The practice of gastroenterology is quickly changing. AGA is working to advise you on how technology will shape your practice today, tomorrow and far into the future.
I’m pleased to introduce our first AGA Tech Report, which summarizes some of the hot topics discussed at our 5th annual AGA Technology Summit. Please take a few minutes to read these short reports and you’ll have new information that is relevant to your practice's future.
Be on the look-out for more reports in the future. If you have any ideas or questions to share with the AGA Center for GI Innovation and Technology, please email us at email@example.com.
Michael Kochman, MD, AGAF, chair, AGA Center for GI Innovation and Technology
Both perspectives come together at AGA’s Center for GI Innovation and Technology, which supports innovation and technology development in the GI community while serving as a resource for gastroenterologists, innovators, industry, investors and regulators. One of those resources, the annual AGA Technology Summit, looks at challenges and unmet needs from the perspectives of both the surgeon and the endoscopist.
Medical technology must grow beyond its traditional silos to become a common effort with support from the entire community of stakeholders. If innovation withers, all of the stakeholders are to blame. If it grows, all will benefit.
Surgeons see two key procedural gaps: endoscopic closure of leaks and fistulas and endolumenal full thickness resection of colon cancer.
Gastrojejunal anastomotic leaks — one of the most difficult GI surgery closures — are associated with significant morbidity, including delays in oral nutrition, deviations from standard pathways of care, physical and mental debilitation, and cost.
Brian J. Dunkin, MD, FACS, professor of clinical surgery, head of endoscopic surgery and medical director, Methodist Institute for Technology Innovation & Education, Houston, TX, said that no good solutions for closing gastrojejunal anastomotic leaks currently exist. Surgery is often not an option for these patients. Clips and sutures do not work. Stents are expensive and can further damage weakened tissue and cause pain.
In the area of endolumenal full thickness resection, the unmet need is enormous, with estimates of 96,380 new colon cancer cases and 40,000 new rectal cancer cases in 2014.
Current surgical techniques require the removal of about a third of the colon even though colon tumors require only a one to two centimeter negative margin for good oncologic control.
Surgical technique includes three steps: divide tissue, manage bleeding and rejoin tissue. A laparoscopic colon resection can be accomplished in about seven minutes using electrocautery, Dr. Dunkin said, but at present there are no endoluminal devices with the necessary energy output and tissue handling capabilities. Laparoscopic energy-based vessel sealing devices are used routinely to rejoin tissue.
In both areas, advances have been made, but more development is needed. Radio frequency (RF) energy devices for endoluminal use welding soft tissue have been tested successfully in animal models — the same devices used in laparoscopic procedures reengineered for endoluminal use. Technologies such as the Endo-SPONGE, initially developed for wound use, may be adaptable to treatment of GI leaks and fistulas.
Endoscopists also know many unmet procedural needs remain — in acute disease to save lives, in chronic disease to improve quality of life, and in neoplasia to prevent and cure disease. Those needs include new approaches to functional GI disorders such as IBD, faster and safer en bloc excisions and the development of flexible endoscopic intraluminal treatment options for obese patients.
Plenty of research and development is underway to meet those immediate clinical needs, said Christopher Gostout, MD, director of the developmental endoscopy unit, Mayo Clinic, Rochester, MN, but systemic barriers hinder the creation and adoption of new technologies that could help fill some of those clinical gaps.
On the research side, it is easy and often appealing to follow esoteric paths “just in case” something pans out. Research and researchers could get better results by focusing on immediate clinical needs and utilizing techniques that work in other technology industries, including pay-for-performance at the research level and prioritization of programs and projects using input from multiple sectors.
On the development side, stakeholders must think clinically and put patient needs first. A new technology or procedure that fails to solve an unmet medical is a dead end in the world of evidence-based, value-based health care.
The parochial, capricious and often obstructive coding, coverage and reimbursement process must be revised, noted Dr. Gostout. The health-care system will not adopt even the most effective new technologies until it is appropriately reimbursed. The current CPT coding system thwarts prompt and appropriate reimbursement for new devices and procedures regardless of their effectiveness. Policies that favor the bundling of codes create disincentives to invest in the development of new technologies.
