Have a Problem? Contact the New Ombudsman in the Office of Regulatory Affairs

By: Melinda K. Plaisier

Melinda PlaisierWhether we are inspecting your facilities, sampling your products, or conducting investigations, the primary goal of FDA’s Office of Regulatory Affairs (ORA) is to protect the public. But I understand the impact our actions can have on you, so I am committed to making ORA’s processes as transparent as possible and quickly addressing problems you may encounter.

That’s why I’m happy to announce a new resource: an ORA ombudsman who can help you with unresolved concerns. While you may continue to bring issues to my staff, Ombudsman Jessica Zeller is dedicated solely to helping you with assessing and resolving problems.

Jessica, who has worked in both industry and government, understands that FDA’s perspective is often different from that of industry and other stakeholders. Her experience makes her an ideal candidate to carry out two primary objectives:

  • To informally and in an unbiased manner, find solutions, when possible, to problems that arise with our external partners, including industry, other governmental agencies, and consumers.
  • To improve communications between ORA employees and stakeholders through outreach and education, helping both sides become more aware of each other’s needs.

“Understanding the pressures that each side faces are critical to working out solutions and allaying fears,” says Jessica. “I intend to hear what you are saying and feel what you are feeling. I will not always be able to get you what you want, but I promise you will have an opportunity to share your concerns, and I will attempt to achieve the best solution possible.”

Although Jessica reports directly to me, and ORA leaders will continue to make final decisions, Jessica is an unbiased third party who will consider and work on your concerns. You may contact her by phone or email, and she will keep conversations as confidential as possible within the limits of the law.

Jessica gained her expert knowledge from more than a decade of work in FDA regulation. During her eight-year tenure at FDA, from 2004 to 2013, she served in the Office of the Chief Counsel and as deputy director of the Office of Compliance and Enforcement in the Center for Tobacco Products. From 2013 until she returned to FDA late last year, Jessica was in-house counsel for Proctor & Gamble. She also previously worked as a congressional staffer, earned a law degree and a master’s degree in bioethics from the University of Virginia, and a bachelor’s degree in biology.

The International Ombudsman Institute defines an ombudsman as a person of prestige and influence who operates with objectivity, competence, efficiency, and fairness. We are proud that Jessica fits that lofty definition so well. I encourage you to reach out to her when issues remain unresolved.

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

Launching a New Natural History Grants Program: Building a Solid Foundation for Rare Disease Treatments

By: Katherine Needleman, Ph.D. and Gumei Liu, M.D., Ph.D.

Today, on Rare Disease Day 2016, FDA’s Office of Special Medical Programs/Office of Orphan Products Development (OOPD) is proud to announce the launch of a new grants program to fund natural history studies with the hope of bringing new and important diagnostics and therapeutics to patients with rare diseases.

Kathy Needleman

Katherine Needleman, Ph.D., is the Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development

A rare disease, by definition, affects fewer than 200,000 individuals in the United States. Its impact, however, is far from rare. Altogether, about 7,000 known rare diseases affect about 30 million Americans. Yet the vast majority of rare diseases do not have adequate diagnostic tools or treatments.

Developing such diagnostics or treatments — whether it’s a drug, biologic, or medical device — has been compared by many to building a house. Both require a solid, sound foundation. For any rare disease treatment development program, that foundation consists of having a thorough understanding of the natural history of a disease.

How do you define the natural history of a disease? Think about it as the course a disease takes – from the time of its onset, progressing through its pre-symptomatic phase and clinical stages, to the end of the disease. Insight into a disease’s natural history can help lead to better, more well-designed trials that can accelerate the development of life-saving diagnostics and therapeutics.

Gumei Liu

Gumei Liu, M.D., Ph.D. is a reviewer and grant project officer in FDA’s Office of Orphan Products Development

A lack of understanding of the natural history is often a major obstacle to developing life-saving products for patients with rare diseases. Without it, it becomes very difficult to decide what to study, know what to look for within a study, and capture the data necessary for approval of a treatment or even a cure.

OOPD’s new Natural History Grant Program is intended to provide much needed support and complement ongoing efforts to help change the trajectory of rare disease product development. The funded studies should help characterize the natural history of a rare disease or condition, identify genotypic and phenotypic subpopulations, and develop and/or validate clinical outcome measures, biomarkers, and companion diagnostics.

