Clinical studies a trial team inherits from another company or department typically present a range of problems; they can include shoddy data quality and integrity, missed deadlines, mismanagement and more. Pharma companies and their contract research organizations (CROs) can face an uphill climb in untangling the problems and salvaging the research.
Outsourcing-Pharma (OSP) recently discussed these challenging trials with Dan Gebow (DG), PhD, chief innovation officer at Bioclinica, on how to best tackle rescue studies, including pinpointing problems and optimizing project management.
OSP: Could you please describe what rescue studies are and what unique attributes/challenges they have?
DG: “Rescue studies” are clinical trials that have been previously run by another vendor or in-house. They are often plagued by questionable data quality and integrity, regulatory non-compliance, missed deadlines, and overall mismanagement that necessitates a change in management.
As an example, in 2018, Bioclinica worked with a pharmaceutical organization that was facing major challenges in a global clinical trial program with 30 studies for an uncommon event type. Not only did they need to transition all ongoing clinical trials to a single software platform for better analysis — but they also needed to do it within 60 days. The event adjudication system they were using had caused numerous issues that jeopardized the program including:
- More than $1M in change orders to accommodate trial design, leading to budget overruns
- Solution provider did not pass validation audits after a year of support
- The software failure required the team to move to antiquated, paper-based data collection processes and manual spreadsheets that caused compliance concerns and the potential for error
- Imaging source document files were not always properly redacted and were physically transported via courier, causing potential privacy violations
- Inadequate and slow-moving support for sites and adjudicators in their local time zones and languages which resulted in both delays and frustrated staff
Bioclinica “rescued” the program with major improvements across data quality and integrity. Today, the program continues to grow and is now at over 40 studies.
OSP: Similarly, you mention rescue studies frequently face problems with data quality/integrity, scheduling, etc. What are the risks associated with these problems?
DG: Whether it is a clinical trial or a clinical adjudication program within the clinical trial, data must be appropriately collected and de-identified, reviewed by a clinical expert, and the results must be accessible to the trial sponsor. There are all kinds of hurdles that can crop up during this process.
When we take over (or “rescue”) a study, it’s not uncommon to find that source documents are incomplete or have missing information such as exam date, incorrect timepoints, incomplete datasets, duplicate source document submissions and incorrect patient submission. They may also contain protected health information (PHI) hidden in DICOM images, or visible PHI, or are not submitted in a timely manner.
Left unaddressed, these issues can result in costly regulatory fines or medico-legal exposures, which can compromise the outcome of a clinical trial. Tight timelines and frustrated adjudicators can also increase costs and create delays with bringing treatments to market.
OSP: How can trial teams planning and executing such studies avoid, or fix, these problems?
DG: A successful rescue requires a relationship based on mutual trust. Through a strong working partnership trial teams can address all expectations and needs, provide guidance, ensure data integrity, and deploy the right people in the right positions for ongoing support. Key areas for refinement and what trial teams should look for include the following:
Collaborative project plans are critical success factors in effectively meeting timelines and deliverables. A strong project management team will fully manage the coordination of the Clinical Event Committee (CEC) meetings, facilitate global trials at the country level with dedicated project managers, provide localized language support, translate user interface and training materials, engage professional project managers, nurses, and medical writers to ensure a study is consistent with charter requirements and initiate rapid launch of new studies or transition of existing data with rescue studies.
A centralized online repository of source documents, DICOM, videos, photos, and ECGs, simplifies the management of the adjudication process. The time-to-review is minimized by worklists, auto-routing, and built-in reminders.
These automations save sponsors from paying exorbitant project management costs and prevent prolonged data delivery. They also reduce manual errors and costs with automatic routing and de-identification and integrate easily with 3rd-party applications including electronic data capture (EDC) and safety systems.
Leveraging a customizable dashboard and report generator puts actionable key performance indicators at the sponsor's fingertips in real-time and on the sponsor's terms. An in-house comprehensive web-based platform will support an event adjudication program and gather insights throughout the trial with full data transparency that displays research site, user, and adjudicator performance metrics visually.
With electronic image handling in place, trial teams can eliminate the need to manually redact image sets PHI and ship them via courier. This means sensitive information is much more secure, enabling the client to meet compliance regulations for the handling of protected information.
An AI engine can also redact videos, photos, and medical images, as well as quality control (QC) and query management for all source document types for patient privacy and enforce compliance with 21 CFR Part 11 and EU GDPR requirements.
Trial teams should consider a source document module that eliminates the clutter pervasive in clinical adjudication and one that offers a customizable reminder system that reduces the paper chase when trying to get source documents/event data from the site. They should also look for a clinical adjudication partner with veteran adjudication specialists and clinicians to provide expert guidance on charter design and recruitment of the adjudication committee. A cloud-based source document repository can be shared with in-house or external safety teams to reduce redundancies for AE and SAE reporting.
OSP: Do you have any other advice or remarks to share?
DG: When it comes to vetting a new vendor, it’s critical to evaluate their ability to provide a comprehensive solution for your project. Below are important questions to ask when performing your due diligence to help ensure a successful transition:
- How many project managers experienced in clinical adjudication do you have on staff, and what are their years of experience?
- How do you ensure that source documents are redacted within the geographical region in which they were obtained (i.e., EU)?
- If there are language translations involved, are they routed to an EU GDPR-compliant translation service automatically?
- How do you, as the sponsor, have visibility into status and progress, including overdue source documents and open queries?
- Do you have a 24/7 support team that covers all applicable time zones and major languages?
- Does your clinical adjudication system ensure proper routing of cases to the correct adjudicator and auto-route discordant ones for secondary review, or is it a manual process?
- In your current system, if you have a configuration change order to the software, is there an additional charge? What is the lag time on development changes?
- Does your adjudication system automatically have alerts for overdue adjudication, reminders for the adjudicator, and automatic escalations to the project manager?
- Does your system provide customized sponsor KPIs accessible in real time by study, program, event type, and site?