Traveling to the Heartland to Discuss Antimicrobial Resistance

By: Michael R. Taylor

One of the great privileges and pleasures of my job is getting to see the food system at work. Whether it’s a big cereal manufacturer in Minnesota, a small New England produce operator, or, most recently, a Midwest cattle feeding operation, I always learn something new, and I get to meet people who are working hard to put food on our tables.

Michael R. TaylorLast month, I traveled with some FDA colleagues to Kansas at the invitation of U.S. Sen. Jerry Moran to learn about the practicalities of beef production, including how animal drugs are being used and managed. Senator Moran, who goes by “Jerry” back home and clearly enjoys being there, graciously accompanied us the whole day. We had a great experience.

For starters, to paraphrase Dorothy, when you spend a day in Kansas, you know you’re not in Washington any more. It’s partly the famous Midwestern friendliness, which we encountered at every turn as we walked the Kansas State campus, toured the K-State College of Veterinary Medicine, and visited Great Bend Feeding, Inc.

But it’s also the tangible presence of the land itself and people who for generations have built small communities on the foundation of agriculture and food production. These are folks who live and work far from Washington, and who often view Washington skeptically, but with whom we have a common cause in providing Americans the safest possible food supply.

FDA’s Center for Veterinary Medicine (CVM) regulates the safety and effectiveness of drugs for both food animals and our pets. When it comes to food animals, this includes ensuring that the meat, milk or eggs do not contain any unsafe drug residues. But it also includes minimizing the risk of antimicrobial resistance, which is a natural biological response to the use of antibiotics, whether in human medicine or in animal production. The public health problem occurs when drugs we rely on to treat human infections are rendered ineffective.

FDA is addressing this problem through an initiative that, by December 2016, will make illegal the use of medically important antibiotics for animal production purposes – such as growth promotion – and bring remaining uses for legitimate animal health purposes under veterinary supervision. CVM’s Dr. Bill Flynn, who is leading this initiative, was my partner on our trip to Kansas.

Kansas Cattle

Cattle on the Great Bend Feeding land in Kansas.

Kansas is a leading beef producer and our trip gave us an opportunity for us to see first-hand the work being done to manage antibiotic use and the real challenges that exist so that together we can find the most practical and effective ways to ensure that these drugs are used judiciously to protect both animal and human health.

Our first stop was Kansas State University’s prestigious College of Veterinary Medicine in Manhattan. Dean Tammy Beckham joined us at the college, which prides itself on teaching, research and service to the community. We met with about 25 students involved in the care of all kinds of animals, from those found on farms, including horses and cows, to companion animals like dogs and cats. We saw a horse and cow being cared for and watched students examine, with great kindness, a tiny dog in a radiology laboratory using computer imaging technology.

We also visited the Veterinary Diagnostic Laboratory, which supports the college’s public role in animal agriculture by examining samples taken from ailing farm animals and helping determine the right treatment. We were joined for the day by Dr. Michael Apley, a professor in the college’s clinical sciences department and a newly appointed member of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. As a researcher and educator who reaches out to the animal production industry, Dr. Apley is at the forefront of efforts to properly manage the use of antimicrobials in food animals.

With Dr. Apley, we drove for more than two hours through the scenic Kansas prairie to reach Great Bend Feeding, a mid-size feed yard with about 30,000 head of cattle. Manager Paul Woydziak is a native of the area and the facility is staffed by local people. This is their life and their livelihood, and they take the issues of food safety and animal health very seriously.

Their job is to optimize the growth of cattle with a custom feeding program, keeping them from 120 to 280 days before they are harvested to enter the food supply. The animals are fed three times a day with feed that is produced in a mill on the property and highly controlled in terms of quality and quantity. Modern day cowboys on horseback constantly patrol the dozens of large pens looking for signs of illness, with potentially sick animals immediately evaluated by a veterinarian.

There are lessons to be learned at farms and feed yards like Great Bend. It is critical that we identify and implement the best “stewardship” practices to ensure that medically important antimicrobials are used judiciously, including for preventing disease in the animals.

And we need solid data to ensure that our strategy to promote judicious use of antimicrobials is working. We were encouraged by the detailed system that was in place at the Great Bend operation for tracking animal health and drug use. Understanding how such information is monitored in actual animal production settings is important to our ongoing discussions about practical strategies for collecting data on antimicrobial use.

