Computer Simulation Study Favors Tomosynthesis over Digital Mammography

MedicalResearch.com Interview with:

Aldo Badano, Ph.D. Deputy Director, Division of Imaging, Diagnostics, and Software Reliability Office of Science and Engineering Laboratories Center for Devices and Radiological Health Silver Spring, MD 20993

Aldo Badano, Ph.D.
Deputy Director, Division of Imaging, Diagnostics, and Software Reliability
Office of Science and Engineering Laboratories
Center for Devices and Radiological Health Silver Spring, MD 20993 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Expensive and lengthy clinical trials can delay regulatory evaluation of innovative technologies, affecting patient access to high-quality medical products. Although computational modeling is increasingly being used in product development, it is rarely at the center of regulatory applications.

Within this context, the VICTRE project attempted to replicate a previously conducted imaging clinical trial using only computational models. The VICTRE trial involved no human subjects and no clinicians. All trial steps were conducted in silico. The fundamental question the article addresses is whether in silico imaging trials are at a mature development stage to play a significant role in the regulatory evaluation of new medical imaging systems. The VICTRE trial consisted of in silico imaging of 2986 virtual patients comparing digital mammography (DM) and digital breast tomosynthesis (DBT) systems.

The improved lesion detection performance favoring DBT for all breast sizes and lesion types was consistent with results from a comparative trial using human patients and radiologists.  Continue reading

FDA Approves Dupixent: Only Self-Administered Biologic for Moderate-to-Severe Asthma

MedicalResearch.com Interview with:
RegeneronNeil Graham,  M.B.B.S., M.D., M.P.H
VP of Immunology & Inflammation
Regeneron

MedicalResearch.com: 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. Continue reading

FDA Fast Tracks Development of PaxVax Vaccine for Chikungunya

MedicalResearch.com Interview with:

Lisa Danzig, MD Chief Medical Office PaxVax

Dr. Danzig

Lisa Danzig, MD
Chief Medical Office
PaxVax

MedicalResearch.com: Would you briefly explain what is meant by Chikungunya infection?  Whom does it primarily affect?  How is it transmitted and what the  complications?

Response: Chikungunya is caused by the chikungunya virus (CHIKV), an arthropod-borne virus (arbovirus) spread by infected mosquitos.

Infection with chikungunya virus results in severe, often debilitating joint pain in infected patients, known as arthralgia. Symptoms can include intense discomfort in joints, such as the wrists, fingers, ankles, and feet, in the knees and in the hips or shoulders. Those affected can also frequently suffer from headaches, fever, and severe muscle pain, rashes on the torso and limbs and swelling in one or more cervical lymph nodes. Individuals who are at a higher risk for contracting chikungunya include infants, elderly and those with chronic conditions.

The virus is a small, spherical, enveloped, positive-strand RNA virus. The virus is transmitted by the Aedes aegypti and Aedes albopictus mosquito, which originated in Africa, first spreading to Asia and recently expanding to the western hemisphere.  Outbreaks are rapid and widespread.  In February 2005 a major outbreak of chikungunya occurred in the islands of the Indian Ocean after which over 1.9 million cases have been reported in India, Indonesia, Maldives, Myanmar and Thailand.

Chikungunya spread has been identified in 45 countries in the Americas alone with more than 1.7 million suspected cases reported to the Pan American Health Organization since 2015, increasing the incidence of the disease and risk to U.S. travelers. In 2016 there were approximately 60,000 cases of chikungunya across India. Beyond the Indian subcontinent, the Caribbean, Central America and South America, inhabitants and travelers visiting sub-Saharan Africa and Southeast Asia are also at risk.

Continue reading

FDA Grants Fast Track Designation to Nintedanib for Scleroderma with Lung Disease

MedicalResearch.com Interview with:

Dr. Thomas Leonard, Ph.D. Executive director, Clinical Development and Medical Affairs, Specialty Care Boehringer Ingelheim Pharmaceuticals, Inc.

Dr. Thomas Leonard

Dr. Thomas Leonard, Ph.D.
Executive director, Clinical Development and Medical Affairs, Specialty Care
Boehringer Ingelheim

MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by systemic sclerosis? What are the disease symptoms and manifestations?

Response: The FDA recently granted Fast Track designation to nintedanib for the treatment of systemic sclerosis with interstitial lung disease (SSc-ILD) – paving the way for Boehringer Ingelheim to take an important step in advancing this potential therapy for those affected by this disease. The designation was based on Boehringer Ingelheim’s Investigational New Drug application (IND) and the anticipated efficacy and safety data from SENSCIS™ (Safety and Efficacy of Nintedanib in Systemic SClerosIS), a double-blind, randomized, placebo-controlled global Phase III trial which is fully enrolled and includes more than 520 patients from 32 countries.

