Early clinical development studies have become increasingly complex – and expensive – in recent years. While costs in every drug development stage experienced more than a 60 percent rise in between 2008 and 2013, recent estimates show that early-stage trials saw triple-digit growth in some areas. This is largely due to the greater inclusion of patients in Phase I trials, sometimes across multiple sites and geographies, which adds time, cost and risk to the process.
For many Phase I-IIa studies, the smaller patient numbers required mean that a commercial site or network of commercial sites can be used to recruit all, or a large proportion of the patients to the trial. A commercial site will typically be more expensive than a hospital/academic site, but will often be able to start up and recruit faster than a hospital/academic site.
As such, one of the most important decisions a biopharma company can make about these early phase trials is site selection. Often, prior experience with a site may play a heavy part in a sponsor’s decision to use them. Alternatively a study award may be based on a proposal document plus one or more follow on meetings. However, while a positive relationship or first impression is a good place to start, selecting a site primarily based on these factors can be a risky strategy and can also mean that the best site or sites are not identified.
Ideally the widest possible portfolio of sites should be scanned to identify those most likely to be suitable for the trial and once a smaller subset is selected, the following criteria should be considered when looking at sites:
- The medical safety judgment of the site’s medical team – how they will effectively and safely handle challenging and potentially life threatening situations that can arise in an early phase trial
- The physical infrastructure and training of site staff to conduct the study
- The ability of the site to recruit the volunteers or patients needed for the study. Where relevant this may include the ability they have to tap into local treating physicians and thought leaders
This can be easier said than done. A sponsor may not have the resources to vet a wider range of sites, or they may be looking to cut down on the management process of working with a new site. However, without taking these factors into consideration, it can create early delays or challenges that can impact the entire research program or even damage the reputation of the sponsor. Recent high profile incidents in Phase I trials have again highlighted the critical importance of an in-depth assessment of a site’s medical judgment, but this requires significant investment to do it right.
How good partners help
To minimize many of the risks associated with selecting the wrong site, sponsors can rely on their partnership with a CRO to assist them in site selection. At IQVIA, we follow three-phased vetting approach for early phase trial sites.
It begins with the relationships that we have built with a wide network of sites around the world. We gather data on their scientific, therapeutic, regulatory, site management, and project management experience and expertise, so we can understand where their strengths and weaknesses lie. These relationships have been developed over many years, and our past experience with these sites helps us quickly define a short list for potential projects. If we don’t feel that any of the sites in our network meet the criteria of the trial, we will look further, assessing new potential sites to incorporate into our network who are likely to fit these needs. As this activity is carried out to the benefit of multiple sponsors a greater level of investment is justified.
From there, we ask each site on the short list to complete a very detailed questionnaire about the site’s capabilities and experience. If the responses align with our needs, our early clinical development (ECD) team will conduct an on-site qualification visit. This team always includes a Phase I experienced physician, an ECD QA expert and an ECD operations expert. The detailed 1-2 day process carefully probes the site to understand how the site is managed; what training is conducted; the strategies they have in place for testing, data capture, and risk monitoring; and how they will deal with any safety issues or protocol changes that occur. This helps us both assess the capability of the site to take on specific trials and also importantly decide which types of studies we would not place there.
So, before selecting your next site, think beyond relationships alone to make critical early phase site decisions. Whether you engage us to help you choose the best sites for your needs, or conduct these assessments on your own, we want to ensure that you feel certain that a site has all of the expertise, patient access, training, infrastructure and experience to manage these trials on your behalf. Taking the time to make the right choices up front will set your research on the right path, and help create a culture of quality, efficiency and commitment to excellence for the entire research program.