The U.S. Food and Drug Administration issued draft guidance, Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics, regarding clinical trial design considerations to support accelerated approval applications. The accelerated approval pathway is commonly used for approval of oncology drugs in part due to the serious and life-threatening nature of cancer and because of available intermediate clinical endpoints likely to predict clinical benefit.

“The FDA’s accelerated approval program has provided patients with cancer earlier access to novel treatments that can be practice changing,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Today’s draft guidance provides recommendations to sponsors for designing clinical trials to support accelerated approval. Building quality and efficiency into the design of oncology clinical trials is a crucial component in providing maximum benefit to those living with cancer.”

The draft guidance discusses the design of clinical trials, and ways to improve the data available at the time of accelerated approval and reduce clinical uncertainty for patients by initiating postmarketing confirmatory studies in a timely manner. Specifically, the draft guidance addresses the design, conduct and analysis of data through two randomized clinical trial approaches – conducting two separate randomized controlled clinical trials or using one trial for both accelerated approval and to verify clinical benefit. The draft guidance also provides considerations for sponsors to determine the adequacy of single-arm studies to support an application.
  
For drugs granted accelerated approval, postmarketing confirmatory trials have been required to verify and describe the anticipated clinical benefit. The draft guidance discusses a potential advantage of randomized clinical trials–compared to single-arm trials–by highlighting that use of the one-trial approach, in appropriate cases, may not require separate clinical trials because longer term follow-up in the same trial could fulfill a postmarketing requirement to verify clinical benefit. Moreover, confirmatory trials that are in progress at the time of accelerated approval are more likely to result in a timely verification of clinical benefit, therefore minimizing the period of uncertainty for patients.

In a commentary in the New England Journal of Medicine in 2022External Link Disclaimer, Oncology Center of Excellence staff outlined the concepts included and expanded upon in the draft guidance. The Oncology Center of Excellence has also launched Project Confirm, as an initiative that promotes the transparency of outcomes related to accelerated approval for oncology indications and  fosters discussion and research on the accelerated approval program. The project developed a searchable database with information on the status of all oncology accelerated approvals, a model that was then adopted by FDA’s Center for Drug Evaluation and Research for all accelerated approvals.

Related Information

• Oncology Center of Excellence Guidance Documents
• Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics Guidance for Industry 
• Accelerated Approval Program
• Project Confirm

Source: FDA

The U.S. Food and Drug Administration today issued draft guidance that provides food manufacturers with recommendations on how and when to use Dietary Guidance Statements on the label of food products to ensure the label statements promote good nutrition, provide greater consistency in labeling, and assist consumers in making informed choices. This guidance is part of the FDA’s overall goal to help reduce the burden of chronic disease and advance health equity through improved nutrition. 

“Diet-related chronic diseases, are the leading causes of death and disability in the U.S. and disproportionally impact communities of color and people living in rural areas,” said FDA Commissioner Robert M. Califf, M.D. “The FDA is committed to being a part of the solution to improve the health of millions of Americans. Today’s action is another step towards helping consumers make informed choices about the foods they eat.”

Today’s eating patterns in the U.S. do not align with current federal dietary recommendations, which focus on the entirety of the diet and how foods and beverages work together to affect health. Dietary Guidance Statements are statements in food labeling which are based on key recommendations from consensus reports, such as the Dietary Guidelines for Americans, 2020-2025, that discuss how a food or food group can be a part of a nutritious dietary pattern. The statements may include symbols or pictures that convey to consumers that a food or a food group may contribute to, or help maintain, a nutritious dietary pattern. 

Examples of Dietary Guidance Statements include: “Make half your grains whole grain,” and “Eat leafy green vegetables as part of a nutritious dietary patten.” The draft guidance provides the agency’s thinking about the use of such statements, including recommendations that products contain a meaningful amount of the food, or category of foods, that is the subject of the statement, and that they also not exceed certain amounts of saturated fat, sodium and added sugars. The recommendations in the guidance can enhance consistency in the use of such statements and consumer understanding as well as facilitate industry innovation toward healthier foods. Like other labeling statements and claims, Dietary Guidance Statements act as quick signals on food packages to help consumers better understand nutrition information and make healthier food choices. 

Today’s action is part of the FDA’s overall nutrition initiatives, which include empowering consumers by providing more informative labeling and education, including tailored messages for various audiences to help consumers identify foods that can contribute to healthier diets. It is also part of the Biden-Harris Administration’s National Strategy on Hunger, Nutrition, and Health, which provides a roadmap of actions the federal government will take to end hunger and reduce diet-related diseases by 2030 – all while reducing disparities. Complementing today’s guidance and the National Strategy, the FDA issued a proposed rule in September 2022 to update the definition of “healthy” on food labels and help consumers more easily identify healthy food choices. The agency’s work also supports the Biden-Harris Administration’s White House Challenge to End Hunger and Build Healthy Communities, a nationwide call-to-action to stakeholders across all of society to make bold commitments to advance the Strategy’s goals. The 
Challenge builds on the success of the $8 billion package of private and public sector commitments that the Administration announced as part of the historic conference.

