Applied Clinical Trials
Over the past three decades, clinical imaging has become an integral part of the drug development process for biopharmaceutical companies.
Over the past three decades, clinical imaging has become an integral part of the drug development process for biopharmaceutical companies. Clinical researchers and patients welcome medical imaging-based techniques because they facilitate non-invasive screening methods for study recruitment, can detect disease, monitor outcomes, and predict therapy response.1 As more medical imaging disease biomarkers are identified and validated, the number of clinical trials that use imaging is expected to grow.2
Implementing medical imaging technology created with the end-user (site staff) in mind can simplify processes and ultimately improve data quality and patient safety. Sponsors and Imaging Core Labs, or imaging laboratories leveraged for centralized quality control and assessment of images, can help to ensure trial success by remembering that while imaging is often a key to trial efficacy, there are people who do not have the time to implement confusing and manual processes. Technology can improve the site experience by:
An Imaging Core Lab’s investment in technological and operational upgrades to remove labor-intensive processes should improve a site’s day-to-day experience, leaving site staff feeling supported and with more time to focus on what matters most: patient care, safety and data quality. Thus, study planning, should incorporate as many tools as possible to ease the burden on site staff so they can spend more time with patients, get patients on therapy sooner and deliver results to sponsors faster. Focusing on the site experience can ultimately save a sponsor valuable time and effort, and reduce cost.
Sponsors face two primary challenges when engaging in a clinical trial: finding sites and recruiting patients. Often, a site that performs well in recruitment will not be a facility that can provide the best medical imaging data at the start. It is the responsibility of the Imaging Core Lab to quickly get the site “imaging-ready” so patients can be randomized as quickly as possible. Every week that patient recruitment is delayed can cost between $600,000 in lost sales of niche drugs and up to $8 million in lost sales of “blockbuster” drugs, according to a recent study.3
There are numerous ways an Imaging Core Lab can support site onboarding and enrollment:
•Don’t make multiple requests for the same information.
Unfortunately, the norm in the healthcare industry is to request resubmissions of data/demographic information. Nothing annoys a site more than the constant and repeated request for the same information. The experience is akin to arriving at a doctor’s office and being asked to complete the same form, with the exact same information, every time you see your physician. Sponsors should ensure that their Imaging Core Lab utilizes a comprehensive database of all sites that the Imaging Core Lab has worked with previously to support feasibility and also avoid duplicate requests for data. Experienced sites need not perform rework as their information and performance is already logged, while poor performing sites that require additional training and support can be flagged prior to first patient in.
•Not everyone speaks English.
Patient recruitment will only become more complex as trials continue to expand globally into new countries and communities. Site materials must be provided electronically with access to quick translations. Sites unable to comprehend guidelines will need to spend their own resources to understand requirements. This will delay patient enrollment and result in poor quality imaging.
•If new information is needed, remember it’s 2015, not 1985.
Sites who have not worked with an Imaging Core Lab before should be able to provide data in a format that is standard with today’s technology. Fax machines, pen to paper surveys, and limited audit trails are recipes for site irritation. Study coordinators can easily submit forms and surveys through an online survey that allows for faster qualification and full chain of command.
•Question test transfers.
Requiring an approved imaging test transfer to qualify for a trial should not be necessary for all sites or trials. In fact, test transfers should only be required if the test ultimately improves end data quality. Previously, test transfers were necessary to ensure sites could follow the guidelines and ensure that images could be extracted from the transfer medium (optical disc CD-R, etc.). The latter is no longer a significant reason to require test transfers, since image formatting has become more common and electronic image transfer standardizes how images are sent to the Imaging Core Lab. Furthermore, if the required imaging for a trial is standard per clinical protocol, it is more likely than not that the site will be able to acquire a good quality image. Test transfers should only be required to check that difficult imaging parameters are followed in trials that use a novel imaging methodology or technology. Thus for many sites that are using standard imaging, requiring a test transfer can cause a delay in patient enrollment without resulting in improved image quality.
•Make eligibility determinations truly central.
An Imaging Core Lab considers central eligibility determination an independent review that occurs outside the site. However, the way that data is communicated to sites is far from standardized. Imaging-based eligibility results are often disseminated separately from other randomization events, forcing coordinators to look multiple places to discover whether their patients are indeed eligible. For studies requiring centrally determined eligibility, the process can be improved significantly to help sites identify faster and more accurately which patients meet imaging-based inclusion/exclusion criteria. Manual feedback should be replaced with automatic reports that can be fed directly to the Interactive Response Technology or Electronic Data Capture (EDC) system so a study coordinator has the ease of collecting all required inclusion/exclusion criteria in one centralized place.
•Engage the radiology staff.
An Imaging Core Lab can greatly support study coordinators by providing tools that can be used by the radiology facility directly, negating the need for the study coordinator to play middleman between the Imaging Core Lab and the imaging technician at the site. It is the responsibility of the Imaging Core Lab to help sites acquire the best quality data possible.