FDA has improved its performance assessing medical technology, but payors have not. A recurrent theme was that CMS and the commercial payors must develop clear and consistent standards for coverage and reimbursement approval that work in concert with FDA marketing approvals.
The crosscurrents of innovation and reimbursement in 2013 emerged as a key theme during the 2014 AGA Technology Summit, sponsored by AGA’s Center for GI Innovation and Technology (CGIT). Complacency is as much a disease as colorectal cancer. Without intervention, both can be fatal.
Fortunately, innovation in GI technology surged forward in 2013. New colonoscopy instrumentation showed dramatic improvement in polyp detection, peroral endoscopic myotomy (POEM) emerged as a key minimally invasive technology for achalasia, and fecal transplants gained approval for treatment of Clostridium difficile. Whether reimbursement keeps pace with these and other new emerging technologies remains an open question.
Pivotal studies bring new devices toward clinical adoption, but reimbursement issues can impede clinical progress.
“It’s easy to become complacent about colonoscopy,” said Michael Kochman, MD, AGAF, CGIT chair and Wilmott family professor of medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. The aging baby boomer population and the Affordable Care Act bring more older adults into the health-care system.
The latest innovation in colonoscopy, full spectrum endoscopy (FUSE) offers a 330-degree view and a potential improvement in polyp detection rates. The combination of innovative technology, an expanding patient base, and assured reimbursement offers little incentive for legacy practitioners to shift away from colonoscopy in the short-term. Long-term, however, colonoscopy cannot endure as the primary support for most GI practices.
Many expect CMS to cut colonoscopy reimbursement rates in the coming years. Competing technologies for colorectal cancer screening have improved, and at some point will likely equal the polyp detection rates demonstrated by the best gastroenterologists, and potentially at a lower overall cost to the system. GIs who want to adopt new technologies such as FUSE must invest in equipment and training without any assurance that reimbursement will increase as their outcomes improve. The interplay of innovation and reimbursement means GIs must diversify their practice beyond colonoscopy.
New data, new practices
Equally significant changes in the treatment of Barrett’s esophagus are on the way. New outcomes data question the need for frequent endoscopic surveillance of nondysplastic Barrett’s. These new data could affect guidelines on both the surveillance interval for patients with Barrett’s and the use of ablation.
Emerging evidence in gastroesophageal reflux disease (GERD) suggest more opportunities for non-pharmacologic intervention. Recent studies show clinical benefit from endoscopic barriers, surgical barriers and pacer/electrical stimulation. There are no clearly superior technologies at this point, but clinical changes are likely.
Natural orifice surgery is showing clear signs of success. The U.S. NOSCAR cholecystectomy study has been completed, but the results are still sealed. Trials have shown very strong early evidence for POEM, and the procedure may be able to replace laparoscopic Heller myotomy; but the lack of a clear coverage and reimbursement pathway could hinder adoption as the Heller procedures have established reimbursement.
The past year also brought progress in fecal microbiome transplantation as the FDA reversed initial objections and accepted FMT for select C. difficile infections. The agency is developing FMT regulations, but reimbursement remains an issue. (More about FMT: fmt.gastro.org)
New codes for endoscopic mucosal resection may allow for physician reimbursement, but the reimbursement amount remains poor in comparison to the time and risk incurred. The current CMS reimbursement structure gives far greater weight to costs incurred than to costs avoided; a selective focus that disadvantages new technologies and procedures that carry higher initial costs but lower overall expenditures to the health system.
New investment climate
The long drought in medtech investment is easing, which made 2013 positive for investors.
The continuing record-low interest rates encourage all varieties of investors. A sharp spike in the number of adults turning 30 will foster investment just as a similar spike fed the investment boom of the 1990s, predicts Jason Mills, managing director and equity research analyst for Canaccord Genuity, San Francisco, CA.
That positive investment climate favors technologies with strong growth. But the most sought-after technologies will be those that offer strong growth plus strong gross margins. Strong margins require appropriate reimbursement. Medical societies can help to bring new technologies to market with an assured reimbursement pathway by acting as impartial intermediaries between industry, payors, regulatory authorities and patients.