So it was a great trip, and we are grateful to Sen. Moran and all of the Kansans who were so generous with their time. Keeping food safe will always involve collaboration between the public and private sectors, and to build that collaboration there is no substitute for being there in person, seeing how our food is produced, and learning from the people who dedicate their lives to that work.

The food safety problem posed by antimicrobial resistance is one that we can solve, working together.

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

The Merging of Medical Products: Enhancing review of therapeutic and diagnostic combination products

By: Robert M. Califf, M.D. and Jill Hartzler Warner, J.D.

Combination products – medical products that do not fit into the traditional categories of drugs, devices, or biological products – are a growing and important category of therapeutic and diagnostic products under FDA’s regulatory authority.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

These products, that combine drugs, devices, and/or biological product (“constituent parts”) with one another, come in three configurations. The constituent parts may be physically or chemically combined, co-packaged, or separately distributed with specific labeling for their combined use.

Products in this category range from familiar products such as prefilled syringes and surgical kits to novel and innovative products, which target and enhance therapies. Examples of groundbreaking combination products include antibodies combined with drugs for targeted cancer therapy and products that mimic or replace organs, such as an artificial pancreas.

Combination products pose unique challenges – both because they may involve new, complex technologies – and because their review at FDA often involves the expertise of more than one Center.

While review of such products falls to a cross-center team of experts, it is led by the medical product Center responsible for the constituent part that provides the product’s primary mode of action, which, in the case of a syringe prefilled with a drug, for example, would be FDA’s Center for Drug Evaluation and Research.

Effective coordination among FDA staff, and between FDA and the company, is essential – and depends on identifying the proper experts across Centers, supporting processes for communication, and implementing systems for efficient data access and sharing.

Jill Warner

Jill Hartzler Warner, J.D., FDA’s Associate Commissioner for Special Medical Programs.

FDA’s Office of Combination Products (OCP), within the Office of Special Medical Programs, oversees and coordinates FDA’s regulation of combination products. This includes helping to resolve differences of opinion between Centers or with sponsors, developing guidance and regulations, and working with the medical product Centers to develop processes and policies..

Congress has expressed interest in FDA’s regulation of combination products as part of the 21st Century Cures legislative initiative, with one major theme being the assurance that the premarket review process runs smoothly.

While we already have policies and processes in place to address such issues, we know we can do more. To that end, we’ve recently conducted a focus group study with reviewers from the different Centers based on input from industry to assess how we’re doing. The report confirmed that differences in communication, policies, practices, systems and application types can be challenging when the Centers work together on a review of a combination product. The report also recommended actions to take, confirming the value of efforts already underway. Consistent with these findings, we’re taking a number of steps to clarify regulatory requirements and improve our internal processes and IT systems. It may sound a bit mundane, but doing this work could help us work more efficiently and avoid unnecessary surprises for sponsors. These steps include:

  • Issuing more guidance for review of combination products (e.g., our pending draft guidance document on human factors);
  • Enhancing and simplifying data access and sharing for internal staff;
  • Making it easier for staff to request and monitor inter-center consults;
  • Updating and maintaining our internal contact directory for experts to review a combination product; and
  • Improving our internal standard operating procedures for premarket reviews and compliance activities.

Some improvements are already in place and others will be coming this year and next. We continue to want to hear your ideas for enhancing how we work with you on combination products. We are listening — and excited to do our part by evaluating innovative combination products and helping to improve the well-being of patients by approving new safe and effective therapies.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.

Jill Hartzler Warner, J.D., is FDA’s Associate Commissioner for Special Medical Programs.

Fresh Empire: FDA launches an Innovative Tobacco Public Education Campaign

By: Dr. Jonca Bull

Tobacco use can damage the body and lead to a range of diseases and conditions, such as cancer, heart disease, and respiratory illness. Unfortunately, the health burdens of tobacco use can disproportionately affect some minority communities.

Jonca BullI’m proud that FDA has recently launched a new tobacco public education campaign, “Fresh Empire.” “Fresh Empire” targets multicultural youth who identify with the hip-hop peer crowd – a hard-to-reach group that historically has been underserved by tobacco prevention campaigns. The aim of the campaign is to associate living tobacco-free with desirable hip-hop lifestyles through a variety of interactive marketing tactics including the use of traditional paid media, engagement through multiple digital platforms, and outreach at the local level.

While multicultural teens identify with multiple peer crowds, FDA is targeting youth who are at risk for tobacco use and who identify with the hip-hop peer crowd because research estimates that these youth are more likely to use tobacco than other youth.

