FDA Blood Supply and Demand Simulation Model Could Help Nation Prepare for Emergencies

By: Arianna Simonetti, Ph.D., and Richard Forshee, Ph.D.

Keeping the nation’s blood supply and demand system working efficiently can be a matter of life and death. That often means moving blood to meet critical needs when an area of the country experiences shortages. In fact, ensuring that blood gets to where it is needed, when it is needed, during emergencies is an important part of national security preparedness, and part of FDA’s mission.

Arianna Simonetti

Arianna Simonetti, Ph.D., is a Mathematical Statistician at FDA’s Office of Surveillance & Biometrics, Division of Biostatistics in the Center for Devices and Radiological Health

That’s why FDA developed a blood supply model that estimates the amount of blood available in the system during both routine conditions and emergencies. This model is designed to help public health officials effectively plan strategies that will minimize any disruption of the blood supply should blood collection efforts be reduced as a result of an emergency. The model has the advantage of being easily customized to explore various “what-if” scenarios, so it could assist in the development of sound regulatory policy and strategic planning for emergency preparedness and medical responses requiring blood transfusions.

The model estimates how much blood is available during two types of emergencies—a pandemic influenza outbreak and a mass casualty event caused by the detonation of an improvised nuclear device. Either scenario could threaten the blood supply in two ways—by reducing the number of people available to donate or by increasing the amount of blood needed to respond to such an emergency.

Richard Forshee

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

To our knowledge, this model is the first attempt to estimate how much blood would be available for the U.S. blood system during potential national emergencies.

One of the challenges in dealing with an emergency is that red blood cells (RBCs) have a relatively short shelf life. The model allows us to calculate the supply—and the potential for shortages—based on how long RBCs have been in storage.

An earlier model designed by our group provided overall national daily estimates of the number of RBC units available in the demand system. Our new, inter-regional model divides the U.S. blood supply into four regions: East, West, South, and Midwest. This gives us a more fine-tuned look at the blood supply system’s response to emergencies by tracking the collection and transfer of blood across the different regions. It can also give us a snapshot of the blood supply at any time and in any region. This suggests that the model could help in planning for emergencies that trigger higher demands of blood in potentially affected regions.


Blood Availability: A Model of Supply and Demand

The amount of blood that is collected and used in different regions of the country varies. The FDA model of the U.S. blood supply enables public health officials to estimate the availability of blood in each region at any given time. This helps minimize disruption and avoid shortages in the blood supply.The amount of blood that is collected and used in different regions of the country varies. The FDA model of the U.S. blood supply enables public health officials to estimate the availability of blood in each region at any given time. This helps minimize disruption and avoid shortages in the blood supply.In the South, as shown in the example above, the amount of blood donated in a region may be less than the amount needed for transfusions in that region. This potential shortage in donations can be mitigated by blood transfers from other regions, as indicated by the arrows. The FDA model accounts for blood transfers among regions based on data provided by America’s Blood Centers, which collects about 55% of the U.S. blood supply.In the South, as shown in the example above, the amount of blood donated in a region may be less than the amount needed for transfusions in that region. This potential shortage in donations can be mitigated by blood transfers from other regions, as indicated by the arrows. The FDA model accounts for blood transfers among regions based on data provided by America’s Blood Centers, which collects about 55% of the U.S. blood supply.

To build a model that reflected actual blood collection and use in the four regions as closely as possible, we went to real-world sources of data. For example, we used the daily report on the national blood supply produced by America’s Blood Centers to determine how much blood was available in each region. To track blood use in each region, we calculated regional daily RBC units transfused from the 2007-2012 Center for Medicare and Medicaid Center for Medicare and Medicaid Services database. We also used national estimates of blood collections and use from the 2011 National Blood Collection and Utilization Survey. Using this information, the model estimates the average number of RBC units available each day for each region.

To create our scenario for a pandemic, we used data on the outbreak of Pandemic A(H1N1) influenza from the Centers for Disease Control and Prevention and the weekly flu-like activity levels reported by the states.

Guided by a previously-developed computer model simulating the effect of a pandemic on blood donations and blood supplies in Germany, we ran a simulation on how the pandemic could affect the inter-regional supplies of blood in the U.S. One important finding was that the new model estimated that 541,000 RBC units were lost overall and that the South region had the highest percentage of blood lost (15.5%), while the East region had the lowest lost (13.8%), compared to the levels at the beginning of the pandemic.

For our simulation of the demand for RBC units needed following a mass casualty event caused by an improvised nuclear device, we used data on the expected casualties from each type of injury from a previous study. Our own inter-regional simulation let us predict the effect of such an event on the U.S. blood supply. For example, we saw that if the event occurred in the East region, given the current data available, this area of the country rapidly recovered to its original level of blood supply due to increased blood transfers from other regions.

