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Articles from 2015 In March

How to Stay Competitive in 2015: Three Pillars of New Device Development

How to Stay Competitive in 2015: Three Pillars of New Device Development

Manufacturers that implement adaptive trial design, health economics, and risk-based monitoring will have a competitive advantage.

Vicki Anastasi and James Eaton

Regulatory and reimbursement reform is moving rapidly on a global level. Regulators and payers expect real-world evidence that demonstrates efficacy, safety, and an improvement over standard-of-care relative to the cost of the device.

To stay competitive, medical device manufacturers must take a three-pillared approach to product development:

  • adopt adaptive designs to acquire higher quality clinical evidence that improves trial and portfolio decision-making
  • collect solid health economic data to justify pricing and reimbursement
  • employ error-analysis driven risk-based monitoring approaches to reallocate resources to high-risk clinical sites to improve operational efficiency

These pillars are not mutually exclusive, but they tackle different issues encountered when bringing a device to market.

Adaptive Clinical Trials

Collection of health economic data and risk-based monitoring work best in the framework of an intelligently designed trial. Adaptive trial designs, which use preplanned adaptations to a trial to correct initial incorrect assumptions, enhance the efficiency of device development by reducing the need to repeat trials that narrowly miss a clinical endpoint and eliminating unnecessary patient recruitment for overpowered designs. For small patient populations, this can reduce recruitment time by many months. Adaptive designs that incorporate economic models can ensure that a device launches with the right clinical and safety data, as well as a strong economic value proposition.

In the worst-case scenario, adaptive designs can also prevent unnecessary expenses by terminating trials that show no benefit early on over a predicate. Though an adaptive design will not be possible for all medical device studies, the upfront feasibility analysis that is required focuses the trial and improves sponsor decision-making even if an adaptive design is not used.

Although adaptive trial designs are not as well known in the medical device space, they are employed in 20% of trials in the pharmaceutical space and their prevalence is expected to increase. Adaptive design makes an interim data analysis possible and so can shorten a trial’s timeline, reduce operating and development costs, limit unnecessary patient exposure, and, importantly, generate higher quality data that enable sponsors to ask better questions and make better decisions.

Three types of adaptive design are particularly applicable to medical device trials. Sample size reestimation allows sponsors to use interim data to right-size their trial by adding or removing patients in order to achieve statistical significance. This is the most popular type of adaptive design for medical device trials, making up 80% of adaptive design submissions to FDA’s Center for Devices and Radiological Health from 2007 to 2012.1 Adaptive group sequential designs, the second type, allow for early stopping for futility, efficacy, harm, or safety. Finally, seamless adaptive designs combine the pilot and pivotal studies into one trial and allow the same patients to be used for the entire duration of the trial.

Regulators are generally open to the use of adaptive designs in medical device trials when appropriate, as evidenced by the release of regulatory framework on the topic. The greater hurdle is obtaining organization-wide buy-in for the additional upfront planning time and infrastructure to design and execute these types of trials. Interim analyses require fast and efficient electronic data capture and cleaning. An independent data monitoring committee that controls data flow will minimize operational bias associated with interim analyses and maintain trial integrity.

Health Economics

Device reimbursement is increasingly contingent upon the presentation of solid health economic (HE) data that demonstrate a device’s value both in terms of patient benefit and in comparison to competitors.

Collecting HE data before reimbursement hurdles appear is not a common practice in the device industry. However, understanding how a device offers value and capturing relevant economic endpoints early can be vital to maximizing a device’s health economic story. Data collection strategies differ when justifying a technology that may not improve efficacy, but does reduce resource use and costs through demonstrated safety or patient usability improvements.

To avoid the unnecessary expense of a separate study, the best strategy is to collect HE data during regulatory trials or prospective registries. Measuring product attributes against existing comparators during preclinical development can help evolve the technology and clarify what additional clinical and economic data are needed to support the value story.

Early evaluation of HE data cultivates a better understanding of a device’s value proposition and thus a more informed discussion about the likely price that the market will bear. Naming a competitive price is particularly important in countries outside the United States that have adopted health technology appraisal with cost-effectiveness. Although only the United Kingdom specifies a cost per quality adjusted life year threshold, representing the amount the National Health Service is willing to spend on a new intervention, many other countries have implicit thresholds beyond which a product is highly unlikely to be reimbursed.

Health economic arguments must be adaptable to different reimbursement agencies, as there is no singular solution appropriate for every jurisdiction. Building long-term relationships with HE advisors can cultivate greater understanding and appreciation of the value of the product on a global level. Onboarding advisors early in the process will ensure that manufacturers receive the right HE advice early on in the development cycle.

Risk-based Monitoring

As clinical trials become more complex, clinical investigators are burdened with more complicated procedures, frequent protocol amendments, and lengthier case report forms. At the same time, clinical research associates (CRAs) are unable to properly train and communicate with investigators because they spend the majority of their time at trial sites manually verifying all source data. These issues can lead to delayed recruitment and protocol non-compliance, both of which lengthen trial duration and slow time to market.

