Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Identification and in vitro functional assessment of 10 CYP2C9 variants found in Chinese Han subjects.

Cytochrome P450 2C9 (CYP2C9) participates in about 15% of clinical drug metabolism, and its polymorphism is associated with individual drug metabolism differences, which may lead to the adverse drug reactions (ADRs). In this study, 1163 Chinese Han individuals were recruited to investigate their distribution pattern of CYP2C9 gene and find out the variants that may affect their drug metabolic activities. We successfully developed a multiplex PCR amplicon sequencing method and used it for the genetic screening of CYP2C9 in a large scale. Besides the wild type CYP2C9*1, totally 26 allelic variants of CYP2C9 were detected, which included 16 previously reported alleles and 10 new non-synonymous variants that had not been listed on the PharmVar website. The characteristics of these newly detected CYP2C9 variants were then evaluated after co-expressing them with CYPOR in S. cerevisiae microsomes. Immunoblot analysis revealed that except for Pro163Ser, Glu326Lys, Gly431Arg and Ile488Phe, most of newly detected variants showed comparable protein expression levels to wild type in yeast cells. Two typical CYP2C9 probe drugs, losartan and glimepiride, were then used for the evaluation of metabolic activities of variants. As a result, 3 variants Thr301Met, Glu326Lys, and Gly431Arg almost lost their catalytic activities and most of other variants exhibited significantly elevated activities for drug metabolism. Our data not only enriches the knowledge of naturally occurring CYP2C9 variants in the Chinese Han population, but also provides the fundamental evidence for its potential clinical usage for personalized medicine in the clinic.

Adding high-sensitivity C-reactive protein to frailty assessment to predict mortality and cardiovascular events in elderly inpatients with cardiovascular disease.

OBJECTIVE: Chronic inflammation is associated with major adverse cardiovascular events (MACEs), mortality, and frailty. Our aim was to add high-sensitivity C-reactive protein (hsCRP) to the frailty assessment to predict its association with prognosis of older adults with cardiovascular disease (CVD). METHODS: A comprehensive geriatric assessment was conducted at baseline in 720 in-patients aged ≥65 years with CVD. We divided the population into frailty and non-frailty groups according to the Fried phenotype, and hsCRP was further combined with frailty to stratify all patients into c-frailty and non-c-frailty groups. Predictive validity was tested using Cox proportional hazards regression model analysis and the discriminative ability was evaluated by receiver operating characteristic (ROC) curves. RESULTS: Of all the subjects enrolled, 51.0% were male and the mean age was 75.32 ± 6.52 years. The all-cause death and MACE rate was 6.4% at the 1-year follow-up. Frailty and c-frailty were independent predictors of all-cause death and MACE (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.35-4.83, p = 0.004; HR: 3.67, 95% CI: 1.83-7.39, p < 0.001). Adding hsCRP to the frailty model resulted in a significant increase in the area under the ROC curve from 0.74 (95% CI: 0.70-0.77) to 0.77 (95% CI: 0.71-0.84) (p = 0.0132) and a net reclassification index of 7.9% (95% CI: 1.96%-12.56%, p = 0.012). CONCLUSION: Adding hsCRP to the frailty assessment is helpful to identify a subgroup of older CVD patients with a higher risk of death and MACE over a period of 1 year. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018. URL: http://www.chictr.org.cn/showproj.aspx?proj=28931.

The effect of comprehensive assessment and multi-disciplinary management for the geriatric and frail patient: A multi-center, randomized, parallel controlled trial.

BACKGROUND: A comprehensive geriatric assessment (CGA) of elderly patients is useful for detecting the patients vulnerabilities. Exercise and early rehabilitation, nutritional intervention, traditional Chinese medicine (TCM), standardized medication guidance, and patient education can, separately, improve and even reverse the physical frailty status. However, the effect of combining a CGA and multi-disciplinary management on frailty in elderly patients remains unclear. The present study assessed the effects of a CGA and multi-disciplinary management on elderly patients with frailty in China. METHODS: In this study, 320 in patients with frailty ≥70 years old will be randomly divided into an intervention group and a control group. The intervention group will be given routine management, a CGA and multi-disciplinary management involving rehabilitation exercise, diet adjustment, multi-drug evaluation, acupoint massage in TCM and patient education for 12 months, and the control group will be followed up with routine management for basic diseases. The primary outcomes are the Fried phenotype and short physical performance battery (SPPB). The secondary outcomes are the clinical frailty scale (CFS), non-elective hospital readmission, basic activities of daily living (BADL), 5-level European quality of life 5 dimensions index (EQ-5D), nutrition risk screening-2002 (NRS-2002), medical insurance expenses, fall events, and all-cause mortality. In addition, a cost-effectiveness study will be carried out. DISCUSSION: This paper outlines the protocol for a randomized, single-blind, parallel multi-center clinical study. This protocol, if beneficial, will demonstrate the interaction of various intervention strategies, will help improve elderly frailty patients, and will be useful for clinicians, nurses, policymakers, public health authorities, and the general population. TRIAL REGISTRATION: Chinese Clinical Trials Register, ChiCTR1900022623. Registered on April 19, 2019, http://www.chictr.org.cn/showproj.aspx?proj=38141.

Predicting non-elective hospital readmission or death using a composite assessment of cognitive and physical frailty in elderly inpatients with cardiovascular disease.

BACKGROUND: We aimed to assess the utility of the combination of the mini-mental state examination (MMSE) + clock drawing test (CDT) and the Fried phenotype for predicting non-elective hospital readmission or death within 6 months in elderly inpatients with cardiovascular disease (CVD). METHODS: A single-center prospective cohort was conducted from September 2018 to February 2019. Inpatients ≥65 years old were recruited. Predictive validity was tested using a Cox proportional hazards regression model analysis, and the discriminative ability was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 542 patients were included. Overall, 12% (64/542) screened positive for cognitive impairment, 16% (86/542) were physically frail and 8% (44/542) had cognitive impairment combined with physical frailty, showing an older age (P < 0.001) and a lower education level (P < 0.001) than physically frail patients. A total of 113 patients (20.9%) died or were readmitted at 6 months. Frail participants with a normal (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.06-2.82, P = 0.028) or impaired cognition (HR: 2.50, 95% CI: 1.27-4.91, P = 0.008) had a higher risk of non-elective hospital readmission or death than robust patients after adjusting for the age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and history of stroke. The area under the ROC curve (AUC) showed that the discriminative ability in relation to 6 months readmission and death for the MMSE + CDT + Fried phenotype was 0.65 (95% CI: 0.60-0.71), and the AUC for men was 0.71 (95% CI: 0.63-0.78), while that for women was 0.60 (95% CI: 0.51-0.69). CONCLUSIONS: Accounting for cognitive impairment in the frailty phenotype may allow for the better prediction of non-elective hospital readmission or death in elderly inpatients with CVD in the short term. TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.