There are several ways to conduct natural history studies. They can look back in time (retrospective), look ahead (prospective), or be a survey study (collection of data through questionnaires). Each has its pros and cons and the method will to a great extent depend on what we know about a specific rare disease and the currently available treatment options.

Patient advocacy groups can and do play a critical role in collecting natural history data as is highlighted in FDA’s video discussion (watch video below) on natural history studies featuring perspectives from patient advocates. Often what prevents organizations, like patient advocacy groups, from conducting natural history studies is funding. And that’s where the grants program can make a difference.

The Orphan Products Natural History Grants Program is open to funding all types of natural history studies that are appropriate for the rare disease being studied and can aid in development of diagnostics and treatments. There are two funding levels and durations that will be offered:

  • A maximum of $400,000 in total costs per year for up to five years for prospective natural history studies involving clinical examination of affected individuals; and
  • A maximum of $150,000 in total costs per year for up to two years for retrospective natural history studies or survey studies.

The Orphan Products Natural History Grants Program is built upon OOPD’s Orphan Products Grants program that was established by the Orphan Drug Act more than 30 years ago and which has typically funded clinical trials. OOPD has successfully utilized its budget to help bring over 50 products to market with that clinical trial grant program.

We hope that this new Orphan Products Natural History Grants Program will help build the important foundation necessary to accelerate the development of life-saving diagnostic and treatments for the many rare disease patients who need them.

Katherine Needleman, Ph.D., is the Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development

Gumei Liu, M.D., Ph.D. is a reviewer and grant project officer in FDA’s Office of Orphan Products Development

FDA Offers Free, Continuing Education Course to Help Health Care Providers Understand ‘Biosimilars’

By: Leah Christl, Ph.D.

You may have heard about a new category of products called “biosimilars.” What are biosimilars and how do they relate to biological products already widely in use?

Leah ChristlBiological products derived from living organisms can treat patients with cancer, chronic kidney disease, rheumatoid arthritis, inflammatory bowel disease, and other serious conditions. Biological products that are “biosimilar” to, or “interchangeable” with, an already-approved FDA biological product (an FDA-licensed reference product) are one way to improve access and increase treatment options at potentially lower cost for our nation’s health care system.

These products are licensed through a new pathway created in the United States in 2009. FDA is well aware that health care professionals–including prescribers, the nurses who will administer them, and the pharmacists who will dispense them–need to understand how these drugs work and how they are intended to be used.

To that end, FDA has developed a free, Continuing Education Course for health care professionals – titled, FDA Overview of Biosimilar Products – to help them strengthen their knowledge and understanding of biosimilars and interchangeable products. Biosimilars and interchangeable products, for instance, are not generic products, and this education course will help health care professionals fully appreciate the distinction.

There’s a growing interest in biosimilars and interchangeable products in the pharmaceutical industry. The first biosimilar in the U.S. was approved in 2015. It boosts the production of white blood cells and helps to ward off infection in patients receiving strong chemotherapy for some tumors. FDA is reviewing several other marketing applications for proposed biosimilar products.

This course also will help health care professionals understand how a biosimilar can be prescribed and dispensed, and how and when an interchangeable product can be substituted for another biological product.

The program will inform healthcare professionals about the development process and approval pathway for biosimilars and interchangeable products. It also includes information about FDA’s general review process for these products that will help attendees gain a better understanding of the relationships between biosimilars and interchangeable products.

The course is available to health professionals on FDA’s CDERLearn Website, and can be completed on a tablet for those on the go and not at their desktop computer.

Leah Christl, Ph.D., is the Associate Director for Therapeutic Biologics in the Office of New Drugs, at the Center for Drug Evaluation and Research at FDA

What is FDA Doing to Improve the Health of African-Americans?

By: Jovonni Spinner, M.P.H., C.H.E.S.

Every February, we celebrate Black History Month – a time to reflect, celebrate, and honor the contributions of African-Americans to our society. We know that achieving and maintaining good health is a long-standing issue for this group, many of whom may experience worse health outcomes in critical areas like heart disease and diabetes. But, we want to focus on the positive and provide consumers with health education materials to support healthy behavior changes!