The FDA model showed that, based on current levels of blood collection, use, and other factors, the U.S. blood supply and demand system is flexible and reliable enough to respond to these events.

But our simulation model is just an attempt to replicate the workings of the U.S. blood supply and demand system under various circumstances. Our conclusions could change if patterns of blood donation and use change. However, our experience with this model thus far shows that, as we add more accurate and current data and, make it available to planners, it could help the nation prepare for disruptions of blood collection and demand.

Arianna Simonetti, Ph.D., is a Mathematical Statistician at FDA’s Office of Surveillance & Biometrics, Division of Biostatistics in the Center for Devices and Radiological Health

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

The One-Year Anniversary of the Oncology Center of Excellence

By: Richard Pazdur, M.D.

One year ago, Jan. 19, 2017, FDA officially launched the Oncology Center of Excellence to leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics and devices (including diagnostics).

Dr. Richard PazdurIn doing so, we hoped to help expedite the development of oncology and hematology medical products and support an integrated approach to the clinical evaluation medical products for the treatment of cancer.

Significantly, OCE is the first center to focus on a specific disease rather than FDA’s traditional orientation toward centers that focus on specific products. In this new era of cancer therapeutics development, biologic products like gene and cellular therapies and vaccines, and devices like next-generation sequencing in vitro diagnostics, are increasingly being integrated with drug therapies into patient care.

Looking back over the past year, it is clear that FDA — and patients — have benefited from this unique disease-specific center. To get started we established procedures for collaboration across the centers. We created disease-specific interest groups so that experts across the various FDA review divisions can talk about cutting-edge science. We also created an internal scientific council to advise the OCE. By breaking down traditional silos and focusing on a specific disease, we increased our communication and collaboration, creating best practices to integrate our reviews of these exciting new technologies.

Altogether in 2017, we approved 16 new drug and biologic applications, including the first two cell-based gene therapies. We also approved 30 supplemental drug and biologic applications, two biosimilar applications in oncology, and cleared or approved several in vitro diagnostics.

And we used creative approaches for approval. For example, last May, FDA granted the first approval of a cancer treatment based on a tumor’s biomarker without regard to the tumor’s original location. Pembrolizumab is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), abnormalities that affect the proper repair of DNA inside the cell. Rather than requiring separate development programs for each disease site, we created a single therapeutic approach for patients with different tumor types, allowing extrapolation of the observed treatment effect to diverse tumors.

Notable Oncology Products Approved in 2017

Drugs and Biologics

  • The first two cell-based gene therapies – chimeric antigen receptor (CAR) T-cell immunotherapies for the treatment of advanced hematologic malignancies – tisagenlecleucel for pediatric precursor B-cell acute lymphoblastic leukemia and axicabtagene ciloleucel for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. To treat a serious adverse event known as cytokine release syndrome associated with tisagenlecleucel, tocilizumab was concurrently approved with that drug.
  • The first cancer drug product label update describing how certain patients could STOP taking nilotinib once their cancer,  Philadelphia chromosome positive chronic myeloid leukemia, had responded after at least three years of taking the drug.

IVDs

  • The Oncomine DX Target Test that detects mutations in 23 genes, including BRAF, ROS1 and EGFR mutations in non-small cell lung cancer
  • Memorial Sloan Kettering Cancer Center’s IMPACT next-generation sequencing (NGS) tumor profiling test that detects mutations in 468 unique genes that can identify a higher number of genetic mutations (biomarkers) that may be found in various cancers than any test previously reviewed by the agency
  • FoundationOne CDX, an NGS test that detects genetic mutations in 324 genes, two genomic signatures and tumor mutational burden in solid tumors for use as a companion diagnostic to identify patients with specific mutations who may benefit from certain FDA-approved treatments for non-small cell lung cancer, melanoma, breast cancer, colorectal cancer or ovarian cancer—extending beyond the previous “one test for one drug” model

Outreach and Collaboration

In addition to product review, the Oncology Center of Excellence is also tasked with external outreach and the academic development of our staff. To be effective, we must collaborate with our stakeholders to develop discussions and conferences that will have an impact on drug regulation. In the past year, we held more than 30 symposiums bringing academics and key therapeutic leaders to FDA. We also held a workshop for patient advocates to discuss the important role they can play in oncology product development. Often these conferences were conducted jointly with oncology professional societies, patient groups, and leading cancer centers.

Now that we have been in business for a year, it is time to ask our stakeholders about the new center. We have scheduled a public listening session on March 15 to hear recommendations from stakeholders regarding their expectations of the OCE, specifically, what stakeholders desire of the OCE in terms of structure, function, regulatory purview, and activity.