The FDA’s Fast Track designation facilitates the development of new therapies that treat serious conditions and fulfill an unmet medical need in an effort to get treatments to those in need sooner, like those living with systemic sclerosis.

Systemic sclerosis, also known as scleroderma, is a rare disease characterized by thickening and scarring of connective tissue of multiple organs in the body, typically affecting women between ages 25 and 55. Most people with the disease will develop some degree of lung scarring, or interstitial lung disease (ILD), which is the leading cause of death among people with systemic sclerosis.

Nintedanib, currently marketed as Ofev®, is approved for treatment of a rare lung disease called idiopathic pulmonary fibrosis, or IPF, and has been shown to slow disease progression as measured by annual rate of decline in lung function. Because SSc-ILD and IPF share similarities in how the underlying lung scarring, or fibrosis, forms in people with the disease, Boehringer Ingelheim is evaluating the impact of nintedanib on SSc-ILD.

Continue reading

LUXTURNA Proves Effectiveness of Single Gene Therapy To Cure Rare Cause of Blindness

MedicalResearch.com Interview with:

Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting Blindness

Foundation Fighting Blindness

Dr. Stephen Rose PhD
Chief Research Officer
Foundation Fighting Blindness (FFB)

Dr. Rose comments on the announcement of the FDA approval of voretigene neparvovec (LUXTURNA™) gene therapy for inherited blindness due to mutations in the RPE65 gene.

What is the background for this announcement? What were the main findings from the study?

Response: While it has been 30 years since the RPE65 gene was identified as causing Leber’s Congenital Amaurosis, this shows that it is possible to have an effective gene therapy for an inherited disease. As the first gene therapy for the eye or for an inherited disease, LUXTURNA is a historic milestone in the search for cures for all inherited retinal diseases (IRDs). As a one-time gene therapy, LUXTURNA will not only be life-changing for patients with vision loss due to mutations in the RPE65 gene, it also provides critical momentum for gene therapies – for the eye and other diseases – now in the clinic.  Continue reading

Sex and Ethnicity Data Missing From Many FDA Medical Device Approval Reports

MedicalResearch.com Interview with:

Sanket Dhruva, MD, MHS, FACC Cardiology, VA Connecticut Healthcare System Robert Wood Johnson Foundation Clinical Scholar Yale University

Dr. Dhruva

Sanket Dhruva, MD, MHS, FACC
Cardiology, VA Connecticut Healthcare System
Robert Wood Johnson Foundation Clinical Scholar
Yale University

MedicalResearch.com: 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.

Continue reading

FDA Reports on Patient Satisfaction With LASIX Procedure

MedicalResearch.com 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.

Dr. Malvina Eydelman

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.

MedicalResearch.com: 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.

Continue reading

Smoking Warnings in Pictures Worth a Thousand Words?

MedicalResearch.com Interview with:

Marissa G. Hall, MSPH Doctoral Candidate, Department of Health Behavior Gillings School of Global Public Health University of North Carolina at Chapel Hill

Marissa Hall

Marissa G. Hall, MSPH
Doctoral Candidate, Department of Health Behavior
Gillings School of Global Public Health
University of North Carolina at Chapel Hill

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The US Food and Drug Administration (FDA) requires pictorial warnings on cigarette packs, but implementation was stalled by a 2012 lawsuit by the tobacco industry. The US Court of Appeals for the DC Circuit ruled against pictorial warnings, saying that FDA had “not provided a shred of evidence” that the pictorial warnings reduce smoking. To address this critique, our randomized trial examined the impact on smoking behavior of adding pictorial warnings to the front and back of cigarette packs. We found that smokers with pictorial warnings on their packs were more likely to attempt to quit and to successfully quit than those whose packs had text-only warnings.

Continue reading

Incomplete Follow Up Rates Exceed 10% in Oral Antithrombotic Trials

Victor Serebruany, MD, PhD HeartDrug Research, Towson, Maryland Department of Neurology Johns Hopkins University Baltimore, Maryland

Dr. Victor Serebruany

MedicalResearch.com Interview with:
Victor Serebruany, MD, PhD
HeartDrug Research, Towson, Maryland
Department of Neurology Johns Hopkins University Baltimore, Maryland

Medical Research: What is the background for this study? What are the main findings?

