There were 15 STREAM trial sites from eight countries in Africa, Asia and Europe – all with very different local contexts. It was essential to the success of the trial to understand local variations and effectively adapt implementation in response.
One example was MDR-TB patient referral patterns. Only by building support for the trial at frontline health facilities where patients are diagnosed with MDR-TB can potential trial participants be referred to trial sites for trial enrolment.
When STREAM began in India, diagnosis and treatment of MDR-TB was centralized at centers that were shortlisted for the STREAM trial, but decentralization was expected to occur. To address this challenge, the trial Sponsor appointed a local expert with close connections to the national TB program (NTP) and deep knowledge of MDR-TB management in the country. This enabled the trial to understand the decentralization strategy of the NTP, to prepare trial sites for expected changes to referral patterns, and to conduct outreach to the frontline units that would ultimately refer participants to the trial. As a consequence, the India trial sites were able to meet their recruitment objectives, even after decentralization.
There were also significant variations in local regulatory environments, and deep local knowledge and relationships were crucial to navigating them. Regulatory requirements can be difficult to understand without access to local experts because clinical trial regulations are not always available publicly or easy to interpret, and practices of regulatory agencies may be unwritten. Gaps in local regulations can also exist, making it essential to work collaboratively with regulatory bodies to resolve questions during the course of a trial. In China, initiation of STREAM was ultimately abandoned when it became clear the country’s clinical trial regulations, which only recognized industry sponsors, were incompatible with an NGO sponsor like Vital Strategies. The trial’s absence of experienced local regulatory contacts contributed to a delay in reaching that conclusion. In contrast, in Mongolia, where STREAM was the country’s first international clinical trial of such scope and complexity, the study team’s strong relationship with the Ministry of Health and the national ethics committee enabled them to work collaboratively to address novel issues in the context of the trial.