A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method

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Brief Title

A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method

Official Title

A Series of N-of-1 Trials on Bronchiectasis Treated With Traditional Chinese Medicine Based on Bayesian Model

Brief Summary

      The guiding role of parallel randomized controlled trials in clinical practice is limited due
      to the insufficiency of individual information. Our previous studies showed that Single case
      randomized controlled trials (referred to as N-of-1 trials) could reflect the individualized
      characteristics of traditional Chinese medicine (TCM) syndrome differentiation with good
      feasibility, but the sensitivity was low.

      This study aims to compare the efficacy of treatment based on syndrome differentiation with
      controlled decoctions (placebo, and the method of strengthening the body resistance and
      removing phlegm) among patients with stable bronchiectasis through a series of N-of-1 trials
      (single-patient, double-blind, randomized, multiple crossover design), with the 7
      point-likert scale of the most concerned symptoms as the main outcome. Hierarchical Bayesian
      statistical methods and some parameters and variables will be introduced, such as TCM
      syndrome type, potential residue effect of TCM, etc. The sensitivity and applicability of
      various mathematical models (Hierarchical Bayesian, paired t-test and Meta-analysis) for
      N-of-1 trials of TCM will be tested, for the purpose of improving the sensitivity and
      applicability of N-of-1 trials of TCM both on individual and group levels.
    

Detailed Description

      TCM has made great progress in the context of modern science and technology, but compared
      with the rapid development of modern medicine, the development of TCM has been relatively
      slow. The randomized controlled trial based on population is incompatible with the
      characteristics of TCM syndrome differentiation. The lack of reliable efficacy evaluation
      methods based on evidence-based medicine has hindered the internationalization and
      development of TCM.

      The clinical trial (International clinicaltrials.gov Identifier: NCT03147443) the
      investigators just finished found that the improved mixed effects model can detect the
      residual effect of TCM in the N-of-1 trials and improve the sensitivity of group data
      statistics. However, the sensitivity of this study method is low at the individual
      statistical level due to the inherent nature of N-of-1 trials, and more cases need to be
      studied for further improvement. Now that hierarchical Bayesian statistical method has become
      one of the major statistical methods in a series of N-of-1 trials. Compared with the
      frequentist statistical methods, the advantages of Bayesian method are as follows: (1) the
      integration analysis of both individual and group data can be carried out at the same time;
      (2) it is easy to introduce confounding variables, such as the physique or gene type of
      different subjects, or different TCM syndrome types (which are helpful to distinguish
      different TCM syndrome types and the difference of the effects); (3) in addition, there is a
      special advantage: if a large number of patients have completed similar N-of-1 trials with
      the variance within an individual patient greater than that between the patients, through
      "borrowing from strength" , the results of other patients can be used to improve the accuracy
      of an individual result, that is, to improve the sensitivity of N-of-1 trials, without the
      need to increase the pairs of N-of-1 trials. At present, this statistic method is rarely used
      in N-of-1 trials of TCM, so it is worth using for reference in our future research.

      The key hypothesis of this study is that: (1) the efficacy of syndrome differentiation will
      be better than placebo in patients with stable bronchiectasis through N-of-1 trials. (2) the
      efficacy of syndrome differentiation will be better than the same prescription minus
      heat-clearing Chinese herbs in patients with stable bronchiectasis through N-of-1 trials.
      However, at the individual level, with the severity of individual phlegm heat, the efficacy
      will be different, reflecting the effect of individual treatment based on syndrome
      differentiation of Chinese medicine. (3) Hierarchical Bayesian statistical model will improve
      the sensitivity and applicability of N-of-1 trials of TCM both on individual and group
      levels.

      In this study, the investigators will conduct a single center N-of-1 trials in 71 patients
      with stable bronchiectasis without hemoptysis and respiratory failure. These N-of-1 trials
      will be randomized, double-blind, crossover comparisons of individualized herbal decoction
      with control decoction within individual patients. Each N-of-1 trial will have 3 pairs of
      treatment periods. The duration of each treatment period will be 4 weeks. The investigators
      will compare: (1) the efficacy of syndrome differentiation (individualized decoction) with
      placebo, (2) the efficacy of syndrome differentiation (individualized decoction) with the
      same prescription minus heat-clearing Chinese herbs, in patients with stable bronchiectasis
      through a series of N-of-1 trials. The primary outcome is patient self-reported symptoms
      (such as cough, expectoration, shortness of breath, chest pain, and fatigue) scores on a 7
      point likert scale. Secondary outcomes are 24-hour sputum volume and the chronic obstructive
      pulmonary disease (COPD) Assessment Test (CAT) scores. Hierarchical Bayesian statistical
      methods and some parameters and variables will be introduced, such as TCM syndrome type,
      potential residue effect of TCM, etc. The sensitivity and applicability of various
      mathematical models (Hierarchical Bayesian, paired t-test and Meta-analysis) for N-of-1
      trials of TCM will be tested, for the purpose of improving the sensitivity and applicability
      of N-of-1 trials of TCM both on individual and group levels.
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Patient Self-Rated Symptom Score (likert scale)

Secondary Outcome

 24 hours sputum volume

Condition

Bronchiectasis

Intervention

Individualized Decoction

Study Arms / Comparison Groups

 Individualized Decoction
Description:  It is the highly individualized treatment of TCM, the modification of Bronchiectasis Stabilization Decoction (Rhizoma Fagopyri Cymosi 30g, Radix Lithospermi 15g, Radix Ophiopogonis 15g, Poria cocos 15g, Radix Astragali 20g, Rhizoma Bletillae 10g, Platycodon grandiflorum 10g, Semen Coicis 30g) based on syndrome differentiation. For subjects with lung and spleen qi deficiency syndrome, the investigators added Radix Codonopsis Pilosulae, Pericarpium Citri Reticulatae, and Atractylodes Macrocephala Koidz. The investigators can adjust the individualized decoction in accordance with the change in the patient's condition throughout the whole study duration.
The Chinese herbal decoction is taken by one decoction a day and divided into 2 doses, for 3 weeks in each observation period.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

71

Start Date

December 1, 2019

Completion Date

December 31, 2022

Primary Completion Date

December 31, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  according to the consensus of domestic experts, combined with the guidelines for the
             management of adult bronchiectasis published by the European Respiratory Society in
             2017;

          -  male or female, aged 18-70 years;

          -  being in the stable stage, and no acute exacerbation of bronchiectasis within the past
             three weeks;

          -  frequency of acute exacerbation of bronchiectasis ≤3 times every year;

          -  signed informed consent for participation.

        Exclusion Criteria:

          -  failing to meet the above criteria for diagnosis and inclusion;

          -  having developed respiratory failure with estimated survival time less than one year;

          -  having hemoptysis as a comorbidity;

          -  having complications by active tuberculosis;

          -  being pregnant or with severe heart, liver, or kidney dysfunctions;

          -  participating in other pharmacological clinical trials within the past 3 months.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

, 008602165161782, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT04601792

Organization ID

haiyin huang


Responsible Party

Sponsor

Study Sponsor

Shanghai University of Traditional Chinese Medicine

Collaborators

 Guangzhou University of Traditional Chinese Medicine

Study Sponsor

, , 


Verification Date

September 2020