Dr. Serebruany: Missing data are common challenges to the validity of trial results, yet it is unclear how to characterize the extent of missing data.  We compared the published lost-to-follow-up rates to incomplete follow-up rates determined from subject records submitted to the FDA for major oral antithrombotic trials.  The 21 trials having both sets of rates included 270,089 patients followed for a median duration of 20 months.  The mean published lost-to-follow-up rates is 0.4% (median 0.3%, range 0.005% to 2%), consistently much lower than the FDA incomplete follow-up rates: mean 12% (median 13%, range 2% to 23%).  There is no correlation between the publication and FDA-calculated  rates (R 0.07, p = 0.76).   The FDA rates exceed greatly the endpoint rate differences: mean 1.3% (median 1,0%, range 0.2% to 3.0%).

Medical Research: What should clinicians and patients take away from your report?

Dr. Serebruany: That the FDA incomplete follow-up rates greatly exceed the endpoint rate differences raises questions of whether the endpoint differences may be due to differential follow-up rather than drug effect.  That they greatly exceed the measures routinely reported for trials, i.e., lost-to-follow-up rates, suggests that current trial reporting is inadequate.  Completeness of follow-up and other indicators of trial data quality should be considered when interpreting trial results.

Continue reading

FDA Proposes Restricting Sunlamps To Adults: Tanning = Skin Damage

Dr. Jennifer A. Stein MD PhD Associate Professor Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center

Dr. Jennifer Stein

MedicalResearch.com 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.

Continue reading

FDA Study Compares Anaphylactic Risk of IV Iron Products

Cunlin Wang, MD, PhD Division of Epidemiology I, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research US Food and Drug Administration

Dr. Wang

MedicalResearch.com Interview with:
Cunlin Wang, MD, PhD
Division of Epidemiology I,
Office of Surveillance and Epidemiology,
Center for Drug Evaluation and Research
US Food and Drug Administration

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Wang:  IV Iron has been known for its risk of anaphylactic reaction, but there has been little research on the comparative safety of individual IV Iron products from a large population-based study. This study included 688,183 new users of IV iron not on dialysis from the U.S. Medicare program over a ten-year span (January 2003 to December 2013). The main findings of the study are:  the risk for anaphylaxis at first exposure was higher for iron dextran than non-dextran IV iron products combined (iron sucrose, gluconate and ferumoxytol).  When individual IV Iron products were compared, the data suggested that iron dextran has the highest risk of anaphylaxis and Iron sucrose has the lowest risk, estimated both at the first time exposure and after cumulative exposures.  The low and high molecular weight dextran products could not be individually identified during most of study period. However,  from January 2006 through March 2008, during which the use of two dextran products could be distinguished, there was very low use of high molecular weight dextran (Dexferrum@). This suggested that the study results likely represent the risk of the low molecular weight dextran (Infed@).

Continue reading

New Immunotherapy May Extend Lives Of Some Lung Cancer Patients

MedicalResearch.com Interview with:
Dickran Kazandjian, MD
Office of Hematology and Oncology Products
Center for Drug Evaluation and Research
US Food and Drug Administration
Silver Spring, Maryland

Medical Research: What is the background for this study? What are the main findings?

Dr. Kazandjian: Nivolumab is the first approved immunotherapy, for the treatment of metastatic squamous non–small-cell lung cancer (NSCLC) after platinum-based chemotherapy.  FDA initiated an expedited review after obtaining the data monitoring committee report of a planned interim analysis of a second-line squamous NSCLC trial demonstrating a large overall survival benefit (CheckMate 017).

Nivolumab efficacy in metastatic Squamous (SQ) NSCLC has been previously reported in two studies.  CheckMate 063 was a single-arm trial in 117 patients with metastatic SQ NSCLC who had progressed after previous treatment with 2 systemic regimens including platinum-based doublet chemotherapy (Rizvi et al)  CheckMate 017 was a randomized study of nivolumab compared to docetaxel in 272 patients with metastatic SQ NSCLC who had progressed after prior platinum-based doublet chemotherapy (Brahmer et al).  The median survival of patients randomized to nivolumab was 9.2 months vs 6.0 months for docetaxel (hazard ratio, 0.59; 95%CI, 0.44-0.79; P < .001) a 41% improvement in the risk of death. Approval was supported by the single-arm study which demonstrated an objective response rate of 15% and at the time of analysis, 10 of the 17 responding patients (59%) had response  durations of 6 months or longer. The FDA approved nivolumab on March 4, 2015, saving 6 months by not waiting for formal preparation of data by the sponsor and 2.5 months by expediting review.

Continue reading

“Breakthrough” FDA Labeling of New Drugs Can Lead To Unwarranted Expectations

Dr. Tamar Krishnamurti PhD Department of Engineering & Public Policy Carnegie Mellon University Pittsburgh, PA 15213MedicalResearch.com 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).

