Site Management

Studies often fail to achieve their goals because of inadequate enrolment or poor compliance. Effective site management is therefore a cornerstone of every successful research program. At Syreon, we draw on our global experience to ensure that the most committed and capable investigators are recruited, trained and supported throughout the study to ensure enrolment and performance goals are met. Detailed procedures ensure monitoring of site performance and withdrawal of non-performing or non-compliant Investigators to avoid delays in database lock or analytical deadlines.

ClinStream™ technology facilitates on-line site training and certification, study education and GCP training to speed IRB submission and approval, and to facilitate patient selection, enrolment and randomization. Targeted time-and-motion studies conducted at selected academic and community sites can identify the real costs of research and care, and quickly generate a realistic and verifiable budget for site reimbursement. Finally, a comprehensive compliance program with continuous education and support measures helps to maintain study momentum and ensure satisfactory completion of the trial on time and within budget.

Contact, Evaluation and Set-up

Syreon works closely with study sponsors to identify and recruit active and committed investigators at academic institutions and community locations via a rigorous and proven process for recruitment and training.

>  Contact: Syreon draws on its large international database of clinical sites, distributes trial invitations to all potential investigators, and confirms receipt and response to assess investigator interest and willingness to participate.

>  Evaluation: Potential sites complete a detailed survey of current clinical activity, research experience and personnel support to assess the ability to meet the study requirements and to determine whether a site visit is required to assess qualifications and capabilities.

>  Set-up: Syreon then prepares and distributes all study documents, correspondence, recruitment and training materials including the study agreement, documentation for central IRB approval (as required for community sites), study supplies (forms, consent templates, instructions for data submission) and communicates actively with the sites to review instructions and ensure that all procedures are completed prior to study commencement.

Ethics Review and Approval

Syreon supports academic sites with submission of applications to their local Institutional Review Board by providing Consent Form templates and other necessary documents which may be customized to meet local requirements.

Community sites, more common in Phase IV trials, normally require central IRB review, and Syreon interacts with many highly respected national and international clinical review boards for this purpose. IRB Services based out of Aurora, Ontario is one such agency which is widely employed for Canadian studies. IRB Services is a fully accredited central IRB meeting all regulations and requirements for the conduct of ethical review services and board membership.

Site Training

Syreon provides comprehensive training for site personnel, study monitors and clients. This is normally performed remotely using ClinStream™ technology to maximize efficiency and economy, but personal training at the study launch meeting is available upon request. Training is customized to the level of user computer competence, and is scheduled at a time convenient for study site personnel. Training covers all aspects of study operation, including patient screening and registration, and completion, submission and correction of all data forms.

Each site is issued a first set of "training data" through the web site, and guided to enter the data, make corrections, trigger on-line electronic checks and submit updates. Site personnel are trained to run on-line reports on the status of queries, and can view cumulative data summaries for each or all of their patients over time. Site personnel are required to enter a second set of training data without assistance, a process requiring an additional 15 to 30 minutes. The Syreon coordinator monitors the receipt of the data, reviews it for accuracy, and then advises the site whether the data was submitted properly. If training is successfully completed, the site coordinator receives a Certificate of Competence and the process (date and time of training, who was involved, a copy of the sample data set etc.) is documented and stored for audit purposes. The user's password is then switched from "training" to "active" status (change is made on the back-end, user's ID and password remains the same for simplicity purposes).

Study Support and Help Desk

Syreon provides continuous support to all study personnel throughout the trial to guarantee a rapid learning curve and improve protocol adherence. Project managers maintain close contact with sites for issues pertaining to study conduct, while data managers handle data queries and verification. Detailed data entry and operational support materials are provided on the ClinStream™ study site, and frequently asked questions are updated on a regular basis. Syreon can also provide a 1-800 Help Desk through which and experienced project manager or medical advisor can respond to queries from investigators and subjects.

Investigator Agreements

Syreon study agreement templates define the responsibilities of all parties, including role of the Investigator in protocol adherence and data submission. Syreon provides this, or the sponsor's own Agreement, to all Investigators for review, negotiation and sign-off prior to study commencement, and returns all signed agreements to the sponsor for sign-off. Issues requiring legal advice are normally dealt with by the sponsor's legal counsel or Syreon will provide support from its external legal counsel if required.

Investigational Product Shipping and Tracking

Syreon manages the distribution, tracking and documentation of investigational product to and from investigational sites for its studies. Research associates collaborate with the sponsor's inventory control (drug distribution) center to ensure accurate contact information for drug shipment and to confirm receipt by the designate at each site. At academic centers this is normally the pharmacy, while in the community, the shipment normally goes directly to the physician's office where it must be securely stored. Syreon provides drug accountability forms for completion when the study drug is provided to each subject, along with instructions and support to track compliance and return unused medication when subjects discontinue therapy prematurely. Study monitors perform drug reconciliation at a routine visits and are responsible for the return/destruction of study medication at the site close out visit.

Financial Management

Syreon employs an objective costing method to determine site participation costs and reimbursement rates.

>  Site budgets: Syreon draws on its cumulative experience of multiphase clinical trials and that of the study sponsor, combined with a focussed time and motion study in representative sites, to establish direct and pass-through costs including overhead, protocol review, IRB submission, study training, laboratory fees, patient recruitment, subject consent and other procedures that are not part of routine practice. This is reviewed and approved by the study sponsor and participating sites to formalize the study reimbursement rate.

>  Investigator Payments: Syreon establishes a separate account for investigator payments for each study. The investigator payment schedule is designed to include an up front payment followed by sequential payment based on the enrolment of subjects and receipt of complete and accurate data over the study period. Syreon invoices the study sponsor based on the projected payments for each quarter, disburses the funds as agreed over this period, and provides each site with a statement which clearly defines the specifics of each payment. Sponsors receive a detailed monthly accounting statement showing the disbursement of funds to each investigative site and an updated balance for budgeting purposes.

>  Pass-Through Accounts: Syreon manages pass-through accounts to cover indirect expenses related to the purchase of third party services required for the conduct of the study. These are invoiced to the Sponsor based on quarterly projections of expenditures over time, and funds are used as required over the period to cover the cost of pass-through expenses over time. Regular accountability statements are provided to the Sponsor to enable close monitoring of pass-through expenditures.