We are planning other public meetings as well, including a public workshop on Jan. 29 to seek input from experts and patients to discuss how to best implement genetic sequencing data in patient management, and later this year workshops on trial designs for early stage lung cancer and how best to combine immunotherapy and radiation therapy.

The OCE also must be a leader in the development of regulatory science in oncology. Some of our recent initiatives include:

  • Re-evaluating clinical trial eligibility criteria to ensure patients who enter clinical trials will reflect patients treated in the community. Our work with the American Society of Clinical Oncology and Friends of Cancer Research was detailed in the Journal of Clinical Oncology.
  • Encouraging the development of site-agnostic indications. Our perspective on this topic was published in the New England Journal of Medicine.
  • Advocating for the use of master protocols, umbrella protocols, and the use of common controls. We have worked with sponsors to use seamless design trials that eliminate the conventional division of phase 1, 2, and 3 trials that may delay drug development. Working with professional groups and sponsors, we have promoted the use of these innovative designs to reduce redundancy and inefficiency of clinical trials.
  • Devoting resources to the use of real-world evidence for potential regulatory decision-making. This emerging area will in the future provide important safety and efficacy information and a window on how drugs are actually used.
  • Working with colleagues across FDA, at the National Cancer Institute, and the HHS Office of Human Research Protections, as well as many other external stakeholders to foster research into patient-reported outcomes measurement and generating science-based recommendations for regulatory policy.

Looking to 2018 and beyond, I am optimistic about the outlook for the future of oncology drug development. Maintaining the OCE’s emphasis on excellence in regulatory science will ensure the rapid development of highly effective and less toxic therapies for patients with cancer. At the end of the day, patients with a life-threatening disease want to live longer, with a better quality of life. We can never lose sight of our dedication toward progress against this disease.

Richard Pazdur, M.D., is Director, FDA Oncology Center of Excellence

Patient Reps – Bringing the Voice of Patients to FDA

By: Jack Kalavritinos

At FDA we never lose sight of the fact that the work we do in evaluating and approving new medical products is done to benefit patients.

Increasingly, that means taking into account the views and expertise of patients and their caregivers, because they provide a unique voice and perspective and know best what they are living with on a day-to-day basis. Earlier this month, for instance, we announced the creation of the first advisory committee made up solely of patients and caregivers, who will provide advice on complex issues related to medical devices.

Another way we incorporate the patient viewpoint is through FDA’s Patient Representative Program. This program brings patients – and their caregivers – and the extraordinary breadth of knowledge and personal experience in more than 300 diseases and conditions they possess, directly into the regulatory medical product development and review process. They serve on 47 FDA Advisory Committees and panels to advise on drugs, devices and biologics currently being considered for approval or clearance. They also serve as a consultant for the review divisions (doctors and scientists who review data to determine whether the medical product’s benefits outweigh the potential risks), and as presenters at FDA meetings and workshops on disease-specific or regulatory and health policy issues.

Jack Kalavritinos , FDA’s Associate Commissioner for External Affairs

Members of FDA’s Patient Representative Program together with Jack Kalavritinos, Associate Commissioner for External Affairs, during a recent training session in suburban Washington, D.C.

Every year our team at FDA’s Office of Health and Constituent Affairs brings new FDA patient representatives to the Washington, D.C. area, for training and orientation. They receive briefings on everything from medical product review policies and clinical trials to the life cycles of drugs, biologics, and devices, and even a brief primer on statistical analysis.

Without a doubt, the most moving moments of the recently completed two-day workshop  were when the patient representatives told their own stories, how they are making a difference in so many lives as advocates for their own patient communities, and explaining why they had decided to make the commitment to become patient reps. One was more compelling than the next. Here are some of their stories:

  • A woman with fibromyalgia who said she joined the program “to give a voice to those who suffer with chronic, life-altering conditions.”  She believes her training in qualitative research, combined with her personal experience with her disease, will help her listen to and understand patient experiences and to “sort out the ‘noise.’”
  •  A caregiver whose husband survived for three years after being diagnosed with glioblastoma multiforme, a form of brain cancer. During that period, he received four surgeries and took 15 different chemotherapy drugs. She became a patient advocate as a result of her experience so she could be involved in the process of finding new treatments for “this daunting disease.” She also works with other caregivers to help them cope with the diagnosis. As she explained, “Being able to talk to someone who has experienced this same disease helps to reduce their level of anxiety and some of the unknowns that accompany this diagnosis.”
  • A patient with schizoaffective disorder who talked about how her disease first appeared when she was in college, when the voices she would hear interfered with her ability to learn and function. But with proper treatment, and incredible discipline and support, she was able to learn to control her disease and not let it take over her life. Today, she is a mental health therapist who works to combat stereotypes that prevent psychiatric patients from getting the help they need, when they need it. Her goal has been “to put a face to those of us who struggle with psychosis, but yet are seen as being ‘functionally well.’”
  • A father and uncle to two women with Friedreich’s ataxia, a life-shortening genetic mitochondrial nerve disorder that has no treatment. He has watched as his daughter, now 31, has become a quadriplegic. As he said with incredible honesty and pain, “she will die soon.” But he also has turned his pain into action. In addition to assisting his daughter and niece, he also has lent his energy to helping others with the disease and to generating attention and resources for finding a treatment. He became a patient representative, in part, he explained, so that he “could be at FDA on the day a treatment needs his yes or no vote.”

