The QTPP defines the intended use of the drug product, drug product quality criteria, dose strength, dosage form, container closure system, storage conditions, stability criteria, dosing device, shelf life, and attributes affecting the pharmacokinetic characteristics.
However there was substantial heterogeneity of the results, inclusion criteria, dose, duration and methodological quality of these studies, as well as evidence of publication bias.
Ninety percent of entries for both handwritten and CAP groups complied with the specified criteria (dose, route, frequency).
Details of the seven included studies, together with entry criteria, dose and duration of treatment, outcomes and quality and validity scores are shown in (additional file 1).
Patient selection criteria, dosing regimen, and use of ipilimumab as salvage therapy for patients in the control arm were potential reasons for the lack of survival benefit.
The reason for the difference in results between the two studies is unclear since the studies had identical designs, including entry criteria, doses of study medication, and outcome measures.
On the basis of pre-defined safety and efficacy criteria, doses of Flec CR could be increased to a maximum of 200 mg per day or reduced by 50 mg per day to a minimum of 100 mg per day, where applicable.
The primary criterion for dose modification is the relative frequency of a dose-limiting event (DLE) at a given dose level.
The criterion for dose selection may be further restricted, for example, by further requiring nonnegative trends (one-sided P > 0.90, equivalent to two-sided P < 0.20 favouring placebo).
Admittedly, HES was administered without regard to exclusion criteria and dose limitations in this study.
