Remarks by Lauren Silvis
FDA Chief of Staff
Food and Drug Law Institute
Advertising and Promotion for Medical Products
"Advertising and Promotion in an Age of Rapid Scientific Advancement"
(Remarks as Prepared for Delivery)
Good morning. I’m honored to be here.
Before joining FDA, and in my time since I’ve been at the Agency, I’ve spent a lot of time thinking about how to communicate effectively to patients and providers about the benefits and risks of drugs and devices. I’ve reviewed and advised on drug and device advertising and promotion and considered from many perspectives whether promotional pieces are in compliance with the relevant FDA requirements.
And I know that at the beginning and at the end of our review of medical product promotion, we have the final FDA labeling. The FDA labeling is our reference point, our set of guiding principles, and the place where we go to help put the benefits and risks in context for patients and providers.
We’ve heard Commissioner Gottlieb say that science is at the heart of everything we do. And that we are experiencing a period of rapid scientific and technological advancement, which means that FDA needs to be modern and flexible to bring new therapies to patients.
This is exactly what we’re doing at FDA under Commissioner Gottlieb’s leadership. As our evaluation of complex medical product benefits and risks becomes more sophisticated, so does the information in the FDA labeling. We’re at a two-day conference focused on advertising and promotion. But at the heart of the issues you’ll be considering over these two days—the way manufacturers communicate information to patients and providers—is the scientific progress happening in drug development and at the agency. It drives the information in the final labeling, which in turn serves as the basis for promotional communication about medical products. In addition to the work FDA is undertaking to innovate ourselves, we are also taking steps to incorporate new and important sources of evidence into product labeling.
Drugs and biologics are becoming increasingly tailored based on molecular or genomic features of the disease state being targeted and guided by innovative diagnostics like Next Generation Sequencing assays.
As we plumb the biology behind diseases like cancer or cystic fibrosis, we hope the labeling can be updated in tandem with our mechanistic understanding of the disease state.
For instance, in the case of cancer, a drug or biologic that launches with one indication may be supplemented with information on a tissue agnostic biomarker that offers the opportunity to expand the approved use to a wide variety of tumor types expressing that genetic feature.
Medical device development is becoming similarly agile and tailored through in silico modeling, 3D printing, and sponsors’ ability to harness real-world data to help ensure safe and effective use after a product has an initial marketing authorization. In some cases, this may allow rapid iteration of a product design and continued technological improvement. In other cases, it might be accomplished through a cloud-based software update.
In short, we have an increasing ability to harness information through a growing number of platforms and channels to help ensure the right medical product is used in the right patient, at the right time, to maximize potential benefits, and minimize potential risks.
And these opportunities are emerging at an accelerated pace.
Across the FDA, we’re modernizing our programs, pathways, and regulations to ensure that the development and regulatory review process for medical products keeps up with the science driving product development, and that we’re applying appropriate risk-based regulations to the technology and the disease state under consideration.
We want to ensure that the agency is a bridge, not a barrier, to facilitating new opportunities to mitigate and even cure more ailments, and to do so as efficiently as possible while maintaining our gold standard for safety and effectiveness.
As FDA modernizes review and approval pathways to better promote and protect public health, at the same time, we strive to see product labeling that is more modern, agile, and science-driven, and incorporates the digital technologies we’re harnessing across the healthcare system.
I started by saying the labeling is the central tool in developing advertising and promotion. It’s the content that should drive claims and help advise patients and providers of relevant risk information.
Labeling is also a critical tool for advancing scientific information in the day and age when we are all bombarded with information from an ever-growing number of digital channels and social media platforms. As we move to a world that increasingly relies on digital advances and the dissemination of rapidly evolving information, I believe we’re also moving toward a future where more of the scientific information about a medical product’s safety and efficacy will exist in a curated digital environment that is accessible to patients and providers through a variety of trusted formats that incorporate new technologies.
For now, “Dr. Google” is often the first source of information patients and family members turn to when then they have a question about a medical product or condition.
With a few taps of their smartphone or tablet, they can pull up millions of documents and commentary about an FDA regulated product.
I did a few myself this morning. “Treatment for Crohn’s Disease” turned up about 12.4 million hits on Google. “Treatment for asthma” turned up about 129 million. “Hip replacement” showed about 150 million.
There’s a lot of real knowledge and science to be found on the Web but trying to sort it efficiently—never mind find the most accurate and relevant information about safety and effectiveness—can be incredibly challenging.
Incorporating the results of scientific advances into the final product labeling, and having FDA serve as the curator of that information, can help patients make better treatment choices and lead healthier lives.