Cardiology built a highly successful model using patient registries in transcatheter valves (TVT registry) and left ventricular assist devices (INTERMACS). CGIT has launched a similar initiative with the STAR registry. STAR will collect real-world data comparing laparoscopic fundoplication versus transoral fundoplication for GERD. Evidence from both the clinical and cost perspectives will be key to winning the marketing and reimbursement approval that clinicians need to bring innovation into clinical practice.
The move from volume-based reimbursement to value-based payment for colorectal cancer (CRC) screening and other GI procedures means the days of colonoscopy as the primary practice revenue stream for GI could be numbered. But what will replace fee for service? When will that happen? The only clear answer is that fee for service is a model whose time is passing.
The 2014 AGA Technology Summit included a broad discussion of how value-based and accountable care affects gastroenterology. Sponsored by the AGA Center for GI Innovation and Technology, the fifth-annual gathering focused sharply on reimbursement and business issues, as well as on technology development.
CMS has already requested comments from specialty practices on how to transition specialists to value-based payments. Betsy Thompson, MD, DrPH, chief medical officer for CMS Region IX in San Francisco, CA, said that the agency does not expect to release proposals immediately, but that CMS does believe that they have to move from a volume-based payment system to a value-based system.
CRC screening has reduced the CRC burden by 46 percent from peaks for incidence and mortality in the early 1950s, but screening has become one of the largest expenditures in health care. As more Americans obtain health coverage under the Affordable Care Act (ACA), payors want to blunt the increase in screening costs.
The result is growing pressure from payors to pay less for care, including GI care, said James Robinson, PhD, MPH, the Leonard D. Schaeffer professor of health economics and director of the Berkeley Center for Health Technology at the University of California, Berkeley. Public payors are beginning to bundle payments and reduce the procedure time assigned to some of the most common procedures such as colonoscopy. The ACA favors the creation of accountable care organizations and other value-based programs. Private-sector plan sponsors seeking to reduce spending and add value are using tools such as price transparency and reference pricing.
Reference pricing is not a cap on provider charges, Dr. Robinson said, but a cap on the amount providers will contribute toward provider charges. He likened reference pricing for procedures such as colonoscopy or knee and hip arthroplasty to per diem payment for business travel. The traveler, like the patient, is free to spend any amount for a luxury hotel, but the employer sets a maximum contribution, perhaps $150 for a hotel, for example, or $1,250 for a colonoscopy or $30,000 for a joint replacement. The consumer — whether a traveler or patient — pays any excess.
Accountable care organizations (ACO) take a different approach. Rather than capping benefit contributions to patients, ACOs share risk with providers to seek the triple aim of improving the patient experience, reducing per-capita costs and improving population health. While reference pricing selectively targets high-expenditure procedures such as colonoscopy, there is no concerted effort to reduce GI compensation in the ACO world. Instead, ACOs reward providers for improving quality and controlling costs.
ACOs actively seek to share the financial risks of providing care, explained Anton Decker, MBBCh, MRCP, chief medical officer, Banner Medical Group, Phoenix, AZ, a Pioneer ACO that employs more than 1,300 providers. The key to succeeding in an ACO environment is to understand the needs of the different stakeholders: health systems, insurers, providers, medical groups, hospitals and ACOs themselves. All have a stake in helping the ACO become and remain profitable, either by reducing expenses (decreasing unit costs or utilization) or by increasing revenues (attracting new members).
ACOs offer many opportunities because they deal with big data, big dollars and multiple stakeholders. Small changes can translate into large savings, which can increase the potential amount that can be shared between providers and other stakeholders.
Providers have a powerful information advantage in the ACO world, Dr. Decker said. Achieving the triple aim relies on evidence-based medicine, and providers are often the only stakeholders who know and understand the medical evidence favoring a particular technology or technique. That creates tremendous clinical and financial opportunities for efficient and innovative providers on the clinical side that also are creative on the business side.
