FDA Working to Lift Barriers to Generic Drug Competition

By: Scott Gottlieb, M.D.

Too many patients are being priced out of the medicines they need. While FDA doesn’t have a direct role in drug pricing, we can take steps to help address this problem by facilitating increased competition in the market for prescription drugs through the approval of lower-cost, generic medicines.

Dr. Scott GottliebOver the last decade alone, competition from safe and effective generic drugs has saved the health care system about $1.67 trillion. When generics are dispensed at the pharmacy, the immediate savings to each of us are clear. We could see even greater cost savings if we helped more safe and effective generic drugs get to market sooner, after patent and statutory exclusivity periods have lapsed, by addressing some of the scientific and regulatory obstacles to generic competition across the full range of FDA-approved drugs. These barriers may delay and, in some cases, ultimately deny patient access to more affordable drugs.

That’s why we’re working on a Drug Competition Action Plan. As part of this effort, today, we’re announcing in the Federal Register our intent to hold a public meeting on July 18, 2017, to solicit input on places where FDA’s rules – including the standards and procedures related to generic drug approvals – are being used in ways that may create obstacles to generic access, instead of ensuring the vigorous competition Congress intended.

Innovation in pharmaceutical development is essential because it creates new and sometimes life-saving therapies. But access to lower-cost alternatives, once patent and exclusivity periods lapse, also is critical to the nation’s health.

We know that sometimes our regulatory rules might be “gamed” in ways that may delay generic drug approvals beyond the time frame the law intended, in order to reduce competition. We are actively looking at ways our rules are being used and, in some cases, misused.

One example of such gaming is the increasing unavailability of certain branded products for comparative testing. To perform the studies required to develop a generic alternative to a branded drug, a generic sponsor generally needs 1,500 to 3,000 doses of the originator drug. I understand that generic sponsors are willing to buy these products at fair market value; but, in some cases, branded companies may be using regulatory strategies or commercial techniques to deliberately try to block a generic company from getting access to testing samples.

This might occur, for example, when branded companies might use restrictions they place in their commercial contracts or their agreements with distributors to make it hard for intermediaries in the drug supply chain to sell the drugs to generic drug developers.

We also see problems accessing testing samples when branded products are subject to limited distribution – whether the company has voluntarily adopted limitations on distribution, or the limitations have been imposed as part of a Risk Evaluation and Mitigation Strategy, or REMS, a program that FDA implements to help ensure the safe use of certain drugs. I have been made aware that, in some of those cases, branded sponsors may use these limited distribution arrangements, whether or not they are REMS-related, as a basis for blocking generic firms from accessing the testing samples they need.

Besides limiting access to testing samples, some branded companies may be using the statutory default requirement to have a single shared REMS across both the branded and generic versions of a drug as a way to block generic entry. They might prolong negotiations with the generic firms over the implementation of these single shared systems, which could delay the entry of safe and effective generic drugs onto the market.

I want to take steps to address these concerns, to make sure that we are facilitating appropriate competition in circumstances where Congress intended. The forthcoming public meeting is intended to solicit public comment to inform us of circumstances where generic competition may be thwarted by these and other techniques.

As we solicit additional information, we also are going to be looking at policy and programmatic changes to address these issues. Some of these steps may be actions we can take by using our own authorities more forcefully. Other steps might involve our need to collaborate with sister agencies.

We’re also going to be looking hard at how best to coordinate with the Federal Trade Commission in identifying and publicizing practices that the FTC finds to be anti-competitive. FDA is not the FTC. It is the FTC’s responsibility to prevent anticompetitive business practices. But Congress set out certain laws that are meant to strike a careful balance between pharmaceutical innovation and access to lower cost generic products, and FDA has an important responsibility to enforce those laws in a manner that adheres to the balance struck by Congress.

We’ll be unveiling additional aspects of our larger Action Plan and providing updates, as these initial elements are implemented. I’m confident that these actions and the dedicated work of the outstanding staff in our generic drug program will help to address the issues patients are facing today when they’re priced out of buying the drugs they need. At the meeting on July 18 we want to hear from the public about ways our current rules may not be having their intended effects, and where current policies are falling short in ensuring the careful balance between new innovation and patient access.