Across FDA’s medical product centers, we’re taking steps that should better align product labeling, and based on that, communication about medical products, with the new science and technologies driving medical product development. We’re also enlisting key stakeholders in the medical community to help curate and communicate state of the art scientific information to patients and providers.
Over the past 18 months, we’ve advanced a policy framework for the development of novel therapies that will allow FDA to make better informed judgments about a drug’s benefits and risks. We’ve issued a series of guidance documents aimed at modernizing our clinical trial framework, including promoting the appropriate use of master protocols and adaptive trial designs.
For example, in adaptive approaches to clinical trials, as the trial evolves, and data accrue, the adaptive design changes based on what’s learned about the safety and benefits of the experimental drug. These designs, if used successfully, could allow us to study more patients with more effective therapies, correctly identifying the right drugs for specific subgroups of patients based on their biomarker profiles. This approach could offer a greater chance of detecting a drug’s treatment effect in smaller, more targeted patient populations.
In regenerative medicine, with its incredible promise to transform patient care, we’ve proposed a framework for facilitating the availability of safe and effective therapies, including new stem-cell treatments. To make sure we’re keeping up with the way this field is evolving, we’re proposing tools to encourage individual or small groups of physicians to collaborate in support of the development of a stem-cell or other regenerative medicine product, which could ultimately lead to the receipt of a biologics license by each of the physicians or groups.
If the clinical data that are submitted in conjunction with the manufacturing information show a favorable benefit–risk profile, the FDA could rely on that pooled data in determining whether the product is safe and effective. This strategy could help facilitate responsible development of a technology that is being driven forward by small, often academic based researchers
When it comes to new device innovations, FDA released a draft guidance that lays out a proposed approach for how we systematically address uncertainty in making benefit and risk determinations. It applies to our pre-market approval process, de novo classifications, and humanitarian device exemptions. We proposed a consistent, methodical, and science-based approach for how to consider uncertainty as part of the benefit-risk determinations. The aim is to support premarket decisions that are based on the totality of scientific evidence available at the time of a device’s market entry.
This approach will promote innovation in treatment options, including technologies for small, more targeted patient populations. We’ll consider specific factors such as the public health need for the device, including the availability of alternative treatments; feasibility of extensive clinical evidence generation premarket based on appropriate considerations; the ability of a sponsor to be able to reduce or resolve uncertainty in the post-market setting; and patient perspectives, among others.
As we put forth these innovative frameworks, we are mindful of the effect it will have on our related regulatory processes and tools, including the product labeling. We expect to see that essential starting point for communicating about a product’s benefits and risks reflect our increasingly advanced scientific evaluations of novel therapies.
At the same time FDA itself is evolving to keep pace with changing technology, we are looking to new resources and approaches to appropriately incorporate additional clinically important information into product labeling.
We’re all aware of the enormous public health toll created by the opioid crisis. And we all know the vital role providers can play in reducing this toll, by reducing unnecessary or excessive exposure to opioids, while still providing appropriate opioid analgesic therapy to patients who have a medical need for these products.
Evidence-based prescribing guidelines can help providers determine the appropriate duration of use for opioid analgesics for a given indication. That’s why we’re working with medical practice societies to arm health care providers with the most current and comprehensive guidance on appropriate pain management by developing a framework for creating evidence-based guidelines on appropriate opioid analgesic prescribing.
To support that effort, we’ve contracted with the National Academies of Sciences, Engineering, and Medicine (NASEM) to conduct a consensus study and report. This will help advance the development of evidence-based guidelines for appropriate opioid-analgesic prescribing for acute pain resulting from specific conditions or procedures.
This work will help us understand what evidence is needed to ensure that current and future clinical practice guidelines for opioid-analgesic prescribing minimize the risk of addiction and abuse, and what research is still needed to generate that evidence in a practical and feasible manner.
We’re optimistic that this new effort will result in new, data-driven guidelines from medical professional societies that can be easily accessible to prescribers and that can also be used to inform product labeling, or even REMS requirements, to help ensure that opioid analgesic prescribing more closely comports with clinical need.
Another example of how the agency is taking steps to modernize product labeling in the face of a rapidly evolving public health need is our work to combat antimicrobial resistance (AMR).
Prescribing a drug that’s only going to be met with resistance from the bacteria or fungi it’s intended to treat doesn’t help that patient and can accelerate the development of AMR. Physicians can use antimicrobial susceptibility test (AST) results to help choose an appropriate antibacterial or antifungal drug to treat a patient’s infection.
These tests rely on criteria — called susceptibility test interpretive criteria or “breakpoints” — that help determine whether a specific bacteria or fungi are susceptible to antibacterial or antifungal drugs.