In the shift toward value-based reimbursement, physician-led groups find themselves in a strong position to provide the greatest improvements in clinical care and in health-care value.
The technique long known simply as endoscopic imaging has been renamed white light endoscopy. The broad-spectrum light source has not changed, but almost everything else surrounding endoscopic imaging has shifted.
From a single technology of imaging tissue via a device, endoscopic imaging has evolved in a variety of technologies. New techniques and devices employ contrast agents, specific wavelengths of light, autofluoresence, magnification and extremely high-resolution endoscopy, multi-modal techniques, and light sources that can penetrate tissue to visualize specific tissue planes that can be combined to produce useful images and optical tissue biopsy.
All of the new imaging technologies focus on familiar goals: improve lesion detection, enhance surveillance for the detection of dysplasia, help target biopsies and enhance therapy to improve patient outcomes.
The 2014 AGA Technology Summit surveyed the latest, best and most promising new imaging modalities. Imaging, like other medical technologies, is more than discovery and development. The AGA’s Center for GI Innovation and Technology, sponsor of the summit, has long emphasized the need to move innovation from development to device to widespread and appropriate adoption.
Innovation must improve clinical outcomes or lower costs (ideally both) to be endorsed for widespread clinical application. New and different are not enough. Any new imaging technology or device must address a genuine need, said Uri Ladabaum, MD, MS, director of the gastrointestinal cancer prevention program at the Stanford University School of Medicine, CA.
In order to change the standard of care in the community, a new technology cannot discourage a broad spectrum of gastroenterologists from investing the time and resources required to abandon a practice they know for a new device they must learn. It also must be technically and clinically feasible beyond a narrow universe of academic experts and clinical investigators, while having a clear pathway for reimbursement at a level that supports adoption.
Potential targets for innovation in imaging are familiar. In the esophagus, clinicians need to identify early squamous cell cancer, gastroesophageal reflux disease with minimal change, Barrett’s esophagus and early carcinoma. In the stomach, targets include atrophic gastritis, intestinal metaplasia, gastric antral vascular ectasia and early gastric cancer. In the duodenum, objectives are dealing with celiac disease, adenomas and focal lesions. In the colon, primary interests include adenomas and IBD surveillance.
Superiority over current techniques can be difficult to prove, he said. For instance, confocal and high-resolution techniques can show very good results in expert hands, but factors such as operator expertise and comparators can have large effects in trial results.
Traditional white light endoscopy remains the most common modality in the U.S., said Mel Wilcox, MD, MSPH, professor of medicine and director of gastroenterology and hepatology at the University of Alabama at Birmingham. Chromoendoscopy is gaining ground in Europe, using both reflective and absorptive properties.
Some techniques use stains such as methylene blue and indigo carmine to enhance the contrast of the mucosal surface. U.S. clinicians tend to see dyes as unnecessarily cumbersome and messy and have been slow to adopt the techniques.
Other techniques use image enhanced processing, including narrow band illumination (NBI) to enhance vascular patterns, which can be extremely useful. Different wavelengths penetrate tissue to different depths to help enhance vascular patterns. Short wavelengths of blue and green are selectively absorbed by hemoglobin in capillary vessels, which can highlight neoplastic lesions.
High-resolution endoscopy (HRE) captures images with up to 1 million pixels to allow for virtual magnification while retaining useful resolution of fine details.
Autofluorescence imaging (AFI) uses very short wavelengths to excite tissue leading to autofluoresence, which may help distinguish normal versus abnormal tissue. Data comparing AFI to white light imaging are inconclusive, Dr. Wilcox said. The same goes for tri-modal imaging, a combination of NBI, HRE and AFI.
Endomicroscopy uses a low-power laser to illuminate target tissue at a specific depth and visualize a specific tissue plane. Horizontal and vertical planes are reconstructed to show tissue at the cellular level. When used in Barrett’s esophagus, endomicroscopy triples neoplasia detection and avoids up to 60 percent of biopsies indicated under white light.
High-resolution endomicroscopy is significantly more accurate than other imaging modalities, Dr. Wilcox said and in certain applications may potentially be more cost-effective than current techniques. It is not yet clear whether clinicians and payors are ready to broadly adopt this technology.
