Abstract: Activating a clinical research project at an academic medical center requires significant planning and effort from study teams. Research sponsors often have difficulty understanding any process lacking in consistency and transparency and so start-up becomes a barrier to study enrollment. This article breaks down such barriers by advocating specific project management and communication tools and techniques that accelerate the study start-up process without sacrificing quality.
Declaring Goals for Study Start-up
Study start-up is the project calibration stage of any clinical research project. There are many rules, regulations, and processes to be followed when conducting clinical research, and so it is essential to first have a strategy for successful completion of a project.
Table 1 highlights the goals for study start-up. From the onset, it is necessary for stakeholders to have a clear understanding of the institutional process as well as the more local program-specific process for study start-up. Individual program areas have their own priorities, so even within the same academic medical center, the start-up can take on a variety of forms, often for good reason. If it is difficult to create a one-size-fits-all model, it is then necessary to cultivate a flexible predictability via organizational consensus, staff training and education, and clear and regular communication with sponsors. Striving to meet sponsor expectations while executing organizational mandates are key objectives during start-up.
Identifying Barriers to Study Start-up
Executing on institutional mandates and minimizing the duration of study start-up are not mutually exclusive goals, but the interplay is often complicated. Institutional mandates account for sound legal, safety, and financial considerations. Study teams must be empowered to promote and act on these goals while also advocating for the priorities of clinical investigators and sponsors who wish to partner on a study.
There can be a lack of predictability in study start-up (Table 2). Portfolio complexity can be a barrier to site activation. For example, UCLA Pediatrics has about a dozen medical sub-specialty divisions conducting clinical research at a given time: clinical trials, retrospective analyses, biorepositories, and longitudinal and non-interventional studies of rare diseases, etc. These divisions can be even further sub-specialized down to the investigator portfolio level.
Perhaps understandably then, there is a great deal of variety in the types of sponsors and research in this space. At a given time, about 50% of our projects are likely to be industry-sponsored, 30-35% non-profit sponsored, and 15-20% collaborative (industry and non-profit involvement). We must be intelligent in the way that we manage this because complexity readily travels into the legal, safety, finance, and operations arenas.
At UCLA, the sponsor types and project types dictate specialized contracting unit workflows. To avoid delays in start-up, knowing which office to engage for support in negotiation of a sponsored agreement is essential.
The Office of Contracts and Grants Administration (OCGA)2 manages all federally-funded research awards as well as research awards funded by non-profit organizations or the state. This office supports the university at large, not only the health sciences.
UCLA also supports clinical research partnerships with private industry. There are two specialized contracting units for these partnerships:
Clinical Trials Contracts and Strategic Relations (CTC&SR)3 deals in clinical trial research awards for the investigation of medical devices, biologics, and investigational drugs. This office supports the health sciences specifically.
The Technology Development Group4 supports industry-sponsored clinical research awards that are not clinical trials. Like OCGA, this office supports the university at large, not only the health sciences.
In instances of for-profit and non-profit partnership, the general process guidelines are modified to suit the needs of the project.
Finance and Operations
Gaining approvals from the variety of ancillary medical services necessary to accommodate all protocol requirements can be another barrier to completing start-up. Upon receiving an application and completing a service analysis, each support unit produces its own budget that will be included in the sponsor’s overall project budget.
A non-exhaustive list of these ancillary service units includes the investigational pharmacy, the clinical and translational research center, clinical radiology, clinical pathology, anesthesia, pheresis and stem cell units, nuclear medicine, ophthalmology, a functional assessment lab, highly specialized core laboratories5, a medical device formulary, and a gene and cell therapy manufacturing facility.6
When sponsor clarification is required, it can be challenging for teams to pull together all of the necessary ancillary service agreements in a timely fashion, but it is essential to the financial and operational success of the project.
Putting aside the well-known and valuable role of medical IRBs in clinical research, and considering for a moment a specific aspect of the process as it relates to the whole, what may not be obvious to sponsors, and which may not be true at all academic medical centers, is the role that the IRB plays in holding its approval back until other important safety or scientific approvals are shown to be in place.
At UCLA, a non-exhaustive list of these other approvals includes committees for internal scientific peer review; medical radiation safety, biosafety, and/or a central IRB approval. If our IRB has not issued its local approval, it may very well intend to do so once these other committees provide theirs. If study teams do not make this distinction clear to sponsors or to colleagues within the organization, the issue may be confused and complicate the overall outlook for start-up at the site.
