薬理と治療

新型コロナ感染症が蔓延していた頃,コロナワクチンの有効率に関する総説を書きました1).今回はもう少し一般的に,くすりの有効率について語りたいと思います.いくつかの疾患に対するくすりの有効率の計算例も示したいと思います.有効率は2通りあります(Box 1).特定の1群に関する有効率と,対照群との比較における有効率です.特定の1群に関しては,単純に全体で有効と判定された人の割合のことです.有効率と呼ぶことが多いですが,癌の腫瘍縮小効果については奏効率,関節リウマチの症状改善に関しては改善率と呼ぶこともあります.対照群との比較に対しては,イベント率の相対差をもって有効率(Efficacy rate)と呼ぶことがあります.イベントとは,COVID-19ワクチンなら重症化や発症などです.高血圧症などの慢性疾患では,心臓死や脳卒中の発症などを指します.ワクチン群の重症化率(A)とプラセボ群の重症化率(P)に対して,その絶対差は(P - A)です.通常P > Aなので,PからAを引きます.一方,相対差=(絶対差÷P)×100%と定義されます.ワクチン有効率(Vaccine efficacy)は,この相対差で定義されています.慢性疾患ではこの値を有効率とは呼ばず,そのまま相対リスク低下率と呼びます.

Objective We aimed to clarify the effect of a nutritional supplement containing chondroitin sulfate oligosaccharides (CSOS) on blood pressure reduction and blood vessels in healthy adults with a tendency toward hypertension. Methods We conducted a randomized, double–blind, placebo–controlled, parallel–group study on participants aged 40 to under 70, and with high blood pressure (130 mmHg < systolic blood pressure [SBP] < 140 mmHg and diastolic blood pressure [DBP] < 90 mmHg). The participants were randomly assigned to receive either the test supplement or the placebo supplement, daily for 12 weeks. The daily dose of the test supplement contained 100 mg CSOS. We measured blood pressure as the primary outcome and CAVI (Cardio–Ankle Vascular Index) and FMD (Flow–Mediated Dilatation) as the secondary outcomes. Results 69 participants were eligible for efficacy analyses. There were no significant differences in blood pressure between the groups (estimated difference 1.00 mmHg, 95% CI –4.26 to 6.25, P = 0.71 in SBP; estimated difference –2.30 mmHg, 95% CI –5.91 to 1.30, P = 0.21 in DBP), and no significant changes were observed in CAVI (estimated difference –0.01, 95% CI –0.27 to 0.25, P = 0.93) and FMD (estimated difference –0.27, 95% CI –1.24 to 0.70, P = 0.58), either. However, the analyses on a subgroup of men with total cholesterol levels above 200 mg/dL showed significant decrease in DBP (estimated difference –7.74 mmHg, 95% CI –14.8 to –0.7, P = 0.034) and creatine kinase (estimated difference –46.69 U/L, 95% CI –80.67 to –12.71, P = 0.010) Conclusion The results of this study suggest that 12 weeks of continuous intake of CSOS may not affect blood pressure reduction and blood vessels (UMIN ID: UMIN000052732) Although, in men with total cholesterol levels exceeding 200 mg/dL, continuous intake of nutritional supplements containing CSOS for 12 weeks was shown to significantly reduce diastolic blood pressure and CK levels. Therefore, further detailed studies are necessary for these findings. (Jpn Pharmacol Ther 2025;53:959‒72)

Objectives The aim of this study was to evaluate the effect of a food containing eggshell–derived hydroxyapatite on the oral environment. Methods A randomized, double–blind, placebo–controlled, parallel–group study was conducted with Japanese men and women aged 25 to 65 years with oral health concerns. Participants continuously consumed one control food or test food (containing 500 mg of hydroxyapatite) daily for 4 weeks. Results After consumption of test foods containing eggshell–derived hydroxyapatite, no significant improvement was observed in the primary endpoint of CPI, but inhibition of periodontopathogenic bacteria and subjective improvement in hypersensitivity were observed. In addition, subgroup analysis showed improvement in subjective perception of tooth yellowing and improvement in plaque index. Furthermore, no adverse safety findings were observed with the continued consumption of the test food, indicating that the food was safe for long–term intake. Conclusion Eggshell–derived hydroxyapatite–containing foods were continuously consumed for 4 weeks by Japanese men and women aged 25 to 65 years with oral health concerns, and their oral environment was found to be improved. (UMINID: UMIN000053446) (Jpn Pharmacol Ther 2025;53:973‒86)

Japan introduced a formal cost–effectiveness evaluation system in 2019, adjusting the prices of pharmaceuticals and medical devices based on the Incremental Cost–Effectiveness Ratio (ICER), which is calculated using Quality–Adjusted Life Years (QALYs). While special considerations are granted for conditions such as cancer, rare diseases, and pediatric cases–where higher ICER thresholds are applied–these adjustments are uniformly applied without a quantitative assessment of disease severity. In contrast, countries like Norway, the Netherlands, and the United Kingdom (NICE) incorporate a severity modifier into their health technology assessments using QALY shortfall metrics. These include Absolute and Proportional QALY Shortfall, which are used to weigh QALYs or adjust ICER thresholds according to the assessed severity of the condition. This review outlines how these countries implement severity modifiers and explore their ethical and policy foundations, including ethical principles such as “Fair Innings” and the “Rule of Rescue.” We also present the results of a trial estimation of QALY shortfalls in selected Japanese cases using the NICEʼs assessment framework. Based on these findings, the paper briefly discusses potential challenges for Japan, such as the need for ethical consensus–building, methodological standardization, and data infrastructure development. The approaches adopted by these three countries may serve as useful references for designing and refining Japanʼs future cost–effectiveness evaluation system. (Jpn Pharmacol Ther 2025;53:989‒1001)