Guidance for Anticounterfeiting Measures; Crackdown on Rogue Investigators; Better Access to Experimental Drugs; Federal Law May Not Be Needed to Regulate DTC Genetic Tests; Newspaper Sued over Story on Drug Manufacturer; Postmarketing Adverse Events Must Be Reported Electronically; Genzyme Plant Problems Causing FDA to Ease Restrictions on Experimental Drug Access; Pfizer Fined Again for Off-Label Promotion; Postmarketing Studies Being Performed as Ordered; FDA Warning Letters to Be Easier to View; Experimental Diabetes Drug to Become More Readily Available

2009 ◽  
Vol 28 (5) ◽  
pp. 592-595
Keyword(s):  
Adverse Events ◽  
Experimental Diabetes ◽  
Drug Manufacturer ◽  
Federal Law ◽  
Genetic Tests ◽  
Off Label ◽  
Experimental Drugs ◽  
Drug Access ◽  
Experimental Drug ◽  
Diabetes Drug

Testing Meldonium: Assessing Soviet pragmatic alternatives to the randomized controlled trial

2021 ◽  
pp. 174077452110085
Author(s):  
Anastasiya Chirkova ◽  
Alexander Petrenko ◽  
Pavel Vasilyev
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trial ◽  
Soviet Union ◽  
Drug Testing ◽  
Controlled Trial ◽  
Randomized Controlled ◽  
Experimental Drugs ◽  
The Soviet Union ◽  
Experimental Drug ◽  
Second World

Background/aims Current research largely tends to ignore the drug-testing model that was developed in the “Second World” as an explicit alternative to the randomized controlled trial. This system can be described as “socialist pharmapolitics,” accounting for the specific features of state socialism that influenced the development and testing of experimental drugs. The clinical trials model employed in the “Second World” was heavily influenced by the Soviet Union, which was by far the most influential player in the socialist bloc during the Cold War. Based on extensive archival research, this article presents an empirical case of a late Soviet clinical trial as a pragmatic alternative to the randomized controlled trial model. It accounts for the divergences between the official model prescribed by the Soviet authorities and the messy realities of healthcare practice. It further outlines different factors that ultimately shaped how clinical trials were organized in Soviet institutions “on the ground.” Accordingly, this article presents a “real-life” history of “socialist pharmapolitics” and outlines the problems that this system faced in practice. Methods Archival research was conducted at the Russian State Archive of Scientific and Technical Documentation in Moscow. Archival files include scientific, technical, and registration documentation such as biochemical, pharmacological, and clinical descriptions of the experimental drug Meldonium, letters between various hospitals, research institutes and the Soviet regulatory body, as well as 26 reports of completed clinical trials. Manual content analysis was used for the interpretation of results. Results This article presents an empirical case of a late Soviet clinical trial as a pragmatic alternative to the randomized controlled trial model. It demonstrates some key differences from the randomized controlled trial model. This article also highlights some of the discrepancies between the model that was officially prescribed by the Soviet authorities and the realities of experimental drug testing in the Soviet Union in the late 1980s and early 1990s. In particular, it notes some elements of randomization, double-blinding, and the use of placebo that were present in Meldonium trials despite being formally denounced by Soviet bioethics. Conclusion The Soviet model for testing experimental drugs differed from the Western one substantially in a number of respects. This difference was not only proclaimed officially by the Soviet authorities, but was for the most part enforced in clinical trials in practice. At the same time, our research demonstrates that there were important differences between the official model and the clinical realities on the ground.

Genetic Privacy Laws and Patients' Fear of Discrimination by Health Insurers: The View from Genetic Counselors

2000 ◽  
Vol 28 (3) ◽  
pp. 245-257 ◽  
Author(s):  
Mark A. Hall ◽  
Stephen S. Rich
Keyword(s):  
Health Insurance ◽  
Genetic Information ◽  
Federal Law ◽  
Genetic Privacy ◽  
Genetic Tests ◽  
Group Health ◽  
Privacy Laws ◽  
Similar Legislation ◽  
Do So ◽  
Health Insurers

