By Aiden Flynn. Exploristics CEO
With the increasing complexity of clinical trials involving larger quantities of varied data and pressure to deliver better returns on expensive R&D investment, pharmaceutical and biotechnology companies have increased the volume, scope, and types of activities it outsources to Contract Research Organisations (CROs). While this can improve efficiency reducing timelines and costs, it adds another dimension to the development process; maintaining adequate oversight of the outsourced work to ensure its quality meets regulatory requirements and Good Clinical Practice (GCP).
Effective CRO oversight can be challenging and time-consuming. Nevertheless, it is possible for Sponsors to avoid many potential difficulties by investing time into building effective relationships with partner CROs to ensure successful project delivery. This often involves:
Being proactive
FDA and EMA ICH guidance outline that while risk-based monitoring can be delegated to a CRO, the Sponsor is ultimately responsible for ensuring the quality and integrity of its clinical trial. Therefore, it is incumbent on study Sponsors to take the initiative in identifying possible risks and mitigating them when outsourcing work to a CRO. Being proactive in communicating with partner CROs helps Sponsors to identify risks early and intervene if problems do arise reducing the chances of errors that could have an impact on the quality, timelines, logistics and delivery of a clinical trial.
Keeping it clear
Building a mutually considerate relationship with partner CROs supported by transparent communication is the cornerstone to maintaining effective oversight of outsourced activities. It is also important to consider the interactions between partner CROs. For example, one CRO may provide statistics support while another may be supporting clinical operations or data management. Siloed mindsets and misunderstandings can be avoided by implementing a clear oversight plan that defines the:
- shared objectives, scope, reporting obligations and quality expectations for the work
- critical processes involved, the required roles, key responsibilities, and lines of accountability.
- documentation required to provide comprehensive evidence of oversight.
- communication strategy required outlining how concerns, issues or changes will be communicated between the Sponsor and CRO partner that also covers a plan for escalation.
Avoiding micromanagement
It is possible to use different paths to reach the same goal. Therefore, it is important to be flexible about how the goal is reached rather than micromanaging each step. Partner CROs may have specific capabilities that can be leveraged to deliver work outputs. While this might involve an alternative approach to completing a task, if it delivers the required outcome efficiently at the appropriate quality to meets regulatory requirements then this is a valuable benefit of outsourcing work.
Being considerate
Effective communication between the Sponsor and a partner CRO negates the need for micromanagement but is a two-way street. It may seem obvious but is worth remembering that it is in everyone’s interest to be considerate communicators. Regular updates from a Sponsor keeps the CRO informed of any issues that may have an impact on their work leading to greater efficiency, high quality output, and less rework. In return, CROs should ensure the Sponsor is regularly updated on their progress. Such effective bilateral communication can be important in flagging any potential risks to outputs early enough to manage them.
While these steps can help build and maintain an effective working Sponsor/CRO partnership, it may be that you have additional needs that exceed what the original remit of your agreement. In this case it is important to:
Assess additional risk
It can be tempting to stick to a tried and tested CRO partner with whom you have already had a good experience. However, without evaluating the new risks involved you may be inadvertently setting yourself up for expensive failure. Your current partner may not have the specific experience and expertise to cover your expanding needs, or the systems and processes required to ensure a successful outcome for them. While it can feel time efficient simply to expand an ongoing CRO partner’s scope, if they can’t deliver the right expertise this will end up costing time and money to address subsequent problems that might arise. Therefore, it is important to be prepared to review and assess the suitability of your partner afresh for each new piece of work. If you are not experienced in assessing and managing risk, it is possible to bring in another CRO to support this.
Develop an adaptive approach
While it is valuable to nurture long-term relationships with partners it is also vital for growing companies to be rigorous, flexible, and forward looking. Therefore, it is important to:
- establish a robust partner selection process that involves your relevant study teams.
- evaluate if potential partners have the right resources, will follow GCP (Good Clinical Practice), the study protocol, processes, and relevant regulations.
- consider how best to manage succession.
- keep consistent practices.
- stay abreast of project progress and be accessible when decision-making is required.
- be realistic with regards to the need and timelines
- keep all relevant teams in the loop e.g., operations, finance.
- maintain respectful open two-way communication.
- keep sight of the outcomes rather than the process.
Be diplomatic
As a Sponsor the buck stops with you in terms of clinical trial quality and integrity so it can be frustrating if timelines and milestones are not met. While it can be tempting to allocate blame, the best way to resolve any issues that arise is to keep communication with your CRO partner respectful and open. This allows you to get to the bottom of what went wrong rather than creating barriers to putting things right. It also makes it easier if you need to bring in a third party to provide additional support.
Focus on the data
Making good decisions in drug development is founded on good quality data so it is critical that the data collected, and the associated data handling processes are robust and aligned with the needs of all stakeholders. For the Sponsor, the success of the study, development programme and, at times, the company itself hinges on the data.
Common problems that can arise with data processes and analyses cover the entire study lifecycle from concept to study reporting. These include:
- Misalignment between company strategy and study objectives
- Lack of statistical expertise on the side of the sponsor
- Study design assumptions are unrealistic, creating a high-risk study that is likely to fail
- Primary objective and statistical analysis strategy are misaligned
- Definition of success is inappropriate given the nature of the study
- Data management and validation processes focus on raw (input) data and not the output data used in the analysis, resulting in additional data cleaning cycles
- Instructions given to programmers are ambiguous and open to interpretation
- Handling of the primary and secondary endpoints do not take account of the data structures
- Poor understanding of how the results should be presented, leading to misunderstanding and difficulties in interpretation
- Presentation of results in isolation and without providing context
These issues can cause major problems with the study and may result in delays, rework, additional costs and study failure. These can be avoided with the use of appropriate statistical experts who understand the needs of the sponsor whilst also appreciating the requirements of the CRO.
Get the right help
Maintaining any good relationship in life requires realistic expectations, respect, time, and effective communication. Your relationship with a partner CRO is no exception. Keeping this in mind ensures you can navigate the complexities of CRO oversight successfully. Additional statistical support keeps everyone aligned and ensures costly errors and misunderstandings do not derail the project.
To find out more on how Exploristics can support CRO oversight, book a call with us today.
Read more:
Flexible Functional Service Provision for Drug Developers of All Sizes
FSP Case study: Supporting a vaccine clinical trial