Our goal is to broaden access to safe and effective generic drugs that can improve access to medicines and help consumers lower their health care costs. As in all of the things we do, we will steadfastly maintain FDA’s gold standard for rigorous, science-based regulation.

Over the past five years our generic drug program staff has evolved and grown remarkably, while implementing the first generic drug user fee program. The staff has demonstrated that they can rise to new challenges and they have my full support. Their hard work will serve as a strong foundation for the program as it moves forward. I want the policy framework they operate under to be as efficient, fair, and robust as the review program that they’re operating.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

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

#IAmHHS: Fighting Misleading Prescription Drug Ad Claims

By: Mike Sauers

These days, you can hardly turn a magazine page, watch a TV show or sit in the lobby of your doctor’s office without seeing advertising and promotions for prescription drugs. They’re everywhere you go. And they tend to be impressive and reassuring. But are they accurate?

A big part of my career at the Department of Health and Human Services has been about helping to make sure those ads are truthful and not misleading.

At the FDA, I’m staff supervisor of the Office of Prescription Drug Promotion’s (OPDP) Advertising and Promotion Policy Staff, which helps develop policies for advertising and promotion of prescription drugs across the United States. In my job, I help make sure that drug companies’ communications of information about their prescription drugs to consumers and healthcare professionals are truthful and not misleading. In my role, I also help to make sure our stakeholders in the pharmaceutical industry understand the rules of the road.

I started my career as a drug representative in Philadelphia, promoting a pharmaceutical company’s drugs. It was a good job in a great industry.

But to be 100 percent honest, it was not personally fulfilling and I decided to pursue public service. I went back to school, earned a master in public policy from Georgetown Public Policy Institute (now McCourt School of Public Policy), and then joined HHS as a budget analyst in the Office of the Secretary through the Presidential Management Fellows Program. Working in the Office of the Secretary gave me the chance to see many of the incredible programs that HHS operates to help improve the lives of Americans on a daily basis.

After my fellowship ended, I decided to continue my HHS career at FDA by focusing on a subject area I knew very well: prescription drug advertising.

I became a regulatory review officer in OPDP and looked at specific ads aimed at doctors or consumers to make sure the claims were truthful and not misleading.

That work prepared me to move into my current role in OPDP where I lead the group that helps develop industry-wide policies for all prescription drug advertising and promotion. One of the highlights of my government service was co-creating the Bad Ad Program, an initiative designed to educate health care providers about misleading prescription drug promotion and to make it easier for them to report this activity to the agency.

It’s an awesome responsibility and very challenging, but I truly believe I am making a difference by helping to ensure that advertisements provide accurate and truthful information about the effectiveness and potential risks of prescription drugs.

You just can’t quantify the type of job satisfaction that comes from knowing that every day you come to work, you have the opportunity to make an impact.

I’m Mike Sauers. I work for the FDA and I am HHS.

Mike Sauers is a staff supervisor in FDA’s Office of Prescription Drug Promotion, Center for Drug Evaluation and Research

Mike is one of more than 79,000 people who make HHS run every day. You can share his story and see others on Twitter and Facebook using #IAmHHS.

In cancer treatment, there’s more than one way to measure patient benefit

By: Richard Pazdur, M.D.

We all want a cure for cancer. But the reality is that advances in cancer treatment rarely come in one big discovery, but rather with the continued step-by-step progress in developing new therapies. Currently, a few cancers—such as childhood leukemia and testicular cancer—can be cured. There are many ways of evaluating cancer therapies, including an improvement in overall survival, stabilizing the disease, and reducing tumor burden and tumor-related symptoms. Over the years, we have discussed with many patients facing serious and life-threatening diseases how to evaluate cancer treatments. The patients have told us there is a need for flexibility in our evaluation process.

