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.
An independent PHASTAR statistician was assigned and was responsible for reviewing the IDMC charter and reviewing, interpreting and presenting the blinded and unblinded results. Alongside this, PHASTAR’s statistician was responsible for leading the internal PHASTAR production team in the creation of all reports for the open and closed IDMC sessions. The independent statistician scheduled and attended all open and closed sessions, leading the discussion of results and documenting all decisions and actions. Any ad-hoc analyses that was requested and agreed by the IDMC was produced by this independent statistician.
For IDAC support using model one as outlined above, the sponsor provided raw/SDTM/ADaM datasets and dummy randomisation to PHASTAR. Blinded IDAC packages were produced based on SAP/mock shells using internal PHASTAR systems, tools & processes. These packages were sent to the sponsor review and any updates. Actual randomisation was transferred to PHASTAR by external vendor or dedicated randomisation coordinator, which was then used to produce unblinded package for each IDAC meeting. The IDAC package was released to IDMC members through a password protected area which is hosted on PHASTAR’s server.
When utilising model two, the sponsor provided raw/SDTM/ADaM datasets, dummy randomisation and code via a secure PHASTAR portal. Blinded outputs and analyses based on SAP/mock shells were reproduced in the PHASTAR reporting environment, utilising the sponsors code. Once produced, the results were cross validated, ensuring that any discrepancies were identified and resolved. Actual randomisation transferred to PHASTAR by external vendor or dedicated randomisation coordinator. Actual randomisation was used to produce the unblinded package for each IDAC meeting. The IDAC package released to IDMC members via password protected area on PHASTAR server.
Working via two models brought several challenges and advantages. Utilising ‘model one’ as outlined above, the greater separation between IDAC and sponsor allows for a lesser risk of unblinding, with no need for cross-validation against sponsor results. Independent programming can start using ﬁnal mock shells without waiting for availability of sponsor programs and ad-hoc IDMC requests can be handled more easily without the potential for sponsor unblinding. However, this model requires greater resource and can see some duplication in programming effort.
Using model two added a further QC of the IDMC package, due to the secondary validation of sponsor’s original code. Alongside this, model two can be more eﬀective as IDAC code can be re-used for CSR analyses. However, model two sees less independence between sponsor and IDAC, as well as increased sponsor resources being required to provide programs and manage transfers.
PHASTAR has received high praise, both from the sponsor and from the IDMC members, for our conscientious work ethic, professionalism, attention-to-detail, and flexibility. PHASTAR has assembled one of the largest teams of statisticians with IDAC experience, covering all phases of studies and a broad range of therapeutic areas.