Another priority of the FDA’s nutrition efforts is to create a healthier food supply for all. In October 2021, the FDA issued final guidance for the food industry that provided voluntary, short-term sodium reduction targets for a broad range of processed, packaged and prepared foods to help reduce the amount of sodium in the U.S. food supply. 

“In addition to the Dietary Guidance Statements draft guidance, reducing sodium intake and updating the definition of “healthy” are two other examples of how the agency is showing its commitment to fostering a healthier food supply for all and empowering consumers with more informative and accessible labeling to choose healthier diets,” said Susan Mayne, Ph.D., director of the FDA’s Center for Food Safety and Applied Nutrition. “We are making great strides in our nutrition initiatives in order to improve the health and wellness of our nation.” 

The FDA remains committed to doing its part in the all-of-government approach to improving nutrition, which can have a lasting generational impact on reducing chronic diseases and advancing health equity. The agency is moving forward with additional nutrition and labeling priorities, including exploring a “front-of-pack” labeling initiative and recommendations for nutrition labeling for online grocery shopping sites. Additionally, the FDA will begin assessing further strategies to reduce added sugar consumption, which includes collaborating with others in the U.S. Department of Health and Human Services and the U.S. Department of Agriculture to hold a public meeting regarding future steps the federal government could take to reduce intake of added sugars.

Related Information

• Draft Guidance: Questions and Answers About Dietary Guidance Statements in Food Labeling: Guidance for Industry
• Constituent Update: FDA Issues Draft Guidance on Dietary Guidance Statements on Food Labels
• Press Release: FDA Proposes Updated Definition of ‘Healthy’ Claim on Food Packages to Help Improve Diet, Reduce Chronic Disease
• Press Release: To Improve Nutrition and Reduce the Burden of Disease, FDA Issues Food Industry Guidance for Voluntarily Reducing Sodium in Processed and Packaged Foods
• FDA’s Nutrition Initiatives

Source: FDA

Manufacturer Must Monitor Consumer Impact; FDA May Withdraw Authorization as Needed to Protect Public Health

Today, the U.S. Food and Drug Administration authorized U.S. Smokeless Tobacco Company’s Copenhagen Classic Snuff, a loose moist snuff smokeless tobacco product, to be marketed as a modified risk tobacco product (MRTP). Copenhagen’s moist snuff smokeless tobacco product is a pre-existing tobacco product that has been marketed in the U.S. for years without modified risk information. Today’s action now allows the product to be marketed as a modified risk product with the claim: “IF YOU SMOKE, CONSIDER THIS: Switching completely to this product from cigarettes reduces risk of lung cancer.”

“No tobacco product is safe or ‘FDA approved,’ so those who do not use tobacco products shouldn’t start,” said Brian King, Ph.D., M.P.H. “But tobacco products do exist on a spectrum of risk, with those that are smoked having the greatest risk. In this case, the FDA’s scientific review found that if an adult smoker completely switched from cigarettes to this smokeless product, it would reduce their risk of getting lung cancer.” 

After a rigorous review of the available evidence, including recommendations from the Tobacco Products Scientific Advisory Committee, public comments, and other available scientific information, the FDA concluded that the specific claim related to lung cancer risk is scientifically accurate with respect to Copenhagen Classic Snuff. The data show if current smokers switch completely from cigarettes to this product, they would reduce their risk of getting lung cancer. The review also found those public health gains are not expected to be offset by nonusers starting to use this product. 

The risk modification order granted by the agency does not permit the company to market the product with any other modified risk claims—including those related to any other outcomes besides lung cancer risk—or statements that convey or could mislead consumers into believing that the product is endorsed or approved by the FDA, or that the FDA deems the product to be safe for use by consumers. 

The company is required to conduct postmarket surveillance and studies that include an assessment of product users’ behavior, understanding, and any previous use of cigarettes, as well as a scientific model to assess continued impact on population health. 

This modified risk granted order will expire in five years; the company must request and receive FDA authorization to continue marketing the product as a modified risk product. If at any point the agency determines that the order no longer benefits the public health, the agency must withdraw the order.  

“The ball is now in the company’s court to conduct postmarket studies and surveillance on consumer impact, and to submit this information to FDA annually,” said Dr. King. “If scientific evidence indicates that the net gains of these products no longer outweigh the risks at the population level—or if the company fails to conduct the required postmarket surveillance and studies—the FDA is committed to taking action as appropriate, including withdrawing the order, to protect public health.”

The MRTP process outlined in the 2009 Family Smoking Prevention and Tobacco Control Act allows companies to submit applications for the FDA to evaluate whether a tobacco product may be sold or distributed for use to reduce harm or the risk of tobacco-related disease. By law, the FDA must also ensure that the advertising and labeling of modified risk products enables the public to understand the modified risk or modified exposure information and to understand the significance that information has in the context of total health and in relation to all tobacco-related diseases and health conditions.

Related Information

• Modified Risk Tobacco Products
• Modified Risk Granted Orders
• Copenhagen Classic Snuff Modified Risk Tobacco Product Application

Source: FDA