Hip-hop culture encourages positive values, such as working hard to be successful and overcoming personal struggles, but at times it can also portray tobacco use as a desirable behavior. Additionally, by including tobacco use as part of lyrics and modeling the behavior in music videos and magazines, some hip-hop influencers help establish tobacco use as a peer-crowd norm. The “Fresh Empire” campaign seeks to break that norm – we want youth who identify with the hip-hop peer crowd to associate living tobacco-free as compatible with a hip-hop lifestyle.

An important pillar of hip-hop culture is remaining in control. However, because smoking represents a loss of control, tobacco use innately conflicts with the authentic hip-hop lifestyle. With the “Fresh Empire” campaign, we are asking teens to take control of their lives and choose to live tobacco-free. Most of the youth cast in the Fresh Empire ads are real teens and young adults who identify with this peer crowd and who, in many cases, have seen firsthand the damage that tobacco use has done in their communities. Take a look at some of the Fresh Empire ads.

The “Fresh Empire” campaign is another step we are taking towards making tobacco-related disease, disability, and death a part of America’s past, not its future.

Jonca Bull, M.D., is FDA’s Assistant Commissioner for Minority Health

A Quarter Century of Groundbreaking Science: The Forensic Chemistry Center

By: Stephen M. Ostroff, M.D.

This month marks the 25th anniversary of our Forensic Chemistry Center (FCC) in Cincinnati, Ohio. I recently joined former and current administrators and staff of this lab—one of FDA’s many incredible field laboratories—at an event celebrating this milestone.

Acting FDA Commissioner, Stephen Ostroff, M.D.One thing is clear: The last quarter-century has been a period of tremendous success at the FCC. FCC scientists use their scientific analysis and original research to investigate the physical and chemical characteristics and effects of adulterants on products regulated by the Agency, including chemical fingerprinting of poisons, glass, pharmaceuticals, food products and product packaging materials. By analyzing physical samples they can identify counterfeits, trace the origin of a pathogen or solve a crime.

In short, they are the CSI of FDA.

The commitment, expertise, and curiosity of FCC scientists have helped FDA overcome many scientific challenges, and made an extraordinary difference in the lives and safety of millions of Americans. Time and again the sophisticated analyses of puzzling substances by our scientists—often using innovative, esoteric methods, and groundbreaking research, along with the development of new processes and procedures—have made a critical difference in FDA’s ability to investigate and enforce–and protect the American public.

FCC Anniversary group photo

Former and current administrators and staff of the Forensic Chemistry Center (FCC) in Cincinnati, Ohio, at an event celebrating the 25th Anniversary. From left to right: Paul Norris, Director, Office of Regulatory Science; Steve Solomon, Deputy Associate Commissioner for Regulatory Affairs; Dr. Ostroff, Acting Commissioner of Food and Drugs; Phil Walsky, Deputy Director, Office of Criminal Investigations; Fred Fricke, former Director of FCC; and, Duane Satzger, Director of FCC.

FCC’s work has paved the way for passage of important laws, legal prosecutions, and consumer protection activities like recalls. And it has helped strengthen international relationships and advance international cooperation to ensure product quality and consumer safety.

Just a few highlights of FCC’s important efforts include:

  • In the 1990s, the lab supported some of FDA’s early work evaluating nicotine, which was recently cited in the proposed rule to deem additional tobacco products subject to the agency’s tobacco product authorities;
  • In 2001, after 22 people died in the Croatian Republic after receiving dialysis using certain devices, FCC’s analysis identified the presence of a toxic performance fluid in those devices that resulted in their recall by the manufacturers;
  • FCC investigated numerous illnesses and deaths of cats and dogs during 2007-8, which led to the determination that the pet food was adulterated with melamine and related compounds;
  • FCC’s investigation and analysis following the death of cattle in Washington State helped the FBI rule out the possibility that it was caused by terrorism;
  • Following the deaths of a number of infants in India who had been given the measles vaccine, FCC investigated the vaccine’s manufacturing process and discovered that the cause was not, as initially feared, a vaccine of poor quality. Instead the children had received pancuronium bromide, a muscle relaxant, which had been packaged in vials with similar size and shape to the vaccine, rather than the vaccine itself. This discovery was communicated to the Indian government, leading to a critical change in their immunization practices; and,
  • FCC developed a method for examining the sea animals impacted by the Deepwater Horizon oil spill, which helped determine when the seafood would be safe to consume.