Dr. Richard PazdurBefore a new drug is approved, FDA evaluates clinical trials in which the drug is tested in patients. We hope that the study will show a result, or endpoint, that helps us understand if the drug is safe and effective. When evaluating drugs that treat life-threatening illnesses like cancer, the risk-benefit analysis may involve weighing relatively higher risks against relatively smaller benefits.

The gold standard for determining benefit from a new cancer drug traditionally has been a randomized controlled study that demonstrates an improvement in overall survival, or OS. This is a measure of how much longer patients live who take the drug compared with patients who take another drug. An overall survival endpoint clearly demonstrates the drug’s value in extending a patient’s life.

But achieving an improvement in overall survival may not always be possible. Some cancers grow very slowly, so it might take many years for a trial to evaluate whether a potential new drug helps people live longer. Many oncology drugs target specific mutations in the tumor and there may be a limited number of patients with the mutation. Because of the small number of patients, randomized studies evaluating OS may not be possible. Also, many patients in the trial may be taking additional therapies at the time their disease progresses. This may make it difficult to accurately assess the new drug’s effect on overall survival.

When emerging data shows that a new drug demonstrates substantial benefit compared to available drugs, it may not be possible to conduct a randomized trial with certain endpoints comparing the new drug to a standard therapy with modest benefit. This is known as loss of equipoise.

Endpoints other than overall survival can shorten the duration of clinical trials so that drugs can be available sooner to patients. These alternative endpoints include progression-free survival—a measurement of how long a drug may have prevented the cancer from getting worse—and overall response rate—an evaluation of the portion of patients in the trial whose tumor size was reduced by a treatment.

Thousands of patients who previously had few therapeutic options available have already benefited from cancer therapies that were approved based on alternative endpoints, including those with renal cell carcinoma, Merkel cell carcinoma, medullary thyroid cancer, gastrointestinal stromal tumor, metastatic basal cell carcinoma, pancreatic neuroendocrine tumor, multiple myeloma, chronic myelogenous leukemia, chronic lymphocytic leukemia, and certain types of lung cancer.

We’ve held many advisory committee meetings and have heard directly from patients who believe that delaying the growth of cancer or reducing the cancer’s size are of benefit to them, since these endpoints may relate to reduced symptoms and the ability to carry on with many daily activities.

Patients have benefited, too, from the Breakthrough Therapy Designation, which was established in the FDA Safety & Innovation Act of 2012 to expedite the development and review of transformative therapies that show great promise in early clinical trials, compared to available therapy. Drugs that are designated as breakthrough therapies receive more intensive FDA consultation throughout their development period and may also qualify for other expedited development programs such as fast track and priority review. Many oncology drugs have breakthrough therapy designations, and this designation enables FDA to expedite the review of therapies that may meet patient’s needs.

There is still much more to learn about what patients need and expect from their cancer drugs. Our patient-focused drug development program has sponsored daylong meetings with patients and caregivers to discuss their views on a specific disease. A patient at our breast cancer meeting said: “As long as I can live my life and continue to work full-time, that is my goal.”

Based on these and other patient interactions, we are actively investigating ways to incorporate the patient’s experience and quality of life in benefit-risk assessments of new cancer treatments.

It’s also important to recognize that the drug approval process does not end with the drug’s approval. This is just the beginning. By looking at real-world use of the drug in the broader patient population, we may learn more about new uses for the drug, previously unknown side effects, and how different subsets of patients may respond. This information may be added to the drug labeling and can help inform our future regulatory decisions.

Our ultimate goal is to approve products that make a meaningful difference for patients and their loved ones living with the devastating effects of their disease.

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

FDA Commissioner Asks Staff for ‘More Forceful Steps’ to Stem the Opioid Crisis

By: Scott Gottlieb, M.D.

As Commissioner, my highest initial priority is to take immediate steps to reduce the scope of the epidemic of opioid addiction. I believe the Food and Drug Administration continues to have an important role to play in addressing this crisis, particularly when it comes to reducing the number of new cases of addiction.

Dr. Scott GottliebToday, I sent an email to all of my colleagues at FDA, sharing with them the first steps I plan to take to better achieve this public health goal. With this, my first post to the FDA Voice blog, I also wanted to share my plans with you.