Bacteria and fungi change over time, which may result in decreased susceptibility to some drugs. When this occurs, breakpoints may need to be updated. Until recently, the labeling of each individual drug and AST device had to be updated whenever breakpoints changed, leading to unnecessary delays in reaching healthcare professionals with new, clinically relevant information.
To overcome this challenge, and under the 21st Century Cures Act, FDA publishes and updates breakpoints information through an FDA-managed website. FDA revises the website as necessary so that the breakpoints information on the site is up-to-date. As the breakpoints information on FDA’s website changes, AST device developers can update their devices in a timelier manner. This helps health care professionals make more informed prescribing decisions that will benefit their patients and help prevent the development and spread of resistant strains. FDA’s breakpoints website also allows FDA to simultaneously update the breakpoints for multiple drugs that have the same active ingredient and share that information quickly and transparently. There’s a dedicated FDA web page that will list FDA-recognized breakpoints for each active ingredient.
In its own breakpoint setting, FDA sometimes leverages the work done by standards-development organizations. When FDA agrees that these breakpoints are appropriate, the Agency recognizes and adopts them by posting them on its website.
FDA has issued guidance explaining drug manufacturers’ obligation to update their labeling by December of this year to include a reference to the FDA breakpoints website. This will relieve sponsors from having to continuously update their labeling with new breakpoint information. The process of communicating breakpoint information will be more efficient -- and we’ll have a reliable reference in the labeling to the most up-to-date information needed by healthcare professionals and patients.
To help speed up the process of getting breakpoints information to healthcare professionals for newly approved drugs, our drug and device centers also collaborated on developing a draft guidance to facilitate the availability of diagnostic devices to test organisms for antimicrobial susceptibility at the same time or very shortly after approval of a new antimicrobial drug.
Coordinated product development between drug and device developers can help streamline regulatory reviews, and this coordination has resulted in antimicrobial susceptibility devices being available almost immediately or within weeks of recent new drug approvals.
Another example of FDA employing novel approaches to help product review and labeling keep pace with scientific advances can be found in the rapidly developing field of next-generation sequencing, which can detect tens of thousands of gene or protein variants in a single test. This technology is increasingly used to help guide clinical decision making for diseases like cancer and certain rare diseases. To support innovation in NGS testing, FDA developed an approach focused on leveraging publicly available databases to support claims of clinical validity. One potential example of such a consensus database would be the NIH’s ClinGen, which works to standardize the clinical annotation and interpretation of genomic variants through evidence-based expert consensus.
FDA-recognized databases can support sponsors’ assertions about the meaning and clinical significance of germline or somatic mutations, rather than requiring the test developer to generate their own evidence for each variant.
Eventually, we believe that this guidance will encourage expert-based crowd sourcing of NGS evidence generation, curating, and data sharing – which can all advance the development of high quality precision medicine treatments and diagnostics, with validated new information used to update medical product labeling through an agile scientific process.
I’ve talked about why I believe putting science at the heart of all we do will promote innovation -- in drug and device development, in FDA’s regulatory decision making, and in the information contained in the product labeling, that’s ultimately communicated to doctors and patients. In addition to these steps, today we’re announcing important new actions that are intended to advance the accuracy and relevance of prescription drug promotion.
First, we’re announcing a new draft Guidance for industry titled “Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements.”
We know that translating the complex results of clinical trials into usable information for consumers can be challenging, but research suggests that summarizing the results in quantitative terms – numerical information on the likelihood or magnitude of effectiveness or risk of a drug – can make that information a lot easier for consumers to understand and remember.
The draft guidance we’re releasing today offers recommendations and concrete examples for presenting consumer-friendly quantitative efficacy and risk information. It’s for direct-to-consumer (DTC) promotional labeling and advertisements for prescription human drugs and biologics, as well as animal drugs.
These recommendations cover all promotional mediums, including print, electronic, audiovisual, or broadcast, and suggests how visual aids can be used to illustrate quantitative information about benefits and risks.
For instance, rather than saying “most patients responded to drug X after 12 weeks”, which can be confusing, firms could present the absolute frequency: In a clinical trial, 78 out of 100 patients experienced a response after 12 weeks of treatment with Drug X.
If a drug presents fewer side effects, sponsors could present both the relative and absolute frequencies to help consumers understand the information – drug X produced a 50% reduction in side effects compared to drug Y, reducing the rate from 4% to 2% of all patients treated.
Conveying quantitative efficacy and risk information in these ways can make the information more accessible and easier to understand and reduce the risks of patients over- or underestimating the drug’s likely effects.
