Conduct of Clinical Trials
Recruitment
The main source for recruitment is often the clinic patients of the PI and sub-investigators. There are some tools at Duke that may help with recruitment: D.E.D.U.C.E and DISCERN and Research Match. You must have an account to access DEDUCE and DISCERN. Research match is accessed through DOCR. Please contact the CRU RPM or ARPM for account access. Duke policy does not allow for cold-calling of potential subjects. Someone known to the patient must get assent from the patient to be introduced to the study staff. Recruitment may be enhanced by advertising. All advertising, even a flyer posted in the clinic, must adhere to Duke brand guidelines and be approved by the IRB.
Enrollment
The Duke IRB considers participants enrolled in a study once the consent form is signed. Enrollment is to be documented in MaestroCare. An enrollment log is required by FDA regulation.
A log must be maintained for all subjects who are screened and/or enrolled in the study. The CRC or PI will maintain these logs. These logs may be the same or separate. A sample enrollment log can be found on the DOCR website. Enrollment logs must be kept in password protected computer files on shared network drives having appropriate levels of security as defined by the Duke Medicine Information Security Office. However, it is advised that hard copies of enrollment logs also be maintained for those studies where the sponsor requires faxed enrollment logs (and then only with the release of one identifier that is listed in the subject’s signed consent form). Hard copies of enrollment logs should be stored with other documents and records in locked file cabinets.
From a fiscal perspective, each division is ultimately responsible for monitoring of enrollment status for each study. The CRU Leadership will be responsible for oversight of enrollment trends and aggregate reporting for the CRU.
Screening and enrollment data is reported to the IRB on an annual basis at the time of the annual review (renewal). This report includes numbers of persons approached, number of persons who signed the consent form, number completed, number withdrawn and gender and ethnicity of each person. Documentation of this information on the log will create efficiency at the time it is necessary for the annual report.
Obtaining Informed Consent
The participant’s consent must be obtained before any study procedures can begin. Duke policy does not allow for “cold calling”. All potential subjects must have the study introduced to them by their care provider; someone who is known to them before being approached by the study team. The potential subject must be given ample time to read and understand the consent form, discuss with their family and have their questions answered. The IRB requires the consent process be described in the protocol submission, and the process must be followed for all potential subjects. The consent process should always be documented in the medical and/or research record.
The original consent form is to be kept with the study record. A signed copy of the consent form is to be provided to the participant and another copy sent to Health Information Management to be uploaded to MaestroCare.
The informed consent document and the process by which informed consent is obtained are keys to conducting ethical research. The process of informed consent is ongoing over the entire course of the trial. Only appropriately trained staff members are qualified to obtain consent. Please view the IRB policy pertaining to who may obtain Informed Consent, available on the IRB website.
Classes are available in the Informed Consent process, writing an informed consent, and a workshop for practicing obtaining informed consent. Registration for these classes is through the Learning Management System (LMS).
If you have any questions related to obtaining or documenting informed consent, please contact the Research Practice Manager.
Outpatient Research Appointment Scheduling
All participants who have consented to participate in a study and who have outpatient study clinic visit(s) will be scheduled by the Central Grant Scheduling Team (Research Appointment Hub) or CRC/designee responsible for the study. CRCs or other staff members who schedule research appointments are required to have special MaestroCare research schedule training before scheduling research appointments. For specific research appointment schedule training information, please contact the CRU Research Practice Manager.
Research Billing
Participants enrolled into studies generate three types of research charges:
1) standard of care only; 2) research only; or 3) a combination of standard of care and research. The type of research charge generated is determined based on the approved billing grid.
Research appointments must be appropriately linked to the study timeline for appropriate processing of charges. All study staff must attend research specific MaestroCare training.
Research teams are responsible for regular review of research charges within the MaestroCare system. Several training resources, including on-line trainings, classes and tip sheets are available related to charge review and appropriate distribution of charges.
Charge corrections can be made in MaestroCare. Once the correction has been processed by PRMO, the corrected charge will be available for review.
Some study groups are using Trial Trackers for CRU centralization of financial management. This is a system of spreadsheets designed to monitor the subject related and invoice-able study activity. The trial trackers are created by the FPM prior to study approval. Please contact the CRU leadership for any questions related to the trial trackers.
CRU financial staff will reconcile each charge after confirmation from the study team as to the appropriateness of the charges.
Source Documentation
Any document where data is originally recorded is a source document and should be saved. Source documents are used to verify data on case report forms. Forms may be provided by a sponsor, but some sponsors may expect the sites to develop their own. Source documents should not be copies of the Case Report Forms provided by sponsors. Demographic data in a subject’s medical chart, medical history data, progress notes, lab data and procedure reports are all source data.
Any information collected per the study protocol must be documented. All studies, regardless of sponsorship have source documentation that should be readily accessible.
Source documents become a part of the research record, and should never be destroyed.
Case Report Forms
Case report forms are used to document protocol required data. CRFs standardize the study data collection. It is the deliverable of study activity and the basis for all study analysis. Most industry sponsored trials are now using EDC (electronic data capture) systems. These are often web-based databases for study data entry. Whether paper or electronic, it is important to make sure the data is accurate and complete, that all blanks are filled in and there is consistency across all forms. All forms should be identified in a consistent manner, with the subject’s initials and study number or other required identifier and dated. Duke requires two subject identifiers on each page.
Errors should be corrected by crossing through the error with one line and dating and initialing the correction. Corrections to the EDC systems are managed in the system through an audit trail.
General characteristics for good data are that they can be evaluated and analyzed, they allow valid conclusions to be drawn, they are complete and accurate and they are consistent across subjects and sites. Specific characteristics include documentation that the subject meets the entry criteria, all fields are complete, entries are legible and understandable and logical, values are within range for the population and the units of measurement are correct.
Study staff responsible for data collection are required to complete the DOCR Study Documentation GCP class. All personnel involved in clinical research are encouraged to complete this class.
Shipping of Samples
Often the shipping of samples is required by sponsors to a central lab. The packaging and shipping of samples is highly regulated by several government agencies. The International Air Transport Association (IATA) regulation is the standard in the US. This training is often provided by the sponsor. Many sponsors will require documentation of this training for any study staff responsible for packaging and shipping samples.
When a PI chooses to send samples to another institution for analysis, a Materials Transfer Agreement (MTA) will be required. This contract is handled by ORC and the fully executed contract must be uploaded to the IRB as an amendment for approval before any samples are sent from Duke.
Compensation for Subjects
Subjects may be financially compensated for participation in some trials. The IRB must approve this compensation. Some are compensated for each study visit, others at specific milestones during the course of the study and some at the end of participation. The amount of compensation varies, but is usually meant to cover the cost of transportation, parking and meals.
Documentation for compensation is required for each payment at Duke. The preferred method of payment is the Duke ClinCard. ClinCard system utilizes a debit card that can be “recharged” for participant payments. There is a charge for using this system, which should be built into the study budgets.
Some groups use a cash fund, some use gift cards and some compensate with checks through the travel and reimbursement office.
All subjects receiving compensation in any form are required to fill out an IRB Personal Data Disclosure Form that includes name, address and SSN. Any paper forms collected for payment purposes are required to have the SSN removed or redacted once payment has been made.
Duke will issue a Form 1099 for tax purposes for any amount over $600 per year.
If the study subject is a Duke employee, any compensation will be added as a supplemental payment to their paycheck.
All projects that require the collection of the SSN from a participant must be registered at https://egrc.duhs.duke.edu. An exception will be granted to allow for temporary storage of SSNs.