I believe it is within the scope of FDA’s regulatory tools – and our societal obligations – to take whatever steps we can, under our existing legal authorities, to ensure that exposure to opioids is occurring under only appropriate clinical circumstances, and for appropriate patients.

Patients must be prescribed opioids only for durations of treatment that closely match their clinical circumstances and that don’t expose them unnecessarily to prolonged use, which increases the risk of opioid addiction. Moreover, as FDA does in other contexts in our regulatory portfolio, we need to consider the broader public health implications of opioid use. We need to consider both the individual and the societal consequences.

While there has been a lot of good work done by FDA to date, and many people are working hard on this problem, I have asked my FDA colleagues to see what additional, more forceful steps we might take.

As a first step, I am establishing an Opioid Policy Steering Committee that will bring together some of the agency’s most senior career leaders to explore and develop additional tools or strategies FDA can use to confront this crisis.

I have asked the Steering Committee to consider three important questions. However, the Committee will have a broad mandate to consider whatever additional questions FDA should be seeking to answer. The Committee will solicit input, and engage the public. I want the Committee to go in whatever direction the scientific and public health considerations leads, as FDA works to further its mandate to confront the crisis of opioid addiction.

The initial questions I have tasked the Steering Committee to answer are:

  1. Are there circumstances under which FDA should require some form of mandatory education for health care professionals, to make certain that prescribing doctors are properly informed about appropriate prescribing recommendations, understand how to identify the risk of abuse in individual patients, and know how to get addicted patients into treatment?
  2. Should FDA take additional steps, under our risk management authorities, to make sure that the number of opioid doses that an individual patient can be prescribed is more closely tailored to the medical indication? For example, only a few situations require a 30-day supply. In those cases, we want to make sure patients have what they need. But there are plenty of situations where the best prescription is a two- or three-day course of treatment. So, are there things FDA can do to make sure that the dispensing of opioids more consistently reflects the clinical circumstances? This might require FDA to work more closely with provider groups to develop standards for prescribing opioids in different clinical settings.
  3. Is FDA using the proper policy framework to adequately consider the risk of abuse and misuse as part of the drug review process for the approval of these medicines? Are we doing enough when we evaluate new opioid drugs for market authorization, and do we need additional policies in this area?

These are just some of the questions I will be asking this new Steering Committee to consider right away, given the scope of the emergency we face. In the coming days, I’ll continue to work closely with the senior leadership of FDA. I want to know what other important ideas my colleagues at FDA may have, so that we can lean even further into this problem, using our full authorities to work toward reducing the scope of this epidemic.

Despite the efforts of FDA and many other public health agencies, the scope of the epidemic continues to grow, and the human and economic costs are staggering. According to data from CDC and SAMHSA, nearly 2 million Americans abused or were dependent on prescription opioids in 2014, and more than 1,000 people are treated in emergency departments each day due to misusing prescription opioids.

Opioid overdose deaths involving prescription opioids have quadrupled since 1999. In 2015, opioids were involved in the deaths of 33,091 people in the United States. Most of these deaths – more than 22,000 (about 62 people per day) – involved prescription opioids.

We know that the majority of people who eventually become addicted to opioids are exposed first to prescription opioids. One recent study found that in a sample of heroin users in treatment for opioid addiction, 75% of those who began abusing opioids in the 2000s started with prescription opioid products.

This March, a study published in CDC’s Morbidity and Mortality Weekly Report, found that opioid-naïve patients who fill a prescription for a one-day supply of opioids face a 6% risk of continuing their use of opioids for more than one year. This study also found that the longer a person’s first exposure to opioids, the greater the risk that he or she will continue using opioids after one, or even three years. For example, when a person’s first exposure to opioids increases from one day to 30 days, that person’s likelihood of continuing to use opioids after one year increases from 6% to about 35%.

