Current situation and challenge of registry in China

Abstract

Increasing emphasis has been placed on registries for an organized system used in developing clinical research to improve health care. China has sufficient data that can be applied broadly, but the heterogeneity and irregularity of registries limit their applicability. This article aims to describe the status of registries in China and the related challenges. Patient registries for observational studies were retrieved from the International Clinical Trials Registry to quantitatively evaluate the number of comparatively high-quality registries in China. A literature search was also performed to provide support and updates. A total of 64 patient registries were retrieved from ClinicalTrials.gov using disease, product, and health service as criteria. The sample sizes ranged from 15 to 30 400, with only 12 registries marked as completed. This article describes and compares the detailed information in many aspects. The efficient use of registries has already made considerable progress in China; however, registries still require standardization, high-quality transition, and coordinated development.

Keywords

Chinese / registry study / patient registries / observational study

1 Introduction

A randomized controlled trial (RCT) is the typical method for analyzing the effect of interventions; however, an increasing number of researchers have realized that observational studies, especially registry studies, may compensate for the inadequacy of RCTs, including their inability to quickly reflect the safety and effect of different intervention measures in the real world [1].

In 1974, a publication from the World Health Organization introduced and described registries in health information systems [2]. The first study based on a registry system, which utilized 56 000 obstetric records, was a collaborative study on cerebral palsy to analyze neuropsychological deficits in children of diabetic mothers [3]. In recent years, registry studies have attracted considerable attention. As the National Committee on Vital and Health Statistics delineated, registries are used for a broad range of purposes in public health and medicine as “an organized system for the collection, storage, retrieval, analysis, and dissemination of information on individual persons who have either a particular disease, a condition (e.g., a risk factor) that predisposes [them] to the occurrence of a health-related event, or prior exposure to substances (or circumstances) known or suspected to cause adverse health effects” [4]. At present, 875 patient registries from all over the world are enrolled in ClinicalTrials.gov; 87 of these registries are developed in China (64 in the mainland of China, 1 in Hong Kong, and 22 in Taiwan). Nevertheless, the number of registries in China still lags behind that in Europe and the United States [5].

According to the Registries for Evaluating Patient Outcomes: A User’s Guide, most registries use three general categories with multiple subcategories and combinations to classify patients with exposure to a product or service, a particular disease or condition, or various combinations thereof [6]. In practice, these registry categories overlap, thereby complicating the classification process. For example, a registry may refer to the incidence of thrombosis after implantation of drug-eluting stents in patients with coronary artery disease [7]. An important objective of these health service registries is to generate an assessment with respect to outcomes [6]. The US Food and Drug Administration has introduced the pregnancy registry, which actively collects information on medical product exposure during pregnancy and the neonatal consequences [6].

Patient registries, which can provide a real-world view of clinical practices, patient outcomes, safety, and comparative effectiveness, have been widely utilized for scientific, clinical, and health policy purposes [6]. Registries are frequently used to monitor product safety under real-world clinical practices; to assess effectiveness, especially of long-term treatments; to develop a post-marketing commitment to the government; to observe the natural history of diseases; to understand real-world treatment use and provide suggestions for clinical decision making; and to reduce the burden of rare conditions [1,8]. The present article aims to describe the status of registries in China and provide some suggestions on how to face the related challenges.

2 Current situation of registries in China

To assess the current situation of registries in China, we quantitatively evaluated the number of comparatively high-quality registries in China by retrieving “patient registries for observational studies” from www.clinicaltrials.gov [9]. A total of 64 patient registries (3 were repeated) from January 2009 to April 2014 were obtained. The sample sizes ranged from 15 to 30 400. Fig.1 shows the variation in the registries and clearly reflects the steady increase in the number of registries in China. Twenty-three registries should have been completed by the end of April 2014. However, only 12 registries have been completed thus far. Additional details are shown in Table 1.

Table 2 shows the general characteristics of the registries, including the scope of the studies and the sample sizes. Most registries in China, especially those with large sample sizes (some studies are calculated twice or thrice because of the combinations), are developed according to disease or condition.

Table 3 classifies the registries by diseases based on ICD-10. Endocrine, nutritional, and metabolic diseases have the highest percentage of relation to the registries, followed by diseases of the circulatory system and neoplasms. Drug and device registries are relatively scattered. These registries are always combined with specified diseases or conditions, including drugs used for the following diseases: neoplasms (e.g., bevacizumab), diseases of the digestive system (e.g., pancreatic enzyme), diseases of the blood and blood-forming organs, diseases related to the immune mechanism hematological system (e.g., idarubicin), diseases of the circulatory system and cardiovascular diseases (e.g., clopidogrel), diseases of the nervous system (e.g., lurasidone), diseases of the skin and subcutaneous tissue dermatology (e.g., topical corticosteroids), traditional Chinese medicine injections (e.g., cinepazide maleate injection), biomarkers (lung cancer biomarker panel), and some devices related to medical operations (e.g., stenting and colonoscopy).

This study also compared the objectives and sponsors of the registries in China. The main purpose of the disease registries is to obtain epidemiological features, such as disease incidence [10]. Drug and device registries are developed for surveillance, such as for post-marketing safety. Combined registries serve multiple purposes, including for efficacy and safety evaluation and for social planning [11]. As sponsors, hospitals and universities are generally the main parties that develop registries; only a few registries are developed by the government and some professional associations in China.