Jovonni SpinnerIt’s true that the health equity gap has narrowed over time, but there is still significant room for improvement. Here are few things that the FDA and the Office of Minority Health (OMH) have done over the past year to reduce health disparities.

Public Engagement: More than 29.2 million blacks/African-Americans are on social media — and we want to meet consumers where they are. So we’re using Facebook, Twitter, and other social media platforms and electronic communications (e.g. our newsletter and e-blasts) to educate African- Americans on issues such as heart disease, diabetes, and sickle cell disease among others, and also provide tangible solutions to help manage these chronic conditions.

For example, to mark American Heart Month in February, we developed a social media toolkit to help our stakeholders engage with their members and partnered with the Association of Black Cardiologists to spearhead an #ILoveMyHeart social media campaign.

Stakeholder Engagement: We have cultivated relationships with a core set of partners to better understand their health needs, aligned our priorities to meet those needs, and worked together to leverage each other’s resources for the common good. By doing so, we’ve increased our stakeholder’s capacity to communicate with the agency on regulatory issues. For example, multicultural stakeholders are now better able to make their voice heard in FDA-sponsored public meetings and on open dockets.

Minority Health Research: We worked with academia to fund African-American-based research projects (e.g. HIV/AIDs and triple negative breast cancer) and research fellows working on topics like genomics and digital communications. This allows us to increase the knowledge base on these issues and ensure a diverse workforce is in place to solve these complex health problems.

Resources: We have taken care to tailor our health education resources, such as infographics and fact sheets, to African Americans. Our website has valuable information on sickle cell disease and lupus, both of which affect African Americans more than any other racial/ethnic group.

Clinical Trial Diversity: Did you know that sometimes minority populations may respond differently to medical products? One example is an FDA-approved heart failure medication that reduces the risk of death and hospitalization in people with certain types of long-lasting/chronic heart failure.

During clinical trials, it was found there was an increased risk of an allergic reaction called angioedema in blacks. In this trial, only 5% of the participants were black, even though blacks represent 13% of the U.S. population and experience heart failure at rates higher than the rest of the population. This is why we continue to work toward increasing clinical trial diversity, to ensure that medical products are safe and effective for everyone!

President Obama has said, “If you’re walking down the right path and you’re willing to keep walking, eventually you’ll make progress.” OMH will continue walking down the path to improving health equity and we want you to join us, because this work cannot be done alone.

Visit FDA’s OMH at: www.fda.gov/minorityhealth

Follow us on Twitter @FDAOMH

Jovonni R. Spinner, M.P.H., C.H.E.S., is a Public Health Advisor in FDA’s Office of Minority Health

Using Social Media to Teach Consumers About Heart Health

By: Jonca Bull, M.D.

Jonca BullFebruary is American Heart Month. Heart disease remains a significant problem in the United States – it’s the leading cause of death, disproportionately affecting minorities. In particular, minorities have higher rates of hypertension, diabetes, and smoking, which are risk factors that can cause heart disease. This month, we’ll be working with the Centers for Disease Control and Prevention and the National Institutes of Health to help raise awareness.

Our social media platforms will be key to engaging the multicultural population. And they have a proven reach: 65% of Hispanics and 56% of African Americans use social media. In 2014, on average 40% of all cell phone owners used a social media site, with blacks and Hispanics leading the trend at 48% and 49%, respectively.

So, how will FDA’s Office of Minority Health use social media to reach key populations? Here are just a few things we have in store for February:

  • Sharing culturally relevant messages for Twitter and Facebook. We want to stimulate dialogue on two key areas: (1) knowing your risk factors and (2) using our resources to help manage them. This month, our outreach will provide information and resources on the following:
    • Heart Disease: Who does it affect and what are the risk factors?
    • Smoking: Smoking is a risk factor for developing heart disease. FDA has resources to help you quit.
    • Healthy Eating and Living: FDA has materials to help consumers make heart healthy decisions (e.g. how to read the food label), manage their risk factors through FDA-approved medications, and tips for preparing healthy meals.
  • Working with stakeholders to use social media as an engagement tool. We have developed a social media toolkit to guide stakeholders in communicating with their members. The toolkit will contain drafted social media messages, infographics, and links for consumers on heart disease and risk factor management. Email omh@fda.hhs.gov to receive the toolkit.
  • Hosting a bilingual Twitter chat with our partner, @SaludToday on Tuesday, Feb. 16th from 1 p.m. – 2 p.m., EST. We’ll chat about risk factors for heart disease and provide tips to lead a heart healthy lifestyle. We hope you can join us and provide your insights on this important topic.
  • Spearheading an #ILoveMyHeart social media campaign with our partners @SaludToday and @ABCardio1 asking you to show us how much you love your heart! Participants will upload pictures with the #ILoveMyHeart hashtag describing their heart healthy activities. Be sure to post your picture and tag @FDAOMH!