Working together, we need to do all we can to get ahead of this crisis. That’s why we’ll also be soliciting public input, through various forums, on what additional steps FDA should consider. I look forward to working closely with my FDA colleagues as we quickly move forward, capitalizing on good work that has already been done, and expanding those efforts in novel directions. I will keep you updated on our work as we continue to confront this epidemic.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Reducing Preventable Harm from Medications: Too Big for FDA to Do Alone

By: John J. Whyte, M.D., M.P.H.

Sometimes a drug can be used exactly as FDA approved it, taken just the way a doctor prescribed it, and a patient can still experience adverse events. When it comes to drugs, not all risks are known – even after approval.

John WhyteSadly, however, harm from medications also may come from known risks that could have been prevented. The Institute of Medicine (now called the National Academy of Medicine) estimated that at least 1.5 million preventable adverse drug events occur within our health care system each year. It’s a complex system where safety issues can arise at any turn.

Among the many challenges, prescribers and other providers often struggle with the intricacies of today’s health care system, patients can have difficulty following detailed directions, and manufacturers must carefully package and label their products to avoid confusion and misunderstanding for how they are used.

Even giving a child a dose of acetaminophen, the commonly-used over-the-counter pain reliever and fever reducer, can lead to tragic results. The product was available in a strongly concentrated form for infants so they could take a very small amount, as well as a much weaker form for older kids to swallow by the teaspoonful. Unfortunately, over the years, some parents accidentally gave their infants a full teaspoonful of the stronger concentrated form, resulting in serious liver damage and even death. The Consumer Healthcare Products Association (CHPA) worked with their members to voluntarily remove the more concentrated form from sale and market a uniform less concentrated form. Their effort was instrumental in eliminating a preventable medication error.

Safe Use blog imageReducing preventable harm from medications is a big part of FDA’s mission. It requires teamwork across all of health care and the medication manufacturing, distribution, and delivery system.

As one of many ways we facilitate that teamwork, FDA’s Center for Drug Evaluation and Research’s Professional Affairs and Stakeholder Engagement Staff is hosting a one-day public meeting on June 15, 2017, called “Safe Use Symposium: A Focus on Reducing Preventable Harm From Drugs in the Outpatient Setting.”

We’ll gather with patients, caregivers, prescribers, pharmacists, manufacturers, distributors, and others to discuss sources of preventable harm from drugs in the outpatient setting. Attendees will consider situations such as the use of inappropriate medications in certain age groups, the use of drugs that interact with one another, and unintended exposures of dangerous medications to children.

Those attending will include representatives from:

  • Federal agencies such as the Drug Enforcement Agency, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and the Centers for Medicare and Medicaid Services;
  • State regulatory bodies, including professional licensure and oversight boards;
  • Healthcare insurers; and
  • Patient advocacy organizations.

During this symposium, we want to generate ideas for specific solutions to reduce preventable harms and discuss how to evaluate the ideas’ effectiveness. These new ideas for future research can be funded by grants from FDA’s Safe Use Initiative. A variety of important research projects have been completed and FDA offers new opportunities on an ongoing basis.

There is no registration fee but early registration is recommended because seating is limited. More information about registration is available online.

We encourage all parties interested in the safe use of medications to attend. Some jobs, such as reducing the many forms of preventable harms from medication, are too big for one organization. It truly requires a communal and collaborative effort for success.

John J. Whyte, M.D., M.P.H., is Director of Professional Affairs and Stakeholder Engagement at FDA’s Center for Drug Evaluation and Research

Updated June 1, 2017

FDA and NIH Release Final Template for Clinical Trial Protocols

By: Peter Marks, M.D., Ph.D.

A little more than a year ago, FDA and NIH announced the availability of a draft template for investigators to use when organizing clinical trial protocols, which are essentially roadmaps for conducting a clinical trial.

Peter MarksToday, we are excited to announce that the NIH-FDA Joint Leadership Council has issued a final version of the template, a development which is likely to contribute important efficiencies to the process of protocol development, saving medical product development time and money.

The final version is intended for clinical investigators who are writing protocols for phase 2 and phase 3 NIH-funded studies requiring investigational new drug or investigational device exemption applications, but could also be helpful to other investigators conducting studies of medical products that are not regulated by FDA. It provides both instructional and sample text and reflects input from the public, consisting of nearly 200 comments from over 60 individuals. Importantly, it also has been harmonized with a separate protocol template that was recently developed by the private sector organization, Transcelerate Biopharma, for industry-sponsored research.