Endoscopic mucosal resection (EMR), the standard of care for the removal of precancerous and early cancerous lesions confined to the superficial mucosal and submucosal layers of the GI tract, also serves as the first step for techniques and devices that allow endoscopic submucosal dissection (ESD) and full-thickness resection that incorporate a combination of endoscopic and surgical techniques.
Advancing the practice of endoscopic procedures requires more than new techniques and new devices. The profession needs innovators to develop new technology, device makers willing and able to pursue marketing approval, and a coverage and reimbursement climate that allows clinicians to bring the safest and most effective new techniques to patient care.
The AGA Center for GI Innovation and Technology focused attention on both reimbursement and technology during the 2014 AGA Technology Summit.
Some of the necessary devices for endoscopic resection already exist, such as the BELA flexible bipolar hemostasis forceps. While it appears to be as effective as laparoscopic control of vessels two to five mm, it has not yet received FDA approval for use in the U.S.
The combination of EMR and energy-based techniques such as radio frequency ablation has already replaced surgical treatment for dysplasia and early stage tumors in the esophagus. In Japan, clinicians commonly use ESD for early gastric cancers. Worldwide, the management of rectal polypoid lesions has evolved from open surgery to endoscopy-assisted laparoscopy to transanal excision to transanal endoscopic surgery with EMR and ESD techniques.
Gastroenterology must enable new technology, not just develop it, said AGA Center for GI Technology and Innovation Chair Michael Kochman, MD, the Wilmott family professor of medicine in the Perelman School of Medicine, University of Pennsylvania, Philadelphia. Full-thickness endoscopic resection may be technically feasible, but it remains impractical until innovative reimbursement strategies catch up with innovative GI technologies. Under the current Relative Value Units system, it is not practical to propose adoption of a two- to four-hour full-thickness endoscopic resection when current techniques are reimbursed based solely on the work effort and not on the overall cost-savings to the system.
Interventional endoscopists keep pushing the bounds of the possible despite the adverse reimbursement climate. Janak Shah, MD, director of pancreatic and biliary endoscopy at California Pacific Medical Center in San Francisco, reviewed the field from the gastroenterologist’s perspective.
Efficacy for EMR, now the standard for the removal of precancerous lesions and early cancers from the esophagus to the colon, has reached better than 95 percent for lesions even greater than 2 cm, with low recurrence and complication rates. EMR offers a short procedure time than surgery, but safe en bloc resection may not be possible for lesions larger than about 25 mm.
ESD allows for large area en bloc resection, but the procedure often takes a minimum of 60 to 90 minutes or more. ESD also requires specialized training, a major reason the technique is not commonly used in the U.S. The field needs innovative techniques and devices that allow the removal of more advanced lesions with fewer complications and shorter procedure times.
Surgical endoscopist Brian J. Dunkin, MD, FACS, professor of clinical surgery, head of endoscopic surgery and medical director at Methodist Institute for Technology Innovation & Education, Houston, TX, provided summit attendees a surgical prospective. ESD is a very practical approach in the rectum but can be challenging farther into the GI tract. The laparoscopic approach provides a better safety profile for treating large lesions in the colon, but full-thickness endoluminal resection techniques for gastric and colorectal lesions are being developed.
The evolution of minimally invasive surgical approaches for rectal cancer helps illustrate the technique transition. Radical surgery has a mortality rate of 2 to 8 percent and morbidity between 30 and 50 percent, said Elisabeth McLemore, MD, associate professor of surgery at the University of California, San Diego. Transanal excision is associated with less morbidity and mortality for benign disease (adenomas), but recurrence rates were as high as 32 percent. Transanal endoscopic microsurgery (TEM) halved local recurrence rates with morbidity and complication. Only a single head-to-head randomized comparison of TEM and anterior resection for well selected, early stage rectal cancer (T1N0M0 without high-risk pathologic features) has taken place, but TEM showed similar outcomes with significantly less complication and morbidity compared to radical resection.