Space prevents including every one of their stories, but each of these remarkable individuals offered a compelling history of courage. All are committed to fighting the disease that had so directly affected them, whether as a patient or a caregiver. But, in a comment that could be applied to all of them, one woman noted, she “works hard to not let my identity be defined by my illness.” They do this, remarkably, by turning their focus outward, rather than inward, and using their strength and expertise to the benefit of others.

This understated, but courageous, spirit is echoed in one way or another by each of FDA’s patient representatives. We want to thank each of these individuals for their inspiring commitment — to the FDA, to better health, and for their role in these critical public health efforts.

Jack Kalavritinos is FDA’s Associate Commissioner for External Affairs

FDA Collaborates to Promote Safety, Quality in Clinical Trials Done in India

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By Leslie Ball, M.D., Letitia Robinson, Ph.D., R.N, and Elizabeth Wiley, M.D., J.D., M.P.H.

After more than 16 hours of travel, we touch down in Mumbai late in the evening and are greeted by a wave of heat and humidity as we exit the airport terminal. As we drive from the airport to the hotel, the vast Mumbai skyline is striking. India is home to 17% of the world’s population but accounts for about 20% of the global disease burden including both communicable and non-communicable diseases.

As a result, India holds a vast potential for clinical research and has become a global leader in the production of generic drugs. An estimated 40% of generic drugs imported into the U.S and used by American consumers are manufactured in India. Generic medications play a critical role in reducing drug costs for both patients and payers.

Leslie Ball, M.D., FDA Assistant Commissioner of International Programs and Elizabeth Wiley, M.D., J.D., M.P.H., AAAS Science and Technology Policy Fellow

Leslie Ball, M.D., Assistant Commissioner of International Programs (left), and Elizabeth Wiley, M.D., J.D., M.P.H., AAAS Science and Technology Policy Fellow, share some highlights from their recent training trip to India.

In an effort to promote the safety and efficacy of imported drugs, the FDA’s Office of International Programs (OIP) and the agency’s India Foreign Office have adopted a strategic engagement approach which includes inspections, targeted engagements including training, and the collection and use of data to inform FDA decision-making.

The purpose of our trip in mid-May was to participate in a joint training workshop for Indian regulators, academic representatives, and the drug industry on scientific and ethical standards for clinical trials. In addition to representatives from FDA, the European Medicines Agency, the Indian Central Drugs Standard Control Organization, and the Drug Information Association (DIA) were part of this first joint training.

FDA presenters included Jennifer Adams, M.P.H., Assistant Director, FDA India Office, and Sam Haider, Ph.D., Deputy Director of FDA’s Center for Drug Evaluation and Research (CDER) Office of Study Integrity and Surveillance. Sean Kassim, Director, CDER’s Office of Study Integrity and Surveillance, and Mathew T. Thomas, M.B., M.S., Senior Advisor, CDER’s Office of Scientific Investigations, provided critical planning for the event.

Recent changes in Indian regulation of clinical trials have seemingly impacted the number of registered drug clinical trials. Based on data from clinicaltrials.gov, registered drug clinical trials in India declined from 2010 to 2015. These numbers are predicted to increase in response to recent regulatory changes in an effort to create a more supportive regulatory environment in India. Moreover, there has been a sharp increase in the number of bioavailability or bioequivalence studies in India over the last decade as India has become the world’s largest supplier of generic drugs.

Letitia Robinson, Ph.D., R.N., Director of the FDA India Office.

The collaborative workshop, hosted by DIA, included an intensive two-day whirlwind of sessions, discussions, and case studies addressing key quality and ethical issues in clinical trials. Workshop participants included sponsors, contract research organizations, firms conducting bioavailability or bioequivalence studies, clinical investigators, regulators and academic researchers. These joint workshops sought to provide practical training on emerging issues, regulatory updates, clinical trial data integrity and inspectional methods. The specific goals of these workshops include:

  • Identifying general concepts in inspections of clinical investigators, clinical trial sites, ethics committees, and bioanalytical study sites;
  • Identifying techniques for maintaining data integrity in clinical trials; and
  • Reviewing inspections to develop evidence and determining appropriate observations to include in inspection reports.