Adopting a risk-based approach results in a more efficient deployment of resources that allows for a more meaningful CRA interaction at each trial site. Traditional clinical trial onsite monitoring practices are frequency-based and rigid, with most employing 100% source data verification (SDV) at all times regardless of the risk profile of the trial or site. In pharma trials, employing 100% SDV consumes an estimated 25–30% of the total cost of a Phase III trial2 and detects random errors that are not likely to significantly impact the outcome of a trial.3 Though these numbers may differ in magnitude for device trials, it is generally accepted throughout both industries that 100% SDV is extremely time-consuming, can provide a false sense of data integrity, and may not be as effective as intended.

Regulators and pharmaceutical industry working groups support centralized monitoring strategies that reduce SDV, including risk-based monitoring.4 According to FDA, a risk-based approach does not result in any less vigilance in site monitoring and is “dynamic, more readily facilitating continual improvement in trial conduct and oversight.”4c

Taking a statistical approach to site monitoring can improve the effectiveness and efficiency of the process by helping a CRA prioritize and guide site visits. A novel approach called Verification by Statistical Sampling (VSS)5 uses a risk-based, adaptive monitoring algorithm to reduce the number of data points to be verified at each visit when appropriate. Each trial has a unique risk profile that is determined by factors such as study phase, objectives, protocol design, complexity, size, and endpoint. The risk profile dictates an acceptable quality limit (AQL) that then defines the number of acceptable errors in site data. Sites whose data are near or below the AQL require fewer monitoring visits, while sites whose data are above the AQL require more visits and greater scrutiny, in some cases 100% SDV.

VSS and a risk-based approach to site monitoring can reduce the cost of premarket, postmarket, and IVD studies while effectively managing trial risk and without compromising data quality. For example, in a hypothetical premarket cardiovascular device study involving 194 subjects across 30 sites in a single country, with a duration of 44 months from start of activity to final study report, deploying VSS can reduce monitoring visits per site by 63%, from eight to three, and can cut monitoring costs by 46%.6

There are significant technology requirements for implementing an offsite, centralized risk-based monitoring approach.7 Sponsors will require the ability to adjust risk profile and monitoring approaches based on incoming data. Clinical investigators and study personnel will benefit from a platform that includes training, performance support, and study management tools.

An Integrated Approach

Increased regulatory burden and the demand for a compelling health economic story are signs of a changing tide in the medical device industry.

Adaptive design, health economics, and risk-based monitoring can provide the opportunity for a manufacturer to make informed commercial and development decisions without compromising trial integrity. When integrated, these approaches can ensure that technology not only launches with the right clinical and safety data, but also a strong economic value proposition.

Manufacturers that are able to implement these approaches will not only have a competitive advantage, but also the confidence that their device truly benefits patients.

Stay on top of the latest trends in medtech by attending the MD&M East Conference, June 9–11, 2015, in New York City.

Vicki Anastasi is Vice President and Global Head of Medical Device and Diagnostics Research at ICON plc.

James Eaton is Director of Health Economics at ICON plc.


1. Gao, Y. C., DIA/FDA workshop on adaptive designs. 2012.

2. (a) Eisenstein, E. L.; Lemons, P. W., 2nd; Tardiff, B. E.; Schulman, K. A.; Jolly, M. K.; Califf, R. M., Reducing the costs of phase III cardiovascular clinical trials. Am. Heart. J. 2005, 149, 482-488; (b) Funning, S.; Grahnen, A.; Eriksson, K.; Kettis-Linblad, A., Quality assurance within the scope of Good Clinical Practice (GCP): what is the cost of GCP-related activities? A survey with the Swedish Association of the Pharmaceutical Industry (LIF)'s members. Qual. Assur. J. 2009, 12, 3-7.

3. Sheetz, N.; Wilson, B.; Benedict, J.; Huffman, E.; Lawton, A.; Travers, M.; Nadolny, P.; Young, S.; Given, K.; Florin, L., Evaluating source data verification as a quality control measure in clinical trials. Therapeutic Innovation & Regulatory Science 2014, 48, 671-680.

4. (a) Risk-adapted approaches to the management of clinical trials of investigational medicinal products. MDC/DH/MHRA Joint Project: 2011; (b) "Position paper: Risk-based monitoring methodology;" TransCelerate Biopharma, Inc.: 2013; (c) Guidance for industry: Oversight of clinical ivestigations - A risk-based approach to monitoring. U.S. Food and Drug Administration (FDA): 2013; (d) Reflection paper on risk based quality management in clinical trials. European Medicines Agency (EMA): 2011.

5. (a) Grieve, A. P., Source data verification by statistical sampling: issues in implementation. Drug. Inf. J. 2012, 46, 368-377; (b) Grieve, A. P.; Fardipour, P.; Zippel, E. "AptivInSite and verification by statistical sampling (VSS): A novel approach to risk-based monitoring;" Aptiv Solutions White Paper: 2013.

6. "An innovative adaptive monitoring methodology for medical device & diagnostic trials;" Aptiv Solutions White Paper: 2013.

