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Uncovering the key elements that together help shape a high-quality site.
In the world of pharmaceutical drug development, if we were to build the perfect imaging clinical site, what would it be? From the core lab perspective, the ideal site would have a blend of therapeutic experience, flexibility, and excellent communication skills.
Sites with the most experience in the areas of modality, treatment, target population, and clinical trials are already a step ahead of the pack. Based on our years of experience, these sites also tend to provide the highest quality data. Sites that can effectively communicate with all the participating parties (i.e., sponsor, medical imaging personnel, imaging core lab, and patient volunteers) are able to perform at more consistent levels and meet significant dates related to study timelines.
PAUL BURNS, GETTY IMAGES
Not all clinical sites are held to the same rigor, nor should they be. It is difficult to expect an ophthalmology site to be experts in acquiring ECGs for cardiac safety testing. So much depends on the type of study being conducted. But when a protocol demands such expertise, it is imperative that the site be as perfect as possible.
For example, a site selected in an oncology clinical study where the Response Evaluation Criteria In Solid Tumors (RECIST) will be used must be able to acquire imaging data that is usable for consistent measurements and observations by independent reviewers.
According to Janie Petti, assistant director of project management at Biomedical Systems, "Sponsors should select a clinical site with strong expertise in the patient population of the disease state being targeted for the clinical trial. Asking the right questions upfront in site surveys can provide sponsors with better information on the experience and capabilities of sites."
Knowing how to operate the equipment is not enough. "Sites that are associated with imaging centers that have experienced, registered technologists understand the importance of good image quality," said Petti. "The measures required to attain quality imaging data defined by the protocol are second nature to them."
Once the data is acquired and transmitted by the site, high-end software programs are used by the reviewers to make the required measurements per protocol specifications.
According to Ingrid Van Rompaey, PhD, associate director for project management in the Hematology and Oncology Therapeutic Group for PPD in Brussels, Belgium: "It is essential that the imaging data be of sufficient quality to allow reviewers to make exactly the same measurement each time the data is evaluated. For this reason it is important to have sites that can comply with study specific protocols when the independent reviewers are using RECIST criteria."
Sites that acquire MRI images and use equipment with a 1.5 to 3.0 strength magnet will produce the highest quality imaging data. The magnet strength has a direct relation to the pixel size of the data acquired. The smaller pixel size results in clearer images and allows for more efficient use of the software tools utilized by the independent reviewers.
Sites are strongly recommended to use equipment that is accredited by the American College of Radiology (ACR). ACR accredited equipment in good working order and operated by experienced technologists can prevent ghosting and other effects, which can diminish image quality.
Imaging centers should have a radiologist on-site to evaluate the images while the patient is on the premises. For safety and convenience, any issues with the image data can be quickly resolved and should not require rescheduling of patient(s) involved in the study. If contrast is being used for MRI data, sites should have a Power Injector on site to facilitate the protocol requirements. This will avoid any potential time point impacts or patient attrition.
According to Van Rompaey, the perfect site would have calibrated equipment to ensure the data the imaging center is provided is consistently interpreted by the independent reviewer. To ensure this consistency, it is important that the site uses the same modality and machine for a clinical trial subject throughout their enrollment in the study.
Computed Tomography (CT) imaging equipment tends to offer a wider spectrum of capabilities. Sites that can meet the stricter protocol requirements are preferred, as this will reduce variability between independent reviewers. If the protocol calls for a 5mm slice thickness, the perfect site would be able to acquire image data that meets the specification.
With the availability of newer CT equipment and added experience with clinical trial requirements, imaging centers associated with academic research sites tend to produce data that is of higher quality. These sites also tend to follow processes that result in a reduced number of queries, according to Chris Schaefer, director of operations at Biomedical Systems.
So as we continue to build our "perfect" site, it will have the latest generation of CT equipment, follow the imaging protocol, and deliver the imaging data to the core lab within the time constraints detailed in the protocol.
Electronic imaging data in native DICOM format is important to the transfer and integrity of high-quality CT imaging. DICOM transferred data will maintain its quality should any postprocessing, 3D or multiplan reconstruction be required. The header of the DICOM data will reveal the parameters used to create the images.
"The study coordinator and imaging technologist need to understand that the imaging protocols for clinical trials are often different than the protocols the imaging centers follow on a daily basis," said Schaefer. "The site must understand the importance of the information in the site procedure manuals and how important it is to follow the imaging protocol."
Van Rompaey said while it is not necessary for the study coordinator to understand the exact details of why they are doing certain things dictated in the protocols, there are key elements of it that they must master. The areas of time and events are the most important to ensure subjects meet the requirements and progress through the various time points (see Table 1).
Expected Time Requirements
Clinical Study coordinators also must be good facilitators, and if needed, put the imaging center in direct contact with the core lab so that issues can be resolved efficiently. The study coordinator must make sure the order for the subject's exam is written correctly. This must be accompanied by a call to the imaging center to inform them that a patient enrolled in a clinical trial is scheduled for an appointment.
The study coordinator should be able to assist the technologist with completing the necessary forms and answering any questions that may arise about the imaging protocol. The technologist should have a Site Procedure Manual and be familiar with the required imaging sequences or, if necessary, have contact with the imaging core lab facilitated by the study coordinator for clarifications.
Petti commented: "The very nature of a university clinical site and its associated imaging center offers openness to new ideas, experienced technologists, and doctors with an abundance of resources...Because of the teaching environment, many of the necessary modalities are located in close proximity on campus. The flexibility of a university site is also a valued quality in that they operate in an extended time manner to allow for more flexibility for their students."