The panels featured regulators from India, Europe, and the United States, as well as industry representatives. Participants fielded many questions on inspections, regulations, and standards – all in an effort to promote data integrity, credible and accurate results, and protection of subjects in clinical trials.

These questions helped clarify areas of harmonization among far-flung regulatory authorities, as well as differences such as the requirements for compensation of clinical trial participants after injury in India.

A second training in mid-May in Hyderabad, known as the City of Pearls and a technology center within India, began with a new audience of industry, academic and regulatory representatives. And, much like Mumbai, participants quickly engaged in two days of intense lectures, case studies and discussions with no shortage of questions and comments.

Informal feedback from participants was overwhelmingly positive and suggested that significant progress toward the goal of FDA participation in these workshops, including ensuring necessary capacity within regulatory and academic communities is developed and contributes to a sustainable training curricula, had been achieved.

Leslie Ball, M.D., is FDA Assistant Commissioner for International Programs; Letitia Robinson, Ph.D., R.N., is the incoming Director, FDA India Office; and Elizabeth Wiley, M.D., J.D., M.P.H., is an AAAS Science & Technology Fellow, Office for International Programs

FDA Science: Working at the Speed of Emerging Technologies

By Luciana Borio, M.D.

Let’s face it, we’ve all gotten used to nearly instant access to almost anything.

Today, with a tap of an app, we order a car ride, a book, or pizza for dinner. Need to navigate past traffic in downtown city streets? No problem. There’s an app for that, too.

Some may wonder: Why hasn’t rapid medical product development partaken of this need for speed that has reshaped other sectors of our economy? Well, in many ways, it has.

Innovation is happening extraordinarily fast in the biomedical sciences and at FDA. As FDA’s Acting Chief Scientist responsible for leading and coordinating FDA’s cross-cutting scientific and public health efforts, I see close up that years of scientific research, collaboration, and investment are paying off.

FDA Acting Chief Scientist Lu Borio

FDA Acting Chief Scientist Luciana Borio

When I testified at a congressional hearing recently, my colleague, Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, gave a tangible example of what I mean. He said it took his team about three months to begin clinical testing of a Zika vaccine candidate developed from scratch. In 2003, it took the same team 18 months to develop a candidate vaccine to address the SARS outbreak and begin clinical testing of that product.

And in just over two decades, a disease like multiple sclerosis has gone from being untreatable to one for which clinicians are nearly “flummoxed by the options,” according to a headline I saw recently.

There is a reason for this success. In the last several years, scientists have identified and begun using “safety-risk biomarkers.” Rather than those for efficacy, these biomarkers identify which patients are at highest risk for certain adverse events. They have opened up an array of therapeutic options for patients who might do just fine with some treatments that may not otherwise have been developed due to our previous inability to properly assess their risk.

None of these successes would be possible without our FDA product reviewers working at breakneck pace to guide these innovative development programs.

It’s not always fully understood that FDA scientists play an essential role in advancing many biomedical innovations. That’s why we invite the public to participate in a two-day Science Forum at FDA every other year to showcase the agency’s robust scientific research and the important work done by our 11,000 scientists.

Just as industry focuses on product development research and academia focuses on the scientific foundation, FDA research concentrates on creating test methods and developing knowledge of processes to ensure that our products are safe and effective or, with tobacco, at least with reduced harm.

I like to think that this year’s Science Forum was better than ever. Over two days, hundreds of participants were treated to 230 scientific posters and some 50 presentations by FDA scientists and others, organized under eight broad categories:

  1. Identification and Evaluation of New Biomarkers;
  2. FDA Response to Urgent Public Health Needs;
  3. Microbiome and Human Health;
  4. Advanced Manufacturing and 3D Printing;
  5. Omics Technologies at FDA;
  6. Patient and Consumer Engagement and Communication;
  7. Computational Modeling and Simulation at FDA; and,
  8. Current Progress in Nanotechnology Research at FDA.

Four poster sessions during the two days augmented the presentations that featured the authors of studies describing the methodology, challenges, and results of their research one-on-one with those at the forum. Among the meaty topics discussed were:

  • The emerging technology of additive manufacturing and medical devices, produced by 3D printing. Bioengineers at FDA’s Center for Devices and Radiological Health have positioned themselves at the forefront of knowledge and research about this cutting-edge manufacturing process, by looking into patient matching, imaging, and phantoms. With our proactive posture, FDA is paving the way for safe and effective innovation that will usher in life-saving advanced treatments for patients.
  • The growing use in medical products of nanomaterials – equal to about one-billionth of a meter – so small that they can’t be seen with a regular microscope. Silver nanoparticles are now used in wound dressing for their antimicrobial properties. And liposomal nanoparticles are used as drug carriers to reduce toxicity and increase circulation time in the blood. Characterizing these complex nanomaterials is challenging. FDA scientists highlighted their analytical methods for characterizing nanomaterials in over-the-counter FDA-regulated products. This will help us with assessing risk, developing industry guidelines for characterizing nanomaterials, postmarket surveillance, and determining shelf life of nanomaterials in consumer products.
  • In the area of food safety, FDA has contributed to enhancing antimicrobial resistance monitoring in a collaborative effort with USDA and the Centers for Disease Control and Prevention. And, genomics studies conducted by FDA scientists have demonstrated that we can use the emerging technology whole genome sequencing as an effective tool for predicting antimicrobial resistance of certain foodborne pathogens.

