Review article: the evolution of endpoint assessments for chemotherapy-induced nausea and vomiting and post-operative nausea and vomiting-a perspective from the US Food and Drug Administration.

BACKGROUND: Nausea and vomiting can result in decreased compliance with oncologic therapies for patients with chemotherapy-induced nausea and vomiting (CINV); and increase complications and recovery time for patients with post-operative nausea and vomiting (PONV). CINV refers to nausea and vomiting after antineoplastic therapy administration and PONV is nausea and/or vomiting that occurs in the post-anaesthesia care unit or during the 24 hours following surgery.

AIM: To analyse the evolution of endpoint assessments utilised in clinical trials to support FDA approval of CINV and PONV therapeutics.

METHODS: A review supported by the US FDA analysed 31 approved New Drug Applications, respective clinical trial protocols and product labelling for CINV or PONV therapeutics with an emphasis on primary endpoint selection.

RESULTS: Analysis revealed primary endpoints have become more refined and now often include the assessment of both vomiting and rescue medication use (ie, Complete Response). Additionally, the visual analogue scale was recognised as the most prevalent instrument to assess nausea as 58% of reviewed applications included this assessment. An imbalance between available therapies for adults and paediatric patients was also identified as only 39% of the reviewed approved products were indicated for paediatric use.

CONCLUSION: The goal of this research was to inform and identify future opportunities for enhanced clinical trial design. Nausea assessment was identified as an opportunity for continued research and development due to the large heterogeneity of instruments used. Furthermore, there is a need for the development of safe and efficacious antiemetic treatments for paediatric patients.