It is an extraordinary record. And it’s meant so much to FDA—and the nation—over the past 25 years. But the anniversary and success of this one lab also underscores the remarkable work done by all of FDA’s laboratories across the country. These labs and the districts in which they are located are the critical front line eyes and ears of FDA. And they are the springboard for excellent science.

Good science is fundamental to the mission of FDA. We need it to make good regulatory decisions. It’s what the public expects and deserves. By being able to handle and apply the science of today and anticipate the science of tomorrow we can be more flexible and adaptive, and support innovation.

Having seen the impressive and important work our labs are doing, I’m more committed than ever of the need to invest in better facilities and the best support. We must maintain state-of-the-art laboratories and research facilities, and attract, hire, and retain the best scientists to work in them. First-rate regulatory science requires first-rate scientists working in first-rate facilities.

It’s why I’ve made this a priority for FDA. And why we will put it high on our list of subjects for discussion with Congress as they shape future budgets for the Agency.

The scientists in FDA’s field laboratories are among the unsung heroes of FDA’s work to protect the public health. So let me congratulate and thank those at the FCC and across FDA on the milestone occasion of the 25th anniversary of the Forensic Chemistry Center.

Stephen M. Ostroff, M.D., is Acting Commissioner of the U.S. Food and Drug Administration

Why Partnerships are Key to the Science of Patient Input

By: Nina L. Hunter and Robert M. Califf, M.D.

We recently announced the first FDA Patient Engagement Advisory Committee (PEAC), supported by the Center of Devices and Radiological Health (CDRH). The Committee will provide advice to the FDA Commissioner on complex issues relating to medical devices, the regulation of devices, and their use by patients. The PEAC will bring patients, patient advocacy groups, and experts together for a broader discussion of important patient-related issues, to increase integration of patient perspectives into the regulatory process, and to help drive more patient-centric medical device innovation, development, evaluation, and access.

Nina Hunter

Nina L. Hunter, Ph.D., a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

With the PEAC offering an important avenue for patient views to be incorporated in the assessment of new medical devices, complementary programs in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are continuing to explore multiple approaches to patient involvement in development programs for drugs and biologic products, respectively. The Patient-Focused Drug Development (PFDD) Program, led by Dr. Theresa Mullin, provides a way for scientists from across the Agency to obtain patients’ input on specific disease areas, including their perspectives on their condition, its impact on daily life, and available therapies. As part of this program, FDA is holding a series of public meetings, each focused on a specific disease area. Outcomes of these meetings include detailed descriptions of patient perspectives on the most significant symptoms and treatments.

While FDA continues our work on patient engagement through our newly formed advisory committee and the PFDD Program, public-private partnerships (PPPs) are key to empowering patients across the spectrum of medical product development and evaluation. Here we will describe three such important partnerships.

FDA is a founding member of the Medical Device Innovation Consortium (MDIC), a PPP created with the objective of advancing medical device regulatory science. MDIC recently issued a catalog of available methods that can be used for collecting data on patient preferences, along with a framework for considering how to incorporate patient preferences across the total lifecycle of a device. The ultimate goal is to use these data to guide the development, assessment, and delivery of medical devices that better meet patients’ needs. As the scientific evidence and methodological approaches in this area mature, FDA will continue to collaborate with others on efforts to collect and use patient preference data for regulatory purposes.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

Like the MDIC, the Kidney Health Initiative (KHI) is a PPP that includes representatives from the FDA, healthcare professional societies, patient groups, and the medical products industry. Recently, KHI convened a workshop under the leadership of Dr. Frank Hurst and Ms. Carolyn Neuland, with patients, care partners, scientists, doctors, nurses, technicians, companies, and FDA, to hear discussions about the issues that patients with kidney diseases consider most important. More than 80 patients attended this workshop; many of these were not members of an organized patient advocacy group, but instead individuals truly driven to improve the plight of all patients with kidney disease. CDRH and CDER are working with the KHI to advance scientific understanding of the implications for patient health and safety posed by new and existing medical products, as well as fostering development of new therapies for kidney diseases. This PPP creates a transparent infrastructure and processes that facilitate collaboration and communication among the greater Nephrology community and FDA.