A literature search was performed using PubMed to provide support and updates. We found that the National Cancer Registry is frequently used, with the focus mostly on the trend of mortality or prediction of breast cancer, oral cavity and pharyngeal caner, esophageal cancer, and colorectal cancer [12–18]. Only one research was found to be related to a specific cancer, that is, the “Esophageal and gastric cardia cancers on 4238 Chinese patients residing in municipal and rural regions: a histopathological comparison during 24-year period” [19]. In addition, many publications are based on the China Quality Evaluation of Stroke Care and Treatment (QUEST) registry study [20,21], Chinese Transcatheter Interventional Therapy (TIT) of congenital heart disease registry study [22], China National Stroke Registry (CNSR) [23], Chinese Coronary Artery Bypass Grafting (CABG) registry [24]. Sino-global registries, such as the China Non-ST Elevation Acute Coronary Syndromes registry and the Sino-Global Registry of Acute Coronary Events, were also found. Table 4 shows the characteristics of the four influential registries [25].

We also investigated some important registries that provide services or surveillance to the government without being published. These registries included reports about the registration of dialysis and transplantation in China, emergency center database, Chinese monitoring system for the rational use of drugs, Chinese birth defects registry, and infectious disease registry (e.g., tuberculosis).

The results showed that the use of patient registries varies based on priority condition, with cancer, stroke, and cardiovascular diseases having a relatively large number of registries and with rare diseases having very few registries [2]. Thus, the application of patient registries is continuously and aggressively increasing.

Given the conditions described previously, the transformation of the registry status in China still involves many issues that need to be solved [11].

3 Facing the challenges in the registry status of China

3.1 Enhancing the quality of registries

The quality of registries in China varies significantly. Some registries are inconclusive because of a small sample size, and only less than half of the registries in China were accomplished on time. Several quality issues emerged upon further examination of the study population preferred in China. The present study offers some suggestions based on similar rules and successful experiences abroad [1,2,6,11,26]. The first step in registry development should be to confirm the minimum sample size and to define the quality assurance requirements, including identifying the most likely errors and potential lapses in procedures [27]. Attention should be paid to the recruitment and supervision of providers and to the management of patients [6]. In fact, most data collectors in China have not been properly trained. Hence, researchers should consider how data elements are structured and defined, how personnel are trained, and how data problems are handled (e.g., missing, out of range, or logically inconsistent values) [6]. Collecting data in accordance with established procedures and guidelines recommended by experts can ensure that registries meet the requisite quality standards and consequently accomplish their purposes. Guaranteeing the criteria for each procedure, including collecting, cleaning, storing, monitoring, reviewing, and reporting registry data, is difficult but necessary [6]. Continuously evaluating registries is also important in preventing bias [9].

3.2 Developing multicenter registry and linking registry data

The fragmentation and heterogeneity of Chinese registries often limit their general applicability. The results discussed above highlight the apparent advantages and growing trend of multicenter registries, such as QUEST, CNSR, TIT, and CABG. The results also reveal the trend in the cooperative analysis of rare diseases with an adequate sample size. However, coordinating with every center, balancing financial and production benefits, and providing motivation to data providers are big challenges.

Registry data should be linked to other data sources, such as administrative and other registry data sources, to examine questions that cannot be addressed by using the registry data alone. However, the following should be considered: how to make the linkage feasible and legal, how to support the process technically, and how to solve the statistical problems (e.g., matching) in linking records. We should also focus on developing global patient registries [6].

3.3 Interfacing registries and electronic health records

Most of China’s registry sponsors are hospitals. The number of hospital-based registries with electronic health records (EHRs) is increasing along with the increase in population and the standardization of EHRs. However, data exchange accuracy in software-as-service may be an obstacle [6]. Thus, ensuring the interoperability of syntactic and semantic communication and content is important [6]. Continuously developing, testing, and adopting open-standard building blocks toward incrementally advancing interoperability is difficult. Researchers should thus consider critical ethical practices and specify data ownership to ensure the attainability of data records in the beginning of the registry development process. Other important concerns include the transparency of activities and supervision.

3.4 Sharing and allocating benefits

One big challenge in the usage of Chinese registries is the allocation of benefits to stakeholders from multiple centers. This problem may be solved by considering an effective system design and establishing a set of benefits with incentive mechanisms.

4 Conclusions

The collection of real-world data and the development of observational studies, especially in patient registries, are important in evidence-based decision making [1,9,26,28,29]. Registries, along with RCTs, can promote the improvement of public health care in China, which is known for its huge population [28]. The focus of registries on actual use, such as describe natural history of disease, analyze short- and long-term safety and effectiveness, and determine meaningful health outcomes, dictate design decisions and the choice of analytic methods [6]. The status of registries in China has made considerable progress. However, the evaluation of the curative effect of registry use on policymaking is still lacking. Researchers should continue developing systematic methodologies, state-of-the-art technologies, and relevant laws and regulations [1,6,26–28]. More important, we must establish a uniform guideline through which researchers can expand the application of this study. In sum, the status of registries in China needs a standardized, high-quality transition with coordinated development [6].

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