The Feasibility and Preliminary Effectiveness of a Large Language Model-Driven Chatbot in Addressing Reproductive Concerns Among Adolescent and Young Adult Cancer Survivors: A Pilot Randomized Controlled Trial

Methods/Design This is single-blind, two-arm randomized controlled trial. The study will adhere to the CONSORT 2010 checklist for pilot and feasibility trials. The subjects are people aged from 15 to 39 years with cancer diagnosis and self-reported reproductive concerns.

Participants, recruitment, and randomization Simple random sampling with a fixed sample size will be employed to recruit subjects. Inclusion criteria are as follows: (1) 15-39-year-old females; (2) cancer diagnosis between ages 15-39; (3) current or prior concerns regarding fertility; (4) proficiency in Mandarin Chinese; and (5) access to a mobile device for intervention delivery. Exclusion criteria include: (1) involvement in the chatbot co-design phases; (2) inability to provide informed consent; (3) significant sensory, cognitive, or psychological impairments precluding meaningful participation; and (4) acute illness at the time of recruitment. Each interested participant will be screened by a trained research assistant to confirm their eligibility and safety to participate in this study. All participants should voluntarily agree to take part and will be asked to provide informed consent with signatures after being informed of the study purposes, procedures, risks, and benefits. For participants under 18 years old, informed consent will be obtained from their parents or legal guardian, and assent will be sought from the minor participants themselves, ensuring they understand the study's purpose and procedures. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental or the control group. Randomization will be automatically performed using a computer-generated randomization sequence embedded in the chatbot backend. The allocation sequence will be concealed from the research assistant involved in subject recruitment.

Intervention group Participants assigned to the intervention group will receive daily prompts to engage with chatbot over a four-week period. The chatbot was developed by a multidisciplinary research team which consists of domain experts in engineering, oncology, reproductive health, and psychology. To mitigate LLM hallucinations for accuracy, we incorporated a knowledge base for model retrieval, including multi-turn ACT dialogues adapted from ACT tutorials, onco-fertility/gynecology/oncology question-answer pair dataset, the list of medical institutions approved to conduct human assisted reproductive technologies (ART) and relevant policies. During the subsequent follow-up phase (weeks 4-8), participants will be encouraged to interact with the chatbot as often as they wish.

Control group Participants assigned to the control group will receive an electronic brochure which contains ACT psychoeducational materials, verified medical question-answer pairs, and relevant policy information. Participants will be encouraged to review the brochure daily over a four-week period to reinforce understanding and engagement with the material. During the subsequent follow-up phase (weeks 4-8), participants will be encouraged to read the brochure as often as they wish.

Data collection Data will be collected at three time points: baseline (T0), immediately post-intervention at 4 weeks (T1), and follow-up at 8 weeks (T2). All outcome assessments will be administered through the study platform integrated into the chatbot backend system. Given the nature of the intervention, neither participants nor intervention providers can be blinded to group allocation. To minimize measurement bias, outcome assessments will be automatically delivered by the backend system at predefined study time points and completed by participants via self-report without researcher involvement. De-identified coded data will be used for analysis, and the data analysts will remain blinded to group allocation until database lock and data cleaning are completed.