Blinded outputs were programmed internally by a sponsor and we had an independent statistician who attended the meetings and gave statistical advice. The sponsor created blinded outputs outside of their standard reporting environment so that we could easily recreate outputs using a standalone SAS environment. We were supplied the DMC charter for review prior to finalization.
PHASTAR was engaged to rescue another CRO’s reporting of a large phase III study in mild asthmatics to evaluate the efficacy and safety of the experimental compound. With a primary objective to prove superiority in asthma control, analyses consisted of a complex primary endpoint and a broad range of secondary endpoints which are typically observed in respiratory.
PHASTAR began a relationship with a top ten pharmaceutical company carrying out statistical consultancy and were subsequently asked to bid to be a partner in a traditional outsourcing model (i.e. the reporting of clinical trials is done independently by PHASTAR using PHASTAR systems and processes). An RFI/RFP process was undertaken, and we responded, giving details of how we would deliver the results of the clinical trials and related deliverables. We were then selected to be one of two strategic partners after agreeing processes, pricing and governance structure. A two-layer governance structure was established, with a quarterly executive review.
PHASTAR was awarded as a preferred supplier to a top 20 pharmaceutical sponsor, supporting five new studies per year. Each study was several years in length, with IDMC meetings taking place every 3-6 months. PHASTAR worked with this pharmaceutical sponsor through two models for IDAC support; model one offering independent programming of the blinded and unblinded IDMC package, with model two utilising sponsor programming code to produce blinded and unblinded IDMC package.
A PHASTAR statistician was tasked to assist with the design of a modular protocol to assess safety, tolerability and pharmacokinetics in a novel oncology compound in an acute indication. The first module consisted of a dose escalation portion with the aim of defining the maximum tolerated dose (MTD).
PHASTAR helped to design and analyse a placebo-controlled crossover trial using an anti-epileptic to assess cognitive function in children. The study had a large number of outcome measures, covering cognitive function but also seizure frequency, an ambulatory EEG assessment, IQ and a behavioural assessment using the Conners Rating Scales. The study was also attempting to determine the relationship between transient ischemic attacks and short-term impacts on cognitive function.
A new formulation under investigation was planned to be submitted for use in both the US and Europe. As the reference formulation in the US differs from that in Europe, two separate bioequivalence studies were needed to gain approval from the FDA and EMA. Study 1 was conducted for FDA approval and successfully demonstrated bioequivalence. Study 2 was conducted for EMA approval and whilst AUC was within the bioequivalence limits, Cmax was not, and bioequivalence could not formally be declared..