Author Interviews, Diabetes, FDA, JAMA / 07.03.2021 Interview with: Marie C. Bradley, PhD, MPharm, MScPH Office of Surveillance and Epidemiology Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring, Maryland What is the background for this study? Response: Long-acting insulin analogs, insulin glargine (glargine) and insulin detemir (detemir) are increasingly used in the management of type 2 diabetes mellitus (T2DM).  In recent years the price of long-acting insulin analogs has increased substantially2 Higher costs for these insulin analogs may limit patient access.1 Clinical trials showed the risk of severe hypoglycemia did not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus (T2DM). An observational study examining severe hypoglycemia in T2DM patients found similar results. However, these previous studies did not focus on patients aged ≥65 years, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use. Therefore, to investigate this further we used Medicare data to assess the risk of severe hypoglycemia among older T2DM patients who initiated a long acting analog ( glargine or detemir) compared to NPH in real-world settings. (more…)
Author Interviews, Dermatology, FDA, Regeneron, Sanofi / 31.07.2020 Interview with: Elizabeth Laws, PhD Vice President and Global Project Head for Dupilumab/Dupixent Sanofi Marcie Ruddy, MD, MA Strategic Program Direction, Immunology and Inflammation Regeneron  Dr. Laws and Dr. Ruddy discuss the FDA approval of a 300 mg single-dose pre-filled pen for Dupixent® (dupilumab) for all indications in patients aged 12 years and older. What is the background for this announcement? What are the main indications for Dupixent? Response: Until now, Dupixent 300 mg dose was available only in pre-filled syringe for administration. The approval of the pre-filled pen provides an additional, easy-to-use option for patients to self-administer Dupixent. Dupixent is approved to treat patients aged 6 years and older with uncontrolled moderate-to-severe atopic dermatitis (AD) and can be used with or without topical treatments. Dupixent is also approved for use with other medicines for the maintenance treatment of uncontrolled moderate-to-severe eosinophilic or oral steroid dependent asthma in patients aged 12 years and older, and with other medicines for the maintenance treatment of uncontrolled chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults, respectively. The pre-filled pen is approved for use in patients prescribed Dupixent who are 12 years of age and older across current indications, at the 300 mg dose. (more…)
Author Interviews, Neurology, Parkinson's / 22.06.2020 Interview with: Stewart A. Factor, D.O. Professor of Neurology Director of the Movement Disorders Program Vance Lanier Chair of Neurology Emory University School of Medicine What is the background for this study? Would you briefly explain what is meant by OFF episodes.  Response: Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease characterized by motor symptoms, including tremor at rest, rigidity and impaired movement, as well as significant non-motor symptoms, such as cognitive impairment, psychiatric symptoms and autonomic symptoms (i.e. urinary issues, constipation, low blood pressure). It is the second-most common neurodegenerative disease after Alzheimer’s disease and it is predicted that the prevalence of Parkinson’s disease will double by the year 2040. The symptoms of PD are in substantial part, due to loss of dopamine nerve cells in the brain. The current standard of care for PD includes replacing the dopamine loss by the use of oral carbidopa/levodopa. Levodopa is a precursor of dopamine, converted in the brain. OFF episodes have been a significant unmet need in Parkinson’s disease since the emergence of levodopa. Initially, levodopa controls PD symptoms in a continuous fashion throughout the day. With time the response becomes less predictable and patients experience a re-emergence or worsening of PD symptoms. These episodes are what we mean by OFF episodes. OFF episodes can be characterized, in part, by re-emergence of motor symptoms including tremor, stiffness or slowed movement that can happen at any point during the day. OFF episodes typically begin within the first five years of treatment and occur at the end of a dose. This is referred to as end of dose failure or wearing off. Within the first four to six years after diagnosis, regardless of disease severity, up to 60 percent of people with PD experience OFF episodes. With time these episodes become longer, more severe and disabling, more frequent and less predictable as PD progresses. They can take up more than half the day OFF episodes may alter a persons’ ability to perform everyday activities by slowing or even precluding their completion. The result is significant burden and distress