INTRODUCTION:
The global clinical research landscape is governed by various international and national frameworks, but many lack guidance on core principles of randomised clinical trials (RCTs). The Good Clinical Trials Collaborative (GCTC) was established to develop guidance that promotes the scientific and ethical value of RCTs across diverse settings. We report on awareness, perceptions, and practices regarding the GCTC Guidance among key clinical trial stakeholders in South Africa, focusing on local adoption.

METHODS:
A convergent parallel mixed-methods design was employed with qualitative and quantitative data collected concurrently, analysed separately, and integrated during interpretation. Data came from participatory workshops (n=9), surveys (n=242), and key informant interviews (n=22) with relevant stakeholders. Quantitative data were analysed with descriptive statistics, and qualitative data were thematically analysed.

RESULTS:
Awareness of the GCTC Guidance among South African clinical trial stakeholders was limited, but participants reported strong alignment with existing South African clinical research and Good Clinical Practice (GCP) frameworks. The Guidance was applicable across organisations and aimed to improve the scientific rigour and ethical conduct of RCTs. Adoption was viewed as feasible but likely to face barriers, including resistance and resource constraints. Participants emphasised the need for coordinated, multisectoral implementation led by the National Department of Health, involving regulators, funders, academics, ethics committees, industry, and community stakeholders.

CONCLUSIONS:
Despite limited prior awareness, the GCTC Guidance was perceived as compatible with South African regulatory and research practices. Its adoption was deemed feasible if integrated into established clinical research guidelines, potentially improving the quality and ethical conduct of RCTs in South Africa.