薬理と治療

過去,当CRC と臨床試験のあり方を考える会議を含めて,さまざまな人たちが「症例集積性向上」に関して議論を続けている.しかしながら,諸外国にくらべてまだまだ改善すべきとの声が止まず,近年,顕著となっているドラッグロス・ドラッグラグの一因としてクロ-ズアップされている状況にある.もちろん過去,現在において,この課題解決へさまざまな人たちが立ち向かい,創意工夫を重ねた歴史により改善傾向にあると考えられるが,さらなる工夫を求められていることも事実である.その工夫の一つとして昨今,国内において充実してきている医療デ-タ(リアルワ-ルドデ-タ:RWD)の利活用の可能性を検討してみた.

症例集積性とは,臨床試験において治験対象となる症例を効率的に集める能力を指す.治験依頼者にとって症例集積性の向上は新薬の早期導入や市場価値の最大化,治験コストの適正化といった観点からきわめて重要な要素となっている.またドラッグロスを防ぐという観点でも症例集積性の向上は重要であり,日本の治験環境改善に欠かせないポイントの一つである.本稿では,製薬企業,とくに外資系製薬企業の日本法人視点に基づき,症例集積性の意義について論じる.

Objective　The present study was designed to examine the influence of hyaluronic acid(HA)on the production and secretion of substance P(SP)from PC–12 cells in vitro; SP is an important molecule in the development of knee osteoarthritis(OA). Methods　PC–12 cells(1×104 cells)were cultured with 10.0 ng/mL nerve growth factor (NGF)in the presence or absence of various concentrations of HA for 72h. The cells were then stimulated with 100.0 ng/mL capsaicin and the culture supernatants were obtained after 6h. SP levels were measured with ELISA. The influence of HA on the total number of neurites per PC–12 cell and on the percentage of PC–12 cells with outgrowing neurites were examined at 24h or 72h after the start of culture, respectively. Results　Treatment of NGF–stimulated PC–12 cells with HA increased the capsaicin–induced secretion of SP. HA also increased the ability of PC–12 cells to produce SP in response to NGF stimulation. The minimum concentration of HA that caused a significant increase in both the production and secretion of SP was 3.0 mg/mL. On the other hand, HA did not inhibit the total number of neurites and the percentage of PC–12 cells with outgrowing neurites, even when PC–12 cells were cultured with HA at 7.0 mg/mL. Conclusion　The present results strongly suggested that HA increases the production and secretion of SP from neural cells and can improve the clinical conditions of knee OA.(Jpn Pharmacol Ther 2025;53:593‒602)

Objectives　The fermented botanical extract is expected to improve immunity and the intestinal environment. This study aimed to evaluate the effects of a fermented botanical extract on immune activation, intestinal health, and sleep in healthy adults. Methods　In this randomized, double–blind, placebo–controlled parallel–group study, healthy participants aged 18 to 64 were randomly assigned to receive either 25 mL/day of a fermented botanical extract or a placebo for 4 weeks. Primary endpoints included salivary secretory immunoglobulin A(s–IgA)concentration, s–IgA secretion rate, Profile of Mood States(POMS)score, and bowel movement frequency. Secondary endpoints included natural killer(NK)cell activity, the middle–aged and aged version of the Oguri–Shirakawa–Azumi Sleep Inventory (OSA–MA), and intestinal flora composition. Results　The number of subjects analyzed in the intention–to–treat set was 18 in each group. Changes from baseline at week 4 were compared between the fermented botanical extract group and the placebo group. There were no statistically significant differences in salivary s–IgA concentration, salivary s–IgA secretion rate, or POMS scores. However, the mean increase in the number of bowel movements from baseline to week 4 in the fermented botanical extract group(0.12±0.13, 95% CI[0.06, 0.19])was significantly greater than that in the placebo group(-0.02±0.14, 95% CI[-0.09, 0.06])(P=0.005). Among the secondary endpoints, significant increases in NK cell activity and the relative abundance of Bifidobacterium in feces were observed in the fermented botanical extract group compared with the placebo group. Conclusions　These results suggest that the fermented botanical extract may improve bowel movement frequency by affecting the intestinal flora and enhancing NK cell activity.(UMIN–CTR ID: UMIN000052021)(Jpn Pharmacol Ther 2025;53:603‒14)

臨床試験論文では,サブグル-プ解析をよく見かけます.誤った使い方をしている論文が多いので,その目的と留意点について解説しようと思います.

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.