Clinical trial protocols are critical components of any medical product development program, describing trial objectives, trial design, methodology, statistical considerations, and trial organization.

Having a standard protocol format will facilitate review of protocols by regulators and others (e.g., institutional review boards). We believe that the template will help investigators prepare protocols that are consistent and well organized, contain all the information necessary for the clinical trial to be properly reviewed, and follow the International Conference on Harmonisation (ICH) E6 Good Clinical Practice guidelines. By clarifying expectations, the template will contribute important time and money-saving efficiencies.

Guidance is available from FDA on the content that should be included in a protocol to help ensure human subject protection and high data quality, but the guidance does not describe a standardized format for presenting this information. Placing relevant information in a standardized location in a clinical trial protocol can expedite the development and review of protocols thus enabling a quicker start of a clinical trial, potentially leading to more timely completion of studies and getting important new treatments to patients more quickly. What’s more, with the increased complexity of clinical development, such as use of combinations of different medical products, it is more important than ever that investigators understand protocol development expectations and capture important components right from the start.

NIH, which supports and conducts biomedical research, and FDA, which evaluates the safety and effectiveness of medical products and depends on high-quality research to inform its decisions, agreed that developing a protocol template would be an excellent opportunity to help improve the design of clinical trials. Our agencies believe that the availability of this template and accompanying instructional information will be very useful to investigators in creating well-organized, high-quality protocols — a benefit to everyone involved in medical product development.

Peter Marks, M.D., Ph.D., is the Director of FDA’s Center for Biologics Evaluation and Research

Working to Raise Awareness and Reduce Health Disparities

By: Jonca Bull, M.D.

Minority Health Month imageApril is National Minority Health Month and this year’s theme is “Bridging Health Equity Across Communities.”

FDA’s Office of Minority Health (OMH) is committed to the HHS mission of advancing health equity, and our office works year-round to advance FDA’s message of ensuring the safety and efficacy of our nation’s food supply and medical products to all communities, but with a focus on minority groups. The first HHS Office of Minority Health was established nearly three decades ago and FDA’s own office came into being in 2010.

Jonca Bull, M.D., is Director of FDA’s Office of Minority HealthIn the intervening years, we have made significant progress. But we are reminded daily that there is still more to be accomplished in the fight to reduce and eliminate health disparities.

Today, minority communities and those at the lower socioeconomic rungs still remain disproportionately burdened by chronic disease and are much more likely to succumb to certain illnesses.

Within the past year, we have worked diligently to connect our communities to resources to help educate and raise awareness about these issues. Highlights from our two programmatic teams include:

Outreach and communications –

Released English and Spanish language videos to encourage minority participation in clinical trials, with the most recent video being released this month;

  • Worked closely with the health fraud team in the Office of Regulatory Affairs to raise awareness about tainted and fraudulent products that target some ethnic groups;
  • Exhibited and presented at nearly a dozen conferences throughout the year; and,
  • Spearheaded the agency’s Language Access plan to help ensure that FDA materials are available to all consumers in their native language.

Research and Collaboration –

  • Worked with FDA centers and external partners to support research studies around minority health and health disparities. Projects included: Racial Disparities in Multiple Myeloma, Underutilization of Generic Medications in Underserved Patients, and Advertising and Promotional Labeling in Adult Immunization Disparities.
  • Funded multiple Centers for Excellence in Regulatory Research Science and Innovation (CERSI) projects with Georgetown University (Targeting triple negative breast cancer in African American women), University of California San Francisco/Stanford (Safer Labeling of Pediatric Medications: Reducing Literacy-related Health Disparities among Chronically Ill Adolescents), Johns Hopkins University (Workshop Clinical Trials: Assessing Safety and Efficacy for a Diverse Population);
  • Supported a genomics and health disparities fellow at Harvard University School of Medicine; and,
  • Hosted more than half a dozen fellows and pharmacy students from Howard University, the University of Washington, and Florida Agricultural and Mechanical University, among others.