Removing the redundancies of the qualification processes gets patients on drug faster and eliminates the noise of requesting coordinators to adhere to steps that may not add to image quality. As a result, happier sites will provide better quality data.
Once a site has been qualified for a study, staff has been trained and the trial gets underway, the next step – and potential burden for sites – is the data submission.
Recent improvements in imaging eTransfer technology enable image transfers in just seconds with a full audit trail. As eTransfer technologies have spread across clinical trials sites, it has become apparent that any system-even clunky file transfer protocols (FTP)-is better than courier.
Yet some eTransfer systems are clearly better than others. Sponsors must be mindful of pain points within eTransfer that can hinder a site’s efficiency. eTransfer systems should:
An intelligently designed eTransfer system that has evolved to reduce study coordinator and radiology facility staff effort is essential for reducing site burden. An added benefit to sponsors is that eTransfer is not only more secure and faster, but also environmentally friendly and less expensive.
The most successfully designed and safe clinical trials manage to mirror clinical practice, not an easy feat considering that trials very often engage hundreds of sites simultaneously in different languages around the world. In clinical practice, decisions are not made in a silo. Different experts (e.g., internists, radiologists, and oncologists) come together to discuss the best course of action for a patient. The same type of collaboration can be seen at study start at Investigator Meetings. These meetings manage to connect all the sites in an interactive and educational space to promote consistent messaging and training. However, this type of collaboration generally doesn’t continue for the duration of the trial.
Imaging Core Labs can and should utilize an electronic environment to facilitate ongoing communication and engagement throughout the course of the study.
Such an environment should include:
Sites that use an electronic collaboration environment are more engaged, not just on the present study but potentially for future studies as well.
Before the development of integrated medical imaging technology suites, queries were one of the biggest pain points for sites. The required steps for resolution were often unclear and tedious. Sites would receive queries from the Imaging Core Lab via phone, fax or email. The site would manually log the query into a study binder then provide feedback in the same manner. Oftentimes, sites’ responses would be incomplete or insufficient to close the query and the cycle would begin anew. Additionally, the process was not secure, as many sites were located in hospitals or busy medical centers where fax machines were centrally located.
The old querying process required significant investment of staff time and effort and did not improve end data quality. Today’s medical imaging technology suites eliminate query bottlenecks by completely removing redundant steps and facilitating communication between sites, monitors and the Imaging Core Lab. Sites can view their web-based queries in an easy-to-use, intuitive format and can respond to the Imaging Core Lab using the system. Queries can be closed by the Sponsor or monitors and sites need not be hindered by a paper process that lacks an audit trail. If a site responds to a query via an electronic portal, their response is logged and time-stamped and the site will never have to resubmit the document again.
By helping to close queries faster and prioritizing those that may require a rescan, electronic processes and portals help accelerate query resolution and have a direct effect on final data quality.
If the purpose of providing training materials and documentation is to help ensure high quality data, inundating sites with unnecessary documentation rather than using a simple method of delivering trial materials and updates, will most certainly produce a negative effect.
The common requirement of forcing sites to store and reference physical study binders in their offices is antiquated. Not only is it inefficient for a site to have to reference a study binder and replace materials as they are updated, but significant time is spent on the monitoring visits for the CRAs to check to make sure the right materials are available. Keeping track of binders, data and patients, in addition to communicating with sponsors, CRAs, and the Imaging Core Lab could be a full-time job for site staff – although for nearly all coordinators, these are just some of their responsibilities.
A document repository that allows for the rapid distribution of all essential study materials to the study community can alleviate site burden, keep sites engaged, eliminate the need for the site to store physical materials, and reduce courier and printing fees for sponsors. A coordinator can only spend so much time on a trial and removing the annoyance of metaphorically drowning in paperwork can help focus the coordinator’s energy on the patient.
Today, with medical imaging technologies, both CRAs and sponsors have quick and easy real-time access to trending site performance metrics that enable a better understanding of common queries and provide better visibility to site qualification events, image status and review progress. Monitors are provided with interactive tools to allow users to drill down, evaluate, and manipulate data on the fly.
An electronic reporting portal grants sponsor study leaders, directors and senior management the ability to easily glean accurate, up-to-date snapshots of study progress. As the entire study community becomes more engaged and informed, the sites are in turn better supported.
A site is a sponsor’s most important client. Improving the site experience ultimately helps achieve more rapid site onboarding and patient enrollment, time efficiencies gained from improved data submission, better communication with sites and quicker query resolutions. The benefits ultimately lead to faster study completion, cost reductions for sponsors and improved patient safety.
From a site’s perspective, a medical imaging technology suite can simplify day-to-day tasks to return the focus back to what matters – patient safety and helping to support drug approval.
Additionally, engagement between CRAs and the Imaging Core Lab staff is key to promoting site happiness. The goal for both parties – Imaging Core Lab and full service CRO – is to support endpoints by creating simple processes and requirements that a site can easily follow.
Elizabeth Dalton is the Associate Director, Medical Imaging Client Operations for PAREXEL Informatics.