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’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.

National Preparedness Month: FDA and Access to Medical Countermeasures During Public Health Emergencies

By: Brooke Courtney, J.D., M.P.H.

Just weeks after witnessing the fall of the World Trade Center on Sept. 11, 2001, I was a student volunteer in a New York City hospital emergency department when several people arrived saying they had been exposed to anthrax.

Brooke CourtneyOne had even brought a small plastic bag holding white powder. Around this time, the media was reporting on letters mailed that were laced with white powder confirmed to be Bacillus anthracis, which causes anthrax.

At the hospital, we wondered whether we might become exposed to anthrax and how it could be prevented or treated. We quickly escorted the patients who had been exposed to white powder safely away from others to be examined by physicians.

Fortunately, our patients hadn’t been exposed to anthrax. But the letters contaminated with the agent tragically led to five deaths, and 17 more people became ill. Many others were treated with antibiotics as a precaution.

That year, 2001, was a turning point in our nation’s readiness for public health emergencies, including those that result from deliberate attacks or from natural causes like a disease outbreak. In particular, the U.S. government has invested substantially in medical products required for diagnosis, prevention or treatment of a wide range of threats, including anthrax. FDA is part of that national preparedness.

At FDA, we work to help ensure the availability of safe and effective medical countermeasures (MCMs). These are the medical products, including drugs, vaccines, and in vitro diagnostics (IVDs), to counter chemical, biological, radiological and nuclear (CBRN) threats, including emerging infectious diseases like Ebola.

In 2010, FDA launched an agency-wide effort, the Medical Countermeasures Initiative (MCMi), to advance and coordinate the challenging, ongoing MCM development and emergency use work that was occurring in FDA’s product centers and other offices and with other federal partners. Our most recent program update details many of FDA’s MCM achievements since that time, including important, exciting product approvals and regulatory science advances.

At the foundation of FDA’s MCM efforts is a legal and regulatory framework strengthened by Congress after 2001 with the enactment of several MCM-related laws. For example, FDA now has the authority:

  • When the Secretary of HHS declares that the circumstances justify such an authorization, to authorize the use of unapproved MCMs and unapproved uses of approved MCMs under Emergency Use Authorizations (EUAs) during or in preparation for an emergency, and,
  • For approved MCMs, to authorize emergency dispensing by stakeholders, waive certain manufacturing requirements, and extend the useful life of product held in state and local stockpiles.

As an example of our legal authorities in action, we’ve issued multiple EUAs to facilitate access to uncleared IVDs to support disease detection and diagnosis during the H1N1 influenza pandemic and for H7N9 influenza, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Ebola virus that emerged in West Africa in 2014.

Today, our nation is far more prepared than at the time of the anthrax attacks with flexible emergency legal authorities, critical MCMs stockpiled or under development, and enhanced knowledge about how to prevent or treat threats. But, as the recent Ebola epidemic and MERS outbreak show, threats both known and unknown continue to evolve or emerge and require our constant attention and vigilance.

September is National Preparedness Month. And while FDA and other agencies work hard every day to help prepare the nation for potential threats, everyone can be involved in disaster readiness. As we approach the end of Preparedness Month, here are a few things you can do now:

  • Become familiar with disasters that might occur where you live; plans for your community, workplace or school; and what HHS is doing. You can also download a variety of free disaster apps.
  • Make and test a family plan (e.g., communicating during an emergency).
  • Make an emergency kit of supplies, including medical products, you’ll need for at least three days.

Brooke Courtney, J.D., M.P.H., is Senior Regulatory Counsel in FDA’s Office of Counterterrorism and Emerging Threats.

Destroying Certain Imported Drugs: A New Rule to Protect Patients

By: Howard Sklamberg and Melinda K. Plaisier

Recently, FDA published the final rule implementing section 708 of the Food and Drug Administration Safety and Innovation Act (FDASIA). This new rule, which will take effect on October 15, 2015, provides FDA with an administrative process for the destruction of certain drugs refused admission to the United States. Why is this important? These drugs can pose a serious public health risk to consumers in the United States.

Howard Sklamberg

Howard Sklamberg, FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

On July 9, 2012, President Obama signed FDASIA into law. Title VII of FDASIA provides FDA with important new tools to help the agency better protect the integrity of the drug supply chain. One of those new tools is in section 708, which grants FDA the authority to use an administrative procedure to destroy a drug valued at $2,500 or less (or such higher amount as the Secretary of the Treasury may set by regulation) that was refused admission into the United States.

The majority of refused drug products subject to FDA’s new destruction authority come into the United States via international mail. Some of these mail parcels may include one or more drugs that are unapproved, adulterated, and/or misbranded, including counterfeit drugs and drugs that purport to be dietary supplements.

