Establishing clear research questions, reducing variation, randomizing and stratifying, blinding, placebos/shams, and selecting a control group are fundamental clinical trial design principles that reduce the chance that unmeasured bias or confounding will mask treatment effects.
Tracking accruals allows academic medical centers and Clinical and Translational Science Awards hubs to document study milestones to industry sponsors, recover contractual earned revenue, and keep up with invoices and reimbursement. Unfortunately, accessing accrual information requires reconciling data across disparate systems.
Designing a Trial
Starting a clinical trial can be an arduous endeavor, yet getting it underway as quickly as possible is essential to its success. A detailed plan should outline who needs to do what and by when along with regular progress checks. A strategy should also be devised for managing risks associated with failure as part of this plan.
First, create a clear therapeutic question and check that its answer has not already been provided by previous research studies. Next, plan the trial design by determining target populations to study and endpoints for evaluation; selecting control groups; blinding; as well as planning interim analyses.
Trials can only be successful if they meet the goals and regulators’ objectives, which is why it is critical to form a strong project management team from its inception. This should include assigning responsibility for essential processes like recruitment monitoring, data management, raising project profile (promotion), and safety reporting and analysis per an approved project plan.
At every step, collaborative groups should feel that they own their trials. This can be accomplished by including them from protocol creation through recruitment and publication of results. Furthermore, credit should be divided fairly among participants who contributed, including any joint authorship arrangements that may arise as a result.
Finaly, the trial must have enough resources available to be completed on time and within budget. This requires having sufficient staff available, an attainable timeline for completion, and an efficient statistical analysis plan in place to evaluate results. Furthermore, any potential issues should be identified and dealt with promptly so as to reduce the risk of its failure.
Right-Sizing a Trial
Step two of planning and designing a clinical trial entails selecting an adequate sample size, including determining minimum patient enrollment requirements as well as ensuring there is sufficient variation among population samples. An insufficient or excessively large trial could have detrimental consequences on its outcome, so researchers must calculate an adequate size before beginning.
Planning is also key when it comes to overseeing a trial efficiently and effectively, including understanding how best to identify potential issues quickly, prevent them from occurring again, and resolve them swiftly. For this, an efficient process automation platform with access to multiple data sources, essential performance metrics, real-time reporting features, and increased visibility helps reduce on-site visits needed for monitoring purposes while increasing compliance assurance thereby saving costs and improving compliance assurance.
Poorly managed clinical trials can result in slow or incomplete studies, delaying regulatory approval of lifesaving drugs from making an early market debut. To avoid costly mistakes, consider adopting an all-encompassing clinical trial management system with streamlined processes for everything from startup through monitoring and reporting – providing end-to-end visibility without delays and inefficiencies along the way.
Finally, a trial manager must create open lines of communication with all stakeholders involved to ensure all team members are on the same page and reduce miscommunication and improve collaboration. Furthermore, an ideal solution should enable secure data sharing through a unified data fabric to expedite faster decisions.
As well as providing all staff with access to up-to-date and accurate information, project managers must also address how credit for the trial will be distributed. Individuals who contributed towards its success must receive due recognition based on individual contributions; collaborative authorship policies provide this option, or professional training opportunities can promote career structures for trial managers who wish to enter this profession.
Identifying Trial Milestones
Trial milestones must be clearly understood and communicated to ensure progress against plans is being met, keeping trials on schedule. Establishing milestones helps alleviate uncertainty and increase communication, ultimately shortening trial completion timeframes. Milestones could include key dates such as commencing recruitment or finishing an interim analysis target date, but they could also include tasks like document submission for regulatory submissions or creating a database.
Establishing clear processes both inside and outside the office, for managing communications and human resources is central to clinical trial management. Trial managers spend considerable time on this aspect, with many trials having several people involved in coordinating and executing the work; this may involve setting up regular communication channels via email, phone calls, and face-to-face meetings.
Initial investments for trial setup activities require significant capital, yet can pay dividends during maintenance and closeout stages of a trial, where checks on data integrity, mitigating risks, and preparing publications and archives (Figure 5.1) need to be conducted smoothly.
Trials that require ongoing maintenance must be monitored closely to ensure deliverables meet their schedule and budget, and to mitigate risks. Delays in recruiting participants could threaten timelines or budget, so regular communication with potential participants and clinicians during recruitment is vital to its success. Furthermore, its scope must also be closely observed so as not to create “scope creep”, compromising delivery dates or results quality.
Closeout must be monitored carefully to ensure that regulatory reports are submitted and published on time, samples are safely stored, transported onward, or destroyed according to agreed requirements, and any outstanding issues are resolved in time. In this stage it’s also essential that paperwork be ready for auditing purposes.
Trial closure is essential to building public trust in drugs and vaccines. More and more researchers are calling for standardized trial management methods to be established – this would involve funders, trialists, trial managers and others coming together to create one approach for running all trials to produce evidence useful in decision-making processes.
An effective clinical trial requires significant resources and time, and accrual performance should be monitored at critical points throughout its process, such as initial patient enrollment, expected completion date of trial or projected accrual period for particular study. Assessing accrual metrics regularly enables researchers and leadership to quickly recognize obstacles that prevent them from reaching target accrual rates and respond accordingly.
To facilitate evaluation, several methodologies have been created to track and assess a clinical trial’s progress towards an accrual milestone. Many of these methodologies use predictive models to estimate participant arrival into studies; conditional models (which assume each site enrolls participants according to a known probability distribution) and Poisson models (which allow time-dependent probabilities calculations) have proved especially helpful tools in estimating how many participants will be needed for multicenter randomized clinical trials.
Other methodologies use actual data from sites to measure progress toward meeting enrollment goals. For instance, the National Cancer Institute Community Cancer Centers Program (NCCCP) has designed a web-based system for collecting screening efforts at research sites; seven NCCCP sites tracked their performance using this tool during an open accrual period for chronic lymphocytic leukemia trials during this recent study.
This study’s results demonstrated that for most trials, actual recruitment performance matched predictions based on anticipated accrual models. A small number of trials, however, experienced major recruitment challenges early in their trial that prevented them from reaching their targeted recruitment rate and necessitated additional predictors to identify enrollment barriers early and provide proactive intervention strategies.
As part of any clinical trial, it’s critical to create and implement an efficient monitoring system for recruitment in real-time so any problems can be identified and addressed quickly. Unfortunately, many clinical trials rely on spreadsheets for this tracking, necessitating significant manual effort across teams in order to report accurately on these metrics.