Achieving Sponsor oversight of CROs

Recently I posted an update proclaiming how 'rude' I am as a CTO. What I meant by that is, similar to the wider KCR CRO company, I hold a responsibility to provide transparent, honest advice - in my case as it relates to technology - in how we execute our clinical trials with our sponsors. This can present itself as being 'rude' or at least blunt.

Sponsors retain a duty of oversight over the vendor(s) that they work with. Unfortunately, sponsors are increasingly finding it difficult to meet their regulatory obligations with the information and transparency that CROs are providing.

Todays article offers up some advice on some of the do'es and don'ts in achieving effective oversight and therefore in meeting a sponsor's regulatory obligations. Additional, I describe the support that CRO companies should provide in helping their sponsors maintain their oversight role.

Regulatory Oversight Requirements

First of all, I am going to quote from an excellent recent article by Sandra (Sam) Sather, MS, BSN and Jennifer Ray Lawyer of Clinical Pathways on the definition of oversight between Sponsors and CRO companies;

In the 2013 FDA guidance on risk-based monitoring, the section “Delegation of Monitoring Responsibilities to a CRO” (section VI C) clarifies that the sponsor can delegate monitoring to a CRO, but the sponsor retains the responsibility to oversee the work of the CRO. Likewise, ICH E6(R2) (section 5.2) allows for the transfer of any or all trial-related duties to a CRO, with the reminder that the sponsor is ultimately responsible for the quality and integrity of the clinical trial. The recently updated (September 2021)?FDA Bioresearch Monitoring (BIMO) Program Compliance Program Guidance Manual (CPGM)?for sponsors includes a new section, III. F. “Outsourced Services,” related to the oversight of CROs and other vendors as inspectable items. The agency wants to know how the sponsor ensures that its outsourced activities comply with FDA regulations, the protocol, and GCP. Additionally, in many other parts of the updated CPGM, there are new items that focus on vendor selection and oversight (e.g., an expanded section, N. “Data Collection and Handling”). In short, the sponsor can transfer duties, but not the responsibility of proper oversight of the clinical trial.

Oversight through systems control

One of the most common methods of achieving CRO oversight, especially for sponsors that work with multiple CROs is to ask the CRO to use the Sponsors licensed technology. This might be a Clinical Trial Management System (CTMS) or electronic Trial Master File (eTMF) solution or even Electronic Data Capture. What this means is that the Sponsor is the licensee of the technology and they provide access to it for one or more CRO's in order for them to carry out their work.

On the surface, this sounds like a good idea - all CROs use the same tech - the sponsor has control over the tech and can see for themselves in one location exactly what is going on across the CROs - a form of oversight. This is also attractive to the vendors as they increase the number of clients and licenses.

However, if not handled correctly, this can turn into an expensive approach that reduces clinical trial quality and performance for a CRO and onwards to a Sponsor and in fact can reduce the overall oversight achieved. Below I elaborate across 4 distinct areas;

1). Technology Configuration

Today, the vast majority of good clinical trial solutions are cloud based. Of these the best are configurable to meet the requirements of each business and setup. The configuration work can take months and even years to ensure the right setup is achieved that optimizes performance in different geographies with different organizational structures.

If a sponsor company brings in a technology designed to be used by one or more CROs then they need to be prepared to consult, potentially with each CRO they plan to work with, to optimize the solutions implementation. Even for the largest companies such as GSK and Novartis, this might take months if not years to complete.

In practice, often these adjustments are not made and a 'lowest common denominator' approach is followed. This creates a sub-optimal solution for both the Sponsor and CRO leading to gaps between what actually happens 'on the ground' and what is in the systems. This hampers effective oversight.

2). Processes

If processes that a CRO follow do not reflect the technology being applied, then the technology is being under-utilized.

For a CRO to be truly digital, the technology must be part of day-to-day work. This means the processes that are being followed are aligned with the activities and workflow configured into the technology.

If a Sponsor provides their own technology that is not aligned to a CRO's processes, then either a noncompliance occurs, or, the processes are left generic to the point of limited value. Yes - they might be adequate to pass audits, but they will not provide a performant solution.

3). Training

CRO's train their staff in their processes and their technology. This means when a Sponsor contracts with a CRO a chunk of the moneys they are paying is going towards the overhead of training these resources.

If the sponsor wishes to use their own technology, then the training must be re-developed and re-delivered. This is massive. This is not just the vendor training, but the training on the configuration of the solution specific to the Sponsor and CRO. This exercise extends the study startup timelines and puts a strain on resources that must be trained in multiple systems and processes.

In practice, minimal training is often performed leading to quality and compliance issues

4). Continuous Improvement and Validation

This is incredibly important, and often misunderstood.

Configurable cloud clinical trial solutions arrive as a base shell. A framework if you prefer that is ready for improvement through configuration. These systems tend to be vendor managed continuous deployment solutions - meaning new software will be released continuously and automatically - the licensees of the platform must resource for continuous change, and re-validation.

At KCR, we release updated configurations of our Veeva product suite on the 1st of each month. This includes changes to software (from Veeva), changes to the configuration of the software (by KCR), changes to processes and changes to training /manuals. This takes a considerable effort by a decent sized team. This investment means that the KCR Veeva implementation is as good as it can be continuously.

The alternative is that it becomes increasingly out of date, and when it is changed, causes significant disruption.

Few sponsors can adapt and adjust their configurations of any of the configured cloud clinical research systems and carry out importantly re-validation according to Computer Systems Validation processes to meet the requirements of multiple CRO companies.

Alternative Oversight Methods

Sponsors must be able to oversee the work carried out by CRO's and their sites. As per the regulatory requirements summarized at the top of this post, this is mandatory. To this end, it is up to each and every good CRO to enable a Sponsor to achieve this oversight.

Oversight is too often achieved through a PowerPoint presentation and a weekly discussion. This time can be valuable, but we can do so much better.

Oversight is something the sponsors should be capable of achieving 24 hours a day, 7 days a week. This oversight should not just be partial oversight, or oversight broken into as many pieces as the technology governs, but ONE place for oversight.

With connected systems, Sponsors do not need to wait until reconciliation occurs or wait until data is manually transcribed, or wait until information is manipulated into Excel spreadsheets and Powerpoint. Instead, we can (do) present fully integrated Dashboards including the study facts built around Key Performance Indicators on a near-realtime basis. These state EXACTLY what is happening across all operational areas of their clinical trial. This is going beyond basic oversight by providing measures against a plan on what is going well and what requires attention. These KPI's should measure quality as well as performance.

Oversight Gaps

KPI dashboards that compare plans with an actual can be challenging to prepare and maintain at the best of times. Where they become next to impossible to adapt is when some of the plan / actual information is sourced from another system with either no or limited connectivity. This can be the case when, for example, the sponsor chooses a CTMS solution that has no viable APIs for data mining or is not linked to EDC, IWRS or eTMF.

Conclusion

If CRO's continue to fail to provide sufficient usable information in order for their Sponsors to achieve oversight, then Sponsors will seek alternative methods whether it is micro management or systems & data governance. It is the duty of a CRO to deliver information that is in-effect better than sponsors are capable of delivering for themselves.