Since 1991, over half the states have enacted laws that restrict or prohibit insurers’ use of genetic information in pricing, issuing, or structuring health insurance. Wisconsin was the first state to do so, in 1991, followed by Ohio in 1993, California and Colorado in 1994, and then several more states a year in each of the next five years. Similar legislation has been pending in Congress for several years. Also, a 1996 federal law known as the Health Insurance Portability and Accountability Act (HIPAA) prohibits group health insurers from applying “preexisting condition” exclusions to genetic conditions that are indicated solely by genetic tests and not by any actual symptoms.

scholarly journals Off-label-use of sulfur-hexafluoride in voiding urosonography for diagnosis of vesicoureteral reflux in children: A survey on adverse events

2017 ◽  
Vol 6 (1) ◽  
pp. 52
Author(s):  
Alexander Sauer ◽  
Clemens Wirth ◽  
Isabel Platzer ◽  
Henning Neubauer ◽  
Simon Veldhoen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Vesicoureteral Reflux ◽  
Sulfur Hexafluoride ◽  
Off Label Use ◽  
Voiding Urosonography ◽  
Off Label ◽  
Label Use

The Palatability and Tolerability of Deferasirox (Exjade®) Taken with Meals, Different Liquids, or Crushed and Added to Food

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5155-5155
Author(s):  
Stuart L Goldberg ◽  
Patricia Giardina ◽  
Joan Parkhurst Cain ◽  
Deborah Chirnomas ◽  
Jason Esposito ◽  
...  
Keyword(s):  
Adverse Events ◽  
Serum Ferritin ◽  
Research Funding ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelation Therapy ◽  
Age Group ◽  
Baseline Serum ◽  
Off Label

Abstract Abstract 5155 Introduction: Deferasirox (Exjade®, Novartis Pharmaceuticals) is an oral iron chelator indicated for the treatment of transfusional iron overload. The recommended mode of administration is to be taken on an empty stomach in water, apple juice or orange juice ≥30 minutes before food. However, there have been post-marketing reports of discontinuation or reduced compliance of deferasirox secondary to palatability and gastrointestinal adverse events. Registration trials with deferasirox did not evaluate different food combinations in an attempt to maintain predictable plasma levels. Early single dose studies suggested that the bioavailability of deferasirox is increased when administered with or before meals, and is positively influenced by fat content, but is not affected by degree of dispersion nor type of liquid. Long-term pharmacokinetic and tolerability studies involving a food effect have not been conducted to date, and the ability of alternate methods of administration to improve patient compliance with iron chelation therapy is unknown. Method: This is an ongoing single-arm, open-label, multi-center study designed to evaluate the palatability, safety, tolerability and pharmacokinetics of deferasirox when administered with food, dispersed in any liquid of choice, or crushed and added to food. The patient population includes patients with transfusional hemosiderosis (minimum entry serum ferritin ≥500 μ g/L) aged >2 years with thalassemia major, sickle cell disease (SCD), low or intermediate (INT-1) risk MDS or other anemias, who are on, starting, or resuming treatment with deferasirox. The study began with a 1-month run-in phase with deferasirox dosed according to prescribing information, then a 3-month assessment phase where subjects could choose each week from 5 general administration options including with or without meals, in the morning or evening, crushed and added to a soft food, or mixed in a liquid of choice. Subject diaries are used to record the meal and method of administration at the end of each week. Palatability is assessed with a modified facial hedonic scale, with additional directed questions capturing gastrointestinal side effects. This is a data analysis of the run-in phase. Result: Target enrollment has been met with 65 patients. Baseline data on the first 58 subjects include 8 in the 2 to <10 years of age group (median 7.5 years; range 3–9); 42 in the 10 to <60 years of age group (median 18.5 years; range 10–48); and 8 in the ≥60 years of age group (median 74 years; range71-83). Underlying hematologic diagnoses included SCD (41%), thalassemia major (29%), MDS (12%) and other anemias (17%). Sixty-nine percent of subjects were receiving deferasirox prior to entering the study. The median baseline serum ferritin level was 2405 μ g/L (range 560–8660) and was distributed as shown in Table 1. The most frequent adverse events were diarrhea (19%) and nausea (9%) (Table 2), which were more common in MDS (P=0.23 and P<0.01, respectively). Conclusion: This ongoing trial (NCT00845871) is evaluating whether alternative modes of administration improve palatability and tolerability while maintaining safety. Preliminary data from the assessment phase (deferasirox taken with meals, different liquids, or crushed and added to food) will be presented at the meeting. Disclosures: Goldberg: Novartis Oncology: Consultancy, Honoraria, Research Funding, Speakers Bureau. Off Label Use: Exjade, iron chelation therapy, off-label method of administration. Giardina:Novartis: Research Funding. Parkhurst Cain:Novartis: Research Funding. Chirnomas:Novartis: Research Funding. Esposito:Novartis: Employment. Paley:Novartis: Employment. Vichinsky:Novartis: Consultancy, Research Funding, Speakers Bureau; Hemaquest: Consultancy, Membership on an entity's Board of Directors or advisory committees; Apotex: Consultancy, Research Funding.