These drugs can pose a serious public health threat to consumers in the United States because they:

  • might not contain the active ingredient that patients need for treatment of their disease;
  • might have too much or too little of an active ingredient;
  • might contain the wrong active ingredient; and/or
  • might contain toxic ingredients.
Melinda Plaisier

Melinda K. Plaisier, FDA’s Associate Commissioner for Regulatory Affairs

In addition, drugs that are represented and sold as dietary supplements can contain hidden or deceptively labeled active pharmaceutical ingredients, some at levels much higher than those found in FDA-approved drugs. Such products can cause harm and have been associated with serious adverse events for consumers. Other purported dietary supplements, although they may not contain harmful ingredients, are promoted to prevent or treat serious diseases but have not been proven safe and effective for that purpose.

Prior to this rule, drugs imported via an International Mail Facility (IMF) that were refused admission because they appeared to violate the law were generally sent back to the U.S. Postal Service (USPS) for export. There has been little deterrence to prevent sellers from sending drugs that violate the law or resending previously refused drugs into the United States via the IMFs to circumvent import regulatory systems.

In fact, some of the parcels returned by USPS were resubmitted for entry into the United States by the sender, with the sticker indicating prior refusal by FDA still attached and visible. This new rule allows FDA to better deter such importation by having an administrative process in place to destroy a refused drug. Rather than returning the drugs to the sender, these drugs will be destroyed. Compared to the volume of entries at IMFs, the agency has limited on-site resources. By deterring violative imports and re-entry attempts, this new process will allow the agency to more effectively focus its limited resources.

Under the final rule, FDA will provide the owner or consignee of the refused drug with written notice and an opportunity to appear and introduce testimony to the agency prior to the destruction. If the drug is destroyed, section 708 provides that the owner or consignee is responsible for the costs of storage and disposal of the drug. However, FDA generally does not intend to pursue recovery of storage and disposal costs against individual consumers who seek to import a drug for their own personal use that is then refused and destroyed.

By enabling FDA to destroy certain drugs, this important action will allow FDA to continue to protect and promote public health.

You can look up the current status of any FDASIA deliverable and sign up to receive Title VII updates using FDASIA-TRACK.

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy.

Melinda K. Plaisier is FDA’s Associate Commissioner for Regulatory Affairs.

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.

Another tool helping developers navigate the difficult road to approval of drugs for rare diseases

By: Jonathan Goldsmith, M.D., F.A.C.P.

If you personally know 100 people living in the U.S., chances are that almost 10 will suffer from some form of a rare disease. If that makes it sound like rare diseases are not actually very rare in this country, that’s because there are 7,000 different rare diseases, 80% of which are caused by faulty genes. A rare disease is defined as a condition that affects fewer than 200,000 people living in the U.S., a country with almost 320 million people. When we do the math, it turns out there are roughly 30 million Americans who suffer from a rare disease. And sadly, about 50% are children.

Dr. Jonathan GoldsmithWith the vast majority of rare diseases still without FDA-approved treatments, we have recently released a new resource for drug developers — a draft guidance document — designed to help them navigate the difficult and unique challenges of developing and bringing to market new FDA-approved drugs to treat rare diseases.

When it comes to finding ways to test new treatments for rare diseases, we often cannot rely on the same methods that we use for testing treatments for more common, well-known diseases, such as diabetes or high blood pressure. Here’s why: In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease, the lack of medical understanding of the disorder (because relatively few people suffer from it), and the lack of well-defined study results (endpoints) that can demonstrate that a potential treatment for a rare disease is safe and effective.

The new draft guidance is intended to help drug developers create more accurate and timely drug development programs by encouraging

  • a focus on understanding a disease’s “natural history,”
  • creation of study designs with clinically meaningful endpoints,
  • development of evidence needed to establish safety and effectiveness,
  • and the establishment of drug manufacturing specifications to ensure quality.

It is also important to note that FDA regulations provide flexibility in applying regulatory standards because of the many types and intended uses of drugs. Such flexibility is particularly important for treatments for life-threatening and severely-debilitating illnesses and rare diseases.

Our guidance document will help us build on the gains we’ve made in helping patients with rare diseases. Since the passage of the Orphan Drug Act in 1983, the number of new requests for orphan designation has continued to rise. In 2014 we saw 469 requests, the highest number of new requests in one year. Also in 2014, an unprecedented 41 percent of all novel new drugs (17 of 41) approved by FDA’s Center for Drug Evaluation and Research were for the treatment of rare diseases.

Our guidance document is intended to encourage drug developers to think early on in the process about all aspects of their program — and encourages careful planning which includes a foundation in strong science. Drug developers for rare diseases are often pioneers. Pioneers need maps and tools to guide them. We see this guidance as another important resource to help support their efforts.

FDA is committed to working with all drug developers and stakeholders to establish successful drug development programs that include regulatory flexibility, creative approaches and a scientifically sound basis.

Jonathan Goldsmith, M.D., F.A.C.P., is FDA’s Associate Director, Rare Diseases Program, Center for Drug Evaluation and Research