Benefit of Avasopasem Manganese on Severe Oral Mucositis in Head and Neck Cancer in the ROMAN Trial: Unplanned Secondary Analysis.

Purpose: Oral mucositis (OM) is a debilitating side effect of cisplatin and intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. The phase 3 ROMAN trial showed avasopasem manganese (AVA) significantly decreased individual endpoints of incidence and duration of severe oral mucositis (SOM, World Health Organization [WHO] grade 3-4), with nominal decrease in severity (WHO grade 4) and significant increase in the delay in onset of SOM. We sought to determine the Net Treatment Benefit (NTB) of AVA versus placebo (PBO) using the generalized pairwise comparisons (GPC) method.

Design of a clinical trial using generalized pairwise comparisons to test a less intensive treatment regimen.

Background/aims: Showing "similar efficacy" of a less intensive treatment typically requires a non-inferiority trial. Yet such trials may be challenging to design and conduct. In acute promyelocytic leukemia, great progress has been achieved with the introduction of targeted therapies, but toxicity remains a major clinical issue.

Generalized pairwise comparisons of prioritized outcomes are a powerful and patient-centric analysis of multi-domain scores.

Background: Generalized pairwise comparisons (GPC) can be used to assess the net benefit of new treatments for rare diseases. We show the potential of GPC through simulations based on data from a natural history study in mucopolysaccharidosis type IIIA (MPS IIIA).

Methods: Using data from a historical series of untreated children with MPS IIIA aged 2 to 9 years at the time of enrolment and followed for 2 years, we performed simulations to assess the operating characteristics of GPC to detect potential (simulated) treatment effects on a multi-domain symptom assessment.

Generalized Pairwise Comparisons to Assess Treatment Effects: JACC Review Topic of the Week.

A time-to-first-event composite endpoint analysis has well-known shortcomings in evaluating a treatment effect in cardiovascular clinical trials. It does not fully describe the clinical benefit of therapy because the severity of the events, events repeated over time, and clinically relevant nonsurvival outcomes cannot be considered. The generalized pairwise comparisons (GPC) method adds flexibility in defining the primary endpoint by including any number and type of outcomes that best capture the clinical benefit of a therapy as compared with standard of care.

Pupil size variations reveal covert shifts of attention induced by numbers.

The pupil light response is more than a pure reflexive mechanism that reacts to the amount of light entering the eye. The pupil size may also react to the luminance of objects lying in the visual periphery, revealing the locus of covert attention. In the present study, we took advantage of this response to study the spatial coding of abstract concepts with no physical counterpart: numbers.