Monitoring and Safety
Sponsors and investigators have a joint responsibility for patient safety during and after the trial.
Sponsors fund and oversee the research. They are responsible for compiling safety data from all investigators.
Investigators (doctors and nurses) design and implement the trial in a clinical setting. They are responsible for ensuring the protocol is followed, and that all adverse events are recorded and reported.
When sponsors and/or investigators are not impartial, monitoring and safety are impacted. Patient care may be compromised by over-promotion, and biased selection of the therapy.
The sponsor must fully document the safety record of the treatment under investigation, and all potential drug interactions. This allows clinicians to generate risk-benefit profiles for their patients before proposing enrolment.
The sponsor must ensure informed consent documents use plain language and accurately describe the potential risks and benefits to participants. They must also ensure the document is accessible in other specified languages or formats.
The sponsor monitors results as they are accumulated. They may outsource this to a Data Management Committee or Data Monitoring and Safety Committee. This independent group of clinicians and statisticians regularly reviews data received to date. The committee can recommend the study be stopped if they feel it is causing undue harm.
The sponsor must collect adverse event reports from investigators, and share them with other investigators and appropriate regulatory bodies. An adverse event is any side effect or negative change in health of a patient. For each adverse event, the sponsor records a judgement of whether it is related to treatment or not. This requirement is vulnerable to sponsor bias.
A clinician’s first duty is to the patient. If an investigator believes treatment under review may be harming participants, or they can no longer be objective, they are free to stop participating. Unfortunately, clinical investigators often have a vested interest in the outcome. When this happens, they may continue to treat patients inappropriately to remain involved in the trial.
Investigators are responsible for following the detailed clinical trial protocol. They must supervise all clinical staff and research assistants involved at their treatment centre, to ensure collection of valid data.
Investigators and their clinical and research staff must ensure all potential participants (or their parents) understand the potential risks and benefits of being enrolled in the study. They must ensure all participants have adequate information to give fully informed consent.
Investigators must record all adverse events, and report them to the sponsor and the Institutional Review Board, Data Monitoring and Safety Committee or Research Ethics Board. For each adverse event, they must record an independent judgement on whether it is related to treatment. This requirement is vulnerable to investigator bias.
In multicentre studies, the investigators must also review adverse event reports from other sites, sent to them by the sponsor. These reports contain opinion from both the sponsor and the local investigator about the relationship between adverse event and treatment.
Sponsor / Investigator Bias
Investigators must be transparent. However, when an investigator is also the sponsor, or faculty of the sponsor, the trial may not incorporate formal adverse event reports. This is especially the case with single centre studies.
Adverse events may be under-reported and unfavourable results suppressed when sponsors and/or investigators are not impartial. This leads to over-promotion of the treatment in scientific literature, and failure to protect the patient’s complete wellbeing when selecting treatment.