원,최선미 대한침구의학회 2007 대한침구의학회지 Vol.24 No.1

Objectives : To evaluate the methodological quality of Korean Acupuncture Clinical trials Methods : Two independent researchers reviewed 12 protocols of Acupuncture clinical trials which were conducted in Korea 2006. Also, Survey Principal Investigator of those was conducted. We compare the results of protocol review with investigator reponses of actual practice. Quality assessment consisted of 5 items including random sequence generation, randomization method, allocation concealment, subject blinding, assessor blinding. Results : Randomization was performed using the proper procedure to insure that treatment assignment is unbiased and concealed from subjects in all clinical trials, According to protocols, 6(50%) of 12 clinical trials used computer-generated random numbers, 6(50%) remaining trials didn't describe the randomization method. Also all trials used appropriate randomization methods on the basis of the survey results: 8 trials used computer-generated random number, 2 used random table. Of 7 protocols in which allocation concealment was stated, 5(71%) reported appropriate method (Calling a central office or statisticians, Sealed opaque envelopes). However according to survey, 5(42%) of 12 trials used inappropriate allocation concealment (Keeping a master randomization list and referring to when subject entered the trial). In addition, the result of protocol review and survey response was not coincident in 5(42%) trials. Subject blinding was conducted in all except 1 clinical trials. Although 11(92%) of 12 trialswere conducted using assessor blinding in actual practice, only 7(58%) reported that in protocol. Conclusion : Although randomization and blinding were conducted adequately, allocation concealment was used inadequately. Not only appropriate allocation concealment, but also every quality assessment item including randomization, blinding should be stated in more detail in protocol.

Clinical studies of traditional Japanese herbal medicines (Kampo): Need for evidence by the modern scientific methodology

Ichiro Arai 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.3

Background: Japanese Kampo medicine is a traditional medicine with roots in ancient Chinese medicine. Because traditional physicians had been abolished in Japan, the present mainstream of Kampo treatment is that physicians who learned modern Western medicine prescribe Kampo extract products based on Western medical diagnosis. This situation is different from that in other east Asian countries, and the physicians require scientific clinical evidence. Methods: Clinical studies were searched from literature databases, clinical trial registry sites, and “Evidence Reports of Kampo Treatment (EKAT)” published by the Japan Society for Oriental Medicine. Results: At the approval of Kampo products, scientific clinical evidence was not required because they have a long-period experience as a decoction. However, in the 1990s, Kampo products became a subject for national reevaluation; double-blind and placebo-controlled clinical trials. At the time, a methodological foundation for conducting clinical assessments of Kampo medicines was established. From 2000 onwards, with the evidence-based medicine era, the field of Kampo medicine also saw many randomized controlled trials, and their evidence was collected and published as EKAT. In the 2010s, post-marketing clinical trials of Kampo products also had to be conducted in this environment due to the need for ethical and scientific assurance. Currently, there are numerous clinical trials of Kampo products being conducted with high-grade trial designs. Conclusion: The situation of Kampo clinical studies reflects the unique history and position of Kampo medical system and Kampo products in Japan.

Effectiveness and safety of fluoroscopy-guided acupuncture for subacromial impingement syndrome : A protocol for a randomized, patient-assessor blind, parallel clinical trial

Seo, Jihye,Yeom, Seung-Ryong,Shin, Hee-Ra,Park, Kyungtae,Kim, Jae Kyoun,Park, Soo-Ji,Lee, Sangkwan Williams & Wilkins Co 2018 Medicine Vol.97 No.38

<P><B>Abstract</B></P><P><B>Introduction:</B></P><P>Subacromial impingement syndrome (SIS) is one of the most common diseases inducing shoulder pain. Acupuncture is a source of pain relief that has been used for SIS; however, there is no clinical study about image-guided acupuncture for SIS. The aim of this study is to evaluate the effectiveness and safety of fluoroscopy-guided acupuncture in patients with SIS.</P><P><B>Methods:</B></P><P>This is the protocol for a randomized, patient-assessor blind, parallel clinical trial comparing fluoroscopy-guided acupuncture to acupuncture without fluoroscopy. There will be a 1-week run-in period before random allocation to 2 groups. The total duration of the clinical trial will be 3 weeks including 2 weeks for the follow-up period. A total of 57 participants will be enrolled for the clinical trial. Acupuncture will be conducted in 2 sessions for each group, once at baseline and once at the 1-week mark. The primary outcome will be 100 mm pain visual analogue scale. Secondary outcomes will include the Neer and Hawkins test, the Modified Constant Murley Score scale, the Shoulder Pain And Disability Index, the patient satisfaction degree, and the accuracy rate of acupuncture. For the evaluation of safety, adverse events will be monitored.</P><P><B>Discussion:</B></P><P>We designed the clinical trial using image-guided acupuncture. This will be the first trial to study the effectiveness of image-guided acupuncture for SIS compared with acupuncture using the proportional measurements.</P><P><B>Trial registration:</B></P><P>Clinical Research Information Service Registration Number is KCT0002751. Registered on March 23, 2018.</P>

