Balancing Protocol Requirements with Patient Autonomy: A Case Study on Post-Randomization Refusal in an HIV related clinical trial

Background Randomization is central to ensuring the scientific validity of clinical trials. However, real-world complexities such as polypharmacy and individual treatment readiness may lead to post-randomization refusal. Post-randomization refusal presents several challenges to both the ethical integrity and methodological rigor trials. This case report explores a unique scenario in a randomized controlled trial where a participant initially refused their allocated arm due to concerns about pill burden but later agreed to proceed after supportive dialogue. Case presentation: This case report describes an instance where a participant initially refused intervention in a randomized controlled, open-label clinical trial involving a tuberculosis preventive treatment, in which patients were randomized to start the product as in-patient (immediate initiation) or outpatients (delayed initiation). Following the provision of written informed consent, the participant was randomized to the inpatient arm. However, he hesitated to start the intervention as per protocol, citing concerns about his already high pill burden. He requested to be re-randomized to the outpatient arm. The research team held a substantive dialogue with the participant, and together with the caretakers’ support, he ultimately agreed to continue in the assigned arm. The participant later encountered adherence challenges, which were successfully addressed through ongoing counseling support. Conclusion This case underscores the importance of responsive communication and participant-centered care in managing post-randomization uncertainty without compromising trial integrity. We reflect on the ethical, methodological, and design implications of managing participant preference in randomized controlled trials.