The TMF is the official record of the clinical study for Regulatory Authorities, be it…
In clinical research, the process of finding and selecting sites is essential to the success of a study, as it leads to sites activated quickly, helps recruiting the target number of patients within the desired time frame, and prevents deviations from study protocol.
There are strong statistical indicators that there’s much room for a rigorous feasibility process to positively impact your clinical trial’s progress.
- 80% of clinical sites do not meet enrollment deadlines and targets
- Up to 50% of sites enroll only one patient or less
- 11% of sites recruit zero patients during a study (1)
To ensure a meaningful contribution to the successful outcome of a trial, selected sites must possess specific qualities. Top sites employ site personnel that are organized, understand how to implement the protocol and its specific procedures, and collect high quality data.
Having sites that enroll a large number of patients but make numerous mistakes or deviations from the protocol – that impede the analysis and interpretation of data – is no more productive than having sites that recruit few or no patients.
CROs must ensure that sites specifically selected for a given trial have what it takes, above and beyond the required patient population, to perform a study. This will greatly facilitate a smooth and compliant study conduct and the recruitment process, making monitoring visits more efficient and productive, significantly contributing to meeting the trial’s timelines and objectives.
Let’s examine what must be considered for the study feasibility and site selection process to be effective.
What Are the Sponsor’s Needs?
The first step undertaken by a qualified CRO is to ensure that the Sponsor’s needs are correctly understood. To do so requires that the CRO: collect pertinent information on the study, the logistics, and involved players; understand the types of sites the Sponsor is looking for, as well as the Sponsor’s priorities and preferences. Some Sponsors prefer certain sites or geographic areas, and the desired criteria in terms of experience and qualification of the sites and Investigators. For example, it may be appropriate to consider sites led by key opinion leaders, since this provides access to expert advice during the development of the study protocol.
In all cases, and in-depth understanding of the local landscape where sites will be selected is critical to the early identification of possible challenges as well as opportunities associated with each study design.
Due to its database and experience with Canadian sites, Scimega clearly understands the qualifications of the different sites in Canada and corresponding average study start-up times, which allows for a list of potential sites to be compiled within a very short time frame.
What about Feasibility Questionnaires?
Once a site has expressed an interest in a study and a confidentiality agreement has been signed between the site and the Sponsor, the next logical step is to gather more detailed information for the Sponsor about the site. To do so requires an effective and thorough feasibility questionnaire that is yet not to daunting to complete by site personnel. This questionnaire is sent to each site and contains general questions about the patient population, site staff, ethics board, and studies the site and Investigator have conducted in the past.
Key at this stage is the collection of more precise data, confirmation the site will be able to verify eligibility criteria, and inquiry into the site’s equipment and logistics as well as the staff’s experience and availability. It is at this point that the site receives a summary of the protocol, at the very least. A required step as familiarity with the content of the protocol and list of procedures helps potential sites in evaluating their ability to perform the study and recruit patients.
Important here too is that the CRO undertakes to assess and clearly identify potential obstacles to the smooth conduct of the study, and that these are included as discussion points within the questionnaire. In the case of oncology studies, these may be specific medical procedures, a population of rare patients, and the duration of patient visits to the site, competing studies, or the local availability of specific material or drug comparator.
The site selection process should not be limited to screening questionnaire data. Once a confidentiality agreement is in place with potential sites, exchanges are encouraged between the study team (CRO and/or Sponsor) and key site personnel, such as the investigator, the main study coordinator and/or site manager, and any other key site personnel for the specific design of the trial. This early contact with potential sites will help establish a strong relationship early on in the project, validate key aspects of the screening questionnaire data, and prepare for foreseeable obstacles in setting the site up. Relying on a CRO with long-standing relationships with sites will go a long way in facilitating this critical pre-study activity.
Another reason for this level of rigor at this stage of the feasibility process is to help eliminate certain sites from the list of potential sites, which saves time and money, and will further contribute to the potential success of the study.
Is a Qualification Visit Necessary?
If answers to the feasibility questionnaire look promising a screening visit of the site should be conducted. During this visit, the protocol and study logistics are examined in detail to identify any potential obstacle and/or risk to the adequate conduct of the study. The site and installations are toured. Site procedures are also discussed, as well as the experience and availability of the staff to conduct a new study, the presence of any competing studies, and, of course, recruitment strategies and sources of potential patients. At this stage, the timeline for study start-up is discussed and a plan is created including a tentative date for the initiation visit.
Care must be taken when sites appear too good to be true: when a site sees no obstacles to the conduct of a study, asks no questions, and agrees with everything, it may be a sign that future problems will arise because the study was misunderstood. Sites that are well prepared and ask a lot of questions have seriously thought about the conduct of the study at their location. Responses that can only be gleaned through personal contact.
It is important that as much information as possible is collected during the screening visit in order to provide the Sponsor with an informed recommendation as to the selection of the site.
Top 5 Reasons Why Recruitment Objectives Are Not Met
Once sites are active, there may be many reasons why recruitment objectives are not met.
From the point of view of study sites, the main obstacles are:
- Eligibility criteria that restrict the potential population. Usually, the difficulty in recruiting is caused by only one or 2 criteria.
- Complex protocol
- Competing studies
- Slow start-up and activation process
- Site personnel changes
It is important that these obstacles are identified as early as possible in the feasibility process to allow the CRO to select the right sites and help the Sponsor make informed decisions.
While it is a fact that the success of a clinical study is often measured in terms of the speed and efficiency of the recruitment process, the work performed prior to the selection of sites and start-up of these sites should be given its due diligence. If done right your CRO’s feasibility and site selection process can contribute significantly to your clinical trial success. A close collaboration between the Sponsor and the CRO makes this step effective and productive.
Contributed by: Maëva Roques, Clinical Trial Leader