for people living with Parkinson’s disease (PD) and their care partners. CTH-300 was a Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel group, study examining the efficacy, safety and tolerability of apomorphine hydrochloride sublingual film (KYNMOBI) in people with levodopa-responsive PD complicated by OFF episodes. The primary endpoint was a mean change in the score from pre-dose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination at 30 minutes after dosing at the 12-week visit of the maintenance treatment phase. The key secondary endpoint was the percentage of people with PD with a patient-rated full ON (or best) response within 30 minutes at the 12-week visit of the maintenance treatment phase. (more…)
Author Interviews, Cancer Research, JAMA / 04.05.2020 Interview with: Emerson Y. Chen, MD Assistant Professor of Medicine, Medical Oncology Knight Cancer Institute, Oregon Health & Science University Portland, OR 97239 What is the background for this study? Response: Our research group had previously studied how oncology drugs are approved in these two previous papers listed below. One is focused on the time delay trade-off from surrogate endpoints (i.e. response rate and progression-free survival) over definite endpoints (i.e. overall survival and quality of life). The other is focused on how promising the response rate of a drug candidate have to be to be considered for oncology drug approval.  (more…)
Author Interviews, Schizophrenia / 12.02.2020 Interview with: Andrew Satlin, M.D. Chief Medical Officer Intra-Cellular Therapies What is the background for this announcement? How does CAPLYTA (lumateperone) differ from other medications for schizophrenia? Response: Schizophrenia is a serious mental illness and complex disease that presents itself differently in various patients. Antipsychotics are associated with side effects such as weight gain and metabolic disturbances and movement disorders. Many patients often discontinue treatment as a result of these side effects. The U.S. Food and Drug Administration (FDA) has approved CAPLTA (lumateperone) for the treatment of schizophrenia in adults. We are excited to provide a new option for treating patients living with schizophrenia with an established efficacy and a favorable weight, metabolic and motor side effect profile. (more…)
Author Interviews, Dermatology, Environmental Risks, JAMA / 22.01.2020

Comments from the FDA on this JAMA Dermatology study: Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial  Sunscreen CDC Phil What is the background for this study? Response: A prior pilot study published in JAMA in May 2019 demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients, and how quickly absorption occurs.  This study assessed the systemic absorption of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate and octinoxate) in 4 sunscreen products under single and maximal-use conditions.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 04.09.2019 Interview with: Bishal Gyawali, MD, PhD Department of Medicine Brigham and Women’s Hospital What is the background for this study? Response: Cancer drugs are prescribed to the patients based on results from trials. Usually, these are superiority trials meaning the cancer drugs prove that they are better than the treatment we already have. Recently, more and more cancer drugs are approved on the basis of non-inferiority trials. In these trials, the cancer drugs only prove that they are not worse than the treatment we already have ( instead of proving they are better). Such an approach is considered justified if the new drug provides any other benefit such as lower cost, easy to administer or improved quality of life. (more…)
Author Interviews, Bayer, FDA, Prostate Cancer / 16.08.2019 Interview with: Neal D. Shore, MD, FACS Director, CPI, Carolina Urologic Research Center Atlantic Urology Clinics Myrtle Beach, South Carolina Neal D. Shore, MD, FACS is the Medical Director for the Carolina Urologic Research Center. He practices with Atlantic Urology Clinics in Myrtle Beach, South Carolina. Dr. Shore discusses the recent announcement that the FDA has approved Nubeqa®(darolutamide),  for the treatment of patients with non-metastatic castration-resistant prostate cancer.. What is the background for this study? How does NUBEQA®(darolutamide) differ from other treatments for nmCRPC?  Response: In 2017, patients did not have an approved therapy for non-metastatic castration-resistant prostate cancer, or nmCRPC. If untreated, patients with this diagnosis will go on to develop metastases, or progression of the cancer throughout the body. NUBEQA® (darolutamide) became the third and most recently approved treatment for nmCRPC, demonstrating a benefit of metastasis-free survival, or MFS. NUBEQA is different due to its adverse event and safety profile reported in the Phase III ARAMIS trial. In that study, there were no significant findings of falls and fractures as well as other adverse events reported from the earlier Phase III trials.  (more…)
