薬理と治療

昨今,グロ-バル治験も含め治験環境は激変しており,日本は必ずしも優先的に治験の対象症例が配分される国では,もはやなくなってきている.また,いわゆるドラッグ・ラグ,ドラッグ・ロスを回避し,治験におけるわが国のプレゼンスを向上するためにも,医療機関における症例集積性を向上させ,明確な治験全体のパフォ-マンスを改善することは非常に重要である.とくに,契約面も含めて,早急な治験の立ち上げや確実な症例集積を行うことは,医療機関としての治験実績の信頼を獲得することに役立つだろう.上記を達成するため,日本医科大学研究統括センタ-では,臨床研究部門内に治験ブランディンググル-プを設置し,本学内の治験環境の改善と合わせ,さまざまな革新的な取組みを行うこととした.その一つに多面的な症例集積の計画と実務的な対応を行うことを掲げ,この取組みに対応するリクル-トマネ-ジャ-という新たな専門職種を開発,設置した.本発表では,上記の取組みについて概説した.

愛知県がんセンタ-では,2022 年よりかかりつけ医療機関と協力してオンライン診療を行う完全リモ-ト治験を実施している.このリモ-ト治験の目的は,医薬品開発におけるPatient Centricity(患者中心)の概念に基づき,被験者の通院による距離的・時間的な負担を軽減し,治験へのアクセス向上を高めることである.また,新型コロナウイルス感染症のように未知の感染症の発生,蔓延や,大規模な災害により被験者の治験実施施設への来院が困難な場合においても,非接触にて治験を継続できることは被験者および医療者の感染リスクの低減をさせ,治験の中断を回避でき,被験者の治験参加中の安全性の確保にもつながる.このように,本来の目的は戦略的な症例登録ではなかったが,このリモ-ト治験を実施したことで予想を超えるスピ-ドで症例登録が進み,結果として,リモ-ト治験の仕組みが戦略的な症例登録の促進につながった.筆者は治験実施医療機関のCRCの立場からリモ-ト治験の仕組みと症例登録について報告する.

岡山医療連携推進協議会(Council for Medical Alliance, Okayama;以下,CMA-Okayama)は,岡山医療圏における健康寿命の延伸と健康格差の縮小に向け,良質で安定的な医療提供体制の継続的整備のために,その根幹となる医療人材育成および治験・臨床研究の発展的連携を推進することを目的に,岡山市,国立大学法人岡山大学,社会福祉法人恩賜財団済生会,独立行政法人国立病院機構,独立行政法人労働者健康安全機構,日本赤十字社を構成団体として,2017年6月に設立された.また,CMAOkayamaでは,医療人材育成連携と治験・臨床研究連携の専門部会が構成され,治験・臨床研究連携の専門部会のもと,岡山市内の主要6 病院からなるCMA-Okayama 治験・臨床研究ネットワ-ク(以下,CMA 治験NW)が2019 年1 月より活動している.本稿では,CMA 治験NW における症例集積性向上に向けた取組み,治験実施施設として選定され続けるための今後の課題について紹介する.

Background　The artificial intelligence(AI)has been actively used as an innovative technology in the medical and pharmaceutical industries. The introducing of AI technology into the pharmacological research has been expected to revolutionize drug discovery and development process in broad disease areas. Objective　We conceptualized this study to get an overview of the current status of AI technology usage in pharmacological research from basic research to clinical trials. Method　Free articles registered on PubMed® from 2019 to 2023 were reviewed and analyzed. Articles were selected with keywords of“AI”“, pharmacology”and“machine learning”. The usage of AI technology in pharmacology research was analyzed in 8 subdivided categories, including“Study Type”“, Clinical phase”“, Institution of lead author”“, Funded by”“, AI Technology applications”“, Disease area”“, Country”and“Application Fields of AI”. Results　The United States had the highest number of reports. The top two disease areas examined were“Infectious disease”and“Oncology”“. Efficacy prediction”was the most frequently analyzed item. In Japan, twelve reports were found. The majority of those used AI technology to study“Oncology”and“Neurological diseases”as disease areas and mainly focused on“Drug system(Chemical synthesis, Drug interactions, Binding prediction)”“, Outcome prediction”and“Imaging analysis”rather than“Efficacy prediction”. Conclusion　This review revealed the current trend in pharmacological research using AI technology, which is conducted in the area of“Infectious disease”“, Oncology”, and“COVID–19”, with focus on“Efficacy prediction”. It suggests that this may be related to the worldʼs three leading causes of death.(Jpn Pharmacol Ther 2024;52:1017‒33)

Objectives　The aim of this study was to investigate the effect of 2, 3–dihydro–3, 5–dihydroxy–6–methyl–4H–pyran–4–one(DDMP)–containing beverage on physical activity in healthy Japanese adults. Methods　This was a randomized, double–blind, placebo–controlled parallel study. One hundred sixty–six healthy subjects, 20 years of age or older, who felt their physical function was impaired, were randomly assigned to a placebo or DDMP group. Subjects consumed either the test product(65 mL fermented milk drink containing 2.2 mg DDMP)or the control product (65 mL fermented milk drink without DDMP)once daily for 12 weeks. 6–minute walks and other physical fitness measures were examined at Weeks 0, 6, and 12. Results　There was no statistically significant difference between the placebo and DDMP groups in the physical fitness test. However, in the subgroup that walked more than 0.3 km in the 6–minute walk test at baseline, there was a trend toward an increase in the DDMP group in repetitive lateral jumping after 6 weeks and a significant increase after 12 weeks. In addition, no adverse events attributable to the investigational product were observed in this study. Conclusions　The results of this study showed that a fermented milk beverage containing DDMP did not improve explosive power performance in healthy adults with low physical activity.(UMIN–ID:UMIN000051522)(Jpn Pharmacol Ther 2024;52:1035‒47)

