Table_1_Fighting for recovery on multiple fronts: The past, present, and future of clinical trials for spinal cord injury.xlsx

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.S. National Library of Medicine at ClinicalTrials.gov. We conducted a systematic analysis of these SCI clinical trials, using publicly accessible data downloaded from ClinicalTrials.gov. After extracting all available data for these trials, we categorized each trial according to the types of interventions being tested and the types of outcomes assessed. We then evaluated clinical trial characteristics, both globally and by year, in order to understand the areas of growth and change over time. With regard to clinical trial attributes, we found that most trials have low enrollment, only test single interventions, and have limited numbers of primary outcomes. Some gaps in reporting are apparent; for instance, over 75% of clinical trials with “Completed” status do not have results posted, and the Phase of some trials is incorrectly classified as “Not applicable” despite testing a drug or biological compound. When analyzing trials based on types of interventions assessed, we identified the largest representation in trials testing rehab/training/exercise, neuromodulation, and behavioral modifications. Most highly represented primary outcomes include motor function of the upper and lower extremities, safety, and pain. The most highly represented secondary outcomes include quality of life and pain. Over the past 15 years, we identified increased representation of neuromodulation and rehabilitation trials, and decreased representation of drug trials. Overall, the number of new clinical trials initiated each year continues to grow, signifying a hopeful future for the clinical treatment of SCI. Together, our work provides a comprehensive glimpse into the past, present, and future of SCI clinical trials, and suggests areas for improvement in clinical trial reporting.

历经数十年的临床前研究，学界在阐明脊髓损伤（spinal cord injury, SCI）的复杂病理本质方面已取得长足进展。临床前研究工作为临床试验的开展提供了指导并塑造了其发展方向，且临床试验的数量正逐年攀升。目前，美国国家医学图书馆旗下的ClinicalTrials.gov平台上，共计注册有1149项旨在改善脊髓损伤患者预后的临床试验。本研究基于从ClinicalTrials.gov下载的公开可获取数据，对上述脊髓损伤临床试验展开了系统性分析。在提取所有试验的可用数据后，我们依据受试干预类型与评估结局类型对每项试验进行了分类。随后，我们从全球维度与年度维度分别评估了临床试验的特征，以期明晰随时间推移的研究热点演变与发展变化。关于临床试验的属性特征，我们发现多数试验的入组人数偏低，仅测试单一干预手段，且主要结局指标数量有限。部分报告环节存在明显缺失：例如，超过75%状态为“已完成”的临床试验未公开研究结果；部分虽测试药物或生物制剂的试验，其试验分期被错误归类为“不适用”。在基于受试干预类型开展分析时，我们发现占比最高的试验类别为康复/训练/运动、神经调控以及行为矫正类试验。占比最高的主要结局指标包括上下肢运动功能、安全性与疼痛情况。占比最高的次要结局指标则包括生活质量与疼痛情况。在过去15年间，我们观察到神经调控与康复类试验的占比有所提升，而药物类试验的占比有所下降。总体而言，每年启动的新增临床试验数量仍在持续增长，这预示着脊髓损伤临床治疗领域的未来充满希望。综上，本研究全面梳理了脊髓损伤临床试验的过去、现状与未来，并为临床试验报告环节的改进指明了方向。