We know that social media is becoming a valuable health education tool to reach minorities. And, we will continue to use it to engage with our audience. Please follow us and share heart-healthy messages all month.

For more information about FDA’s OMH visit us at: www.fda.gov/minorityhealth

Follow us on Twitter @FDAOMH

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

Making Progress in Protecting Consumers from Unsafe Supplements

By: Stephen Ostroff, M.D.

An estimated 200 million Americans take dietary supplements to maintain or improve their health. Protecting consumers from unsafe or contaminated dietary supplements is extremely important to FDA.

Acting FDA Commissioner, Stephen Ostroff, M.D.We’ve recently taken a number of important steps to prevent illnesses and deaths from unsafe supplements, and, while our current authority over supplements is arguably limited, we are doing what we can to strengthen our existing oversight. I’d like to give you a picture of the challenges, achievements and opportunities regarding the regulation of these products, beginning with the challenges.

One challenge is sheer volume. The dietary supplements industry is one of the fastest-growing in the world. When the Dietary Supplement Health and Education Act (DSHEA) was passed by Congress in 1994, annual sales of dietary supplements totaled about $5.8 billion. Since then, sales have risen six-fold to about $35 billion annually. Large volumes of supplements are also now sold on the Internet. The significant growth in the dietary supplements industry, and the various ways supplements reach consumers, outpace FDA’s resources to regulate this industry.

Moreover, tracing these products can be difficult because supply chains are often fragmented, with a single product sometimes passing through numerous suppliers, manufacturers and distributors of all kinds, sizes, and locations (including those overseas). Ultimately, when proper quality control and recordkeeping procedures are not followed across the supply chain, it can be difficult to guarantee what ingredients in what amounts are in the final product, and whether the ingredients are safe or even qualify as dietary supplements.

Under DSHEA, FDA does not have the authority to approve dietary supplements before they are marketed to consumers. However, we do have the authority to take enforcement actions after a product is on the market – only when we can establish that the dietary supplement is adulterated (e.g., unsafe); misbranded (e.g., misrepresentations are made on the product labeling); or cannot be marketed as a dietary supplement (e.g., an unapproved new drug). We monitor the marketplace through market surveys, undercover buys, label reviews, a review of reports of illness or deaths, and product testing. When necessary, we take actions to protect public health, including issuing public warnings, taking legal action, and working with the company to recall the product. But all this must be done based on evidence and within the bounds of our legal authority and limited resources.

Despite these constraints, our actions have produced important results over the past year. Here are just a few key accomplishments:

  • At the request of FDA, this month U.S. Marshals seized almost 90,000 bottles of dietary supplements labeled as containing kratom. Kratom has been indicated to have both narcotic and stimulant-like effects.
  • Use of pure powdered caffeine products has already resulted in the deaths of two teenagers. We took action to help prevent harm, including deaths, from the use of these products, by issuing warning letters to five distributors of these potentially dangerous products.
  • In 2015, FDA identified products containing BMPEA, DMBA and picamilon that are unlawfully marketed and issued a series of warning letters to 24 companies that marketed dietary supplements containing these ingredients. The companies that received the warning letters market products that are either misbranded for falsely declaring the ingredients as dietary ingredients or marketing products containing new dietary ingredients without the required pre-market notification.
  • We worked closely with our government partners, including the Department of Justice, the Federal Trade Commission and the U.S. Postal Inspection Service, on a year-long sweep to identify potentially unsafe products and/or products containing undeclared ingredients. In November 2015, that sweep culminated in civil injunctions and criminal actions against 117 manufacturers and/or distributors of dietary supplements and tainted products.
  • We issued more than 100 consumer alerts warning about products falsely marketed as dietary supplements that were found to contain active pharmaceutical ingredients.
  • We conducted more than 600 inspections of dietary supplement firms in the U.S. and other countries. We also worked with companies on voluntary compliance actions, such as removing illegal claims, destroying inventory and ceasing distribution.

