This toolkit provides best practices to implement an investigator-initiated clinical research trial in more than one site across the Cleveland CTSC (Cleveland Clinic, MetroHealth, University Hospitals) to enhance rapid study start-up.
Please note that the best practices:
- Are not all-inclusive
- Provide a general roadmap to help the investigator navigate different sites’ research processes
Are you ready to begin your study?
The following four steps must be completed prior to engaging study start-up across the CTSC:
- Funded, finalized protocol is available with draft Lab Manual (if applicable)
- Principal Investigator has selected collaborative site PIs
- PI and site PIs are committed to study start-up less than or equal to 90 days
- Preliminary budget has been drafted and reviewed with each site and legal agreements for collaboration are in negotiation
For the above to be true, it means you’ve already completed/finalized (as applicable):
- Sample size assessment, feasibility assessment and statistical analysis plan/clinical data management plan at each selected site with REDCap database ready to move to production;
- Identifying site PIs & responsibilities, and defining deliverables/organizational structure;
- Protocol, including recruitment plan for each site, investigator’s brochure, pharmacy manual, MOP, and informed consent document(s);
- DSMB Charter/Monitoring plan;
- Submitted FDA IND/IDE regulatory applications
And are in the process of finalizing negotiations of (as applicable):
- Site-specific budgets
- Site-specific legal documents, including invoicing process
- Start date for release of funds to support site-specific research activities
Resources Available for Pre-implementation and Implementation (by CTSC Site)
Each of the Cleveland CTSC sites have similar resources available to support your clinical research. Please speak with representatives at each site to include fees in site-specific budgets for applicable support services.
To request services across the CTSC, use SPARCRequest.
Site-specific resources can be found on individual Clinical Research Unit websites:
|Cleveland Clinic||MetroHealth||University Hospitals|
|Research administration for study budget development for each local site||✓||✓||✓|
|Site-specific study feasibility assessment (e.g. population, budget, resources)||✓||✓||✓|
Clinical Research Unit (CRU): research-dedicated facilities and equipment
|Project management services||✓||✓||✓|
|Research Participant Recruitment services||✓||✓||✓|
Regulatory support services
Research Study Coordinator services includes the availability of the following:
|Research Compliance education and support||✓||✓||✓|
|Institutional Review Board including a Reliant Review IRB Specialist||✓||✓||✓|
Research Finance Services including creation of coverage analysis
|Investigational Drug Services including Pharmacy Services||✓||✓||✓|
|Clinical lab analyses for research lab draws||✓||✓||✓|
Site-specific Research Roadmaps and Contacts
Starting up a study across multiple, diverse sites can be daunting for even the most experienced researcher.
The Cleveland Clinic, MetroHealth and University Hospitals collaborate through the CTSC Hub Research Capacity (HRC) core to support rapid study start-up across more than one CTSC site. It doesn’t eliminate the steps at each site, but your institution’s HRC representatives will help you and your site PIs navigate and access the resources you need. The sites have agreed on similar start-up steps and provide contacts.
Please see the downloadable spreadsheets with institution-specific contacts for study start-up:
Best Practices for Local Multi-site Study Start-up
See Step 1: Study Start-up Checklist above
See Step 3: Site-Specific Contact Information above
If a study is recruiting human subjects from a site or uses a site’s property or services, and the study’s PI is not a member of that site’s faculty, then a site-specific investigator, who is a member of the site’s faculty, is needed to collaborate to manage study implementation logistics and protect that site’s human subjects and other resources. The site specific investigator will be listed as that site’s PI, even if the site is not the IRB of Record. Why is this important?
Each site needs a representative to be responsible and accountable for activities occurring on the site. This may include:
- Budget development & finalization/contract review/coverage analysis,
- IRB review submissions and associated human subject protection processes, management and protection of PHI,
- use and reimbursement of the site’s services and resources, including management of clinical research expense invoicing, or
- PI responsibilities associated with management of the clinical protocol responsibilities and team from study start-up through study closure at your site.
|PI’s selecting site-specific PI’s should do so during protocol development (before study implementation start-up activities) to ensure the site has sufficient sample population for recruitment, organizational infrastructure to support the study, and the site PI is sufficiently knowledgeable and engaged to help the lead PI create a budget for the site and support a rapid study start-up process.|
|If you’ve never been a lead or site-specific PI before, gain a better understanding of the role and responsibilities. Seek guidance from your Clinical Research office. They’re happy to help ensure your first experience is a positive one.|
Each site has a mandatory process for assessing the feasibility of implementing your protocol at that site and sets minimum standards for the feasibility assessment process but usually with an emphasis on recruitment, site logistics, and financial resources for implementation and completion of the study. Each site may have different standards for assessing feasibility.
You should be prepared to provide:
- Inclusion and exclusion criteria (preferably in the form of ICD or CPT codes)
- Drug & Device information
Feasibility assessment may be staged based on query of EMR to assess patient population size. Best practice standards for measuring recruitment feasibility are:
- Feasible = recruitment query returns ≥ 5 times Anticipated Accrual at Local Site.
