Forecasting Trial Milestones: A Predictive Analysis for Early Termination of the SOUL Study.

IF 3.8 3区医学 Q2 Medicine

Diabetes Therapy Pub Date : 2024-10-01 Epub Date: 2024-08-08 DOI:10.1007/s13300-024-01635-1

Binayak Sinha, Samit Ghosal

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Abstract

Introduction: Semaglutide, a glucagon-like peptide 1 receptor agonist (GLP1RA), is available in both parenteral and oral preparations. Studies of injectable preparations have convincingly demonstrated its beneficial effect on major adverse cardiac events (MACE). This predictive analysis was undertaken to forecast early termination of the SOUL trial (oral semaglutide) as well as the primary events.

Methods: SOUL is a multicenter, double-blind, placebo-controlled randomized controlled trial (RCT) evaluating the reduction in MACE associated with oral semaglutide versus placebo in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. A sample of 9642 participants will be followed for 5 years and 5 months. A random-effects model meta-analysis, pooling hazard ratios from previous RCTs, was conducted using R software to inform the predictive model. The background CV event rates from the placebo arms of previous RCTs with semaglutide were matched with the pre-adjudicated assumptions of the SOUL trial to create the predictive model. The truncated trial duration, MACE, and its individual components in the intervention and placebo arms were estimated. The predicted difference between the two groups was estimated using the chi-squared test.

Results: A pooled analysis of 10,013 patients revealed a significant reduction in the number of MACEs associated with semaglutide (HR 0.79, 95% CI 0.69-0.91). Predictive analysis indicated that 1225 events would be achieved by 3.78 years, suggesting premature termination.

Conclusion: The mathematical model based on the meta-analysis predicts that the SOUL study on oral semaglutide will be terminated early, with oral semaglutide showing benefits in terms of MACE compared to placebo. If the SOUL study corroborates the findings of this model, it may not only form the basis for the calculation of power but also define the duration of such studies, reducing costs and easing the process of designing cardiovascular outcome trials (CVOTs).

Protocol registration: INPLASY202460061.

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预测试验里程碑：SOUL 研究提前终止的预测分析。

简介塞马鲁肽是一种胰高血糖素样肽 1 受体激动剂（GLP1RA），有肠外注射剂和口服制剂两种。有关注射制剂的研究令人信服地证明了它对重大心脏不良事件（MACE）的有利影响。本预测分析旨在预测 SOUL 试验（口服塞马鲁肽）的提前终止以及主要事件：SOUL 是一项多中心、双盲、安慰剂对照随机对照试验 (RCT)，旨在评估口服塞马鲁肽与安慰剂相比对 2 型糖尿病 (T2D) 和心血管疾病 (CV) 患者 MACE 的降低作用。该研究将对 9642 名参与者进行为期 5 年零 5 个月的随访。我们使用 R 软件进行了随机效应模型荟萃分析，汇集了以往 RCT 的危险比，为预测模型提供了信息。根据 SOUL 试验的预先判断假设，匹配了之前使用塞马鲁肽的 RCT 研究安慰剂组的背景 CV 事件发生率，从而创建了预测模型。对干预组和安慰剂组的截断试验持续时间、MACE 及其各个组成部分进行了估算。使用卡方检验估计了两组之间的预测差异：对 10,013 名患者进行的汇总分析显示，与塞马鲁肽相关的 MACE 数量显著减少（HR 0.79，95% CI 0.69-0.91）。预测分析表明，到3.78年将发生1225起事件，这表明治疗将提前结束：基于荟萃分析的数学模型预测，口服塞马鲁肽的SOUL研究将提前结束，因为与安慰剂相比，口服塞马鲁肽在MACE方面显示出优势。如果SOUL研究证实了这一模型的结论，那么它不仅可以作为计算功率的基础，还可以确定此类研究的持续时间，从而降低成本并简化心血管结局试验（CVOT）的设计过程：Inplasy202460061.

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来源期刊

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.