PRAgmatic Clinical Trial Design of Integrative MediCinE (PRACTICE): A Focus Group Series and Systematic Review on Trials of Diabetes and Kidney Disease

Abstract

Background: Pragmatic trials inform clinical decision with better generalizability and can bridge different streams of medicine. This study collated the expectations regarding pragmatic trial design of integrative medicine (IM) for diabetes and kidney diseases among patients and physicians. Dissonance between users' perspective and existing pragmatic trial design was identified. The association between risk of bias and pragmatism of study design was assessed.Method: A 10-group semi-structured focus group interview series [21 patients, 14 conventional medicine (ConM) and 15 Chinese medicine (CM) physicians] were purposively sampled from private and public clinics in Hong Kong. Perspectives were qualitatively analyzed by constant comparative method. A systematic search of four databases was performed to identify existing IM pragmatic clinical trials in diabetes or kidney disease. Primary outcomes were the pragmatism, risk of bias, and rationale of the study design. Risk of bias and pragmatism were assessed based on Cochrane risk-of-bias tool and PRECIS-2, respectively. The correlation between risk of bias and pragmatism was assessed by regression models with sensitivity analyses.Results: The subtheme on the motivation to seek IM service was analyzed, covering the perceived limitation of ConM effect, perceived benefits of IM service, and assessment of IM effectiveness. Patients expected IM service to retard disease progression, stabilize concomitant drug dosage, and reduce potential side effects associated with ConM. In the systematic review, 25 studies from six countries were included covering CM, Korean medicine, Ayurvedic medicine, and western herbal medicine. Existing study designs did not include a detailed assessment of concomitant drug change and adverse events. Majority of studies either recruited a non-representative proportion of patients as traditional, complementary, and integrative medicine (TCIM) diagnosis was used as inclusion criteria, or not reflecting the real-world practice of TCIM by completely dropping TCIM diagnosis in the trial design. Consultation follow-up frequency is the least pragmatic domain. Increase in pragmatism did not associate with a higher risk of bias.Conclusion: Existing IM pragmatic trial design does not match the patients' expectation in the analysis of incident concomitant drug change and adverse events. A two-layer design incorporating TCIM diagnosis as a stratification factor maximizes the generalizability of evidence and real-world translation of both ConM and TCIM.

Add-on Rehmannia-6–Based Chinese Medicine in Type 2 Diabetes and CKD

“…Most existing trials assessed single Chinese medicine formulation either (1) in all participants without personalization or (2) in a phenotype-based subset with limited representation of the diabetic CKD population. 10,16 Assessing Chinese medicine as a program intervention 20 better mimics clinical practice. Phenotype-stratified randomization facilitates the analysis of effectiveness at both the program level (in the whole diabetic CKD population) and formulation level (in each phenotype subgroup) without excluding patients by phenotypes.…”

Applying the PRECIS-2 tool to pragmatic acupuncture trials: are they pragmatic? A systematic review

“…Along with the recruitment domain for which 31.2% of the studies were left blank, the rate of the score 'blank' was 84.9% and relatively higher than other domains, and this tendency was shown in a previous study assessing integrative medicine research. [22] In the real-world setting, methods such as sending messages or making phone calls for upcoming appointments may plausibly be used; however, attendance would not be compulsorily forced. Future PATs should explore this issue in more detail.…”

Potential Therapeutic Targets of Rehmannia Formulations on Diabetic Nephropathy: A Comparative Network Pharmacology Analysis

“…Free energy was used to estimate the strength of bonding for better estimating the binding affinity instead of using root-mean-square deviation from geometric assessment ( Cournia et al, 2017 ; Mobley and Gilson, 2017 ). Subsequent validation from clinical samples screening the biomarkers of key mechanisms would serve better to evaluate the whole-system effect and the relative involvement of different mechanisms of the formulations in real clinical settings ( Chan et al, 2021c ).…”

“…Previous registry studies showed that individualized Chinese medicine (CM) treatment was associated with slower decline of kidney function and reduced risk of end-stage kidney failure and mortality among patients with CKD and diabetes ( Hsieh et al, 2014 ; Lin et al, 2015 ; Huang et al, 2018 ; Chan et al, 2022 ). CM formulations are prescribed based on symptom-based diagnosis ( Chan et al, 2020a ; Chan et al, 2020b ; Chan et al, 2021a ; Chan et al, 2021b ; Chan et al, 2021c ; Shu et al, 2021 ), which predicts renal function decline independent of blood pressure, blood glucose, lipids, and urine albumin control ( Chan et al, 2021b ). The CM used in these cohorts mostly contained a classical CM formulation, namely, Rehmannia-6 complex (R-6, Liu-wei-di-huang-wan) with variations according to the symptom-based diagnosis.…”