Clinical efficacy of integrated Chinese-Western medicine therapy for metastatic colorectal cancer

Table 1 Emulated target trial framework for Jianpi Bushen Jiedu method in treating metastatic colorectal cancer

Study process	Real-world study protocol	Target trial emulation protocol
Inclusion criteria	(1) Age ≥ 18 years, any sex; (2) Pathologically confirmed colorectal cancer; (3) TNM stage IV; (4) Received standard Western medicine treatment; (5) First use of Jianpi Bushen Jiedu herbal medicine at baseline; (6) Expected survival ≥ 3 months at baseline; and (7) Complete baseline medical records including TCM four diagnostic methods and syndrome differentiation	Same
Exclusion criteria	(1) Patients with two or more concurrent malignancies; (2) Severe cardiac, hepatic, or renal dysfunction at baseline; (3) Patients who have undergone curative treatment and are tumor-free; and (4) Participation in any interventional clinical trial within 3 months prior to enrollment	Same
Treatment strategy	Treatment group: Oral Jianpi Bushen Jiedu herbal medicine initiated within 30 days after T0, using syndrome-specific core prescriptions with individualized modifications, duration ≥ 3 months	Observed duration-based comparison. The therapeutic principle was standardized, whereas prescriptions were individualized by syndrome. Because duration was determined after T0, this comparison may be affected by immortal time bias and is interpreted as associational
	Control group: The same therapeutic principle and individualized prescribing process, duration < 3 months. Prescription changes and self-reported use were reviewed at follow-up; a validated adherence metric was not available for all patients
Assignment procedure	Randomly assigned to one treatment strategy at baseline	Observed initiation within 30 days after T0; subsequent duration was not assigned at baseline
Treatment initiation	Randomization time	From T0 to within 30 days after T0
Blinding	Open-label	Non-blinded
Time zero	Time of intervention assignment (randomization)	Date of first oral Jianpi Bushen Jiedu prescription; duration-based classification after T0 may still introduce immortal time bias
Follow-up	From baseline until death	From T0 until death
Primary outcome	OS	Same
Causal contrast	Per-protocol effect	Adjusted associational contrast; not a definitive causal effect because treatment duration was observed during follow-up
Statistical analysis plan	Per-protocol analysis	IPW-adjusted observational analysis of measured baseline confounders; landmark and time-varying exposure analyses are needed for a complete assessment

TNM: Tumor-node-metastasis; TCM: Traditional Chinese medicine; IPW: Inverse probability weighting; OS: Overall survival.