7. Barnes, S.; Katta, N.; Sanford, N.; Staigers, T.; Verish, T., Technology considerations to enable to the risk-based monitoring methodology. Therapeutic Innovation & Regulatory Science 2014, 48, 536-545.


3-D Printed Prosthetics: This Is How You Get Them to Children

The international volunteer group E-Nable has become a catalyst when it comes to children receiving 3-D printed "robohands" and other prosthetics.

Chris Newmarker

They aren't a company. They don't sell devices. But what the nonprofit volunteer organization E-Nable does provide is a volunteer community with open source information for creating 3-D printed "robohands" and other prosthetics for children.

The stories continue to mount. One of the latest involves 7-year-old Faith Lennox, who lives outside Los Angeles, and the robotic hand she recently received. Her parents were on a waiting list with E-Nable. But their luck changed when a nearby 3-D printing studio called Build It Workspace was willing to create the hand on its own at a cost of $50 using E-Nable's designs.

Now Faith is looking forward to riding her bike with one hand instead of two, according to media outlets including The Associated Press  and the Long Beach Press-Telegram.

The 3-D printed prosthetics are revolutionary because children such as Faith often outgrow expensive limbs, Build It's Mark Lengsfeld told the AP.

Another recent story involves Alyson Pring's son Alex. He was born missing most of his right arm, and her family couldn't afford a $40,000 prosthetic once he was in elementary school. But through E-Nable, she discovered Albert Manero, a 3-D printing enthusiast who is a mechanical engineering doctoral student and Fulbright Scholar at the University of Central Florida, according to the university's Pegasus magazineManero was inspired enough by the elementary school student's need that he created LimbitlessSolutions with 14 other friends with skills ranging from engineering to nursing. They created a 3-D printed bionic arm for Alex during an eight-week sprint.

Check out this video of actor Robert Downey Jr. of Iron Man fame presenting the arm to Alex:

E-Nable's roots go back to 2011, when South African carpenter Richard Van As lost two fingers in a table saw accident, according to an NPR report. Van As ended up forming a long-distance partnership with Ivan Owen, a special effects artist and puppeteer in Bellingham, WA. They created a working mechanical finger for Van As, and then kept on with it--starting to help children and utilizing 3-D printers to make better devices. Along the way, they made the information about their inventions open source.

Jon Shull, a research scientist at the Rochester Institute of Technology, soon started the original E-Nable Group on Google+.  A community of 3-D printing enthusiasts interested in creating prosthetics for children was born. 

Refresh your medical device industry knowledge at BIOMEDevice Boston, May 6-7, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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Ted Cruz Wants to Repeal Every Word of Obamacare, But Are Physicians Buying?

Ted Cruz Wants to Repeal Every Word of Obamacare, But Are Physicians Buying?

Republican Senator Ted Cruz wants to dismantle Obamacare word for word, but physicians seem to be on board with many of the changes the law has wrought. 

Arundhati Parmar

Conservative Republican Senator Ted Cruz launched his presidential campaign saying he wants to "repeal every single word of Obamacare. 

That was before personal circumstances at home - his wife, through whose employer the Senator from Texas receives healthcare coverage, decided to stop working to help on the campaign - led him to say that he is signing up for healthcare through the healthcare exchanges that Obamacare has created.

Whether that promise to repeal is realistic is besides the point. Is the healthcare industry, more specifically physicians, buying the message that the trends that Obamacare unleashed will be rolled back?

The answer, it appears, is no. 

This seems to hold true at a recent meeting of the nation's orthopedic surgeons. All the more interesting given that at the annual meeting of the American Academy of Orthopedic Surgeons in Las Vegas last week, the keynote speaker was none other than Dr. Benjamin Carson, a retired neurosurgeon, Fox News contributor and harsh critic of Obamacare.

While Carson took shots at the law in his address, speaker after speaker at the meeting talked about the new world of healthcare where reducing costs and improving quality of care, would be critical. They spoke about evidence-based medicine and patient-centered outcomes. And all these are healthcare trends that have been accelerated by Obamacare whose essential goal is to increase patient access while reducing healthcare costs overall.

Speakers also exhorted their colleagues to take a place at the table and help to decide the quality metrics that will not only improve patient care but also help physicians to get paid more in the future through alternative payment models gaining currency these days.

Here's what Mark Piasio, orthopedic surgeon and medical director of quality and medical performance management at Highmark, a large integrated health network in Pennsylvania, told attendees of the AAOS symposium entitled: Evidence, Quality, Costs and Reimbursement: Connecting the Dots. 

Be open to new things. Understand that fee-for-service is not going to last. Start to learn about population health.... Lets be accountable. Let's not let malpractice lawyers and the government be the leaders of our profession in terms of the moral high ground. We need to own that. My parting shot is that yes, it's a new market, it's a new world. Embrace it and let's find ways so we can collaborate together so we can drive much more value into the healthcare that we are delivering to our patients, to the employers that are paying for it and the taxpayers that are paying for it as well.

At the same session, Stuart Weinstein, professor in the Department of Orthopedics and Rehabilitation for University of Iowa Health Care, and a former president of AAOS, went a step further and described the political landscape surrounding healthcare costs.