FDA has also held several meetings with the National Institutes of Health (NIH) throughout the PROMIS initiative, including the Patient Reported Outcome Consortium. PROMIS aims to provide clinicians and researchers access to efficient, precise, valid, and responsive patient-reported measures of health and well-being. PROMIS measures can be used as primary or secondary endpoints in clinical studies of the effectiveness of treatment, and PROMIS tools can be used across a wide variety of chronic diseases and conditions and in the general population. These tools pertain to all medical products, and they can be used to understand the burden of their disease and impacts of treatment on how patients feel and function in their daily lives, so that appropriate patient-centered outcome assessments can be developed and integrated into clinical trials to produce meaningful data to guide treatment decisions. Specifically at CDRH, the use of patient-reported outcome measures (PROMs) in regulatory submissions has increased significantly, with approximately 20 submissions per year citing PROMs prior to FDA’s guidance on the topic, to over 120 last year alone. This jump indicates significant interest by industry and clinical researchers in generating patient-centered evidence from studies done for regulatory purposes.

FDA is ready to advance the science of patient input and work with a wider community of patients, clinicians, and social science researchers in a collaborative way. We expect the number of partnerships with patients and their caregivers to grow, and the effort to become more effective as the underlying science and cultural understanding continues to develop.

Nina L. Hunter, Ph.D., is a Regulatory Scientist in the Center of Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.

FDA’s Patient Preference Initiative: The Need for Evolving Tools and Policies

By: Nina L. Hunter, Ph.D., and Robert M. Califf, M.D.

Last week we announced FDA’s first-ever Patient Engagement Advisory Committee, which will provide advice to the FDA Commissioner on complex issues relating to medical devices, the regulation of devices, and their use by patients. We thought it would be good to step back and fill you in about our Patient Preference Initiative.

Nina Hunter

Nina L. Hunter, Ph.D., a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

In 2013, the FDA launched the Patient Preference Initiative, now led by Kathryn O’Callaghan, (Acting) Associate Director for Science and Strategic Partnerships at FDA’s Center for Devices and Radiological Health (CDRH). With this initiative, FDA’s CDRH expanded upon the current approach for capturing patient-centered perspectives in its structured benefit-risk framework, to outline a way of incorporating patients’ views on benefits and risks together with those of FDA’s health care professionals, scientists, and engineers during regulatory decision-making about certain medical devices.

This approach incorporates scientific, empirical evidence from different patients who, as a group, may have a range of views about the degree and types of risks associated with a medical device and how risks should be weighed against the anticipated benefits. When circumstances are appropriate and the data meets the requisite standard, device reviewers at the FDA can consider patient preference data in the overall evaluation of certain devices along with evidence from clinical and nonclinical testing.

If the device is ultimately cleared or approved, the product labeling could include a description of the range of patient preferences and characteristics described by those data, providing patients and healthcare practitioners with key information to make well-informed decisions. It is important to reiterate that FDA would not approve a device if it determines the device would expose patients to an unreasonable or significant risk of illness or injury, or that the benefits do not outweigh the risks for a defined target population.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

As we increasingly work to incorporate the perspectives of patients when evaluating technologies for regulatory approval, we will also need better tools in order to accurately capture and characterize patient views on acceptable balances of benefits and risks. And as this new science of patient preferences continues to evolve, policies must likewise continue to be adapted as approaches are refined.

The FDA, through CDRH and the Center for Biologics Evaluation and Research (CBER), released Draft Guidance on patient preference information this spring. When finalized, this will help device-makers and other stakeholders assess patient valuations of benefit and risk related to relevant device types, illnesses, and conditions. It will also facilitate more systematic consideration of patient views as part of structured benefit-risk assessments for new medical devices. In time, as patient groups, industry, and others conduct more patient preference studies, the FDA and others will better understand patients’ perspectives on benefits and risks, and tradeoffs they are willing to make. This research has the potential to drive more patient-centered device innovation, assessment and access.

The draft guidance provides a case study for such patient-centered device regulation. A recent study conducted by FDA scientists Drs. Martin Ho and Telba Irony and researchers at RTI Health Solutions demonstrated that robust empirical data can be successfully elicited from patients and used to inform deliberations surrounding the approval of a medical product—in this case, the first device for treating obesity to be approved by the FDA since 2007. This pioneering work was a fundamental step forward in our efforts to develop the best methods and practices for systematically incorporating patient preferences into device development and assessment.

As part of the Patient Preference Initiative and other activities to better integrate patient views into our decision making, the FDA is working with others to advance the science of patient input. In our next FDA Voice blog post we will expand on this growing dimension.