Not all of our essential research deals with cutting-edge technology. Scientists from FDA’s Center for Tobacco Products (CTP) shared their work on water pipe, or hookah, smoking. Water pipes, a centuries-old method of smoking, are becoming an increasingly common method of tobacco smoking in young adults. A rare and serious lung disease – water pipe-induced acute eosinophilic pneumonia – has been reported among these smokers. One of the forum’s posters described how CTP scientists identified the disease and made physicians aware of it.

And, as a sign of the times, mobile communications also were part of the poster sessions. Healthy Citizen @FDA will be a holistic, citizen-centric mobile platform for FDA to collaborate and communicate with citizens to improve public health outcomes and to receive timely FDA alerts.

Of course, events like these are equally valuable for what happens before and after the formal presentations. From the snippets of conversation I picked up in the hallways, FDA and outside scientists had plenty of opportunity to interact, share ideas, and even discuss potential collaborations.

Those who attended the 2017 Science Forum gained a deeper understanding of the cutting-edge science we do at FDA to protect and promote the public health. And those who missed the Forum have the option of watching the recorded presentations on FDA’s website. We look forward to future opportunities to share more of the exciting advances we’re making with our partners in the scientific community.

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

FDA Works with Partners to Establish Important Therapeutic Area Data Standards

By:  Janet Woodcock, M.D.

Clarification, November 5, 2012:  CFAST is a joint initiative of CDISC and the Critical Path Institute.  The FDA and TransCelerate Biopharma, Inc. are partnering with CFAST in its Therapeutic Area Standards Program.

A new partnership between the FDA, the Clinical Data Interchange Standards Consortium (CDISC), and the Critical Path Institute (C-Path) was officially launched today at the CDISC International Interchange in Baltimore. This partnership, called the Coalition For Accelerating Standards and Therapies or CFAST, will bring together clinical data experts from the FDA, the pharmaceutical industry, and the information technology sector, to develop and maintain data standards tailored to individual diseases and therapeutic areas.

Janet Woodcock, M.D.While I was preparing my keynote address for the Interchange, I began thinking of how history provides us lessons for the future, and the Great Baltimore Fire of 1904 is a particular example that stands out in my mind. In this tragedy, thousands of firefighters from surrounding cities and states responded to Baltimore’s call for help, but they were unable to assist in putting out the fire because their hoses and equipment were not compatible with the Baltimore hydrant connections.  This terrible event made the need for standardized fire-fighting equipment and connections devastatingly clear.

As part of the changing tide of drug regulation, we are seeing ever-increasing streams of data coming into the agency. However, much like standardized fire-fighting equipment, we need to develop standardized definitions for individual diseases and the therapeutic approaches to treat them to be able to tap into this data stream.

Standardized data elements that are common to all clinical trials, such as age and gender, have been established using CDISC terminology. However, data elements that are unique for a particular disease or therapeutic area still need to be developed so that the data from multiple trials can be more easily grouped for reporting and analysis.

In short, establishing common standards for data reporting will provide new opportunities to transform the massive amount of data from drug studies on specific diseases into useful information to potentially speed the delivery of new therapies to patients.

We at the FDA are excited to be a member of this very important partnership. We believe that CFAST will provide an important resource for drug development and research that will result in enhancements in the evaluation of safe and innovative therapies for the public.

More about the priority therapeutic areas for standards development.
To read more on data standards, please read:  CK Cooper et al. Drug Information Journal. 46(5) 521-22.

Janet Woodcock, M.D. is the Director of the FDA’s Center for Drug Evaluation and Research.

National Mammography Day: Supporting Quality Mammography

By: Marsha B. Henderson, M.R.C.P. and Helen Barr, M.D.

Like millions of women, we go each year to get a mammogram. For us the experience is not just about healthy living. It is also a reminder of the value of our hard work at FDA. Each time we see the FDA certificate in our mammography facility showing that the facility meets FDA’s high standards, we are reminded of the commitment and dedication of FDA employees to supporting mammography services.
Marsha B. Henderson, M.R.C.P. and Helen Barr, M.D.

Marsha B. Henderson, M.R.C.P. (left) and Helen Barr, M.D.