Early results suggest ESD can produce similar results for colorectal neoplasia in select patients. ESD can produce intact specimens and margins in appropriate patients, but widespread adoption will require improved technology, techniques and reimbursement.
The 2014 AGA Technology Summit, sponsored by the AGA Center for GI Innovation and Technology, examined the practical issues involved in innovation, including strategies to convince clinicians to accept new technologies.
“Innovation is not always viewed as a positive,” said Thomas Fogarty, MD, founder of the Fogarty Institute for Innovation, Mountain View, CA, who opened a symposium on adopting and incorporating new technologies into clinical practice.
While in medical school, Dr. Fogarty invented the Fogarty Balloon Embolectomy Catheter, the first of more than 100 medical technology patents he has received.
The Fogarty balloon catheter was initially denounced as a dangerous instrument and as an inappropriate procedure. It was so far beyond 1960s state of the art that one critic said only one so inexperienced and uninformed as a student would dare to think of it. Tens of millions of patients later, the Fogarty balloon is seen as the first in a long line of minimally invasive vascular devices.
“If you want your technology to transform clinical practice, it has to truly advance care,” said John Pandolfino, MD, MSCI, professor and chief of gastroenterology and hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL. “It has to improve diagnostic accuracy, improve outcomes or replace a more expensive or more dangerous intervention. It has to make things easier for clinicians and patients. And it has to show a better risk/benefit ratio than existing interventions.”
A focus on a definable patient process provides the surest path to clinical innovation, said Bruce Ramshaw, MD, chairman and chief medical officer, Surgical Momentum, and clinical associate professor of surgery, Florida State University College of Medicine, and co-director, Advanced Hernia Solutions, Daytona Beach, FL.
Sharp clinical focus can bring quick adoption. High-resolution esophageal pressure topography and manometry (HRM) leapt into clinical practice because it dramatically improved manometry accuracy, simplified the procedure and reduced the time needed to acquire the data while offering patients more comfort. The procedure also provides clinicians with a topographic pressure map of esophageal motility that allows them to accurately classify achalasia and guide their patients towards the most appropriate treatment.
Peroral endoscopic myotomy (POEM) could find similar success. Clinicians want to use the procedure because it is safe, quick and produces excellent outcomes. But payors still concentrate on the traditional laparoscopic Heller myotomy.
“A successful new technology has to answer four questions,” said Scott Melvin, MD, professor and chief of surgery, Montefiore Medical Center and Albert Einstein College of Medicine, New York, and past president of the Society of American Gastrointestinal and Endoscopic Surgeons. “Does it meet a clinical need, does it add value, is it financially viable and is it usable by typical clinicians? You have to address all four questions early in the development process. Just because a technology is new and exciting isn’t enough. It has to show positive benefits for all.”
Dr. Melvin said surgeons adopt new technology for many reasons: to improve patient outcomes, to save time, and to be seen as innovators by their peers.
Hospitals have different motivations. They want to see better patient outcomes while being perceived as innovators in order to attract more patients, all while reducing the cost of care.
“Sometimes those motivations align and you get tremendous clinical acceptance,” he said. “Innovators need to understand the different motivations and create a clear pathway to acceptance by all of the stakeholders.”
The hurdles to clinical innovation have changed, as payors demand long-term safety, efficacy and economic data to justify reimbursement. And without adequate reimbursement, hospitals, health systems and clinicians cannot afford to implement even the most promising innovations.
“Focus on the patient, not on the technology,” advised Naomi Aronson, PhD, executive director of clinical evaluation, innovation, and policy for the BlueCross BlueShield Association, Chicago IL. “The question you have to answer is how can I innovate in a meaningful way to improve outcomes?”
Dr. Aronson outlined the shift in payor perspective during the 2014 AGA Technology Summit. Payors now expect evidence showing effectiveness in the real world where treatment outcomes can be mediated by operator skill, the health delivery system, clinician behavior and patient adherence.
“There is finally a serious recognition of the impact of cost on care,” she explained. “Cost is a patient-centered outcome. Cancer care, successful or not, can bankrupt the patient’s family. Cost needs to become a central part of our conversation about utility.”
