Home › Discussions › Clinical › Superiority vs. non-inferiority studies – can PK-PD bridge this gap? › Reply To: Superiority vs. non-inferiority studies – can PK-PD bridge this gap?
The ability to recruit patients is a complex topic and influenced by many factors, mostly epidemiology of infection caused by resistant pathogens but also organisational factors at CROs and trial sites, number of clinical trials in the same field and location, legal obligations in a specific country or engagement of PIs. In general, superiority design in a randomized controlled trial clearly shows (if successful) that a new antibiotic works against resistant strains in clinical practice when compared with a drug that is not or less effective against resistant strains. This situation is rare and would require pan drug-resistant pathogens or colistin as main active comparator. In case of carbapenem-resistant Enterobacteriaceae this is extremely difficult (see plazomicin trial) but more realistic in case of Acinetobacter (see AIDA trial) or possibly Pseudomonas. Non-inferiority design of clinical studies with urinary tract or intra-abdominal infections is relatively easy and can be done in about one year with about 600 patients. The main problem is that the results don’t tell anything about efficacy in infections in severely sick patients with highly resistant pathogens.
PK/PD is an important part of any expedited regulatory path and gives essential information to inform a clinical program, especially prediction of effective dosing. On the other hand, this predictive and valuable tool doesn’t replace clinical unbiased experience.
You can find a more detailed discussion about this topic here: https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(18)30538-X/fulltext