scholarly journals Analysis of the Safety Profile of Commonly Used Procoagulants Using the FDA Adverse Event Reporting System

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4712-4712
Author(s):  
Emma P. Deloughery ◽  
Joseph J. Shatzel
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Vitamin K ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Off Label Use ◽  
Event Reporting ◽  
Off Label ◽  
Events Data

Abstract Introduction: Though less commonly used than their anticoagulant counterparts, procoagulants have an important role in the reversal of anticoagulation. Four-factor prothrombin complex concentrate (4PCC) is now approved by the U.S. Food & Drug Administration (FDA) for the reversal of major bleeding associated with warfarin, and is often used off-label to reverse direct oral anticoagulants. Three-factor concentrate (3PCC) and off-label use of recombinant activated factor VII (rFVIIa) have filled this role in the past. Vitamin K is also used as a common antidote for warfarin-induced coagulopathy. Comparative data evaluating the safety profiles and relative thrombotic risks of the PCCs and rFVIIa is limited. In order to better evaluate their comparative safety we calculated the rate of adverse events reported to the FDA of each procoagulant. Methods: We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles drug-related adverse events reported to the FDA from 1969 onwards, to assess the rate of adverse events reported with various procoagulants. Safety profiles were assessed using proportional reporting ratios (PRR) with the total number of reported cases as the denominator. Adverse events data for each drug (vitamin K, rFVIIa, 3PCC, 4PCC) was gathered from FAERS. Both generic and brand names were used to query the database. Adverse events data was filtered by including only events reported by healthcare professionals. Specific adverse events were chosen apriori based on hypothesized potential complications and included hemorrhagic and thrombotic complications. The PRR with 95% confidence interval was generated for each event, with a cut-off of 2 being used to identify associations. Results: As shown in Table 1 and Figure 1, rFVIIa was associated with increased reports of mortality while 4PCC was associated with ischemic stroke, and all but rFVIIa were associated with high INR. 3PCC displayed an increased association with reports of intracranial hemorrhage (ICH), although there was a low rate of reports for 3PCC. Lesser associations were found between rFVIIa and myocardial infarction (MI), 3PCC and deep-vein thrombosis (DVT), and 4PCC and DVT and ICH. In general, vitamin K had the weakest associations among adverse events. Conclusions: Our analysis found that the rate of reports of death and MI were higher with rFVIIa than other procoagulants, while reports of ischemic stroke and intracranial hemorrhage were more common with PCCs. rFVIIa has been associated with cardiovascular before, a finding reiterated by our study. There are notable limitations of this type of analysis, including the reliance on the accurate reporting of adverse events to the FDA, possibility of duplications of reports in the FAERS database, and the importance of not conflating correlation with causation as it relates to these events. The association between rFVIIa and increased death may be due to rFVIIa's history of off-label use in trauma patients and other patient groups at higher risk for mortality. While 4PCC may be the procoagulant of the present, it does not have a perfect safety profile, and further study is needed to better characterize the complications of 4PCC and ensure that it is used in such a way as to not under- or over-treat the condition. Disclosures No relevant conflicts of interest to declare.