세균성 질증의 한방외치요법에 대한 무작위 대조군 비교 임상시험 중심의 고찰

황영식,이진욱,김규태,박승혁,이진무,이창훈,장준복,황덕상 대한한방부인과학회 2019 大韓韓方婦人科學會誌 Vol.32 No.2

Objectives: The purpose of this study was to show effectiveness of Korean medicine external treatment on bacterial vaginosis by analyzing randomized controlled clinical trials. Methods: We searched randomized controlled clinical trials related with Korean external treatment on bacterial vaginosis through national and overseas database and analyzed them in detail. Results: 15 articles were included according to our selection criteria and 2,176 women were involved. 1. All treatment groups were treated with intervention including Korean medicine external treatment and their results were statistically more effective than control groups. 2. External washing was the most frequently used method followed by vaginal tablet, fumigation and powder. 3. The most frequently used herbal medicine was Sophorae Radix followed by Phellodendri Cortex, Cindi Fructus, Dictamni Radicix Cortex and Kochiae Fructusa. 4. There were 4 studies reporting side effects of treatment and no significant side effects were observed. Conclusions: There was significant difference in the effectiveness of the intervention including Korean external therapy. Based on the analysis, it could be an effective way for the treatment of bacterial vaginosis in clinical practice. Objectives: The purpose of this study was to show effectiveness of Korean medicine external treatment on bacterial vaginosis by analyzing randomized controlled clinical trials. Methods: We searched randomized controlled clinical trials related with Korean external treatment on bacterial vaginosis through national and overseas database and analyzed them in detail. Results: 15 articles were included according to our selection criteria and 2,176 women were involved. 1. All treatment groups were treated with intervention including Korean medicine external treatment and their results were statistically more effective than control groups. 2. External washing was the most frequently used method followed by vaginal tablet, fumigation and powder. 3. The most frequently used herbal medicine was Sophorae Radix followed by Phellodendri Cortex, Cindi Fructus, Dictamni Radicix Cortex and Kochiae Fructusa. 4. There were 4 studies reporting side effects of treatment and no significant side effects were observed. Conclusions: There was significant difference in the effectiveness of the intervention including Korean external therapy. Based on the analysis, it could be an effective way for the treatment of bacterial vaginosis in clinical practice.

Understanding noninferiority trials

한서경 대한소아청소년과학회 2012 Clinical and Experimental Pediatrics (CEP) Vol.55 No.11

Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies,standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

Understanding noninferiority trials

Hahn, Seokyung The Korean Pediatric Society 2012 Clinical and Experimental Pediatrics (CEP) Vol.55 No.11

Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

제왕절개술 후 발생한 위장관 기능장애에 대한 최신 RCT 연구 동향 분석 -경혈 자극을 중심으로-

정소미,이진무,이창훈,황덕상,장준복 대한한방부인과학회 2020 大韓韓方婦人科學會誌 Vol.33 No.1

Objectives: The purpose of this study was to show effectiveness of Acupuncture treatment on gastrointestinal dysfunctions after Cesarean section by analyzing randomized controlled clinical trials. Methods: We searched randomized controlled clinical trials related with acupuncture treatment on gastrointestinal dysfunctions after Cesarean section through national and overseas database and analyzed them in detail. Results: 6 articles were included according to our selection criteria and 1,084 women were involved. 3 studies used TEAS (Transcutaneous Electrical Acupoint Stimulation), 2 studies used Elastic band and 1 study used Acupressure by hand. Their results were statistically more effective than control groups. The most frequently used acupoints were Neiguan (PC6), Zusanli (ST36) followed by Sanyinjiao (SP6), Hegu (IL4). Conclusions: There was significant difference in the effectiveness of the intervention including Acupuncture treatment. Based on analysis, it could be an effective way for the treatment of gastrointestinal dysfunctions after Cesarean section in clinical practice.

Effect of calcium on premenstrual syndrome: A double-blind randomized clinical trial

( Fatemeh Shobeiri ),( Fahimeh Ezzati Araste ),( Reihaneh Ebrahimi ),( Ensiyeh Jenabi ),( Mansour Nazari ) 대한산부인과학회 2017 Obstetrics & Gynecology Science Vol.60 No.1

Objective Premenstrual syndrome (PMS) affects millions of women and is known as the most important disorder among them. The very aim of the present study was to evaluate the effects of low dose calcium on severity of PMS. Methods This study can be considered as a double-blind randomized clinical trial. Female students of Hamadan University of Medical Sciences diagnosed with PMS in 2014 participated in the present study. Sixty-six female students diagnosed with PMS were involved in the experimental and control groups. The participants were randomly assigned into two groups to receive 500 mg of calcium daily or placebo for two months. Severity of PMS was detected by Daily Record of Severity of Problems, which was used to measure symptoms during one menstrual cycle before and two menstrual cycles after the intervention. Results No signifcant differences were observed in the mean scores of PMS symptoms between calcium and placebo groups before the treatment (P=0.74). However, signifcant differences were noticed between the two intervention groups in the first (P=0.01) and second menstrual cycles (P=0.001) after the intervention. The differences were significant in subgroups of anxiety, depression, emotional changes, water retention, and somatic changes in calcium group compared with placebo group in the menstrual cycle before the intervention and two menstrual cycles after the intervention and among menstrual cycles (0, cycle 1, cycle 2) in calcium group (P=0.01). Conclusion Overall, the results of the present study suggest that treatment with calcium supplements is an effective method for reducing mood disorders during PMS.