The FDA recognizes the potential benefit to be gained from understanding and applying patient input to spur patient-centered medical product innovation and inform patient-centered regulation. We believe that by better understanding patients’ experiences, needs, and views, we will be able to improve the development of medical products and enhance the safe and effective use of those products.

Nina L. Hunter, Ph.D., is a Regulatory Scientist in the Center of Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.

Strengthening the Clinical Trial Enterprise for Medical Devices: An FDA/CDRH Strategic Priority Update

By: Owen Faris, Ph.D., and Jeffrey Shuren, M.D., J.D.

Every day, millions of Americans rely on FDA approved or cleared medical devices to save, sustain, or improve the quality of their lives. At the Center for Devices and Radiological Health (CDRH), we are committed to patients having access to high-quality, safe, and effective medical devices–as quickly as possible. Innovation is key to both speed and excellence in that endeavor. And as we discussed in our blog earlier this year, clinical trials are a key component to the device innovation process.

Owen Faris

Owen Faris, Ph.D., Clinical Trials Director (acting), Office of Device Evaluation in FDA’s
Center for Devices and Radiological Health

In general, clinical trial data are required in premarket submissions for the highest risk devices to demonstrate that they provide a reasonable assurance of safety and effectiveness, and the sooner those trials can safely begin, the sooner patients have access to potentially important, innovative technologies. As part of our 2014-2015 Strategic Priorities, CDRH committed to reducing the time and cost of regulatory and non-regulatory aspects of the U.S. clinical trial enterprise, while assuring the protection of human subjects and the generation of robust data.

In 2015, we have continued to advance our clinical trials program with publication of a new draft guidance document related to how we consider benefits and risks for Investigational Device Exemptions (IDEs) decisions. These decisions are tailored to the type and intent of the clinical study. We’ve also issued a draft guidance that, when final, will encourage the use of adaptive designs for clinical trials and we are considering additional process improvements.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

We’ve also trained our review staff on the practical challenges related to conducting a successful trial. As part of this training, more than 100 review staffers visited sponsors of clinical trials to better understand the context and challenges of initiating and conducting clinical trials in the U.S.

Where has all this led? IDE review times, which had already improved in 2014, have continued to progress in 2015. For example:

  • From 2011 to 2014, the median number of days to full IDE approval decreased from 442 days to 101 days.
  • During 2015, the median number of days to full IDE approval has decreased to 30 days.

Additionally, full approval entails fewer review cycles. In 2011, only 15% of IDEs were approved within two review cycles. In 2015, 74% of IDEs were approved in two review cycles. This performance meets FDA’s strategic goals and, more importantly, means that important technologies have the potential to reach US patients sooner.

Early Feasibility Studies (EFS) are small clinical studies designed to gain early insights into an innovative technology during the development process before starting a larger clinical trial. EFS often are a critical step in device innovation, but they are frequently conducted in other countries rather than in the U.S. Device developers tend to conduct subsequent feasibility and pivotal clinical studies and then bring their products to market earlier in those countries, where they conducted an EFS to leverage clinicians who have gained experience with their technologies.

As part of our 2014-2015 Strategic Priority to Strengthen the Clinical Trials Enterprise, CDRH established a goal of increasing the number of EFS IDEs submitted to each review division in the Center.

Interest in our EFS program has grown substantially, with a 50% increase in the number of EFS submissions during the first nine months of 2015, compared with the same period in 2013. In addition, six of our seven Office of Device Evaluation (ODE) review divisions reported an increase in the number of EFS submissions for 2015 compared with 2013. Recently, we developed a comprehensive educational module to help industry navigate the EFS process. We expect that this is just the beginning and we will continue to see more EFS conducted in the U.S.

To obtain more details regarding our performance for this important strategic priority, see Clinical Trial Performance Update – September 2015.

We are committed to making U.S. patients the first in the world to have access to high-quality, safe and effective medical devices. We believe these results are clear evidence that we are moving the right direction, helping to ensure that robust and efficient clinical trials that provide appropriate human subject protections take place here in the U.S.

Owen Faris, Ph.D., is Clinical Trials Director (acting), Office of Device Evaluation at FDA’s Center for Devices and Radiological Health

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health

Seeing is believing: Making clinical trial statistical data from medical product testing easy to understand

By: Richard A. Forshee, Ph.D.

If you heard that some FDA scientists were helping people pick out colors and designs, you might wonder if the agency had added interior decorating to its responsibilities.