I am excited about the opportunities that await us in this area, and the plans we’re making for the future. For example, within FDA, we have established the new Office of Dietary Supplement Programs and are working on increasing the visibility, capacity and staffing for that new office. This will include hiring permanent leadership to sharpen our focus on potential safety problems and to support regulatory actions.

We want to expand our use of criminal investigation and enforcement tools to address serious safety-related violations and cases of intentional fraud; and further build strategic investigatory and enforcement collaborations with the Federal Trade Commission, Department of Justice, and state governments, including state health departments and attorneys general.

Ultimately our top priority is to protect the consumers who want to improve, not damage, their health and have a right to expect that dietary supplements will be safe for them and their families.

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

Advancing Women’s Health Research

By: Pamela E. Scott, Ph.D.

Career inspiration can come from many sources. My inspiration came from a broken ankle.

Pamela ScottIn the winter of 1999, I broke several bones and had three surgeries to repair my ankle. While working with my doctors on my treatment plan, I had to make some serious decisions about the proposed medical devices that would be used in my care.

I had more information at my fingertips than the average person. I was an FDA insider who had worked on medical devices. I had worked as a statistical reviewer, and I was in the process of completing my PhD in epidemiology and clinical trials methodology. But despite my background and access to information, I still had questions about how well the devices work for women like me.

My experience motivated me to make sure that women have the data and information they need to make informed choices about their medical care. When I returned to FDA, I dedicated my efforts to promoting women’s health research. Years later, I continue this work in my current role as Deputy Director and Director of Research and Development for the FDA Office of Women’s Health (OWH).

Throughout its history, FDA has conducted research to help inform its regulatory and policy decisions. OWH and FDA Centers have supported research that has developed new methods and tools that can help predict the safety and efficacy of FDA-regulated products, identify sex differences, and guide product labeling.

Since its establishment in 1994, the OWH Research and Development Program has played an integral role in promoting sound policies and regulations by supporting research projects, workshops, and training to help FDA answer regulatory questions related to women’s health. OWH has funded more than 300 research projects that have expanded our understanding of the science of women’s health.

New Women’s Health Research Roadmap

To build upon these projects, OWH recently released a Women’s Health Research Roadmap that outlines seven broad areas where new or enhanced regulatory science research would be beneficial to women’s health. Future OWH-funded research will seek to:

  1. Advance Safety and Efficacy
  2. Improve Clinical Study Design and Analyses
  3. Identify Novel Modeling and Simulation Approaches
  4. Advance Biomarker Science
  5. Expand Postmarket Data Sources and Analysis
  6. Improve Health Communications
  7. Identify Sex Differences related to Emerging Technologies.

OWH will work with FDA Centers to increase collaboration and communication on research endeavors related to women’s health. By promoting collaborative research in mission critical areas, the Roadmap will better position FDA to foster the advancement of innovative products that promote and protect the health of all Americans.

While I may never be able to run a marathon, my injury helped guide my career at FDA and my work to strengthen FDA’s commitment to advancing women’s health research. And with the new Roadmap, we are well positioned to continue the progress that has been made in women’s health.

Pamela E. Scott, Ph.D., is Deputy Director and Director of Research and Development, FDA Office of Women’s Health.

Progress and Collaboration on Clinical Trials

By: Barbara D. Buch, M.D.

There are few responsibilities at FDA more important than reviewing the design and outcomes of clinical trials. Understanding the science behind the trials — and the individuals included in them — helps us to ensure that the medical products we approve are safe and effective.

Dr. Barbara BuchLast year, FDA took important steps to support the inclusion of diverse populations in clinical trials. Following Congress’s directive in Section 907 of the Food and Drug Administration Safety and Innovation Act, FDA is looking more closely at the sex, age, and race/ethnicity data that are collected in clinical trials.