Ultimately, UCLA requires legal, financial, and safety approvals from study teams in order to undertake a sponsored clinical research study. Project specifics often mandate the path that a project takes, and it is the site’s responsibility to guide sponsors along the selected path.
Tools and Techniques for Effective Study Start-up
Since infrastructure and priorities naturally vary from one organization to the next, in most cases the following recommendations are purposefully general to allow for easy adoption and modification to the specific needs of individuals, programs, and organizations.
Organizations recognizing value in an independent project management role may find more success in this landscape than those organizations that do not. This is because the many legal, safety, financial, and operational concerns in start-up must be kept on track to meet start-up goals, and they do not cease with site activation. If existing study team members do not have the ability to do project management because they are tending to other essential responsibilities, like coordinating patient visits for active studies, reporting data to sponsors, and maintaining the regulatory body of ongoing studies, etc., then the site might consider appointing a dedicated project manager to provide effort in this space.
UCLA Pediatrics uses a formulated Microsoft Excel spreadsheet to track administrative and scientific tasks required for study start-up. In addition to providing a reliable space to track our process data, we also have the local flexibility to modify and adjust to the real-time environment. We use this approach to track, among other things, the average length of time that it takes to activate a project in our portfolio. Knowing about how long study start-up takes makes it easier to manage expectations and plan for each new project sent down a similar path. We are also able to measure and target slowdowns in any of the major start-up pathways.
The more rapid flow of information is essential to start-up. UCLA made a strategic decision to leverage its existing and familiar webIRB system as the front end of a multi-program research continuum called ResearchConnect.7 The webIRB interfaces with the CTMS, which in turn interfaces with the electronic health record. This fundamentally restructured the study activation pathway from the previous disconnected IRB, finance, and contracting reviews into a parallel review model initiated at the point of webIRB submission. Now legal, safety, and financial reviews happen in parallel, and uniform information is disseminated more broadly to stakeholders, aiming to shorten the period between submissions and approvals to the greatest extent possible without sacrificing quality.
Whether using telephone, email, or in-person meetings, or using all three, regular communication and periodic status check-ins have an uncanny way of advancing a project toward approval.
The Single Application Method
Committee applications take all shapes: hard copy forms, emails, online applications, etc. It is necessary to prospectively identify all required study approvals and prepare the applications at once. Use a major deadline for a target, perhaps the IRB’s deadline. Submit all required applications on the same day to establish a uniform starting point. This approach lends predictability to the work: someone will not need to remember to get something else in later when other approvals may depend on it. One will most likely have their minor approvals in hand when they need to provide them for major approvals. This approach brings alignment and quiet to an unruly information exchange.
Create a Checkpoint
About a month after submission (or sooner if to needed), plan to meet with project stakeholders to ensure completion of initial tasks and to discuss the final steps to be taken to complete start-up. At UCLA Pediatrics, this meeting has taken the form of a finance committee meeting in which we gather ancillary service approvals with cost estimates and present the budget for PI review. We also take it as an opportunity to remind ourselves that we must push ahead with energy to reach the finish line.
Completion of Start-up
Tying up loose ends is easier said than done. As one nears the end of the start-up period, one should not be ashamed to over communicate the team’s desire to complete the agreement. Involve all necessary parties in a single conversation so that nothing is missed. Keep in mind that we do not do clinical research because start-up is a grand challenge; we do start-up so that we may do clinical research.
Declaring the goals for study start-up at the onset is the first step toward clinical trial success, but then, execution and tenacious follow-through are key elements of reaching goals. Study teams should actively engage stakeholders within the organization, and the sponsor, to ensure understanding of the study-specific needs and organizational requirements. Study teams should also employ tools and techniques to keep all parties engaged as necessary throughout study start-up so as to reach an agreement as quickly as possible. One success leads to another!
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Goals for Study Start-Up
- Meeting sponsor expectations
- Executing on institutional mandates
- Stakeholder understanding of the process
- Identifying and overcoming project complexities
Barriers to Study Start-Up
- Specialization vs. Standardization
- Contracting according to project types and sponsor types
- Specialized ancillary support services and budgeting
- Diffused safety and scientific committee approvals
Tools and Techniques for Effective Study Start-Up
- Program trackers
- Software applications
- “Single application” method