10. Roadmap of the Submission Process of a Clinical Trial

10.1 Clinical Trial with Investigational Medicinal Product

The procedure to obtain a CTA includes the following key steps:

• Formal review of the application by the NMPA's Administrative Services Centre.
• Technical review by the CDE, including evaluation of the test report, clinical data, and other supporting information.
• Administrative review and issuance of the CTA by the CDE on behalf of the NMPA.

Before commencing a clinical trial, approval from the relevant independent ethics committee (EC) must be obtained. Generally, the EC reviews the protocol, informed consent form, investigator brochure, and the CTA, to assess if the rights and interests of study subjects can be fully protected.

The amended Drug Registration Rules that took effect on 1 July 2020 stipulate that if the sponsor changes, the new sponsor bears the relevant responsibilities and obligations for the clinical trial. However, the Drug Registration Rules do not provide detailed guidance on how a change of study sponsor is made.

For clinical studies involving approved drugs (which do not aim to expand the drug product's approved indications or use it in a combination study), both companies and investigators can launch post-approval clinical studies without filing a CTA application and obtaining CDE's approval. Such post-approval studies must be approved by the ECs of the participating sites and filed with the local health authorities where the sites are located (Administrative Measures on Clinical Studies by Medical Institutions, in effect from 16 October 2014).

Consent

Investigators must obtain informed consent from each trial subject. The information in the informed consent form must include the following, among others:

• The general overview, purpose, process, timeline, and content of the trial.
• The possibility of trial treatment and randomized distribution to each group.
• The procedures to be followed by the subjects, including medical operations. 
• Subjects' obligations.
• Anticipated benefits and risks to the subject.
• Other optional drugs and treatments available and their potential benefits and risks.
• Treatment and compensation the subject may be entitled to in the event of trial-related injuries. 
• The expected expenses for subjects to participate in the clinical trial.
• The status of and reasons for potential termination of the trial.

The informed consent form must be signed and dated by the investigator and the individual trial subject or, if the subject is a child or incapacitated person, by their legal guardian.

Trial pre-conditions

Under GCP, the sponsor must provide the investigator and the clinical trial site with legal and economic insurance or a guarantee for the trial, and ensure that it is appropriate to the nature and degree of risks of the trial. However, the sponsor is not responsible for any damage caused by the negligence of the investigator or medical institution.

The sponsor must provide the subjects with the investigational products free of charge, and pay the medical testing fees for the clinical trial according to GCP. 

Procedural requirements

A CTA holder must register all NMPA-approved registration studies on a drug clinical study registration platform for public disclosure (www.chinadrugtrials.org.cn). 

Information to be disclosed includes, but is not limited to:

• The drug name and indication
• Information about the sponsor
• Information about the study (objectives, design, phases of trials, grouping methods, endpoints, subject eligibility, and so on)
• Information about the investigator and status of the study (ongoing or completed)

A detailed outcome of the study does not have to be publicly disclosed on the platform.

The privacy of subjects and confidentiality of relevant trial information must be protected under GCP. The sponsor must use a subject identification code to identify the clinical trial data of each subject. Even in case of serious adverse events and follow-up reporting, the subject identification code must be used, rather than the subject's real name, citizen identity number, address, and other identity information. 

Further, any party with direct access to trial data and reports must take reasonable steps to protect the privacy of the subjects and avoid any disclosure of confidential information. 

Laws and regulations on cybersecurity, biosafety, and data privacy, such as specific requirements for the use, storage, sharing, and transmission (including outbound transmission) of a subject's personal or health information, also apply to clinical trials.

If there is an extensive, unexpected serious adverse reaction in a clinical trial, or evidence proving serious quality issues with the investigational drug, the sponsor and the site must stop the trial immediately and report this to the CDE. CDE can order the sponsor to adjust the study protocol and suspend or terminate the trial.

Transparency and reporting requirements

During a trial, the sponsor must submit reports to the CDE periodically for safety and study progress updates, including any serious adverse event reports. The CDE can, based on its review, require the sponsor to adjust the reporting cycle. 

Pursuant to GCP, the sponsor must also promptly report to the investigator, the site, the ethics committee at all participating sites, and the drug and health authorities all suspicious and unexpected serious adverse reactions and other potential serious safety risks arising during the trial. 

All trial-related source data, source documents, and reports must be made available at sites, for monitoring and audit by the sponsor and inspection by the drug administration authorities.

https://uk.practicallaw.thomsonreuters.com/4-500-8862?transitionType=Default&contextData=(sc.Default)&firstPage=true#co_anchor_a721571

10.2 Pediatric Investigation Plan (PIP)

Submission of a PIP is not required in China. The design of proposed clinical studies in pediatric patients should be discussed with NMPA on a case-by-case basis.

10.3 Clinical Study (Interventional or Observational) 

NMPA approval is not required for observational studies where an approved product is being used in accordance with its approved label.