Continue reading

Some Adverse Events Not Reported in Regulated Time Frame To FDA

Dr. Pinar Karaca-Mandic Ph.D Associate Professor, Health Policy & Management School of Public Health Division of Health Policy & Management Minneapolis MN University of MinnesotaMedicalResearch.com 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.

Continue reading

Co-ingestion of Benzodiazepines and Opioids Contributes to Overdose and Death

MedicalResearch.com Interview with:
Christopher M. Jones, Pharm D., M.P.H
Senior advisor, Office of Public Health Strategy and Analysis
Office of the Commissioner, Food and Drug Administration

Medical Research: What is the background for this study?

Dr. Jones: Opioid analgesics and benzodiazepines are the two most common drug classes involved in prescription drug overdose deaths. In 2010, 75% of prescription drug overdose deaths involved opioid analgesics and 29% involved benzodiazepines. Opioid analgesics and benzodiazepines are also the most common drugs associated with emergency department visits due to nonmedical use of prescription drugs.

Combined opioid and benzodiazepine use has been suggested as a risk factor for overdose death.

Opioids and benzodiazepines have complex drug interactions and in combination can result in synergistic respiratory depression, but the exact mechanisms by which benzodiazepines worsen opioid-related respiratory depression are not fully understood.

Widespread co-use of benzodiazepines and opioids has been documented in both chronic pain and addiction treatment settings. Studies suggest that among patients who receive long-term opioids for chronic non-cancer pain, 40% or more also use benzodiazepines. Among patients who abuse opioids, benzodiazepine abuse also is prevalent, and co-users report using benzodiazepines to enhance opioid intoxication.

This study builds on the prior literature by analyzing trends on how the combined use of opioids and benzodiazepines in the U.S. contributes to the serious adverse outcomes of nonmedical use–related ED visits and drug overdose deaths. A better understanding of the consequences of co-use of these medications will help identify at-risk populations, inform prevention efforts, and improve the risk–benefit balance of these medications.

Medical Research: What are the main findings?

Dr. Jones: From 2004 to 2011, the rate of nonmedical use–related Emergency Department visits involving both opioid analgesics and benzodiazepines increased from 11.0 to 34.2 per 100,000 population. During the same period, drug overdose deaths involving both drugs increased from 0.6 to 1.7 per 100,000. Statistically significant increases in Emergency Department visits occurred among males and females, non-Hispanic whites, non-Hispanic blacks, and Hispanics, and all age groups except 12–17-year-olds. For overdose deaths, statistically significant increases were seen in males and female, all three race/ethnicity groups, and all age groups except 12–17-year-olds. Benzodiazepine involvement in opioid analgesic overdose deaths increased each year, increasing from 18% of opioid analgesic overdose deaths in 2004 to 31% in 2011.

Continue reading

Heroin Addiction Most Often Preceded by Opioid Abuse

MedicalResearch.com Interview with:
Christopher M. Jones, Pharm D., M.P.H.

Senior advisor, Office of Public Health Strategy and Analysis
Office of the Commissioner, Food and Drug Administration

Medical Research: What is the background for this study?

Dr. Jones:  Heroin use and overdose deaths have increased significantly in the United States in recent years. Most heroin users have a history of nonmedical use of prescription opioid pain relievers as well, and an increase in the rate of heroin overdose deaths has occurred concurrently with an epidemic of prescription opioid overdoses.

Although it has been postulated that efforts to curb opioid prescribing, resulting in restricted prescription opioid access, have fueled heroin use and overdose, a recent analysis of 2010–2012 drug overdose deaths in 28 states found that decreases in prescription opioid death rates within a state were not associated with increases in heroin death rates; in fact, increases in heroin overdose death rates were associated with increases in prescription opioid overdose death rates.

In addition, a study examining trends in opioid pain reliever overdose hospitalizations and heroin overdose hospitalizations between 1993 and 2009 found that increases in opioid pain reliever hospitalizations predicted an increase in heroin overdose hospitalizations in subsequent years. Thus, the changing patterns of heroin use and overdose deaths are most likely the result of multiple, and possibly interacting, factors. Moreover, there is a lack of research examining recent trends in the prevalence of other substance use among persons using heroin, especially among the high-risk population of heroin users who meet diagnostic criteria for heroin abuse or dependence.

We wanted to better understand how heroin use is changing and identify the demographic and substance using groups that are at greatest risk for use. Knowing this information can help prevention efforts.

