Monitoring is defined by the International Conference on Harmonisation Good Clinical Practice (ICH GCP) section 1.38 as:
"The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded and reported in accordance with the protocol, Standard Operating Procedures, Good Clinical Practice and the applicable regulatory requirements".
The purpose of monitoring is to verify that:
1. The rights and well-being of human participants are protected
2. The reported trial data are accurate, complete and verifiable from source documents
3. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP and with the applicable regulatory requirements
Warwick CTU SOP 18 'Risk assessment and Monitoring' describes how to determine the extent and nature of monitoring appropriate for your trial. This should be discussed and documented prior to the start of the trial.
There are many different ways in which a trial may be monitored and the monitoring plan should be based on considerations such as the objective, purpose, design, complexity, blinding, size and endpoints of the trial. A risk assessment should be undertaken at the planning stage of the trial and this assists in determining the intensity and focus of monitoring required. Monitoring may include site visits to review the teams understanding of the protocol and check essential documents or source data, central data monitoring checks, calendar checks etc.
A Monitoring Plan template document is available which should be used to detail monitoring activities for each trial. The monitoring plan should be reviewed periodically by the Trial management Group to ensure adherence.
For most phase I –IV clinical trials some source data verification (SDV) is required. Source data is defined as all information in original records and certified copies of original records of clinical findings, observations or other activities in a clinical trial that are necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies) and can be said to be the first place where information is recorded/captured.
Source documents include: original documents, data, and records e.g. hospital records, clinical and office charts, laboratory notes, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, X-rays, subject files, and records kept at the pharmacy and at laboratories.
The source documents are one of the “Essential Documents” that permit evaluation of the study and the quality of the data and serve to demonstrate sponsor, investigator and monitor compliance with GCP and regulatory requirements. SDV is standard practice in early phase trials of new compounds, but later stage trials and those not used for drug licensing may not require SDV, but would be requested by the funding body if appropriate.
For the majority of randomised controlled trials, oversight arrangements are put in place:
1. All trials require a 'Trial Management Group' who will oversee the day-to-day running of the trial and usually consists of the Chief Investigator, Trial Coordinator, Statistician and other investigators/collaborators as appropriate. See Warwick CTU SOP 12 part 1: For those involved in the Day-to-Day Running of the Trial' for further details.
2. Large scale randomised controlled trials will also require a 'Trial Steering Committee' (TSC) to provide overall supervision of the trial and ensure it is being conducted in accordance with the principles of Good Clinical Practice (GCP) and the relevant regulatory requirements.
3. A 'Data Monitoring Committee' (DMC) should be considered for every trial. The DMC's primary responsibility is to safeguard the interests of the trial participants, assess the safety and efficacy of the trial interventions and to monitor the overall conduct of the trial.
For full details of the constitution and responsibilities of the oversight committees, please refer to Warwick CTU SOP 12 part 2 - 'Definition of Responsibilities; For Those Involved in the Oversight of the Trial'.
More information on the responsibilities, membership, purpose and timing of DMC meetings can be found in Warwick CTU SOP 13 - Operation of a Data Monitoring Committee'. A template DMC Charter is also available