FDA also conducts important research to inform our approach to regulating promotion. Our drug center has a research agenda focused on evaluating aspects of prescription drug promotion that we believe are most central to FDA’s public health mission, focusing on three main topic areas: advertising features, including content and format; target populations; and research quality.
In keeping with this mission, FDA is issuing Federal Register notices on three proposed studies designed to help us better understand how intended audiences perceive prescription drug information: one on “Physician Interpretation of Information About Prescription Drugs in Scientific
Publications Versus Promotional Pieces,” another on the “Experimental Study of an Accelerated Approval Disclosure in DTC Promotional Materials,” And the last on “ Disease Awareness and Prescription Drug Promotion on Television.”
The first proposal is for research into how physicians interpret information about prescription drugs in scientific publications compared to professionally directed promotional pieces.
Physicians gain knowledge about medical product uses from a variety of sources, including peer-reviewed journal articles, compendia, continuing medical education, and physician-directed promotion by or on behalf of manufacturers. Each of these channels can present information generated through different methodologies and with varying levels of quality.
We believe this research will help us better understand how physicians perceive prescription drug information based on the context in which that information is delivered, the rigor of the methodology behind the study, or the time constraints facing physicians when they access information from these sources.
The second research proposal is for a study on how consumers understand information on accelerated approval included in DTC advertising.
Accelerated approval enables approval of certain prescription drugs intended to treat serious or life-threatening illnesses, based on a determination that a drug product has an effect on: (1) a surrogate endpoint (for example, a particular blood test result or radiographic measurement), or (2) an intermediate clinical endpoint that can be measured earlier than irreversible morbidity or mortality —as long as the endpoint being measured is reasonably likely to predict clinical benefit.
When drugs are approved based on surrogate or intermediate clinical endpoints, there may be uncertainty about the ultimate clinical benefits of the drug. For that reason, sponsors are required to conduct post approval studies of the drug to verify and describe the drug’s predicted clinical benefit.
In a draft guidance, FDA recommended that the INDICATIONS AND USAGE section for accelerated approval drugs should generally describe three elements: indication(s), limitations of usefulness and clinical benefit uncertainty, and continued approval.
As the prescribing information, or PI, is intended for healthcare professionals, the information related to a drug’s accelerated approval generally includes complex concepts and sophisticated wording.
Sponsors sometimes use language from the PI in DTC promotional materials for drugs approved under accelerated approval, but in other cases, DTC promotion of these products may not communicate as much detail about the accelerated approval process.
Our proposed study will examine the presence, wording, and prominence of a disclosure communicating information related to the drug’s accelerated approval in DTC promotional materials.
The study will focus on oncology products because cancer is a life-threatening illness, many oncology products are approved under the accelerated approval pathway, and DTC promotion of oncology drugs is more common.
In the study, participants will view a website for a fictional oncology prescription drug. After viewing the website, participants will complete a questionnaire that assesses whether participants noticed the disclosure and their interpretation of it, as well as perceptions of the drug’s risks and benefits.
We will vary the presence and prominence of the disclosure. We will also vary whether the disclosure is written in consumer-friendly language or uses language, in use by many sponsors, which is the same as or similar to that directed at healthcare professionals in the PI.
We hypothesize that participants will be more likely to notice and understand the disclosure and use it to form their perceptions of the drug if they view the prominent or consumer-friendly language. The study will test whether our working hypothesis is accurate.
The third study concerns disease awareness and prescription drug promotion on television. When pharmaceutical companies market a new drug, they often release disease awareness communications about the medical condition the new drug is intended to treat. We’re interested in whether and to what extent this practice may result in consumers confusing or otherwise misinterpreting the different information and claims presented in disease awareness communications and prescription drug promotion.
Prior research has documented that in both print and online contexts, consumers tend to conflate the information presented in prescription drug promotional materials with information presented in disease awareness communications. The research we intend to do seeks to extend previous studies of print and online promotion to the context of television promotion. It will broadly examine how perceptual similarity between the two communication types, as well as their temporal proximity and exposure frequency, may impact the nature and extent of viewer confusion.
Together, we believe the guidance and the three studies will advance the goals of helping patients and providers be better informed about prescription drug benefits and risks.
In closing, I hope the picture I’ve painted about how medical product benefits and risks are being evaluated will lead to improved communication and understanding for patients and providers. And that FDA’s commitment to promoting innovation will support the work of researchers and sponsors to maximize benefits, and minimize risks, for targeted cohorts of patients, in specific health care settings. And that, as we consider the range of legal and regulatory issues related to medical product advertising and promotion, we keep science at the heart of all that we do.