HHS Secretary Sylvia M. Burwell has made addressing opioid abuse, dependence, and overdose a priority and work is underway within HHS on this important issue. The evidence-based initiative focuses on three promising areas: informing opioid prescribing practices, increasing the use of naloxone – a drug that reverses symptoms of a drug overdose, and using medication-assisted treatment to slowly move people out of opioid addiction.

The Obama Administration is also committed to tackling the prescription drug and heroin epidemic, proposing significant investments to intensify efforts to reduce opioid misuse and abuse.

Medical Research: What are the main findings?

Dr. Jones:  Heroin use has increased significantly across most demographic groups. There were significant increases in heroin use among demographic groups that have had historically lower rates of heroin use, including women, the privately insured, and people with higher incomes. In fact, the gap between men and women, low and high incomes, and people with Medicaid and private insurance have narrowed in the past decade.

Heroin use is occurring in the context of broader poly-substance use, including marijuana, alcohol, cocaine, and prescription drugs. The use of heroin with other substances increases the risk of overdose. Nearly all (96%) people who reported heroin use also reported using at least one other drug in the past year. More than half (61%) used at least three other drugs.

Among heroin users in 2011-2013:

  • 45% had past-year prescription opioid painkiller abuse or dependence
  • 36% had past-year alcohol abuse or dependence
  • 25% had past-year cocaine abuse or dependence
  • 24% had past-year marijuana abuse or dependence

As heroin abuse and dependence have increased, so have heroin-related overdose deaths. From 2002 through 2013, the rate of heroin-related overdose deaths nearly quadrupled.

The strongest risk factor for heroin abuse or dependence was opioid pain reliever abuse or dependence followed by cocaine abuse or dependence.

Medical Research: What should clinicians and patients take away from your report?

Dr. Jones:  Clinicians can follow best practices for responsible painkiller prescribing to reduce opioid painkiller addiction, the strongest risk factor for heroin addiction. This entails

  • 1) using state prescription drug monitoring programs and asking patients about past or current drug and alcohol use prior to considering opioid treatment;
  • 2) prescribing the lowest effective dose of an opioid and only the quantity needed for each patient; and
  • 3) linking patients with substance use disorders to effective substance abuse treatment services, including the use of medication assisted treatment for people with opioid use disorders.

Patients and others can learn more about the risks of using heroin and other drugs and become trained in how to recognize and respond to an opioid overdose. For people who are struggling with substance abuse problems, they can call 1-800-662 HELP for assistance.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: More research is needed to evaluate the impact of interventions designed to reduce prescription opioid and heroin abuse. We also need to conduct additional research to further understand the risk and protective factors for heroin initiation and heroin addiction.

Citation:

Vital Signs: Demographic and Substance Use Trends Among Heroin Users — United States, 2002–2013

Weekly

July 10, 2015 / 64(26);719-725

Christopher M. Jones, Pharm D., M.P.H. (2015). Heroin Addiction Most Often Preceded by Opioid Abuse 

High-Dose Flu Vaccine Prevented More Influenza Infections In Elderly Than Standard Dose

Dr Richard Forshee PhD Food and Drug Administration, Silver Spring, MD MedicalResearch.com 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:

http://dx.doi.org/10.1016/S1473-3099(14)71087-4

A commentary on the study titled “Novel observational study designs with new influenza vaccines” is available at:

http://dx.doi.org/10.1016/S1473-3099(15)70020-4 Continue reading

Raw Milk Link To Higher Risk of Foodborne Illnesses

MedicalResearch.com Interview with:
Benjamin Davis BA
CLF-Lerner Fellow at the Johns Hopkins Center for a Livable Future.

Medical Research: What is the background for this study? What are the main findings?

Response: The Food and Drug Administration banned the inter-state sale of raw (i.e. unpasteurized) milk in 1987. Currently 30 states still allow raw milk sales on local farms or in stores. We were requested by the Maryland General Assembly’s Health and Government Operations Committee to conduct a review of the health benefits and risks of raw versus pasteurized milk in response to proposed legislation that would legalize raw milk in the state. After reviewing over 80 scientific articles we concluded that raw milk carries a substantially higher risk of foodborne illness when compared to pasteurized milk. However drinking raw milk may reduce allergies among children in rural settings. Continue reading

FDA Study on Diabetes Medication Use In US Shows Marked Increase in Number of Prescriptions

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, MDMedicalResearch.com 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

MedicalResearch.com: 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.

Continue reading

FDA Drug Approvals Have Variable Clinical Trial Evidence Record

MedicalResearch.com Interview with:
Nicholas S. Downing, AB
Yale University School of Medicine
New Haven, Connecticut

MedicalResearch.com: 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.
Continue reading