Once the site and the sponsor have made contact about placing a trial, the process of study start-up begins. This term describes the span of time between the initial conversations and the recruitment of the first patients, and covers investigator identification, site feasibility, site selection, clinical trial agreement and budget negotiation, and site initiation.

A whole universe of vendors exists to smooth over the friction between sponsors and sites in this phase of the trial process, so this chapter will not make specific reference to the many, many organizations that provide relevant services here—but AICs should know that any specific problem they face in this process likely has a commercial solution or ten on offer to assist with it.

Evaluating the mutual fit between a site and a trial is a two-sided process. Site feasibility variously refers to the efforts a site makes to scope the trial’s requirements and compare it to their capacities so they can understand budget, the mirror of that process on the CRO or sponsor side to understand whether a site can execute on the trial adequately, and sometimes the specific steps each takes to understand the relevant questions.

Sites can usually expect that the first step (after an NDA) is to field and answer a questionnaire. Sponsors or their CROs send these forms out to sites to attempt to quantitatively understand their fitness relative to the overall population of sites they are considering for the trial. Typically, they’ll want information about the site’s physical and organizational capacity, the researcher’s background, and the patient population the site has access to. 

On the flip side, the sponsor will also start providing information about the study protocol. Sites use the protocol to understand how much of the study they can or can’t do out of the box, and what everything will cost. For the first time, this makes the potential for profit legible to the site. At this point, the protocol will be fairly set in stone for a large industry-initiated drug study, but budget negotiations take place between the site and the sponsor or CRO, not necessarily across all the sponsor/CRO’s relationships with all the sites participating at once.

The other common input here is a physical site visit. Especially for sites that are new to a sponsor, the sponsor’s representatives will usually send someone in person to look at the site and verify that its facilities match the reported capabilities in the questionnaire. Their interest will also include the site’s vibe—since patient engagement and retention are just as critical to trial success as patient enrollment, the site selection visit process screens for patient preferences as well as clinical abilities. AICs tend to invest significantly in patient experience, as compared to hospitals or research institutions, so this is an area where they will typically shine.

The legal format for the arrangement between a sponsor and a site to conduct a clinical trial is a specific type of contract called a clinical trial agreement (CTA). The CTA is originated by the sponsor and most importantly contains the study protocol, but also all the mechanics between the sponsor and the site. Reviewing and negotiating this agreement will be a significant amount of work—the researcher will be on the hook for the actual study, so their input is mandatory, but AICs will likely also want to involve a budget expert who can map the protocol to capabilities and costs, and a lawyer or other person with significant experience reading contracts who can identify necessary adjustments.

The core components of a clinical trial agreement are the study protocol, the recruitment plan, consent forms, monitoring plan, case report forms, legal agreements related to liability, IP, indemnification, and insurance, the study’s expected publication plans and ownership and access to data generated by the study, the timeline for the trial, and the specifics about who gets paid (and when, and how). The CTA will also come with a budget. That budget will be a large area of focus for the site’s negotiators, but all aspects of the CTA need to work for the site and the sponsor both, in addition to securing IRB approval.

For sites, a very specific and very important aspect to focus on will be the sponsor’s recruitment expectations. For nearly all drug trials, recruitment will have an overall target for all participants in the study and a scoped-down cut of that enrollment goal parceled out to each participating site. Sites get paid in three basic buckets: study-scope fees, admin fees for work conducted along the way, and per-patient fees. In addition, sometimes study-level fees have payment schedules and triggers that depend on successfully hitting enrollment goals. Therefore, sites need to very clearly understand the impact on their bottom line of meeting or not meeting patient enrollment milestones.

In addition to the implications for sites’ own payment schedules, trials might use a process called competitive enrollment that puts each site in direct competition with the others. For example: if 10 sites are expected to enroll 100 total patients over 2 years, that might initially shake out into the expectation of 5 patients per site per year. If site A enrolls 10 patients in the first year while site B has only enrolled 3, in some cases site A will be permitted to enroll additional patients out of site B’s allowance. This would of course affect both sites’ revenue, and the expectations in this situation should be thoroughly understood before the site signs the CTA.

There is often some room for adjustment on a per-site basis for the pass-through costs to the sponsor that go directly to patients, usually in the form of compensation or funding for amenities like comped parking or meal coupons during on-site visits. AICs’ existing standards of patient experience might offer savings that sponsors will appreciate over the cost to provide similar comforts to a patient at a research institution. In other cases, there may be factors that sites will specifically call out as must-haves to support patient enrollment. For ethical reasons, these costs should never rise to the level of coercive or excessive compensation, but both parties should agree on the appropriate standards that support engagement and retention goals.