Table 3 Observations sent to sponsors from PBSL’s review of CTA and amendments

General requirements

▪ Trial not registered with a PBSL approved clinical trial registry

• No or incomplete DSMB charter, including membership, the charter of work, study review criteria/stopping rules, curriculum vitae, and conflict of interest details

• Completed PBSL CTA application form not available

• Pharmacy manual not provided

• No contractual agreement between the sponsor and principal investigator

• No local principal investigator was recruited

Clinical protocol

• No specification for assessment of efficacy and safety

• No criteria for participant selection

• Unclear study endpoints

• Studies containing no local sub-investigators and study pharmacists

• Favourable opinion from the SLESRC not available

• A description of the design of the trial to be conducted was not provided

• A description and justification of the trial treatment and the dosage and dosage regimen of the investigational product were not provided

• A detailed description of the “stopping rules” or “discontinuation criteria” is unavailable.

• Valid insurance certificate for the study duration that must be provided before study initiation is not available.

• The informed consent information sheet does not have details of the Chairman of the Sierra Leone Ethics and Scientific Review Committee for participants to contact if they have ethical issues.

• Procedures for monitoring subject compliance not provided

• The sponsor intends to conduct a phase 2 clinical trial, but the phase 1 trial report was not available

• No details of causality assessment parameters and serious adverse events/reaction toxicity grading such as those for haematology and biochemistry

• No evidence of GCP training for the principal investigator and other key staff

• No details of IP data handling and recording keeping

Quality review

• Process validation protocol and report were not available

• Evidence of Good Manufacturing Practice compliance for the manufacturing site(s) of IP and excipients not available

• Analytical Procedures and batch analyses for IP and excipients not provided

• No analysis report of reference standards, including test methods, acceptance criteria, and results

• Post-approval stability protocol and stability commitment for ongoing stability studies of IP not provided

• Sample of labels not available

• The product dossier for the placebo was not provided

• The parameters, test methods, specifications or acceptance criteria and results for the pre-master virus seed are not available

• Genotypic and phenotypic characterisation of the master virus seed was not available

• No read-outs or tracings for characterisation of impurities

• No tracings or read-outs for analytical method validation

Biostatistics review

• Criteria for the termination of the trial are not available

• Timing of any planned interim analysis though, was planned not provided

• Incomplete statistical analysis plan submitted before data lock, with no authors’ name and signature, version number and date, and no inclusion and exclusion criteria

Nonclinical review

• Investigator’s brochure not provided

• No developmental and reproductive toxicity data to support use in pregnancy