Author Interviews, Cancer Research, FDA, Vaccine Studies / 14.08.2019 Interview with: Dr. Graca Dores MD MPH US Food and Drug Administration Center for Biologics Evaluation and Research Office of Biostatistics and Epidemiology Division of Epidemiology Silver Spring, Maryland Oklahoma City, OK What is the background for this study? Would you briefly explain what Sipuleucel-T is used for?  Response: Sipuleucel-T was the first therapeutic vaccine approved by the U.S. Food and Drug Administration (FDA) in 2010.  It is indicated for the treatment of asymptomatic or minimally symptomatic, metastatic, castration-resistant prostate cancer (CRPC; prostate cancer that spreads while an individual is on hormone-blocking therapy).  During the preparation of this product, the patient’s cells are collected (leukapheresis), sent for processing to generate a dose of patient-specific vaccine, and then administered intravenously back to the patient.  This process is repeated approximately every two weeks for a total of three doses. Except for the pre-marketing clinical trials that were reviewed during the sipuleucel-T approval process, post-marketing studies that have evaluated the safety profile of sipuleucel-T are scarce. Therefore, we used the FDA’s Adverse Event Reporting System (FAERS) database to summarize the adverse events reported to FDA by industry, medical professionals, and consumers.  We also assessed whether sipuleucel-T and specific adverse events (product-event pairs) were reported more than expected compared to all other drug/biologic-adverse event pairs in the FAERS database. (more…)
Author Interviews, Dermatology, FDA / 06.06.2019 Interview with: Stephanie L. Kuschel, MD Indiana University School of Medicine Indianapolis, IN, 46202 Robert Dellavalle, MD, PhD, MSPH Professor of Dermatology and Public Health University of Colorado School of Medicine Colorado School of Public Health Chief, Dermatology Service US Department of Veterans Affairs Eastern Colorado Health Care System Denver, CO 80220 What is the background for this study? What are the main findings?  Response: Physicians can serve as external experts and voting members of FDA advisory committee panels, which help determine if a drug is acceptable for the US market. Considering that financial conflicts of interest (FCOI) have been shown to influence voting member habits, the FDA has regulations in place to minimize these FCOI. However, the FDA can grant waivers for some financially conflicted individuals if they meet certain requirements (like offering key insights that may out-weigh the risk of a possible FCOI). Additionally the FDA does not make stipulations regarding post-advisory role financial relationships. In fact, many former FDA committee advisors later engage in financial relationships with pharmaceutical companies. Some worry these post-hoc financial relationships could pose an ethical dilemma whereby future FDA advisory members are incentivized to alter their voting habits in expectation of future rewards. Others argue the situation may be more complex than expected. For example, the author of one study, found that while there was evidence for a pro-industry voting bias among committee members with exclusive financial relationships to the sponsoring manufacturer (of the drug under review), this was not the case for members with nonexclusive financial ties to both the sponsor and its competitors 1. Furthermore, the author found that advisors with many corporate ties were (on average) actually more likely than their peers without any financial ties to vote against the sponsor. The author argued that these advisors were more likely to be experienced researchers, and their voting habits may reflect their experience evaluating medical research. While this author and others have offered valuable insights into financial relationships of advisors during their advisory role, unfortunately little information is available regarding post-advisory role financial relationships and whether these relationship have any influence on the integrity of the voting process. The purpose of our study was to review Open Payment data on industry payments to former physician FDA dermatologic drug committee members.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, FDA, JAMA, Pharmacology / 29.05.2019 Interview with: Bishal Gyawali  MD PhD
  • Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • Department of Oncology, Department of Public Health Sciences, and Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada What is the background for this study? What are the main findings? Response: Accelerated approval pathway from the FDA allows cancer drugs to come to market sooner by showing improvement in surrogate measures such as change in tumor size. Surrogate measures do not reflect clinical benefit in terms of living longer or feeling better. So, when a drug receives accelerated approval, the drug is required to undergo a confirmatory trial to confirm that true clinical benefit from the drug actually exists. Last year, a paper from the FDA argued that accelerated approval pathway is working effectively because 55% of such drugs confirmed clinical benefit. However, we saw that most of those drugs were actually improving only a surrogate measure even in confirmatory trials. So the confirmatory trials were not confirming clinical benefit but actually confirming benefit in a surrogate endpoint. We investigate that issue in our study using updated results from the confirmatory trials that were ongoing at the time of FDA review. Our main finding is that only one-fifth of cancer drugs that received accelerated approval actually improved overall survival later in confirmatory trials. For, 20% of other drugs, the confirmatory trials tested the same surrogate endpoint as did the preapproval trial. For another 21%, the confirmatory trial showed benefit in a surrogate endpoint different from the one used in preapproval trial. Furthermore, when drugs fail to confirm clinical benefits in confirmatory trials, they still continue to remain on market.  (more…)
Author Interviews, Epilepsy, FDA / 29.05.2019 Interview with: Dr. Steven S. Chung, MD Executive Director and Program Chair Neuroscience Institute and Director of the Epilepsy Program Banner – University Medical Center What is the background for this study? How is Nayzilam different from other treatments for epilepsy? Who/How is it administered?  Response: NAYZILAM is the first medication and only FDA-approved nasal option for treating seizure clusters. NAYZILAM allows for administration by a non-healthcare professional to patients when a seizure cluster occurs, which could provide significant value to patients who currently have limited treatment options for SC. The effectiveness of NAYZILAM was established in a randomized, double-blind, placebo-controlled trial (Study 1; NCT 01390220). Study 1 was conducted in two phases: an open-label Test Dose Phase followed by a randomized, double-blind, placebo-controlled, Comparative Phase. In the Test Dose Phase, tolerability was assessed in 292 patients. Patients were excluded from participation in the Comparative Phase if they failed to meet pre-defined blood pressure, heart rate, sedation, electrocardiogram, and peripheral oxygen saturation criteria. In the Comparative Phase, 201 patients treated a single seizure cluster episode in an outpatient setting. Numerical differences in favor of NAYZILAM were observed on each of the components of the treatment success responder definition; termination of seizure(s) within 10 minutes after initial dose of study drug (80.6 versus 70.1%) and the absence of seizure recurrence between 10 minutes and 6 hours after the initial dose of study drug (58.2 versus 37.3%). Study 1 also evaluated the occurrence and time to next seizure after the initial blinded dose of study drug. A smaller proportion of NAYZILAM-treated patients experienced the next seizure within 24 hours after the initial blinded dose of study drug (37.3% versus 46.3%). NAYZILAM-treated patients experienced a statistically longer time-to-next-seizure than the placebo group.   (more…)
Author Interviews, Dermatology, Environmental Risks, FDA, JAMA / 06.05.2019 Interview with: David Strauss, MD, PhD Director, Division of Applied Regulatory Science U.S. Food and Drug Administration Center for Drug Evaluation and Research What is the background for this study? What are the main findings? Response: It is unknown whether most active ingredients in sunscreens are absorbed. FDA has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies. This randomized clinical trial demonstrated systemic exposure of 4 commonly used sunscreen active ingredients on application of sunscreen products under maximal use conditions consistent with current sunscreen labeling. All 4 sunscreen active ingredients tested resulted in exposures exceeding 0.5 ng/mL.  (more…)
