Once a trial reaches the late-phase, it requires expert oversight that is independent from its chief investigator and host institution – this role is performed by a trial steering committee.
Reliable risk analysis, customized quality assurance management systems and responsive monitoring are essential for the successful execution of clinical trials, something which can only be accomplished by having a clearly laid out project management plan in place.
Planning
Planning and conducting trials require an experienced team with diverse expertise. However, many trials fail due to poor planning; this may not just be due to poor preparation; rather it stems from not having an established process for planning and running trials. Experienced trialists usually create formal or informal plans and checklists of essential steps before beginning; those undertaking their first trial usually have to start from scratch; though if lucky enough they might gain access to someone with previous knowledge as part of a clinical trials unit.
One key problem of clinical trial management is its absence of published standards. Some organizations are taking steps to rectify this by creating training courses on practical trial management or developing them themselves; additionally there have been an increasing number of societies and associations of trial managers emerging to share knowledge amongst one another.
Large trials, particularly multicentre ones, typically employ a Trial Steering Committee (TSC), to which the principal investigator reports and can seek guidance or authorization on any aspect of its conduct. Furthermore, each study should establish its own Data Monitoring Committee (DMC), with its main function being protecting participant interests while simultaneously assessing any external information that might impede trial outcomes as well as monitoring its overall conduct.
Success of any trial lies in its ability to recruit and retain trial volunteers as well as to enlist key personnel such as trial managers, project administrators, clinical trials nurses or research assistants. All participants should feel that their work contributes to answering an important clinical question while feeling part of an inclusive team; regular feedback should come not only from TSC but also principal investigator to inform participants on trial progress and results.
Monitoring
Trial managers need to closely track a trial’s progress from its inception through completion in order to be effective at their jobs. By monitoring, trial managers ensure compliance with its protocol and any regulatory guidelines applicable, and that all procedures at each site involved in the study are followed correctly. Furthermore, monitoring allows trial managers to detect and address deviations/nonconformances that might arise during its lifecycle.
Monitoring is critical in protecting participants and research data integrity, while also helping identify problems which should be corrected before they cause harm to participants or research data integrity. For instance, deviation from agreed procedures at one trial site could increase adverse events and unintended consequences; these issues can be rectified quickly if identified early during a trial and reported to those responsible for overseeing it.
Although monitoring is recognized, there is limited guidance available to those conducting clinical trial monitoring. This may be in part due to many sources describing different aspects of monitoring in varied and accessible language. To address this, the MRC-NIHR TMRP DQM has taken material from relevant sources and combined it into principles of monitoring that were endorsed by 86% of those attending UK national academic clinical trial monitoring meetings; they serve as the foundation upon which more detailed guidance can be built upon.
Develop more comprehensive monitoring guidelines will assist in clarifying the purpose of monitoring for those involved with trial policies and monitoring activities, making their tools for monitoring more easily communicated.
Monitoring should include an on-site visit at each trial site to confirm that all queries have been resolved, documents related to the trial have been returned, and its final report is accurate.
Standardised monitoring could make a dramatic impactful statement about future trials’ success, facilitating better coordination and communication between trial participants, encouraging greater rigor in testing methods, and increasing likelihood that future trials are safe for participants. It requires effort from many groups (trial funders, investigators and trial managers) in order to be implemented successfully; so time must pass before its realization becomes reality.
Reporting
Clinical trials play a critical role in medical science, offering new treatments and medications. But managing clinical trials is also an enormously complex undertaking, necessitating a coordinated system of processes and systems tailored specifically for each trial’s investigators and subject populations. As such, they require an expert team consisting of the Chief Investigator, trial manager, data manager, statistical programmer, statistician as well as technical administrative support staff – as well as any applicable support staff to oversee these endeavors successfully.
Many trials utilize a clinical trial management system (CTMS), providing a central repository of information accessible to the entire trial team. CTMS facilitates data transfer and reconciliation for efficient monitoring activities to ensure compliance with good clinical practice (GCP), while also providing executive management with easy access to high-level dashboard information.
CTMSs are particularly beneficial when conducting trials that include multiple sites and participants. A CTMS provides a central platform to manage data collection, analysis and reporting – including at the program, clinical trial or individual site levels – while creating different outputs tailored for specific audiences such as listing data sets or graphic reports.
Data drives scientific results and their interpretation, so its quality from clinical trials is absolutely crucial to their success. Publications in peer-reviewed journals typically only cover a subset of analyzable data sets while researchers often conduct additional exploratory and post hoc analyses not specified in their SAP.
Trial managers must maintain open lines of communication with investigators. Regular updates on progress must be provided, along with tailored feedback that satisfies each investigator’s interests – this will promote positive perceptions of the trial while encouraging participation by investigators and creating buy-in. Furthermore, trial managers should provide timely support in case of problems as documented through standard operating procedures.
Decision-Making
Clinical trial management encompasses numerous functions. This usually requires collaboration among researchers and clinical staff on the trial team; thus it is crucial that each member understand their roles within its success. Assuring all aspects of a trial are attended to expeditiously and any issues or concerns that arise are quickly addressed is key in providing those involved with the best support and advice available to them. The ideal trial team should depend on the needs of each trial, but may typically include: A Trial Manager; Clinical Statistician; Clinical Programmer and Data Manager. Also included could be data clerks, administrative staff and any trial-specific staff as necessary.
Establishing an effective project management plan is vital to any successful trial, with clearly-outlined roles for all participants as well as arrangements to service both a steering committee and independent data monitoring committee. Regular updates to this document should take account of any changes in the trial as it progresses as well as ensure sufficient resources to complete it on schedule. Risk evaluation, tailored quality assurance management systems, real-time monitoring of key parameters are all integral parts of ensuring its success, making funding applications increasingly dependent on these essential measures for success.
Maintaining strong lines of communication among those performing tasks is the cornerstone of effective trial management, and making sure activities are documented to allow auditors/inspectors to reconstruct the trial process is critical to its success. Doing this also demonstrates the trial is taking account of all involved – an essential element of an ethical code as it shows all parties involved are being given their due consideration.
There is an urgent need for those planning and conducting trials to have access to reliable expertise and published standards of trial management (conduct). Multiple organizations including the UK Trial Managers Network have taken steps toward this end; now is also an ideal opportunity for other trial managers to join these efforts.