Around the Globe

Remote Clinical Trials in China During the COVID-19 Pandemic
Ying Liang
Fresenius Medical Care Asia Pacific

n January 23, 2020, Wuhan and other cities in Hubei Province, China, began more than 70 days of mandated lockdown due to the outbreak of Coronavirus Disease 2019 (COVID-19). During this period, most other cities in China were also impacted, especially hospitals and clinics mainly focused on fighting COVID-19. Most ongoing clinical trials were suspended.

In February 2020, DIA China Digital Health Community conducted a survey on The impact of pandemics on clinical trials and the need for digital technology among clinical trial team members.

Organizations surveyed included sponsors, research centers, system providers, regulators, and other types, and encompassed both drug and device clinical trials. Respondent clinical trial team members included investigators, research center staff, patient recruitment staff, clinical research coordinators, CRAs, project managers, data managers, programmers, and statisticians.

Among the 176 responders, 131 (74.4 percent) stated that their projects had been suspended primarily due to failure to conduct patient follow-up visits (71.6 percent), suspension of patient recruitment (67.1 percent), inability to make timely data entries (50 percent), and inability to make timely delivery of the study drugs (40 percent).

Figure 1. The most affected parts of clinical research trials during the COVID-19 pandemic.
Figure 1. The most affected parts of clinical research trials during the COVID-19 pandemic.
Approximately 70 percent of the respondents expressed interest in learning more about remote clinical trial technology, tools, and applications. More than 40 percent of respondents indicated that remote visits and video conferences had already been adopted as part of their business continuity plan; in addition, a significant percentage responded that their trials had also used Direct-To-Patient (DTP) (27.8 percent), remote/centralized data monitoring (20.5 percent), electronic Patient-Reported Outcome (ePRO) (18.2 percent), and electronic Informed Consent (7.4 percent).
Figure 2. Business Continuity Plan in the COVID-19 pandemic.
Figure 2. Business Continuity Plan in the COVID-19 pandemic.
Based on these responses and growing general interest in remote clinical trials and digital clinical trial tools, the DIA China Digital Health Community held a series of Remote Digital Clinical Trials During COVID-19 Pandemic online seminars in March and April. In these seminars, veteran clinicians and researchers shared real cases from their remote clinical trial and digital trial technology implementations in China and introduced solutions and plans from these experiences.

Remote Data Monitoring

When the lockdown in Beijing started on February 10, Beijing Cancer Hospital was one of the first hospitals in China to launch a remote data monitoring system. Min Jiang (Beijing Institute for Cancer Research, Beijing Cancer Hospital) explained that this remote system was established based on existing information and data management systems. For data security, Clinical Research Associates (CRAs) from the sponsor or contract research organization (CRO) were required to submit a completed access application and signed Network and Information Security Commitment to the Institute. CRAs could then access patient panoramic data, including certified copies of all the data in the Electronic Health Record (EHR) system and paper records that were manually scanned with data masking.

As of February 27, users from 63 sponsors were granted access to this system. Clinical data from a total of 2,885 patients in 154 clinical projects across 16 hospital departments have been verified. Issues found across 52 remote monitoring projects included failure to conduct follow-up visits on the protocol schedule (117 times), failure to take the drug on the protocol schedule (105), missing electronic Case Report Form (eCRF) data (79), failure to deliver the drug on the protocol schedule (74), and inconsistency between the CRF and source data (69 times).

Outcomes and Assessments

Patient Reported Outcomes (PROs) must meet ICH-GCP requirements. Le Song (Shanghai Jsure Health) identified distinctions between a Clinical Outcome Assessment (COA) and PRO, highlighting advantages of the ePRO application from the ICH-GCP perspective. The COA consists of Clinician-Reported Outcome (ClinRO), Observer-Reported Outcome (ObsRO), Performance Outcome (Perfo) and the PRO. The PRO is the only one of these four components that is directly reported by the patient. PRO applications currently include Health-Related Quality of Life, symptom, functional assessment, survival assessment, subject compliance, perceived treatment value, and safety assessment.

An ePRO is not only easier for a patient to complete remotely compared to a paper PRO, but it may also improve data quality. A case study comparing the compliance rates for 80 patients keeping either paper or electronic diaries showed that the mean compliance rate was 94 percent (95% CI: 92%-96%) in the electronic diary group but only 11 percent (95% CI: 8%-14%) in the paper diary group.

The most popular ePRO platforms are currently mobile application (APP) and the WeChat Mini-Program. Dong Ma (Taimei Medical Technology) presented an ePRO APP application case. This ePRO APP comprises the eConsent, eVisit, eSource, and EDC functions. Patients can download the APP and register through an invitation code sent by the investigator. The patient must watch an introductory video and pass a test on the informed consent process before signing the electronic Informed Consent Form. After that, the patient enters the ePRO system and completes reports according to protocol requirements. The system sends out reminders for data submission and queries raised by the investigator, and intelligently detects and masks patient privacy information.

Intelligent Systems and Platforms

The full capabilities of intelligent clinical trial systems can be used in epidemiologic research, in strategic assessment for target filter and drug discovery, in synthetic control arm simulation and data-driven site selection for clinical development, in developing strategies to support product launch and sales platforms (including drug sales strategically based on real word data), in patient management programs, and in generating evidence from post-market studies.

Such intelligent platforms can also acquire patient data from different scenarios. For instance, remote data monitoring systems including devices for file scanning and the Patient Management APP allows patients to self-report data, and the WeChat Mini-Program platform features ePRO, visit reminder, and DTP functions. Furthermore, systems are connected with analytic tools that can perform screening, variant selection, variant calculation, and data preview (statistic description). Some full-process intelligent clinical platforms also provide safety, pharmacovigilance, regulatory submission, and AI image evaluation features.

By employing remote clinical trials to address the challenges of conducting traditional clinical trials posed by the COVID-19 pandemic (impacting on-site subject visit, data monitoring, and drug delivery), sponsors and CROs have been able to maintain their business continuity in China. However, because such trials are just getting started in China, it is important to optimize the impact of these technologies and services and pertinent regulations should evolve to appropriately support these developments.