As the study unfolded it became apparent that the data being collected would support a pivotal study, thus outstripping the capabilities of the locally selected CRO. Cmed were invited to rescue all data management responsibilities and as well as adhering to all reporting timelines were able to streamline the external data review process by providing the DSMB with real-time access to the database. Read how...

The trial rescued/recovered by Cmed was presented as a two-year open-label extension to a double-blind placebo controlled study of the long term effects of (product) on Major Adverse Cardiac Events (MACE) and progression of Chronic Transplant Dysfunction in renal transplant patients. In plain
English, the trial was designed to examine the effect of (product), a cholesterol-reducing drug, on MACE free incidence in patients who have had a kidney transplant. In particular, Major Adverse Cardiac Events (e.g. heart attack, cardiac death, by-pass operation) and the ongoing function of the kidney transplant were to be monitored.

The study started as a phase IV Investigator initiated study in Scandinavia. The work was outsourced to a local CRO by the Principal Investigator, not by the pharmaceutical company. The initial purpose for
the data were within the capabilities of the selected CRO, but it rapidly became apparent as the core
study completed that the data being collected would support a pivotal study; as such sponsor involvement
increased rapidly, and with that deficiencies in the existing data management processes became clear.

At this point, Cmed were invited to propose a rescue plan, whereby all data management responsibilities would be assumed from the previous CRO. Through a cooperative effort between the initial CRO and Cmed, the core trial database was successfully locked, before work on the extension phase began.

Challenges:

1. Recovering project and assuming responsibility without disrupting sites and data reporting commitments
2. Maintain critical endpoint review processes
3. Migrating existing project data from internal SAS system to Timaeus with minimal requirement for re-entry of data, whilst maintaining full audit trail
4. Ensuring the rapid and appropriate ramp up of Cmed staff to ensure long term viability of the project

The project

Protocol:

Two year open label extension to a double blind placebo controlled study of the long term effects of
(product) on Major Cardiac Events and progression of Chronic Transplant Dysfunction in renal patients. The extension phase was expected to involve 1,180 randomised subjects across seventy-seven sites: Belgium (six), Canada (four), Denmark (six), Finland (eight), Germany (five), Norway (22), Sweden (25) and Switzerland (one), generating 56,840 CRF pages of data (plus central laboratory data).

The rescue plan

Cmed initially in-sourced 12 staff to work within the CRO. The team was set up and charged with assuming full responsibility for the study, whilst continuing to successfully utilise the existing team. Ultimately Cmed hired several members of the original team and absorbed them into the Cmed organisation, where many still remain today.

Task 1

• Import all SAS datasets from existing database system
  
  – NOTE: Cmed did not re-enter any data
  
  – This involved copying the core study SAS database, which was essentially “locked”, and creating an entire Timaeus database system for storing and reporting the core study data
• 10% QC of all data performed to ensure:
  – Inherited data entry/management processes were acceptable
  – Data transformation/mapping steps were fully compliant with data expectations
• Reconcile any/all issues related to transforming data from SAS system to Timaeus, including previous data validation issues

Task 2

Having addressed the issues identified in the core study, attention was then focused on the extension phase:

• Build the extension database in Timaeus
• Enter all extension data
• Validate all extension data
• Maintain all original timelines

Task 3

• Build the Critical Endpoint Committee database in Timaeus to manage critical endpoint data reported to team of independent medics
• As well as the database, Cmed also managed the complete Critical Endpoint Committee process from:
  Identification and tracking of all potential critical events according to criteria
  Preparation of event case studies (collating all supporting data)
  Set-up and hosting of the endpoint committee meetings
  Track and database endpoint decisions

The result

Cmed successfully adopted the entire study and adhered to all reporting timelines. Furthermore, they streamlined the external data review process by providing the Data Safety Monitoring Board (DSMB) with real time access to the database as well as selected listings.

Cmed performed data management and statistics for the extension study. Cmed delivered the locked extension database on-time and on-budget, and produced statistical tables and listings across the combined core-extension dataset.

Conclusions

The decision to move a project from one vendor to another is always a difficult one; fracturing
relationships and not without significant financial implications for both parties. However, when absolutely necessary, it is important to put the needs of the project first.

Rescuing a study from another organisation is equally difficult, especially if the new partners
are to avoid introducing delays that will ultimately cause further anguish to the Sponsor Clinical team. The incumbent vendor must also approach the situation delicately, balancing the need for knowledge, empathy and speed.

It is vitally important to recognise, in this example, that the initial CRO requested Cmed’s assistance. Indeed, Cmed went on to directly employ several of the core team and relocate them to Cmed’s UK offices.

Cmed has experienced large scale and small scale rescues and in each case has successfully met all of the commitments and delivered on time and to budget.