Clinical Researcher—August 2018 (Volume 32, Issue 7)
There can be a negative perception around a device clinical trial being transitioned to a contract research organization (CRO). It is time, however, that we took a more pragmatic view of why this should happen, and contemplate whether we should be considering and enabling it more often.
Let’s start with “Why?” Why would you transition an ongoing study that is being managing reasonably well, and for which you have obtained your primary objective of gaining regulatory approval?
This evokes a multifaceted response. Let me break down the question into bite-sized chunks—how I like to look at every problem, because the solutions are far less daunting when you take this approach.
Don’t Let Perfect be the Enemy of Good
First up, let’s look at “managed reasonably well.” Whatever your background, whichever company you have worked with, can you really claim perfect delivery? I hope you can, but face it, we all encourage an environment of continual improvement—one which would be redundant in a perfect world.
Professionals in medical device companies are dissimilar to those in drug companies in that their products change and evolve. A drug that changes or evolves is a different drug, plain and simple. Unlike the drug study experts, this means we device folks are often faced with multiple iterations of a product undergoing simultaneous clinical trials. Post-market commitments are maintained for legacy products in parallel with the latest innovations, and it is realistic to assume that the enthusiasm for the latest product garners the greatest attention.
So we have our first challenge. How do you keep true attention on a legacy product that we no longer market or generate revenue from, but for which we have ongoing moral and regulatory obligations to patients and regulators? This is a “soft” challenge—and when I say soft, I don’t mean that it is easy; I mean that it is intangible. It’s not tied to patient outcomes (we usually can’t change those post-hoc) and it’s not tied to revenue.
Approaches to Approval
Let’s now look at our “primary objective of gaining regulatory approval.” The most obvious comment here is that there is so much more that hinges on your pivotal trial than gaining regulatory approval.
Being approved goes only so far, getting buy-in from the medical community is of huge value, and still more importantly, getting the payers to understand your economic proposition is the only way to be truly successful. It’s not about profitability, it’s about viability; even not-for-profit organizations have to remain economically viable.
Bottom line, there aren’t just regulatory commitments that must be delivered upon, but there is also a community of patients, prescribers, and payers to keep happy, for both patient-centric and economic reasons.
Think of it This Way…
Time for some deep soul searching—are the factors described here keeping the leading scientific innovators in your organization working to midnight, and returning to the office before sunrise? I’m sure they aren’t, because these innovators are always seeking a better result than they got today—they are looking forward all the time, and revisit the past only for how it informs the future.
So why would you transition an ongoing project away from our immediate care and into the arms of a CRO? To make sure that it is getting the attention it needs with the scientific and quality rigor that we expect from robust clinical trials and, most importantly, that patients who have been subject to experimental therapies have appropriate follow up and ongoing care.
Taking On the Transition
Now the question is “How?” How exactly do you go from getting an approval after a one-year interim data cut of a five-year (often 10-year) clinical study, to transitioning the post-marketing/post-approval follow-up phase of the same study, without stopping, to a CRO? (This situation also applies to changing from a current CRO to a new CRO—a classic “rescue study.”)
The answer is one that is not always appreciated at first; as with any successful complex delivery, it is down to planning, process, and discipline. Transition or rescue of a study from a sponsor to a CRO, or from a CRO to another CRO, requires highly detailed processes that have been developed over time with insights borne from experience. This is not a place for learning for the first time on the fly—it demands careful application of all the wisdom you have gained from years of conducting research.
It starts with detailed planning; not just amending existing plans (e.g., your data monitoring plan, your clinical monitoring plan, or your communications plan), but overlaying a highly detailed transition plan. This takes into account a wide array of considerations, and takes a deep dive into risks and mitigations, strengths and weaknesses, and opportunities for improvement.
In my experience, I’ve found it helpful to use a detailed agenda and checklist that includes a face-to-face forum where legacy and future teams work together for a smooth transition and reach a common agreement on the management of handing over tasks and responsibilities. This can help disparate teams engage to ensure a smooth and efficient transition of tasks, responsibilities, and, above all, accountability.
Putting Theory into Action
Finally, what are the interpersonal and intercorporate clashes that arise? Can this really be done? I have no doubt there is some variability based on the specifics of each situation, but let me illustrate my answer through a case study.
I was approached in late 2016 by a large transcatheter device manufacturer and asked if we could help with the safety phase of one of its ongoing trials. The development team had surpassed its one-year data cut, had provided the interim results to the U.S. Food and Drug Administration, and had just been granted Premarket Approval.
This study incorporated three iterations of the product in development and multiple registries. The manufacturer’s fear was that handing this over to a CRO would result in a decrease in data quality, reduced performance overall, and negative impacts to a highly valuable brand and image in terms of key opinion leaders, including physicians at leading interventional sites. This was of particular concern, as the company had clinical research associates and field clinical engineers calling these clinicians on an ongoing basis.
Using a detailed transition planning process, we went through a critical process of alignment and a highly detailed planning process with this client. The end result was a very smooth transition, but the real victory was a comparison of leading metrics after a year. Data quality had improved, queries were at an all-time low, and the average time between a visit and final report had dropped sharply. Not only did this deliver exceptional results, but the manufacturer has since redesigned its study approach to include the transition of the safety phase of future studies to a CRO as a standard.
Let me leave you with some parting thoughts. First, if you are a sponsor, should you be focusing the efforts of your brightest minds on your legacy products? Upon contemplating a service provider switch, or even switching from your own teams to a new service provider, do you have robust processes and procedures available to you that will guarantee success?
Second, you must be aware that transition is never any easy proposition. Due consideration of the circumstances, the economic benefits, the risk and mitigations, and the overall strategic objective will allow you to decide whether transitioning to a CRO is an appropriate strategy for closing out your existing clinical trial commitments, and to continue to drive innovation and market dominance.
Finally, if you are in the unenviable position of having a failing provider today, know that there is a way to rescue your study without further jeopardy.
Adam Steadman is Vice President—Clinical Development; Business Unit Head, Medical Device & Diagnostics at Syneos Health.