Summary of Key Points
Over the past month or so, there have been three consecutive deaths of participants in clinical studies (IITs) initiated by doctors in the field of rare diseases, highlighting the shortcomings of IITs in terms of ethical review and protection of participants' rights. As an important approach to treating rare diseases (since pharmaceutical companies are reluctant to invest due to low commercial returns), IITs currently face issues such as an overemphasis on initial review and a neglect of follow-up supervision, as well as inadequate implementation of informed consent. Departments such as the National Health Commission have issued policies emphasizing that ethical reviews must cover the entire research process and that informed consent must be genuine and effective in order to address these safety gaps.
1. What are IITs? Why are they essential for rare diseases?
IITs are clinical studies initiated by doctors, which are different from “registered clinical trials (ISTs)” conducted by pharmaceutical companies for drug development:
- Initiator: Doctors (not pharmaceutical companies);
- Purpose: To address practical clinical problems (e.g., the lack of available treatments for rare diseases or to explore new therapies), not for drug registration;
- Regulatory Authority: Managed by the Health Commission (not the Drug Regulatory Agency).
Why are IITs necessary for rare diseases? Because there are so few patients with rare diseases (for example, only 1 in every 3,500 boys suffers from Duchenne muscular dystrophy), pharmaceutical companies cannot attract enough participants or make a profit from ISTs, so they are not motivated to invest. IITs fill this gap by allowing doctors to directly explore new therapies in clinical settings, giving hope to patients with rare diseases who are often overlooked by the commercial sector.
2. The core issues exposed by the deaths: inadequate ethical review and perfunctory informed consent
The three deaths (a boy with Duchenne muscular dystrophy, a man with systemic sclerosis, and a 6-year-old girl with a rare neurological disorder) reveal two major problems:
- Lack of follow-up supervision: For example, a top-tier hospital in Shenzhen has a 100% follow-up rate for registered clinical trials, but less than 10% for IITs; in a hospital in Shanghai, over 43% of IIT projects did not submit follow-up reports between 2016 and 2021. Once the initial review is completed, no further monitoring is conducted, and potential side effects or risks are not promptly identified and addressed.
- Inadequate informed consent: Some patients or their families may not fully understand the risks involved—e.g., what are the side effects of the new technologies used in the studies, and who will be responsible if something goes wrong? Many informed consent forms merely require a signature without providing clear information.
3. How is the state addressing these issues?
The state has taken action to improve ethical review and informed consent:
- Specific Regulations: The Health Commission, in conjunction with the Ministry of Education, has issued guidelines that require detailed explanations of risks, benefits, and alternative options in the informed consent process, ensuring that patients or their families fully understand before signing.
- Emphasis on comprehensive review: Ethical reviews must not only assess the quality of the research plan but also monitor the entire research process—e.g., checking regularly whether the plan is being followed and whether any adverse events occur, and stopping the study immediately if issues arise.
- Dynamic supervision: The “Order No. 818” (Regulations on the Management of New Biomedical Technologies), implemented in May this year, requires IITs to be registered after passing ethical reviews and to undergo subsequent national inspections, ensuring that the process is not a one-time affair.
- Hospital compliance requirements: During the “15th Five-Year Plan” period, hospitals are required to integrate research ethics into their overall compliance audits, ensuring that all necessary reviews are conducted.
4. Why is comprehensive review crucial for patient safety?
New biomedical technologies (such as gene therapy and cell therapy) carry significant risks, and patients with rare diseases, who often have no available treatments, are particularly vulnerable:
- For example, a cell therapy used in an IIT may seem safe initially, but serious immune reactions may occur later on. Without follow-up monitoring, doctors might not detect these issues, leading to tragic outcomes.
- Comprehensive review allows ethical committees to closely monitor the research, allowing for immediate adjustments to the plan or termination of the study if adverse events occur, thereby minimizing risks.
5. The impact on patients and the industry: Safety ensures the long-term success of IITs
- For patients: IITs represent a last hope, and safety is of utmost importance. With improved review processes, patients can participate with more confidence, knowing that they will be properly cared for throughout the research.
- For the industry: Only with standardized procedures can IITs develop healthily—doctors will be more willing to conduct such studies, and patients will be more willing to participate, leading to the discovery of effective treatments for rare diseases.
In summary, IITs are a vital resource for patients with rare diseases, but their success depends on strict ethical and safety measures. Only by ensuring that these aspects are well-established can they truly provide a light of hope for these patients.