Author Interviews, Cancer Research, FDA, JAMA / 01.04.2019 Interview with: Emerson Chen, MD Chief Fellow, Hematology-Oncology, PGY-6 Oregon Health & Science University What is the background for this study? What are the main findings? Response: Many cancer drugs are approved annually giving the appearance of innovation; however, some drugs may have been approved because of a lower bar. Use of lesser endpoints like response rate (how tumor shrinks) and progression-free survival (how tumor has delayed growth) have been proposed to speed trials when compared against traditional endpoints like overall survival (how long patients might live). Using published trials that led to cancer drug approval from 2006 to 2017, we estimated how long it would take to get each of these three endpoints across all cancer drugs and indications to see how much time we could save by using these weaker but faster endpoints. We see that many trials using overall survival used less time than anticipated, and many trials using response rate or progression-free survival actually took quite a bit of time.  In part that is due to researchers needing to document the duration of the response. But, whatever the reason, the time to get each of the three endpoints is actually more similar than different, and we estimate that our current use of  these faster endpoints are saving us only 11 months compared to using only overall survival. (more…)
Author Interviews, FDA, JAMA / 06.03.2019 Interview with: Craig Alexander Garmendia, PhD Office of Bioresearch Monitoring Operations Office of Regulatory Affairs US Food and Drug Administration Miami, Florida What is the background for this study? What are the main findings?  Response: Clinical trials under the U.S. Food and Drug Administration’s (FDA) purview have been shown to suffer from falsified data. While the FDA warns researchers when falsified data are discovered, these data still make their way into medical literature. In this novel study, Dr. Garmendia and colleagues conducted a systematic review to examine the effects of publications containing falsified data on meta-analyses using sensitivity analyses. Almost half of all meta-analyses had conclusions altered by publications containing falsified data, while nearly one-third of all analyses had considerable changes in outcomes. (more…)
Asthma, Author Interviews, FDA, Regeneron / 31.10.2018 Interview with: RegeneronNeil Graham,  M.B.B.S., M.D., M.P.H VP of Immunology & Inflammation Regeneron What is the background for this announcement?  Response: Patients with moderate-to-severe asthma often have uncontrolled, persistent symptoms despite standard-of-care therapy that may make them suitable for treatment with a biologic therapy. They live with coughing, wheezing and difficulty breathing, and are at risk of severe asthma attacks that may require emergency room visits or hospitalizations. [i],[ii] Oral corticosteroids can provide relief for severe, short-term symptoms. However, their chronic use is limited to the most severe patients due to the potential for serious side effects. [iii],[iv] A particular type of inflammation contributes to the cause of uncontrolled symptoms in multiple inflammatory diseases such as asthma and atopic dermatitis.[v] Dupixent is a medicine that inhibits the overactive signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key proteins that contribute to this type of inflammation. This inhibits cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE; however, the mechanism of action of Dupixent in asthma has not been definitively established. (more…)
Author Interviews, Cancer Research, Pharmaceutical Companies / 20.08.2018 Interview with: Jeffrey S. Humphrey, MD President of Kyowa Kirin Pharmaceutical Development, Inc What is the background for this announcement? Would you briefly explain what is meant by Mycosis Fungoides and Sézary Syndrome? Response: Kyowya Kirin has received FDA approval for Poteligeo (mogamulizumab), based on findings from the MAVORIC trial. Mogamulizumab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets CC chemokine receptor 4 (CCR4), for the treatment of the most common subtypes of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) and Sézary syndrome (SS). MF and SS may have a profound and severe impact on quality of life, including a patient’s functional, emotional and social well-being, as symptoms may include a scaly red rash or light or dark patches in areas of the body that are not usually exposed to the sun; thin, reddened, eczema-like rash; thickened scaly, red skin (or plaques) or psoriasis-like rash; more advanced disease can include tumors (with significant thickness) on the skin, which may develop ulcers and become infected. Because CTCL manifests in skin lesions, it is often mistaken for other skin conditions (early stage MF and SS can be diagnosed as other skin conditions), which can delay conclusive diagnosis and treatment options. MF is the most common subtype of CTCL, affecting 50-70% of individuals. In most patients diagnosed with early stage MF, the skin involvement does not progress, but in some patients, it will slowly progress. SS accounts for approximately 3% of CTCL cases and is a more aggressive, leukemic form of CTCL, affecting the blood, skin, lymph nodes and visceral organs (more…)