Objectives　The aim of this study was to investigate the effect of consuming Tartary buckwheat ʻManten–Kirariʼon the visceral fat mass and its safety in healthy adults. Methods　A randomized, placebo–controlled, double–blind, parallel–group comparison study was conducted in 60 healthy volunteers(aged 20–60, body mass index(BMI)23 or more and less than 30). Subjects were randomly divided into two groups and consumed either Tartary buckwheat or placebo(Buckwheat)100 mg once per day for 12 weeks. Subjects were assessed on abdominal visceral fat area, physical measurement, and safety assessment. Abdominal visceral fat area was the primary outcome, and physical measurements were the secondary outcomes. Results　Abdominal visceral fat area at 12 weeks was significantly lower in the Tartary buckwheat group than in the placebo food group(P=0.004). During the study period, no adverse events attributable to the test foods were observed. Conclusions　This study suggests that Tartary buckwheaʻt Manten–Kirariʼhave an effect of reducing abdominal visceral fat area in healthy adults and is useful functional food for controlling visceral fat.( UMIN–CTR ID: 000051633)(Jpn Pharmacol Ther 2024;52:1051‒63)

Background　Yerba mate(Ilex paraguariensis A. St. Hill.)is native to South America. The leaves of this plant have long been consumed as a drink by locals; this drink is considered one of the three most popular beverages in the world. According to previous animal studies, yerba mate leaf extract(hereafter referred to as MATESOLTM)inhibits lipogenesis, promotes lipolysis, and reduces cholesterol levels. However, only few human studies have reported these effects. Objectives　This study was conducted to assess the efficacy of MATESOLTM in reducing abdominal fat in healthy adults with a relatively high BMI(23.0≤BMI<30.0). Methods　This randomized, double–blind, placebo–controlled parallel–group comparison study comprised 44 healthy Japanese subjects(23.0≤BMI<30.0). The subjects were randomly allocated to either the placebo or test food group(22 per group)to receive the respective intervention for 12 weeks. The primary outcome was the degree of change in abdominal visceral fat area. Moreover, abdominal subcutaneous fat area, abdominal total fat area, low–density lipoprotein(LDL)cholesterol, high–density lipoprotein(HDL)cholesterol, LDL–cholesterol to HDL–cholesterol(L/H)ratio, triglycerides, body weight, BMI, body fat percentage, waist circumference, hip circumference, waist to hip(W/H)ratio, ankle circumference, thigh circumference, triceps subcutaneous fat thickness, subscapular subcutaneous fat thickness, fasting blood glucose, HbA1c(NGSP), resting energy expenditure, and questionnaire were also assessed. Results　Forty–four subjects completed the trial, 22 in the test food group and 22 in the placebo group. No significant reduction in abdominal fat area was found in the test food group compared to the placebo group. In a subgroup analysis excluding five subjects who recorded lifestyle changes in their daily diary during the ingestion period, the degree of change in abdominal visceral fat area and abdominal total fat area at week 12 were found to be significantly lower in the test food group than in the placebo group. Furthermore, by determining the effect of the test food on lipid profiles in a subgroup of subjects with LDL cholesterol levels between 120 and 159 mg/dL, the measured value of L/H ratio at week 12 was found to be significantly lower in the test food group than in the placebo group. No medically problematic changes occurred with the ingestion of MATESOLTM. Conclusions　MATESOLTM reduced the abdominal visceral fat area in healthy subjects with a relatively higher BMI and appeared to be safe under the conditions employed in the present study.Trial Registration　UMIN–CTR: UMIN000051265 Funding　Tokiwa Phytochemical Co., Ltd.(Jpn Pharmacol Ther 2024;52:1067‒76)

Background　In team medical care, pharmacists have expanded their role in pharmaceutical interventions. We investigated the effects an automatic dispensing device that stocks drugs on dispensing times and stress levels during dispensing work as well as its impact on the number of cases for which drug management guidance fees are charged. Methods　The survey period comprised two 6–month periods: between April and September 2021(before the introduction of the automatic dispensing device)and between April and September 2022(after the introduction of the automatic dispensing device). Subjects were nine pharmacists working at our hospital. We conducted a questionnaire on the time spent dispensing drugs(min/day)and the level of stress perceived during this task. We also investigated the number of cases for which drug management guidance fees were charged. Results　The average dispensing time significantly decreased from 109.7±28.2 min/day before the introduction of the automatic dispensing device to 85.3±24.8 min/day after its introduction(P=0.039). Stress levels when dispensing medicines were significantly lower after the introduction of the automatic dispensing device(average of 46.7±0.6 mm)than before its introduction(average of 73.5±0.5 mm)(P=0.008). Furthermore, the number of cases for which drug management guidance fees were calculated significantly increased by 449 after the introduction of the automatic dispensing device(P=0.012). Conclusions　The present study suggests that an automatic dispensing device might reduce time of dispensing and stress. As a result, the number of bills to issue was increased and led to growth in revenue.(Jpn Pharmacol Ther 2024;52:1077‒81)

CONSORT(Consolidated Standards of Reporting Trials: 臨床試験報告に関する統合基準)声明はランダム化比較試験(randomized controlled trial: RCT)の報告を改善するために,世界中で広く用いられている.Kenneth Schulzらは,新たな方法論的エビデンスと蓄積された経験に基づいて改訂した最新版CONSORT 2010を発表した.