Table 4 Observations resulting in ERC requests for clarification or amendment of protocols and associated documents

Beneficence

Benefit, risk to study participants

• Inconsistencies in participant selection criteria and measures to minimize risk for study participants (duration/type of contraceptives, frequency of follow-up, type of follow up examinations, Data Safety Monitoring Board functioning) between studies examining the same intervention in the same phase of development.

• Different standards in the assessment of AEs and SAEs among trials testing the same vaccine.

• Unjustified collection of samples.

Risks to study team or EVD response

• Sub-optimal measures to reduce risk associated with handling of blood samples.

• Suboptimal measures to protect Ebola Treatment Units from effect of information about the study and/or the investigational compound.

Study design - comparator

• Insufficient information on measures to minimize bias in the use of historical controls

Study design - outcome measures

• Inconsistencies in parameters used to characterize intervention risks

• Poor differentiation between deaths due to potential toxicity vs. deaths due to lack of efficacy

Safety data from prior studies and dose justification

• Lack of information on safety data from previous studies

• Lack of documentation on assessment, or insufficient clarity of assessment of safety data by Data Safety Monitoring Board

• Lack of documentation of approval of dose by Data Safety Monitoring Board

• Insufficient dose justification

Justice

Equitable access

• Lack of justification for exclusion of children and pregnant women

• Lack of criteria for trial participant selection when experimental intervention was available in limited quantity

Impact of studies on routine patient care

• Lack of information on how the study could be conducted in the Ebola Treatment Centres without reducing staff capacity to provide best ‘standard-of-care’ to those not participating in the trial

Sample and data sharing

• Lack of information on rules and procedures for sample ownership

• Lack of information on how results would be shared with participants and their communities

Future use of remaining samples

• Lack of information on ownership, storage, and disposal of samples.

• Lack of information on procedures to determine future use of left-over samples

• Lack of information in the Information Documents on future use and shipment of samples.

Collaborative partnership

• Lack of information on the role of country researchers and health system in study design, planning and implementation

Accountability

• Lack of information on roles and responsibilities of different investigators

Respect for persons

Information documents

• Information documents provided in technical language with scientific and legal jargon

• Inconsistencies between protocol and information document

Plans for obtaining informed consent

• Study implementation plans with insufficient time planned between informing participants and consent/start of protocol planned procedures

• Lack of clarity of criteria to determine potential participants’ ability to provide consent.

Confidentiality

• Lack of sufficient information on how potential participants other than those in treatment centres or identified during contract tracing were to be approached, and on measures to keep their participation confidential