To show that a new drug is better than, as good as, or no worse than that of a known effective drug. Theoretically, it is necessary to confirm the efficacy of a treatment, but the current practice of clinical trial suggests that there exists many problems in its confirmation including the objectives of clinical investigation vary based on the fact that more and more clinical trials use active controls. Applied statistical methods have to adapt to these changes. In this paper, we illustrated some statistical issues of confirming efficacy in clinical trials, including its conditions, the determination of clinical margin, the forms of the null and alternative hypothesis and confidence intervals, the choice of endpoints and some miscellaneous considerations. We bly suggests that it is necessary to make biostatisticians and clinical trialists understand the importance of using the right statistical methods when investigating clinical trials. We also think these methods introduced in the paper may provide some help in trial design and evaluation.
Objective To evaluate the efficacy and safety of safflower yellow pigment lyophilized power amp; dripping solution in the treatment of patients with angina, by using parenteral solution of Dan-shen root extraction as control, we designed the nonferiority clinical trial phase Ⅲ. Method 784 patients with stable angina pectoris Ⅰ, Ⅱ, Ⅲ degree and occurred more than twice per week were selected. They were randomly, stratified and blindly assigned into 5 parallel groups including one control. They were treated by using safflower yellow pigment lyophilized power (SYPLP) 80 mg + 0.9% NS 250ml, intravenously guttae, daily (trial group 1); SYPLP 160 mg + 0.9% NS 250 ml, intravenously guttae, daily (trial group 2); safflower yellow pigment lyophilized dripping solution (SYPLDS) 200 ml (160 mg), intravenously guttae, daily (trial group 3); SYPLDS 100 ml (80 mg), intravenously guttae, daily (trial group 4) and parenteral solution of Dan-shen root extraction 20 ml + 0.9% NS 250 ml, intravenously guttae, daily (control group) respectively. Efficacy and safety were evaluated after 14 days of continuous treatment. Results The angina efficacy (per-protocol population, PP): The notable effective rates of trial groups 1 to 4 and control group were 53.27%，69.44%，70.09%，55.09% and 26.00% respectively, and the effective rates were 88.79%，92.59%，93.46%，89.81% and 73.00% respectively。There was significant differences between trial group 1 and 2, trial group 3 and 4. All trial groups showed significant different effect when compared with control (P＜0.05). The effect of trial group 2 was better than those of trial group 1, and trial group 3 better than trial group 4, the four trial groups better than control group. The intention-to-treat (ITT) analysis result was almost the same to PP analysis, but trial group 3 showed no significant difference to trial group 4. In trial group 2, 3 and 4, each occurred one adverse effect, while the number was 10 in control group.Conclusion SYPLP amp; SYPLDS have certain effect on angina. They are more effective than parenteral solution of Dan-shen root extraction. No toxic side effect has been found in clinic tests.
ObjectiveTo systematically review the non-inferiority trials in the cardiovascular domain that utilize medical devices as interventions, and investigate its characteristics and threshold settings. MethodsThe PubMed, Embase, and CENTRAL databases were electronically searched to collect non-inferiority trials in the cardiovascular field involving medical devices from inception to July 26, 2023. Two reviewers independently screened literature and extracted data. The reported information included basic characteristics, features of non-inferiority trials, and threshold-setting features of the included studies. Data analysis was performed using Excel 2020 and R 4.2.1 software. ResultsA total of 214 studies were included, with 167 studies (78.0%) focusing on interventions related to coronary artery stents. The trials predominantly utilized a two-arm design (92.9%), with a prevalent use of non-inferiority absolute thresholds (96.7%) as the criteria for non-inferiority determination. In 150 studies (70.1%), non-inferiority thresholds were established based on estimated control group effect values, while 33 studies (15.4%) did not report the source of these values. The non-inferiority trial endpoint outcomes exhibited diversity, and there were substantial differences in threshold settings. The three most studied qualitative indicators were target lesion failure rates (2.1%-8.6%), target vessel failure rates (2.5%-19.6%), and major adverse cardiovascular events rates (2.1%-10.0%). Late lumen loss (0.1-0.4 mm) emerged as the most frequently studied quantitative indicator. After converting absolute non-inferiority thresholds for all indicators into relative thresholds, the range was 1.20-3.67. ConclusionSignificant variations in non-inferiority threshold settings are observed for identical endpoint outcomes across included studies, highlighting a lack of reporting on the rationale behind threshold settings.