| Background:The gold standard for assessing clinical efficacy is the randomized controlled trial.In Traditional Chinese Medicine(TCM),it is frequently employed.Numerous credible clinical research evidence of TCM has been published in international publications.However,uncertain research objectives,unrealistic control group settings,and the improper use of outcomes are some of the issues that still exist in randomized controlled trial.These issues make it difficult to portray the genuine efficacy of TCM and compromise the reliability of the research results.A crucial concern is how investigators may properly and logically use the clinical resources offered for randomized controlled trial design to produce more high-quality evidence.This study suggests a way for designing randomized controlled trial in TCM using clinical efficacy as the orientation and the PICO model as the framework.This design method will serve as a guide for designing randomized controlled trial in TCM.Randomized controlled trial is designed to provide evidence-based medical evidence for clinical practice.Clinical efficacy also plays a significant role in clinical practice.When treating patients,we modify the plan of treatment in response to the efficacy of treatment,ultimately achieving the goal of treating the disease.Designing randomized controlled trial with clinical efficacy as the orientation will allow trial design components to be developed from clinical efficacy and trial findings to be sent back to the clinic to direct clinical practice and discover fresh questions in clinical practice.This entails a cyclic procedure to accomplish ongoing clinical practice effects optimization.A study model is required for the execution of a clinical efficacy-oriented randomized controlled trial design strategy for TCM since it provides a consistent and organized procedure for the investigation.PICO,which stands for participants,interventions,comparisons,and outcomes,is an internationally recognized approach for creating clinical research questions.It establishes clear,structured research questions that direct research design and boost methodological quality.Objectives:1 To put out and build a design method,which use clinical efficacy as the orientation and the PICO model as the framework for randomized controlled trial in TCM.2 To clarify the design rationale and offer a foundation for its use,with the example of lumbrokinase for acute ischemic stroke.3 To create a clinical efficacy-oriented randomized controlled trial using the design rationale in actual practice,with the the example of lumbrokinase for acute ischemic stroke.Methods:1 Analyze the current state and issues of TCM randomized controlled trial,and provide a solution of clinical efficacy-oriented design method in TCM randomized controlled trial.From the standpoint of the organized development of the research question,the PICO model is employed as the design framework for this method,and the implementation processes of this method are addressed.2 The design rationale of this method is illustrated by using lumbrokinase for acute ischemic stroke as an example.Systematic evaluation and meta-analysis,cross-sectional study,and retrospective cohort study are used to create the PICO model,which is optimized by clinical efficacy to produce design components for randomized controlled trial.3 A randomized controlled trial protocol based on the clinical efficacy as the orientation and PICO model as the framework is created to show this design method in action,using the lumbrokinase for acute ischemic stroke as an example.Results:1 There were issues with the randomized controlled trial design in TCM,including uncertain research objectives,unrealistic control group settings,and the improper use of outcomes.This study suggested a clinical efficacy-oriented randomized controlled trial design method for TCM to overcome these issues.The three implementation steps of this method were systematic evaluation and meta-analysis,real-world cross-sectional study,and real-world retrospective cohort study.Then extracted the PICO model from the three implementation steps as design components.2 The use of lumbrokinase for acute ischemic stroke served as an example of the rationale for the design of this method.(1)In systematic evaluation and meta-analysis,age,sex,time of onset,diagnostic criteria,8 inclusion criteria,and 14 exclusion criteria for participants were taken from the literature of prior randomized controlled trials.There were 4 sizes,7 doses,2 dosing frequencies,8 combinations,and regularly course of treatment for interventions.There were 3 commonly used comparisons.Through meta-analysis,11 intervention-sensitive outcomes were found.The goal of utilizing the literature to optimize the PICO model from the standpoint of clinical efficacy was accomplished.(2)In cross-sectional study,basic study subject characteristics like age,sex,time of onset,history of prior illness,family history of illness,history of smoking and drinking,NIHSS score,mRS score,ADL score,staging of acute ischemic stroke,and TCM syndrome elements were gathered from data of actual acute ischemic stroke patients.Used elevated fibrinogen as an intervention.By using logistic regression,9 distinct outcomes that might be linked to fibrinogen alterations in acute ischemic stroke were identified.PICO models of the patients’ onset characteristics were obtained.(3)In retrospective cohort study,basic study subject characteristics like age,sex,time of onset,history of prior illness,history of smoking and drinking,NIHSS score,mRS score,ADL score,stroke type in TCM,and TCM syndrome elements were gathered from the baseline data of both groups.Obtained common regimens for the interventions,including 3 dosing frequencies and 4 doses.The comparison was blank control.The retrospective cohort study produced one specific outcome.The goal of utilizing the real-world data to optimize the PICO model from the standpoint of clinical efficacy was accomplished.3 As an example,this design method was used to create a clinical efficacy-oriented randomized controlled trial of lumbrokinase for acute ischemic stroke.220 patients with acute ischemic stroke would be included in the study.They would be randomized into two groups:the intervention group(lumbrokinase plus aspirin)and the control group(lumbrokinase placebo plus aspirin).The diagnostic standard used was the Diagnostic criteria of cerebrovascular diseases in China(version 2019).The inclusion criteria were:(1)Participant was diagnosed with acute ischemic stroke for the first time.(2)Symptoms of acute ischemic stroke appeared within 72 hours.(3)Before the onset of symptoms of acute ischemic stroke,the mRS score of the participant was less than or equal to 2.(4)Participant hadn’t received intravenous thrombolysis,arterial thrombolysis or intravascular intervention.(5)The participant’s NIHSS score was greater than 5 and less than 15.(6)The age of the participant was between 35 and 85 years old.(7)Agreed to participate in the trial and signed informed consent form.The exclusion criteria were:(1)The participant had a hemorrhagic cerebrovascular disease.(2)Transient ischemic attack or silent ischemic stroke.(3)Known or suspicion for cardiogenic embolism.There were 15 other exclusion criteria.Lumbrokinase enteric capsules(600,000 units tid)and aspirin enteric tablets(100mg qd)were given to the intervention group.Lumbrokinase placebo enteric capsules(1 capsule tid)and aspirin enteric tablets(100mg qd)were given to the control group.All medications were taken for 90 days,with a 180-day follow-up.The mRS scale was the primary outcome.NIHSS score,ADL score,fibrinogen,platelet aggregation rate,prothrombin time,activated partial thromboplastin time,and hypersensitive C-reactive protein were secondary outcomes.The trial was also assessed for safety,compliance,and collected of Diagnostic Scale for TCM Syndromes of Acute Ischemic Stroke.Conclusions:In order to solve the issues with TCM’s randomized controlled trial design in a methodical and scientific way,the study developed and created a design method using clinical efficacy as the orientation and the PICO model as the framework.In order to provide guidance for the design of a TCM randomized controlled trial and to improve the quality of relevant clinical researches,the design rationale and practice procedure of this design method were outlined using lumbrokinase for acute ischemic stroke as an example. |