Author Interviews, FDA, JAMA, Race/Ethnic Diversity / 25.07.2017 Interview with: Sanket Dhruva, MD, MHS, FACC Cardiology, VA Connecticut Healthcare System Robert Wood Johnson Foundation Clinical Scholar Yale University What is the background for this study? What are the main findings? Response: In 2012, Congress passed the Food & Drug Administration (FDA) Safety and Innovation Act, with the goal of increasing enrollment and availability of data in important patient groups such as the elderly, women, and racial and ethnic minorities. In 2014, as mandated by the legislation, the FDA released an Action Plan to address these issues. This Action Plan included the goal of increasing the transparency by posting demographic information of pivotal (or key) clinical trials used to support approval decisions. We examined how often these data were available in 2015 for all studies used to support approval of all original high-risk medical devices approved in the calendar year following the FDA Action Plan. Examples of these medical devices include stents, bone grafts, heart valves, and spinal cord stimulators. We wanted to understand if age, sex, and race and ethnicity data were available and if the results of clinical studies supporting these medical devices were analyzed to assess if there were differences in safety and effectiveness by these important demographic factors. Our main findings are that FDA Summaries publicly reported age for 65% of study populations, sex for 66%, and race and/or ethnicity for 51%. Analyses to assess if demographic factors may have impacted device safety and effectiveness were only conducted by age for 9%, by sex for 17%, and by race for 4% of clinical studies. (more…)
Author Interviews, FDA, JAMA, Ophthalmology / 02.12.2016 Interview with: Malvina Eydelman, M.D. Division Director; Division of Ophthalmic and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health FDA. What is the background for this study? Response: In October 2009, the FDA, the National Eye Institute (NEI), and the Department of Defense (DoD) launched the LASIK Quality of Life Collaboration Project (LQOLCP) to help better understand the potential risk of severe problems that can result from LASIK. The project aimed to develop a tool to determine the percent of patients who develop difficulties performing their usual activities following LASIK, and to identify predictors for those patients. At the time we developed our project, there was a limited amount of valid scientific data on certain patient-reported outcomes (PROs) related to LASIK. A PRO is a report of a condition experienced and reported by the patient, not the health care provider. Most LASIK studies used tools, such as questionnaires, to assess visual symptoms, but only after the surgery. The Patient-Reported Outcomes with LASIK (PROWL) studies in the LQOLCP assessed visual symptoms both before and after their LASIK surgery to identify changes over time. The studies also measured the impact symptoms directly had on performing usual activities, which had not previously been done. (more…)
Author Interviews, Dermatology, FDA, Melanoma, NYU / 19.12.2015 Interview with: Dr. Jennifer Stein MD Associate Professor Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What is the background for this FDA decision? What is the issue surrounding tanning beds? Dr. Stein:  This is an important proposal from the FDA because it restricts minors from tanning and requires adults to sign an acknowledgement stating they have been informed about the risks of tanning. There is clear evidence that indoor tanning significantly increases a person’s risk for skin cancer, including melanoma, a potentially deadly form of skin cancer. It is important to protect young people from the dangers of tanning beds, especially because many patients report that they started indoor tanning as teens. There are 1.6 million minors using tanning beds every year. MedicalResearch: What is the problem with tanning?  Isn't a tan better than a sunburn? Dr. Stein: Tanning beds deliver intense amounts of UVA. We know that UVA penetrates deep into the skin and causes mutations that lead to skin cancers, including melanoma. Tanning is a sign that skin cells have been damaged by UV light. (more…)
Author Interviews, Opiods, Pain Research / 28.10.2015 Interview with: Richard L. Rauck, M.D. Director of Carolinas Pain Institute Winston Salem, NC Medical Research: How large is the problem of chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment and for whom alternative treatment options are inadequate? Dr. Rauck: Chronic pain affects more than 100 million Americans - more than diabetes, heart disease and cancer combined. It is the most common cause of long-term disability, costing the U.S. billions of dollars annually in medical costs and lost wages and productivity.   Medical Research: What are the main medical conditions associated with this type of pain?  Dr. Rauck: A National Institute of Health Statistics survey indicated that low back pain is the most common cause of chronic pain (27%), followed by severe headache or migraine pain (15%), neck pain (15%) and facial ache or pain (4%). (more…)