The AGA Center for GI Innovation and Technology helps medical technology meet these new challenges. The center has taken a role as a neutral, third-party broker to assist regulators, payors and device makers to develop an observational research registry framework. The center’s first initiative, the STAR Registry, was launched in 2014 to document outcomes for laparoscopic versus transoral fundoplication surgery for patients with gastroesophageal reflux disease.
“This is the first real-world data on outcomes on transoral surgery for GERD compared with laparoscopic surgery,” said AGA Center for GI Innovation and Technology Chair Michael Kochman, MD, the Wilmott family professor of medicine at the Perelman School of Medicine, University of Pennsylvania, Philadelphia. “STAR will provide physicians, patients, purchasers and payors with long-term efficacy data that is invaluable to patient care decisions. We need to mitigate uncertainty to allow industry to direct dollars and efforts in useful directions.”
FDA unveiled process innovations to encourage more first-in-human device trials and approvals in the U.S. The Early Feasibility Study (EFS) aims to boost U.S.-based development by encouraging early consultation and planning between inventors, developers, investigators and regulators.
“Devices are increasingly being tested and developed for non-U.S. markets because of regulatory factors,” said Herbert Lerner, MD, deputy division director-clinical, division of reproductive, gastro-renal, and urological devices at the FDA Center for Devices and Radiological Health, Silver Spring, MD. “There is a cost of not having these new devices for patients in the U.S.”
EFS uses benefit/risk principles to help focus regulatory decision-making on the clinical context, encouraging reviewers to focus on the totality of the risk/benefit profile. That includes considerations such as life-limiting or life-threatening disease conditions and the limitations and risks associated with existing therapies.
“FDA is making a commitment to having devices studied, approved and brought to patients in the U.S. first,” Dr. Lerner said. “We can now consider what the risk is of not having a device here. Work with us to get ready for submission.”
Getting ready for submission should include planning development and clinical trials with FDA’s mission in mind: protecting and advancing public health.
“Meeting an unmet medical need is the reviewer’s primary goal, not the success of your technology,” said Jonathan Seltzer, MD, MBA, president, ACI Clinical, Bala Cynwyd, PA. “FDA reviewers want to promote health and to advance science, but they have to do it within a regulatory framework. When developing your technology, clinical trials should be designed with endpoints that demonstrate clinical utility and benefit. This makes it easier for FDA to grant approval.”
The workshop has improved the information exchange between FDA and innovators, device makers, venture capitalists and other players in the device world. The workshop also helped introduce some of FDA’s own innovations designed to boost device research and development.
Herbert Lerner, MD, deputy division director-clinical, division of reproductive, gastro-renal and urological devices for the FDA Center for Devices and Radiological Health (CDRH), Silver Spring, MD, reviewed the lessons shared by stakeholders at the joint workshop during the 2014 AGA Technology Summit, sponsored by the AGA Center for GI Innovation and Technology.
“We recognize that two of the biggest barriers to innovation in medtech are FDA’s traditional risk-averse stance and the inconsistency with which therapies are reimbursed,” Dr. Lerner said. “They are part of the reason venture capital funding for start-up medical devices and biotech is down 60 percent in the last six years.”
A key lesson for future innovation is that lack of predictability discourages investment in new technology. Venture capital hesitates in the face of changing standards and past precedents that are not predictive of future decisions. Industry too often sees requirements that change during the review process. Reviewer turnover means constant re-education as well as inconsistent feedback from different reviewers.
Delays in scheduling meetings and insistence on further data and studies have real costs. For a company with 30 employees, simply delaying an FDA meeting by eight weeks could cost $1.8 million. An additional preclinical study with 20 animals can cost upwards of $5 million.
An extra year negotiating an investigational device exemption can add $10.8 million to regulatory costs, while requiring an additional 500-patient study with three years of follow-up can cost $24.1 million, or a similar study with 500 patients can reach $68.2 million.
On the FDA side, poor quality submissions impede the review process. What FDA sees as incomplete or unexpected data may be reflected in incomplete or unexpected labeling.