There is currently a mood to get rid of fee-for-service and change the delivery system under which we practice - to go to more integrated systems like ACOs and bundled payments. In the political world you hear more about this from the Democrats, but I can tell you that Republicans feel exactly the same way. They feel that the fee-for-service basis under which we practice is not appropriate....

In my opinion, the healthcare reform train, as you heard from other speakers, left the station a long time ago and for us to complain and resist is not appropriate. It's going to get us absolutely no where....This is the dawning of a new opportunity for us to actually determine what the parameters are in the future for our specialty....

The ACA is not going away. It's in the implementation phase.... We'll continue to fight the bad parts of the ACA....But we need to be working at determining what is value and what is quality. We don't want the government determining it for us and we don't want insurers determining it for us.

In an emailed response after his presentation, Weinstein explained that the Independent Payment Advisory Board is one example of "the bad parts of the law." It's a board whose members are appointed by the president, though no one has been selected yet, and aims to reduce costs.

"Providers representing roughly 37 percent of all Medicare payments, including hospitals and hospice care, are exempt from IPAB cuts until 2020; thus IPAB directed cuts will disproportionately fall on all other providers and suppliers, including orthopaedic surgeons," Weinstein explained.

Despite these "bad parts," Weinstein acknowledges that embracing the change wrought by the law is a better option than resisting the law.

It appears that physicians are separating the reality on the ground from political rhetoric.  

Arundhati Parmar is senior editor at MD+DI. Reach her at and on Twitter @aparmarbb 

[Photo Courtesy of Mark Wilson/Getty Images]

Philips Moves Closer to Breakup with $2.8 Billion Deal

Dutch multinational announces sale of its LED components and automotive lighting business as it turns toward new HealthTech focus.

Chris Newmarker

Royal Philips has set the wheels in motion when it comes to a split-up of the company that includes Philips Healthcare.

Philips said Tuesday that a consortium led by GO Scale Capital will acquire an 80.1% interest in Philips' combined LED components and automotive lighting business, which will operate under the name Lumileds post transaction.

The deal, which will provide Philips with $2.8 billion in cash before tax and transaction related costs, is expected to close in the third quarter of 2015, pending closing conditions and regulatory approvals. Philips will retain a 19.9% interest in Lumileds, and its Lighting Solutions business will remain an important customer.

Next up for Philips is its previously announced plans to split into two companies focused on HealthTech and Lighting Solutions. Philips said Tuesday that it currently intends to spin off its Lighting Solutions business in an initial public offering, though other options will be reviewed.

The company said last September that its new HealthTech focus will "capitalize on the convergence of professional health care and consumer end-markets across the health continuum, from healthy living and prevention to diagnosis, treatment, recovery and home care."

Philips' healthcare lineup includes consumer-facing medical devices such as toothbrushes and baby monitors as well as dedicated medical devices for use in hospitals.

Philips' exit from the lighting industry is mirrored by Siemens AG, which left that market as competition stiffened amid the rise in popularity of light emitting diode (LED) technology. Siemens is actually in the process of spinning off its own healthcare business.

Refresh your medical device industry knowledge at BIOMEDevice Boston, May 6-7, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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New FDA Indication for Medtronic CoreValve: It's a First

CoreValve becomes first transcatheter heart valve approved for valve-in-valve procedures.

Chris Newmarker

Medtronic CoreValve
Rendering of the CoreValve right after its transcatheter deployment. (Image courtesy of Medtronic)

FDA has cleared the way for Medtronic's CoreValve to be used in more patients in the United States.

The agency on Monday announced a new indication for CoreValve in which the device can be used in patients whose existing artificial heart valves are failing, but are considered too high risk for traditional open-heart surgery.

This is the first time that FDA has cleared a transcatheter heart valve for so-called "valve-in-valve" replacement, in which the valve is deployed inside a failing artificial heart valve.

"The approval is an important expansion of the authorized use of the transcatheter aortic valve replacement technology," William Maisel, MD, deputy center director for science and chief scientist in FDA's Center for Devices and Radiological Health, said in a news release.

FDA's decision could provide an extra advantage for CoreValve versus its major competitor in the United States: Edwards Lifesciences' Sapien valves.

The news of the VIV indication comes on the heels of the CoreValve receiving approval in Japan for use in patients with severe aortic stenosis who are unable to undergo surgery.

FDA approved the CoreValve System last year for patients at extreme or high risk for surgery. It received CE Mark for VIV procedures in May 2013.  Since receiving its first CE Mark in 2007, it has been implanted in more than 75,000 patients in more than 65 countries.

CoreValve works for valve-in-valve procedures because of its supra-annular design meant to maximize blood flow, according to a statement Medtronic provided to Qmed.

Medtronic said: "Unlike other TAVR devices available that have an intra-annular valve, the CoreValve supra-annular design allows the artificial valve to be positioned above the failed surgical valve, which allows for a wider valve opening for blood to flow out of the heart.

Additionally, the self-expanding nature of the valve allows it to continue to provide pressure on the failed surgical valve, expanding it outwards, and thereby allowing it to create an essential seal that minimizes valve leakage."

