The modern clinical research evaluation systems have increasingly emphasized the evaluation of individual patients' clinical characteristics, diagnosis and treatment plans, and complex intervention measures. Traditional randomized controlled trials evaluate fixed interventions and non-adaptive treatment plans, which cannot meet the needs of evaluating adaptive interventions. This has made researchers more inclined to explore an individualized and adaptive clinical trial design, and sequential multiple assignment randomized trial (SMART) has emerged as needed. This article introduces the principles, key elements, and implementation points of SMART design, further explores the limitations of the mismatch between traditional Chinese medicine clinical trial design and syndrome differentiation treatment, and proposes that SMART design can meet the needs of traditional Chinese medicine clinical trials to inspire researchers in designing their plans.
In recent years, investment in new drug development in China has surged; however, challenges such as difficulties in efficacy validation, high failure rates, and lengthy, costly clinical trials have been faced. The traditional model is insufficient for addressing these issues, necessitating innovation. Adaptive design (AD), particularly sequential multiple assignment randomized trials (SMART), has emerged as a flexible and efficient new pathway for drug development. This study focused on the two-stage design of SMART, analyzed its principles, and contrasted it with randomized controlled trials, group sequential designs, and crossover designs. The advantages of SMART are highlighted in terms of its precision in evaluating treatment strategies, minimizing sample waste, and enhancing the exploration of complex treatment pathways. Through case analyses, we demonstrated that SMART significantly improved clinical trial efficiency and the quality of treatment decisions, representing an innovative solution to the challenges of new drug development. This study aims to provide strategic references for clinical researchers and promote the adoption of adaptive designs in China, facilitating the efficient advancement of new drug development.
ObjectiveTo investigate the preoperative symptom burden and quality of life of patients undergoing lung cancer surgery.MethodsThis study was a cross-sectional study. We used the MD Anderson Symptom Inventory-lung cancer module (MDASI-LC) and the single-item quality of life scale (UNISCALE) to collect the preoperative patient-reported outcomes of 265 patients with lung cancer from November 2017 to July 2019 in Sichuan Cancer Hospital.ResultsOf 265 patients, 90.9% had preoperative symptoms. The five most common symptoms were coughing (66.8%), dry mouth (53.6%), memory problems (52.8%), disturbed sleep (52.1%) and fatigue (44.2%). The five most common moderate to severe symptoms were disturbed sleep (23.0%), distress (18.5%), memory problems (16.6%), coughing (16.2%) and dry mouth (16.2%). Patients with early-stage lung cancer had less pain, fatigue, shortness of breath, lack of appetite, numbness and coughing, and their symptoms had less impact on work (including housework), relations with other people, walking and enjoyment of life as well as better quality of life before surgery (P<0.05). Patients with adenocarcinoma had milder coughing and a better quality of life before surgery (P<0.05). Symptom score was positively correlated with symptom interference with life score (r=0.66, P<0.01) and negatively correlated with quality of life score (r=-0.41, P<0.01).ConclusionMost patients undergoing lung cancer surgery have a mild symptom burden before surgery. The most common and severe symptoms are coughing, dry mouth, lung cancer and disturbed sleep. Patients with early-stage lung cancer have a milder symptom burden and a better quality of life.
Objective To investigate the current status of constipation during postoperative hospitalization and the factors associated with moderate to severe constipation at discharge in lung cancer patients. Methods Lung cancer patients who underwent surgery in 6 tertiary hospitals in Sichuan Province from November 2017 to January 2020 were enrolled. The MD Anderson Symptom Scale-Lung Cancer Module was used to collect postoperative constipation scores. Unconditional logistic stepwise regression was used to analyze the related influencing factors for moderate to severe constipation on the day of discharge. Results Finally 337 patients were collected. There were 171 males and 166 females, with an average age of 55.0±10.3 years. Constipation scores of lung cancer patients increased from postoperative day 1 to day 3, and showed a decreasing trend from day 3 to day 7. Moderate to severe constipation was present in 68 (20.2%) patients at discharge. The postoperative hospital stay (OR=0.743, P<0.001) and the dose of morphine used during postoperative hospitalization (OR=1.002, P=0.015) were influencing factors for moderate to severe constipation at discharge in lung cancer patients. ConclusionLung cancer patients have the most severe constipation on postoperative day 3. Moderate to severe constipation at discharge is associated with the postoperative hospital stay and the dose of morphine used during postoperative hospitalization.
The 14th Five-Year Plan for National Health explicitly proposes elevating the comprehensive prevention and control strategy for chronic diseases to a national strategy, aiming to address the growing demand for long-term management and individualized treatment of chronic diseases. In this context, the adaptive treatment strategy (ATS), as an innovative treatment model, offers new ideas and methods for the management and treatment of chronic diseases through its flexible, personalized, and scientific characteristics. To construct ATS, the sequential multiple assignment randomized trial (SMART) has emerged as a research method for multi-stage randomized controlled trials. The SMART design has been widely used in international clinical research, but there is a lack of systematic reports and studies in China. This paper first introduces the basic principles of ATS and SMART design, and then focuses on two key elements of the SMART design: re-randomization and intermediate outcomes. Based on these two elements, four major types of SMART designs are summarized, including: (1) SMART designs in which the intermediate outcome corresponds to a single re-randomization scheme (the classical type), (2) SMART designs in which no intermediate outcome is embedded, (3) SMART designs in which the intermediate outcome corresponds to a different re-randomization scheme, and (4) SMART designs in which the intermediate outcome and the previous interventions jointly determine the re-randomization. These different types of SMART designs are suited for solving different types of scientific problems. Using specific examples, this paper also analyzes the conditions under which SMART designs are applicable in clinical trials and predicts that the mainstream analysis methods for SMART designs in the future will combine frequentist statistics and Bayesian statistics. It is expected that the introduction and analysis in this paper will provide valuable references for researchers and promote the widespread application and innovative development of SMART design in the field of chronic disease prevention, control, and treatment strategies in China.