In addition, last fall, OMH issued a draft guidance document titled, Collection of Race and Ethnicity Data in Clinical Trials-Guidance for Industry and FDA Staff with the goal to ensure that subpopulation data is collected consistently by industry. This document outlines FDA’s expectations for, and recommendations on, the use of a standardized approach for collecting and reporting race and ethnicity data in submissions for clinical trials for FDA regulated medical products conducted in the United States and abroad. We also hosted a webinar to walk through the document.

Working collaboratively within FDA and with external stakeholders, we will continue promoting and protecting the health of diverse populations through research and communicating of science information that addresses health disparities.

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

For more information read: The FDA Supports Research to Reduce Health Disparities

FDA Takes Action Against Fraudulent Cancer Products

By: Donald D. Ashley, J.D., and Douglas Stearn, J.D.

A cancer diagnosis often provokes a sense of desperation. Unfortunately, rogue operations exploiting those fears peddle untested and potentially dangerous products, particularly on the internet. FDA responds in two ways: with compliance and enforcement actions against unscrupulous companies and with consumer education to decrease demand.

Donald Ashley

Donald D. Ashley is director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

Every one of FDA’s product centers and the FDA’s Office of Regulatory Affairs (ORA) has staff devoted to rooting out health fraud scams. These teams regularly investigate consumer complaints and monitor the stores and online marketplaces where such products are advertised. Recently the Center for Food Safety and Applied Nutrition and the Center for Drug Evaluation and Research teamed up with ORA to search the Internet and social media for bogus products that falsely claim to diagnose, treat or cure cancer, a violation of federal law.

It was a challenging assignment.

Those marketing fraudulent products – primarily or exclusively on the internet – attempt to subvert compliance and enforcement efforts by changing the names of their products, their companies, and/or their websites.

Nevertheless, today we are announcing that 14 companies peddling bogus cancer cures have received warning letters from FDA. Warning letters are a primary compliance tool that FDA uses to address violations of the Federal Food, Drug and Cosmetic Act.

Douglas Stearn

Douglas Stearn is director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs

These companies used slick ads, videos, and other sophisticated marketing techniques, including testimonials about miraculous outcomes. Often a single product was promoted as a treatment or cure for multiple diseases in humans and animals. Hoping to skirt the law on a technicality, some sellers made false claims and then in small print provided a disclaimer that their products are not intended to diagnose, treat, cure or prevent any disease.

Making such obvious claims and then saying later that you are not doing so might seem clever, but the technique does not comply with federal laws intended to protect public health.

Each of these companies has 15 working days to respond with a plan to come into compliance with the law.

If necessary, FDA also has authority to take further action, including criminal prosecutions, product seizures, and injunctions. Companies that fail to come into compliance after receiving a warning letter can for example, face criminal prosecution and court-ordered decrees that require them to recall products and get written permission from FDA before resuming operations. The violations identified in the warning letters, if not corrected, are punishable by up to one year in federal prison, five years’ probation and a fine of either $100,000 or twice the gain from the offense.

FDA works diligently to monitor and take action against companies marketing unsafe products online and has issued more than 90 warning letters over the past decade to companies marketing fraudulent cancer products.

image of fake cancer curesConsumer education is critical in combating the dangers posed by these types of products. Thus, our recent cancer fraud initiative includes a push to raise consumer awareness and thereby decrease demand. Efforts include contacting media outlets that reach millions of consumers, posting a Consumer Update article at FDA.gov, and encouraging consumer groups, trade associations, and others to help us spread this important “buyer beware” information.

The message to consumers is this: These products are untested. Some contain ingredients that may be a direct risk to your health. The ingredients may interact in a dangerous way with professionally-prescribed treatments. They are not a substitute for appropriate treatments. Using these products can waste your money, and, more importantly, endanger your health.