The new indication comes after an Expanded Use Study, an observational arm of the CoreValve U.S. Pivotal Trial, found low rates of mortality and stroke: a combined rate of 4.2% at 30 days and 10.7% at six months, according to Medtronic.

Refresh your medical device industry knowledge at BIOMEDevice Boston, May 6-7, 2015.

Chris Newmarker is senior editor of Qmed and MPMN. Follow him on Twitter at @newmarker.

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New Nanoneedles Could Be an Important Tool to Reprogram Cells

Scientists in England have used "nanoneedles" to successfully deliver nucleic acids into the back muscles of mice.

Kristopher Sturgis

Imperial College London nanoneedles nucleic acids

Image of nanoneedles delivering nucleic acids to a human cell (Courtesy of Imperial College London)

Researchers from Imperial College London think that a new nanoneedle technique could help deliver nucleic acids to cells. This would then give them the ability to reprogram cells to do many different things, from repairing damaged nerves and organs, to helping transplanted organs thrive in a new system.

Nucleic acids are an essential building block in all living organisms, as they encode, transmit, and express genetic information in living cells. The research team from London has been working in tandem with the Houston Methodist Research Institute to refine a nanoneedle technique that can effectively penetrate and deliver nucleic acids into cells in a safe and effective manner, according to a news release from the university.

The science took a leap when the team was able to demonstrate in a trial the delivery of the nucleic acids DNA and siRNA into human cells in a lab using the nanoneedles. The team found further encouragement when they successfully delivered nucleic acids into the back muscles of mice, resulting in the formation of new healthy blood cells in as little as seven days.

The technique for now has only showed promising results in the generation of new blood vessels. Though, it is worth noting that the mice also exhibited no inflammation or any other harmful side effects during the process.

The group is hopeful that these early results indicate the possibility of one day promoting the generation of new blood vessels in humans, using these nanoneedles as the necessary vessel to carry nucleic acids that can help promote cell function. Researchers believe they could help increase the likelihood of the body accepting transplanted organs. There also might be promise repairing damaged nerves and organs in other areas of the body when needed.

The nanoneedles are tiny porous structures that can act as a sponge imbued with significantly more nucleic acids than traditional solid structures, making them more effective at delivering the payload. They can also bypass the outer membrane of the cell, penetrating and delivering the nucleic acids without harming or killing the cell itself. Each nanoneedle is made from biodegradable silicon, meaning that they can degrade into the body in about two days time, without leaving a toxic residue behind.

Reducing technology to nano-size is becoming a trend in the medtech industry, as researchers continue to shrink technology to increase functionality. From nanolasers utilizing the world's thinnest semiconductor, to biomedical sensors based on silicon nanowires, technologies from every corner are shrinking to microscopic levels in an effort to increase functionality and efficiency.

For now, the London researchers are aiming to develop a material much like a flexible bandage that incorporates nanoneedles. The idea is that this technology could be applied anywhere--on or in the body--to deliver the nucleic acids necessary to reset cell programming and repair the area. The group suspects that harnessing the power of nucleic acids could help them reprogram cells to carry out all kinds of exciting tasks. Repairing scarred tissue, regenerating lost cell and muscle functions, and even promoting the healthy integration of transplanted organs  could all be made possible from these tiny microscopic nanoneedles

Refresh your medical device industry knowledge at BIOMEDevice Boston, May 6-7, 2015.

Kristopher Sturgis is a contributor to Qmed and MPMN.

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Studies: IABPs Don’t Benefit Patients and PVADs Need More Research

Studies: IABPs Don’t Benefit Patients and PVADs Need More Research

Marie Thibault

A pair of studies published this week in JAMA Internal Medicine found that intra-aortic balloon pump (IABP) therapy did not improve mortality in acute myocardial infarction (AMI) patients and called for more randomized clinical trials on the use of a competing technology, percutaneous ventricular assist devices (PVADs).

In an editor's note accompanying the studies, Joseph Ross, MD, MHS, of Yale University School of Medicine, wrote that "despite limited clinical evidence to support their use, these high-risk medical devices have been rapidly adopted into clinical practice."

IABPs are commonly used to treat patients who are suffering from an AMI—a heart attack, essentially—and have gone into cardiogenic shock, unable to pump blood appropriately. These devices are intended to help improve the patient's circulation and blood perfusion through inflation and deflation of the balloon. IABPs are reportedly use in approximately half of AMI patients with cardiogenic shock.  

PVADs are a newer technology that originally looked to IABPs as a predicate device for the 510(k) approval process. These devices do the work of the heart by pumping blood and can achieve cardiac output of up to 5 liters per minute.

In the PVAD study by Khera et al, “Trends in the Use of Percutaneous Ventricular Assist Devices: Analysis of National Inpatient Sample Data, 2007 Through 2012,” the authors found that PVAD use increased 30-fold as IABP use fell. More recent decline in IABP use can be chalked up to the findings of a trial published in Lancet in November 2013, called "Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock" (the SHOCK II trial). This trial showed no mortality benefit from IABP therapy in AMI patients with cardiogenic shock.

