Everyone is demanding more clinical evidence from medical device and diagnostics companies these days.
Regulators want to see more of it before granting market approval. Payers are requiring more of it to substantiate product value claims and approve reimbursement. Healthcare systems and physicians are asking for more of it when making purchasing decisions. Even patients are starting to request it.
This pressure is forcing manufacturers to amass more clinical data on their products than ever before, and they are primarily responding by running more (and/or larger) clinical trials. This trend is manifesting itself even in situations when clinical evidence isn’t mandated, for instance when submitting certain 510(k) applications. Device makers increasingly are turning to clinical trials to differentiate their products from competitors and improve their odds of adoption in the marketplace.
However, most device makers lack the internal resources and expertise to run a complete clinical trial operation in-house. This is especially true for small companies, which have little bandwidth, experience, and margin for error — for them, clinical success or failure can mean life or death for the company.
As a result, we are witnessing a corresponding rise in the outsourcing of clinical services to contract research organizations (CROs). Medical device makers are turning to CROs for assistance with clinical operations management, investigator recruitment, clinical monitoring, data management, biostatistical analysis, health economic and outcomes strategy, quality assurance, regulatory approval, and other needs.
Earlier this month, I joined a group of medical device and diagnostics manufacturers (sponsors), CROs (vendors), physicians (investigators), consultants, and others involved in clinical research for the inaugural Partnerships in Medical Device Trials Conference in Chicago. The event featured two days of presentations on various topics related to medical device clinical trials, along with the opportunity dig deeper into issues, trends, and approaches during networking sessions.
What follows are five best practices for medical device trial outsourcing, based on several recurring themes I heard during presentations and conversations at the event.
Select a CRO with medical device expertise.
Throughout the event, sponsors and vendors alike echoed the belief that medical device experience/expertise is the single most important factor to consider when choosing clinical service providers. The opinion was also corroborated by new research on medical device clinical outsourcing trends that was presented for the first time at the conference by Lisa McKay of The Avoca Group. (See page 5 of the embedded slideshow below.)
Jennifer Dugan, manager of clinical research for Stryker Orthobiologics, warned that many CROs are pharmaceutical-focused and lack sufficient medical device trial experience, a fact that often becomes apparent early in the evaluation process. “When they give you a presentation and start talking about 1572s and Phase II studies, you know they haven’t conducted device trials,” she said during a panel session entitled To Keep In-House or to Outsource? That Is The Question. “The core operational aspects of running pharma and medical device clinical trials are the same, but there are also significant differences. If a CRO starts using some of those key pharma buzzwords right away, you know that the expertise probably isn’t there.”
In fact, you should really be looking for more than general medical device trials experience in a CRO. The ideal vendor for your trial will have demonstrated success conducting clinical research in your product’s therapeutic area and for its specific indication — better still, for product designs that are similar to your own.
Establish an internal clinical research team, even if it’s a team of one.
Outsourcing doesn’t mean completely turning over the reins to your CRO. Nobody knows your product better than you do, and the CRO is going to need your guidance, feedback, and support, based on your expertise. And as the sponsor, you are the one ultimately responsible for project execution and outcomes. You must remain fully involved in the process — or at least commit a member of your team to the job.
Ideally, you should have at least one or two people in-house who have experience running clinical trials. “In running a clinical affairs team, my philosophy has always been ‘know how to do it,’” Omar Dawood, MD, chief medical officer and SVP of medical affairs for Kona Medical (developer of an ultrasound-based renal denervation system), said during his opening keynote address. “There have to be people internally who could run the whole clinical trial themselves, if they had to.”
Be fully transparent with your CRO — and expect the same in return.
Many presenters and attendees stressed the importance of mutual transparency, trust, honesty, and communication on both sides of the sponsor-vendor relationship, beginning as early as the evaluation phase.
Sponsors should be open with a CRO about exactly what they need from the agreement, what their definitions of success and failure are, what they can afford, and how long they expect the work to take. They should be honest about their in-house capabilities (or lack thereof).
It’s also beneficial for sponsors to communicate their strategic approach going forward — not only in clinical, but it in sales and commercial. “I found that with the medical device community, the clinical trials environment is so new that sponsors are not necessarily comfortable sharing long-term strategies, commercial strategies, or managed care strategies,” said Karrie Hilsinger, director of clinical operations for drug delivery device maker Valeritas, during a panel. “For us, though, it is so important for our vendors to understand those long-term strategies and where we’re going.”
On the flip side, sponsors should hold out for a vendor that is candid regarding its specific capabilities, areas of strength and weakness, specific services provided, costs, etc. “A lot of sponsor companies are surprised by change orders, so I think it’s very important, from the get-go, to be very transparent,” said panelist Sophie McCallum, director of operations at Clinovo, a Silicon Valley-based CRO. “You need to be aligned with the sponsor about the project scope, what they will be charged for, and who will be the project manager and members of the team. A lot of times, there is a disconnect between vendor and sponsors.”
The advantages of building a collaborative, mutually respectful relationship with your CRO can be significant. Stryker’s Dugan shared an example from a project she worked on with MedTrials, a CRO based in Dallas. “They came to me and said, ‘I want you to know that we’re more than 50 percent through the allotted budget. Do you want us to keep going?’ That was a good marker for us both to reevaluate what was going on and back things off. I think that that speaks to the integrity of your vendor, when they will say, ‘I don’t want to blow your budget, because then we’re going to have to change order you.’”
Engage vendors early in the development process.
Sponsors can benefit from initiating communication with prospective vendors as early as possible in the development process — before finalizing their trial protocol. CROs can offer device makers valuable input on trial design, ultimately saving sponsors time and money.
Valeritas’ Hilsinger spoke of an experience where she established a strategic partnership with a vendor well before completing trial protocol, resulting in substantial improvements in protocol and process. “At the time, we were thinking of conducting two different studies, and the vendor suggested that we combine them into one,” she said. “We went back and looked at it, and they were absolutely right — their suggestion turned out to be a much better approach for us.” Combining the two trials ended up saving the company both time and cost.
Several participants pointed out that the medical device industry could learn a lot from the pharmaceutical industry, where clinical research and outsourcing models are far more developed and mature. “Over the past five years, pharma and biotech companies have shown us that true cost savings, timeline implications, and quality are achieved by conducting due diligence well prior to when development planning occurs, and certainly prior to the protocol,” said Ken Dhimitri, executive director of clinical operations at Boston Biomedical Associates, a CRO. “Engaging in the relationship in a meaningful way early helps align both parties on SOP [standard operating procedure] and technology.”
Think twice before using bonus/penalty payment models.
While performance bonuses and penalties are a common facet of outsourcing contracts, participants warned of the potential consequences of using them.
“I think it sets up somewhat of a contentious relationship and can cause a bit of a conflict,” Joe Popowicz, principal consulting at Emergent Clinical Consulting and moderator of the panel, said. “If we’re talking about a partnership, it is a bit counterintuitive to being a partner and having transparency, because there is a little uncertainty of how it will go.”
“We don’t do the bonus/penalty,” said Hilsinger of Veleritas. “Our thought is that, if you’re truly aligned with us and you understand and we’re strategic partners, you don’t need that bonus or a penalty to make this happen and be a successful team.”
Obviously, these five tips represent only a fraction of the best practices medical device manufacturers should follow to develop fruitful partnerships with their CROs. What else would you add to the list? Why? Please share your opinions and examples in the Comments section below.