Analysis and Reflection on the Outcome Indicators in Clinical Trials of Traditional Chinese Medicine for Sepsis-induced Acute Lung Injury/Acute Respiratory Distress Syndrome

Background Traditional Chinese medicine (TCM) is effective in the treatment of sepsis-induced acute lung injury (ALI) /acute respiratory distress syndrome (ARDS). However, the lack of standard and uniform outcome indicators in the design of most published clinical trials makes it difficult to combine and compare the results of similar studies, causing the impossibility of generating high-quality evidence to guide clinical decision-making. Objective To analyze the use of outcome indicators in randomized controlled trials on TCM for sepsis-induced ALI/ARDS from 2017 to 2022. Methods CNKI, Wanfang Data, SinoMed, PubMed, Embase, Web of Science and Cochrane Library were searched for RCTs on sepsis-induced ALI/ARDS, with the intervention group treated with TCM combined with other drugs or conventional treatment, and no restrictions in the control group. The ROB.2 tool of the Cochrane Review Group was used to assess the quality of literature and the classification of outcome indicators was summarized. Results 39 papers were included after screening, including 1 (2.56%) with low risk of bias, 3 (7.69%) with high risk of bias and 35 (89.74%) with concerns of bias. The outcome indicators in 5 RCTs were reported with a quality score of ≥5, indicating the complete reporting of outcome indicators. A total of 106 outcome indicators were reported and used for 443 times, including physicochemical testing outcome (55 types, 51.89%), TCM syndrome/sign outcome (2 types, 1.89%), symptom and syndrome outcome (13 types, 12.26%), long-term prognosis outcome (19 types, 17.92%), quality of life outcome (7 types, 6.60%), safety event outcome (8 types, 7.55%) and economic evaluation outcome (2 types, 1.89%). There were four outcome indicators with utilization rate>50%, including oxygenation index (82.05%), Acute Physiology and Chronic Health Evaluation Scoring System (58.97%), mechanical ventilation duration (51.28%) and interleukin-6 (51.28%). The composite outcome indicators of effective rate or TCM syndrome efficacy were used in 21 papers, involving a total of 12 times of effective rate, TCM syndrome score of 8 times and TCM symptom efficacy of 6 times. The total 106 outcome indicators were summarized and categorized sequentially including overall evaluation indicators (36 types, 33.96%), common indicators (36 types, 33.96%) and different focus indicators (34 types, 32.08%) . Conclusion At present, the selection of outcome indicators in RCTs on TCM for sepsis-induced ALI/ARDS is still nonstandard, mainly manifests in unclear differentiation between primary and secondary outcome indicators, trivialization of endpoint indicators, lack of follow-up data and characteristic indicators of TCM. A core outcome set of TCM outcome indicators for septic induced ALI/ARDS should be constructed to promote the high-quality development of TCM in the future.