This week's IABP analysis by Ahmad et al in JAMA Internal Medicine, “Intra-aortic Balloon Pump Therapy for Acute Myocardial Infarction: A Meta-analysis,” largely reiterated the findings from SHOCK II, concluding that IABP use in randomized clinical trials did not improve mortality for patients, no matter whether they had cardiogenic shock or not. 

Maquet, a subsidiary of Getinge AB and a large maker of IABPs, did not immediately return a request for comment.

Ross said in an e-mail, "the reason we rated this paper of high priority and decided to publish it, despite the SHOCK trial findings, was because of the persistent use of these high-risk devices and others like them in the face of poor quality evidence to support their use. This synthesis of the full body of research, including specifically examining shock versus non-shock outcomes, provides a clear assessment of the current state of the science on these high-risk devices."

PVAD seems to be benefiting from the decline in IABP use. According to the JAMA Internal Medicine study on PVADs, the adoption of PVADs was widespread, increasing from 72 hospitals using the technology in 2007 to 477 hospitals in 2011. Penetration of the technology also increased, from no hospitals performing 10 or more PVAD procedures annually in 2007 to 102 with that level of volume in 2011.  This increase in PVAD adoption can be seen in the recent tremendous growth of the Impella product, a PVAD sold by Abiomed Inc. Over the last two years, U.S. Impella quarterly sales have grown 67%, from $31.1M to $51.9M.

The majority of PVADs are used for cardiogenic shock or AMI patients, with the JAMA study noting that 67.3% of PVAD recipients had this diagnosis. In the analysis conducted by Khera et al, a mortality rate of 28.8% was seen in PVAD recipients, with an even higher mortality of 47.5% in cardiogenic shock PVAD patients. Mean hospitalization costs for PVAD patients were $85,580 and for shock PVAD patients, $113,695. 

IABP patients were more likely to have cardiogenic shock and undergo a bypass surgery as opposed to PVAD patients, who were more likely to have a PCI procedure. In the PVAD study's propensity-matched analysis, PVADs were linked to higher mortality than IABPs. The JAMA study points out the rapid adoption of PVAD and states, "Given the high mortality, associated cost, and uncertain evidence for a clear benefit, randomized clinical trials are needed to determine whether use of PVADs leads to improved patient outcomes."

One type of PVAD, Abiomed's Impella 2.5, just received FDA premarket approval (PMA) in late March, though the device has had 510(k) clearance for several years. It is actually the first hemodynamic support device with a PMA indication for use during high-risk percutaneous coronary interventions (PCI), but the company has not yet announced filing of a PMA supplement for an indication covering use in AMI patients with cardiogenic shock. While the JAMA study mentions other types of PVADs, including the TandemHeart from CardiacAssist Inc., the timing of the publication is particularly noteworthy because it comes on the heels of the Impella approval.

The device, originally cleared under a 510(k), was reevaluted under the 515 Initiative and is now the first hemodynamic support device with a PMA indication for use during high-risk percutaneous coronary interventions. FDA's 515 Program Initiative was started in late 2009 to tackle the remaining 26 Class III "grandfathered" device types that were originally regulated as Class III devices but followed the 510(k) process instead of the PMA process. Impella 2.5 fell into a device category that was reconfirmed as Class III devices under the 515 program, so had to follow the PMA process for approval, though the devices remained on the market during the review process.

Though a new trial was not required, FDA reviewed a wealth of data on Impella 2.5, covering 1,638 Impella 2.5 patients and medical device reporting from almost 14,000 patients. The data included results from the U.S. Impella registry, the PROTECT I, and PROTECT II trials.

The PROTECT II trial was a randomized clinical trial that was stopped in December 2010 because an endpoint was triggered. Many onlookers criticized this as a failed trial. Management explained at the time that the endpoint was triggered because release of CK-MB enzyme, an enzyme typically associated with a heart attack, was seen in Impella patients. This was found to be associated with the higher use of rotational atherectomy—a procedure done to clear clogged coronary arteries—in Impella patients. The trial's principal investigator, William O'Neill MD, then at University of Miami, said in a press release at the time, "It is interesting that operators felt that they could do more complex interventions once randomized to Impella..."

Ross said that he understood the 515 Impella 2.5 clearance was decided using PROTECT I and II data. Noting that he has not see any other publicly available supporting material and that PROTECT II did not meet its primary effectiveness endpoint, Ross said in an e-mail, "if this was the extent of the clinical evidence submitted, I do not think it provides strong evidence of safety and effectiveness to support widespread adoption."

An Abiomed spokesperson said in an e-mail, "the Impella 2.5 just received FDA PMA approval for High Risk PCI, which means that it has demonstrated safety and effectiveness. As the highest standard for FDA regulatory approvals...this approval was based on the demonstration of the ability of Impella 2.5 to improve clinical outcomes such as MACCE (major adverse cardiac & cerebrovascular events) and quality of life over the IABP."

