Navigating the Clinical Research Paradigm for Cost Savings and Efficiencies

Companies may encounter many issues and barriers in the course of developing a new device or biologic product for market entry. It is only by working effectively through the timelines and deliverables from reimbursement, the FDA regulatory pathway, data requirements and clearance that companies can take advantage of the opportunities that exist to bring their product to market on schedule, on budget and in regulatory compliance.

But many companies lack the staff or resources required to successfully negotiate the regulatory pathway and bring their product to market within company timelines. A clinical research organization (CRO) can provide the assistance to ensure that requirements of both the company and regulatory agency are fulfilled.

This article provides an overview of the marketplace for new spinal and orthopaedic technology, and provides basic guidance for successfully navigating the commercialization process with the help of a CRO partner.

Current Marketplace
The stock market crash of 2008 contributed to suppressed innovation in spine research due to financial constraints related to funding new trials. Moreover, the FDA process has become so arduous that often the smaller companies simply don’t have the resources to survive the research and commercialization process in the U.S.

In 2011, The New York Times published an interesting article discussing the costs and regulatory challenges faced by companies pursuing FDA clearance for new devices or biomaterial technologies. (“Medical Treatment, Out of Reach,” February

This theme has since echoed in other articles and explains why, due to the FDA process, the U.S. has developed a reputation as a very difficult place to commercialize new products. The article notes a number of device manufacturers moving sales operations to regions like China, India, Brazil, the European Union and emerging markets. The primary reasons? Cost and time to market.

Another stumbling block is heightened scrutiny from FDA of purported conflicts of interest raised by special interest groups relative to principal investigator (PI)/physician relationships and their consulting agreements with those bringing new products to market. These and other factors have led companies to change to-market strategies. A U.S. spinal device company with both cervical and lumbar artificial discs found itself having to forego an initial strategy of commercializing first in the U.S. due to an inability to overcome FDA objections on their device and regulatory plan. The company ultimately decided to sell the discs abroad. This decision revitalized sales and the company itself. A revised strategy was devised to reconsider another presentation to FDA for approval of their products.

Numerous companies have found similar success abroad, partially due to the advent of medical tourism and patient consumer education, which sees many patients willing to travel to receive the latest technology. Another reason they find success is simply by avoiding the resources that are exhausted trying to work through FDA’s tortuous regulatory pathway. Today, companies interested in bringing a product to market must have two or three contingency plans in order to achieve a modicum of success.

Timeline for Device Trials and Market Approval
The typical timeline for approval of a new orthopaedic or spinal medical device via clinical trial and premarket approval application (PMA) might be between three to six years, depending upon the regulatory pathway, predicates in the marketplace and outcome data requirements to support efficacy and superiority against the “gold standard of care.” Site and PI selection must undergo sponsor-initiated due diligence to objectively quantify the patient recruitment potential for either an IDE pivotal trial or an outcome study for a 510(k) application.

Enrollment typically lasts 24 months, but might greatly increase due to nuances in control device selection, randomization, etc. In some cases, no matter how many biomechanical tests a sponsor might perform, these might not satisfy FDA’s requirements. In addition to issues of clinical trial setup and management, the timeline to marketing approval by FDA must be considered. With the average PMA review time of one year, a submission of a clean clinical data set is critical. Although review times have become lower over the years, the number of major submission deficiencies issued by FDA has increased by 74%. Deficiencies lead to increased review times and can potentially extend the time to market for years. Thus, careful selection of your CRO is critical.

Ideally, if you can get through this process in under four years, you are ahead of the game.

Clinical Trial Issues
So, what are the clinical trial challenges for a sponsor? Investigator recruitment is pivotal to success. However, while it’s
often easy to recruit PIs—everyone gets excited about the latest, greatest and newest device—there is often a slight misstep to actually quantifying how those investigators are going to be able to contribute to the trial. With the need to screen everyone carefully, it can be difficult to quantify the actual numbers and volumes of patients a PI will be able to enroll at a site. Patient recruitment and eligibility screening are essential to the success of the trial.

A second challenge is developing appropriate infrastructure and support. The clinical research coordinator is a vital part of any successful clinical research trial. If the PI does not have a coordinator, it will prove very difficult for the site not only to maintain enrollment, but also to ensure the collection of quality data.

Data reporting represents one of the largest challenges, particularly in terms of tracking adverse events, adhering to the protocol requirements, maintaining monitoring schedules and using electronic data capture technology to streamline enrollment. Further, most new products require a variety of specialists and silos to manage the demands of a clinical trial. Coordination of key vendors and their services is critical. For example, how does one coordinate the regulatory requirements with study operations and data management? Another consideration is reimbursement and when to phase this in. How does it impact protocol design or patient recruitment?

Value of Vertical Integration
A vertical integration model, incorporating all the services required for a study, can make trial management much more efficient. Looking at all of the necessary components and proactively planning their inclusion is critical. Industry must put reimbursement at the top of the list (in addition to thinking through regulatory, economic and market issues). It is essential to identify any potential reimbursement obstacles or issues likely to arise as part of the protocol process, as opposed to finishing a trial and then finding out that there are little or no reimbursement options available.

Since a host of issues must be covered, vertical integration of services is optimal. It allows the sponsor to address not only the issues of reimbursement strategies, clinical trial management and regulatory compliance, but also utilization and outcomes measurement, monitoring, patient recruitment, site initiation and site closeout in a seamless fashion.

Vertical integration also lends itself to cost savings and relationship building. It creates an element of communication that allows you to “fast-track” many essential functions of commercialization. Getting to market much sooner, reducing enrollment time for patients, avoiding the need to redo data collection because of corruption and mitigating the scope of post-market studies due to weak data are all essential to the value proposition and are achievable via a vertical integration model.