Under the Mammography Quality Standards Act and Program, FDA employees work to ensure that women can go anywhere in the country and expect to get reliable, high quality breast images. We certify and inspect mammography facilities establishing uniform standards for mammography equipment and staff training. Thanks to these efforts, there are over 8,600 certified mammography facilities in rural and urban communities across the country.

We didn’t stop there. Early on, we realized that regulation was only part of what was needed. FDA recognized that it should also help raise awareness about the importance of mammography. Through the Pink Ribbon Sunday Program, we formed outreach partnerships to teach women the facts about mammography screening. When the Pink Ribbon Sunday Program began in the 1990s, we targeted African American and Latino women because they were least likely to get a mammogram. However, the program quickly spread from minority churches to businesses, sororities, health centers, and other national organizations reaching women from all backgrounds.

Over the years, FDA has touched millions of lives through our mammography initiatives. We have chosen today – National Mammography Day – to thank our colleagues at FDA and our partners in the health care community and state and local governments for their efforts.  We also encourage you to help connect the women in your community to our free mammography resources. Your efforts can help raise awareness, provide hope, and maybe even save a life.

Marsha Henderson, M.C.R.P., is FDA’s Assistant Commissioner for Women’s Health in the Office of the Commissioner

Helen Barr, M.D., is FDA’s Director of the Division of Mammography Quality Standards at the Center for Devices and Radiological Health

Offering Hope: How FDA Engages With the Cancer Community

By: Deborah Miller, Ph.D., M.P.H., R.N.

Deborah Miller, Ph.D., M.P.H., R.N.It’s October and the pink ribbons representing breast cancer awareness month are again a common sighting. These ribbons are reminders that breast cancer is still to be overcome. Breast cancer remains the most common cancer among American women, except for skin cancers. Just about everyone knows someone affected by cancer in general, and many have been touched by breast cancer in some way.

For many years, I worked at the Government Accountability Office (GAO), where I became familiar with FDA. I joined FDA’s Office of Special Health Issues (OSHI) in September 2008 because I wanted to be involved more directly with patients again after working for years during my earlier career with seriously ill patients and their families as a neonatal nurse, research nurse, and hospice volunteer.

Like a lot of people, I have experience with cancer – personal, family members, and friends. As the manager of OSHI’s Cancer Liaison Program, I’ve had many experiences that have enhanced my compassion, respect, and patience as I strive to explain FDA’s role in medical product development and regulation to patients with breast and other cancers.

FDA’s Cancer Liaison Program interacts with many cancer patients and family members asking for help. The program seeks to meet the needs of patients and their families in three basic ways. Listening, educating, and assisting.

First and foremost, we listen to patients and caregivers. They tell us their story – when they were diagnosed, treatments they have tried, providers they have seen, and tests they have been through. Often, they tell us they’re scared.

Some of these patients have been dealing with cancer for a number of years, and they tell us that the approved therapies have not worked or have stopped working. Some have considered or joined a clinical trial of an investigational therapy. Some call with the hope of obtaining a “promising” new investigational product that they have heard about in the news and are convinced may be their last hope.

Secondly, we educate. We spend a significant amount of time explaining to patients and family members how cancer drug development, clinical trials, and expanded access, (known in the community as compassionate use) work. We explain FDA’s role, and what we can and cannot do for patients, and try to guide patients toward practical and appropriate options.

We help bridge the gap between patients, their treating physicians, and FDA scientists who are working to review and approve new treatment options for patients. We strive to provide a human touch for each patient or family member with whom we interact.

Finally, we assist the patients. For example, we try to find potential clinical trials for them, guide them through the expanded access process when it’s appropriate, and work with their healthcare providers throughout the expanded access application process. We give patients, family members, and healthcare providers our contact information so they can reach us to work through regulatory issues at any time, including evenings and weekends.  We periodically call them to see how they’re doing.

And if access to investigational drugs is not practical, we go back to listening. We listen to patients’ expressions of their disappointment, anger, frustration, and fears.

This month, I am thinking about the many breast cancer patients I worked with during this past year who benefited from FDA’s approval of Perjecta in June. But I am equally mindful of the many other patients who did not benefit from the drug and will be calling me, desperately searching for something more.

Deborah Miller, Ph.D., M.P.H., R.N., is the manager of the Cancer Liaison Program in FDA’s Office of Special Health Issues

Looking Back at the Kefauver-Harris Drug Amendments and their Meaning

By: John P. Swann, Ph. D.

The Drug Amendments of 1962, also known as the Kefauver-Harris Drug Amendments, became law five decades ago. But this law’s importance grows with each passing year, making Americans safer than ever from unsafe and ineffective medicines.

John P. Swann, Ph. D.To understand why this law stands today as a pillar of public health in America, it helps to look at how our history shaped it.

