Evaluating the Effects of Heat-Clearing Traditional Chinese Medicine in Stable Bronchiectasis by a Series of N-of-1 Trials.

PURPOSE: The purpose of this study is to study the effects of heat-clearing Traditional Chinese Medicine (TCM) in the stable stage of bronchiectasis via N-of-1 trials. METHODS: The N-of-1 trials in this study were randomized and double-blinded with crossover comparisons consisting of three pairs. Each pair was of two 4-week periods. Each patient took the individualized decoction in the experimental period and the individualized decoction was removed of heat-clearing drugs, mainly including heat-clearing and detoxifying drugs, in the control period for three weeks. After three weeks, the patients stopped taking the decoction for one week. The primary outcome was from patients' self-reporting symptoms scores on a 1-7-point Likert scale. Mixed-effects models were used to conduct statistical analysis on these N-of-1 trials. RESULTS: Of the 21 patients enrolled, 15 completed three pairs of N-of-1 trials (71.43%). (1) Seen from the individual level, no statistical difference between the experimental decoction and the control (P > 0.05) was observed. However, 5 patients found better decoctions according to the clinical criteria. (2) As revealed by the group data of all the N-of-1 trials, the control was better than the individualized decoction in terms of symptom scores on the Likert scale (1.94 ± 0.69 versus 2.08 ± 0.68, P = 0.04, mean difference, and 95% CI: 0.19 (0.01, 0.37)) and on CAT scores (13.66 ± 6.57 versus 13.95 ± 6.97, P = 0.04, mean difference, and 95% CI: 0.86 (0.042, 1.67)), but such differences were not clinically significant. The other outcomes, such as Likert scale score of respiratory symptoms and 24-hour sputum volume, showed no statistical difference. CONCLUSION: The experimental design of this study can make the TCM individualized treatment fully play its role and can detect the individualized tendencies according to the severity of phlegm and heat in some subjects. With the intermittent use or reduced use of heat-clearing drugs, most of the subjects, at the group level, enrolled in the series of N-of-1 trials may improve the symptoms and quality of life while saving the cost of TCM and reducing the potential side effects of heat-clearing TCM. This trial is registered with clinicaltrials.goc (NCT03147443).

Investigation into the Individualized Treatment of Traditional Chinese Medicine through a Series of N-of-1 Trials.

PURPOSE: To compare the efficacy of individualized herbal decoction with standard decoction for patients with stable bronchiectasis through N-of-1 trials. METHODS: We conducted a single center N-of-1 trials in 17 patients with stable bronchiectasis. Each N-of-1 trial contains three cycles. Each cycle is divided into two 4-week intervention including individualized decoction and fixed decoction (control). The primary outcome was patient self-reported symptoms scores on a 1-7 point Likert scale. Secondary outcomes were 24-hour sputum volume and CAT scores. RESULTS: Among 14 completed trials, five showed that the individualized decoction was statistically better than the control decoction on symptom scores (P < 0.05) but was not clinically significant. The group data of all the trials showed that individualized decoction was superior to control decoction on symptom scores (2.13 ± 0.58 versus 2.30 ± 0.65, P = 0.002, mean difference and 95% CI: 0.18 (0.10, 0.25)), 24 h sputum volume (P = 0.009), and CAT scores (9.69 ± 4.89 versus 11.64 ± 5.59, P = 0.013, mean difference and 95% CI: 1.95 (1.04, 2.86)) but not clinically significant. CONCLUSION: Optimizing the combined analysis of individual and group data and the improvement of statistical models may make contribution in establishing a method of evaluating clinical efficacy in line with the characteristics of traditional Chinese medicine individual diagnosis and treatment.