A multicentre randomised controlled trial evaluating whether a rare-disease diagnostic large language model can improve diagnostic quality, efficiency, and health-economic outcomes for physicians managing patients with suspected rare or diagnostically unresolved disease.
Rare disease patients commonly experience prolonged diagnostic odysseys rooted in limited rare disease recognition, phenotypic heterogeneity, and dispersed diagnostic clues. Diagnostic decision-support large language models may improve first-visit consultations by integrating prior records, generating structured analyses, and proposing candidate diagnoses, thereby shortening diagnostic pathways and improving appropriate genetic testing referral. Participating physicians will provide care under both AI-assisted and standard diagnostic workflows. Eligible patients will be individually randomised to receive either AI-assisted diagnostic support or standard clinical practice. In the intervention arm, physicians will have diagnostic support from AI when seeing patients. In the control arm, patients are seen under standard hospital workflow without any generative AI tools. Outcomes adjudicated by an independent Expert Committee blinded to arm assignment; adjudicators access no AI-generated materials. A prospective within-trial economic evaluation will be conducted alongside the randomized trial. Healthcare resource use and costs associated with the diagnostic pathway will be collected.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
SINGLE
Enrollment
1,056
The study AI system will be used to provide diagnostic support during the clinical encounter, including structuring relevant clinical information, generating a clinical analysis, and suggesting candidate diagnoses for review by the treating physician.
Peking Union Medical College Hospital
Beijing, China
Cangzhou Central Hospital
Cangzhou, China
Changchun Sacred Heart Hospital
Changchun, China
Overall Correct Diagnostic Yield
The proportion of all randomised patients whose clinical diagnosis by the end of follow-up is concordant with the blinded-adjudicated final reference diagnosis determined by an independent committee.
Time frame: From the first visit to final reference diagnosis adjudication, an average of 8 weeks.
Candidate Diagnostic Accuracy
The agreement between physician-provided candidate diagnoses in the the initial consultation and the independently adjudicated reference diagnosis.
Time frame: From the first visit to final reference diagnosis adjudication, an average of 8 weeks.
Molecular Diagnostic Yield
The proportion of all randomized patients in whom genetic testing performed as part of the clinical diagnostic pathway identifies a clinically relevant molecular finding that is confirmed through independent genetics review.
Time frame: From the first visit to final reference diagnosis adjudication, an average of 8 weeks.
Time to a Correct Diagnosis
The number of days from the first study visit to the first physician-assigned diagnosis that is subsequently confirmed as concordant with the independently adjudicated reference diagnosis.
Time frame: From enrollment to the end of follow-up, up to 8 weeks.
Appropriate Genetic Testing Recommendation Rate
The proportion of randomized patients for whom physician-recommended genetic testing is concordant with the indication determined by an independent genetics adjudication committee.
Time frame: From the initial consultation to genetic testing indication adjudication, approximately 8 weeks
Duration of the Initial Physician Consultation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Dongguan People's Hospital
Dongguan, China
First People's Hospital of Foshan
Foshan, China
Guizhou Provincial People's Hospital
Guiyang, China
Jilin Central General Hospital
Jilin City, China
The First People's Hospital of Yunnan Province
Kunming, China
Tianjin Children's Hospital
Tianjin, China
Tianshui 407 Hospital
Tianshui, China
...and 3 more locations
In-room consultation time will be recorded, measured, and compared between arms.
Time frame: Assessed at each consultation (day 1), within 1 day.
Physician-Reported Experience
Physicians will assess their experience of the diagnostic workflow. Responses will be recorded using a standardized rating scale (range 1-5, where higher scores indicate more positive experience).
Time frame: Assessed at each consultation (day 1), within 1 day.
Patient-Reported Experience
Patients will assess their experience of the diagnostic workflow. Responses will be recorded using a standardized rating scale (range 1-5, where higher scores indicate more positive experience).
Time frame: Assessed at each consultation (day 1), within 1 day.