scholarly journals 547. A Retrospective Cohort Study of Treatment Patterns and Clinical Outcomes in Patients with COVID-19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S339-S340
Author(s):  
Haley Pritchard ◽  
Jon Hiles ◽  
Batteiger Teresa ◽  
Armisha Desai ◽  
Justin E Wrin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Events ◽  
Hospital Mortality ◽  
Retrospective Cohort ◽  
Research Study ◽  
Panel Member ◽  
Review Panel ◽  
Off Label ◽  
Study Investigator ◽  
Treatment Trends

Abstract Background The SARS-CoV-2 pandemic has caused over 400,000 deaths worldwide thus far, and poses therapeutic challenges for millions of patients. There is currently no treatment for SARS-CoV-2 infection approved by the United States Food and Drug Administration. Multiple agents have been used off-label to treat SARS-CoV-2 infection based on small observational cohorts and in vitro data. Here we present the experience of a large academic medical center in treating SARS-CoV-2 infection. Methods We performed a retrospective cohort study of patients admitted for greater than 24 hours with a nasopharyngeal, oropharyngeal, and/or bronchoalveolar lavage sample positive for SARS-CoV-2 by polymerase chain reaction (PCR). Demographic data, comorbidities, clinical data, and treatment data were collected from the electronic medical record. Off-label therapies were used at the discretion of the treating providers guided by regularly updated treatment guidelines assembled by infectious diseases physicians and antimicrobial stewardship pharmacists. The primary outcome assessed was in-hospital mortality. Secondary outcomes included admission to the intensive care unit (ICU), endotracheal intubation, initiation of vasopressors, and drug-related adverse events. Results Data collection was completed for 448 patients admitted between March 18, 2020 and May 8, 2020. All-cause in-hospital mortality was 13.4% (60/448) during this time. Mortality rates increased with age, up to 45% for patients over 80 years old. Male sex, hypertension, chronic pulmonary disease, end-stage renal disease, chronic liver disease were also risk factors for increased mortality. QTc interval prolongation occurred significantly more frequently in patients who received hydroxychloroquine (HCQ) with or without azithromycin(AZM) than those who did not (HCQ 6%, HCQ+AZM 7.8% vs all other patients, 0%, p&lt; .0001). Review of treatment trends showed close adherence to the treatment recommendations at that time (Figure 1). Patient Characteristics Admission Laboratory Data by Disease Severity QTc Prolongation Conclusion SARS-CoV-2 infection is associated with significant inpatient mortality, and use of off-label treatments was associated with significant drug-related adverse events. Treatment regimens changed rapidly, and providers adhered closely to institutional guidelines as they evolved. Treatment Trends by Week QTC pre/post Treatment by Hydroxychloroquine Use vs. No Hydroxychloroquine Use Disclosures Samir Gupta, MD, Gilead Sciences (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)

scholarly journals Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

2020 ◽  
Author(s):  
Gaurav Joshi ◽  
Ramarao Poduri
Keyword(s):  
Virtual Screening ◽  
Homo Sapiens ◽  
Antiviral Agents ◽  
Drug Repurposing ◽  
Experimental Drugs ◽  
Experimental Drug ◽  
Investigational Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Selection Of

<p>SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (3VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.</p>

Pharmacological management of treatment-resistant schizophrenia: advanced use of clozapine

2018 ◽  
Author(s):  
Siobhan Gee ◽  
David Taylor
Keyword(s):  
Older Adults ◽  
Adverse Events ◽  
Plasma Concentrations ◽  
Practical Experience ◽  
Treatment Resistant ◽  
Serious Adverse Events ◽  
Pharmacological Management ◽  
Off Label ◽  
Theoretical Support ◽  
The Uk

Clozapine is licensed in the UK for use in treatment-resistant schizophrenia, treatment-intolerant schizophrenia, or psychosis associated with Parkinson’s disease. As with many drugs, it is also used outside of these licensing parameters for other conditions or clinical situations—often referred to as ‘off-label’ prescribing. These off-label indications have varying degrees of theoretical support, peer-reviewed evidence, and practical experience associated with them. This chapter discusses the use of clozapine for children and adolescents, older adults, and in the treatment of aggression and mood disorders. The use of supramaximal doses of clozapine to achieve therapeutic plasma concentrations is also off-label, although adding interacting medication to reach the same result is not; these contrasting approaches are also debated. Finally, rechallenging with clozapine in patients who have previously had serious adverse events to the drug is also considered.

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