Collaborative Partner Relationships leads to repeat business and database lock for critical care study
CNS; Aneurysmal Subarachnoid Haemorrhage (aSAH)
This Phase III trial in a critical care setting evaluated a new treatment for aneurysmal sub-hemorrhaging involving 86 sites in 11 countries, enrolling 283 patients within the Sponsor’s timeline. WuXi Clinical provided full-service CRO support in North America, Europe and Asia.
The conduct of this study was particularly complicated for a number of reasons. The study was a double-blind, double-dummy, placebo-controlled, parallel-group, efficacy and safety study that utilized both blinded and unblinded personnel. As such, additional resources and careful planning were involved in maintaining segregation and protection of blinded and unblinded information, and additional procedures had to be put into place to address situations of unblinding. Additional challenges include those listed below:
Patients must be administered the drug within 48 hours of onset of critical event during which time, they will undergo diagnostic procedures and repair operation and may or may not regain consciousness in order to give consent. As such, Legally Authorized Representatives had to be identified during this period as well, if consent was to be obtained. In some cases, re-consent must be administered upon subject regaining consciousness. Also, IP prep was a complicated, technique-dependent procedure required specialized pharmacy and PI training. IP had to be prepared and administered within 4 hours of prep, thereby requiring 24/7 pharmacy support by trained personnel, and getting the IP to bedside and administered within the 4-hour window.
Complex medical monitoring challenges with many expected AEs and SAEs.
Seamless transitions from the surgical, ICU and hospital floor teams were critical to the success of the study.
Complex monitoring of patient charts was coupled with a Risk-Based approach to source document verification to reduce the monitoring burden.
Timelines for negotiation and execution of budgets and contracts are generally much longer than the average across all WuXi Clinical studies. This is due to all these sites being academic institutions. Some US sites also had complex indemnification requirements that took more effort to negotiate.
We handled each of the study’s challenges in close collaboration with the sponsor company. This cooperative approach enabled us to manage each obstacle from multiple sides, in order to implement the best possible solution as quickly as possible. In addition, we were able to remedy a number of specific challenges, including:
Education of the site personnel, PI and pharmacy staff were critical to ensuring success across this continuum, but the underlying reason that sites are successfully accomplishing the acrobatics described is that the treatment has such an enormous potential for altering the course of these patients’ outcomes, from death or permanent disability to a full recovery. WuXi Clinical and the study sponsor believe that the potential for such a positive change resulting from this treatment is the primary driver motivating the investigators and their staff to undertake and succeed in overcoming the challenges described.
In order to reduce the number of SAEs processed by the PVG/Safety team and sponsor, the sponsor pre-identified and vetted with the FDA a list of expected SAEs which are reported in the eCRF as serious, but do not require the rigorous and expedited reporting typically required of all SAEs.
We supported investigators and their teams in the conduct of training sessions with emergency intake personnel and ICU staff to allow for immediate awareness of potential subjects and conscientious attention to protocol required procedures that may or may not follow standard of care procedures, depending upon the hospital practice and region.
The sponsor’s and WuXi Clinical’s cross-functional teams (clinical, data management and statistics) worked collaboratively to create a list of key risk indicators and approaches to data monitoring of electronic records and trend reports to ensure data is reviewed in a timely and efficient manner to ensure inclusion of qualified patients and protocol specified procedures are being followed. An in-house data monitoring approach enabled timely evaluation of incoming data and supportive response to study sites to address any challenges noted with early and ongoing study conduct.
We collaborated closely with our sponsor’s legal team and facilitated calls directly between sites and sponsor to address obstacles regarding timeline and budget as they arose.
We completed this study on-time, with high quality and in accordance with all elements in our contract. In addition, we met site activation and enrollment goals. Our flexible and collaborative approach, quality of team members, and comprehensive understanding of the numerous complexities involved in the Phase III study led to an award of a second study by the sponsor company.