From a purely conventional confirmatory point of view research following publication of data and/or their analyses may be flawed by data-driven research targets or by an abundance of potential research targets, for example, with regard to different subpopulations and/or endpoints.
The second outcome level contained several confirmatory end points enhancing the credibility of the primary end point, such as the rate of breakdown in emotional functioning or global QoL – similar to the example given by Schulz and Grimes (2005) for wound infection and fever.
For secondary confirmatory end points, type I error rate (false-positive results) was controlled by means of a hierarchical (fixed-sequence) testing procedure (Supplementary Fig. 1).
Secondary confirmatory end points tested were number of treatment-emergent confirmed hypoglycemic episodes, change from baseline in central laboratory measured fasting plasma glucose (FPG), within-subject variability as measured by coefficient of variation, and frequency of participants achieving HbA1c <7% (<53 mmol/mol) without confirmed hypoglycemic episodes.
These positive results were supported by two additional confirmatory end points: The number of diseased QoL dimensions per patient was lower in the QoL pathway group than in the control group at 6 months, with more than five dimensions in 4/84 (CI: 1 10) or 5% of the treatment group compared with 13/83 (CI: 7 21) or 16% of the control group (χ -test P =0.035, Fisher's exact test P =0.042).
Any samples tested above the screening and confirmatory cut-points were consider ADA-positive and confirmed ADA-positive, and were further characterized to evaluate the titer and neutralizing activity of the ADA using validated titration ELISA and neutralizing cell based assays respectively.
The screening and confirmatory assay cut points were statistically determined based on the current industry white papers (Jani et al., 2015; Shankar et al., 2008).
The confirmatory assay cut point was derived from the 99th percentile of the log-transformed normalized RLU values from each plate.
The samples were deemed positive and specific if the percentage inhibition was greater than or equal to the statistically derived confirmatory assay cut point.
Though this patient had classic signs and symptoms of renal colic and may have been treated successfully without any imaging, the confirmatory findings with point-of-care ultrasound rapidly solidified the diagnosis for the physician and the definitive evidence was reassuring for the patient.