Richard ForsheeWhat they’re really doing is helping scientists craft statistical graphs and plots of clinical trial safety data so that they tell clear, compelling stories. Key to success? Creating tables and graphs that aren’t so dense with numbers, boxes, lines, and words that extracting meaning from them is like excavating hard rock for minerals.

To do this, the Safety Graphics Working Group, a team from FDA, industry, and academia, created a web-based, publicly available database of graphical designs for reporting clinical trial safety data from tests of new medical products. Graphics expertise and funding provided by Vanderbilt University enabled the development of this web site, which was launched in 2013. More recently, the team published details of the concept of improving statistical graphics design in the journal Statistics in Medicine.

The collaborators developed a step-by-step process for creating statistical graphs and plots that quickly explain important findings by taking advantage of the way people naturally look for patterns in images, not just in pictures of nature, but also in representations of statistical data. They also provide computer codes for re-creating the models available on the website. The choices include some fanciful names, such as spaghetti and lasagna graphs, and violin and forest plots.

Clinical Trials Statistical Data Chart

Designing good graphs and plots for specific types of data requires thoughtful approaches to illustrating how that data can be most clearly displayed. This chart is a guide to choosing the most effective design for displaying data, depending on how much detail is to be displayed and what aspect of the data you want to emphasize. In this case, the chart provides options for displaying a type of data called a “continuous variable,” which could be, for example, how a specific drug has affected blood pressure as measured at the end of treatment.

The authors of the article also demonstrate how to use effective, self-explanatory symbols on graphs to explain the data instead of overwhelming a reader with it. Such data can include any of a wide variety of measurements, from liver enzymes to prolonged Q-T intervals (abnormal electrocardiogram results associated with heart beat abnormalities, fainting, and sudden death).

Of particular importance for FDA regulators, the designs make it easier to clearly illustrate statistical data representing a wide variety of potential adverse effects (AEs) observed during clinical trials of medical products or during post-licensure use (when products are on the market). For example, they might show which AEs are elevated in treatment versus control groups, which AEs are elevated in specific patient subgroups, and which might be a safety signal (potential link between a medical product and an adverse effect).

Creating those compelling graphs and plots is important to other scientists who read journal articles to keep up with the latest research in their field. And it’s also very important to a lot of people who make key decisions based on that data: editors of journals deciding whether a researcher’s paper is important enough to publish, and FDA regulatory officials reviewing clinical trial results of medical products submitted by industry.

Most scientists might think it’s impossible to turn statistical illustration into an art form. But the work of the Safety Graphics Working Group shows that “seeing is believing.”

Richard Forshee, Ph.D., is FDA’s Associate Director for Research at the Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research

FDA and the Department of Defense: A Joint Force to Reduce Tobacco Use in the Military

By: Kathy Crosby

Tobacco use continues to be a serious problem, particularly in the military community. So when I presented FDA’s award-winning The Real Cost ads at the Interagency Committee on Smoking and Health earlier this year, they caught the eye of Public Health Service Capt. Kimberly Elenberg, a program manager from the Department of Defense’s Defense Health Agency (DHA). She was looking for a way that FDA and DHA could work together to reduce smoking rates among the military community, especially youth.

Kathy CrosbyDHA already actively encourages service members to live a healthier life through Operation Live Well (OLW), a program that aims to make healthy living the easy choice and norm for service members, retirees, DoD civilians, and their families. OLW’s goal is to highlight and offer resources that teach and encourage its members to choose wisely about their nutrition, get physically fit, maintain healthy sleep practices, get and stay mentally healthy, and avoid or stop using tobacco products.

The latter goal is especially significant given that military service members smoke at a higher rate (24 percent) than their civilian counterparts (18 percent), and those who identify as heavy smokers often began smoking earlier than their civilian counterparts – at 14 years old or younger.

Since adult tobacco use is almost always initiated and established in adolescence, both Capt. Elenberg and I felt that the military community, especially military kids, would benefit from some of the tobacco prevention materials we develop here at FDA’s Center for Tobacco Products.

Working collaboratively, we developed an agreement where FDA would supply DHA with six advertisements from The Real Cost campaign, to run in more than 100 military installation movie theaters, domestically and internationally, until March 2016. The ads focus on consequences of tobacco use such as loss of control due to addiction, cosmetic health effects and the toxic mix of more than 7,000 chemicals in cigarette smoke.