In August, FDA published an Action Plan designed to address three specific priorities: improving the quality and comprehensiveness of demographic subgroup data collection, reporting and analysis; identifying and eliminating barriers for increased participation in clinical trials; and improving the transparency of subgroup data.

We’ve come far in achieving this plan. As we begin 2016, I want to outline our progress in preparation for the next important milestone: a public meeting on this topic on February 29.

Priority 1 – Quality

  • FDA updated and/or finalized relevant guidance on demographic subgroup data, as illustrated by these two examples of FDA staff training and/or outreach to external stakeholders:
  • The Office of Minority Health (OMH) developed a plan that supports specific research projects and leads to better understanding of medical product clinical outcomes in racial/ethnic demographic subgroups.
  • The Center for Devices and Radiological Health (CDRH), the Center for Drug Evaluation and Research (CDER), and the Center for Biologics Evaluation and Research (CBER) modified their clinical review templates:
    • CDER developed a review process that encourages reviewers to watch for inappropriate clinical trial exclusion and inclusion criteria; accompanying training emphasizes the need to include broad population diversity in clinical trials.
    • CDRH and CBER modified statistical reviewer templates to include analysis of demographic subgroup information.
  • CBER and CDER incorporated discussions on diverse inclusion and subgroup participation and analysis into pre-application submission meetings with industry.
  • FDA updated its MedWatch forms to standardize collection of demographic information on possible adverse events that occur after medical products are broadly available on the U.S. market.
  • And a few days ago, the Office of Women’s Health (OWH) posted their Research Roadmap and its strategic plan for women’s health research. OWH also funded two research projects:
    • Methods to improve data quality in demographic subgroups
    • Examination of sex-specific outcomes with cardiac resynchronization therapy.

Priority 2 – Participation

  • FDA is making demographic information from clinical trials more easily available to consumers through its easy-to-read online Drug Trials Snapshots webpage and a corresponding article for consumers.
  • The Office of Minority Health and the Institute of Medicine convened a Public Meeting to discuss minority health disparities and clinically meaningful differences.
  • FDA and The Johns Hopkins University co-sponsored a clinical trials workshop, Assessing Safety and Efficacy for a Diverse Population.

Priority 3 — Transparency

  • FDA established a Language Access Plan Working Group designed to implement communication strategies sensitive to the needs of under-represented subpopulations, focusing on language access and health literacy.
  • CBER launched a transparency pilot program to make demographic information available to physicians and the public for original Biologics License Applications.
  • CDRH modified templates for certain documents that are posted to the FDA website upon approval of certain medical devices to ensure that demographic information is consistently included.

We’ve certainly made progress, and will continue the forward momentum in the years to come. And we will need the continued investment of our stakeholders and partners.

We look forward to continuing this important and productive conversation with you next month at the public meeting.

Barbara D. Buch, M.D., is the Chair of the 907 Steering committee and the Associate Director for Medicine in FDA’s Center for Biologics Evaluation and Research

FDA 2015: A Look Back (and Ahead) – Part 2: Medical Product Safety and Oversight

By: Stephen M. Ostroff, M.D.

In my first look back on FDA’s 2015 accomplishments, I focused on our achievements in medical product innovation and our constant drive to make safe, effective and innovative products available. Because FDA’s responsibility covers the entire life cycle of products, in this second year-end blog post, I will review FDA’s impact on medical product safety and oversight.

Acting FDA Commissioner, Stephen Ostroff, M.D.Responding to Ebola

In a world where disease knows no borders FDA’s response to the Ebola epidemic in West Africa demonstrates how we use our scientific expertise and regulatory authorities to the fullest extent possible to address a tragic public health crisis of global impact. Our response involved collaborating with partners across government, pharmaceutical and diagnostic companies, international organizations like the World Health Organization, and our international regulatory counterparts. We played a key role in expediting the availability of diagnostic tests and investigational therapeutics and vaccines, as well as investigating fraudulent products marketed to diagnose, prevent and treat Ebola. And many FDA commissioned corps officers of the U.S. Public Health Service served on the front lines, deployed in a humanitarian mission to provide care to patients at the Monrovia Medical Unit in Liberia, one of the West African nations that were hard hit by the outbreak.

