Making CTAs work for both parties usually requires a fair amount of back and forth. Sponsors understandably want to make sure that the study collects as much useful data as possible for the least amount of money in the fastest turnaround. Sites typically want to protect staff’s time and obligations, avoid onerous or unnecessary reporting expectations, maximize the upside for their balance sheet and reputation, and succeed without worrying about pinching pennies or blowing through funding early.

Sites typically want to be thorough in considering all the implications of following the CTA’s exact language over time. A common example is to change words like “must” to “should” and “immediately” to “promptly” for any expectations covering their staff’s responses to a situation—sponsors’ lawyers tend to default to the absolute best level of visibility they can guarantee regardless of the implications for the people conducting the study. On the site’s side, those staff members are typically stretched thin to begin with and (in an AIC especially) torn between competing priorities that involve projects outside of research. Expecting them to drop everything in certain contingencies to fill out a report or notify the sponsor as fast as humanly possible might not make sense.

Another big topic is the recruiting plan. Once the CTA is approved by the IRB and signed, there’s much less flexibility to adjust the channels, tactics, and messages that a site can use to attract patients to the trial, so getting paid down the line is a matter of savvy campaign planning in the negotiation phase. Ensuring that permitted tactics (and budget) support the necessary performance to meet expectations is crucial.

CTAs also detail monitoring expectations. Sponsors negotiate the right to request regular oversight visits, both digitally and in-person, to make sure that study conduct is proceeding according to the exact protocol, and that things like data storage and drug security are on point. These visits can be disruptive to researchers, clinicians, staff, and patients, and sites benefit from being realistic about how much they are willing to do to accommodate monitors (and at what fee level).

Because payment terms are involved, sites will also usually play out different scenarios, like late payments or patient enrollment attrition due to factors outside their control, and ask for contractual language that protects their ability to get paid. One very specific example is late fees for missed payments. Another is format and frequency for billing—recent trends involve sponsors asking for increasingly atomic invoicing, with the effect that capturable fees do not get paid because overworked site staff miss the opportunity to bill for it.

Finally, the fun section. How do AICs know if they can make money on any given trial? And how can they protect their ability to do so?

As we mentioned in the last section, budgets encompass fees in three approximate buckets: the cost to start up and conduct the study, the cost to perform admin and data work related to the study, and the cost of clinical work. In all cases, negotiating fair coverage for the services depends on making a case for fair-market value based on the operating environment the site is specifically situated within, ideally with documentation to prove it.

The absolute most important thing AICs should know about budget negotiation is that the interplay between their budget estimate and the sponsor’s budget estimate will be based on different information. Sponsors and CROs generally use third-party data sources for fair-market-value estimations by CPT code. The most common is GrantPlan, an IQVIA product. Meanwhile, sites can know their actual projected costs by mapping out each step of the study protocol and cross-referencing their own cost of executing plus the cost of having any external partner provide the necessary supplemental care. Most sites will also be careful to model out the cost of following up on contingencies (like additional blood draws or lab work, repeated steps, or missed appointments) to ensure that margin exists to absorb them, or budget is allocated to reimburse for them.

For admin work, CROs do not have an IQVIA database to rely on, but AICs have a wealth of information about how much time it takes their staff to perform most tasks. The challenge then becomes forecasting out all the types of work that admin staff will need to do to support the trial and creating a fairly exhaustive price list for the fees the site intends to charge in different contingencies. Examples include processing paperwork, entering data, liaising with sponsor-side counterparts, time spent in meetings and attending trial training, time spent learning a sponsor or trial’s mandated software systems, work to maintain and secure records, work to accommodate monitor visits, regulatory and IRB submission prep, and conducting pre-screens.

Sites might also want to consider the facilities and utilities costs associated with the trial. Recruiting trials might include dedicated or isolated lines of communication, like phone lines or websites, that likely cost money to buy, make, or operate. Physical storage takes up space (for years). A portion of the cost of providing care comes from electricity and other resources.

For study-level fees, sites often receive a start-up fee, an annual fee, and a fee at study completion or close-out. These fees commonly come from a separate portion of the sponsor-side budget than the per-patient costs do, so they can be a source of negotiation that protects site margins on the overall project. Academic sites typically charge on the order of $10,000 to $15,000 for study start-up fees alone. In addition, sites may want to negotiate overhead fees to cover a portion of the overall cost of doing business (eg. business development, insurance, office supplies). Trial budgets often allocate as much as 40% of their overall costs to overhead.

One last callout in this section is inflation. If a study will run over multiple years, sites often consider specifying the rate at which fees increase to keep up with inflation (often ballparked at 5%).

Once the CTA, marketing plan, and budget have been fully negotiated and everything has been approved by the IRB, the sponsor and the site sign the agreement and move forward. The researcher also has to file a document (FDA 1572, which is available with instructions from FDA’s Clinical Trial Forms page) with FDA to officially notify them of the existence of the study and their intention to conduct it.

The remaining steps before the study begins to enroll patients are mostly the responsibility of the sponsor or CRO. In addition to shipping materials and the investigational product to the site, the sponsor or CRO also has to conduct a site initiation visit—a mandatory step in which the site and site’s staff can receive trial-specific training and information.

Site initiation visits can be dry, but preparation from the site’s side can turn a boring and unhelpful visit into a more productive experience for staff. Typically, a clinical research associate from the CRO comes in-person to present the study protocol, go over specific needs for data collection or reporting, and ensure that the site has all the information it needs. To make the best use of the time, the site can work with the CRO ahead of time to work out the specifics of the visit, especially including schedule alignment to ensure that relevant staff will be able to attend the sections that are most meaningful to them. If the CRO sends the presentation materials in advance, the site can also take time to review them and line up questions where clarification would be helpful.

Once site initiation is complete, the CRO will grant systems access to the site, and the site can begin recruiting and enrolling patients.