The Real Cost educates viewers about the dangers of tobacco use by making them fully aware of the real cost of every cigarette. It portrays in new ways the health and addiction risks associated with tobacco use. By partnering with DHA, we are able to help military service members and their families lead healthier lives by encouraging them to rethink their relationship with tobacco.

I feel honored that DHA sees the potential for our work to make a positive impact on military families. To date, The Real Cost has far exceeded the recommended best practices to achieve behavior change and improve public health, reaching more than 90 percent of the target audience at least 15 times a quarter, and the campaign has generated nearly 2.5 billion digital impressions on youth-focused websites. I hope that our collaboration with DHA will continue to introduce new viewers to the campaign and educate them about the dangers of tobacco use.

Great ideas for collaborating with other agencies and groups come from a variety of places. If you have an idea for how we can continue to help reduce tobacco use, I would love to hear from you.

Kathy Crosby is FDA’s Director, Office of Health Communication and Education, Center for Tobacco Products.

FDA Announces First-ever Patient Engagement Advisory Committee

By: Nina L. Hunter, Ph.D., and Robert M. Califf, M.D.

Although it may seem odd in retrospect, the development of new technologies intended to improve patients’ lives has largely relied upon expert opinions rather than asking patients and families directly what they consider most important.

Nina Hunter

Nina L. Hunter, Ph.D., a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

But that’s changing. We are entering an era of “patient-centered” medicine in which patients and their care partners participate actively in decision-making and priority-setting about all aspects of health care. Americans are becoming increasingly active consumers of health care, making choices about their doctors, diagnostics, treatments, and healthcare experiences rather than simply allowing health care providers to make the decisions for them. Moreover, FDA believes that patients can and should bring their own experiences to bear in helping the Agency define meaningful benefits or unreasonable risks for certain new devices.

Today we are excited to announce FDA’s first-ever Patient Engagement Advisory Committee (PEAC). This body will provide advice to the FDA Commissioner on a range of complex issues relating to medical devices, the regulation of devices, and their use by patients. It will give FDA the opportunity to obtain expertise on various patient-related topics, with the goal of improving communication of benefits and risks and increasing integration of patient perspectives into the regulatory process. Some questions that the PEAC may discuss include where and how best to engage patients across the device development and assessment lifecycle as well as how FDA and sponsors should communicate patient preference information to patients. The PEAC represents a new and exciting opportunity to foster patient partnerships with FDA, and it complements other efforts at FDA to bring the patient into the medical device regulatory process. This includes studies to evaluate patient preferences in medical devices and a recently published draft guidance on patient preference information for PMAs, HDE applications, de novo requests, and inclusion in device labeling that describes how patient tolerance for risk and perspective on benefit, in addition to clinical data and other information, may be considered in FDA’s assessment of the benefit-risk profile of certain devices. While it’s important to consider patient perspectives, we understand that patients still expect FDA to do our primary job — namely, ensuring the safety and effectiveness of FDA-regulated medical devices. This is primarily accomplished at FDA through regulation at the Center for Devices and Radiological Health and the Center for Biologics Evaluation and Research. When assessing whether valid scientific evidence shows that a device’s probable benefit outweighs its likely risks, FDA may consider rigorous, systematically gathered patient preference information as a part of the totality of the evidence from clinical and nonclinical testing. However, patient preference information will not be used to justify approval of unsafe or ineffective devices: if FDA determines the device would expose patients to an unreasonable or significant risk of illness or injury, or that the benefits do not outweigh the risks for a defined target population, FDA would not approve such a device.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

When is patient preference information most useful? These data can be used in several major ways:

  • to help identify the most important benefits and risks of a technology from a patient’s perspective;
  • to assess the relative importance to patients of different attributes of benefit and risk, and clarify how patients think about the tradeoffs of these benefits and risks for a given technology; and
  • to help understand how patient preferences vary across a population.

As part of the Patient Preference Initiative and other activities to better integrate patient views into our decision-making, FDA is working with others to advance the science of patient input. We will discuss these extensive partnerships in an upcoming FDA Voice blog.

FDA’s sharpened focus on patient-centered technology development, evaluation, and use has already begun to positively affect the development of innovative therapies and clinical solutions. These efforts are helping to drive a more patient-centered medical product development and assessment process. We’re excited to invite the patient, industry, and academic communities to join in and help us accelerate this important work.

Nina L. Hunter, Ph.D., is a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.