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What happens in the six months before a trial is just as important as what happens during the trial.
Choosing the optimal study design in a drug development plan requires a high level of experience in the relevant indications, the medical environment, and regulatory requirements. It is also vital for the researchers ethical responsibility and the commercial success of a drug. But expertise in project and logistics management is just as important to the success of a clinical trialand it is often taken for granted. Multicenter trials, and those that are also multinational, especially require extensive planning and management.
Planning is a process that requires management. The reason that most projects fail to meet their timelines is that planning is not managed thoroughly enough. The planning process deserves attention and monitoring in parallel with the other components of clinical research.
Once the need and objectives for a trial are defined, proper planning over a period of at least six months is vital to ensure a successful study management. Planning should equally emphasize ideal scenarios, contingency plans, and risk management at all key steps in the form of what if analyses.Decisions on consequences and solutions for different potential outcomes should be planned up front, not made at the last minute or in crisis situations.
Although perceived as minutious and cumbersome, planning can be organized and structured in a clear, simplified mode. Planning can also be understood as an investment with quantified and specific returns.
The following approach can help optimize the preparation of a multinational multicenter trial. For each month leading up to the enrollment of the first subject, we suggest the key activities outlined in the accompanying checklist for day-to-day use of 100 Points to Consider for Effective Study Preparation.
6 months ahead: Study design
Study planning is only one component of an overall successful drug development plan. Whenever possible, key elements of the respective study designs should preexist and be kept current in a master development plan.
Not all elements can be or need to be finalized at that time, but they all need to be under control for content and timelines, with assigned accountabilities within the core project team.
Thorough evaluation of expert opinions, current literature, and the availability of sufficient pharmacology, toxicology, and clinical data help to achieve consensus among all relevant parties involved regarding study objective, rationale, and scientific methodology. This should include evaluation of expert opinions; current literature; and availability of sufficient pharmacology, toxicology, and clinical data.
Completing this first step should in turn trigger operational planning timelines for targeted final evaluations; availability of study drugs, comparators, and placebo; and selection of countries of interest for study execution.
To prevent delays and cost increases at later stages, the following key risks need to be assessed and options for solutions need to be worked out:
5 months ahead: Feasibility
Although design and strategies are essential, the success of a clinical trial depends on the ability to plan. This includes validation of availability of subjects, and also availability of investigators and study management resources (for example, vendors and geographic deployment of internal resources).
The project team should be identified for all core functions involved.
Key aspects of drug supply management such as labeling and importation requirements, manufacturing, and packaging and distribution plans should be defined and initiated at this stage.
Risks can be reduced by ensuring:
4 months ahead: Vendors and logistics
This plan proposal assumes that generic toolsmaster agreements and contract templatesare already in place for core standard terms for vendors, investigators, and grant management. It is further assumed that a contract research organization (CRO) is not intended to participate in the early study planning phase.
Based on the results of the feasibility study, sites should be selected, the study discussed with investigators, and the terms and conditions negotiated with prequalified sites. A series of operational documents should be prepared: operational sections of protocol, standard informed consent, case report form (CRF), updated investigator brochure, and information and advertisement materials.
An investigator meeting(s) and all related aspects should also be prepared. The importance of a well-thought-through overall communication plan, which defines in detail the structure of the project team, including vendors, and the lines and ways of communication within the project team and with investigators, ethics committees, and regulatory authorities, is often overlooked and should be designed and deployed. This communication plan is critical to success.
At this stage, vendor management should be proceeding well, the budgetary options are ready in case recruitment issues arise, and local standards should be known and in place for study initiation.
3 months ahead: Local applications
Local readiness now needs to be achieved, including:
In parallel, specific plans for data management and quality assurance need to be prepared.At this time in the planning process, resources must be reliably assigned in all operational locations, ensuring a timely study start as well as continuous and updated knowledge of local requirements. Ideally, letters of intent with vendors should be agreed upon.
2 months ahead: CRF and monitoring
Monitoring and data management conventions should be checked for consistency and integrated into training packages and the statistical plan.
The CRF design should be finalized and action taken to work out printing order and logistics for shipment.
Database design, including safety rules, should be put in place and validated.
A quality control check of processes, procedures, and resources should now be conducted so that alterations or corrections can be made before the study starts.
1 month ahead: Training and site management
The project team, vendors, investigators, and study site personnel need an extensive introduction to, and training in, the study details. Suitable tools for accomplishing that include investigators meetings with all parties involved, study initiation visits, project team kickoff meetings, and the use of media tools as appropriate.
After a final check of the availability of all required study prerequisites, subject recruitment can start.
Points to remember
Although everyone seems able to find the time and money to redo, finding the time and budget to plan properly seems very rare. Planning, however, is a key function, not just an intuitive process that scientific professionals can handle spontaneously.
Constant evaluation of operational feasibility and adaptation to project reality is critical. Use of standards that are already in place simplifies work and shortens timelines.
Regularly controlled and proactively managed quality ensures cost containment of projects. Although this concept is routinely used in manufacturing and other industrial sectors, clinical research still has room for improvement.
Finally, communication is key and is too often overlooked.
SIDEBAR: 100 Points to Consider for Effective Study Preparation6 months ahead