| Inclusion/exclusion criteria |
Enrollment failure due to eligibility threshold for randomization after delivery (CD4 ≥ 350 cells/mm3) Laboratory results (i.e., HIV test results) crucial for eligibility criteria not available on time |
Allow more flexibility around critical study timepoints Encourage and facilitate early site involvement in protocol development Streamline procedures to avoid errors and reduce complexity Introduce mobile visits to patients’ homes Use storefront laboratories in lieu of visits to the investigative sites Allow rapid tests Use expectations of normal values for the population of interest Encourage and facilitate close collaboration between clinics and laboratories |
Operational challenges
(Note that operations for the PROMISE study were handled centrally however the team faced multiple issues during the conduct of the trial)
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Long and complex Case Report Forms that take time to hand-write, enter in the database, store Budget challenges (the study was originally budgeted for lower than what costs ended up being) Due to the complexity of the protocol it took sites time to learn how to implement PROMISE Enrollment caps were included in the informed consent which meant enrollment had to stop at cap
(Note that changes in informed consent require IRB approval which delays implementing changes or re-opening to enrolment)
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Streamline forms and procedures to avoid errors and reduce complexity Encourage and facilitate early site involvement in protocol development Expand the level of site engagement Better knowledge of the area and the people’s habits Incorporate walk-throughs and real-world examples/scenarios during investigators’ training Encourage and facilitate cross-site collaboration, with routine study coordinators calls and routine site meetings during the network meetings Write flexible informed consent
Note that in addition to the specific recommendations above, it is also important to establish and monitor minimal requirements for sites to be able to conduct a clinical trial, including appropriate site capacity; clinical, laboratory, and pharmacy capabilities, standard operating procedures, and quality management; staff training and documentation; data and specimen management capabilities, procedures, and timelines; ethics committee and regulatory agency approvals, etc. |
| Unforeseeable obstacles |
Challenge in recruiting formula-feeding mothers and late presenters |
Assess factors that could impact enrollment during study design Begin site selection during protocol development to facilitate discussions around feasibility Review of accrual projections during site selection process to help assess overall study feasibility Consider conducting periodic feasibility assessments by phone Provide 24/7 hotline for sites Provide greater amount of information for the more difficult to reach populations during researchers’ education Include scenarios for changes in feeding methods in sample size assessments Use conservative assumptions for sample size calculations Consider using a central IRB for protocol amendments |
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Changes in WHO guidelines and recommendations |
Encourage and facilitate close collaborations with other key stakeholders, including WHO and MOH guidelines groups, such that study teams are prepared or ahead of such changes in guidelines Convene an Independent Ethics panel and coordinate outreach to Ministries of Health regarding the ethics and importance of study continuation following guideline changes during the conduct of a study Incorporate “what-if” scenarios during the trial design Provide 24/7 hotline for sites |