Addressing Transmission of Infections from Duodenoscopes

This year we took steps to help protect the public from the risk of transmitted infections, including antibiotic-resistant infections, from duodenoscopes. Duodenoscopes are complex devices used during endoscopic retrograde cholangiopancreatography (ERCP), a potentially life-saving procedure to diagnose and treat blockages in the pancreas and bile ducts. In the United States, duodenoscopes are used in more than 500,000 ERCP procedures each year.

Last February, the FDA issued a safety communication to raise awareness about the risk of transmitted infections from duodenoscopes, after it determined that the design of these devices may impede effective reprocessing, even when the manufacturer’s reprocessing instructions are followed correctly. Reports also indicated that some healthcare facilities may not have adequately followed the manufacturer’s reprocessing instructions. To address these concerns, the FDA has been working with the device manufacturers to ensure that the reprocessing instructions for their duodenoscopes are put through the most rigorous testing. The Agency held a public advisory committee meeting in May to discuss the scientific challenges, and it incorporated recommendations for enhancing the safety margin of reprocessing duodenoscopes into a safety communication in August. Also in August, FDA issued Warning Letters to all three duodenoscope manufacturers citing violations found during recent inspections. In October, the FDA ordered the manufacturers to develop postmarket surveillance studies of how the devices are reprocessed in real-world clinical settings.

Our foremost concern is protecting patients, and we are committed to taking steps to assure that duodenoscopes – and all reprocessed medical devices — are safe to use.

Compounding

We continue to respond effectively to the 2012 outbreak of fungal meningitis linked to contaminated compounded drugs. We are implementing the Drug Quality and Security Act and continuing our inspection and enforcement efforts at compounding facilities nationwide. To that end we have issued numerous policy documents regarding compounding and related activities to provide guidance to industry as we implement the new law. We’ve also held meetings with stakeholders, including pharmacy, physician, and consumer groups, and we have continued our active and successful collaborations with state governments.

Addressing the Opioid Abuse Crisis

Over the last year, we’ve been very focused on the growing epidemic of opioid abuse and addiction and its devastating impact on public health. This focus has required us to strike a delicate balance: ensuring medical treatments are available for patients who are in pain, while addressing the often tragic consequences of abuse and misuse, which all too often overwhelm individuals, families, friends and communities. Our approach is multi-pronged, from encouraging scientific investigation to improving the training of practitioners who prescribe these powerful medicines.

We believe it is vitally important to encourage the development of abuse-deterrent formulations of opioids and to support options for medication-assisted treatment of opioid-dependence. Final guidance for industry regarding the development of abuse-deterrent formulations was issued in April and several abuse-deterrent products have been approved. We are also making strides to treat the consequences of overdoses. In November, FDA approved the first nasal spray version of naloxone hydrochloride, to provide a route of delivery in addition to injection for this life-saving medication that can stop or reverse an opioid overdose. And we are working with our federal partners to improve access to naloxone.

While we cannot solve this complex problem alone, we remain committed to making the best use of our regulatory authorities and working with our partners both in and outside government to reduce the risks associated with opioids. To continue to achieve that, we have been engaging in a comprehensive review of our many current activities related to opioids and identifying which measures can and should be strengthened and what further measures are needed to address this crisis during 2016.

Ensuring the safety of the medical products we regulate requires us to manage a wide-range of issues across multiple scientific disciplines; and to employ scientists with the knowledge to solve today’s complex regulatory challenges. The last year brought many challenges, and just as many solutions.

In my final post, I will address some of our accomplishments in the area of food, tobacco product regulation, and antimicrobial resistance.

Stephen M. Ostroff, M.D., is Acting Commissioner of Food and Drugs

What We Mean When We Talk About Data

By: Robert M. Califf, M.D. and Rachel Sherman, M.D., M.P.H.

Robert M. Califf, M.D., MACC, FDA's Commissioner of Food and Drugs

Robert M. Califf, M.D., Commissioner of the U.S. Food and Drug Administration

Medical care and biomedical research are in the midst of a data revolution. Networked systems, electronic health records, electronic insurance claims databases, social media, patient registries, and smartphones and other personal devices together comprise an immense new set of sources for data about health and healthcare. In addition, these “real-world” sources can provide data about patients in the setting of their environments—whether at home or at work—and in the social context of their lives. Many researchers are eager to tap into these streams in order to provide more accurate and nuanced answers to questions about patient health and the safety and effectiveness of medical products—and to do so quickly, efficiently, and at a lower cost than has previously been possible.