“We want to know what happens long-term, but we are not getting that kind of information from sponsors,” Dr. Lerner said. “We label based on the data we receive.”
The good news is that both regulators and industry are becoming more comfortable with a shift from pre-market to post-market assessment of medical devices. The shift helps balance the need for safety data with the financial burden of acquiring that data. The shift also assumes that patients are willing to accept more risk in return for earlier access to new therapies.
A pilot study in obesity found that patients do have preferences when it comes to balancing risk and access. The Patient Preference Initiative (PPI) showed that CDRH can use patient preferences as part of its own decision-making process.
The PPI surveyed about 650 obese individuals drawn from a national cross-sectional panel with more than 11,600 patients. The survey assessed preferences in type of operation, diet restrictions after surgery, projected weight loss, typical duration of weight loss and effect on comorbidities and medication use.
Results help the agency quantify patient values to help define clinically meaningful weight loss and estimate the values patients give to both risks and benefits from treatment. Dr. Lerner said that the method could be adapted for other medical treatments.
Weight loss remains a captivating target. Patients clearly want an easy fix for obesity, preferably a solution requiring little activity or self-deprivation, and two devices in development may meet those requirements.
Allurion Technologies is developing a gastric balloon, the Elipse™, that is swallowed and then left inside the stomach to induce satiety. After three months, the balloon deflates on its own and passes from the body naturally through the digestive tract. “The mechanism of action is the same as familiar endoscopically placed gastric balloons, however the Elipse™ is intended to be swallowed in an office setting and allowed to pass at home,” said Allurion co-founder and Chief Scientific Officer Shantanu Gaur, MD. “When you take out the endoscopy, you take out a lot of the costs,” continued Dr. Gaur. “Our goal is to make Elipse™ accessible to cash-pay patients worldwide.”
Obese patients typically lose about 14.7 kg over six months using endoscopically-placed balloons, he said. The Elipse™ is designed for 90-day use based on extensive data showing that about 80 percent of this weight loss occurs within the first three months.
EndoSphere takes a different approach with its SatiSphere, a temporary insert currently under development. A string of mesh spheres placed endoscopically in the duodenum slows passage of chyme lipids and proteins and stimulates neurohormonal pathways that signal satiety.
“We believe the real action in weight loss is in the duodenum,” said EndoSphere CEO Patrick O’Donnell. “The device tricks the body into thinking it has taken in more calories than it really has.”
SatiSphere is in its third generation of design, with a 50-patient pilot study planned in the U.S. for late in 2014. An earlier iteration gained CE marking, and commercial sales in the EU are planned for 2016. U.S. marketing is projected for 2018.
Alpine Medical Devices is developing what may be the first reusable esophageal/hemorrhoidal ligator to treat bleeding and non-bleeding varices. Jan Kamler, MD, Alpine developer and president, said that a significant portion of the estimated 85 million bleeding patients who live outside advanced economies don’t have access to existing single-use ligators.
“Current ligators work fine, but are not reusable,” Dr. Kamler said. “Most of the world cannot afford the ligators that we use in the U.S. and Europe. Even in these economically advanced areas there is strong pressure to reduce costs. Alpine meets those needs.”
The two-part Kamler DC ligator attaches easily to most standard endoscopes, he said. A simple pull cord on the scope handle activates the ligator. Dr. Kamler has a fully functional prototype and has completed animal cadaver studies.
Endoscape founder and CEO Chul Hi Park, PhD, said his company has two new technologies under development. The first, a tissue engagement device that uses large-area suction devices to assist colon intubation, is inspired by the suction applied by octopus tentacles. The device allows the endoscopist to push, pull and pleat the colon and to stabilize tissue for endoluminal procedures.
“The target is challenging intubations, a few million cases every year in the U.S. alone,” Dr. Park said.
As a utility device, no clinical trials are needed, he continued. Endoscape plans a 510(k) submission in the near future.
The second device is a digitally controlled GI endoscope, called the iScope. A controller under development will provide semi-autonomous bending control during intubation as well as autonomous targeting of lesions, more precise bending control and dynamic stabilization of the endoscope tip.