Author Interviews, FDA, JAMA, University of Pittsburgh / 21.09.2015

Dr. Tamar Krishnamurti PhD Department of Engineering & Public Policy Carnegie Mellon University Pittsburgh, PA Interview with: Dr. Tamar Krishnamurti PhD Department of Engineering & Public Policy Carnegie Mellon University Pittsburgh, PA 15213  Medical Research: What is the background for this study? What are the main findings? Dr. Krishnamurti: In 2012, the Food and Drug Administration Safety and Innovation Act became law. As part of this law, FDA can assign drugs the “breakthrough” designation. Breakthrough drugs are drugs that are intended to treat a serious or life threatening condition and have shown preliminary evidence of a substantial improvement over existing therapies on at least one one clinically significant endpoint. These clinical endpoints can be surrogate outcomes and don't have to be a direct outcome of the disease. All FDA press releases announcing approval of breakthrough-designated drugs use the term “breakthrough” and about half use the term “promising” when describing the drugs. Our study randomly assigned participants to read 1 of 5 short descriptions of a recently approved drug. These vignettes differed by the term assigned to the drug (e.g. "breakthrough" or "promising") or by whether the basis for the designation was clearly and succinctly explained in the description. We found that using the terms "breakthrough" and "promising" to describe these drugs resulted in people having unwarranted confidence about the effectiveness of breakthrough drugs, which could prevent them from making a fully informed decision about whether to take the drug or not. The influence of these terms on peoples' judgments was mitigated by explaining the regulatory meaning of the drug's approval (which is required in the drug's professional label, but not in public discourse about the drug). (more…)
Author Interviews, FDA, JAMA / 27.07.2015

Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of Interview with: Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of Minnesota Medical Research: What is the background for this study? What are the main findings? Dr. Karaca-Mandic: Drug safety has received a lot of attention recently, and FDA's post-marketing drug surveillance program (FAERS) offers and important opportunity to monitor drug safety and update drug warnings. There has been an increasing trend in reports to FAERS of serious adverse drug events and earlier studies suggested that these trends were primarily driven by increased manufacturer reports of serious and unexpected adverse events. While these studies highlighted the overall increase in adverse event rates, manufacturer timeliness in reporting and compliance with the 15 calendar day regulation for expedited reports was unknown, though some recent media coverage has offered anecdotal examples of delay. My co-authors and I were interested in studying not only the reporting of these events, by manufacturers to FDA, but also their timely reporting as required by the Federal regulation. Delays in reporting can have important public health consequences because the FDA uses this information to update drug warnings. We found that about 10% of serious and unexpected adverse events that are subject to the 15-day regulation were not reported by 15 days. We also found that events that involved a patient death were more likely to be delayed. For example, we found that after adjusting for other characteristics of the report and the patient, about 12% of events that involved patient death, and 9% of those that did not involve patient death were delayed beyond 15 days. (more…)
Author Interviews, FDA, Flu - Influenza, Geriatrics, Lancet, Vaccine Studies / 03.04.2015

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD Interview with: Dr Richard Forshee PhD Associate Director for Research in the Office of Biostatistics and Epidemiology Center for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD On behalf of the study authors Medical Research: What is the background for this study? What are the main findings? Dr. Forshee: Influenza continues to be a major public health concern causing illness, hospitalization, and death. The elderly are at highest risk for seasonal influenza complications, including hospitalization and death. As people grow older their ability to raise a strong protective immune response can weaken.  The availability of a vaccine that uses a higher dose to induce a stronger immune response could reduce the serious impact of influenza in this age group.  