In Part 2 of our study start-up series, ICE Global Consulting’s Head of Site Readiness, Maria P. Ladd, explores how factors across the various study teams can lead to site activation delays.
How Does it Happen?
With a heavy Site focus, some of the more common ways in which Site start-up delays can occur were explored in Part 1 of this series, “Factors for Delays.” While all of the previously noted factors for Site activation delays have concrete foundations, it’s worth stating that resourcing is a factor for all – Sites, CROs and Sponsors.
Getting to the meat of the more varying factors, what really poses a challenge beyond resourcing is that the ‘how’ can be very specific to the study and the point in time during which the Sites are being activated. Applying the real-time study information, Site information, and circumstances to the known process hurdles is where the rubber meets the road on accurately mitigating Site activation challenges and proactively working on solutions.
Drilling Into the Details
Every entity involved in the clinical research process has their own distinct issues at hand; how often is are those made more complex by the simultaneous playing out of all teams experiencing individual challenges? Sponsors, CROs and Sites all have independent and overlapping hurdles which impact the ability to move quickly, sometimes avoidable and sometimes not. In the best-case scenarios of the teams working collaboratively, the challenges are more readily overcome; often, though, each doesn’t know or understand what is happening on the other side(s).
Outside of their own organizations, Sponsors don’t often get recognition for the vast network of complications that go into getting a compound or device through the maze that leads to a human-subject trial and the often-illusive approval. Timelines for the trials of the future can be laid long before the protocols are written, defining ‘delays’ before the study work can even begin. As Sponsors near the trial implementation, the work going into protocol finalization can narrow the ‘start’ timelines substantially; competent authority submissions may be delayed here, causing a downstream impact. If a timeline put in place well ahead of this work is already at risk at the point a protocol is being finalized, the pressure is quite high for the Sponsor, as well as any CRO/Service Provider hired to run the trial. Supply chains for ordering what is needed at the Sites, including the manufacture and provision of the IP, selecting vendors, selecting Sites, ramping all of these teams up – all hinge on those initial critical activities. Much of this is not visible to the newly onboarded CRO/Service Provider collaborators and tensions can run high in the fast-paced world of study start-up. In the rush to regain some lost time, looking for any way possible to speed up the process, collaborators may not understand why their cautions for the Sponsor’s desired timelines seem to go unactioned.
CROs are literally the middleman, squarely between the Sponsor and Sites. The services they bring are vitally important – not every pharma or device company has the bandwidth to maintain the many roles and skills that a CRO brings to clinical trials. There is a delicate balance between providing the best in customer service to the Sponsor and maintaining the Site relationship. Probably the trickiest of the issues is that CROs often have an Achille’s Heel existing within their best asset – specialized teams. Often, the teams within a CRO do not always know and understand what their other internal teams are doing, and when. In the stressful environment of study start-up, teams vying for the goal can lose sight that it is the same goal for everyone within their organization; the larger the trials, the larger the teams, and greater risk of the silo effect. The relationship at most peril here is the one with the Site. Sites are finely tuned into this issue when they are asked to duplicate work, end up explaining the same things to multiple people, and are contacted by multiple parties. This can make the work between a CRO and Site more challenging, creating an impression on the Site side that the CRO never intended to impart.
Sponsors and CROs projecting Site timelines go hand in hand with the territory of ramping up the required number of Sites needed in a clinical trial. Having all of the intel to effectively drive the Sites in the order in which they are able to progress is not an exact science and can be tricky to accomplish. Larger institution timelines have protracted processes for various committee approvals required for overall Site approval, finance, scientific, therapeutic, etc.
Getting the information for projecting Site activations involves concrete dates for submissions of various committees and the IRB, and all of the corresponding meeting dates. The process as a whole can involve multiple Site departments for contracting, clinical operations and the administrative document work, even at smaller Sites outside of academia or larger institutions.
Understanding what happens in parallel in the process flow, or what must be done sequentially, is a critical component to knowing where to start prioritization among several Sites. The list of deadlines, activities and actions per Site can be a page long, all with dates to get in the right order. Having the information and nailing down the timelines involves variables apart from the person answering the questions – these are ‘Site factors’ beyond the influence of the Sponsor/CRO facing Site staff. This is where highly accurate information is needed at each critical stage; Feasibility, the Site Qualification Visit and when a Site is ready to start the process. The information usually changes at each of these phases; it becomes a moving target – times the number of Sites on the trial. What is visible per Site is their own timeline – to the Sponsor and CRO/Service Provider, it applies to all of the Sites.
It’s a complex process from every perspective; these illustrations are not exhaustive of what each organization may be facing by way of obstacles. The point and takeaway is that all sides have issues, challenges, and hurdles to overcome. Recognizing the shared experience is the first step toward more cross-organizational communication and collaboration. Some of the resolution must come in the form of open communication, first – most people operate more energetically when the why and how are clear.
Not a One-Angle, One-Solution Problem
What we’re all doing in our own space is many times creating a community result of delays in Site activation – each entity playing an unintentional part. Silos across the broader study team, from each entity, exists whenever any of them are not working in tandem with the others. Working for individual companies brings an inherent risk of operating as if the only team members are the ones within that organization when, actually, each organization’s team is part of the larger study team. The work more often than not does not happen as one study team and there may be little symmetry among the teams. In an industry of islands, each wonders what is missing. We all look around and wonder why no ‘one’ has done anything about a problem that routinely repeats itself and the answer is staring us in the face – no ‘one’ can. In order to be the most effective, despite the invariable hurdles that will always exist, we need to do more within the industry to operate as a cohesive unit.