Challenges
TB
Implementation research is pragmatic by definition and heavily influenced by changes in policy and environmental factors out of the study’s control. The protocol was written such that all medical decision-making, regimen use, and entry criteria were adaptable based on changes in country guidance to limit protocol amendments and satisfy concerns by ethics committees. Environmental factors were collected at the clinic level monthly so as to follow any changes in other projects or programming that could bias the outcome, including stockouts or TPT, culture bottles, or Xpert cartridges that could reduce TPT initiation and bacteriologic confirmation among index patients. In Ethiopia, all clinics were part of the IMPAACT4TB project, and drug delivery will be closely monitored by the parent study. In South Africa, drug stock will be monitored by the study itself and relies on the TB program for drug procurement. Finally, staff shortages including TB focal persons at the clinic and community health teams will be closely monitored. The study will not be able to control the replacement of clinic-based staff. This can influence outcomes and could explain poor performance among clinics/clusters.The COVID-19 pandemic presented numerous challenges to the coordination of this international study as a result of travel restrictions and work delays; the additional strain on the healthcare workers and healthcare systems in South Africa and Ethiopia also impacted the study implementation. The civil conflict in Ethiopia presents additional safety and logistical concerns.