NMPA released the “Clinical Evaluation Guideline for In Vitro Diagnostic Reagents for Cancer Screening” on August 21, 2025. The document provides direction for applicants preparing registration dossiers and clinical evaluation materials for in vitro diagnostic (IVD) reagents used in cancer screening. It also serves as a reference for technical review departments.
The guideline emphasizes that cancer screening IVDs must be developed with strong clinical rationale, grounded in evidence from Chinese populations, and supported by rigorous clinical trials. For cancers with existing screening standards, products must at least match accepted performance. For cancers without established methods, applicants must demonstrate that the proposed screening strategy provides clear population benefits and manageable risks. Special care is required for multi-cancer screening approaches. Ultimately, evaluation must integrate performance, safety, risk–benefit balance, and practical feasibility, ensuring that screening tools contribute meaningfully to public health.
Scope of Application
Cancer screening is focused on cancers with high mortality and heavy disease burden, where early detection leads to effective treatment and better outcomes. Effective screening allows early identification, diagnosis, and treatment, thereby reducing incidence, mortality, and improving quality of life.
The guideline covers IVD reagents that detect biomarkers such as proteins or nucleic acids from human samples to identify, alone or in combination with other methods (e.g., imaging), whether asymptomatic individuals may have cancer or precancerous lesions. Positive cases proceed to diagnostic confirmation and treatment; others may enter follow-up.
Target populations must be defined based on cancer characteristics, risk factors, biomarker features, and expected clinical performance. These factors should align with authoritative clinical guidelines. The guideline applies to both new product registration and changes to existing registrations, focusing primarily on clinical evaluation materials.
Key Points in Registration Review
(a) Selection of Cancer Types
Screening should target cancers that:
- Cause significant mortality and public health burden.
- Have effective methods for early diagnosis.
- Possess clear evidence on intervention effectiveness and risks across disease stages.
- Show better treatment outcomes when detected early.
Applicants should base product design on clinical needs, epidemiology, and natural history, supported by evidence relevant to Chinese populations. WHO currently recommends screening for colorectal, cervical, and breast cancers. In China, evidence also supports screening for high-risk groups in lung, esophageal, liver, gastric, and nasopharyngeal cancers.
(b) Clinical Evaluation Requirements
IVD reagents for cancer screening must undergo clinical trials.
- Cancers with established screening methods:
- Where national guidelines exist and benefits are well supported, applicants can conduct multicenter prospective trials (≥3 qualified institutions).
- Trials must ensure representative populations, with clear inclusion standards (general or high-risk groups). Recruitment can involve community health institutions under trial center oversight.
- Evaluation includes sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. Comparisons with accepted screening methods are recommended.
- Sample size must be statistically justified, considering disease prevalence and expected accuracy.
- Results should undergo stratified analysis (e.g., by cancer stage, histology, risk factors) to ensure robustness.
Performance data should also cover biomarker detection accuracy, ideally compared to laboratory reference methods or existing approved products. Safety assessment must address complications, radiation exposure, false positives/negatives, and acceptability of risks.
- Cancers without established guidelines:
- Screening requires building an evidence-based program, including target populations, methods, frequency, follow-up, cost-effectiveness, and acceptance.
- Clinical evaluation must demonstrate that benefits outweigh risks. Positive cases must have timely diagnostic and treatment pathways.
- Trials should assess not only sensitivity and specificity but also numbers needed to screen (NNS), detection rates by cancer stage, time to diagnosis, and confirmation methods.
- Risk analysis must cover complications, false positives (leading to unnecessary procedures), false negatives (missed diagnosis), overdiagnosis, and psychological effects.
- Benefit evaluation should include short-term (e.g., stage shift, fewer advanced cases) and long-term outcomes (reduced cancer-specific and all-cause mortality). Evidence may come from randomized controlled trials, cohort studies, or published data.
(c) Multi-Cancer Screening Products
When products cover multiple cancers, additional issues must be considered:
- Rationality of cancer combinations.
- Accuracy of tissue-of-origin tracing for positive results.
- Diagnostic complexity and accessibility of follow-up tests.
- Risk–benefit balance, including potential delays or harms in confirmatory processes.
Applicants must prove that organ tracing accuracy and confirmatory pathways meet clinical needs.
Takeaways for Overseas Manufacturers
For international IVD companies, these updated provisions highlight China’s ongoing commitment to supporting the streamlined registration of high-quality diagnostic products. Overseas manufacturers must pay attention to the following:
- Beyond accuracy and safety, applicants are encouraged to assess the aspects below:
- Cost-effectiveness compared to existing methods.
- Acceptance by target populations.
- Effects of screening frequency on outcomes.
- Long-term monitoring after clinical use, including population-level mortality or incidence changes.
- Early engagement with local regulatory and clinical partners will be key to accelerating registration timelines and building a sustainable market presence.