The spokesperson went on to note that another recent article, "National Trends in the Utilization of Short-Term Mechanical Circulatory Support: Incidence, Outcomes, and Cost Analysis," by Stretch et al in Journal of The American College of Cardiology showed PVADs associated with better mortality rates at lower costs while IABP therapy showed the opposite.

Impella is in a number of medical society guidelines at varying levels of recommendation, including the 2013 International Society for Heart & Lung Transplantion Guidelines for Mechanical Circulatory Support and 2013 American College of Cardiology Foundation and American Heart Association Guidelines for the Management of Heart Failure.

Stay on top of the latest trends in medtech by attending the MD&M East Conference, June 9–11, 2015, in New York City.

Marie Thibault is the associate editor at MD+DI. Reach her at and on Twitter @medtechmarie


5 Essential Tips When Hiring a New CEO

5 Essential Tips When Hiring a New CEO

John McLean

For medical device, diagnostics, and other life sciences firms, nothing creates unease like the need for a new CEO.

Whether the current CEO is leaving on amicable or contentious terms, the prospect of having to find a new captain for the ship is daunting. The instinct is to jump right in and start naming names of potential successors. Who do we know? Who out there seems like a good fit? Is there someone internally who can take over the top job?

As much as a firm would like to find out who quickly, it is important to hit the pause button and consider the what and how questions: What type of leader do we really need for this juncture in our evolution? What core competencies must he or she exhibit? How might we find such an individual? How much time should we take?

The point is: Your firm’s idea of what type of leader you need, and can reasonably recruit, needs to be fully planned in advance:

Here are five essential tips for doing so:

  • Determine who will decide what’s needed in the next CEO. Is it the board? Will investors and other senior executives have a say? It is good to be inclusive and get many viewpoints in the early stages (people want to have a voice) in order to build consensus around what really matters in the next CEO.
  • Decide whether to hire a search firm. I’m biased on this matter, but ask yourselves honestly whether you can be objective, efficient and comprehensive in recruiting your next CEO. Will internal politics or disorganization hamper your ability to recruit? My colleagues and I are often asked to get recruitments back on track that were started by firms internally and somehow got derailed.
  • Define your ideal leader. In a perfect world, who would you hire? What experience and expertise would she or he have? Be sure to consider whether that person is a good fit for the current size and stage your firm is currently in, and if there’s a good cultural fit as well. In other words, who is the right person for your firm right now, and will he or she get along with peers and the board? 

            This process should involve metrics. Find eight to 10 criteria that everyone agrees upon, and weigh which are the most             important. Getting this hammered out helps to avoid surprises or conflict in the later stages of a CEO search.

  • Survey the landscape. Once there’s an ideal, the question is can we possibly find this person? Again, here’s where an executive search firm can play a critical role in helping to describe the landscape and whether the right person can be recruited for the price you are offering. If the answer is no, it is not cause for a crisis, merely a recalibration of how you have defined your next CEO.
  • Sell the opportunity. Getting the word out is important, but selling exceptional candidates on the job is just as critical. Be proactive and explain to executives why they would flourish in the opportunity and why your firm is worth their consideration.

Though there is a methodical process required to build a foundation for a successful CEO search, I am not suggesting that this process be slow. That just isn’t the world we live in, nor the industry we inhabit. Take all of these items above into consideration, but do them as fast as possible. If a search firm is involved it will begin to send out feelers and source candidates even as a position profile is being drafted.

When conducting an executive recruitment in the life sciences, stick to a 90-day timeline. This ensures urgency and also that top candidates won’t lose interest or field other intriguing offers. While a comprehensive process is critical, time is of the essence.

John McLean is Managing Partner of the Global Life Sciences practice of the executive search firm Witt/Kieffer and has recruited CEOs and other C-Suite executives for Fortune 500 and life science companies.

[Photo Courtesy of user Jirsak]

Medtech Startup Showdown 2015: Round 2—BioDirection Inc. vs. Drug Free Therapeutix


BioDirection Inc.


Drug Free Therapeutix (DFTx)


Describe your device and how it will benefit healthcare.

The Tbit system is the first point-of-care platform for diagnosing concussions. This system uses a drop of blood to rapidly detect and measure abnormal quantitative levels of brain protein biomarkers released minutes after a concussion, or traumatic brain injury (TBI). Similar to a glucose meter, the low-cost Tbit system uses a drop of blood placed onto a disposable cartridge, which is then inserted into a portable analyzer. The device provides objective results in less than 90 seconds. BioDirection holds exclusive worldwide rights to over 14 issued patents, both domestic and international.


The Exact device maximizes the quality and safety of therapy from existing FDA-approved neurostimulators for chronic pain by linking changes in patient-reported pain symptoms to the measured neural responses to electrical stimulation delivered by an implanted or external (e.g., TENS unit) stimulator. It then transforms the device programming interface from a complicated set of adjustable electrical stimulus characteristics to a set of dials that directly control the quality of pain relief, letting patients convey their experience to the stimulator and teaching it to meet their therapeutic needs. Most neurostimulators can be enhanced with Exact through a firmware or software upgrade.

How does your product differ from the competition?