There was a system of drug controls in place as early as 1905 that took effectiveness into account, but it was voluntary and administered privately by the American Medical Association. Congress passed laws that required effectiveness from the early 1940s on, but only for selected medicines, such as insulin and penicillin. In 1941, FDA developed regulations to ensure good manufacturing practices to ensure a product’s quality and purity, but only for one drug category. Technically, the Federal Trade Commission had been regulating drug advertising since 1938, but there was little strength in its hold on this industry. And the 1938 Food, Drug, and Cosmetic Act required evidence of a drug’s safety, but the nature of that proof and oversight over how it should be developed were not that clear.

In 1959 Sen. Estes Kefauver began hearings that focused on the high cost of medicines—reflected in the comprehensive bill he introduced in April 1961. But priorities shifted substantially in the next year with the global thalidomide disaster, narrowly averted here, in which a sedative used to treat morning sickness caused thousands of birth defects around the world. Substantial legislative input from FDA helped shape the law that President Kennedy signed on October 10, 1962. And it changed everything:  requirements for therapeutic viability of drugs, veracity in marketing, the proper conduct of investigations, verifiable production controls, patient protections, actual FDA assent to constitute approval, and rigorous proof as the essential element of a drug application.

FDA assembled clinical experts to advise the Agency on drugs previously approved for safety only. They reviewed the available evidence on the effectiveness of those drugs and found that on average 4 out of 10 drugs approved before 1962 and still marketed—medicines that physicians prescribed to their sick patients—either did not work or needed more—often much more—evidence that they did. In the following years FDA removed more than 1,000 of these from the market. At the same time, the agency further called upon therapeutic experts through the systematic use of advisory committees to offer their insights into approval decisions, decisions that still ultimately rested with FDA.

In sorting out this therapeutic mess from the pre-1962 era, the investigational, manufacturing, and regulatory communities reached an understanding about what constituted acceptable evidence, which generally meant randomized, well-controlled clinical trials. While that definition shifted over the following years to accommodate, for example, the needs of gravely ill patients facing few if any treatment options, these changes did not come at the expense of good clinical evidence. Science remained the benchmark of Kefauver-Harris’s legacy.

So, the Drug Amendments of 1962 elevated medical practice, pharmaceutical manufacturing, and public health by inserting a much greater degree of certainty in the way drugs are tested, manufactured, approved, advertised, prescribed, dispensed, and taken.

John P. Swann, Ph. D., is an FDA historian

BeSafeRx: FDA Helping Consumers Avoid Risks of Online Prescription Drug Purchases

By: Ilisa Bernstein, Pharm.D., J.D.

As a pharmacist who cares about patients’ individual medication needs, I am delighted to share my thoughts on FDA’s latest effort to protect patients from fraudulent, illegal online pharmacies. We’ve just launched BeSafeRx – Know Your Online Pharmacy, a national campaign to educate consumers about the risks of buying prescription medications over the Internet.

Ilisa Bernstein, Pharm.D., J.D.It’s troubling to hear that some patients don’t recognize the need to carefully select where they buy their prescription medicines, or that the “pharmacy” they’re buying from might not actually be a pharmacy at all. Too often it seems that it has become second nature for many consumers to buy clothes, electronics or even medicines on the Internet. But the reality is that purchasing drugs from Internet sources that are not known to be reliable is a risky business, and today, with the sale of counterfeit drugs escalating worldwide, perhaps riskier than ever.

How risky? According to a recent FDA survey, nearly one in four of the surveyed Internet users reported having purchased prescription medicine online. This fact alone is not surprising, considering that many people, especially those with prescription drug insurance, use the Internet to get their prescriptions safely filled from legitimate and reputable pharmacies. Unfortunately, in many other cases—far more than we’d like to see—consumers are surfing the Web for cheaper or more convenient sources. Our survey showed that about 29 percent of survey participants said they were unsure about how to safely purchase medicine online. Why is this important? Because, according to reviews by the National Association of Boards of Pharmacy (NABP), less than 3 percent of online pharmacies comply with U.S laws and NABP practice standards, making it critically important for online consumers to understand how to recognize fraudulent, illegal online pharmacies and how to identify a safe, legal online pharmacy.

That’s why I’m so excited about the BeSafe Rx campaign! We’re providing consumers with practical and useful tools to help them make informed decisions about their online purchases. All this useful information is just a click away

When I was in pharmacy practice I wanted nothing but the best for my patients, and now, as a pharmacist with FDA, I want nothing but the best for the American public. BeSafe Rx helps FDA protect public health, and I’m proud to be a part of it. So be safe, and make sure you know your online pharmacy!

Ilisa B.G. Bernstein, Pharm.D., J.D., is the Director (Acting), Office of Compliance in FDA’s Center for Drug Evaluation and Research