According to Van Rompaey, study coordinators must understand that although academic centers provide excellent selection of experts in various medical fields, nonacademic centers have advantages also and can be more accepting of varied imaging protocols. The ideal site must be prepared to deal with the potential that the same technologist will not always be available to perform the clinical trial protocol exam on a particular subject due to the academic environment.
In Eastern Europe, there are an increasing number of private imaging centers. Due to the client relationship of these places, they can be open to unique imaging protocols and more motivated to follow the required procedures and time lines that are outside of their normal routine.
If a study coordinator is participating in an international study, it is important that they understand all the logistic processes involved in getting supplies, documents, and clinical trial data in and out of the respective country. These sites must be responsive and receptive to time requirements for shipping and receiving via a courier, or using electronic data capture to transmit data to sponsors and their core lab team.
Language issues play a key role in the success of clinical trial sites. Usually only the principal investigator and the study coordinator speak a language other than the local dialect where the imaging data is being acquired. Local physicians and technologists may only speak the language native to the area where the data is being collected. The perfect site is prepared for these eventualities and is prepared to make a language specialist available.
Communications play an important role in the success of a clinical site. Investigator meetings and training opportunities serve as the best sources of information. Sites attending these meetings should ask questions and maintain regular contact with the imaging core lab. With the proper training, they will become more efficient in resolving issues and completing queries for missing information in study data or documents in a timely and efficient manner.
The perfect site will have good lines of communication to the sponsor. This is important in order to relay information about the study protocol or a problem with a patient. A site will need to report to the sponsor if patients do not show up for their appointments for a specific time point. Clinical sites are on the front line of the trial and need to be able to tell the sponsor what is going on with their protocol.
Equally important, clinical sites have to communicate well with the imaging core lab. Sites must report any issues with the imaging protocol or electronic transfers, and report if they are experiencing issues with the imaging center. Events that interfere with time points or patient withdrawals need to be quickly communicated to the imaging core lab.
According to Petti, the clinical site's understanding of the protocol is easier when there is a good working relationship between the site and the imaging core lab. The number of issues that impact critical timelines is reduced and situations that do develop are resolved more quickly because the clinical site and the core lab are working in concert.
A site's ability to establish good communication with its imaging center is critical. Imaging centers need to know when a subject is scheduled for an exam due to the uniqueness of the imaging protocols used for trials.
The single most important contact clinical sites have is with patients. For oncology studies, it is imperative to communicate the entire plan of therapy and standards of care to the patient. In turn, patients need to understand the imaging procedures that will be performed by the center.
Patients must understand what is required of them during patient preparation and where to go for their exam appointments. At the start of a trial the site must capture a good medical history to ensure there are no factors that would lead to the patient being excluded from the study.
The site must have a good working relationship with the imaging center because although the center acquires the test data, the study coordinator is the mediator of the data collected. The study coordinator is the person everyone consults when questions arise or issues need to be resolved.The perfect site has a study coordinator who knows a little about everything, and even though they might not have all the answers, they know where to get them.
Before a patient is enrolled, the study coordinator at the perfect site will review the imaging protocol with the imaging technologist(s), allowing time for questions to be asked before the start of a trial. Additional time should be factored into the schedule for the site to provide sample test data to the core lab to assure compliance with study requirements.
After the site has acquired the image it is sent to the imaging core lab. The lab will provide a quality assessment of all data and documents received from the sites. Locations that keep information packets together will help speed that process along. Time-consuming queries from the lab are avoided when paperwork is completed correctly by the site.
The perfect site is prepared to manage digital imaging data and operate electronic management software. Sites that understand the requirements of digital imaging data and can efficiently acquire, process, and deliver digital data will fit easier with the electronic-based processes of the core lab.
Digital imaging allows sites a better view of the data prior to sending it to the core lab. Sites that use online applications to send data must be as accurate as possible, such as checking to ensure subject and site ID match between imaging data and documents prior to sending. This helps the core lab manage the data and have it reviewed within a timely manner.
In oncology studies, as with other studies, it is important that everyone join together and recognize the dedicated work performed by the staff.
In referring to the relationship between the sites, staff, and imaging core lab, Petti commented, "Imaging centers must understand how their technologists grow professionally with the experience they gain from being able to work with technologies or imaging protocols being used in the clinical trial. They broaden their knowledge and they stretch beyond their daily routine."
Effective study coordinators can facilitate the education of imaging center staff and help them identify new opportunities to review their existing imaging protocols. Exposure to these new protocols will allow imaging centers to hone their skills and add to their experience of producing quality imaging data under time point constraints.
In the end, even the perfect site sometimes has issues. What makes the site perfect is its ability to quickly and efficiently resolve queries. Sites that are responsive and involved in the query resolutions ensure their clinical trial data is processed quickly, and that the quality is checked and prepared for the independent review by the core lab in a time frame that meets the sponsor's needs and keeps their patients enrolled in the clinical trial.
Perfection in a clinical site is a lofty goal. Experience, communication, good equipment, competent staff, positive relationships, and an understanding of partnerships are key elements that help develop clean imaging data and allow for timely and efficient independent reviews.
The perfect site has all the tools, processes, and people in the right place to perform at the highest levels to meet the protocol requirements of the sponsor. So if we've followed all suggestions and guides, maybe we can one day say: "And the day has come, we've built the perfect site."
Frank Dunn is a medical writer at Biomedical Systems, 77 Progress Parkway, Saint Louis, MO 63043, email: firstname.lastname@example.org