Today’s standard methods for concussion diagnosis rely on subjective, symptom-based tests some 30+ years old, the majority of which are paper-based questionnaires that have major confounding issues. Misdiagnosis, under-diagnosis, and even over-diagnosis of concussions is prevalent. In fact, even in the emergency room, 56% of patients who enter with a concussion are not diagnosed correctly or at all. The Tbit system is the world’s first simple point-of-care objective blood test for concussions.


Exact “learns” how to efficiently and effectively provide therapy based on signals measured from the patient's body and user-entered pain descriptors. An algorithm stores and analyzes the device settings, measured efficacy, and patient-reported efficacy to adapt to each user’s pain-relief needs. This simplifies programming, replacing a complicated stimulus parameter tuning system with a simple set of dials that control individual patient pain. Selling points include elimination of crossinterference, improvement in accuracy, improvement in signal-to-noise ratio, improvement in device robustness, reduction in sample requirements (enabling therapy to be initiated in minutes rather than months), and increase in market acceptance.

Do you have customers yet?

The Tbit system is currently entering clinical testing in the United States.

  We do not have customers yet, but are actively negotiating partnerships and licensing deals with 3 different companies.

How much money have you raised?

Approximately $6 million



Who are your investors?

Primarily high net-worth individuals and one investment fund


Friends and family

What is the next milestone for your device?

Clinical trials


Demonstrate the interoperability of our medical device software platform with third-party neurostimulators and fulfill regulatory requirements for our line of intelligent TENS units (Exact Persona)


Continue to 8 Startups that Rocked SXSW

Medtech Startup Showdown 2015: Round 2—Briteseed vs. Interrad Medical—SecurAcath




Interrad Medical—SecurAcath


Describe your device and how it will benefit healthcare.

The SafeSnips patented, intraoperative platform technology can be integrated into existing surgical cutting tools to facilitate the real-time detection of blood vessels before surgical cuts are made. U.S. hospitals lose billions of dollars in unreimbursed costs due to inadvertent cuts into vasculature each year. Patients who suffer from these cuts face a mortality rate of up to 32%, and those who survive face an increased hospitalization time of nine days and $210,000 in added costs of care.


SecurAcath is a new method for catheter securement that does not require adhesives or sutures. The unique design of the SecurAcath secures right at the catheter insertion site using a small, blunt anchor that deploys in the subcutaneous tissue just beneath the skin. The device decreases the total cost of patient care by reducing complications associated with catheter securement. The SecurAcath dramatically reduces catheter migration and dislodgement, decreases catheter replacement costs, improves efficiency, and allows 360-degree site cleaning while secured. Improved stability combined with better site cleaning may reduce catheter-related infections. 

How does your product differ from the competition?

To date, no company has seamlessly integrated blood vessel detection technology into existing cutting tools. Instead, to locate a vessel during surgery, a surgeon must use a separate laparoscopic Doppler probe or perform intraoperative imaging, such as CT or MRI. All of these alternatives require added steps, which lengthen surgery times and thereby increase the risk of complication. Further, Doppler technology requires surgeons to alter their behavior while imaging alternatives are costly, require contrast agents, and can result in exposure to radiation.  


The SecurAcath subcutaneous catheter securement technology has many benefits compared with adhesive devices or sutures. SecurAcath offers a low catheter dislodgement rate, which dramatically decreases catheter replacement costs. It decreases the time required to secure, maintain, and remove catheters. The SecurAcath lasts the life of the catheter and, unlike all adhesive securement devices, does not need to be replaced at least weekly. The device design allows for improved catheter site cleaning and minimizes catheter movement, which may reduce catheter-related infections. SecurAcath is also sutureless, eliminating the potential for costly needle stick injuries that can occur when suturing catheters. 

Do you have customers yet?

We are at the prerevenue stage. For future clinical testing, we have identified and will engage the chair of the department of surgery and Loyal and Edith Davis professor of surgery Dr. Nathaniel Soper of Northwestern University to participate as a trial investigator. We will focus on out-licensing this single-use technology across a platform of applications. Initial target customers will be manufacturers of thermal ligature devices (a $1.2-billion global market) and end users will be surgeons who perform minimally invasive general and gynecological surgeries. We have already had partnership and licensing discussions with four major medical device companies, including Covidien, Intuitive Surgical, and Novadaq.


The device has FDA and CE clearance and is being sold in the United States, Canada, and Europe.


How much money have you raised?

$46,250 in cofounder contributions; significant business plan awards, including $73,500 in cash; $1.15 million raised in seed round using a convertible note


Approximately $25 million


Who are your investors?

Lead investors include the Evansville, Indiana, Angel Invstors and Grand Order of Successful Entrepreneurs (supported by Dr. Jack Gill, cofounder of Vanguard Ventures); other investors include physicians who would serve as potential end users and domain experienced investors who have spent more than 40 years in the medical device space.


Angel investors

What is the next milestone for your device?

Refine the current prototype for a pilot study planned at Northwestern University in support of FDA 510(k) application. This includes miniaturization of the SafeSnips technology to fit within a 5-mm trocar, which is expected later this year.


Sales revenue growth