Monitoring and Management of Clinical Trials
The purpose of monitoring a trial is to ensure that the trial data is accurate, complete and verifiable from the source documents. The monitor also has a responsibility to ensure that the rights and wellbeing of subjects are protected and that the conduct of the trial is according to the trial protocol, GCP, the various regulations and any local requirements (e.g. documents relating to organisational management approval).
Commercial Trials
The sponsor for the clinical trial has a role in the monitoring of the trial at an organisational level.
Some responsibilities include:
- provision of an annual progress report
- notifications of any amendments to the trial protocol
- notification of any SAEs or SUSARs
- notification on completion of the trial
Investigator/Researcher
If the trial is commercial in nature then a Clinical Research Associate (CRA) or a monitor will visit the site prior to the study starting to ‘initiate the study’ and ensure that all relevant documentation is in place. At this first visit the monitor will ensure that all staff who will be involved in the study are aware of their responsibilities. The monitor will then revisit the site at regular intervals to monitor various aspects of the trial. They will meet with the researcher, scrutinise patient case notes and generally ensure that all relevant details are being recorded as specified within the trial protocol.
They will check that:
- the data is complete, accurate and verifiable from source documents
- there is adherence to the protocol and GCP
- informed consent has been obtained prior to entry to the trial
- only eligible subjects have been included as part of the study
- any adverse events have been recorded and investigated
- that recruitment rates for the trial are as expected
- all documentation is present as appropriate
- the drugs are being stored, used and handled in accordance with the trial protocol
- ‘file notes’ are being produced and filed accordingly
- all regulatory documentation has been processed
- all medication can be accounted for (via dispensing logs, any medication returned by a patients correlates with the amount dispensed vs the amount consumed)
Should the recruitment rate be less than expected then the eligibility criteria may be reviewed to ensure that the researcher is in fact including all who are eligible into the study.
Even if the recruitment rate appears 'normal' the eligibility criteria for each patient should be checked because it may be that ineligible subjects are being included in the trial. If this is the case then this should be brought to the attention of the researcher.
Consent forms should be signed and dated personally by each individual patient and dates of trial related events should be double checked to ensure that no trial events occurred prior to the patient consenting to take part in the study.
The randomisation procedures and documentation should be scrutinised to ensure that randomisation occurred prior to other trial activities.
Documentation for each patient should be scrutinised to ensure that any evidence of adverse events are being captured and reported. One should note at this stage that only those named in the research protocol or the ‘responsibilities log’, should be prescribing and dealing with patients involved in the study. Amendment papers from ethics committees may include additional names as the trial progresses and local documentation need to be updated to reflects this.
Where new researchers are included their CV (indicating their experience, training (e.g. GCP) and qualifications to facilitate the study) also needs to be held as part of the study documentation. The monitor will check the signatures on the prescriptions and also on any laboratory reports as they also need to have been signed by a member of staff authorised to do so.
Accountability of clinical trial supplies is a key task of the monitor. All products received and all products supplied need to be documented and accounted for.
Samples for analysis by e.g. for biochemical analysis need to have been obtained properly, with consent and need to have been labelled and stored according to the protocol. Delivery and collection of 'samples' also needs to be recorded.
If equipment is used within the study then the monitor should be aware of the service requirements and history of the equipment involved.
If a subject withdraws from the trial this needs to be recorded and reported with the reasons (if possible)for the withdrawl from the study stated. The reason may be due to the efficacy of the drug or due to an adverse event and this should be clearly documented.
The monitor will check the investigator’s file to ensure that all correspondence and documentation is being filed accordingly. This will include any electronic information sent or received as part of the trial. Subject identification logs will be reviewed to ensure that as subjects enter the study their details are being recorded.
In commercially run studies, responsibility for continuation of supplies rests with the monitor or supplies may be handled by automated services. Supplies of all items required for the trial should be checked by the monitor as part of their routine visit.
More often for non-commercial trials the pharmacy department are responsible for ensuring that there are sufficient supplies.
The monitoring log for the trial will also be updated by the monitor and the monitor will work with the Trial Management Group (TMG) which generally consists of those individuals responsible for the day-to-day management of the trial, such as:
- the chief investigator
- a statistician (if applicable)
- the clinical trial co-ordinator
- the research nurse
- the data manager (if appropriate)
The TMG group should keep a close eye on all aspects of the conduct and progress of the trial and ensure that the protocol is adhered to and take speedy action as necessary to safeguard participants and the trial itself.
As a trial increases in size and complexity more formal structures become appropriate.
In single-centre trials oversight may be provided through the research governance arrangements made by a health board or university, in larger trials a formal Trial Steering Committee is recommended.
Non Commercial (Academic) Trials
Where the clinical trial is non - commercial in nature, monitoring is the responsibility of the sponsor organisation. Generally the extent and nature of monitoring should depend on the complexity of the trial.
Please check with your local R and D Department for the local arrangements.
Pharmacy
At a pharmacy level the trial should be monitored and the results recorded on a regular basis to ensure:
- suitability of the environmental conditions (temperature, cleanliness of area)
- suitability of the product (expiry dates, potential degradation of the presentation)