Protocol Development
Protocol development is not an event, but a process. Several companies, when attempting to launch new products, met with obstacles that shut them down and inhibited their ability to bring the revolutionary transformation they set out to accomplish. Those products are listed here as food for thought:

The intradiscal electrothermal annulopasty (IDET) minimally invasive outpatient procedure was devastated by a Blue Cross and Blue Shield technology assessment that produced a denial of coverage.

The CHARITÉ lumbar disc may be the first device inmedical history that was cleared by FDA as safe but denied reimbursement by Medicare due to study nuances. Today, many carriers continue to consider lumbar disc arthroplasty as investigational and deny coverage despite a significant amount of data to the contrary. As a result, its utilization has suffered.

Kyphoplasty and Coblation have fought long and hard to overcome investigational claims and denials of coverage in the marketplace.

It’s very important from the outset to think about reimbursement as a pre-planning event.

There are other issues you must think about from the pre-IDE/pre-outcomes study planning perspective. You must look at functional, biomaterial and procedure analyses to define where the technology fits with today’s procedures, particularly those that represent the gold standard and state of the art. You want to investigate the fee structures of professional and facility services, as well as the cost of disposables and product requirements, against the backdrop of usual and customary reimbursement. It may be necessary to explore any opportunity to include payments on the inpatient and/or outpatient side in order to mitigate potential lost revenue from utilization of the product.

Data is critical to the research process, particularly detailed, sound data that supports medical efficacy, comparative effectiveness research and evidence-based care pathways. It will only become more imperative as we move toward the full implementation of healthcare reform. Many insurance carriers are denying coverage and thereby inhibiting the process for innovative treatments to get through to the consumer. This is due to a lack of what the carriers have determined is proper utilization and support in terms of patient outcomes, publications and efficacy in the spine community.

Achieving Accelerated Enrollment
The sponsor is always in search of ways to accelerate enrollment and obtain faster market approval without increasing costs. Companies are starting to utilize the combination of U.S. site and international site data. Utilizing this route, one must carefully determine how you will use the data obtained from international sites and receive FDA permission to use that data.

It’s important to note that each country has its own registration requirements for not only getting the product into the country but also for commercializing the product under its system. Monitoring and audits differ from place to place, and you have to follow each country’s specific guidelines. This is where an experienced CRO with a strong regulatory component can be of tremendous benefit.

Paying for clinical services varies from country to country, and is often very different from the U.S. For example, in the U.K., global packages for clinical services are now fully adopted into their research units, a model that originated in the U.S. Prior to this paradigm shift, it was almost impossible to use a global package payment strategy in the U.K.; everything had to go through the national health system, a process that significantly slowed enrollment. These are just some of the issues the sponsor needs to consider in terms of accelerated enrollment and lower study costs.

Another factor to consider is the tremendous opportunity for commercializing outside the U.S. by receiving a CE Mark. It requires a much smaller number of cases than FDA approval, and getting to market and generating revenue is often easier.

Pre-enrollment and Enrollment Strategies
As mentioned earlier, strategic site selection is critical to a successful trial. There must be a process to pre-qualify the site’s participation and quantify what is reasonable and realistic in terms of enrollment. That comes from its infrastructure, data mining, looking at prior clinical trial history and researching any historical experience the site has with FDA. All of these components are vital.

Marketing strategies for patient recruitment must be multi-focused. Education is a huge driver, as is data mining and community outreach. Print and online advertising are effective tools, with sponsors often helping maximize the trial’s exposure for attracting patients. Social media has become a large force in recruiting patients for clinical trials, and there are even groups that can identify databases of patients you can opt-in to meet your needs.

It is important to note that the recently-passed Sunshine Act makes full disclosure of all compensation agreements for physician consulting as well as clinical and administrative services for clinical trials. Full transparency is now required or organizations may face legal ramifications, not to mention postponement or cancellation of the study.

Post-market Strategies
You have significant work to do once you get through the FDA process, because you must train your sales force and develop tools for distributing the technology to facilities and physicians. Many companies will implement hotline support for questions about sales and pre-op qualifications.

A credentialing program is a requirement for many of these new devices or technologies. This program will be presented to payors and used to sustain a long utilization pattern in the industry.

If you’re proactively working in your markets and looking at opportunities for utilization, you should develop regional programs around your key sites and constantly educate the physicians, hospitals and payors in those communities. Reimbursement and coverage decisions are regional, not national, so it’s very important you develop relationships with the payors around your service sites.

Never stop collecting data. FDA-required post-market surveillance and studies as a condition of approval are becoming the norm. Data collection is not a single event; it’s a process.


Marcy T. Rogers, M.Ed., is President and Chief Executive Officer of SpineMark Corporation, the premier global spine service company for the development of Spine Centers of Excellence and Spine Research Organizations in partnership with medical professionals, hospitals and industry medical manufacturers. She can be reached at This email address is being protected from spambots. You need JavaScript enabled to view it..

SpineMark Corporation


Continue to learn from Ms. Rogers: Attend her educational session at OMTEC 2013 in Chicago.

How to Design and Execute a Clinical Trial
Wednesday, June 12, 11:10 a.m.-12:10 p.m. Badges copy

Just one in every five medical device clinical trials actually finishes on time. Delays lead to lost revenue, rise in expenses and the missed opportunity to be first to market with improved products, instruments and standards of care. Statistics also show that nearly 80% of medical device companies that commit significant time, talent and money to acquiring promising technologies, engineering them into products and conducting exhaustive pre-clinical studies eventually fall short of executing a successful clinical trial.

The presentation will address these specific points:

  • Investigative site selection and initiation
  • Patient recruitment and retention
  • Investigative site management
  • Pre- and post-study reimbursement strategies and payer mandates for coverage
  • Surgeon training and certification