The purpose of this study was to determine whether a high-dose inactivated influenza vaccine was more effective for prevention of probable influenza infections and influenza-related hospital admissions, compared to standard-dose inactivated influenza recipients. In December 2009, the U.S. Food and Drug Administration (FDA) licensed Fluzone High Dose, an injectable inactivated trivalent seasonal influenza vaccine for people ages 65 years and older. This high-dose vaccine contains four times more hemagglutinin—the active ingredient in influenza vaccines that cause the human body to produce antibodies against the influenza viruses—than the standard-dose vaccine. The FDA approved the high-dose vaccine using the accelerated approval regulatory pathway, which allows the agency to approve products for serious or life-threatening diseases based on reasonable evidence of a product’s effectiveness.  This pathway reduces the time it takes for needed medical products to become available to the public.  Studies conducted prior to licensure showed an enhanced immune response to the high-dose vaccine compared with the standard-dose vaccine in individuals 65 years of age and older indicating that the high-dose vaccine was reasonably likely to be more effective in preventing influenza disease. As part of the accelerated approval process, the manufacturer, Sanofi Pasteur, was required to conduct a randomized clinical study post-licensure to confirm that the high-dose vaccine decreased seasonal influenza disease after vaccination relative to standard dose vaccine. This confirmatory study demonstrated that the high–dose vaccine prevented 24% more cases of laboratory-confirmed influenza illness compared to standard-dose vaccines in people 65 years of age and older. However, the study was not large enough to determine efficacy of the vaccine against severe disease. A team of scientists from FDA, the Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services, and Acumen LLC ( an independent research organization) studied the relative effectiveness of the high-dose influenza vaccine in the U.S. population ages 65 years and older.  The observational study, which covered the 2012-2013 influenza season, found a significant reduction both in influenza-associated illness and in influenza-related hospitalizations among individuals who received the high-dose vaccine, compared to those receiving the standard dose. Additional background about this study: “Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis” is available at: A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at: (more…)
Author Interviews, Diabetes, Diabetes Care, FDA, Pharmacology / 20.03.2014

Christian Hampp PhD Senior Staff Fellow/Epidemiologist at FDA Division of Epidemiology-I, Office of Pharmacovigilance and Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Interview with: Christian Hampp PhD Senior Staff Fellow/Epidemiologist at FDA Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD What are the main findings of the study? Dr. Hampp: Our study described U.S. market trends for antidiabetic drugs, focusing on newly approved drugs, concomitant use of antidiabetic drugs, and effects of safety concerns and restrictions on thiazolidinedione use. We found that since 2003, the number of adult antidiabetic drug users increased by approximately 43% to 18.8 million in 2012.  During 2012, 154.5 million prescriptions for antidiabetic drugs were filled in outpatient retail pharmacies.  Since 2003, metformin use increased by 97% to 60.4 million prescriptions dispensed in 2012.  Among antidiabetic drugs newly approved for marketing between 2003 and 2012, the dipeptidyl-peptidase-4 (DPP-4) inhibitor sitagliptin had the largest share with 10.5 million prescriptions in 2012. Possibly triggered by safety concerns, the use of pioglitazone declined in 2012 to approximately 52% of its peak in 2008, when 14.2 million prescriptions were dispensed in outpatient retail pharmacies and the use of rosiglitazone use decreased to fewer than 13,000 prescriptions dispensed in retail or mail-order pharmacies in 2012. (more…)
Author Interviews, FDA, JAMA, Yale / 23.01.2014 Interview with: Nicholas S. Downing, AB Yale University School of Medicine New Haven, Connecticut What are the main findings of the study? Answer: In our systematic review of all new drugs approved by the FDA over an 8 year period, we found that there was real variability in the quality and quantity of clinical trial evidence used as the basis of the agency’s approval decisions. Some drugs were studied in multiple randomized, double-blinded, controlled clinical trials that provide very helpful information for patients and physicians. However, other drugs were studied in clinical trials that did not produce as much information about their safety and effectiveness. (more…)