Donald D. Ashley is director of the Office of Compliance in FDA’s Center for Drug Evaluation and Research

Douglas Stearn is director of the Office of Enforcement and Import Operations within FDA’s Office of Regulatory Affairs

America’s Got Talent – Regulatory Science Style

By: Stephen Ostroff, M.D.

Veni Vidi Vici. It translates into English as “I came, I saw, I conquered.” It also happens to be the name chosen by one of the winners of the recently held America’s Got Regulatory Science Talent Competition.

America's Got Regulatory Science Event

Dr. Ostroff and FDA staff discuss projects with students from the University of Maryland CERSI.

FDA recognizes that young scientists are our future. Now in its fifth year, America’s Got Regulatory Science Talent is one of a number of initiatives FDA supports to encourage young scientists to pursue careers in the rapidly maturing field of regulatory science.

Each year, teams from the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (CERSI), and the University of Rochester’s Clinical and Translational Science Institute (CTSI), compete by presenting their proposed solutions to a current challenge in regulatory science. The students identify the needs by consulting eight priority areas identified in FDA’s Strategic Plan for Regulatory Science.

Winners are decided by a panel of judges after evaluating each presentation for its quality and novelty, and the proposed solution’s potential significance and feasibility. The winning teams come to FDA to formally present their ideas and have discussions with Agency scientists who are working in their project area. The event, held on April 12th, was sponsored by the Office of Regulatory Science and Innovation (ORSI) which is located in the Office of Chief Scientist. The winning teams certainly came, saw, and conquered.

This year’s winners are:

University of Maryland CERSI

Dr. Ostroff with the University of Maryland teams

Dr. Ostroff with the teams from the University of Maryland CERSI

1st Place Team – Veni Vidi Vici

A high-visibility universal labelling system to communicate risks of hazardous drugs. Wonder if your prescription medication has some dangerous side effects that may be noted in “fine print” – or even nowhere – on the label? A universal symbol in red and yellow in a prominent place on the label is the “Veni Vidi Vici” Team’s solution.

2nd Place Team – Biomarker Boys

Platform to improve transparency for biomarker integration in Accelerated Approval pathway. Tackling a challenge experienced in this growing area of biomedical innovation, the “Biomarker Boys” created a form that facilitates transparent and structured integration of biomarkers into rare disease state drug development.

University of Rochester CTSI

Dr. Ostroff with the University of Rochester teams

Dr. Ostroff with the teams from the University of Rochester CTSI

1st Place Team – Simple English Explanation Directive (SEED)

Making clinical trial results more accessible and functional. Team “SEED” takes the incredibly complicated language that is often found when describing a clinical trial, and puts it in easy-to-understand form.

2nd Place Team – 3-Defining Patient Matched Implants

A streamlined process to test 3-D printed personalized implants. The “3-Defining Patient Matched Implants” Team decided that a quality systems approach is needed to streamline the process of validating the integrity of individual patient-matched 3-D printed implant systems. Their proposal introduces an alternative approach to the current method used in 3-D printing to ensure implants are safe for implantation.

This competition reminds us that good science makes for good regulation. And it was great to see the outside-the-box thinking and innovative approaches these contestants took in addressing some of the challenges that FDA faces with the products we regulate. It’s also a good reminder that the future of regulatory science depends on training and education – and we cannot underestimate the importance of educational activities like these.

The innovative approaches from this year’s teams also show the power of collaboration, mirroring the collaborative approach FDA takes in leveraging the brainpower of our teams of scientists, engineers, statisticians, social and behavioral scientists, medical officers, communicators, and others. The teams from the University of Maryland and the University of Rochester demonstrate just how teamwork produces great results.

Congratulations to the schools for organizing the competitions and to the FDA mentors who encouraged the competitors. Each year the quality of the work improves and I’m certain it will benefit patients and consumers over the coming years. Please check out this year’s talent –including a presentation from a freshman at Maryland. Who knows? Maybe one of these students will be FDA Commissioner some day!

To see the finalists present their innovative solutions to regulatory science challenges, visit FDA’s America’s Got Regulatory Science Talent web page.

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

FDA flickr photos from FDA’s America’s Got Regulatory Science Talent