Clinical trial sites invest significant time and efforts to get prepared for the start of a clinical trial. Sites need to work on site-specific informed consent, collaborate with their Ethics Committees and/or Review Boards, perform submissions, review a lot of study documentation (protocol, investigator brochures, manuals etc.), attend trial-specific trainings and meetings, negotiate clinical trial agreements and budgets, and perform numerous of other actions before the trial actually starts.

Every work shall be paid – this principle surely applies to the above-described extensive work made by the site. To cover the invested time and efforts the Sponsors usually offer Start-up fee, which can vary significantly depending on the trial, region and/or site-specific requirements from USD 500 to tens of thousands of US dollars. Start-up fee is usually paid within some agreed period after full execution of the clinical trial agreement.

In practice there can be some issues with the Start-up fee.

Issue 1. Is the Start-up fee amount fair?

Fair market value of the Start-up fee is hardly identifiable. The fee is so specific that even for one trial in one country it can be very different from site to site. One site can accept initial Start-up fee proposed by the Sponsor, another site may request a ten-times increase – and both will be right. In many cases the Start-up fee serves as indicator of the site’s experience.

For example, Site X is happy to estimate their start-up activities to USD 500, Site Y requests USD 5000 providing the exhaustive justification such as references to the previous similar trials, the number of hours they need to get prepared for the trial and corresponding per-hour rates, staff allocations etc.

So, both sites seem to act fairly: Site X accepts a lower fee, Site Y requires a higher fee providing the rationale for that. We can only guess of the reason of such approach, but in most cases the reason is Site X may be not very experienced and cannot calculate their time and effort investments to the start-up phase of the trial.

Issue 2. Start-up work is performed by the site, but the trial is cancelled.

This is a multi-level issue, and it is important to understand the consequences of the trial cancellation. These can be:

• Trial is cancelled by the Sponsor for whatever reason beyond Site’s control.

In this case the Start-up fee should be paid to the Site at full. It’s not an issue if the clinical trial agreement was fully executed, but what if it wasn’t?

Some jurisdictions require that such payment shall be based on some legally binding instrument, some kind of contract. Depending on the region this can be either Start-up fee agreement which shall be signed by both Sponsor and the Site or simple letter of reimbursement signed by the Sponsor only.

• Trial is cancelled due to disapproval of the trial by the regulatory authority.

Sponsor always understands that there is a risk of the regulatory authority disapproval. In such situation the Start-up fee should be paid to the Site in the manner described above.

• The Site was so slow in in performing the start-up phase of the trial that the Sponsor had to cancel the Site’s participation (aka “drop the Site”).

This is the most complicated situation. From the one hand, the Site might have done their best to collect all the essential documents, negotiate the clinical trial agreement(s) and budget(s), but due to resourcing issues, pandemic or high workload they simply couldn’t meet the Sponsor’s expectations on the timelines – it is totally understandable. But from the other hand, if the Site is so slow that the global patient enrollment target was met, that means for the Sponsor the ‘slow’ Site is in no longer being onboarded.

In case the Site is dropped, should it be paid for the partially accomplished start-up phase? There is hardly an exact and correct answer. It depends on the Sponsor approach, the amount of actual work performed by the Site, Site-Sponsor professional relationship. Ideally the Sponsor and the Site should agree on some reasonable reimbursement which covers actual efforts of the Site.

Thus, the usual budget item known as Start-up fee is far more complicated than a tiny line in the Site budget. Depending on how the Parties treat this line in non-standard situations, it can either improve their future cooperation or spoil it.