While federal regulations monitor the conduct of clinical research, the practical application of these regulations varies depending upon the specific protocol and site. Every day clinical trial management involves screening and recruitment of subjects for enrolment and follow-up, communicating with the sponsor and IRB, collecting data, and preparing report forms for monitoring visits. This article gives an overview of the first step in conducting a clinical trial
Once the protocol, informed consent form, case report form and other essential documents are developed and are ready for implementation, the sponsor selects investigative sites for conducting a clinical trial. A Site Feasibility Study which also known as Site Qualification Study is carried out for selection of investigative sites. The purpose of the feasibility study is to evaluate the site’s ability to conduct the study according to ICH GCP and the protocol of the trial. The sponsor appoints a monitor or a clinical research associate through a CRO for carrying out the site feasibility study.
Selection of investigative sites
Sites with well qualified, trained, experienced investigators and well-trained support staff are first identified. The success of clinical trial is heavily influenced by the selection of research nurses, coordinators and other trained staff.
After selection of a particular site the protocol is given to the investigator of that site for review. However, prior to this the sponsor sends a confidentiality agreement to be signed by the investigator. This agreement legally binds the investigator to keep all information regarding study, investigational drug, protocol and investigational process confidential. Upon receipt of the signed confidentiality agreement, the sponsor sends investigator a copy of the protocol for evaluation. This provides an opportunity for the investigator of the site to ask questions related to the protocol before any commitment
Patient population
In addition to qualifications, sites are selected based on their enrolment projections. The number of sites selected is determined by the number of patients required, a need for broad geographic distribution, the length or duration of the trial and the sponsor’s monitoring resources.
The investigators of selected sites ensure whether the patient population is adequate to accrue the requested number of subjects. The investigator considers the specific eligibility criteria and the patient population to assess enrolment projections. Investigators also evaluate their ability to meet the enrolment projection. A realistic assessment of patient population has to be made. A review of patient medical records or a database with relevant patient information provides an estimate of recruitment potential.
Work space, lab & drug storage facilities & equipment
Along with the time that will be spent conducting a trial, the investigator has to consider the space that is required for personnel, equipment and supplies.
There are specific tests and procedures which require special equipment and/or access to diagnostic materials that may not be readily available to the investigative site. Storage spaces for supplies, diagnostic materials, equipments and cold storage chain for investigational drugs and vaccines can be an issue, especially in an already overcrowded office.
Laboratory testing is either done at clinical site or at an outside laboratory. When the study is large and involves hundreds of sites across the country, the sponsor signs a contract with a central laboratory to process all of the specimens. This ensures the same laboratory conditions for all of the specimens being tested.
Budgets and contracts
Budget of the trial is negotiated between the investigator and the sponsor after all logistic issues have been resolved and the investigator has decided to participate in the study. Compensation estimates are calculated by anticipating the workload required to conduct the study. The estimated amount of time and support staff a study requires will depend upon the intensity of the protocol, the schedule of procedures and tests, the disease state of the population being studied and the phase of testing. Some sponsors negotiate a budget with each site, while others simply make a take-it-or-leave-it offer. Most often, investigators are paid per subject they enrol.
The institution conducting the clinical research requires the sponsor to provide an indemnification agreement that promises to indemnify, defend, and hold harmless the institution and the IRB that approved the study against any claims or suits. Negligence and wrongful acts are excluded from this agreement.
Sponsors often hold centralized meetings with investigators and coordinators to review the protocol requirements, study plan, obligations, and timelines. This gives the site the chance to become fully educated about the study and ask questions, if necessary.
Role of CRA
The basic responsibility of a CRA/Monitor is to work as per predetermined Standard Operating Procedures (SOPs).
A CRA/Monitor checks for adequacy of staff, equipments, facilities (infrastructure) on investigative site before start of the study. The monitor visits investigator before, during and after the study to ensure adherence to the protocol, complete and accurate data collection and check for informed consent.
A CRA/Monitor also ensures training of investigator’s staff on protocol requirements, study procedures, recruitment rate of subjects. He/she checks storage and dispensing of study drugs. A discussion is done to explain the Investigator’s Brochure, briefing of protocol is done, recruitment rate is decided, adequacy of resources is checked, training of staff to handle drugs and samples is given, and informed consent procedure is discussed by the CRA/Monitor. The frequency of ethics committee meeting in the institutive site is taken in to account and it is ensured by the monitor that the protocol, informed consent, case report form and trial related essential documents are been approved before the study starts. The staff is trained by the CRA/Monitor how to fill in the case report form, adverse event form, reporting of adverse event in timely manner before the study starts.
-The author is Project Co-ordinator, IARC HPV Vaccine Trial,Department of Preventive Oncology, Tata Memorial Hospital, Parel, Mumbai.