Insights on the design and recommendations
infection
VIRUS, DISEASE, RECRUITMENT, INFECTION, DISEASES
The study was underpowered for the primary endpoint as 34.2% (13/38) of patients in the SOC arm had virological clearance at day 7, much higher than the expected 20% [Although a patient population with higher risk may have increased the potential to detect differences in outcome between the treatment groups, this was not an option. Even though only two patients required hospitalisation during the study, one had to be treated at home with supplemental oxygen because of a lack of hospital beds and social unrest [In retrospect, having fewer virological outcomes would have simplified trial management and analysis. However, although the RT-PCR-driven primary endpoint seemed appropriate at the time of design, it later became evident that while this was a sensitive indication of initial infection it was a poor indicator for clearance of replicating virus. For new diseases, validated endpoints are likely unavailable and there is a balance between anticipating the most relevant endpoints and maintaining trial feasibility. Similarly, disease severity was evaluated using the WHO Ordinal Scale for Clinical Improvement [Conducting a five-arm trial at a single site in a pandemic was ambitious. Additional trial sites would have supported recruitment and should be considered where infection incidence progresses in waves or is seasonal. In the early stages of the pandemic, a more compact three-arm study would have increased feasibility. An alternative approach is to adopt a platform trial approach where treatment options are tested, reviewed, and either progressed or replaced depending on the findings under a single protocol. These studies require considerable efforts to establish, an ongoing funding commitment, and usually involve multiple trial sites often across several countries [