by Eric Distad, Senior Director, Medical Device & Diagnostics, Novella Clinical
Heart disease remains the world’s number one killer. Fortunately, many innovative physicians and smaller device companies are helping to drive new product development in an attempt to better serve the increasing cardiovascular (CV) patient population. When it comes to marketing these new products, a company’s clinical program can mean the difference between commercial success and failure. As such, we have identified seven steps that small CV device companies should follow as they seek to launch or expand their clinical research programs.
- Select Sites Objectively
While guidance, input or advice from external medical experts can greatly aid the efficient design and refinement of prototype devices and feasibility studies, these advantages may not extend readily to the conduct of larger clinical trials on which regulatory decisions, and hence speed to market, will rely. Site selection must be objective, and questionnaires must include data beyond the disease indications a practice may treat as this can impact a site’s ability to enroll qualified patients.
How a site handles the specific device type and the related procedures along with checking a principal investigator’s (PI) history must also be considered before sites are selected. Novella recommends smaller sponsors develop feasibility questionnaires for site assessments and inquire about knowledge and experience with the product, depending on its stage of development, or of a similar, marketed counterpart device. Diving into a PI’s history helps to ensure no surprises lurk to derail a trial, as a change in PI can mean decreased transparency to previous site audit experiences and issues.
- Assess Start-Up Timelines
The management logistics of larger, pivotal clinical trials vary greatly from one- or two-site feasibility studies. Managing each site’s start-up timelines can challenge smaller device companies. To best move timelines forward, three start-up aspects must be managed effectively: Centers for Medicare and Medicaid Services (CMS) submissions, institutional review board (IRB) approvals and regulatory documentation.
Gaining CMS approval can have a significant financial and timeline impact at sites unfamiliar with the process. Yet nearly half of U.S. sites lack first-hand knowledge of the CMS submission processes necessary for managing hospital and treatment billing related to patients’ ongoing healthcare needs while participating in trials. As such, sponsors need to know how CMS-related variations within a national study might affect trial participants and conduct.
The U.S. Food & Drug Administration (FDA) requires IRBs to consider the risk of harm from a device or additional required procedures related to the device use. To speed the review and approval process, sponsors must know how to properly prepare the documentation and required data.
Many sponsors have experience with some aspects of regulatory documentation and submissions related to study credentialing, but if the staff have not yet prepared and reviewed a complete FDA packet or gone through a face-to-face review of a packet with the FDA, the sponsor should consider seeking assistance. Specific expertise is needed to understand the detailed nature of these documents.
- Calculate Clinical Training and Monitoring
Before patient enrollment can begin, participating sites must complete the site initiation visit (SIV). This training verifies that each site’s PI, sub-investigators and research team members understand the study protocol, procedures and expectations. The SIV is a critical time to determine and document each study team member’s individual responsibilities for the conduct of the trial, and their roles in ensuring data quality and patient safety.
Training must also encompass all aspects of study monitoring, which includes, but is not limited to face-to-face and remote communications with investigators and site staff members; review of the processes, procedures and records; and confirmation of data accuracy. While such monitoring training and related compliance activities can be scheduled with corresponding resource allocations, because of the volatility of SIV scheduling, sponsors with limited trial experience may have added success in partnering with an experienced CRO to aid in accurately calculating the time and resources involved.
- Design Data Management
Data collection and maintenance begins with protocol development. Verifying the trial protocol procedures and data points enable sponsors to determine if they have all the data necessary to power study endpoints. Sponsors who reuse an approved feasibility protocol for a larger scale clinical trial may fail to account for changes in the trial scale and are thus forced to make protocol modifications to address data variability as well as to adjust statistical concepts and calculation methods. After the data needed for endpoints and evaluations are confirmed, sponsors must determine the most effective and cost efficient means to collect and monitor study data.
Many smaller sponsors have successfully managed data collection in small feasibility studies via a paper case report system. Investing in a good electronic data capture (EDC) system creates efficiencies downstream in the trial, which could also benefit a trial budget. Not only are EDC systems more efficient for data collection, they also facilitate real-time immediacy in interim and final reviews, including analyses that are endpoint- and site-specific as well as comprehensive.
- Prioritize Patient Enrollment
Many factors can influence patient recruitment and frequently the trial enrollment experience differs in larger scale trials from feasibility studies. Sponsors must prioritize enrollment sites by assessing the capabilities and potential of each location’s respective staff and facilities to timely navigate through the steps and SIVs to reach the enrollment starting gate. Variables throughout the enrollment phase must be constantly monitored, with steps taken to mediate any slowed enrollment.
Also, a consistent evaluation process should be implemented early in a trial to map plans for addressing enrollment issues. Adding performance metrics into site contracts are valuable tools to hold sites accountable and provide leverage to close underperforming sites. A best practice is to offer positive contractual items, such as offering sites that meet or exceed an established enrollment target increased compensation as allowed by their IRBs.
- Evaluate CRO Experience
A CRO should have experience and expertise both in trial management and the therapeutic category or disease indication. Moreover, the CRO should demonstrate a strong, successful CV device, rather than a CV pharmaceutical, track record. While understanding CV disease pathogenesis and diagnosis from both therapeutic sectors is valuable, experience-based skills and knowledge particular to CV devices is more relevant and applicable. Sponsors should also ask about the experience of the proposed project team manager, clinical team manager and other team members, not just the historic experience of the CRO, in case staff members have changed.
- Plan Vendor and Task Outsourcing
Feasibility study teams and tasks need modification for larger study success. Relying solely on feasibility study vendors for task outsourcing in larger trials often does not account for how changes in the trial scale may increase expertise needs, workloads and work streams for vendors – all of which can have significant impact on budgets, resources and timeliness of deliverables. A CRO can help small sponsors review potential vendors for their CV device trial experience and capabilities against project needs for both trial planning and execution, including the current and potential later phase studies.
Eric Distad, Senior Director, Medical Device and Diagnostics Division at Novella Clinical. Mr. Distad has over 17 years’ experience in all facets of clinical research including 13 years in medical device clinical research, ranging from one of the top three medical device companies to startup companies. Geographically, he has significant experience managing trials in the United States, Canada, Europe, and Hong Kong/China. He can be reached at firstname.lastname@example.org.
The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of MassDevice.com or its employees.