As The Pendulum Swings, More Sponsors Initiate Site Identification And Feasibility
By Megan Liles, founder, Liles Clinical Trials
The clinical research industry is, if anything, predictable. Among other things, we are slow to adopt new ways of doing things, a little wary of using technology, and still heavily dependent on Excel-based trackers. And, we have a curious habit with in-sourcing and outsourcing. Early in my career, it was described to me as a pendulum swing where pharma/biotech outsources all activities to CROs and then slowly brings activities in-house before shifting again to an outsourcing model. I’ve seen the pendulum swing a few times now, but this time, as pharma/biotech once again moves more activities in-house, it seems different. This time, I believe we will settle on a middle ground with sponsors initiating site identification and feasibility before bringing a CRO on board, especially for complex therapeutic areas, and several months before the targeted first patient in date.
Site Identification And Feasibility Timelines Keep Ticking Upward
CROs used to anticipate three months of start-up, which included private sites as well as academic medical centers (AMCs) using a central IRB. Now, even with most AMCs using a central IRB, start-up timelines have stretched to six+ months as the study moves through local review committees, coverage analysis, and contract negotiations, which also translate to higher outsourcing costs.
In addition, it continues to be a very congested clinical trial space. There are over 21,000 interventional studies in the U.S. marked as “not yet recruiting” or “recruiting” on clinicaltrials.gov. Most are competing within a therapeutic area as well as for site resources, notably site staff. In the early development space where I focus, sponsors, who often collaborate with universities to develop an investigational product, are very aware that they need to build strong relationships with potential investigators outside of their primary collaborators. They smartly initiate engagement before and during protocol development because these investigators provide invaluable input into study design, differences in standard of care, necessary procedures, and data collection. Together, these factors combine for an overall increase in study start-up timelines at the site level.
Because of this, I have seen several companies, especially the small and emerging biotechs, initiate site identification and feasibility questionnaires, and in some cases complete remote site qualification visits, before they bring the CRO on board.
Can Short-Form Feasibility Questionnaires Save Time?
The short-form feasibility questionnaire, which focuses on access to the target participant population, competing trials, basic site infrastructure, and overall trial experience, seems to be the most popular way for sponsors to target in on key questions while also saving the site staff some time for completion. Ideally, this questionnaire would help determine if the investigator is interested, has access to the target population, and has access to any equipment or facilities specific to that clinical study. If so, the process would advance to a site qualification visit where additional details would be obtained about the site infrastructure, start-up processes, etc.
At a site-focused conference, I heard site representatives (academic, private, and site network) lament the feasibility questionnaire and how they must answer the same questions repeatedly, even from sponsors or CROs they are currently working with. Site staff, therefore, have begun to develop site profiles that highlights their research experience, available equipment and facilities, and information regarding their start-up process to address standard questions. While these are great resources and help answer the usual questions (e.g., What is your start-up process? Do you have access to a minus 70 degree C freezer?), these profiles can be several pages long and consist of several documents, so make sure you set some time aside to go through them.
Site Qualification Visits Are Worth The Effort
About 10 or so years ago, a large AMC implemented a new policy that limited organizations to one on-site site qualification visit (SQV) per year. The decision came after it had repeatedly hosted multiple SQVs from the same CROs. Then, during the COVID-19 pandemic, many sites conducted SQVs via phone, with some offering virtual tours or even using Zoom to show the CRA around its facility.
With feasibility questionnaires being increasingly detailed, I was surprised to hear a coordinator from a large AMC advocate for SQVs. She prefers remote visits, which I have also seen most sites request. Having this visit allowed her to think more deeply about the study — whether the site had the patient population, the complexity of the trial, procedure requirements, which departments needed to be engaged, etc. Even though this site had previously conducted a trial for the same sponsor, in the same therapeutic area, and with the same investigational product, the coordinator continued to use the remote SQV as a kickoff to the study.
I am a big advocate of doing what makes sense, regardless of previous sponsor or CRO experience with the site, which is typically what enables remote visits or even waived visits. Even with prominent AMCs, I have seen sponsors continue to perform remote SQVs with an on-site tour noted as an action item for the site initiation visit (SIV). Sponsors and CROs instead reserve on-site visits for less experienced sites and/or investigators or if the site did not have specific therapeutic area experience. So, despite the availability of site profiles and past site experience, the need for some type of SQV remains.
Making The Sponsor-Site-CRO Collaboration Work
Having worked on both the CRO and sponsor sides for the last several years, I have an appreciation for this. From a sponsor perspective, I have seen CROs take too long to initiate contact with a site after it was transitioned to them for follow-up which in some instances resulted in the site losing interest in participating. From the CRO perspective, I have seen some missing information that necessitated follow-up from the CRO team. Admittedly, while on the sponsor side, I have been guilty of doing as well. So, how do we make this collaboration work?
For sponsors taking on these activities, they should leverage tools and forms from previous trials to collect the information. Relevant information should be tracked in a central location (contact details, site start-up processes, documents required to initiate start-up, recruitment potential, etc.) and organized for transfer to the CRO. This may include the SQV report, feasibility questionnaires, site selection letter, and any site information, such as site SOPs, site questionnaires, handbooks, and investigator CVs.
When it is time to bring the CRO on board, sponsors should deliver a formal handover of each site to the CRO, preferably via teleconference. This allows the sponsor to talk through the documentation collected, review key points from the feasibility questionnaire and the remote SQV, and note any outstanding action items the CRO team needs to address. In turn, this allows the CRO project team to ask questions and determine the next steps for the site. At this step, any documents required by the site should be discussed, including the timeline of when these documents will be available. These range from manuals (laboratory, pharmacy, and/or imaging) to eligibility worksheets and requirements, data monitoring committee charters, and case report form completion guidelines.
As the pendulum of outsourcing continues to swing, overall, the timeline from site identified to site activated is only increasing. It is beneficial not only from a cost-saving perspective but also in developing site relationships for the sponsor to assume site identification and feasibility activities. It is equally important for the CRO project team to facilitate the transfer of knowledge from the sponsor so that overall timelines are not impacted. Working together as a team allows for site start-up activities to seamlessly transfer from sponsor to CRO.
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