Successful selection of a study site can provide significant benefits to sponsors, CROs, the sites themselves and, of course, patients. But choosing the right site partner is far from simple: It must be suited to the needs of sponsors and CROs, aligning these with their own capabilities and goals. The best fit for some might be choosing large multinational site networks, while others might opt for a smaller trial site.
Regardless of scale, sites come with their own sets of advantages and disadvantages. In this post we explore what successful site selection looks like and how size is not always the most significant criterion by which to judge a site.
Large organizations will likely have more personnel dedicated to specific tasks when compared with smaller sites. There will be staff dealing exclusively with clinical matters, data management, legal and administrative tasks or business development. At smaller sites, you may find fewer people taking on more and varied responsibilities, explains Elizabeth Weeks-Rowe at Pharmatimes.
The conclusion to draw is that when clinical trials demand highly trained and specifically focused staff, larger sites may well be the best option.
There are four key factors to guide site selection: predicted enrollment rates, predicted/planned site capacity, site attributes and past performances, and previous professional relationships between sponsors/CRO and site.
However, using a criteria approach will not necessarily help to lead sponsors or CROs to make the right choice, write Dr. Vadim Paluy and Vladimir Shnaydman, Ph.D., of Novartis and ORBee Consulting, respectively.
A criteria-based focus, the pair argues, may miss nuanced information. For instance, choosing a site based on predicted enrollment rates won’t factor in cost per patient, site size or the facility's past experience.
Most prudent would be for sponsors to assign a site to one of three tiers. Tier one refers to reliable sites with high enrollment; tier two is less expensive than tier one but provides a promising option; tier three is the cheapest but often beset with the most problems.
Rather simplistically, tier one is the most attractive; however, tier one sites also tend to have limited capacity, fierce competition among sponsors and CROs to secure the site and a hefty price tag.
While opting for tier two or three sites could be easier, it won’t necessarily result in a successful trial. It’s important that those responsible for site selection monitor whether sites move between tiers and update their records accordingly.
Larger facilities will have more capabilities to offer sponsors. These might include laboratory and radiology services, sample tissue processing machines, more personnel power and even improved storage options, explains Soon Wen Xian, a clinical research associate based in Malaysia.
But Xian is quick to note that while some presumably smaller facilities may lack these capabilities, they do have the option to outsource some of the services. What is key, in both contexts, is choosing a site team that is experienced, led by a principal investigator with a proven track record.
Clinical trials have a long history of recruitment challenges. But site selection can also be a battle for many sponsors and CROs. As many as 70 percent of trials suffer delays, says Anais Silva, communications coordinator at Technical Resources International.
Selecting the most appropriate site to suit a trial’s needs will help to overcome these challenges. Key considerations include aligning a site’s capabilities with the study protocol, the sponsor’s strategies, regulatory constraints and study timelines.
While nearly one-third of sponsors have used the same site more than once because of reduced startup times, in-use contract templates and familiarity with the team and its processes, Silva argues that this is not always the best approach. Past performance won’t guarantee the same results in a different trial. She advises instead using tools to pre-select sites based on key metrics such as size, location and specialty. A further step is to analyze previous site performance for any similarities with the planned trial.
Current site selection strategies need improvement. Often paper-based and tech-shy, sponsors rely on information from sites that cannot always be verified, site consultant Kate O’Brien explains. Sponsors should seek information before the site visit to better understand the site’s capabilities and assess whether they could form positive relationships with the trial staff.
Following the simple but effective ‘Rule of Ps’ will help sponsors make the right site selection. Does a site focus on profit? Of course, they will and should, but not without the other three Ps: patients, protocol and performance. These three are the starting point to evaluate the site team. And, as O’Brien says, if sites take care of patients, protocol and performance, profits will follow.
Site networks offer greater stability to sponsors looking for site partners than individual sites can. Consider that many trials span years and multiple countries. Site networks are more robust, enduring and having larger financial resources available. Stability was just one of the reasons site networks were favored by research network customers polled by Bioclinica.
Another advantage is simplicity — particularly when a trial requires multiple sites — as sponsors need only one partner to manage all of the sites. Bioclinica’s clients also cited cost savings, greater efficiency, standardized processes and reliable experts as key reasons for choosing site networks.
But scale is important too. A trial might investigate a disease in multiple countries or track seasonal illnesses. Having a network that can scale up in a hurry can be an enormous advantage for sponsors.
Patient enrollment is a tough number to predict. But failure to get it right or close to right can have major cost impacts. Part of this expense is because sponsors sometimes have to enlist new and additional sites from what was originally planned to meet enrollment targets, explains David Fogel, chief scientist at Trials.ai.
Fogel gives the example of a trial studying how effective coronary bypass surgery was in patients with heart failure. The trial was initially planned to study patients in the US and Canada across 32 study sites. But after poor enrollment, the scope of the trial was enlarged to 26 countries and 171 study sites.
Even with the expansion, 44 approved sites failed to meet enrollment targets. Fogel says the cost for each deactivated site was around $10,000, and notes the added burden of diverting study funds to recruit more patients at a later point in the trial and amend the protocol.
He advises sponsors to select a site that has six to ten studies completed — as they will be more likely to meet enrollment rates — and that have a proven record of fast recruitment of the first patient.
Clinical trial liaisons can provide value to sponsors because of their education and current knowledge of the market. These attributes, according to clinical trial liaison Russell Brown, Ph.D., help investigators and sites understand the full scope, ambition and requirements of the treatment development.
Liaisons can also help select the best site for the trial’s needs and establish relationships between sponsors and site staff. It’s best, Brown explains, to include the liaison at the beginning of the trial planning so they can meet the site team during site initiation to understand the trial’s objectives. Doing so will improve the site’s attempts to recruit patients.
While sponsors and CROs should demand a lot from their potential site partners, asking probing questions and testing capabilities, sites should also make demands of their prospective collaborators. This is why Kristina Lopienski at Forte Research advises that sites conduct a reverse feasibility questionnaire.
Sites and sponsors should know what is expected so they can both make the right decision for their needs. Collaboratively, parties should discuss and set expectations, categorize the non-negotiables and share key information. Lopienski says that while it may seem unlikely that sponsors would agree to this, some are starting to see the value of a more candid and collaborative approach to site selection.
Sponsors should look for sites that celebrate collaborative cultures — regardless of their size — and enable and empower their staff to thrive. One way to tell that site managers are doing this is whether they are using gamification to motivate teams. This could include rewarding teams and sub-teams for reaching milestones, explains Jim Lane, chief business officer at Longboat Clinical.
Engaged site teams lead to better patient engagement, Lane argues, but adds that sponsors also have a duty to motivate and empower entire study teams. Lane says that sponsors that can enhance startup performance, speed up operations and recruiting, and manage multiple personnel proposal will see site teams also perform better.
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