‘Bundled’ or ‘umbrella’ protocols
We use adaptive protocols about 7 times per year, to execute first-in-human (FIH) trials with as many as 6 parts. Adaptive protocols work well and save time, so they’re the best choice when time is more important than cost. The MHRA refers to such protocols as ‘bundled’ protocols: they’re also known as ‘fusion’ or ‘umbrella’ protocols. MHRA and research ethics committees (REC) look favourably upon adaptive FIH protocols, which typically include SAD, MAD, food/fasting, elderly, and patient cohort(s).
We’ve submitted many ‘bundled’ protocols to MHRA and REC. The submissions are complex and time-consuming to prepare, because
- protocols must incorporate the necessary flexibility, while being prescriptive enough to reassure reviewers
- text must be crystal clear, to avoid ambiguity
- doses in each part must be defined in relation to what’s been given in previous parts
- multiple information and consent forms (ICFs) are usually needed, to cover each part of the trial
- protocol & ICF must be very carefully constructed, to allow flexibility of dosing levels without recourse to amendments that need regulatory or REC review