- Not feasible = recruitment query returns < 5 times Anticipated Accrual at Local Site
- Exempt* = recruitment query returns < 5 times Anticipated Accrual at Local Site.
*Due to special considerations including rare disease or specific patient population that cannot be queried, protocol exemptions may be given.
Contact a site’s feasibility assessment team contact to learn more about the feasibility assessment process at that site.
One site budget isn’t necessarily suitable for all sites. Because each site may (or may not) have its own negotiated DHHS rate for investigator-initiated research, pricing, especially for patient care fees, will differ from site to site. The same with salaries and fringe benefits. So each site budget needs to be developed and negotiated individually. This takes time.
The lead PI is responsible for the overall financial health of the research project.
Each site PI is responsible for the overall financial health of the project at their site and avoiding grant deficits. The site PI is responsible for knowing the study’s contractual and payment terms and ensuring that the site’s grant accounting team and Research Finance Services/Coverage analysis team receive timely communication of completion of patient visits and milestones to facilitate timely and accurate invoicing.
The site PI will work with Research Finance Services to complete and approve the site’s coverage analysis and overall study budget to ensure accurate reimbursement of:
- Fixed costs/invoiceable fees
- Patient care invoiceable fees
- Investigational drug or other ancillary service fees
- Salaries and fringe benefits
- Contracted milestone invoicing
- Indirect costs
As applicable, this may also require data input into the site’s clinical trial management system to assist in study tracking invoicing and reporting.
|Allow plenty of time for budget and contract approval. As described in other areas of this toolkit, start your budget and contract activities before you are ready to submit to the IRB for review.|
Take advantage of the reliance relationships between IRBs at Cleveland CTSC sites to streamline the IRB review process! Through formal reliance agreements between the CTSC sites, Reliant Review is a process allowing one institution to be the reviewing “IRB of Record” and the other sites will “rely” on the IRB of Record to review, approve, and monitor the study through study closure. This will streamline the IRB process throughout the life of the study, while still providing strong protection of human subjects.
Consult with your local IRB administration staff to determine if the IRB is willing to act as the IRB of record or a relying site. Each will have different responsibilities and you - as either the IRB of Record PI or the Relying IRB PI – will have associated responsibilities.
|Read your institution's IRB Reliant Review SOP.|
|Determine which site will be the IRB of Record and which site(s) will rely.|
|Consult early and often with your site's IRB Reliant Review team. They are a wealth of information and will work, on your behalf, with the other sites' IRB Reliant Review teams to support human subject protections for your multi-site study.|
Studies involving the use of standard of care or unapproved, investigational drugs or devices will require additional support from your institution’s research office(s).
- Does use of the drug or device require an IND or IDE?
- For drugs or devices, what is the distribution plan between sites and tracking of administration/use?
- For drugs, does the investigational pharmacy need to be involved for storage, distribution, assisting in development of physician orders?
- Does the study involve patient randomization, and if so, what is your plan and who is responsible for randomizing? Is randomization double-blinded?
- For drugs or devices, will third party-payors pay for administration/implant charges?
|Involve your Research Finance Service teams, at each site, early in the budget development process.|
See Step 1: Study Start-up Checklist above
The CTSC is dedicated to engaging underrepresented populations – like those distinguished by language, disability, condition, risk, culture, geographic location/dispersion, socioeconomic status, race or ethnicity – at all levels of research and in all of our programs. Your site has Participant Recruitment Specialists ready to provide consultations to meet your recruitment goals.
Your site has Participant Recruitment Specialists ready to provide consultations to meet your recruitment goals. They can help you access institutional expertise in recruiting special populations. They can assist in the development of a recruitment plan and guide you in creating advertising, social media and hospital network or community recruitment events.
REDCap (Research Electronic Data Capture) is a secure web platform used to build and manage online surveys and projects. It may be used to collect almost any type of data, but is intended to support online or offline data capture for research studies and operations. At your institution, REDCap is managed as a HIPAA-compliant platform.
As an employee of your institution, you have free, unlimited access to REDCap as a benefit of the CTSC. This easy-to-use database allows you to create customized complex data-capture projects, associated surveys and data queries, and record dashboards.
At each CTSC site, through the Clinical Research Unit, you have access to free REDCap consultation services to help you build and refine your projects. Once created, you can share your project’s data dictionary with your multisite research partners to create clinical research electronic case report forms to standardize and enhance data quality and regulatory compliance.
Each CTSC site has also enabled REDCap’s research E-consent module.
Check your institutions policies and procedures for more information on access and data sharing.
If you are requesting services from more than one site, you may want to begin by placing your request through SPARCRequest, the CTSC’s service catalog. Submitting a service request initiates a consult with a site’s services. But you should be prepared to submit additional information to each site through site-specific request forms.