But before we can realize the dramatic potential of the healthcare data revolution, a number of practical, logistical, and scientific challenges must be overcome. And one of the first that must be tackled is the issue of terminology.

Defining Terms

Although “data,” “information,” and “evidence” are often used as if they were interchangeable terms, they are not. Data are best understood as raw measurements of some thing or process. By themselves they are meaningless; only when we add critical context about what is being measured and how do they become information. That information can then be analyzed and combined to yield evidence, which in turn, can be used to guide decision-making. In other words, it’s not enough merely to have data, even very large amounts of it. What we need, ultimately, is evidence that can be applied to answering scientific and clinical questions.

So far, so good. But what do we mean when we talk about “real-world data” or “real-world evidence”?

Rachel Sherman

Rachel Sherman, M.D., M.P.H., FDA’s Associate Deputy Commissioner for Medical Products and Tobacco.

Clinical research often takes place in highly controlled settings that may not reflect the day-to-day realities of typical patient care or the life of a patient outside of the medical care system. Further, those who enroll in clinical trials are carefully selected according to criteria that may exclude many patients, especially those who have other diseases, are taking other drugs, or cannot travel to the investigation site. In other words, the data gathered from such studies may not actually depict the “real world” that many patients and care providers will experience—and this could lead to important limitations in our understanding of the effectiveness and safety of medical treatments. Clinicians and patients must be able to relate the results of clinical trials—studies that are done in controlled environments with certain patient populations excluded and which may therefore be challenging to generalize—to their own professional and personal experiences. It seems straightforward, then, to think that studies including a much fuller and more diverse range of individuals and clinical circumstances could ultimately lead to better scientific evidence for application to decisions about use of medical products and healthcare decisions.

But “real-world evidence” has its own issues that must be understood and dealt with carefully. First of all, the vague term “real-world” may imply a closer relationship with the truth—that the real-world measurement is preferable to one taken in a controlled environment. For example, is “real-world” blood pressure data gathered from an individual’s personal device or health app better (e.g., more reliable and accurate) than a blood pressure measurement from a doctor’s office? It could be, because a patient’s blood pressure might be uncharacteristically elevated during a visit to the physician. But at the same time, do we know enough about the data gathered from the patient’s personal device—how accurate is it? Is the patient taking their own blood pressure correctly? What other factors might be affecting it?—to use it for generating evidence? Already we are being reminded of the complexities of potentially relying on data that were gathered for purposes other than the ones for which they were originally intended.

In most cases “real-world evidence” is thought of as reflecting data already collected, i.e., epidemiologic or cohort data that researchers review and analyze retrospectively. Also of interest is whether randomized trials can be conducted in these “real-world” environments. In considering comparisons of treatments, one must always consider the possibility that the treatments were not assigned randomly, but reflected some relevant patient characteristic. This is, of course, the reason for doing randomized clinical trials.

Better Terms for Complex Subjects

There is little doubt that the new sources of data now being opened to researchers, clinicians, and patients hold enormous potential for improving the quality, safety, and efficiency of medical care. But as we work to understand both the promise and pitfalls of far-reaching technological changes, we need a more functional vocabulary for talking about these complex subjects, one that allows us to think about data, information, and evidence in ways that capture multiple dimensions of quality and fitness for purpose (e.g., for appropriate use in regulatory decision making). The incorporation of “real-world evidence”—that is, evidence derived from data gathered from actual patient experiences, in all their diversity— in many ways represents an important step toward a fundamentally better understanding of states of disease and health. As we begin to adapt “real-world data” into our processes for creating scientific evidence, and as we begin to recognize and effectively address their challenges, we are likely to find that the quality of the answers we receive will depend in large part on whether we can frame the questions in a meaningful way.

Robert M. Califf, M.D., previously FDA’s Deputy Commissioner for Medical Products and Tobacco, became FDA’s Commissioner of Food and Drugs on Feb. 25, 2016.

Rachel Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco.