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Sample records for product surveillance postmarketing

  1. Postmarketing surveillance.

    PubMed

    Vlahović-Palčevski, Vera; Mentzer, Dirk

    2011-01-01

    Postmarketing drug surveillance refers to the monitoring of drugs once they reach the market after clinical trials. It evaluates drugs taken by individuals under a wide range of circumstances over an extended period of time. Such surveillance is much more likely to detect previously unrecognized positive or negative effects that may be associated with a drug. The majority of postmarketing surveillance concern adverse drug reactions (ADRs) monitoring and evaluation. Other important postmarketing surveillance components include unapproved or off-label drug use, problems with orphan drugs, and lack of paediatric formulations, as well as issues concerning international clinical trials in paediatric population. The process of evaluating and improving the safety of medicines used in paediatric practice is referred to as paediatric pharmacovigilance. It requires special attention. Childhood diseases and disorders may be qualitatively and quantitatively different from their adult equivalents. This may affect either benefit or risk of therapies (or both), with a resulting impact on the risk/benefit balance. In addition, chronic conditions may require chronic treatment and susceptibility to ADRs may change throughout the patient's lifetime according to age and stage of growth and development. Therefore, paediatric pharmacovigillance aspects need to be tailored to a number of variables based on heterogeneity of paediatric population. This chapter will summarize and discuss the key issues.

  2. Postmarketing surveillance for "modified-risk" tobacco products.

    PubMed

    O'Connor, Richard J

    2012-01-01

    The U.S. Food and Drug Administration (FDA) acquired authority to regulate tobacco products in 2009. This authority will provide a structured process for manufacturers to introduce products that may have "modified-risk" for morbidity or mortality relative to traditional tobacco products, with postmarketing surveillance and studies a condition of marketing. A narrative review approach was taken. The author searched and integrated publicly accessible literature on tobacco product surveillance as well as drug and medical device postmarket activities currently performed by FDA. FDA relies on active and passive methods for postmarket surveillance and can require specific studies and risk evaluation and mitigation strategies for certain products, including those with abuse liability. Past efforts at examining the individual and population effects of reduced harm tobacco products provide an example of integrating different data streams. Postmarket surveillance can be viewed in terms of the Agent-Host-Vector-Environment model, and concepts from diffusion of innovations are relevant to understanding factors associated with the adoption of new products by the population. Given that active and passive surveillance approaches have different strengths and weaknesses, multiple approaches may be necessary to evaluate population-level effects. Assuring that required studies are properly conducted and reported and that data indicating significant public health harms are quickly recognized will be important going forward. The advent of broad regulatory authority over tobacco provides opportunities for policy evaluation research. The research community can provide FDA with the independent science it needs to evaluate the public health impact of novel tobacco products.

  3. Postmarketing Surveillance for “Modified-Risk” Tobacco Products

    PubMed Central

    2012-01-01

    Introduction: The U.S. Food and Drug Administration (FDA) acquired authority to regulate tobacco products in 2009. This authority will provide a structured process for manufacturers to introduce products that may have “modified-risk” for morbidity or mortality relative to traditional tobacco products, with postmarketing surveillance and studies a condition of marketing. Method: A narrative review approach was taken. The author searched and integrated publicly accessible literature on tobacco product surveillance as well as drug and medical device postmarket activities currently performed by FDA. Results: FDA relies on active and passive methods for postmarket surveillance and can require specific studies and risk evaluation and mitigation strategies for certain products, including those with abuse liability. Past efforts at examining the individual and population effects of reduced harm tobacco products provide an example of integrating different data streams. Discussion: Postmarket surveillance can be viewed in terms of the Agent–Host–Vector–Environment model, and concepts from diffusion of innovations are relevant to understanding factors associated with the adoption of new products by the population. Given that active and passive surveillance approaches have different strengths and weaknesses, multiple approaches may be necessary to evaluate population-level effects. Assuring that required studies are properly conducted and reported and that data indicating significant public health harms are quickly recognized will be important going forward. Conclusions: The advent of broad regulatory authority over tobacco provides opportunities for policy evaluation research. The research community can provide FDA with the independent science it needs to evaluate the public health impact of novel tobacco products. PMID:21330282

  4. Postmarket surveillance of natural health products in Canada: clinical and federal regulatory perspectives.

    PubMed

    Murty, Mano

    2007-09-01

    Postmarket surveillance, particularly adverse reactions (ARs), forms an integral part of the ongoing safety evaluation for natural health products (NHPs). ARs can be related to many factors, including inherent toxicity, misuse, hypersensitivity, NHP-drug interactions, or product quality. High consumer use and limited safety and efficacy data from human clinical trials for many NHPs present a challenge to consumers, healthcare practitioners, and federal regulators. Canada's Natural Health Products Regulations mandate NHPs to be licensed. As the currently available unauthorized NHPs are being brought into compliance in Canada, the transition has produced some challenges, requiring ongoing public communication and education to promote the safe use of NHPs. This article will highlight Health Canada's key postmarket initiatives in strengthening the regulation of NHPs.

  5. Development, Production, and Postmarketing Surveillance of Hepatitis A Vaccines in China

    PubMed Central

    Cui, Fuqiang; Liang, Xiaofeng; Wang, Fuzhen; Zheng, Hui; Hutin, Yvan J; Yang, Weizhong

    2014-01-01

    China has long experience using live attenuated and inactivated vaccines against hepatitis A virus (HAV) infection. We summarize this experience and provide recent data on adverse events after immunization (AEFIs) with hepatitis A vaccines in China. We reviewed the published literature (in Chinese and English) and the published Chinese regulatory documents on hepatitis A vaccine development, production, and postmarketing surveillance of AEFI. We described the safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine was associated with fever (0.4%–5% of vaccinees), rash (0%–1.1%), and elevated alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with fever (1%–8%), but no serious AEFIs were reported. Live HAV vaccine had seroconversion rates of 83% to 91%, while inactivated HAV vaccine had seroconversion rates of 95% to 100%. Community trials showed efficacy rates of 90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine. Postmarketing surveillance showed that HAV vaccination resulted in an AEFI incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse events reported to the China AEFI monitoring system. There was no difference in AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV vaccines manufactured in China were immunogenic, effective, and safe. Live HAV vaccine had substantial horizontal transmission due to vaccine virus shedding; thus, further monitoring of the safety of virus shedding is warranted. PMID:24681843

  6. New horizons in post-marketing surveillance.

    PubMed

    Waller, P; Wood, S

    1993-01-01

    Post-marketing surveillance is the process of monitoring and evaluating the safety of marketed medicines using a variety of methods. However, many doctors believe that post-marketing surveillance has a more limited meaning, ie an observational study of a new medicine sponsored by a pharmaceutical company. Although such studies were performed extensively in the United Kingdom during the 1980s, few have been published. Their purpose was to study large populations of users in ordinary practice with the aim of identifying hazards that had been missed, because clinical trials were too small, too short or did not always reflect real life. To some extent these studies have now fallen into disrepute, both on scientific grounds and because they have often been thought to be a thinly-disguised promotional exercise. The purpose of this article is to examine some of the previous problems with post-marketing surveillance and to propose new directions for the future.

  7. 77 FR 52745 - Leveraging Registries With Medical Device Data for Postmarket Surveillance and Evidence Appraisal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... Postmarket Surveillance and Evidence Appraisal Throughout the Total Product Life Cycle AGENCY: Food and Drug... Device Data for Postmarket Surveillance and Evidence Appraisal Throughout the Total Product Life Cycle... relatively short, product life-cycle. For these reasons, FDA's Center for Devices and Radiological...

  8. Registries in European post-marketing surveillance: a retrospective analysis of centrally approved products, 2005-2013.

    PubMed

    Bouvy, Jacoline C; Blake, Kevin; Slattery, Jim; De Bruin, Marie L; Arlett, Peter; Kurz, Xavier

    2017-03-26

    Regulatory agencies and other stakeholders increasingly rely on data collected through registries to support their decision-making. Data from registries are a cornerstone of post-marketing surveillance for monitoring the use of medicines in clinical practice. This study was aimed at gaining further insight into the European Medicines Agency's (EMA) requests for new registries and registry studies using existing registries and to review the experience gained in their conduct. European Public Assessment Reports were consulted to identify products for which a request for a registry was made as a condition of the marketing authorisation. All centrally authorised products that received a positive opinion of the EMA Committee for Medicinal Products for Human Use between 1 January 2005 and 31 December 2013 were included. Data regarding registry design and experiences were collected from EMA electronic record keeping systems. Of 392 products that received a positive Committee for Medicinal Products for Human Use opinion during 2005-2013, 31 registries were requested for 30 products in total. Sixty-five percent were product registries whereas 35% were disease registries and 71% of the registries had a primary safety objective. Most commonly reported issues with registries were delayed time to start and low patient accrual rates. The delays found in getting new registries up and running support the need to improve the timeliness of data collection in the post-marketing setting. Methodological challenges met in conducting this study highlighted the need for a clarification of definitions and epidemiological concepts around patient registries. The results will inform the EMA Patient Registry initiative to support use of existing patient registries for the post-authorisation benefit-risk monitoring of medicinal products. © 2017 Commonwealth of Australia. Pharmacoepidemiology & Drug Safety StartCopText© 2017 John Wiley & Sons, Ltd. © 2017 Commonwealth of Australia

  9. Active surveillance of postmarket medical product safety in the Federal Partners' Collaboration.

    PubMed

    Robb, Melissa A; Racoosin, Judith A; Worrall, Chris; Chapman, Summer; Coster, Trinka; Cunningham, Francesca E

    2012-11-01

    After half a century of monitoring voluntary reports of medical product adverse events, the Food and Drug Administration (FDA) has launched a long-term project to build an adverse events monitoring system, the Sentinel System, which can access and evaluate electronic health care data to help monitor the safety of regulated medical products once they are marketed. On the basis of experience gathered through a number of collaborative efforts, the Federal Partners' Collaboration pilot project, involving FDA, the Centers for Medicare & Medicaid Services, the Department of Veteran Affairs, and the Department of Defense, is already enabling FDA to leverage the power of large public health care databases to assess, in near real time, the utility of analytical tools and methodologies that are being developed for use in the Sentinel System. Active medical product safety surveillance is enhanced by use of these large public health databases because specific populations of exposed patients can be identified and analyzed, and can be further stratified by key variables such as age, sex, race, socioeconomic status, and basis for eligibility to examine important subgroups.

  10. Postmarketing surveillance of quinolones, 1990 to 1992.

    PubMed

    Davey, P; McDonald, T

    1993-01-01

    During the last 2 years, the major event in the postmarketing surveillance of quinolones has been the worldwide withdrawal of temafloxacin after only 15 weeks on the USA market. The Adverse Drug Reaction (ADR) reports that led to the withdrawal have been reviewed and show that the frequency and type of ADR and serious ADR were highly unusual in comparison with other quinolones marketed in the USA (ciprofloxacin, norfloxacin and ofloxacin). The difficulty in establishing causality between drugs and ADRs is discussed. Prescription event monitoring and computerised databases are beginning to reach the size required to pick up rare ADRs but, even so, they can only establish association rather than causality. Perhaps a more important question is the issue of acceptable risk. This requires better definition in order to apply decision analysis to the options available for the treatment of bacterial infections.

  11. Postmarketing surveillance: practical experience with ketotifen.

    PubMed Central

    Maclay, W P; Crowder, D; Spiro, S; Turner, P

    1984-01-01

    In a postmarketing surveillance of ketotifen (Zaditen), an oral preparation for the prophylaxis of bronchial asthma, 8291 patients completed records every three months for one year. The objectives were to record adverse events and efficacy and to communicate appropriate information to participating doctors and regulatory authorities. The patients recruited appeared to represent a typical cross section of patients with asthma in the United Kingdom. By subjective assessment 70% of patients found the medication efficacious. There were no unexpected or unacceptable side effects and those found were similar to those reported in clinical trials of ketotifen. Though this exercise showed that the pharmaceutical industry, regulatory authorities, and prescribing doctors were able to collaborate, the major outcome of the survey was already known. It remains to be seen whether this type of survey is of value in the continuing search for control and safety in prescribing. PMID:6423140

  12. 21 CFR 822.5 - How will I know if I must conduct postmarket surveillance?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... surveillance? 822.5 Section 822.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.5 How will I know if I must conduct postmarket surveillance? We will send you a letter (the postmarket surveillance order) notifying...

  13. 21 CFR 822.8 - When, where, and how must I submit my postmarket surveillance plan?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... surveillance plan? 822.8 Section 822.8 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.8 When, where, and how must I submit my postmarket surveillance plan? You must submit your plan to...

  14. 21 CFR 822.5 - How will I know if I must conduct postmarket surveillance?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... surveillance? 822.5 Section 822.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.5 How will I know if I must conduct postmarket surveillance? We will send you a letter (the postmarket surveillance order) notifying...

  15. 21 CFR 822.5 - How will I know if I must conduct postmarket surveillance?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... surveillance? 822.5 Section 822.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.5 How will I know if I must conduct postmarket surveillance? We will send you a letter (the postmarket surveillance order) notifying...

  16. 21 CFR 822.5 - How will I know if I must conduct postmarket surveillance?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... surveillance? 822.5 Section 822.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.5 How will I know if I must conduct postmarket surveillance? We will send you a letter (the postmarket surveillance order) notifying...

  17. 21 CFR 822.8 - When, where, and how must I submit my postmarket surveillance plan?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... surveillance plan? 822.8 Section 822.8 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.8 When, where, and how must I submit my postmarket surveillance plan? You must submit your plan to...

  18. 21 CFR 822.5 - How will I know if I must conduct postmarket surveillance?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... surveillance? 822.5 Section 822.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.5 How will I know if I must conduct postmarket surveillance? We will send you a letter (the postmarket surveillance order) notifying...

  19. 21 CFR 822.30 - May I request exemption from the requirement to conduct postmarket surveillance?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... conduct postmarket surveillance? 822.30 Section 822.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Waivers and Exemptions § 822.30 May I request exemption from the requirement to conduct postmarket surveillance? You may...

  20. 21 CFR 822.30 - May I request exemption from the requirement to conduct postmarket surveillance?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... conduct postmarket surveillance? 822.30 Section 822.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Waivers and Exemptions § 822.30 May I request exemption from the requirement to conduct postmarket surveillance? You may...

  1. 21 CFR 822.30 - May I request exemption from the requirement to conduct postmarket surveillance?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... conduct postmarket surveillance? 822.30 Section 822.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Waivers and Exemptions § 822.30 May I request exemption from the requirement to conduct postmarket surveillance? You may...

  2. 21 CFR 822.11 - What should I consider when designing my plan to conduct postmarket surveillance?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... conduct postmarket surveillance? 822.11 Section 822.11 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.11 What should I consider when designing my plan to conduct postmarket surveillance...

  3. 21 CFR 822.11 - What should I consider when designing my plan to conduct postmarket surveillance?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... conduct postmarket surveillance? 822.11 Section 822.11 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.11 What should I consider when designing my plan to conduct postmarket surveillance...

  4. 21 CFR 822.11 - What should I consider when designing my plan to conduct postmarket surveillance?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... conduct postmarket surveillance? 822.11 Section 822.11 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.11 What should I consider when designing my plan to conduct postmarket surveillance...

  5. 21 CFR 822.11 - What should I consider when designing my plan to conduct postmarket surveillance?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... conduct postmarket surveillance? 822.11 Section 822.11 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.11 What should I consider when designing my plan to conduct postmarket surveillance...

  6. Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies

    PubMed Central

    Sinaci, A. Anil; Laleci Erturkmen, Gokce B.; Gonul, Suat; Yuksel, Mustafa; Invernizzi, Paolo; Thakrar, Bharat; Pacaci, Anil; Cinar, H. Alper; Cicekli, Nihan Kesim

    2015-01-01

    Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR) data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases. PMID:26543873

  7. Postmarketing surveillance versus clinical trials: which benefits the patient?

    PubMed

    Lawson, D H

    1994-01-01

    Both randomized controlled clinical trials and observational postmarketing surveillance studies have a place in providing information to physicians and patients on effectiveness and safety of new medicines. Prelicensing is the realm of the basic scientist producing a medicine which is available for investigation by clinical trial. In this context, manufacturers attempt to define the efficacy for desired indications and to establish an appropriate dosage for the drug. To do so, they usually confine attention to idealized standard patients, excluding all complex problems, such as pregnancy, renal or other organ failure, comorbidity, the elderly, the child, and so forth. Postmarketing surveillance covers the range of observational studies undertaken after marketing including cohort studies, case-control studies, and spontaneous reports of suspected adverse drug reactions. These observational studies are less rigorous than clinical trials, but have the potential to provide information from a representative sample of 'real-life' patients. Neither postmarketing surveillance studies nor clinical trials are capable of answering questions fully. In future, record linkage techniques may play a greater role by providing information on data linking drug exposures and outcomes in general practice.

  8. Postmarketing surveillance study of permethrin creme rinse.

    PubMed Central

    Andrews, E B; Joseph, M C; Magenheim, M J; Tilson, H H; Doi, P A; Schultz, M W

    1992-01-01

    BACKGROUND. An observational, epidemiological study was undertaken to evaluate the safety of permethrin 1% creme rinse (Nix) for treatment of head lice infestations. METHODS. Thirty-seven local public health departments enrolled a total of 38,160 patients for 47,578 treatments with permethrin or other pediculicides from September 1, 1986, through January 31, 1988. Follow-up safety information was collected between 7 and 14 days following treatment via return visit or telephone contact. RESULTS. One hundred three adverse events were reported among 41,955 evaluable treatments. The rates of reported adverse events were 2.2 per 1000 treatments among permethrin treatments, 3.4 per 1000 treatments among lindane treatments, and 1.5 per 1000 treatments among other over-the-counter treatments. No serious, unexpected adverse events were detected in the 18,950 patients treated with permethrin. CONCLUSIONS. This study confirmed the safety profile of permethrin in conditions of general use, as seen in clinical trials. Postmarketing safety monitoring in public health departments of drugs used to treat public health conditions was shown to be feasible. PMID:1375002

  9. 21 CFR 822.8 - When, where, and how must I submit my postmarket surveillance plan?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.8.... For devices regulated by the Center for Biologics Evaluation and Research, send three copies of your submission to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food...

  10. 21 CFR 822.8 - When, where, and how must I submit my postmarket surveillance plan?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Postmarket Surveillance Plan § 822.8.... For devices regulated by the Center for Biologics Evaluation and Research, send three copies of your submission to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food...

  11. Social Media Listening for Routine Post-Marketing Safety Surveillance.

    PubMed

    Powell, Gregory E; Seifert, Harry A; Reblin, Tjark; Burstein, Phil J; Blowers, James; Menius, J Alan; Painter, Jeffery L; Thomas, Michele; Pierce, Carrie E; Rodriguez, Harold W; Brownstein, John S; Freifeld, Clark C; Bell, Heidi G; Dasgupta, Nabarun

    2016-05-01

    Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. A third-party vendor acquired 24 months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26 % of posts also contained benefit information. Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

  12. 21 CFR 822.6 - When will you notify me that I am required to conduct postmarket surveillance?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... conduct postmarket surveillance? 822.6 Section 822.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.6 When will you notify me that I am required to conduct postmarket surveillance? We will notify...

  13. 21 CFR 822.28 - If I stop marketing the device subject to postmarket surveillance, what must I do?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... postmarket surveillance, what must I do? 822.28 Section 822.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Responsibilities of Manufacturers § 822.28 If I stop marketing the device subject to postmarket surveillance, what...

  14. 21 CFR 822.6 - When will you notify me that I am required to conduct postmarket surveillance?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... conduct postmarket surveillance? 822.6 Section 822.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.6 When will you notify me that I am required to conduct postmarket surveillance? We will notify...

  15. 21 CFR 822.6 - When will you notify me that I am required to conduct postmarket surveillance?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... conduct postmarket surveillance? 822.6 Section 822.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.6 When will you notify me that I am required to conduct postmarket surveillance? We will notify...

  16. 21 CFR 822.28 - If I stop marketing the device subject to postmarket surveillance, what must I do?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... postmarket surveillance, what must I do? 822.28 Section 822.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Responsibilities of Manufacturers § 822.28 If I stop marketing the device subject to postmarket surveillance, what...

  17. 21 CFR 822.6 - When will you notify me that I am required to conduct postmarket surveillance?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... conduct postmarket surveillance? 822.6 Section 822.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.6 When will you notify me that I am required to conduct postmarket surveillance? We will notify...

  18. 21 CFR 822.28 - If I stop marketing the device subject to postmarket surveillance, what must I do?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... postmarket surveillance, what must I do? 822.28 Section 822.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Responsibilities of Manufacturers § 822.28 If I stop marketing the device subject to postmarket surveillance, what...

  19. 21 CFR 822.6 - When will you notify me that I am required to conduct postmarket surveillance?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... conduct postmarket surveillance? 822.6 Section 822.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Notification § 822.6 When will you notify me that I am required to conduct postmarket surveillance? We will notify...

  20. An epidemiologic postmarketing surveillance study of prescription acne medications.

    PubMed Central

    Facklam, D P; Gardner, J S; Neidert, G L; Westland, M M

    1990-01-01

    After the Food and Drug Administration approved a topical antibiotic for the treatment of acne, we began a postmarketing surveillance study to measure the frequency of antibiotic-associated colitis and diarrhea in acne patients treated with topical antibiotics and low doses of oral antibiotics. Pharmacists recruited 13,465 patients who presented a prescription for an acne medication, and we obtained detailed information on the use of the medications, perceived acceptability, and the occurrence of new health events from 6,453 with computer-assisted telephone interviews. Three cases (less than 0.1%) of antibiotic-associated diarrhea and one case (less than 0.1%) of antibiotic-associated colitis were confirmed. We conclude that this methodology can provide further information about the safety of a drug once it is in customary use, at a fraction of the cost of Phase III clinical trials. PMID:2136713

  1. Japanese Physicians’ Views on Drug Post-Marketing Surveillance

    PubMed Central

    Maeda, Kazuki; Katashima, Rumi; Ishizawa, Keisuke; Yanagawa, Hiroaki

    2015-01-01

    Background Registration trials leading to the approval of drugs are paramount in drug development. After approval, continuous efforts are necessary to ensure proper use of the approved drugs. In Japan, post-marketing surveillance (PMS) by drug companies is conducted in accordance with good post-marketing study practice (GPSP). Although the global standard for pharmacovigilance is incorporated into GPSP, attention has recently been focused on disassociating them. In this study, we examined physicians’ views on PMS with the aim of conducting PMS more effectively. Methods We retrospectively reviewed records between 2009 and 2013 from the institutional review board of Tokushima University Hospital, an academic hospital in rural Japan. The annual number of times PMS was performed was then determined. Next, we assessed physicians’ attitudes toward drug PMS, including ethical issues, in a cross-sectional study using a questionnaire designed for this study. Five- and two-point scales were used. The questionnaire was distributed in 2014 to 221 physicians listed as investigators in PMS contracts. Results Of the 221 physicians, 103 (46.6%) responded to the questionnaire. About 50% of the respondents had experience writing PMS reports. Many of the physicians considered PMS to be important but burdensome. Furthermore, from the viewpoint of research ethics, many physicians considered it improper within the present PMS framework to collect and provide data beyond the scope of routine clinical practice without obtaining informed consent in the case of extra blood sampling, provision of images, monitoring and controlled studies. Conclusions Beyond practical factors such as workload, attention should be given to establishing an ethical infrastructure and globally harmonized system with regard to the Japanese PMS system. Given the limitations of this single-institution study, further research is needed to collect information for developing a suitable infrastructure. PMID:26566409

  2. Japanese Physicians' Views on Drug Post-Marketing Surveillance.

    PubMed

    Maeda, Kazuki; Katashima, Rumi; Ishizawa, Keisuke; Yanagawa, Hiroaki

    2015-12-01

    Registration trials leading to the approval of drugs are paramount in drug development. After approval, continuous efforts are necessary to ensure proper use of the approved drugs. In Japan, post-marketing surveillance (PMS) by drug companies is conducted in accordance with good post-marketing study practice (GPSP). Although the global standard for pharmacovigilance is incorporated into GPSP, attention has recently been focused on disassociating them. In this study, we examined physicians' views on PMS with the aim of conducting PMS more effectively. We retrospectively reviewed records between 2009 and 2013 from the institutional review board of Tokushima University Hospital, an academic hospital in rural Japan. The annual number of times PMS was performed was then determined. Next, we assessed physicians' attitudes toward drug PMS, including ethical issues, in a cross-sectional study using a questionnaire designed for this study. Five- and two-point scales were used. The questionnaire was distributed in 2014 to 221 physicians listed as investigators in PMS contracts. Of the 221 physicians, 103 (46.6%) responded to the questionnaire. About 50% of the respondents had experience writing PMS reports. Many of the physicians considered PMS to be important but burdensome. Furthermore, from the viewpoint of research ethics, many physicians considered it improper within the present PMS framework to collect and provide data beyond the scope of routine clinical practice without obtaining informed consent in the case of extra blood sampling, provision of images, monitoring and controlled studies. Beyond practical factors such as workload, attention should be given to establishing an ethical infrastructure and globally harmonized system with regard to the Japanese PMS system. Given the limitations of this single-institution study, further research is needed to collect information for developing a suitable infrastructure.

  3. 21 CFR 822.25 - What are my responsibilities after my postmarket surveillance plan has been approved?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... surveillance plan has been approved? 822.25 Section 822.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Responsibilities of Manufacturers § 822.25 What are my responsibilities after my postmarket surveillance plan has been...

  4. 21 CFR 822.25 - What are my responsibilities after my postmarket surveillance plan has been approved?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... surveillance plan has been approved? 822.25 Section 822.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Responsibilities of Manufacturers § 822.25 What are my responsibilities after my postmarket surveillance plan has been...

  5. 21 CFR 822.25 - What are my responsibilities after my postmarket surveillance plan has been approved?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... surveillance plan has been approved? 822.25 Section 822.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE Responsibilities of Manufacturers § 822.25 What are my responsibilities after my postmarket surveillance plan has been...

  6. Post-marketing surveillance and vigilance for medical devices: the European approach.

    PubMed

    Randall, H

    2001-01-01

    The extent to which the medical device manufacturers are responsible for actively monitoring the performance of their products after they have successfully passed the rigorous pre-market approval process has always been a matter of diverse opinion. Within Europe, the law is unhelpfully vague on this point. While there are some comparatively clear obligations for reporting incidents to the authorities (known as the 'vigilance system'), little detail is given on how diligently the manufacturer should try to find out about such incidents. In the early stages of the European Community Directives covering medical devices, there was much emphasis upon formulating guidance to help interpret the vigilance reporting requirements. It is, however, only recently that attention has turned to attempting to clarify what is expected from post-marketing surveillance (PMS) in its broader sense. This article discuses both the vigilance and PMS processes and outlines the currently available European, and particularly UK, guidance documents which are aimed at promoting a more level playing field across industry where these activities are concerned. In particular, it explains the principle differences between vigilance and post-marketing surveillance: the former being the reporting of adverse incidents by manufacturers to the regulatory authorities and their subsequent sharing of key incident data between each other; the latter being the process by which information on overall devise performance is captured, analysed and acted upon. Nevertheless, it is still a struggle to gain widespread appreciation that these two activities are not in fact one and the same.

  7. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    PubMed

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. [Exploration of how to formulate guidelines on post-marketing traditional Chinese medicine surveillance].

    PubMed

    Zhang, Wen; Xie, Yan-Ming; Yu, Wen-Ya

    2013-09-01

    Combining the world health organization's (WHO), the United States and the European union's relevant laws and guidelines on post-marketing drug surveillance to judge the status of post-marketing surveillance of traditional Chinese medicine(TCM) in China. We found that due to the late start of post-marketing surveillance of traditional Chinese medicine, the appropriate guidelines are yet to be developed. Hence, hospitals, enterprises and research institutions do not have a shared foundation from which to compare their research results. Therefore there is an urgent need to formulate such post-marketing surveillance guidelines. This paper has used as guidance various technical documents such as, "procedures to formulate national standards" and "testing methods of management in formulating traditional Chinese medicine standards" and has combined these to produce a version of post-marketing surveillance particular to Chinese medicine in China. How to formulate these guidelines is discussed and procedures and methods to formulate technical specifications are introduced. These provide a reference for future technical specifications and will assist in the development of TCM.

  9. Monitoring product safety in the postmarketing environment.

    PubMed

    Sharrar, Robert G; Dieck, Gretchen S

    2013-10-01

    The safety profile of a medicinal product may change in the postmarketing environment. Safety issues not identified in clinical development may be seen and need to be evaluated. Methods of evaluating spontaneous adverse experience reports and identifying new safety risks include a review of individual reports, a review of a frequency distribution of a list of the adverse experiences, the development and analysis of a case series, and various ways of examining the database for signals of disproportionality, which may suggest a possible association. Regulatory agencies monitor product safety through a variety of mechanisms including signal detection of the adverse experience safety reports in databases and by requiring and monitoring risk management plans, periodic safety update reports and postauthorization safety studies. The United States Food and Drug Administration is working with public, academic and private entities to develop methods for using large electronic databases to actively monitor product safety. Important identified risks will have to be evaluated through observational studies and registries.

  10. Patients' motives for participating in active post-marketing surveillance.

    PubMed

    Härmark, Linda; Lie-Kwie, Miguel; Berm, Lisette; de Gier, Han; van Grootheest, Kees

    2013-01-01

    Web-based intensive monitoring is a method to actively collect information about adverse drug reactions (ADRs) using patients as a source of information. To date, little is known about patients' motivation to participate in this kind of active post-marketing surveillance (PMS). Increased insight in this matter can help us to better understand and interpret patient reported information, and it can be used for developing and improving patient-based pharmacovigilance tools. The aim of this study is to gain insight into patients' motives for participating in active PMS and investigate their experiences with such a system. A mixed model approach combining qualitative and quantitative research methods was used. For both parts, patients participating in a web-based intensive monitoring study about the safety of anti-diabetic drugs (excluding insulins) were used. A questionnaire was developed based on the results from qualitative interviews. The data collected through the questionnaires was analysed with descriptive statistics. Relations between patient characteristics and motives were analysed using a t-test or a Chi-squared test. 1332 (54.6%) patients responded to the questionnaire. The main motive for participation was altruism. Often experiencing ADRs or negative experiences with drugs were not important motives. The patient's gender played a role in the different motives for participation. For men, potential future personal benefit from the results was more important than for women. The overall opinion about the system was positive. The knowledge that patients participate in this kind of research from an altruistic point of view may strengthen patient involvement in pharmacovigilance. Copyright © 2012 John Wiley & Sons, Ltd.

  11. [Research on foreign countries laws and regulations on surveillance and reporting of postmarketing drugs adverse reactions].

    PubMed

    Tian, Feng; Xie, Yanming

    2009-06-01

    Following more and more new drugs are authorized into market, new, serious or unexpected adverse drug reactions appear frequently, which is a serious threat to people health and life. Through making laws and guidelines, governments of various countries aim to strengthen and standardize the surveillance and reporting of postmarketing drugs. The drugs management department of our country are doing related jobs positively, but there are some problems, such as drug risk-menagement is not emphasized well, and the management department lacks clarity on operating related regulations. This article tries to explore foreign countries' laws and regulations on the surveillance and reporting of postmarketing drugs, aiming to provide reference for our courtry.

  12. 21 CFR 822.15 - How long must I conduct postmarket surveillance of my device?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false How long must I conduct postmarket surveillance of my device? 822.15 Section 822.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Radiological Health's (CDRH') Web site...

  13. 21 CFR 822.15 - How long must I conduct postmarket surveillance of my device?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false How long must I conduct postmarket surveillance of my device? 822.15 Section 822.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Radiological Health's (CDRH') Web site (www.fda.gov/cdrh/ombudsman/). The 36-month period refers to...

  14. 21 CFR 822.15 - How long must I conduct postmarket surveillance of my device?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false How long must I conduct postmarket surveillance of my device? 822.15 Section 822.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Radiological Health's (CDRH') Web site...

  15. 21 CFR 822.15 - How long must I conduct postmarket surveillance of my device?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false How long must I conduct postmarket surveillance of my device? 822.15 Section 822.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Radiological Health's (CDRH') Web site (www.fda.gov/cdrh/ombudsman/). The 36-month period refers to...

  16. 21 CFR 822.15 - How long must I conduct postmarket surveillance of my device?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false How long must I conduct postmarket surveillance of my device? 822.15 Section 822.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Radiological Health's (CDRH') Web site (www.fda.gov/cdrh/ombudsman/). The 36-month period refers to...

  17. A post-marketing surveillance study of formoterol (Foradil): its use in general practice in England.

    PubMed

    Wilton, Lynda V; Shakir, Saad A

    2002-01-01

    At the time of marketing, experience of long-term use of prescription medicines in general clinical practice is limited. Postmarketing surveillance is particularly important at this time when medicines may be prescribed to large numbers of patients of all ages, for long-term use. Following marketing of formoterol (Foradil) in the UK in 1996 we undertook a postmarketing surveillance study of formoterol use in general practice. A non-interventional observational cohort study was conducted using the technique of prescription-event monitoring. Exposure data were obtained from prescription details; outcome data from questionnaires sent to general practitioners approximately 12 months after the first prescription was dispensed for individual patients. Incidence rates were calculated for reported events, reasons for stopping treatment and outcomes of pregnancy were determined. Data were collected for 5777 patients aged 3 to 96 years, 65% of whom continued treatment for >12 months. Formoterol was prescribed 'off label', to 258 children, (4.5%) of the cohort. The most commonly reported events excluding those related to respiratory disease, were headache, tremor, palpitation, cramp and nausea/vomiting. These events were also among the more common reasons for stopping treatment and reported as suspected adverse drug reactions. 33 patients took formoterol during pregnancy. The cause of death was established for 186 of the 190 deaths (3% of cohort). Formoterol appears to have been well tolerated by the majority of patients in this study. The most frequently reported adverse events were those known to be associated with beta(2)-agonists, although the frequency of nausea/ vomiting was greater than given in Summary of Product Characteristics.

  18. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

    PubMed

    Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

    2014-10-07

    Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

    PubMed

    Silva, Ivair R

    2017-09-25

    Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Identifying optimal postmarket surveillance strategies for medical and surgical devices: implications for policy, practice and research.

    PubMed

    Gagliardi, Anna R; Umoquit, Muriah; Lehoux, Pascale; Ross, Sue; Ducey, Ariel; Urbach, David R

    2013-03-01

    Non-drug technologies offer many benefits, but have been associated with adverse events, prompting calls for improved postmarket surveillance. There is little empirical research to guide the development of such a system. The purpose of this study was to identify optimal postmarket surveillance strategies for medical and surgical devices. Qualitative methods were used for sampling, data collection and analysis. Stakeholders from Canada and the USA representing different roles and perspectives were first interviewed to identify examples and characteristics of different surveillance strategies. These stakeholders and others they recommended were then assembled at a 1-day nominal group meeting to discuss and prioritise the components of a postmarket device surveillance system, and research needed to achieve such a system. Consultations were held with 37 participants, and 47 participants attended the 1-day meeting. They recommended a multicomponent system including reporting by facilities, clinicians and patients, supported with some external surveillance for validation and real-time trials for high-risk devices. Many considerations were identified that constitute desirable characteristics of, and means by which to implement such a system. An overarching network was envisioned to broker linkages, establish a shared minimum dataset, and support communication and decision making. Numerous research questions were identified, which could be pursued in tandem with phased implementation of the system. These findings provide unique guidance for establishing a device safety network that is based on existing initiatives, and could be expanded and evaluated in a prospective, phased fashion as it was developed.

  1. National post-market surveillance assessment of veterinary medicines in Korea during the past decade.

    PubMed

    Kang, JeongWoo; Park, Hae-Chul; Jang, Yang Ho; Hossain, Md Akil; Jeong, Kyunghun; Jeong, Mi Young; Yun, Seon-Jong; Park, Sung-Won; Kim, Dae Gyun; Lee, Kwang-Jick

    2017-05-22

    Veterinary medicines have been widely used for the prevention and treatment of diseases, growth promotion, and to promote feeding efficacy in livestock. As the veterinary medicine industry has steadily grown, it is crucial to set up a baseline for the quality of medicine as well as the insufficiency or excessiveness of the active ingredients in drug products to ensure the compliance, safety and efficacy of these medicines. Thus, the 10 years data of post-marketing quality control study was summarized to determine the rate and extent of non-compliance of these medicines and to establish baseline data for future quality control measures of veterinary medicine. In this study, 1650 drugs for veterinary use were collected per year from each city and province in Korea and analysed for the quantity of active ingredients according to the "national post-market surveillance (NPMS) system" over the past decade. The NPMS assessment was performed using liquid and gas chromatography, titration, UV/Vis spectrophotometry, and bioassays. A total of 358 cases were deemed noncompliant, with the average noncompliance rate for all medicine types being 2.0%. The average noncompliance rates for antibiotics, biologics and other chemical drugs except antibiotics (OCD) were 1.1%, 1.2%, and 3.0%, respectively. The first leading cause for noncompliant products was insufficient quantity of major ingredients (283 cases), and the second leading cause was the existence of excess amount of active ingredients (60 cases). Tylosin, spiramycin, ampicillin, tetracyclines and penicillins were most frequently found to be noncompliant among antibiotics. Among the OCD, the noncompliance was found commonly in vitamin A. The overall trend presented gradually decreasing violation rates, suggesting that the quality of veterinary medicines has improved. Consistent application of the NPMS assessment and the establishment of the Korea Veterinary Good Manufacturing Practice (KVGMP) will help to maintain the good

  2. Postmarketing surveillance of adverse drug reactions: problems and solutions.

    PubMed Central

    Lortie, F M

    1986-01-01

    The surveillance of adverse drug reactions (ADRs) is an unqualified must. However, the optimal means of surveillance is still unclear. Although anecdotal reports are the backbone of an ADR surveillance system, they are not enough. The pharmaceutical industry, academics and regulatory agencies need to expand their efforts in monitoring ADRs. The author discusses the various techniques for counting and evaluating adverse reactions and suggests ways in which the system could be improved. PMID:3719483

  3. [Withdrawal of cerivastatin revealed a flaw of post-marketing surveillance system in the United States].

    PubMed

    Saito, Mitsuo; Hirata-Koizumi, Mutsuko; Miyake, Shinji; Hasegawa, Ryuichi

    2005-01-01

    Cerivastatin, a lipid-lowering agent, was voluntarily withdrawn from the market because of high risk of rhabdomyolysis when used as monotherapy and as comedication with fibrates, especially gemfibrozil. Thereafter, investigators found a five-fold increase in the area under the curve (AUC) when cerivastatin was used as comedication with gemfibrozil and theorized that the increase was associated with inhibition of the hepatic uptake and metabolism. By contrast, a number of pharmacoepidemiological investigations--one of which involved evaluation of the Food and Drug Administration (FDA) database for suspected adverse drug reactions and 11 cohort studies of statin and fibrate users in United States showed the risk of rhabdomyolysis to be greater in cerivastatin than in other statins used in either monotherapy or in comedication with fibrates, especially gemfibrozil. This incident regarding risk of rhabdomyolysis in cerivastatin monotherapy was taken to court in the United States and unpublished company (manufacturer of cerivastatin) documents were opened. The incident was then analyzed and discussed in the Journal of American Medical Association (JAMA) as a concern of the current US post-marketing surveillance system. The company's action and timing were judged and found to be inappropriate (although companies of this sort generally have insurmountable conflicts of interest), and the work of the US regulatory system and funding for post-marketing safety management were found to be insufficient. On the basis of the current situation, the authors and editors recommend further improvement of post-marketing regulations including the establishment of an independent drug safety board to oversee post-marketing surveillance. Among the opened, unpublished data, was the finding that cerivastatin obviously induced myopathy in a dose-dependent manner when administrated as monotherapy. As for other statins, only limited data was available for the relationship between the dosage and

  4. Systematic review of reporting rates of adverse events following immunization: an international comparison of post-marketing surveillance programs with reference to China.

    PubMed

    Guo, Biao; Page, Andrew; Wang, Huaqing; Taylor, Richard; McIntyre, Peter

    2013-01-11

    China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse. To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally. Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages. Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3-37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3-181.1/100,000 doses for DTwP; range 3.5-92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world. Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Estimating post-marketing exposure to pharmaceutical products using ex-factory distribution data.

    PubMed

    Telfair, Tamara; Mohan, Aparna K; Shahani, Shalini; Klincewicz, Stephen; Atsma, Willem Jan; Thomas, Adrian; Fife, Daniel

    2006-10-01

    The pharmaceutical industry has an obligation to identify adverse reactions to drug products during all phases of drug development, including the post-marketing period. Estimates of population exposure to pharmaceutical products are important to the post-marketing surveillance of drugs, and provide a context for assessing the various risks and benefits, including drug safety, associated with drug treatment. This paper describes a systematic approach to estimating post-marketing drug exposure using ex-factory shipment data to estimate the quantity of medication available, and dosage information (stratified by indication or other factors as appropriate) to convert the quantity of medication to person time of exposure. Unlike the non-standardized methods often used to estimate exposure, this approach provides estimates whose calculations are explicit, documented, and consistent across products and over time. The methods can readily be carried out by an individual or small group specializing in this function, and lend themselves to automation. The present estimation approach is practical and relatively uncomplicated to implement. We believe it is a useful innovation.

  6. 21 CFR 822.21 - What must I do if I want to make changes to my postmarket surveillance plan after you have...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What must I do if I want to make changes to my postmarket surveillance plan after you have approved it? 822.21 Section 822.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES POSTMARKET SURVEILLANCE...

  7. [The problem of post-marketing surveillance planning on drugs for infectious disease].

    PubMed

    Sato, J

    2001-12-01

    In principle, a new drug is approved via the assessments of safety and efficacy by the Ministry of Health, Labor and Welfare (MHLW). After approval, conduct of post-marketing surveillance is requested by law in order to assess the safety and efficacy of the drug in a large number of patients. Before initiating a surveillance, submission to MHLW of a document on the plan of survey is necessary in the purpose of inspection if it includes any ethical or regulatory problem or not. Through the inspections of the plans submitted during the period of April 1998 and March 2000, many problems have been pointed out. In this report, the author introduces some of the concrete problems noted in the plans on drugs for infectious diseases and shows some of the guidance made by the authority how to improve them. It is expected that such practical analyses of cases may be useful for future planning of post-marketing surveillance on drugs for infectious diseases.

  8. Continuous versus group sequential analysis for post-market drug and vaccine safety surveillance.

    PubMed

    Silva, I R; Kulldorff, M

    2015-09-01

    The use of sequential statistical analysis for post-market drug safety surveillance is quickly emerging. Both continuous and group sequential analysis have been used, but consensus is lacking as to when to use which approach. We compare the statistical performance of continuous and group sequential analysis in terms of type I error probability; statistical power; expected time to signal when the null hypothesis is rejected; and the sample size required to end surveillance without rejecting the null. We present a mathematical proposition to show that for any group sequential design there always exists a continuous sequential design that is uniformly better. As a consequence, it is shown that more frequent testing is always better. Additionally, for a Poisson based probability model and a flat rejection boundary in terms of the log likelihood ratio, we compare the performance of various continuous and group sequential designs. Using exact calculations, we found that, for the parameter settings used, there is always a continuous design with shorter expected time to signal than the best group design. The two key conclusions from this article are (i) that any post-market safety surveillance system should attempt to obtain data as frequently as possible, and (ii) that sequential testing should always be performed when new data arrives without deliberately waiting for additional data.

  9. An introduction to analytical methods for the postmarketing surveillance of veterinary vaccines.

    PubMed

    Siev, D

    1999-01-01

    USDA. In quantitative summaries, AERs received from lay consumers are usually weighted equally with those received from veterinary health professionals, although arguments have been advanced for separate classifications. The emphasis on AER rate estimation differentiates the surveillance of veterinary vaccines by the USDA CVB from the surveillance of veterinary drugs as practiced by the Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM). The FDA CVM does, in fact, perform a retrodictive causality assessment for individual AERs (Parkhie et al., 1995). This distinction reflects the differences between vaccines and drugs, as well as the difference in regulatory philosophy between the FDA and the USDA. The modified Kramer algorithm (Kramer et al., 1979) used by the FDA relies on features more appropriate to drug therapy than vaccination, such as an ongoing treatment regimen which allows evaluation of the response to dechallenge and rechallenge. In tracking AERs, the FDA has emphasized the inclusion of clinical manifestations on labels and inserts, while the USDA has been reluctant to have such information appear in product literature or to use postmarketing data for this purpose. The potential for the misuse of spontaneous AER data is great. Disinformation is likely when the nature of this type of data is misunderstood and inappropriate analytical methods blindly employed. A greater danger lies in the glib transformation of AER data into something else entirely. Since approval before publication is not required, advertisements for veterinary vaccines appear with claims such as "over 3 million doses, 99.9905% satisfaction rating," or "11,500,000 doses, 99.98% reaction free." These claims, presumably based on spontaneous AERs, are almost fraudulent in their deceptiveness. Are we to suppose that 11.5 million vaccinations were observed for reactions? In comparing the two advertisements, we find the second presumed AER rate is double the first. (ABSTRACT

  10. The ethics of post-marketing surveillance of therapeutic agents.

    PubMed

    Beran, R G

    2001-01-01

    Trials of new therapies have strict codes of conduct which expect the highest of ethical practice. Local ethics committees review protocols, patient information, consent. National research councils delineate guidelines for minimum standards regarding subjects in such trials. Once medications enter the market place, there is less definition of minimal codes of conduct. Clinical trials are designed to meet regulatory demands to access commercial markets. Prior to marketing, there is a usual drug trial exposure of less than 5,000 individuals which diminishes identification of rare adverse events. Australian case law has found negligence for not warning of a 1:14,000 risk of sympathetic ophthalmia and more recently, in Chappel v Hart, even a speculative risk was grounds for negligence. Recent reports of serious adverse events for conditions such as epilepsy or depression resulted in companies appearing to expend considerable effort to suppress concern rather than to seriously investigate these complications in the post marketing period. This paper will explore such cases and discuss approaches to improve post marketing surveillance and patient protection.

  11. Post-market surveillance to detect adverse events associated with Melody® valve implantation.

    PubMed

    Hill, Kevin D; Goldstein, Bryan H; Angtuaco, Michael J; Chu, Patricia Y; Fleming, Gregory A

    2017-08-01

    The aim of this study was to describe previously unrecognised or under-recognised adverse events associated with Melody® valve implantation. In rare diseases and conditions, it is typically not feasible to conduct large-scale safety trials before drug or device approval. Therefore, post-market surveillance mechanisms are necessary to detect rare but potentially serious adverse events. We reviewed the United States Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database and conducted a structured literature review to evaluate adverse events associated with on- and off-label Melody® valve implantation. Adverse events were compared with those described in the prospective Investigational Device Exemption and Post-Market Approval Melody® transcatheter pulmonary valve trials. We identified 631 adverse events associated with "on-label" Melody® valve implants and 84 adverse events associated with "off-label" implants. The most frequent "on-label" adverse events were similar to those described in the prospective trials including stent fracture (n=210) and endocarditis (n=104). Previously unrecognised or under-recognised adverse events included stent fragment embolisation (n=5), device erosion (n=4), immediate post-implant severe valvar insufficiency (n=2), and late coronary compression (n=2 cases at 5 days and 3 months after implantation). Under-recognised adverse events associated with off-label implantation included early valve failure due to insufficiency when implanted in the tricuspid position (n=7) and embolisation with percutaneous implantation in the mitral position (n=5). Post-market passive surveillance does not demonstrate a high frequency of previously unrecognised serious adverse events with "on-label" Melody® valve implantation. Further study is needed to evaluate safety of "off-label" uses.

  12. Combining multiple healthcare databases for postmarketing drug and vaccine safety surveillance: why and how?

    PubMed

    Trifirò, G; Coloma, P M; Rijnbeek, P R; Romio, S; Mosseveld, B; Weibel, D; Bonhoeffer, J; Schuemie, M; van der Lei, J; Sturkenboom, M

    2014-06-01

    A growing number of international initiatives (e.g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e.g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.

  13. Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin

    PubMed Central

    Hajak, Göran; Lemme, Kathrin

    2015-01-01

    Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1–2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1–5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep–wake cycle stabilization with PRM in the treatment of insomnia. PMID:25054634

  14. Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin.

    PubMed

    Hajak, Göran; Lemme, Kathrin; Zisapel, Nava

    2015-01-01

    Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each, <1%). There were no serious adverse events and no adverse events were reported after discontinuation. The persisting treatment effect and very low rebound rate suggest a beneficial role of sleep-wake cycle stabilization with PRM in the treatment of insomnia.

  15. 21 CFR 822.7 - What should I do if I do not agree that postmarket surveillance is appropriate?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false What should I do if I do not agree that postmarket surveillance is appropriate? 822.7 Section 822.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Radiological Health's (CDRH's) Web site...

  16. 21 CFR 822.7 - What should I do if I do not agree that postmarket surveillance is appropriate?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false What should I do if I do not agree that postmarket surveillance is appropriate? 822.7 Section 822.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Radiological Health's (CDRH's) Web site (http://www.fda.gov/cdrh/ombudsman/dispute.html)....

  17. 21 CFR 822.7 - What should I do if I do not agree that postmarket surveillance is appropriate?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What should I do if I do not agree that postmarket surveillance is appropriate? 822.7 Section 822.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Radiological Health's (CDRH's) Web site (http://www.fda.gov/cdrh/ombudsman/dispute.html)....

  18. 21 CFR 822.7 - What should I do if I do not agree that postmarket surveillance is appropriate?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false What should I do if I do not agree that postmarket surveillance is appropriate? 822.7 Section 822.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Radiological Health's (CDRH's) Web site...

  19. 21 CFR 822.7 - What should I do if I do not agree that postmarket surveillance is appropriate?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false What should I do if I do not agree that postmarket surveillance is appropriate? 822.7 Section 822.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Radiological Health's (CDRH's) Web site (http://www.fda.gov/cdrh/ombudsman/dispute.html)....

  20. A distributed, collaborative intelligent agent system approach for proactive postmarketing drug safety surveillance.

    PubMed

    Ji, Yanqing; Ying, Hao; Farber, Margo S; Yen, John; Dews, Peter; Miller, Richard E; Massanari, R Michael

    2010-05-01

    Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is of great importance. The current approach to postmarketing surveillance primarily relies on spontaneous reporting. It is a passive surveillance system and limited by gross underreporting (<10% reporting rate), latency, and inconsistent reporting. We propose a novel team-based intelligent agent software system approach for proactively monitoring and detecting potential ADRs of interest using electronic patient records. We designed such a system and named it ADRMonitor. The intelligent agents, operating on computers located in different places, are capable of continuously and autonomously collaborating with each other and assisting the human users (e.g., the food and drug administration (FDA), drug safety professionals, and physicians). The agents should enhance current systems and accelerate early ADR identification. To evaluate the performance of the ADRMonitor with respect to the current spontaneous reporting approach, we conducted simulation experiments on identification of ADR signal pairs (i.e., potential links between drugs and apparent adverse reactions) under various conditions. The experiments involved over 275,000 simulated patients created on the basis of more than 1000 real patients treated by the drug cisapride that was on the market for seven years until its withdrawal by the FDA in 2000 due to serious ADRs. Healthcare professionals utilizing the spontaneous reporting approach and the ADRMonitor were separately simulated by decision-making models derived from a general cognitive decision model called fuzzy recognition-primed decision (RPD) model that we recently developed. The quantitative simulation results show that 1) the number of true ADR signal pairs detected by the ADRMonitor is 6.6 times higher than that by the spontaneous reporting strategy; 2) the ADR detection rate of the ADRMonitor agents with even moderate decision-making skills is five

  1. Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

    PubMed

    Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

    2017-08-16

    Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

  2. A Distributed, Collaborative Intelligent Agent System Approach for Proactive Postmarketing Drug Safety Surveillance

    PubMed Central

    Ji, Yanqing; Ying, Hao; Farber, Margo S.; Yen, John; Dews, Peter; Miller, Richard E.; Massanari, R. Michael

    2014-01-01

    Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is of great importance. The current approach to postmarketing surveillance primarily relies on spontaneous reporting. It is a passive surveillance system and limited by gross underreporting (<10% reporting rate), latency, and inconsistent reporting. We propose a novel team-based intelligent agent software system approach for proactively monitoring and detecting potential ADRs of interest using electronic patient records. We designed such a system and named it ADRMonitor. The intelligent agents, operating on computers located in different places, are capable of continuously and autonomously collaborating with each other and assisting the human users (e.g., the food and drug administration (FDA), drug safety professionals, and physicians). The agents should enhance current systems and accelerate early ADR identification. To evaluate the performance of the ADRMonitor with respect to the current spontaneous reporting approach, we conducted simulation experiments on identification of ADR signal pairs (i.e., potential links between drugs and apparent adverse reactions) under various conditions. The experiments involved over 275 000 simulated patients created on the basis of more than 1000 real patients treated by the drug cisapride that was on the market for seven years until its withdrawal by the FDA in 2000 due to serious ADRs. Healthcare professionals utilizing the spontaneous reporting approach and the ADRMonitor were separately simulated by decision-making models derived from a general cognitive decision model called fuzzy recognition-primed decision (RPD) model that we recently developed. The quantitative simulation results show that 1) the number of true ADR signal pairs detected by the ADRMonitor is 6.6 times higher than that by the spontaneous reporting strategy; 2) the ADR detection rate of the ADRMonitor agents with even moderate decision-making skills is five

  3. Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines

    PubMed Central

    Ayres, J G; Frost, C D; Holmes, W F; Williams, D R R; Ward, S M

    1998-01-01

    Objective To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler. Design This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months. Setting 646 general practices throughout the United Kingdom. Subjects 6614 patients with obstructive airways disease (1667 patient years of exposure). Main outcome measures Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects. Results There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively). Conclusion The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies. Key messagesCredibility of postmarketing surveillance studies is expected to increase after the introduction of guidelines covering their conduct The study design successfully fulfilled the requirements of these guidelines in terms of the number, rate, and

  4. Composite sequential Monte Carlo test for post-market vaccine safety surveillance.

    PubMed

    Silva, Ivair R

    2016-04-30

    Group sequential hypothesis testing is now widely used to analyze prospective data. If Monte Carlo simulation is used to construct the signaling threshold, the challenge is how to manage the type I error probability for each one of the multiple tests without losing control on the overall significance level. This paper introduces a valid method for a true management of the alpha spending at each one of a sequence of Monte Carlo tests. The method also enables the use of a sequential simulation strategy for each Monte Carlo test, which is useful for saving computational execution time. Thus, the proposed procedure allows for sequential Monte Carlo test in sequential analysis, and this is the reason that it is called 'composite sequential' test. An upper bound for the potential power losses from the proposed method is deduced. The composite sequential design is illustrated through an application for post-market vaccine safety surveillance data.

  5. [Research on the issues in the process of post-market surveillance for medical devices based on the typical case analysis].

    PubMed

    Zhang, Sumin; Zhang, Liang

    2011-11-01

    Regarding the information collected, analysis and actions that have been taken, the issues in the process of the Post-market Surveillance for Medical Device were analyzed, and some suggestions were given at the same time.

  6. Tolerability of modified tick-borne encephalitis vaccine FSME-IMMUN "NEW" in children: results of post-marketing surveillance.

    PubMed

    Pavlova, Borislava G; Loew-Baselli, Alexandra; Fritsch, Sandor; Poellabauer, Eva Maria; Vartian, Nina; Rinke, Ingeborg; Ehrlich, Hartmut J

    2003-01-30

    A new, highly purified, inactivated tick-borne encephalitis (TBE) vaccine FSME-IMMUN "NEW" has been developed by Baxter using a production virus seed derived from chick embryo cells instead of mouse brain. In clinical trials, the vaccine was shown to be highly immunogenic and well tolerated in adults and children. Following licensure in 2001, the tolerability of half the adult dose of FSME-IMMUN "NEW" (1.2 microg antigen/0.25 ml) was investigated in a post-marketing surveillance in 1899 children aged 6 months to 12 years. Rectal body temperature was measured daily for 3 days after the first vaccination. An overall fever rate of 20.3% (95% CI=18.5; 22%) was observed, which was mostly mild in nature (>38.0 to surveillance population). These results demonstrated that, in routine medical practice, FSME-IMMUN "NEW" vaccine at a dose of 1.2 microg antigen/0.25 ml is safe for the first vaccination in children.

  7. A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis.

    PubMed

    Holmén, Carolina; Piehl, Fredrik; Hillert, Jan; Fogdell-Hahn, Anna; Lundkvist, Malin; Karlberg, Elin; Nilsson, Petra; Dahle, Charlotte; Feltelius, Nils; Svenningsson, Anders; Lycke, Jan; Olsson, Tomas

    2011-06-01

    A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing-remitting MS patients (n=901), mean Expanded Disability Status Scale (EDSS, -10.7%), Multiple Sclerosis Severity Scale (MSSS, -20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical -9.9%, psychological -13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

  8. [Results of a post-marketing surveillance of meropenem for febrile neutropenia].

    PubMed

    Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

    2015-08-01

    The post-marketing surveillance of meropenem (Meropen) for febrile neutropenia (FN) was conducted between July 2010 and June 2012 to evaluate safety and efficacy under actual clinical use. There were 1191 and 1124 evaluable cases for safety and efficacy respectively, of 1207 case cards collected from 180 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 15.7% (187/1191 cases), and the main ADRs were alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hepatic function abnormal, and liver disorder, which were similar to these observed in the clinical study for FN or post marketing surveillances of meropenem conducted before. In efficacy analysis, the overall efficacy was 81.8% (919/1124 cases). Also, it was 79.2% (708/894 cases) for hematological malignancy and 91.8% (213/232 cases) for solid cancer. These results confirmed meropenem (Meropen) is one of the well-tolerated and potent antimicrobial agents for febrile neutropenia.

  9. Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan

    PubMed Central

    Suga, Osamu

    2016-01-01

    Prospective postmarketing surveillance of Selara (eplerenone), a selective mineralocorticoid receptor antagonist, was performed to confirm its safety and efficacy for hypertension treatment in Japan. The change in blood pressure after initiation of eplerenone treatment was also examined. Patients with essential hypertension who were eplerenone-naïve were recruited regardless of the use of other antihypertensive drugs. For examination of changes in blood pressure, patients were excluded if eplerenone was contraindicated or used off-label. Patients received 50–100 mg of eplerenone once daily and were observed for 12 weeks. No treatments including antihypertensive drugs were restricted during the surveillance period. Across Japan, 3,166 patients were included for safety analysis. The incidence of adverse drug reactions was 2.4%. The major adverse drug reactions observed were hyperkalemia (0.6%), dizziness, renal impairment, and increased serum potassium (0.2% each). The mean systolic blood pressure decreased from 152.1 ± 19.0 mmHg to 134.8 ± 15.2 mmHg at week 12, and the mean diastolic blood pressure decreased from 85.8 ± 13.7 mmHg to 77.7 ± 11.4 mmHg. There were no significant new findings regarding the type or incidence of adverse reactions, and eplerenone had a clinically significant antihypertensive effect, leading to favorable blood pressure control. PMID:27843645

  10. Postmarketing surveillance of new food ingredients: design and implementation of the program for the fat replacer olestra.

    PubMed

    Slough, C L; Miday, R K; Zorich, N L; Jones, J K

    2001-04-01

    Following U.S. Food and Drug Administration (FDA) approval for the use of olestra, a noncaloric fat substitute (brand name Olean) in food snacks, the manufacturer agreed to provide safety updates on market experience to the FDA. However, guidelines for food product postmarketing surveillance (PMS) are not available and those typically used with medical products were only partly applicable. In modeling the Olean program, we drew from experience with consumer products and incorporated elements typical of medical product PMS. A cooperative effort was established with Olean snack manufacturers and a two-tiered, multidisciplinary approach enlisting Consumer Relations and Medical Affairs personnel was used to maximize use of specialized skills. The result of this effort was implementation of a reliable PMS system which could handle a high volume of reports from consumers while providing pertinent data required for medical interpretation of these reports. Summaries of data for the Olean snack manufacturers and FDA were generated in timely fashion. In addition to collection of the spontaneous reports from consumers, a clinical studies program was undertaken and an independent medical advisory panel was established. Through these, we gained perspective on the spontaneous reports and additional confirmation of the safety of olestra in savory snacks.

  11. [Results of a post-marketing surveillance of meropenem administered over 2 g/day for serious infectious diseases].

    PubMed

    Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

    2015-10-01

    The post-marketing surveillance of meropenem (Meropen®) administered over 2g/day for serious infectious diseases was conducted between August 2011 and June 2013 to evaluate safety and efficacy under actual clinical use. There were 382 and 322 evaluable cases for safety and efficacy respectively, of 399 case cards collected from 87 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 19.1% (73/382 cases), and the main ADRs were hepatic function abnormal, aspartate aminotransferase increased, alanine aminotransferase increased, liver disorder, and diarrhoea, which were similar to these observed in the post-marketing surveillances of meropenem conducted before. In efficacy analysis, the efficacy was 73.6% (237/322 cases), which is as same as 71.4% (3214/4504 cases) of post-marketing surveillance of meropenem conducted after first approval under 2 g/day for infectious diseases. These results confirmed meropenem (Meropen®) is one of the useful antimicrobial agents for serious infectious diseases.

  12. Safety and effectiveness profile of raloxifene in long-term, prospective, postmarketing surveillance.

    PubMed

    Iikuni, Noriko; Hamaya, Etsuro; Nihojima, Shigeru; Yokoyama, Shunji; Goto, Wakana; Taketsuna, Masanori; Miyauchi, Akimitsu; Sowa, Hideaki

    2012-11-01

    This large-scale postmarketing surveillance of raloxifene (60 mg/day) was conducted to assess the safety and effectiveness of raloxifene for long-term use in postmenopausal Japanese women with osteoporosis. The baseline examination included 6,967 women (mean age, 70.4 years). Participants completed observation after 6, 12, 24, and 36 months of therapy. Adverse drug reactions (ADR) were reported in 776 participants (11.14 %), with a total of 87 serious ADR cases occurring in 76 participants (1.09 %). The most frequently reported ADRs were edema peripheral (45/6,967, 0.65 %) and venous thromboembolism (11/6,967, 0.16 %). Of the 6,967 participants, 2,784 were included in the effectiveness analysis. Lumbar spine bone mineral density (BMD) increased significantly (p < 0.001, paired t test) compared with baseline at 6, 12, 24, and 36 months (2.51 %, 2.85 %, 4.76 %, and 3.51 %, respectively). Significant decreases in serum and urinary cross-linked amino-terminal telopeptide of type I collagen (NTX) and urinary deoxypyridinoline levels from baseline were observed at 3 months, followed by a significant decrease of serum bone alkaline phosphatase at 6 months [p < 0.001 for all comparisons except serum NTX (p = 0.011), Wilcoxon signed-rank test]. Early reductions in the biochemical markers of bone turnover (BTM) observed at 3 months with raloxifene treatment correlated negatively with subsequent increases in lumbar spine BMD at 1 year (r = -0.347, p = 0.008). The incidence of any new clinical fractures within 3 years was 1.18 % (82/6,967 participants). In summary, no new signals in safety were observed in the daily use of raloxifene. Moreover, the effectiveness profile of raloxifene was confirmed in practical use by this large-scale, long-term, postmarketing surveillance.

  13. Postmarketing Surveillance Study of the Efficacy and Safety of Phentermine in Patients with Obesity

    PubMed Central

    Kim, Hyun Ok; Lee, Jung Ah; Suh, Hee Won; Kim, Bum Soo; Ahn, Eun Sook; Roh, Young Jun; Jung, Seong Gil; Kim, Jin Mok; Kang, Moon Kuk; Ahn, In Soon; Park, Young Gyu

    2013-01-01

    Background Obesity is a complex problem that is now considered a chronic metabolic disease. In Korea, phentermine has been widely used for the treatment of obesity in the primary care setting since 2004. However, there have been very few studies on the safety and efficacy of phentermine. To investigate the safety and efficacy of this drug, a postmarketing surveillance study was performed. Methods A total of 795 patients with obesity (body mass index ≥ 25 kg/m2) were enrolled from 30 primary care centers in Korea from September 2006 to November 2007. Patients were examined to ascertain safety and efficacy at 4-, 8-, and 12-week intervals. The criterion for efficacy was defined as a weight loss ≥ 5% of body weight. Results Of the 795 enrolled patients, 735 (92.5%) were evaluated in safety assessments and 711 (89.4%) was included in efficacy assessments. A total of 266 adverse events (AEs) were reported by 218 patients (30.6%), and no serious AEs were reported. Among 711 patients, 324 patients (45.6%) lost ≥ 5% of their body weight. The mean weight loss was 3.8 ± 4.0 kg. Conclusion AEs are commonly associated with phentermine, even though phentermine is effective for weight loss and relatively well-tolerated. PMID:24106582

  14. Post-marketing surveillance of generic amoxicillin using a microbiological assay and pharmacokinetic approach in rats.

    PubMed

    de Mattos, Livia I S; Ferraris, Fausto K; Machado, Tiago S C; de Brito, Thais M; Chaves, Amanda S; Pereira, Heliana M; Pinto, Douglas P; da Silva, Diego M D; Amendoeira, Fabio C

    2016-12-01

    Generic medicines were developed to increase population access to health treatment, to reduce costs and to allow drugs with the same outcomes to be purchased at lower prices. They are therapeutically equivalent to their brand-name counterparts and are interchangeable with them. However, the acceptance of generic medicines by physicians and general consumers is often affected by distrust related to quality and efficacy. In this study three different brands of generic amoxicillin were tested. The results showed that two of them were indistinguishable from the innovator in terms of microbiological potency; however, generic B was unable to reach the Brazilian Pharmacopoeia specifications for potency limits. In contrast, generic B was bioequivalent to the innovator amoxicillin in pharmacokinetic assessment and, surprisingly, generic A, which was approved in the microbiological potency assay, lacked pharmacokinetic equivalence compared with the innovator. Both tests, when used singly, may not be effective at detecting quality deviations in antimicrobial medicines, which indicates that pharmacokinetic tests in rats in association with microbiological potency assays are a valuable tool for post-marketing surveillance of generic antibiotics.

  15. Postmarketing surveillance of new food ingredients: results from the program with the fat replacer olestra.

    PubMed

    Allgood, G S; Kuter, D J; Roll, K T; Taylor, S L; Zorich, N L

    2001-04-01

    Market introduction of savory snacks containing olestra offered an opportunity to evaluate the safety of olestra in a free-living population and thereby compare the outcome to the previously established safety profile determined in clinical trials in which subjects were required to eat predetermined amounts at prescribed intervals. Therefore, a multifaceted postmarketing surveillance program was designed to evaluate consumer experience and safety of olestra in the marketplace. Customer comments were solicited through toll-free telephone numbers. Collected data were evaluated by both internal and external medical experts. About 10% of toll-free telephone calls reported health effects, most of which were gastrointestinal (GI) in nature. Clinical studies were designed and conducted to determine potential GI effects under the range of consumption patterns reported by toll-free calls. Health effects reported were those found commonly in the general population and analyses of the data found no biological reason to conclude that serious or meaningful health effects were the result of olestra consumption.

  16. Transvenous implantable cardioverter-defibrillator lead reliability: implications for postmarket surveillance.

    PubMed

    Kramer, Daniel B; Hatfield, Laura A; McGriff, Deepa; Ellis, Christopher R; Gura, Melanie T; Samuel, Michelle; Retel, Linda Kallinen; Hauser, Robert G

    2015-05-29

    As implantable cardioverter-defibrillator technology evolves, clinicians and patients need reliable performance data on current transvenous implantable cardioverter-defibrillator systems. In addition, real-world reliability data could inform postmarket surveillance strategies directed by regulators and manufacturers. We evaluated Medtronic Sprint Quattro, Boston Scientific Endotak, and St Jude Medical Durata and Riata ST Optim leads implanted by participating center physicians between January 1, 2006 and September 1, 2012. Our analytic sample of 2653 patients (median age 65, male 73%) included 445 St Jude, 1819 Medtronic, and 389 Boston Scientific leads. After a median of 3.2 years, lead failure was 0.28% per year (95% CI, 0.19 to 0.43), with no statistically significant difference among manufacturers. Simulations based on these results suggest that detecting performance differences among generally safe leads would require nearly 10 000 patients or very long follow-up. Currently marketed implantable cardioverter-defibrillator leads rarely fail, which may be reassuring to clinicians advising patients about risks and benefits of transvenous implantable cardioverter-defibrillator systems. Regulators should consider the sample size implications when designing comparative effectiveness studies and evaluating new technology for preventing sudden cardiac death. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Transvenous Implantable Cardioverter-Defibrillator Lead Reliability: Implications for Postmarket Surveillance

    PubMed Central

    Kramer, Daniel B; Hatfield, Laura A; McGriff, Deepa; Ellis, Christopher R; Gura, Melanie T; Samuel, Michelle; Retel, Linda Kallinen; Hauser, Robert G

    2015-01-01

    Background As implantable cardioverter-defibrillator technology evolves, clinicians and patients need reliable performance data on current transvenous implantable cardioverter-defibrillator systems. In addition, real-world reliability data could inform postmarket surveillance strategies directed by regulators and manufacturers. Methods and Results We evaluated Medtronic Sprint Quattro, Boston Scientific Endotak, and St Jude Medical Durata and Riata ST Optim leads implanted by participating center physicians between January 1, 2006 and September 1, 2012. Our analytic sample of 2653 patients (median age 65, male 73%) included 445 St Jude, 1819 Medtronic, and 389 Boston Scientific leads. After a median of 3.2 years, lead failure was 0.28% per year (95% CI, 0.19 to 0.43), with no statistically significant difference among manufacturers. Simulations based on these results suggest that detecting performance differences among generally safe leads would require nearly 10 000 patients or very long follow-up. Conclusions Currently marketed implantable cardioverter-defibrillator leads rarely fail, which may be reassuring to clinicians advising patients about risks and benefits of transvenous implantable cardioverter-defibrillator systems. Regulators should consider the sample size implications when designing comparative effectiveness studies and evaluating new technology for preventing sudden cardiac death. PMID:26025935

  18. Treatment of comorbid anxiety and depression with escitalopram: results of a post-marketing surveillance study.

    PubMed

    Laux, G; Friede, M; Müller, W E

    2013-01-01

    In this 16-week post-marketing surveillance (PMS) study, antidepressant effects and tolerability of escitalopram was examined in 2 911 patients with comorbid depression and anxiety. Antidepressant effects were assessed using a modified version of the Montgomery-Åsberg depression rating scale (svMADRS), the Hamilton anxiety scale (HAMA) and the hospital anxiety depression scale (HADS-D) and the clinical global impression scale (CGI-S, CGI-I). Treatment was completed by 2 718 patients, whose severity of depression decreased from a mean svMADRS total score of 33.0 to 8.9. At the end of the study, the remission rate (svMADRS≤12) was 72.9% and the response rate (≥50% decrease in svMADRS score) was 83.1% (LOCF). Similarly, the severity of anxiety symptoms decreased from a mean HAMA total score of 28.8-8.8; the remission rate (HAMA<10) was 63.9% and the response rate (decrease≥50%) was 80.2%. The most frequent adverse events were nausea (1.6%), agitation (1.1%) and fatigue (0.7%). Antidepressant effects and good tolerability of escitalopram were confirmed in everyday practice in patients with comorbid depression and anxiety. The high response and remission rates were within the range reported in previous RTC's of escitalopram vs. comparators or vs. placebo. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Efficacy and safety of garenoxacin tablets on bacterial pneumonia: postmarketing surveillance in Japan.

    PubMed

    Izumikawa, Koichi; Watanabe, Akira; Miyashita, Naoyuki; Ishida, Tadashi; Hosono, Hiroaki; Kushimoto, Satoru; Kohno, Shigeru

    2014-09-01

    We performed a postmarketing surveillance study to determine the efficacy and safety of the oral quinolone antibacterial agent, garenoxacin (Geninax(®) Tablets 200 mg), against bacterial pneumonia. Between October 2009 and March 2011, patients with community-acquired pneumonia visited 174 facilities in Japan; we collected survey forms from 739 patients of these patients who were suspected with bacterial pneumonia on the basis of factors, e.g., the presence of purulent sputum or suspected presence of bacterial pathogens in clinical specimens. We examined the safety in 730 patients and the efficacy in 535 patients. The efficacy rate of garenoxacin for bacterial pneumonia was 92.8% (479/516 patients). The eradication rates for Streptococcus pneumoniae and Haemophilus influenzae, the major pathogens of bacterial pneumonia, were 98.5% (65/66 strains) and 100% (65/65 strains), respectively. The incidence of adverse drug reactions (including abnormal laboratory tests) was 7.9% (58/730 patients). Among the main adverse drug reactions, abnormal laboratory tests were observed in 2.1% patients (15/730), hepatobiliary disorders were observed in 1.8% patients (13/730), and skin and subcutaneous tissue disorders were observed in 1.6% patients (12/730). In conclusion, garenoxacin showed an efficacy rate of greater than 90% for bacterial pneumonia and is considered to be useful in daily practice.

  20. Security and privacy qualities of medical devices: an analysis of FDA postmarket surveillance.

    PubMed

    Kramer, Daniel B; Baker, Matthew; Ransford, Benjamin; Molina-Markham, Andres; Stewart, Quinn; Fu, Kevin; Reynolds, Matthew R

    2012-01-01

    Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients' stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware.

  1. Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan.

    PubMed

    Ninomiya, Haruhiko; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Nishiwaki, Kaichi; Matsumura, Itaru; Shichishima, Tsutomu; Okamoto, Shinichiro; Nishimura, Jun-Ichi; Ohyashiki, Kazuma; Nakao, Shinji; Ando, Kiyoshi; Kanda, Yoshinobu; Kawaguchi, Tatsuya; Nakakuma, Hideki; Harada, Daisuke; Akiyama, Hirozumi; Kinoshita, Taroh; Ozawa, Keiya; Omine, Mitsuhiro; Kanakura, Yuzuru

    2016-11-01

    Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count ≥150 × 10(9)/L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention.

  2. [The role of drug registries in the post-marketing surveillance].

    PubMed

    Traversa, Giuseppe; Sagliocca, Luciano; Magrini, Nicola; Venegoni, Mauro

    2013-06-01

    The aim of this article is to provide an introduction to issue of Recenti Progressi in Medicina, devoted to the role of drug registries in the post-marketing surveillance. We first motivate the need to implement registries as a tool in promoting the appropriateness of drug use and acquiring additional information on the risk-benefit profile of drugs. Then, the different role that can be played by registries in comparison with prescription monitoring systems and observational studies is clarified. The presentation of some of the most relevant registries established in Italy since the end of the '90s, with the analysis of their strengths and weaknesses, helps to understand some of the crucial issues that should be taken into account before a new registry is adopted. Specifically, we deal with the relationship between objectives - of appropriateness, effectiveness and safety - and methods; the overlapping between drug-based registries and disease-based ones; the duration and extension of data collection, which may be either exhaustive or based on a sampling frame; the importance of ensuring the quality of the data and to minimize the number of subjects who are lost to follow-up; the importance of infrastructures, and of ad hoc funding, for the functioning of a registry; the independence in data analysis and publication of findings.

  3. Safety and effectiveness of interferon β-1a intramuscular therapy: results of the postmarketing drug surveillance in Japan.

    PubMed

    Makioka, Haruki; Nakaya, Fuyuki; Ling, Yan; Torii, Shinichi; Saida, Takahiko; Kira, Jun-Ichi

    2017-09-30

    To investigate the safety and effectiveness of the interferon β-1a intramuscular injection under clinical conditions in Japan, we conducted an all-case postmarketing surveillance with a 2-year follow-up of patients who were registered during the period between November 2006 (product launch) and December 2010. Case reports were collected from 397 institutions. The safety analysis included 1,476 patients, and the effectiveness analysis included 1,441 patients. Of the patients included in the safety analysis, 86.3% had relapsing-remitting multiple sclerosis. The most common adverse drug reaction was pyrexia (19.24%). Serious adverse events included multiple sclerosis relapse (26 cases) and abnormal hepatic function (10 cases). In the effectiveness analysis, the annualized relapse rate improved significantly from 1.07 to 0.29 (P < 0.001). There was also a significant improvement in in the expanded disability status scale from 3.08 to 2.94 (P < 0.001). The results of the safety and effectiveness profile were consistent with those in previous reports.

  4. The DELTA Network Study of Distributed Automated Post-Market Cardiovascular Device Safety Surveillance

    PubMed Central

    Kumar, Amit; Matheny, Michael E.; Ho, Kalon K.L.; Yeh, Robert W.; Piemonte, Thomas C.; Waldman, Howard; Shah, Pinak B.; Cope, Richard; Normand, Sharon-Lise; Donnelly, Sharon; Robbins, Susan; Resnic, Frederic S.

    2016-01-01

    Background Current approaches for post-market medical device safety surveillance are limited in their ability to produce timely and accurate assessments of adverse event rates. Methods and Results The DELTA (Data Extraction and Longitudinal Trend Analysis) network study was a multicenter prospective observational study designed to evaluate the safety of devices used during percutaneous coronary interventions (PCI). All adult patients undergoing PCI from January 2008 through December 2012 at five participating Massachusetts sites were included. A safety alert was triggered if the cumulative observed adverse event rates for the study device exceeded the upper 95% confidence interval of the event rates of propensity-matched control cohort. Pre-specified sensitivity analyses were developed to validate any identified safety signal. A total of 23,805 consecutive PCI procedures were evaluated. Two out of 24 safety analyses triggered safety alerts. Patients receiving Perclose vascular closure device (VCD) experienced an increased risk of minor vascular complications (relative risk [RR] 4.14; p <0.01) and any vascular complication (RR: 2.06; p = 0.01) as compared with propensity-matched patients receiving alternative VCD; a result primarily driven by relatively high event rates at one participating center. Sensitivity analyses based on alternative risk adjustment methods confirmed the a pattern of increased rate of complications at one of the five participating sites in their use of Perclose VCD. Conclusions The DELTA network study demonstrates that distributed automated prospective safety surveillance has the potential of providing near real-time assessment of safety risks of newly approved medical devices. PMID:25491915

  5. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    PubMed

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  6. Postmarketing safety reports for human drug and biological products; electronic submission requirements. Final rule.

    PubMed

    2014-06-10

    The Food and Drug Administration (FDA or we) is amending its postmarketing safety reporting regulations for human drug and biological products to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. FDA is taking this action to improve the Agency's systems for collecting and analyzing postmarketing safety reports. The change will help the Agency to more rapidly review postmarketing safety reports, identify emerging safety problems, and disseminate safety information in support of FDA's public health mission. In addition, the amendments will be a key element in harmonizing FDA's postmarketing safety reporting regulations with international standards for the electronic submission of safety information.

  7. Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance

    PubMed Central

    Kramer, Daniel B.; Baker, Matthew; Ransford, Benjamin; Molina-Markham, Andres; Stewart, Quinn; Fu, Kevin; Reynolds, Matthew R.

    2012-01-01

    Background Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients’ stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. Methods We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Results Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Conclusions Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware. PMID:22829874

  8. Post-marketing surveillance of the safety of cimetidine: twelve-month morbidity report.

    PubMed

    Colin Jones, D G; Langman, M J; Lawson, D H; Vessey, M P

    1985-03-01

    A total of 9928 patients taking cimetidine and 9351 controls were included in a post-marketing drug surveillance study in Glasgow, Nottingham, Oxford and Portsmouth; 98.8 per cent of the takers and 97.7 per cent of the controls were successfully followed up for at least one year during which hospital visits and deaths were recorded. Methods of identification of subjects and 12-month mortality results have been reported previously. A general analysis of the morbidity experienced by these patients during the study year is presented here. Thirty-nine per cent of takers and 21 per cent of controls were seen at outpatient clinics, and 18 per cent of takers and 8 per cent of controls were admitted to hospital; 15 325 individual diagnoses in takers and 5002 diagnoses in controls were reviewed. An association with cimetidine treatment was found, as expected, for gastrointestinal diseases. Weaker associations were found for haematological disorders, some tumours, infections, disorders of the locomotor system and respiratory diseases. Detailed examination revealed that these were mainly due to confounding from several sources, for example, from the underlying cause of the dyspepsia which resulted in cimetidine use, from the higher level of physician contact in cimetidine takers, and smoking. The scheme successfully detected and quantified some already known adverse effects of cimetidine and did not detect any new effects. It is concluded that this method of collecting information is feasible and useful, but several interpretive pitfalls arise, some of which can be avoided by careful analysis. No evidence of any major unrecognised risk of cimetidine treatment emerged from the study.

  9. Safety of the long-acting neuraminidase inhibitor laninamivir octanoate hydrate in post-marketing surveillance.

    PubMed

    Kashiwagi, Seizaburo; Yoshida, Sanae; Yamaguchi, Hiroki; Niwa, Shinpei; Mitsui, Noriko; Tanigawa, Masatoshi; Shiosakai, Kazuhito; Yamanouchi, Naoki; Shiozawa, Tomoo; Yamaguchi, Fumie

    2012-11-01

    Laninamivir octanoate hydrate (laninamivir) is a long-acting neuraminidase inhibitor (NAI) that completes treatment with only a single inhalation. It was launched in Japan in October 2010 as an anti-influenza agent. A post-marketing surveillance study was conducted in the 2010/2011 influenza season to assess the safety of this drug in clinical settings. Adverse drug reactions (ADRs) were observed in 50 patients (59 events) out of 3542 patients subjected to safety evaluation (incidence 1.41%). Commonly reported ADRs were psychiatric disorders (abnormal behaviour, etc.), gastrointestinal disorders (diarrhoea, nausea, etc.) and nervous system disorders (dizziness, etc.), with incidences of 0.48% (n=17), 0.45% (n=16) and 0.17% (n=6), respectively. No serious ADRs occurred. ADRs usually emerged on the day on which laninamivir was inhaled (52.5%) and ADRs emerged within 3 days after inhalation in >90% of adversely affected patients. ADRs resolved or improved within 3 days in >85% of patients. The incidence of adverse events involving abnormal behaviour was 3.1% (30/959) among patients <10 years of age, 0.7% (8/1088) among patients aged 10-19 years, 0.1% (2/1431) among adult patients aged 20-64 years and 0.0% (0/64) among patients aged ≥65 years. It was confirmed that laninamivir is unlikely to cause delayed ADRs or a prolonged duration of ADRs despite this drug being a long-acting NAI. Furthermore, the incidence of ADRs was not found to have increased compared with that observed during clinical trials, and the types of ADR observed during this study were similar to those previously observed. Thus, laninamivir octanoate hydrate was confirmed to have no noticeable problem with safety. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  10. 75 FR 6036 - Agency Information Collection Activities; Proposed Collection; Comment Request; Postmarket...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... Collection; Comment Request; Postmarket Surveillance AGENCY: Food and Drug Administration, HHS. ACTION... on information collection requirements for Postmarket Surveillance. DATES: Submit written or... of information technology. Postmarket Surveillance--21 CFR Part 822 (OMB Control Number 0910- 0449...

  11. In vitro and in vivo postmarketing surveillance of valsartan, alone or in combination with amlodipine or hydrochlorothiazide, among Palestinian hypertensive patients

    PubMed Central

    Zaid, Abdel Naser; Ghanem, Masshour; Shweiki, Dua’a; Shtewi, Hala; Shaheen, Raja’; Al Helaly, Sondos; Khayyat, Zeina; Al Ramahi, Rowa’a; Zyoud, Sa’ed H

    2016-01-01

    Objectives The objectives of this study were to evaluate the general quality of the most prescribed products of valsartan (VL; alone or in combination) and to evaluate their efficacy and safety among Palestinian population through in vivo postmarketing surveillance. Patients and methods The first part was pharmacopeial quality control assay, including dissolution, disintegration, friability, and weight uniformity for VL. The second part was a 3-month cardiology clinics, observational, postmarketing surveillance pilot study that included 103 hypertensive patients who were prescribed 80 mg or 160 mg of VL as monotherapy or combination therapy. The end points were reduction in blood pressure (BP) and the rate of incidence of adverse effects (AEs) at weeks 4 and 8. Results According to our quality control tests, all VL products showed high-quality standards according to the international guidelines. A reduction in BP was observed at weeks 4 and 8, and no significant difference was observed between the strengths of 80 mg and 160 mg. Higher BP reduction was observed after the use of combination therapy. Moreover, VL was well tolerated; most of the AEs were of mild-to-moderate intensity. In general, the most frequently reported AEs included headache (17.5%), dizziness (11.75%), and weakness (11.7%). No serious AEs or death cases were reported during the study period. Conclusion High quality of VL tablet products was used; hence, the observed efficacy and safety results should be related to patient’s factors and not due to any product defects or substandard quality. Moreover, VL is an effective treatment for essential hypertension. PMID:27703364

  12. Post-marketing surveillance of immediate allergic reactions: polygeline-based versus polygeline-free pediatric TBE vaccine.

    PubMed

    Zent, Olaf; Hennig, Renald

    2004-12-16

    Scattered cases of immediate allergic reactions occurred in the nineties after widespread use of the original (polygeline-based) pediatric tick-borne encephalitis (TBE) vaccine and were reported to Pharmacovigilance, Chiron Vaccines. Although, still indicating a very rare frequency of about two cases per 100,000 doses sold, the benefit/risk assessment resulted in its withdrawal from the market in early 1998. An intensive evaluation revealed that polygeline used as a vaccine stabilizer was the most probable cause of the reported allergic reactions. Consequently, an improved pediatric TBE vaccine, free of polygeline and other protein-derived vaccine stabilizers, was developed. A post-marketing surveillance analysis covering the first two vaccination seasons after the introduction of this new pediatric TBE vaccine in early 2002 reveals a very low reporting rate of immediate allergic reactions post immunization (within the range as noted for other widely used vaccines for childhood immunization), i.e., 0.08-0.24 cases per 100,000 doses sold depending on case definition and medical assessment. In conclusion, this analysis provides post-marketing surveillance evidence that the change in the vaccine formulation, with regards to the potential risk of immediate allergic reactions, has led to an intended improvement in the vaccine's safety profile.

  13. A potential causal association mining algorithm for screening adverse drug reactions in postmarketing surveillance.

    PubMed

    Ji, Yanqing; Ying, Hao; Dews, Peter; Mansour, Ayman; Tran, John; Miller, Richard E; Massanari, R Michael

    2011-05-01

    Early detection of unknown adverse drug reactions (ADRs) in postmarketing surveillance saves lives and prevents harmful consequences. We propose a novel data mining approach to signaling potential ADRs from electronic health databases. More specifically, we introduce potential causal association rules (PCARs) to represent the potential causal relationship between a drug and ICD-9 (CDC. (2010). International Classification of Diseases, Ninth Revision (ICD-9). [Online]. Available: http://www.cdc.gov/nchs/icd/icd9.html) coded signs or symptoms representing potential ADRs. Due to the infrequent nature of ADRs, the existing frequency-based data mining methods cannot effectively discover PCARs. We introduce a new interestingness measure, potential causal leverage, to quantify the degree of association of a PCAR. This measure is based on the computational, experience-based fuzzy recognition-primed decision (RPD) model that we developed previously (Y. Ji, R. M. Massanari, J. Ager, J. Yen, R. E. Miller, and H. Ying, "A fuzzy logic-based computational recognition-primed decision model," Inf. Sci., vol. 177, pp. 4338-4353, 2007) on the basis of the well-known, psychology-originated qualitative RPD model (G. A. Klein, "A recognition-primed decision making model of rapid decision making," in Decision Making in Action: Models and Methods, 1993, pp. 138-147). The potential causal leverage assesses the strength of the association of a drug-symptom pair given a collection of patient cases. To test our data mining approach, we retrieved electronic medical data for 16,206 patients treated by one or more than eight drugs of our interest at the Veterans Affairs Medical Center in Detroit between 2007 and 2009. We selected enalapril as the target drug for this ADR signal generation study. We used our algorithm to preliminarily evaluate the associations between enalapril and all the ICD-9 codes associated with it. The experimental results indicate that our approach has a potential to

  14. Levodopa therapy with entacapone in daily clinical practice: results of a post-marketing surveillance study.

    PubMed

    Kupsch, Andreas; Trottenberg, Thomas; Bremen, Dirk

    2004-01-01

    The catechol-O-methyl transferase inhibitor entacapone is given in combination with levodopa/dopa decarboxylase inhibitor for Parkinson's disease (PD) patients experiencing end-of-dose wearing-off. This 4-week post-marketing surveillance study was undertaken to assess patients' responses to levodopa combined with entacapone in a real clinical practice setting. Overall, 466 patients with idiopathic PD treated with levodopa and experiencing symptoms of wearing-off were recruited. Both physicians and patients recorded the response to therapy, including improvements and side-effects. Following initiation of entacapone treatment, the average daily levodopa dose was reduced from 510 to 453 mg. Physician assessment of entacapone efficacy was judged to be "very good" or "good" in 77.6% of the patients, and tolerability was considered to be "very good" or "good" in 92.4% of patients, with only 12 patients (2.6%) withdrawing from the study. Compared with baseline, there was a decrease in the mean duration of daily 'off' time from 3.0 to 1.3 h per day during the treatment period. Adverse events were in line with those previously reported, with diarrhoea being the most frequent event. The percentage of patients suffering from dyskinesia decreased from 46 to 34%, and of those patients still suffering from dyskinesia, the average daily duration of dyskinesia was reduced from 2.2 to 1.7 h. The use of adjunct dopamine agonists decreased from 67 to 59%. At study end, the percentage of patients who rated their quality of life (QoL) as "very good" or "good" increased from 12.1 to 51.7% and the percentage of patients who rated their QoL as "bad" or "very bad" decreased from 40 to 10.7%. In summary, the results of this survey conducted in real clinical practice support the findings of previous clinical trials demonstrating the efficacy and tolerability of entacapone, as well as the benefits of improved QoL, for patients achieved with entacapone.

  15. Post-marketing surveillance study with iodixanol in 20 185 Chinese patients from routine clinical practices.

    PubMed

    Zhang, B-C; Hou, L; Lv, B; Xu, Y-W

    2014-02-01

    To determine the incidence of immediate and delayed adverse drug reactions (ADRs), and to assess patient discomfort following administration of iodixanol during imaging examinations in routine clinical practice. A total of 20 185 patients across 95 clinical centres were enrolled in a prospective post-marketing surveillance registry with iodixanol. Patients were monitored for occurrence of ADRs immediately following iodixanol administration and for up to 7 days after administration. The overall rate of ADRs was 1.52%, of which 0.58% was immediate and 0.97% was delayed onset. Two patients had non-fatal serious ADRs (0.01%). The ADRs were significantly more common in patients who underwent contrast-enhanced CT/coronary CT angiography vs others (p < 0.001), in those receiving pre-heated iodixanol vs non-heating (p < 0.001), in those aged 70 years or younger (p < 0.001), in those in whom a power injector was used for contrast delivery (p < 0.001) and in those with a history of an allergic reaction to contrast (p = 0.024). Multivariate analysis showed that female gender, intravenous route of contrast injection, body weight ≥ 80 kg, age less than 65 years, contrast flow rate ≥ 4 ml s⁻¹ and prior reaction to iodinated contrast medium were all significant and independent contributors to ADRs. Pre-treatment contrast volume and history of cardiac disease, gout, hypertension, diabetes mellitus or asthma did not affect the rate of ADRs. Discomfort was generally mild, with 94.8% of patients reporting a composite score of 0-3. The safety of iodixanol in routine clinical practice was shown to be similar to the published safety profiles of other non-ionic iodinated contrast agents. Patient discomfort during administration was mild or absent in most patients. The major strength of this study is that it included 20 185 patients enrolled in various types of imaging examinations. The safety profile of iodixanol was comparable to previously published work.

  16. Panitumumab in Japanese patients with unresectable colorectal cancer: a post-marketing surveillance study of 3085 patients.

    PubMed

    Boku, Narikazu; Sugihara, Kenichi; Kitagawa, Yuko; Hatake, Kiyohiko; Gemma, Akihiko; Yamazaki, Naoya; Muro, Kei; Hamaguchi, Tetsuya; Yoshino, Takayuki; Yana, Ikuo; Ueno, Hiroshi; Ohtsu, Atsushi

    2014-03-01

    Panitumumab was approved in Japan in April 2010 for the treatment of Kirsten rat sarcoma-2 virus oncogene wild-type unresectable and recurrent colorectal cancer. We conducted a post-marketing surveillance study to evaluate the safety and effectiveness of panitumumab. After panitumumab was commercially available in Japan, all patients to be treated with panitumumab were enrolled. Data on baseline characteristics, treatment outcome, and incidence and severity of adverse drug reactions were collected. In total, 3091 patients were registered. In the safety analysis set (n = 3085), panitumumab was administered as monotherapy (40.7%) or combination therapy (59.4%). The median treatment duration was 113 days (range: 1-559 days), and 451 (14.6%) patients received panitumumab for ≥10 months. The overall incidence rate of adverse drug reactions was 84.1%, and the most common adverse drug reaction was skin disorders (78.4%). The incidence rates (all grades) of interstitial lung disease, infusion reaction, electrolyte abnormalities and cardiac disorders were 1.3% (mortality rate: 0.6%), 1.5, 19.3 and 0.2%, respectively. The median survival time of patients treated with panitumumab monotherapy as the third-line, or later, therapy was 10.3 months. This post-marketing survey in clinical practice confirmed the safety and effectiveness of panitumumab. The benefit/risk balance for panitumumab in Japanese patients with unresectable colorectal cancer remains favorable.

  17. Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic lesions in Japanese patients with coexisting hepatic disorders

    PubMed Central

    Makino, Isao; Nakamura, Kimihide; Sato, Yoichi; Sato, Yuzuru; Sezai, Shuichi; Ikeda, Yusei; Shinmura, Wahei; Watahiki, Hajime; Yamamoto, Hideaki; Hioki, Yayuki; Suzuki, Masao; Kumada, Takashi; Honda, Takashi; Rikitoku, Tomoo; Hisanaga, Yasuhiro; Fukui, Hiroshi; Yamao, Junichi; Kawasaki, Hironaka; Hosoda, Akihide; Onji, Morikazu; Matsui, Hidetaka; Sata, Michio; Torimura, Takuji; Oho, Kazuhiko; Maekawa, Ryuichiro; Takagi, Yoshiyuki; Shakado, Satoshi; Nakayama, Masafumi; Gondo, Kazuhisa; Fukushima, Hirofumi; Kusaba, Taku; Tsubouchi, Hirohito; Hayashi, Katsuhiro; Hori, Takeshi; Iida, Yozo; Yutoku, Kouki; Maetani, Noboru; Kubo, Yoshitsugu; Miyata, Yoshifumi

    2006-01-01

    Background: Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels. Objective: The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders. Methods: This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement. Results: A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59

  18. Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic lesions in Japanese patients with coexisting hepatic disorders.

    PubMed

    Makino, Isao; Nakamura, Kimihide; Sato, Yoichi; Sato, Yuzuru; Sezai, Shuichi; Ikeda, Yusei; Shinmura, Wahei; Watahiki, Hajime; Yamamoto, Hideaki; Hioki, Yayuki; Suzuki, Masao; Kumada, Takashi; Honda, Takashi; Rikitoku, Tomoo; Hisanaga, Yasuhiro; Fukui, Hiroshi; Yamao, Junichi; Kawasaki, Hironaka; Hosoda, Akihide; Onji, Morikazu; Matsui, Hidetaka; Sata, Michio; Torimura, Takuji; Oho, Kazuhiko; Maekawa, Ryuichiro; Takagi, Yoshiyuki; Shakado, Satoshi; Nakayama, Masafumi; Gondo, Kazuhisa; Fukushima, Hirofumi; Kusaba, Taku; Tsubouchi, Hirohito; Hayashi, Katsuhiro; Hori, Takeshi; Iida, Yozo; Yutoku, Kouki; Maetani, Noboru; Kubo, Yoshitsugu; Miyata, Yoshifumi

    2006-01-01

    Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels. The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders. This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement. A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90 patients; 20-mg

  19. Transdermal buprenorphine in clinical practice--a post-marketing surveillance study in 13,179 patients.

    PubMed

    Griessinger, Norbert; Sittl, Reinhard; Likar, Rudolf

    2005-08-01

    The objective of this post-marketing surveillance study was to collect effectiveness and safety data on the labelled use of buprenorphine transdermal patches (Transtec*) under routine clinical conditions. For this open, observational study, patients with moderate to severe cancer or non-cancer pain requiring treatment with an opioid analgesic were recruited at hospitals, outpatient clinics and general practitioners' practices in Germany. Buprenorphine transdermal patches (35 microg/h, 52.5 microg/h or 70 microg/h) were prescribed at physicians' discretion in accordance with the product's Summary of Product Characteristics (SmPC). Patients assessed their pain relief as 'very good', 'good', 'satisfactory', 'poor' or 'no effect'. Investigators were instructed to report all adverse events throughout the observation period. On completion, effectiveness and tolerability were evaluated for the overall study population, cancer and non-cancer patients, and patients < 70 years and > or = 70 years. Other analyses assessed pain relief with respect to previous opioid treatment and increased patch strength, and in patients who remained on their original dose. The total observation time was 9 months, and the average individual documented treatment time was 60.8 days. A total of 13,179 patients were evaluated; 3690 (28%) with cancer pain and 9489 (72%) with non-cancer pain. The most frequent diagnoses in non-cancer patients were musculoskeletal disorders (77%) and neuropathy (23%). In the great majority of cases (78%), treatment was started with the 35 microg/h patch. The initial dose needed to be increased subsequently only in about 18% of subjects. Buprenorphine transdermal patches provided effective, sustained and dose-dependent analgesia in patients with cancer and non-cancer pain, irrespective of the patients' age or pain syndromes. Whereas good or very good pain relief was documented only for 6% of the patients with the initial assessment, this percentage increased to 71% at

  20. All-case post-marketing surveillance of 1371 patients treated with pirfenidone for idiopathic pulmonary fibrosis.

    PubMed

    Ogura, Takashi; Azuma, Arata; Inoue, Yoshikazu; Taniguchi, Hiroyuki; Chida, Kingo; Bando, Masashi; Niimi, Yuka; Kakutani, Shinichi; Suga, Moritaka; Sugiyama, Yukihiko; Kudoh, Shoji; Nukiwa, Toshihiro

    2015-09-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with a median survival of 2-5 years and limited treatment options. In 2008, pirfenidone became the first drug to be approved for IPF treatment in Japan. The aim of this study was to assess the safety of pirfenidone for IPF treatment in a clinical setting. We conducted a safety-oriented post-marketing surveillance of all patients with IPF who were administered pirfenidone in the first year after its launch in Japan. This was a prospective, non-interventional, observational study. Case report forms were used to collect survey data, comprising adverse events, acute exacerbations, patient demographics, concomitant drug use, and concurrent treatment data. Of the 1371 patients available for safety evaluation, two-thirds had stage III-IV disease. The incidence of total adverse drug reactions (ADRs) was 64.6%. ADRs with an incidence of ≥3% were decreased appetite, photosensitivity reaction, nausea, abdominal discomfort, malaise, somnolence, and hepatic function abnormal. This safety profile was consistent with the findings in phase II and III trials in Japan. The discontinuation rates due to adverse events at 12 months for each disease stage were similar; however, discontinuation caused by disease progression increased with disease severity. Treatment with pirfenidone stabilized both vital capacity and subjective symptoms in most patients (70-80%) treated for at least 6 months. This post-marketing surveillance in Japan showed that pirfenidone was generally well tolerated in patients with IPF, including those with severe lung function impairment. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  1. Risk Management Post-Marketing Surveillance for the Abuse of Medications Acting on the Central Nervous System: Expert Panel Report

    PubMed Central

    Johanson, Chris-Ellyn; Balster, Robert L.; Henningfield, Jack E.; Schuster, Charles R.; Anthony, James C.; Barthwell, Andrea G.; Coleman, John J.; Dart, Richard C.; Gorodetzky, Charles W.; O’Keeffe, Charles; Sellers, Edward M.; Vocci, Frank; Walsh, Sharon L.

    2010-01-01

    The abuse and diversion of medications is a significant public health problem. This paper is part of a supplemental issue of Drug and Alcohol Dependence focused on the development of risk management plans and post-marketing surveillance related to minimizing this problem. The issue is based on a conference that was held in October, 2008. An Expert Panel was formed to provide a summary of the conclusions and recommendations that emerged from the meeting involving drug abuse experts, regulators and other government agencies, pharmaceutical companies and professional and other non-governmental organizations. This paper provides a written report of this Expert Panel. Eleven conclusions and eleven recommendations emerged concerning the state of the art of this field of research, the regulatory and public health implications and recommendations for future directions. It is concluded that special surveillance tools are needed to detect the emergence of medication abuse in a timely manner and that risk management tools can be implemented to increase the benefit to risk ratio. The scientific basis for both the surveillance and risk management tools is in its infancy, yet progress needs to be made. It is also important that the unintended consequences of increased regulation and the imposition of risk management plans be minimized. PMID:19783383

  2. Post-market surveillance of GM foods: applicability and limitations of schemes used with pharmaceuticals and some non-GM novel foods.

    PubMed

    Wal, J-M; Hepburn, P A; Lea, L J; Crevel, R W R

    2003-08-01

    Post-market surveillance (PMS) is increasingly required by some regulatory authorities for the marketing approval of GM-Novel Foods. This requirement, in addition to a complete conventional safety assessment, aims to show that unexpected (adverse) effects do not occur after long-term everyday exposure. Large food manufacturers have systems to obtain feedback from consumers on their products. We show that such systems can be enhanced to collect information on possible health effects of specific products and relate these to intake in specific groups of consumers. The term post-launch monitoring (PLM) is proposed to distinguish the process from that used for pharmaceuticals. GM foods differ from branded products to which existing systems have been applied. The paper discusses whether and how such systems could be applied to GM foods and what additional elements would need to be incorporated in them. A PLM system should define and organize the flow of information between the different stakeholders. We conclude that because such data will be generated from a range of sources and will need to be collated, verified, and integrated, an independent agency will be essential to undertake this activity in order to balance the interests of all stakeholders and ensure public trust.

  3. Freeze-dried live attenuated smallpox vaccine prepared in cell culture "LC16-KAKETSUKEN": Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice.

    PubMed

    Nishiyama, Yasumasa; Fujii, Tatsuya; Kanatani, Yasuhiro; Shinmura, Yasuhiko; Yokote, Hiroyuki; Hashizume, So

    2015-11-09

    In Japan, production of smallpox vaccine LC16m8 (named LC16-KAKETSUKEN) was restarted and was determined to be maintained as a national stockpile in March 2002. To conduct a post-marketing surveillance study of the vaccination of freeze-dried live attenuated smallpox vaccine prepared in cell culture LC16-KAKETSUKEN using attenuated vaccinia strain LC16m8. The study complied with Good Clinical Practice, focusing on a comparison between primary vaccinees and re-vaccinees. 268 personnel (261 males and 7 females) of the Japan Ground Self-Defense Force were inoculated with LC16-KAKETSUKEN and thereafter adverse events and efficacy were evaluated. Among 268 vaccinee participants, the following vaccinees showed adverse events, none serious: 53 of 196 primary vaccinees (without previous smallpox vaccination), 4 of 71 re-vaccinees (with previous smallpox vaccination) and 1 vaccinee with unknown previous vaccination history. A breakdown of adverse events observed in this study (total 268 vaccinees) showed the following minor or mild adverse events: 52 (19.4%) swelling of axillary lymph node, 4 (1.5%) fever, 2 (0.7%) fatigue, 1 (0.4%) of rash, 14 (5.2%) erythema at the inoculation site, 1 (0.4%) swelling at the inoculation site and 1 (0.4%) autoinoculation. The incidence of adverse events for primary vaccinees (53/196; 27.0%) was significantly higher than for re-vaccinees (4/71; 5.6%). However, the proportion of vaccine take was significantly higher for primary vaccinees (185/196; 94.4%) than for re-vaccinees (58/71; 81.7%). Although the proportion of vaccine take of re-vaccinees was significantly lower than for primary vaccinees due to preexisting immunity by previous vaccination, no significant difference was found in neutralizing antibody titers between primary vaccinees and re-vaccinees at 1, 4 and 7 months after LC16-KAKETSUKEN vaccination. The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the

  4. Effectiveness and tolerability of parenteral testosterone undecanoate: a post-marketing surveillance study.

    PubMed

    Wolf, Jan; Keipert, Dieter; Motazedi, Heiko; Ernst, Michael; Nettleship, Joanne; Gooren, Louis

    2017-08-16

    This observational post-marketing study of parenteral testosterone undecanoate (TU) in a non-selected population aimed to: examine the effectiveness of TU as treatment of hypogonadism; record adverse drug reactions (ADR) quantitatively particularly regarding polycythemia, prostate safety and cardiovascular-related metabolic risk factors; and verify whether recommended injection intervals apply to routine clinical practice. Eight hundred and seventy subjects from 259 outpatient units scheduled to visit the clinic six times were included. Effectiveness and tolerability of TU administration were assessed on a 4-point scale. Body weight, waist girth, blood pressure, hemoglobin levels, hematocrit, prostate-specific antigen (PSA), and digital rectal prostate examination were assessed. Over 90% of subjects completed the observational duration of 52.8 ± 9.7 weeks (mean ± SD) and 56% judged effectiveness as very good, 30.8% as good. 63.1% judged tolerability as very good, and 24.4% as good. No adverse effects on indicators of cardiovascular risk were observed. Polycythemia occurred in one subject and a supranormal hematocrit in one subject. Four subjects developed supranormal PSA levels. Prostate carcinoma was found in one subject, one subject had recurrence of a previously surgically treated prostate carcinoma, and the other two showed no indication of malignancy. Parenteral TU is safe, effective, and well-tolerated in clinical practice proving a good therapeutic option for hypogonadism.

  5. Feasibility of using recipients of health promotional newsletters for post-marketing surveillance.

    PubMed

    Mead, L A; Ford, D E; Roht, L H; Beach, C L; Klag, M J

    2000-06-01

    Achieving an adequate sample size is one of the major difficulties in performing post-marketing observational studies of health outcomes in persons taking specific drug preparations. We assessed the feasibility of recruiting participants for such a study of Cardizem CD from approximately 400,000 U.S. recipients of a health promotion newsletter. A three-page questionnaire was sent to a 2.5% random sample (n = 10,000) of recipients, stratified by geographic region. After two mailings, 2779 (28%) returned the questionnaire. Of the 2779 respondents, 2132 (77%) reported having high blood pressure. Eighty-seven percent indicated a willingness to participate in a long-term prospective study. In a multivariate model, calcium channel blocker (CCB) use was associated with a history of coronary heart disease, duration of hypertension medication use greater than 1 year, a rating of good or excellent hypertension care, higher systolic blood pressure, higher education level, family history of cardiovascular disease, and history of smoking. These results indicate that self-reported CCB users may be at greater risk of cardiovascular heart disease and that it is feasible to use health promotion newsletters as a source of participants in prospective studies of cardiovascular disease.

  6. Suspected adverse reactions to contrast media in Campania Region (Italy): results from 14 years of post-marketing surveillance.

    PubMed

    Sessa, Maurizio; Rossi, Claudia; Mascolo, Annamaria; Grassi, Enrico; Fiorentino, Sonia; Scavone, Cristina; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

    2015-01-01

    During the last years in Italy, contrast media (CM) use increased. An increase of monitoring activities on CM-induced adverse drug reaction (ADR) is necessary, also in our regional territory. The main aim of this study was to give a preliminary evaluation of all Spontaneous Reports of ADRs (SRA) attributed to CM sent to Campania Pharmacovigilance Regional Center (CRFVC) from 01 January 2001 to 31 October 2014. For each SRA we evaluated: frequency and source, ADRs onset (time to event, seriousness and outcome), socio-demographic characteristics and risk factors of cases, the most reported CM (checking for pharmacodynamic and pharmacokinetic interactions). A total of 111 SRA were sent to CRFVC; specialist in radiology was the main source of reports. Ninety-seven SRA (87.3%) were referable to hypersensitivity reactions. Thirty-four SRA (30.6%) reported serious ADRs. The most reported CM were iopamidol, gadobenic acid and gadoteric acid. We identified two SRA induced by pharmacokinetic and/or pharmacodynamic interactions. During 14 years of post-marketing surveillance, only few SRA concerning CM-induced ADRs were sent to CRFVC probably due to underreporting. We aim to improve monitoring activity on CM-induced ADRs especially in hospitals. Most reported ADR and CM were in line with current body of literature.

  7. [Safety and efficacy of docetaxel in prostate cancer patients: based on the post-marketing surveillance in Japan].

    PubMed

    Mera, Takeshi; Saijo, Nagahiro; Akaza, Hideyuki

    2012-04-01

    The safety and efficacy of docetaxel in prostate cancer were evaluated based on the results of post-marketing surveillance. 149 patients were enrolled between September 2008 and May 2010. The starting dose of docetaxel was 75 mg/m² in 53 patients(36%), 70 mg/m² in 55 (37%), and ≤ 60 mg/m² in 41(28%). The median number of treatment cycles was 8 (range, 1 to 10). There was no age difference observed in the starting doses and the treatment cycles. The most common ≥ grade 3 adverse drug reactions (ADRs) were neutropenia (71%)and leukocytopenia (51%), and they occurred more frequently in patients receiving ≥ 70 mg/m². However, the multi-variate analyses revealed that ≥ grade 3 ADRs did not correlate with the starting doses. Infection-related events (≥ grade 3) and interstitial pneumonia were observed in 15% and 1% of patients, respectively. Prostate-specific-antigen (PSA) flare appeared in 19% of 95 evaluable patients at median period of 26 days from treatment initiation. It continued with median duration of 39. 5 days. PSA response rate as defined ≥ 50% level decline was 37%(95%confidence interval: 27-47) in evaluable patients. It was low in patients receiving ≤ 60 mg/m² (18%). There was no notable difference between patients with initial dose of 75 and 70 mg/m². Further investigation for the longer term is warranted.

  8. Postmarket Drug Surveillance Without Trial Costs: Discovery of Adverse Drug Reactions Through Large-Scale Analysis of Web Search Queries

    PubMed Central

    Gabrilovich, Evgeniy

    2013-01-01

    Background Postmarket drug safety surveillance largely depends on spontaneous reports by patients and health care providers; hence, less common adverse drug reactions—especially those caused by long-term exposure, multidrug treatments, or those specific to special populations—often elude discovery. Objective Here we propose a low cost, fully automated method for continuous monitoring of adverse drug reactions in single drugs and in combinations thereof, and demonstrate the discovery of heretofore-unknown ones. Methods We used aggregated search data of large populations of Internet users to extract information related to drugs and adverse reactions to them, and correlated these data over time. We further extended our method to identify adverse reactions to combinations of drugs. Results We validated our method by showing high correlations of our findings with known adverse drug reactions (ADRs). However, although acute early-onset drug reactions are more likely to be reported to regulatory agencies, we show that less acute later-onset ones are better captured in Web search queries. Conclusions Our method is advantageous in identifying previously unknown adverse drug reactions. These ADRs should be considered as candidates for further scrutiny by medical regulatory authorities, for example, through phase 4 trials. PMID:23778053

  9. Safety and effectiveness of certolizumab pegol in patients with rheumatoid arthritis: Interim analysis of post-marketing surveillance.

    PubMed

    Kameda, Hideto; Nishida, Keiichiro; Nannki, Toshihiro; Watanabe, Akira; Oshima, Yukiya; Momohara, Shigaki

    2017-01-01

      Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis. Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal. The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response. In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

  10. Post-marketing surveillance study of the efficacy and safety of vardenafil among patients with erectile dysfunction in primary care.

    PubMed

    Kim, C M; Kim, Y S; Sunwoo, S; Cho, B; Rho, M; Yang, Y J; Kim, C H; Shin, H C; Lee, S Y; Kim, D H

    2007-01-01

    To evaluate the safety and efficacy of vardenafil in primary care, we undertook a post-marketing surveillance study in 384 men with erectile dysfunction (ED), enrolled by 22 family physicians in Korea, from July 2004 to August 2005. Of the 384 patients enrolled, 343 (89.3%) returned for efficacy assessment and safety evaluation. Among the latter, 279 patients (81.3%) reported that their erectile function improved, 292 (92.1%) showed enhanced IIEF (International Index of Erectile Function)-5 scores and 265 (77.9%) responded that they were 'very satisfied' or 'satisfied' with vardenafil treatment. The most frequent reason for patient satisfaction with vardenafil was erectile potency (62.4%), followed by safety (42.4%), rapid onset (35.3%), adequate duration of efficacy (28.5%) and easy administration (25.9%). A total of 23 adverse events were observed in 18 patients, with the most frequent being hot flushes (3.2%), followed by headache (1.2%), nasal congestion (0.6%), color vision disturbance (0.3%), dizziness (0.3%), dry mouth (0.3%), dyspepsia (0.3%), nausea (0.3%) and diarrhea (0.3%). Only one patient discontinued vardenafil as a direct result of an adverse event. These results suggest that vardenafil prescribed by primary care physicians improved erectile function and was well tolerated by patients with ED.

  11. An update on the safety and tolerability of pimecrolimus cream 1%: evidence from clinical trials and post-marketing surveillance.

    PubMed

    Langley, Richard G B; Luger, Thomas A; Cork, Michael J; Schneider, Dirk; Paul, Carle

    2007-01-01

    In this report, we review the data on the safety and tolerability of pimecrolimus cream 1% (Elidel) from clinical trials and post-marketing surveillance in patients with atopic dermatitis. These data demonstrate that topically applied pimecrolimus is minimally absorbed through the skin and has a favourable safety margin. The most common treatment-related adverse events are transient local reactions, particularly skin burning (16.1 and 12.9 events per 1,000 patient-months of follow-up in adults and children, respectively). When compared to the vehicle, the use of pimecrolimus cream 1% is associated with an increased incidence of herpes simplex virus infections in children (relative risk: 2.5; 95% confidence interval: 1.2-5.8; p = 0.017). However, pimecrolimus cream 1% does not increase the incidence of any skin infection in comparison with moderately potent topical corticosteroids and lacks other corticosteroid-related side effects such as skin atrophy. While cases of malignancy have been reported in patients who have used pimecrolimus cream 1%, there is no clinical evidence to establish that treatment with pimecrolimus cream 1% increases the risk of malignancy. Copyright 2007 S. Karger AG, Basel.

  12. A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer.

    PubMed

    Ishiguro, Megumi; Watanabe, Toshiaki; Yamaguchi, Kensei; Satoh, Taroh; Ito, Hideyuki; Seriu, Taku; Sakata, Yuh; Sugihara, Kenichi

    2012-04-01

    Cetuximab (Erbitux(®)) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval. All patients to be treated with cetuximab were enrolled by the central enrolment method. Data on treatment status, and incidence and severity of adverse drug reactions were collected. The target number of patients was 1800. A total of 2126 patients were enrolled from 637 institutions. Among 2006 patients analysed, 93.2% received cetuximab as third-line or later treatment. The median duration of treatment was 15.3 weeks, and 11.1% of patients received treatment for >48 weeks. The incidence of adverse drug reactions was 89.6%, of which ≥grade 3 was 21.5%. The incidence of infusion reactions was 5.7% (any grade), with 83.3% of them occurring at the first administration. The incidence of skin disorders was 83.7% (any grade), and the time to event varied for each skin disorder. The incidence of interstitial lung diseases was 1.2% (any grade). Diarrhoea and haematotoxicity scarcely occurred with cetuximab alone. In this surveillance, the incidence and categories of adverse drug reactions are not distinct from previous reports. Although most patients received cetuximab as third-line or later treatment, treatment was maintained with a median duration of 15 weeks. Cetuximab treatment in practical use is considered to be well tolerated and clinically useful in Japanese patients with metastatic colorectal cancer.

  13. The US Postmarketing Surveillance Study of Adult Osteosarcoma and Teriparatide: Study Design and Findings From the First 7 Years

    PubMed Central

    Andrews, Elizabeth B; Gilsenan, Alicia W; Midkiff, Kirk; Sherrill, Beth; Wu, Yun; Mann, Beth H; Masica, Daniel

    2012-01-01

    The Osteosarcoma Surveillance Study, an ongoing 15-year surveillance study initiated in 2003, is a postmarketing commitment to the United States (US) Food and Drug Administration to evaluate a potential association between teriparatide, rhPTH(1–34), a recombinant human parathyroid hormone analog (self-injectable medication to treat osteoporosis), and development of osteosarcoma in response to a finding from preclinical (animal) studies. Incident cases of primary osteosarcoma diagnosed in adults (aged ≥40 years) on or after January 1, 2003, are identified through population-based state, regional, and comprehensive cancer center registries in the US. Information on possible prior treatment with teriparatide, on demographics, and on risk factors is ascertained by patient or proxy telephone interview after patient consent. Between June 2004 and September 30, 2011, 1448 cases (diagnosed 2003 to 2009) were identified by participating cancer registries (estimated to be 62% of all adult cases in the US for that time period); 549 patients or proxies were interviewed. Interviewed patients were similar to noninterviewed patients with regard to mean age, sex, race, and geographical distribution and tumor type and site of tumor. Mean age of those interviewed was 61 years, 46% were female, 86% were white, and 77% were alive when the case was reported to the study investigators. Data collected in the study provide descriptive information on a large number of adults with osteosarcoma, an uncommon malignant bone tumor. After 7 years of the study, there were no osteosarcoma patients who had a prior history of teriparatide treatment. Thus, approximately halfway through this 15-year study, the study has not detected a pattern indicative of a causal association between teriparatide treatment and osteosarcoma in humans. © 2012 American Society for Bone and Mineral Research. PMID:22991313

  14. Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

    PubMed

    Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Murakami, Masahiro

    2017-05-01

    To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

  15. Safety/Tolerability and efficacy of rivastigmine in taiwanese patients with Alzheimer's disease: a prospective post-marketing surveillance study.

    PubMed

    Chiu, Pai-Yi; Dai, Dao-En; Hsu, Hai-Pei; Lee, Chao; Lin, Juei-Jueng; Kuo, Hung-Chou; Huang, Ying-Chih; Liu, Yung-Chang; Tsai, Ching-Piao

    2009-01-01

    Rivastigmine is approved for the symptomatic treatment of mild to moderate dementia in patients with Alzheimer's disease. The drug was launched in Taiwan in 2000. The primary objective of this post-marketing surveillance (PMS) study was to describe the safety/tolerability of treatment with rivastigmine capsules in patients with Alzheimer's disease. The secondary objectives of this study were to define the optimal titration pattern, maintenance dose, efficacy and patient satisfaction with treatment with rivastigmine capsules. This was a prospective, non-interventional post-marketing observational study in patients who met the criteria for mild or moderate Alzheimer's disease. The primary outcome measure for this trial was the incidence of emerging adverse events. Dosages related to titration patterns and maintenance doses were summarized. Efficacy evaluations conducted using the Mini-Mental State Examination, Clinical Dementia Rating and modified Instrumental Activities of Daily Living scales were also primary outcome measures, and results are shown descriptively. The patients' therapeutic responses to rivastigmine and satisfaction with rivastigmine were secondary outcome measures. Therapeutic response and treatment satisfaction were summarized descriptively. A total of 264 patients were enrolled into the study. The mean duration of exposure to rivastigmine during the study was 151.1 days. Patients were taking rivastigmine 1.5-6 mg twice daily and the most frequent maintenance dose level was 4.5 mg twice daily. Among patients treated with rivastigmine, all primary and secondary outcome measures showed improvement or stabilization of cognition and global functioning. Of the 253 safety analysis patients, 155 patients (61.3%) reported at least one adverse event. The most frequent adverse events by system organ class were psychiatric disorders (9.1%) and gastrointestinal disorders (8.3%). The most common adverse events observed were dizziness (5.5%), insomnia (5

  16. Grepafloxacin: a review of its safety profile based on clinical trials and postmarketing surveillance.

    PubMed

    Lode, H; Vogel, F; Elies, W

    1999-01-01

    The safety profile of grepafloxacin has been characterized in a number of preclinical and clinical studies. Preclinical investigations have shown that its toxicologic profile is similar to that of other fluoroquinolones, and phase I studies in humans have confirmed these data. A photosensitivity study demonstrated equivalence with ciprofloxacin, and a study in elderly patients taking the highest clinical dose of grepafloxacin indicated that prolongation of the QTc interval by grepafloxacin was less than 2 ms, 15 times less than that observed in a study of erythromycin. In phase II and III clinical investigations conducted in the United States and the United Kingdom, safety data have been gathered from more than 3000 patients with either community-acquired pneumonia or acute bacterial exacerbations of chronic bronchitis. The most common adverse events with grepafloxacin 400 or 600 mg were gastrointestinal, such as nausea, vomiting, and diarrhea. The frequency of these adverse events was similar to that seen with ciprofloxacin. Significantly more patients reported a mild, unpleasant metallic taste with grepafloxacin than with ciprofloxacin, but <1% of patients withdrew from therapy because of this. Headache was observed significantly more often in ciprofloxacin-treated patients than in grepafloxacin-treated patients. Recent postmarketing data confirm the good tolerability and safety profile of grepafloxacin. These data, from a case-report study of more than 9000 patients in Germany, demonstrated that only 2.3% of patients reported adverse events when grepafloxacin was used in routine clinical practice. The most frequently reported events were nausea (0.8%) and gastrointestinal symptoms (0.4%). Dizziness was reported by only 0.3% of patients, and only 4 patients (0.04%) reported photosensitization. Adverse events did not appear to be either dose dependent or related to diagnosis. More than 400,000 patients world-wide have received grepafloxacin treatment. No new

  17. The safety of quetiapine: results of a post-marketing surveillance study on 1728 patients in England.

    PubMed

    Twaites, Beverley R; Wilton, Lynda V; Shakir, Saad A W

    2007-06-01

    The safety of the atypical antipsychotic quetiapine as used in general practice in England was examined by prescription-event monitoring (PEM). Patients were identified from dispensed National Health Service (NHS) prescriptions issued by general practitioners (GPs) for quetiapine between October 1997 and July 1999. The outcome data were event reports obtained by sending questionnaires ('green forms') to the prescribing doctor at Least 6 months after the first prescription for an individual patient. Green forms with clinically useful information on 1728 patients (median age 39 years (IQR 30-56); 53% female) were received. The most frequently reported event during the first month of treatment was 'drowsiness/sedation' (47; 3% cohort). This was also the most frequently reported specified adverse drug reaction (ADR) to quetiapine (7; 11% of 65 reported ADRs) and the highest reported clinical reason for stopping quetiapine (51; 6% of the 734 reported reasons for stopping). There was a low incidence of extrapyramidal disease (21 during treatment, 1% of cohort) and hyperprolactinaemia (three during treatment, 0.2%) in this study. Three cases of diabetes mellitus in this cohort were reported to be a new diagnosis. Six pregnancies were reported during treatment with quetiapine, five of which were exposed during the first trimester only. There were four Live births with no reported congenital abnormaLities. Fifty-six deaths were reported during this study (3% cohort). The most frequently reported causes of death reLated to the cardiovascular (18) and respiratory (15) systems. The results of this post-marketing surveillance study demonstrated that quetiapine is generally well-tolerated when used in general practice.

  18. Post-marketing surveillance in the published medical and grey literature for percutaneous transluminal coronary angioplasty catheters: a systematic review

    PubMed Central

    2013-01-01

    Background Post-marketing surveillance (PMS) may identify rare serious incidents or adverse events due to the long-term use of a medical device, which was not captured in the pre-market process. Percutaneous transluminal coronary angioplasty (PTCA) is a non-surgical procedure that uses a balloon-tipped catheter to enlarge a narrowed artery. In 2011, 1,942 adverse event reports related to the use of PTCA catheters were submitted to the FDA by the manufacturers, an increase from the 883 reported in 2008. The primary research objective is to conduct a systematic review of the published and grey literature published between 2007 and 2012 for the frequency of incidents, adverse events and malfunctions associated with the use of PTCA catheters in patients with coronary artery disease (CAD). Grey literature has not been commercially published. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and PubMed for medical literature on PMS for PTCA catheters in patients with CAD published between January 2007 and July 2012. We also searched the grey literature. Results This review included 11 studies. The in-hospital adverse events reported were individual cases of myocardial infarction and hematoma. In studies of patients with coronary perforation, more patients with balloon angioplasty were identified compared with patients who required stenting. Conclusions Our systematic review illustrates that the volume and quality of PMS studies associated with the use of PTCA catheters in patients with CAD are low in the published and grey literature, and may not be useful sources of information for decisions on safety. In most studies, the objectives were not to monitor the long-term safety of the use of PTCA catheters in clinical practice. Future studies can explore the strengths and limitations of PMS databases administered by regulatory authorities. PMID:24112460

  19. Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study.

    PubMed

    Osawa, Masahiro; Kudoh, Shoji; Sakai, Fumikazu; Endo, Masahiro; Hamaguchi, Tetsuya; Ogino, Yumiko; Yoneoka, Miyo; Sakaguchi, Motonobu; Nishimoto, Hiroyuki; Gemma, Akihiko

    2015-12-01

    Drug-induced interstitial lung disease (ILD) is one of the most serious adverse reactions associated with the molecularly targeted drugs. Panitumumab has been approved for advanced or recurrent colorectal cancer. Although there were no adverse reaction reports of ILD in panitumumab monotherapy, 4 cases in combination chemotherapy were reported prior to its approval in Japan in 2010. Several studies also reported that the incidence of drug-induced ILD was higher in Japan than in other countries. The clinical features of ILD and the associated risk factors therefore need investigation. We analyzed the data from 3085 unresectable, advanced or recurrent colorectal cancer patients enrolled in a postmarketing all-case surveillance study of panitumumab in Japan. ILD case reports were assessed based on the clinical and radiologic findings by a committee of external experts. Multivariate analysis using Cox's hazard model identified the risk factors. ILD incidence (1.3 %) and mortality rates (51.3 %) were similar to those of patients receiving another anti-epidermal growth factor receptor (EGFR) monoclonal antibody in Japan. No specific onset timing was determined. Although panitumumab-specific ILD findings were not observed in computed tomography images or clinical practice, panitumumab can induce ILD with diffuse alveolar damage, as do the other anti-EGFR targeting drugs. A history/complication of ILD, male sex, poor general condition, and 65 years or older were identified as ILD risk factors, and no history of previous drug treatment was an apparent risk factor. Panitumumab-induced ILD can occur at any time after initiation, and close and regular monitoring is needed.

  20. Frovatriptan in the practice of office-based neurologists/pain therapists: Results of postmarketing surveillance study ALADIN.

    PubMed

    Wallasch, Thomas-Martin

    2010-01-01

    Large postmarketing surveillance (PMS) studies have demonstrated the efficacy and tolerability of frovatriptan for treatment of acute migraine in patients attending general practitioners (GPs). The aim of the ALADIN (Allegro Anwendung durch interessierte Neurologen [Allegro application by interested neurologists]) PMS study was to evaluate frovatriptan in patients attending neurologists or pain therapists. Patients fulfilling International Headache Society criteria for migraine, with or without aura, were enrolled. Patients completed an attack diary, including details of the attack, time to onset of action of frovatriptan, and recurrence of headache. Physicians completed a case report form detailing prior and actual migraine treatment. Frovatriptan 2.5 mg was administered for up to three consecutive attacks. In total, 2160 patients were enrolled and data were obtained for 5831 attacks. Patients attending neurologists had more frequent attacks and longer history of migraine compared with those attending GPs. Median time to frovatriptan onset of action was 40 min and time to freedom from headache 70 min. An average of 1.2 frovatriptan tablets was required per attack, and mean additional analgesic use was 0.13. Recurrent headache occurred in 13.6%-15.5% of patients. Physicians as well as patients judged frovatriptan onset and duration of action as at least "good" in approximately 80% of attacks. A similar number judged the efficacy of frovatriptan against headache as "better" than previous treatment. The study drug was generally well tolerated. The frequency of adverse events was 0.6%. Frovatriptan, with fast onset of action and low rate of headache recurrence, was efficacious and well accepted by migraineurs attending neurologists or pain therapists. Approximately 80% of patients wished to continue migraine treatment with frovatriptan.

  1. Frovatriptan for acute treatment of migraine associated with menstruation: results from an open-label postmarketing surveillance study.

    PubMed

    Newman, Lawrence C; Harper, Samira; Jones, Beverly A; Campbell, John

    2009-08-01

    To examine the effectiveness and tolerability of acute treatment with frovatriptan in women experiencing menstrual migraine (MM) vs. female migraineurs with non-MM. This was an open-label postmarketing surveillance study (n = 7107) conducted in Germany to assess acute treatment with frovatriptan in one to three migraine attacks. This retrospective subanalysis evaluated acute frovatriptan treatment in women who experienced >or=1 MM attack vs. those women with non-MM attacks. Effectiveness and tolerability were graded using a 4-point scale (1 = very good, 2 = good, 3 = satisfactory, 4 = poor). Demographics were similar in MM (n = 1931) and non-MM patients (n = 2080), except that mean age (38.3 vs 45.3 years, respectively) and number of migraine attacks per month were less in the MM group than in the non-MM group (both p < 0.001). Although 98% of women reported that their previous migraines were moderate or severe, only one third in each treatment group previously used triptans. Prestudy medications were rated as good or very good for effectiveness by 20.3% and 19.2% of the MM and non-MM groups, respectively. In contrast, the effectiveness of frovatriptan was rated as very good or good by 92.7% and 90.9% of women in the MM and non-MM groups, respectively. Forty-three percent and 96% of all women rated their previous medication and frovatriptan, respectively, as having good or very good tolerability. Among women rating their previous medication as poor or satisfactory, most (94%) rated frovatriptan as very good or good. Acute frovatriptan treatment improved patient ratings of treatment effectiveness and tolerability in women with migraine associated with menses.

  2. Efficacy, tolerability and safety of nebivolol in patients with hypertension and diabetes: a post-marketing surveillance study.

    PubMed

    Van Bortel, L M

    2010-09-01

    Hypertension is a widely prevalent condition of elevated blood pressure (BP) and is the leading risk factor for the development of cardiovascular disease (CVD). Many patients have additional risk factors such as diabetes mellitus (DM) or previous history of CVD. Nebivolol is a third-generation beta (beta)-blockers which has been shown not to influence metabolic parameters in patients with DM. This postmarketing surveillance study aimed to collect information on the efficacy, safety and tolerability of nebivolol in hypertensive patients with concomitant DM. Hypertensive patients with DM followed by 52 cardiologists, internal medicine specialists and general practitioners, between 24 August 2003 and 9 January 2007 in The Netherlands were included in this study. Physicians were asked to survey nebivolol treatment for 6 months. A total of 510 patients were enrolled. Overall, 93.3% of patients were diagnosed with essential hypertension and 6.7% with secondary hypertension. All patients were co-diagnosed with DM. Nebivolol therapy was associated with a significant reduction in both systolic blood pressure (BP) and diastolic BP versus baseline (p < 0.001 for both). These reductions were seen regardless of reason for initiation of nebivolol (i.e. first diagnosis of hypertension, resistance or intolerance to previous antihypertensive medication, or other reasons). A significant improvement in blood glucose was seen at 4 months (-0.6 mmol/L; p = 0.021). Significant reductions in total cholesterol (-1.45 mmol/L; p = 0.006), low density lipoprotein (LDL) cholesterol (-1.32 mmol/L; p = 0.003) and LDL/high density lipoprotein (HDL) cholesterol ratio (-0.77; p = 0.011) were observed at 2 months. No significant changes were seen in HDL cholesterol and triglycerides. Nebivolol treatment was associated with a significantly reduced BP, improved blood glucose and LDL cholesterol levels and was well tolerated in hypertensive patients with concomitant DM.

  3. Memantine effects on behaviour in moderately severe to severe Alzheimer's disease: a post-marketing surveillance study.

    PubMed

    Clerici, Francesca; Vanacore, Nicola; Elia, Antonietta; Spila-Alegiani, Stefania; Pomati, Simone; Da Cas, Roberto; Raschetti, Roberto; Mariani, Claudio

    2012-02-01

    The aim of this study is to evaluate memantine effectiveness on behavioural and psychological symptoms of dementia (BPSD) in clinical practice and to identify variables that may predict the therapy effects. The effects of memantine on behaviour were analysed in the database of a post-marketing surveillance study promoted by the Lombardy Region Health Office and involving 43 Alzheimer's disease (AD) Units. From July to December 2005, 399 moderately severe-to-severe AD patients free of cholinergic medications were enrolled, treated with memantine and followed-up for 6 months. BPSD were assessed in a subgroup of 297 patients [mean age 77 ± 8 years; 73% females; mean neuropsychiatric inventory (NPI) score 28 ± 24] for whom the 12-item NPI subscores at baseline, and at 3 and 6 months were available. The 12 BPSD were clustered as follows: affect, physical behaviour, psychosis and hypomania. The main outcome measure was the proportion of individual cluster responders at 6 months of therapy. The proportion of individual cluster responders was 30% affect, 24% physical behaviour, 29% psychosis, 27% hypomania. Patients taking 20 mg memantine daily during the study period had a statistically significant higher probability to experience behavioural improvement than those who discontinued treatment or did not complete memantine titration (affect OR 9.0; 95% CI 3.8-21.6; physical behaviour OR 17.8; 95% CI 5.9-53.6; psychosis OR 23.6; 95% CI 5.1-110.8). The logistic regression analysis was not applicable to the hypomania subsyndrome because of the low cluster prevalence. The standard 20 mg daily memantine treatment regimen was found to be associated with a modest 6-month behavioural improvement in the affect, physical behaviour and psychosis domains in 24-30% of patients.

  4. Hepatoxicity associated with weight-loss supplements: A case for better post-marketing surveillance

    PubMed Central

    Lobb, Ano

    2009-01-01

    There is a growing number of case reports of hepatoxicity from the widely marketed weight-loss supplement Hydroxycut, which contains the botanical ingredient Garcinia cambogia. These case reports may substantially undercount the true magnitude of harm. Based on the past experience with harmful dietary supplements, US regulators should assume the more precautionary approach favored by Canada and Europe. Lacking effective adverse event surveillance for supplements, or the requirements to prove safety prior to coming to the market, case reports such as those summarized here assume added importance. PMID:19360927

  5. Hepatoxicity associated with weight-loss supplements: a case for better post-marketing surveillance.

    PubMed

    Lobb, Ano

    2009-04-14

    There is a growing number of case reports of hepatoxicity from the widely marketed weight-loss supplement Hydroxycut, which contains the botanical ingredient Garcinia cambogia. These case reports may substantially undercount the true magnitude of harm. Based on the past experience with harmful dietary supplements, US regulators should assume the more precautionary approach favored by Canada and Europe. Lacking effective adverse event surveillance for supplements, or the requirements to prove safety prior to coming to the market, case reports such as those summarized here assume added importance.

  6. Post-marketing surveillance of methadone and buprenorphine in the United States.

    PubMed

    Dasgupta, Nabarun; Bailey, Elise J; Cicero, Theodore; Inciardi, James; Parrino, Mark; Rosenblum, Andrew; Dart, Richard C

    2010-07-01

    There have been recent increases in the use of methadone and buprenorphine in the United States. Methadone is increasingly being used for pain management, and buprenorphine use has expanded to include treatment for opioid addiction, leading to exposures of these drugs in new populations. There is a debate about the relative safety of these two drugs in routine outpatient medical use. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Programs were used to analyze rates of abuse, misuse, and diversion using the Drug Diversion, Key Informant, Poison Center and Opioid Treatment Programs, 2003-2007. National rate and rate ratios were calculated using population and person-time exposed denominators. Detailed data are presented on severity of medical outcome and drug formulations. Between 2003 and 2007, there were steady increases in the rates of abuse, misuse, and diversion of both methadone and buprenorphine. Rate ratios (per 100,000 population per quarter) of abuse, misuse, and diversion were consistently higher for methadone than buprenorphine. RADARS System poison centers received 7,476 calls for methadone and 1,117 calls for buprenorphine. After accounting for availability, there were higher rates of calls for methadone misuse, abuse, and diversion than buprenorphine in three of the four programs. The numbers of exposures requiring medical attention correspond to 46.8% and 25.8% of all calls, for methadone and buprenorphine, respectively. The most commonly diverted form of methadone was solid oral tablets (which are typically dispensed at pharmacies, not at opioid treatment programs), comprising 73% of cases. Buprenorphine appears to have a better safety profile than methadone during routine outpatient medical use. However, both medications have roles in the treatment of pain and opioid addiction, and further research into their respective benefits and risks should be conducted.

  7. Post-marketing surveillance of CustomBone Service implanted in children under 7 years old.

    PubMed

    Frassanito, Paolo; Tamburrini, Gianpiero; Massimi, Luca; Di Rocco, Concezio; Nataloni, Angelo; Fabbri, Greta; Caldarelli, Massimo

    2015-01-01

    The CustomBone Service is a bioceramic implant suitable for cranial repair in both adults and children, although there are no clinical data about its use in children under 7 years of age. This surveillance study investigates the outcome in this age group. Twenty-eight children under 7 years old (range, 2.5-6 years) received CustomBone Service from July 2006 to May 2013 in 16 international hospitals. Data of 23 children (12 males and 11 females), harboring 24 prosthesis, were available with a minimum follow-up of 1 year. Sites of the cranial defect were frontal or parietal (20.8 % each), parieto-temporal (16.7 %), fronto-parietal or occipital (12.5 % each), fronto-parieto-temporal or fronto-temporal (8.3 % each). Initial diseases were trauma (54.2 %), malformation (37.5 %), or tumor of the bone/skin (8.3 %). Rupture of the implant occurred in a single case during the implant (1/26 surgeries, 3.8 %) and the cranial repair was achieved by means of the back-up prosthesis. Five adverse events were registered during the follow-up period consisting of three cases of fracture and two of exposure/infection of the prosthesis. All cases required the removal of the device (20.8 %). The failure rate of CustomBone Service under 7 years of age was higher than reported in adults and children over 7 years old (20.8 vs. 3.8 %), However, CustomBone Service may be considered a valid option under 7 years old since other materials are burdened by more significant rates of complications in the long-term period. Due to specific properties of this material, indication to CustomBone Service in toddlers should be carefully evaluated by the surgeon on a case-by-case basis.

  8. Part IV: effects of zolmitriptan orally disintegrating tablet on migraine symptoms and ability to perform normal activities: a post-marketing surveillance study in Germany.

    PubMed

    Diener, Hans-Christoph; Gendolla, Astrid

    2005-01-01

    Zolmitriptan has been developed in an orally disintegrating tablet (ODT) formulation that rapidly dissolves on the tongue and can be taken quickly, conveniently and discreetly without fluid intake. In this 3-month, non-comparative, observational, post-marketing surveillance (PMS) study, 5,570 physicians prescribed the zolmitriptan 2.5 mg ODT for 16,261 patients with migraine. Of the 14,543 patients who were evaluable for efficacy analysis, 94% had reduced headache intensity within 2 hours of taking zolmitriptan 2.5 mg ODT for the first attack. Improvements were reported within 30 minutes in 35% of patients and within 15 minutes in 7% of patients. Non-headache migraine symptoms and normal daily activities improved for the majority of patients within 2 hours of taking zolmitriptan ODT. Ninety-one percent of patients required only a single dose of zolmitriptan 2.5 mg ODT to treat each attack. Ninety-two percent of patients considered zolmitriptan ODT as having very good or good efficacy and 96% said that tolerability was very good or good. This study also demonstrated that 94% of patients would be willing to continue to use zolmitriptan ODT in the future and 81% of patients considered that being able to take the ODT without water was important or very import ant. In summary, zolmitriptan ODT has demonstrated high efficacy and excellent tolerability. In addition, patients found zolmitriptan ODT to be convenient and easy to use, and were willing to continue using the product. Following placebo-controlled studies, these PMS results provide insight into the use of zolmitriptan ODT in a setting more representative of real life than randomised clinical trials, further demonstrating that it provides a reliable and convenient alternative to conventional tablets.

  9. [Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

    PubMed

    Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

    2002-02-01

    As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In

  10. Postmarketing safety surveillance of trivalent recombinant influenza vaccine: Reports to the Vaccine Adverse Event Reporting System.

    PubMed

    Woo, Emily Jane; Moro, Pedro L; Cano, Maria; Jankosky, Christopher

    2017-09-05

    On January 16, 2013, the Food and Drug Administration approved recombinant hemagglutinin influenza vaccine (RIV3) (Spodoptera frugiperda cell line; Flublok), which is the first completely egg-free flu vaccine licensed in the United States. To improve our understanding of the safety profile of this vaccine, we reviewed and summarized reports to the Vaccine Adverse Event Reporting System (VAERS) following RIV3. Through June 30, 2016, VAERS received 88 reports. Allergic reactions, including anaphylaxis, were the most common type of adverse event. Based on medical review, 10 cases met the Brighton Collaboration case definition of anaphylaxis, 21 reports described allergic reactions other than anaphylaxis, and 11 reports described signs and symptoms that suggested hypersensitivity. Other adverse events included injection site reactions, fatigue, myalgia, headache, and fever. The occurrence of anaphylaxis and other allergic reactions in some individuals may reflect an underlying predisposition to atopy that may manifest itself after an exposure to any drug or vaccine, and it does not necessarily suggest a causal relationship with the unique constituents that are specific to the vaccine product administered. Further research may elucidate the mechanism of allergic reactions following influenza vaccination: it is possible that egg proteins and influenza hemagglutinin play little or no role. Vaccination remains the single best defense against influenza and its complications. The information summarized here may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies. Published by Elsevier Ltd.

  11. [A perspective for the role of drug registries in the post-marketing surveillance].

    PubMed

    Traversa, Giuseppe; Sagliocca, Luciano; Magrini, Nicola; Venegoni, Mauro

    2013-06-01

    Drug registries are implemented after the authorization of new products and represent a tool for systematic collection of data aimed at obtaining additional knowledge on appropriateness, effectiveness and safety. The design of registries needs to be coherent with the main objective and a study protocol is required before the implementation. A registry aimed at the appropriateness of drug use should be primarily considered for high cost drugs when there is a risk, either for the patients' safety or for public expenditure, in using the drug outside the approved indications. Since the registry is a condition for the access to drugs, and all users are included, an extremely simplified data collection is required. However, the data should be available at regional level to allow record linkage procedures with other databases for conducting outcome studies. When registries are aimed at acquiring new information on the risk profile, the duration and the regional extension of data collection should be coherent with the expected incidence of events of interest. A great attention should be devoted in preventing that patients are lost to follow-up, since the reasons for being lost are frequently associated with harmful outcomes, such as adverse drug reactions. In a registry focused on effectiveness, the main aim consists in ascertaining the reasons (the prognostic factors), for possible discrepancies between premarketing studies and clinical practice. Taking into account the greater incidence of the expected events, there are fewer reasons for extending data collection to all users, whereas the main attention should focus on quality controls and the ascertainment of confounding factors. Given the relevance of the validity issues, in the set out of a registry it is important to think about ad hoc resources and the adequacy of infrastructures. As for any epidemiological study, an adequate qualification of the researcher/clinician in charge of conducting a registry should be

  12. 78 FR 28853 - Agency Information Collection Activities; Proposed Collection; Comment Request; Postmarket...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Collection; Comment Request; Postmarket Surveillance AGENCY: Food and Drug Administration, HHS. ACTION... on information collection requirements for postmarket surveillance of medical devices. DATES:...

  13. Post-marketing surveillance on the long-term use of dabigatran in Japanese patients with nonvalvular atrial fibrillation: Preliminary report of the J-dabigatran surveillance

    PubMed Central

    Inoue, Hiroshi; Uchiyama, Shinichiro; Atarashi, Hirotsugu; Okumura, Ken; Koretsune, Yukihiro; Yasaka, Masahiro; Yamashita, Takeshi; Ohnishi, Makiko; Yagi, Nobutaka; Fukaya, Taku

    2016-01-01

    Background/aim A post-marketing surveillance (PMS) study is being conducted to investigate the safety and effectiveness of the long-term use of dabigatran etexilate (dabigatran) in Japanese patients with nonvalvular atrial fibrillation (NVAF). Results of an interim analysis of this prospective cohort study including patient characteristics and adverse drug reactions (ADRs) collected up to September 17, 2014 are reported here. Methods Patients with NVAF who began to receive dabigatran for the first time from December 2011 to November 2013 were enrolled at 1042 study sites in Japan. Clinical parameters included patient characteristics, dabigatran dose strength, concomitant medications and outcome events. All outcome events were collected as serious and non-serious adverse events (AEs). ADRs were evaluated in this report. Pre-defined safety events of special interest for intensive survey were serious and non-serious outcome events such as myocardial infarction, as well as the total number of hemorrhage and gastrointestinal disorders. Results A total of 6772 patients were registered. The safety analysis set included 6148 patients; mean age was 70.8±9.9 (SD) years: 2323 patients (37.8%) were aged 75 years or older. Males accounted for 66.8% of the patients. Mean CHADS2 score was 1.8±1.3; the CHADS2 score was 0 in 13.6%, 1 in 31.3%, 2 in 25.9%, 3 in 14.9%, and 4 to 6 in 11.1% of the patients. Of the 6148 patients, 1701 patients (27.7%) were switchers from warfarin and 4407 patients (71.7%) were non-switchers (OAC naïve patients). Treatment adherence was assessed for the first 3 months from the start of treatment for this analysis. Total 5656 patients (92.0%) reported taking dabigatran twice daily (bid) every day according to the label recommendation. During the follow up period [mean duration of follow up: 498±259 days (corresponding to 8386 patient-years)], pre-defined safety events of special interest for intensive survey (reported as serious ADRs) were: myocardial

  14. Post-marketing surveillance on the long-term use of dabigatran in Japanese patients with nonvalvular atrial fibrillation: Preliminary report of the J-dabigatran surveillance.

    PubMed

    Inoue, Hiroshi; Uchiyama, Shinichiro; Atarashi, Hirotsugu; Okumura, Ken; Koretsune, Yukihiro; Yasaka, Masahiro; Yamashita, Takeshi; Ohnishi, Makiko; Yagi, Nobutaka; Fukaya, Taku

    2016-04-01

    A post-marketing surveillance (PMS) study is being conducted to investigate the safety and effectiveness of the long-term use of dabigatran etexilate (dabigatran) in Japanese patients with nonvalvular atrial fibrillation (NVAF). Results of an interim analysis of this prospective cohort study including patient characteristics and adverse drug reactions (ADRs) collected up to September 17, 2014 are reported here. Patients with NVAF who began to receive dabigatran for the first time from December 2011 to November 2013 were enrolled at 1042 study sites in Japan. Clinical parameters included patient characteristics, dabigatran dose strength, concomitant medications and outcome events. All outcome events were collected as serious and non-serious adverse events (AEs). ADRs were evaluated in this report. Pre-defined safety events of special interest for intensive survey were serious and non-serious outcome events such as myocardial infarction, as well as the total number of hemorrhage and gastrointestinal disorders. A total of 6772 patients were registered. The safety analysis set included 6148 patients; mean age was 70.8±9.9 (SD) years: 2323 patients (37.8%) were aged 75 years or older. Males accounted for 66.8% of the patients. Mean CHADS2 score was 1.8±1.3; the CHADS2 score was 0 in 13.6%, 1 in 31.3%, 2 in 25.9%, 3 in 14.9%, and 4 to 6 in 11.1% of the patients. Of the 6148 patients, 1701 patients (27.7%) were switchers from warfarin and 4407 patients (71.7%) were non-switchers (OAC naïve patients). Treatment adherence was assessed for the first 3 months from the start of treatment for this analysis. Total 5656 patients (92.0%) reported taking dabigatran twice daily (bid) every day according to the label recommendation. During the follow up period [mean duration of follow up: 498±259 days (corresponding to 8386 patient-years)], pre-defined safety events of special interest for intensive survey (reported as serious ADRs) were: myocardial infarction, reported in 5

  15. [Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

    PubMed

    Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

    2003-10-01

    As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial

  16. Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia.

    PubMed

    Regan, Annette K; Tracey, Lauren; Gibbs, Robyn

    2015-11-17

    In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p=0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p=0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  17. Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

    PubMed

    Okubo, Sumiko; Nishiuma, Shinichi; Kobayashi, Noriko; Taketsuna, Masanori; Taniai, Hisashi

    2012-11-01

    Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

  18. Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

    PubMed Central

    Okada, Kenya; Sudo, Yohei; Itoh, Hiromichi; Yoshida, Hisao; Kuroda, Tatsuhiko

    2014-01-01

    Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7%) of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%). No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy. PMID:26770729

  19. Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group.

    PubMed

    Takahashi, H; Pool, V; Tsai, T F; Chen, R T

    2000-07-01

    We determined the reporting rates for adverse events following the administration of inactivated mouse-brain derived Japanese encephalitis vaccine (JEV) based on post-marketing surveillance data from Japan and the United States. The rate of total adverse events per 100,000 doses was 2.8 in Japan and 15.0 in the United States. In Japan, 17 neurological disorders were reported from April 1996 to October 1998 for a rate of 0.2 per 100,000 doses. In the United States, no serious neurological adverse events temporally associated with JEV were reported from January 1993 to June 1999. Rates for systemic hypersensitivity reactions were 0.8 and 6.3 per 100,000 doses in Japan and the United States, respectively. Passively collected VAERS surveillance data indicate that characteristic hypersensitivity reactions with a delayed onset continue to occur among JEV recipients and that conservative recommendations limiting its use to travelers at high risk of infection with Japanese encephalitis are appropriate.

  20. Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up.

    PubMed

    Yagi, Nobuyuki; Okada, Kenya; Sudo, Yohei; Itoh, Hiromichi; Yoshida, Hisao; Kuroda, Tatsuhiko

    2014-01-01

    To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7%) of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%). No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy.

  1. 21 CFR 822.24 - What are my responsibilities once I am notified that I am required to conduct postmarket...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... that I am required to conduct postmarket surveillance? 822.24 Section 822.24 Food and Drugs FOOD AND... SURVEILLANCE Responsibilities of Manufacturers § 822.24 What are my responsibilities once I am notified that I am required to conduct postmarket surveillance? You must submit your plan to conduct postmarket...

  2. 21 CFR 822.24 - What are my responsibilities once I am notified that I am required to conduct postmarket...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... that I am required to conduct postmarket surveillance? 822.24 Section 822.24 Food and Drugs FOOD AND... SURVEILLANCE Responsibilities of Manufacturers § 822.24 What are my responsibilities once I am notified that I am required to conduct postmarket surveillance? You must submit your plan to conduct postmarket...

  3. 21 CFR 822.24 - What are my responsibilities once I am notified that I am required to conduct postmarket...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... that I am required to conduct postmarket surveillance? 822.24 Section 822.24 Food and Drugs FOOD AND... SURVEILLANCE Responsibilities of Manufacturers § 822.24 What are my responsibilities once I am notified that I am required to conduct postmarket surveillance? You must submit your plan to conduct postmarket...

  4. Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse.

    PubMed

    Swank, Kimberley A; Wu, Eileen; Kortepeter, Cindy; McAninch, Jana; Levin, Robert L

    The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to

  5. Safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): Interim results of a post-marketing surveillance study.

    PubMed

    Terauchi, Yasuo; Yokote, Koutaro; Nakamura, Ichiro; Sugamori, Haruko

    2016-01-01

    To determine the incidence of adverse drug reactions (ADRs) associated with ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus. We report interim results of a postmarketing surveillance survey. Japanese physicians recorded ADRs in elderly patients (≥ 65 years old) who were first prescribed with ipragliflozin within 3 months of its launch (April 2014). Incidence of ADRs within 1 year of starting treatment with ipragliflozin. 898 ADRs occurred in 721/7,170 patients (10.06%). Skin complication-, volume depletion-, genital infection-, polyuria/pollakiuria-, urinary tract infection-, and hypoglycemia-related ADRs occurred in 2.23%, 1.90%, 1.45%, 1.32%, 0.77%, and 0.32%, respectively. ADRs were classified as serious in 44 (0.61%) patients. Half of the ADRs occurred within 30 days of starting treatment. There were no cases of Stevens-Johnson syndrome or toxic epidermal necrolysis. Most (92.1%) of the ADRs resolved or improved. Glycated hemoglobin, fasting blood glucose, body weight, and systolic blood pressure decreased by 0.6% (baseline 7.8%), 22.7 mg/dL (baseline 163.0 mg/dL), 2.3 kg (baseline 67.4 kg), and 3.1 mmHg (baseline 133.2 mmHg), respectively, from baseline to treatment discontinuation/last visit. Ipragliflozin is well tolerated and reduced surrogate endpoints in elderly Japanese patients with type 2 diabetes mellitus. Clinicaltrials.gov identifier: NCT02297620.

  6. Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in refractory ascites: Post-marketing surveillance results.

    PubMed

    Hanafusa, Norio; Isoai, Ayako; Ishihara, Tomoaki; Inoue, Tetsuya; Ishitani, Ken; Utsugisawa, Taiju; Yamaka, Toshihiko; Ito, Tetsuya; Sugiyama, Hiroshi; Arakawa, Atsushi; Yamada, Yosuke; Itano, Yasuo; Onodera, Hirokazu; Kobayashi, Ryosuke; Torii, Naoko; Numata, Toyoko; Kashiwabara, Taihei; Matsuno, Yoshihiro; Kato, Michio

    2017-01-01

    We performed post-marketing surveillance to evaluate the safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART sessions in 147 patients at 22 centers were performed. The most common primary disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine volume, body weight and abdominal circumference were significantly improved after CART. Body temperature increased significantly, by 0.3°C on average. Concomitant steroids and/or NSAIDs use before reinfusion was significantly and negatively associated with increases in body temperature. Most adverse events were fever and chills. This study examined a large number of patients compared with previous studies, and showed that CART is an effective and relatively safe treatment for refractory ascites, such as malignant ascites.

  7. Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in refractory ascites: Post-marketing surveillance results

    PubMed Central

    Isoai, Ayako; Ishihara, Tomoaki; Inoue, Tetsuya; Ishitani, Ken; Utsugisawa, Taiju; Yamaka, Toshihiko; Ito, Tetsuya; Sugiyama, Hiroshi; Arakawa, Atsushi; Yamada, Yosuke; Itano, Yasuo; Onodera, Hirokazu; Kobayashi, Ryosuke; Torii, Naoko; Numata, Toyoko; Kashiwabara, Taihei; Matsuno, Yoshihiro; Kato, Michio

    2017-01-01

    We performed post-marketing surveillance to evaluate the safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART sessions in 147 patients at 22 centers were performed. The most common primary disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine volume, body weight and abdominal circumference were significantly improved after CART. Body temperature increased significantly, by 0.3°C on average. Concomitant steroids and/or NSAIDs use before reinfusion was significantly and negatively associated with increases in body temperature. Most adverse events were fever and chills. This study examined a large number of patients compared with previous studies, and showed that CART is an effective and relatively safe treatment for refractory ascites, such as malignant ascites. PMID:28510606

  8. An immunogenicity, safety and post-marketing surveillance of a novel adsorbed human diploid cell rabies vaccine (Rabivax) in Indian subjects.

    PubMed

    Sudarshan, M K; Bhardwaj, S; Mahendra, B J; Sharma, H; Sanjay, T V; Ashwathnarayana, D H; Bilagumba, Gangaboraiah

    2008-01-01

    In 1999, Serum Institute of India indigenously developed an adsorbed human diploid cell rabies vaccine (Rabivax). During 2000-04, this new vaccine was subjected to a series of immunogenecity and safety studies. Initially, an experimental batch of Rabivax (adsorbed) was assessed on ten healthy adult volunteers and its response was comparable with that of Merieux inactivated rabies vaccine (MIRV, lyophilized) which was used as a control. Subsequently, Rabivax (adsorbed) was assessed on forty-five suspect rabid dog bite cases with MIRV as control. The vaccine was found to be equally safe and immunogenic as MIRV and showed better rabies virus neutralizing antibody (RVNA) response on day 90 than MIRV. A post-licensing study conducted on 150 cases of suspect rabid animal bites showed it to be safe and immunogenic. To assess its long-term sero-efficacy some of these subjects tested after one year of follow up showed that 84% of them had adequate RVNA titers. In addition, a routine post-marketing surveillance done on 1608 animal bite cases demonstrated that Rabivax (adsorbed) was safe and efficacious. The adverse events to Rabivax (adsorbed) included pain at injection site (3.4%), swelling with induration (2.8%), fever and headache (1.4%). No serious adverse event was reported from the studies. In conclusion, Rabivax (adsorbed) is an immunogenic, safe and efficacious vaccine for rabies prophylaxis in humans.

  9. Safety and efficacy of micafungin for prophylaxis against invasive fungal infections in Japanese patients undergoing hematopoietic stem cell transplantation: Results of a post-marketing surveillance study.

    PubMed

    Kobayashi, Chie; Hanadate, Tomoko; Niwa, Toshiro; Hirano, Yasuno; Yoshiyasu, Takashi; So, Masahiro; Matsui, Keita

    2015-06-01

    Invasive fungal infections are a major cause of morbidity and mortality in patients with hematopoietic stem cell transplantation. A prospective multicenter post-marketing observational surveillance study was conducted from July 2007 to June 2010 to assess the safety and efficacy of micafungin, an echinocandin antifungal, for prophylaxis against invasive fungal infections in Japanese patients undergoing hematopoietic stem cell transplantation. Among 241 patients evaluated for safety, 143 adverse drug reactions were reported in 86 patients (35.7%), with hepatobiliary disorders the most frequently reported adverse drug reactions. The success rate for prophylaxis at the end of observation was 72.8% (131/180 patients), and the incidence of breakthrough infections was only 4.4% (8/180 patients). In conclusion, micafungin had sufficient safety and efficacy for prophylaxis against invasive fungal infections in Japanese patients with various backgrounds undergoing hematopoietic stem cell transplantation. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  10. Post-marketing safety surveillance conducted in Korea (2008–2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™)

    PubMed Central

    Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

    2016-01-01

    ABSTRACT Purpose: According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). Methods: During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. Results: A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. Conclusions: We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice. PMID:27494163

  11. Post-marketing safety surveillance conducted in Korea (2008-2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™).

    PubMed

    Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

    2016-10-02

    According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice.

  12. Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy.

    PubMed

    Asakura, Hidesaku; Takahashi, Hoyu; Tsuji, Hajime; Matsushita, Tadashi; Ninomiya, Hideyuki; Honda, Goichi; Mimuro, Jun; Eguchi, Yutaka; Kitajima, Isao; Sakata, Yoichi

    2014-03-01

    Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy. All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated. The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated. This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. [Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

    PubMed

    Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

    2014-04-01

    The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

  14. Post-Marketing Surveillance of Fluvoxamine Maleate Used Long-Term in Patients with Social Anxiety Disorder in Japan.

    PubMed

    Asakura, Satoshi; Koyama, Tsukasa; Hosokai, Takeshi; Kawano, Hitoshi; Kajii, Yasushi

    2014-12-01

    No data on the long-term 'real-world' use of fluvoxamine for the treatment of social anxiety disorder (SAD) in Japanese patients are currently available. To evaluate the long-term safety and efficacy of fluvoxamine for SAD in the clinical setting. Japanese patients with SAD who initiated treatment with fluvoxamine were enrolled in this 53-week post-marketing survey from 407 institutions nationwide. Data including rates of adverse drug reactions (ADRs) and efficacy were collected. Overall improvement was assessed using the Clinical Global Impression for Improvement. SAD symptoms and treatment responses were assessed with the Japanese version of the Liebowitz Social Anxiety Scale. From the 1,974 patients surveyed, 1,790 and 1,504 patients were eligible for analysis of safety and efficacy, respectively. ADRs were reported in 18.2 % of patients, with nausea, somnolence, and constipation the most common. Over 50 % of these ADRs developed in the first 4 weeks of treatment. Serious ADRs were reported in 0.8 % of patients and included six cases of suicide attempt and three cases of suicidal ideation. Response to fluvoxamine was reported in 78.4 % of patients. In patients comorbid with depression, improvement in SAD symptoms with fluvoxamine treatment was significantly affected by clinical improvement in the depression. These findings support the long-term safety and efficacy of fluvoxamine in patients with SAD. Most ADRs developed during the early treatment phase, and higher doses during the later phase were not associated with an increase in ADRs.

  15. Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers

    PubMed Central

    2013-01-01

    Background After several exploratory and confirmatory clinical trials, the intralesional administration of human recombinant epidermal growth factor (hrEGF) has been approved for the treatment of advanced diabetic foot ulcers (DFU). The aim of this work was to evaluate the effectiveness and safety of this procedure in medical practice. Methods A prospective, post-marketing active pharmacosurveillance was conducted in 41 hospitals and 19 primary care polyclinics. Patients with DFU received hrEGF, 25 or 75 μg, intralesionally 3 times per week until complete granulation of the ulcer or 8 weeks maximum, adjuvant to standard wound care. Outcomes measured were complete granulation, amputations, and adverse events (AE) during treatment; complete lesion re-epithelization and relapses in follow-up (median: 1.2; maximum 4.2 years). Results The study included 1788 patients with 1835 DFU (81% Wagner’s grades 3 or 4; 43% ischemic) treated from May 2007 to April 2010. Complete granulation was observed in 76% of the ulcers in 5 weeks (median). Ulcer non-ischemic etiology (OR: 3.6; 95% CI: 2.8-4.7) and age (1.02; 1.01-1.03, for each younger year) were the main variables with influence on this outcome. During treatment, 220 (12%) amputations (171 major) were required in 214 patients, mostly in ischemic or Wagner’s grade 3 to 5 ulcers. Re-epithelization was documented in 61% of the 1659 followed-up cases; 5% relapsed per year. AE (4171) were reported in 47% of the subjects. Mild or moderate local pain and burning sensation, shivering and chills, were 87% of the events. Serious events, not related to treatment, occurred in 1.7% of the patients. Conclusions The favorable benefit/risk balance, confirms the beneficial clinical profile of intralesional hrEGF in the treatment of DFUs. PMID:24004460

  16. Safety of 3-year raloxifene treatment in Japanese postmenopausal women aged 75 years or older with osteoporosis: a postmarketing surveillance study.

    PubMed

    Takeuchi, Yasuhiro; Hamaya, Etsuro; Taketsuna, Masanori; Sowa, Hideaki

    2015-10-01

    Long-term safety of medication is a concern for older persons because they may have several comorbidities that can influence drug metabolism, efficacy, and safety. In Japan, raloxifene is an effective and well-tolerated medication for the treatment of osteoporosis in postmenopausal women, but there is little available evidence on whether raloxifene has an acceptable safety profile in older women. The objective of this post hoc analysis was to investigate the safety of raloxifene as a long-term treatment of osteoporosis in Japanese postmenopausal women aged 75 years or older. We report a post hoc analysis of a safety dataset (6,960 participants) from a published postmarketing surveillance study (postmenopausal women treated with raloxifene 60 mg/d for ≤3 y). The safety dataset was divided into two groups: (1) women younger than 75 years at baseline (4,522 participants) and (2) women aged 75 years or older at baseline (2,438 participants). Incidence of adverse drug reactions and reactions of note in each age group were compared using Fisher's exact test. Approximately 10% of women in each group reported at least one adverse drug reaction. This analysis did not identify any clinically important differences in the incidence or type of adverse drug reactions reported or in reactions of note between women aged 75 years or older and younger women. There were no obvious additional safety concerns for women aged 75 years or older who were treated with raloxifene. The findings in this post hoc evaluation suggest no differences in adverse events in the age groups evaluated.

  17. Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

    PubMed

    Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Yasuda, Moriyoshi; Okada, Mitsuru; Bando, Kosuke; Fukuta, Yasuhiko

    2017-10-01

    Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained. © 2016 The Japan Society of Hepatology.

  18. Postmarketing surveillance study of KOGENATE Bayer with Bio-Set in patients with haemophilia A: evaluation of patients' satisfaction after switch to the new reconstitution system.

    PubMed

    Vidovic, N; Musso, R; Klamroth, R; Enriquez, M M; Achilles, K

    2010-01-01

    KOGENATE Bayer (rFVIII-FS) with Bio-Set is designed to prevent patient contact with exposed needles during recombinant factor VIII reconstitution. This postmarketing surveillance study evaluated patient satisfaction before and after switching to the new Bio-Set reconstitution method. Male children and adults with haemophilia A were enrolled from nine European countries. A preference questionnaire was administered to patients after Bio-Set training and at the end of the observation period (> or =20 exposure days or 3 months). Physician assessments of patient compliance and satisfaction were conducted at the end of the observation period. Patients (N = 306) received a mean +/- SD of 28 +/- 23 infusions of rFVIII-FS with Bio-Set. A majority of patients (82%) preferred the Bio-Set method, with domain scores for ease of use, safety from needlesticks, and speed of reconstitution being highest after training and at the end of the observation period. The Bio-Set method received higher mean scores than previous reconstitution methods for worry/safety and ease/confidence domains at both time points. Physician-reported patient compliance with the Bio-Set method was similar or greater compared with the previous method for 94% of the patients, with physicians reporting that 92% of the patients were satisfied or very satisfied with Bio-Set. Thirteen adverse events (AEs) occurred in nine patients, and five serious AEs occurred in five patients; none was related to rFVIII-FS. No de novo or recurrent inhibitor development was observed during the observation period. rFVIII-FS with Bio-Set was well tolerated and well accepted by haemophilia A patients, which may improve treatment compliance.

  19. Examining the Quality of Medicines at Kenyan Healthcare Facilities: A Validation of an Alternative Post-Market Surveillance Model That Uses Standardized Patients.

    PubMed

    Wafula, Francis; Dolinger, Amy; Daniels, Benjamin; Mwaura, Njeri; Bedoya, Guadalupe; Rogo, Khama; Goicoechea, Ana; Das, Jishnu; Olayo, Bernard

    2017-03-01

    Promoting access to medicines requires concurrent efforts to strengthen quality assurance for sustained impact. Although problems of substandard and falsified medicines have been documented in low- and middle-income countries, reliable information on quality is rarely available. The aim of this study was to validate an alternative post-market surveillance model to complement existing models. The study used standardized patients or mystery clients (people recruited from the local community and trained to pose as real patients) to collect medicine samples after presenting a pre-specified condition. The patients presented four standardized conditions to 42 blinded facilities in Nairobi, Kenya, resulting in 166 patient-clinician interactions and dispensing of 300 medicines at facilities or nearby retail pharmacies. The medicine samples obtained thus resemble those that would be given to real patients. Sixty samples were selected from the 300, and sent for analysis at the Kenya National Quality Control Laboratory. Of these, ten (17%) did not comply with monograph specifications (three ibuprofen, two cetirizine, two amoxicillin/clavulanic acid combinations, and one each for prednisone, salbutamol and zinc). Five of the ten samples that failed had been inappropriately prescribed to patients who had presented symptoms of unstable angina. There was no association between medicine quality and ownership, size or location of the facilities. The study shows that the standardized patient model can provide insights into multiple dimensions of care, thus helping to link primary care encounters with medicine quality. Furthermore, it makes it possible to obtain medicines from blinded sellers, thus minimizing the risk of obtaining biased samples.

  20. Zilver PTX Post-Market Surveillance Study of Paclitaxel-Eluting Stents for Treating Femoropopliteal Artery Disease in Japan: 12-Month Results.

    PubMed

    Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Snyder, Scott A; Dake, Michael D

    2016-02-08

    This multicenter, prospective, post-market surveillance study in Japan evaluates the paclitaxel-coated Zilver PTX stent in real-world patients with complex lesions. The Zilver PTX stent is the first drug-eluting stent (DES) approved for the superficial femoral artery. Previously, results from a large randomized study and a complementary, large single-arm study supported the safety and effectiveness of the DES. There were no exclusion criteria, and consecutive patients with symptomatic peripheral artery disease (PAD) treated with the DES were enrolled in the study. Clinically driven target lesion revascularization (TLR) was defined as reintervention performed for ≥50% diameter stenosis after recurrent clinical symptoms of PAD. Clinical benefit was defined as freedom from persistent or worsening symptoms of ischemia. Patency was evaluated by duplex ultrasound where physicians considered this standard of care. In this study, 907 patients were enrolled at 95 institutions in Japan. There were numerous comorbidities including high incidences of diabetes (58.8%), chronic kidney disease (43.8%), and critical limb ischemia (21.5%). Lesions were also complex, with an average length of 14.7 cm, 41.6% total occlusions, and 18.6% in-stent restenosis. In total, 1,861 DES were placed in 1,075 lesions. Twelve-month follow-up was obtained for >95% of eligible patients. Freedom from TLR was 91.0%, and clinical benefit was 87.7% through 12 months. The 12-month primary patency rate was 86.4%. Despite more challenging lesions, results from the current study are similar to outcomes from the previous Zilver PTX studies, confirming the benefit of the Zilver PTX DES in a real-world patient population. (Zilver PTX Post-Market Study in Japan; NCT02254837). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Clinical analysis of 207 patients who developed renal disorders during or after treatment with edaravone reported during post-marketing surveillance.

    PubMed

    Hishida, Akira

    2007-12-01

    The post-marketing surveillance of edaravone has reported serious adverse reactions, including renal and hepatic disorders. Renal disorders were the most frequently reported serious/important adverse reactions, which led to the evaluation of their causation by edaravone, their severity, and the recovery of renal function. A retrospective review was carried out of 207 Japanese patients with acute stroke who developed renal disorders on edaravone treatment. No particular factor other than edaravone was found as a possible cause of the renal disorders in 17 patients (8.2%). In 91.8% of the patients evaluated, factors other than edaravone were associated with the development of renal disorders. Severe deterioration of systemic status (e.g., a severe infection or a decrease in blood pressure) was considered to be a highly probable cause of renal disorders that occurred before or during treatment with edaravone in 135 patients (65.2%). Fifty-nine patients (28.5%) underwent blood purification treatment (BPT). In the remaining 148 patients without BPT, the peak serum creatinine (SCr) level during follow-up was 3 mg/dl or more in 93 patients (44.9%) and less than 3 mg/dl in 55 patients (26.6%). The severity of renal disorders was moderate to severe in 73.3% of the 207 patients, and renal function recovered in 43%. Appropriate treatment of deteriorated systemic status and the discontinuation of edaravone administration following the early discovery of renal disorders are recommended to reduce the development of severe renal disorders during edaravone treatment. The precise role(s) of edaravone in the pathogenesis of renal disorders should be evaluated in the future.

  2. Effectiveness and satisfaction with zolmitriptan 5 mg nasal spray for treatment of migraine in real-life practice: results of a postmarketing surveillance study.

    PubMed

    Diener, Hans-Christoph; Evers, Stefan

    2007-01-01

    Addressing the needs of migraineurs by actively seeking patient feedback on disease-related disability and treatment satisfaction may lead to improved management and treatment outcomes. Patient feedback can be collected in postmarketing surveillance (PMS) studies. The objective of this PMS study was to evaluate the efficacy and tolerability of zolmitriptan 5 mg nasal spray in the acute treatment of migraine attacks. Patients received zolmitriptan 5 mg nasal spray to treat migraine attacks of any severity and were followed up after a maximum of 4 months. Patients evaluated the efficacy and tolerability of zolmitriptan nasal spray, and were asked whether they wished to continue using zolmitriptan nasal spray and their preference compared with previous treatments. Physicians also assessed the efficacy and tolerability of zolmitriptan nasal spray. A total of 1838 patients (84.8% females) participated in the study. Within 30 minutes of administration of zolmitriptan nasal spray, 85.0% of patients reported improvements in headache pain, with 25.1% reporting an improvement within 10 minutes. At 1 hour post-dose, 57.9% of patients were pain free and 61.7% were able to resume usual daily activities. Most patients (72.9%) rated zolmitriptan nasal spray as 'better' than previous therapy. The majority (88.8%) expressed a wish to continue using zolmitriptan nasal spray. Physicians evaluated the efficacy of zolmitriptan nasal spray as 'excellent' or 'good' in 89.4% of patients. Tolerability was evaluated as 'excellent' or 'good' in 91.6% of patients. Zolmitriptan 5 mg nasal spray provides favourable efficacy and tolerability in the acute treatment of migraine attacks. Most patients assessed zolmitriptan nasal spray as 'better' than previous treatment, with nearly all wishing to continue using it.

  3. Reactogenicity and safety of the human rotavirus vaccine, Rotarix™ in The Philippines, Sri Lanka, and India: a post-marketing surveillance study.

    PubMed

    Bravo, Lulu; Chitraka, Amarjeet; Liu, Aixue; Choudhury, Jaydeep; Kumar, Kishore; Berezo, Lennie; Cimafranca, Leonard; Chatterjee, Pallab; Garg, Pankaj; Siriwardene, Prasanna; Bernardo, Rommel; Mehta, Shailesh; Balasubramanian, Sundaram; Karkada, Naveen; Htay Han, Htay

    2014-01-01

    Regulatory bodies in The Philippines, Sri Lanka, and India require post-marketing surveillance to provide additional safety data on Rotarix™ in real-life settings. In such studies conducted in The Philippines (November 2006 to July 2012; NCT00353366), Sri Lanka (November 2008 to August 2009; NCT00779779), and India (August 2009 to April 2010; NCT00938327), 2 doses of Rotarix™ were administered according to the local prescribing information (PI). The occurrence of at least Grade "2"/"3" solicited adverse event (AE) (fever, vomiting, or diarrhea), within 15 days in The Philippines or 8 days in Sri Lanka and India; unsolicited AEs within 31 days and serious adverse events (SAEs) throughout the study were recorded. Of the 1494, 522, and 332 infants enrolled in The Philippines, Sri Lanka, and India, 14.7% 14.9% and 12.7% infants, respectively recorded at least Grade "2"/"3" solicited AEs. The most commonly reported solicited AEs were irritability in The Philippines (32.2% post-Dose-1; 23.5% post-Dose-2) and India (23.0% post-Dose-1; 13.2% post-Dose-2), and fever (18.0% post-Dose-1; 20.2% post-Dose-2) in Sri Lanka. Unsolicited AEs were recorded in 24.5% (The Philippines), 4.8% (Sri Lanka), and 6.9% (India) of infants. Forty-one SAEs were recorded in the Philippines of which 6 (decreased oral intake with increased sleeping time and constipation; pneumonia, urinary tract infection, and intussusception) were considered by the investigators as causally related to vaccination. One vaccine-unrelated SAE occurred in a Sri Lankan infant. All SAEs resolved and the infants recovered. Two doses of Rotarix™, administered to healthy infants according to local PI, were well tolerated in The Philippines, Sri Lanka, and India.

  4. Long-term efficacy of sirolimus-eluting stent for small vessel disease--subanalysis of Cypher Stent Japan Post-Marketing Surveillance Registry.

    PubMed

    Fujimoto, Hajime; Ikari, Yuji; Nakamura, Masato

    2013-01-01

    Percutaneous coronary intervention for lesions with small vessel diameter may have high event rates. Although drug-eluting stents reduce the risk of restenosis, the long-term efficacy of drug-eluting stent implantation in small vessels is unclear. We reviewed the data of Cypher Stent Japan Post-Marketing Surveillance Registry including 2356 lesions of 1959 patients, and retrospectively investigated the angiographic outcomes at 8 months, and the clinical outcomes at 1800 days after sirolimus-eluting stent (SES) implantation in vessels with diameter less than 2.5mm (small vessel group) compared to that with diameter of 2.5mm or more (non-small vessel group). The rate of major adverse cardiac events (MACE) at 1800 days was slightly higher in the small vessel group than in the non-small vessel group, but not statistically significant (24.4% vs 21.0%, p=0.086). The rate of target lesion revascularization was higher in the small vessel group than in the non-small vessel group (10.2% vs 6.4%, p=0.004). The rate of stent thrombosis was almost the same in the two groups. Multivariate Cox hazard model analysis revealed that a vessel diameter less than 2.5mm was not an independent risk factor for MACE. SES implantation for vessels with diameter less than 2.5mm is safe and provides good long-term outcomes. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  5. Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea.

    PubMed

    Kim, Tae Heon; Lee, Sang Eun; Lee, Hahn-Ey; Lee, Kyu-Sung

    2016-08-01

    The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive bladder (OAB) in routine clinical practice. This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator's discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy. A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p < 0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration. These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

  6. The occurrence rate of cerebrovascular and cardiac events in patients receiving antihypertensive therapy from the post-marketing surveillance data for valsartan in Japan (J-VALID).

    PubMed

    Yamazaki, Tsutomu; Kohro, Takahide; Chujo, Mitsuaki; Ishigaki, Masahide; Hashimoto, Takafumi

    2013-02-01

    It is well known that blood pressure (BP) management reduces the incidence of cerebrovascular and cardiovascular events. However, it is unclear how many of these events occur in hypertensive patients who receive pharmacological treatment. The aim of this survey was to evaluate the occurrence rate of both types of events in patients receiving valsartan-based treatment. Of 30 366 patients treated with valsartan, 28 356 patients were observed for 2.93 years. Antihypertensive drugs other than valsartan were used in 56.8% of patients. After the administration of valsartan, the systolic and diastolic BP significantly decreased from 161.1±19.1/90.4±13.1 to 139.9±18.1/79.6±11.9 mm Hg. Cerebrovascular events were observed in 550 patients (1.94%, 9.29/1000 patient-years), and cardiac events were observed in 576 patients (2.03%, 9.73/1000 patient-years). A comparative analysis of the hazard ratios for cerebrovascular and cardiac events according to the BP level at the endpoint showed a BP-dependent reduction of risk for cerebrovascular events, and the change in risk exhibited a J-curve phenomenon in the relationship between cardiac events and systolic BP. The J-curve phenomenon was not observed in patients aged <75 years, but it was observed for the systolic BP in patients aged 75 years. Adverse drug reactions were observed in 1925 of 28 420 patients (6.77%). This post-marketing surveillance data for valsartan showed the outcomes for treated hypertensive patients in a large population in Japan who were followed for up to 3 years. These data will add important knowledge regarding the treatment of hypertension in Japan.

  7. Postmarketing surveillance of adverse drug reactions in general practice. II: Prescription-event monitoring at the University of Southampton.

    PubMed

    Inman, W H

    1981-04-11

    An independent, non-regulatory drug surveillance research unit has been established at the University of Southampton. Its first task will be to set up a prescription-event monitoring scheme in general practice to enable the pattern of adverse events, as distinct from suspected adverse reactions associated with new drugs to be compared with that of older medicines. Prescriptions for selected drugs will identify patients and a simple questionnaire, designed to be completed in under five minutes, will be used to obtain the required information. Medical opinions about causation need not be given, and the scheme will not interfere with normal prescribing practice.

  8. 21 CFR 314.540 - Postmarketing safety reporting.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Postmarketing safety reporting. 314.540 Section... New Drugs for Serious or Life-Threatening Illnesses § 314.540 Postmarketing safety reporting. Drug products approved under this program are subject to the postmarketing recordkeeping and safety...

  9. 21 CFR 314.630 - Postmarketing safety reporting.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Postmarketing safety reporting. 314.630 Section... Human Efficacy Studies Are Not Ethical or Feasible § 314.630 Postmarketing safety reporting. Drug products approved under this subpart are subject to the postmarketing recordkeeping and safety...

  10. OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results

    PubMed Central

    Kimball, Alexa B.; Rothman, Kenneth J.; Kricorian, Gregory; Pariser, David; Yamauchi, Paul S.; Menter, Alan; Teller, Craig F.; Aras, Girish; Accortt, Neil A.; Hooper, Michele; Rice, Kara Creamer; Gelfand, Joel M.

    2016-01-01

    Background OBSERVE-5 was a 5-year FDA-mandated surveillance registry of psoriasis patients. Objective To assess long-term etanercept safety and effectiveness. Methods Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events (SAEs), serious infectious events (SIEs), events of medical interest, psoriasis-affected body surface area, physician global assessment, and Dermatology Life Quality Index. Safety outcomes were assessed relative to data from the MarketScan database. Results For 2,510 patients, 5-year cumulative incidence (95% confidence interval [CI]) was 22.2% (20.3%, 24.2%) for SAEs; 6.5% (5.4%, 7.7%) for SIEs; 3.2% (2.3%, 4.1%) for malignancies excluding nonmelanoma skin cancer (NMSC); 3.6% (2.7%, 4.5%) for NMSC; 2.8% (2.0%, 3.6%) for coronary artery disease; 0.7% (0.3%, 1.2%) for psoriasis worsening; 0.2% (0.0%, 0.4%) for CNS demyelinating disorder; 0.1% (0.0%, 0.3%) for lymphoma and for tuberculosis; 0.1% (0.0%, 0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, NMSC, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. Limitations No internal comparator group was included; rare events may not have been detected. Conclusion No new safety signals were observed with long-term, real-world etanercept use. PMID:25264239

  11. Retrospective hospital based surveillance of intussusception in children in a sentinel paediatric hospital: benefits and pitfalls for use in post-marketing surveillance of rotavirus vaccines.

    PubMed

    Lloyd-Johnsen, C; Justice, F; Donath, S; Bines, J E

    2012-04-27

    Evaluation of the safety of rotavirus vaccines, particularly with respect to the risk of intussusception, is recommended for countries planning to introduce rotavirus vaccines into the National Immunisation Program. However, as prospective studies are costly, require time to conduct and may be difficult to perform in some settings, retrospective hospital based surveillance at sentinel sites has been suggested as an option for surveillance for intussusception following introduction of rotavirus vaccines. To assess the value of retrospective hospital based surveillance to describe clinical and epidemiological features of intussusception in children aged <24 months and to investigate any temporal association between receipt of a rotavirus vaccine and intussusception. A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne, Australia over an 8-year period including before and after rotavirus vaccine introduction into the National Immunisation Program, was conducted using patients identified by a medical record database (ICD-10-CM 56.1). Patient profile, clinical presentation, treatment and outcome were analysed along with records of immunisation status obtained using the Australian Childhood Immunisation Register. A 9% misclassification rate of discharge diagnosis of intussusception was identified on critical chart review. The incidence rate of intussusception at the Royal Children's Hospital over the study period was 1.91 per 10,000 infants <24 months (95% CI 1.65-2.20). Intestinal resection was required in 6.5% of infants (95% CI 3.6%, 11.0%). Intussusception occurred within 30 days after vaccination in 2 of 27 patients who had received at least 1 dose of a rotavirus vaccine. Valuable data on the incidence, clinical presentation and treatment outcomes of intussusception can be obtained from data retrieved from hospital medical records in a sentinel paediatric hospital using standardised methodology. However

  12. Safety and effectiveness of controlled-release paroxetine in routine clinical practice: results of a postmarketing surveillance study of patients with depression

    PubMed Central

    Kato, Masaki; Kimura, Toshifumi; Kimura, Takeshi; Hara, Terufumi

    2015-01-01

    Objective Selective serotonin reuptake inhibitors are commonly used in the pharmacotherapy of depression. However, adverse events can lead to their early discontinuation. This study evaluated the safety and effectiveness of paroxetine controlled-release (CR) tablets in Japanese patients with depression/depressive state (hereafter referred to as depression) in routine clinical practice in Japan. Patients and methods This was an open-label, noninterventional, prospective, postmarketing surveillance study. A total of 3,213 patients aged 12–92 years with depression were prescribed paroxetine CR for 8 weeks at the physician’s discretion. Safety was evaluated on the basis of the reporting of adverse drug reactions. Effectiveness was evaluated on the basis of the physician’s assessment using the Clinical Global Impression-Global Improvement (CGI-GI) and the Clinical Global Impression-Severity of Illness (CGI-SI) scales, as well as on the basis of the patients’ self-reported satisfaction. The primary effectiveness outcome was the improvement rate based on the physician’s assessment using the CGI-GI. Results The incidence of adverse drug reactions was 11.2% (359/3,213; 95% confidence interval [CI]: 10.1%–12.3%). The common adverse drug reactions that accounted for 1.0% or more of the incidence were nausea (3.5%) and somnolence (2.7%). The proportion of patients who continued paroxetine CR at week 8 was 80.2% (2,577/3,213; 95% CI: 78.8%–81.6%). The improvement rate at week 8 (last observation carried forward) was 72.8% (2,132/2,927; 95% CI: 71.2%–74.4%). The proportion of patients with CGI-SI scores of moderately or severely ill decreased from 63.6% at baseline to 17.9% at week 8. The proportion of patients who were satisfied with paroxetine CR treatment was 69.8% (2,040/2,921; 95% CI: 68.1%–71.5%). Conclusion The results of this study suggest that paroxetine CR is a well-tolerated and efficacious treatment for depression in routine clinical practice. PMID

  13. [Post-marketing surveillance of acetylcysteine oral solution 17.6% "SENJU" for the antidote to acetaminophen overdose--use--results surveillance].

    PubMed

    Suenobu, Toshihide; Yoshioka, Toshiharu; Maruta, Shinichi; Shimoji, Hidemi

    2006-10-01

    Use-result surveillance was conducted to investigate the safety and efficacy of Acetylcysteine Oral Solution 17.6 % "SENJU" having the indication for the antidote to acetaminophen (Paracetamol) overdose. Ninety six cases (patients) were collected for the safety evaluation, and 13 cases (incidence was 13.5 %) showed 29 adverse drug reactions as follows: 4 cases of nausea; 3 cases of vomiting; 2 cases each of liver dysfunction, headache, abdominal pain, diarrhea, blood bilirubin increased; and one case each of CK increased, anaemia, prothrombin time prolonged, gamma-glutamyltransferase increased, LDH increased, body temperature increased, proteinuria, blood potassium decreased, thrombocytopenia, platelet count increased, white blood cell decreased, and blood amylase increased. One case of severe liver dysfunction which was ameliorated later was found. Neither case showing transitional chronic liver dysfunction, nor case of death was observed. Patient background analysis showed that 79.2% of the total patients was female, and that 28.1% was patients with mental disease. Gastrolavage, active charcoal administration, and extracorporeal removal of toxins were performed in cases of 71.9%, 50.0% and 7.3%, respectively. Those concomitant treatments, however, showed no influence for the incidence of adverse drug reaction or the drug effectiveness. Blood acetaminophen assay was performed in only 43.8% of the total cases. This rate indicates that the medical treatment procedure needs more consideration on the clinical standard for the antidote to acetaminophen overdose and on its practical application.

  14. National addictions vigilance intervention and prevention program (NAVIPPRO): a real-time, product-specific, public health surveillance system for monitoring prescription drug abuse.

    PubMed

    Butler, Stephen F; Budman, Simon H; Licari, Andrea; Cassidy, Theresa A; Lioy, Katherine; Dickinson, James; Brownstein, John S; Benneyan, James C; Green, Traci Craig; Katz, Nathaniel

    2008-12-01

    The National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) is a scientific, comprehensive risk management program for scheduled therapeutics. NAVIPPRO provides post-marketing surveillance, signal detection, signal verification and prevention and intervention programs. Here we focus on one component of NAVIPPRO surveillance, the Addiction Severity Index-Multimedia Version (ASI-MV) Connect, a continuous, real-time, national data stream that assesses pharmaceutical abuse by patients entering substance abuse treatment by collecting product-specific, geographically-detailed information. We evaluate population characteristics for data collected through the ASI-MV Connect in 2007 and 2008 and assess the representativeness, geographic coverage, and timeliness of report of the data. Analyses based on 41,923 admissions to 265 treatment centers in 29 states were conducted on product-specific opioid abuse rates, source of drug, and route of administration. ASI-MV Connect data revealed that 11.5% of patients reported abuse of at least one opioid analgesic product in the 30 days prior to entering substance abuse treatment; differences were observed among sub-populations of prescription opioid abusers, among products, and also within various geographic locations. The ASI-MV Connect component of NAVIPPRO represents a potentially valuable data stream for post-marketing surveillance of prescription drugs. Analyses conducted with data obtained from the ASI-MV Connect allow for the characterization of product-specific and geospatial differences for drug abuse and can serve as a tool to monitor responses of the abuse population to newly developed "abuse deterrent" drug formulations. Additional data, evaluation, and comparison to other systems are important next steps in establishing NAVIPPRO as a comprehensive, post-marketing surveillance system for prescription drugs. Copyright (c) 2008 John Wiley & Sons, Ltd.

  15. Characteristics of safety information obtained from postmarketing observational studies for re-examination in Japan.

    PubMed

    Watanabe, Tatsuya; Narukawa, Mamoru

    2016-01-01

    In Japan, postmarketing surveillance (PMS) studies are required for newly approved drug products to further collect safety information in clinical settings. "PMS study" is a general term encompassing both postmarketing observational (PMO) studies and postmarketing intervention studies for re-examination. Each PMS study is conducted under contracts between the pharmaceutical company and medical institutions in accordance with Good Postmarketing Study Practice. It has been reported that the safety information collected postmarketing is limited because of underreporting. The objective of this investigation was to identify differences among profiles of the drug product safety information collected through intervention studies and observational studies before and after approval. Our study addressed whether the issue of underreporting, generally considered as associated with observational studies, occurs in PMO studies for re-examination. In addition, we considered potential causes of such underreporting. The overall adverse reaction rate was lower in PMO studies than in intervention studies before approval in almost all cases. The adverse reaction rate in intervention studies exhibited similar profiles regardless of whether they were conducted prior to or following approval. In addition, we found that one reason for a lower adverse reaction rate in PMO studies was that the number of reports of adverse reactions that had occurred frequently prior to approval decreased postmarketing. Underreporting was observed even in PMO studies for re-examination under the Japanese regulation. Although it was suggested that expected and common adverse reactions were more likely to be subject to underreporting, further investigation is warranted to explore the reasons for the under-reporting in PMO studies.

  16. Hysteroscopic Sterilization With Essure: Summary of the U.S. Food and Drug Administration Actions and Policy Implications for Postmarketing Surveillance.

    PubMed

    Walter, Jessica R; Ghobadi, Comeron W; Hayman, Emily; Xu, Shuai

    2017-01-01

    In September 2015, the U.S. Food and Drug Administration (FDA) convened a meeting of the Obstetrics and Gynecology Advisory Board Committee to address the sudden increase of patient-reported adverse events surrounding Essure, a Class III device offering a less invasive method for permanent female sterilization. After a review of the premarketing and postmarketing data and existing scientific literature, the FDA concluded there was insufficient evidence to remove the device from the market. However, the FDA did release a new guidance document requiring a black box warning for the device and ordered a new postmarketing study comparing Essure's safety and efficacy with laparoscopic tubal sterilization. The device was first approved in 2002 based on nonrandomized, single-arm prospective clinical studies. Since its approval, the device has grown in popularity, particularly in the United States. The driving forces for the sudden increase in adverse event reporting starting in 2013 related to the device remain unclear. Until completion of the new postmarketing study, there will continue to be significant uncertainty of the technology's risk-benefit profile. The controversy with Essure underscores the need for obstetricians and gynecologists to be actively involved in the lifecycle of medical devices. This includes actively reporting adverse events associated with devices to the FDA, supporting the implementation of unique device identifiers enriched with clinical records and paired with insurance claims, and stewarding robust device-specific registries.

  17. Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis, pustular psoriasis or psoriatic erythroderma: Results from the prospective post-marketing surveillance.

    PubMed

    Torii, Hideshi; Terui, Tadashi; Matsukawa, Miyuki; Takesaki, Kazumi; Ohtsuki, Mamitaro; Nakagawa, Hidemi

    2016-07-01

    A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma. © 2015 Japanese Dermatological Association.

  18. Impact of Chronic Renal Failure on Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: Subgroup Analysis from Zilver PTX Post-Market Surveillance Study in Japan.

    PubMed

    Ogawa, Yukihisa; Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Saunders, Alan T; Dake, Michael D

    2017-05-09

    Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported. This study compares the results with the DES in patients with CRF and those without CRF. This retrospective analysis from the Zilver PTX Japan Post-Market Surveillance Study included 321 patients with CRF and 584 patients without CRF. Outcomes included freedom from target lesion revascularization (TLR) and patency. Of the patients included in this subgroup analysis, 2-year data were available for 209 patients in the CRF group and 453 patients in the non-CRF group. The two groups were similar in terms of lesion length and the frequency of in-stent restenosis. Critical limb ischemia, severe calcification, and diabetes were more common in patients with CRF, whereas total occlusion was more common in patients without CRF. Freedom from TLR rates were 81.4 versus 84.9% (p = 0.24), and patency rates were 70.7 versus 70.3% (p = 0.95) in patients with and without CRF at 2 years, respectively. This is the first comparative study of the DES in femoropopliteal artery lesions in patients with and without CRF. These results indicate that the DES placed in femoropopliteal artery lesions of CRF patients is safe and effective with similar patency and TLR rates to patients without CRF. Level 3, Post-Market Surveillance Study.

  19. Six-year multi-centre, observational, post-marketing surveillance of the safety of the HPV-16/18 AS04-adjuvanted vaccine in women aged 10-25 years in Korea.

    PubMed

    Kim, Chul-Jung; Song, Rok; Chen, Jing; Tavares Da Silva, Fernanda; Gopala, Kusuma B; Kim, Joon Hyung; Bi, Dan; Park, Jong Sup

    2017-07-01

    To evaluate the safety of HPV-16/18 AS04-adjuvanted vaccine when administered as per the PI in Korea. A total of 3084 women aged 10-25 years were enrolled in this post-marketing surveillance from 2008 to 2014. Subjects were invited to receive three doses of the vaccine (0, 1 and 6 months), and participants who received at least one dose were included in the analysis. Adverse events (AEs), adverse drug reactions (ADRs) and serious AEs (SAEs) were recorded after each dose. All AEs, ADRs and SAEs were presented with exact 95% confidence intervals (CI) (NCT01101542). Injection-site pain was the most frequent AE and ADR reported by 322 subjects (10.4% [95%CI: 9.4-11.6]); the local pain was transient and lasted 4-7 days in most cases. Dysmenorrhoea and vaginitis were the most common unexpected AEs reported by 30 (1.0% [95%CI: 0.7-1.4]) and 16 subjects (0.7% [95%CI: 0.3-0.8]), respectively. Pain (toe pain, leg pain and body pain [one case each]; foot pain [two cases]) was the most common unexpected ADR reported by five subjects (0.2% [95%CI: 0.1-0.4]). Four subjects reported a single SAE (one case each of exostosis, gastroenteritis, abortion and tonsillitis); none were fatal. All SAEs were assessed as unlikely to be related to vaccination; gastroenteritis, exostosis and tonsillitis resolved during the study period. This is the first post-marketing surveillance study in Korea that provides 6-year safety data for HPV-16/18 AS04-adjuvanted vaccine. The vaccine showed an acceptable safety profile and favourable benefit/risk ratio when given to women aged 10-25 years in Korea. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  20. [Post-marketing surveillance on treatment of 5,665 patients with atopic dermatitis using the calcineurin inhibitor pimecrolimus: positive effects on major symptoms of atopic dermatitis and on quality of life].

    PubMed

    Sunderkötter, Cord; Weiss, Johannes M; Bextermöller, Raphael; Löffler, Helena; Schneider, Dirk

    2006-04-01

    Topical application of the calcineurin inhibitors pimecrolimus and tacrolimus is a current major advance in the therapy of atopic dermatitis. The aims of this post-marketing surveillance were: a) to acquire data on the efficacy and tolerability of pimecrolimus ointment (Elidel) on a very large cohort of patients from outpatient clinics, and b) to assess changes in their quality of life, a parameter not often considered in previous studies. Included were 5,665 patients with atopic dermatitis. During the observation period, data on efficacy and tolerability were obtained at the beginning of the study, 3 to 10 days after initiation of therapy and after 4 to 6 weeks. Evaluation of symptoms as well as assessment of efficacy and tolerability were based on linear scales and on the percentage of the body surface area (% BSA) involved. Quality of life was assessed by the German version of the "Dermatology Life Quality Index (DLQI)" or the "Children's Dermatology Life Quality Index (CDLQI)". In this largest post-marketing surveillance hitherto performed in Germany, the efficacy of pimecrolimus was judged as "good" by 79.3 % of physicians and by 76.5 % of patients. Tolerability was assessed as "good" by 87.2 % of physicians and by 83.1 % of patients. Major symptoms of atopic dermatitis such as pruritus, erythema or lichenification showed marked reduction after just 3 to 10 days, signalling general improvement of the skin disease. In addition, application of pimecrolimus resulted in a significant improvement of the quality of life scores in both children and adults. The present study demonstrates that the good efficacy and tolerability of pimecrolimus ointment which had been shown in controlled trials: i) could also be demonstrated on a very large cohort of patients with atopic dermatitis when used in the outpatient setting, and ii) were paralleled by a significant improvement in the quality of life.

  1. 76 FR 1170 - Draft Guidance for Industry on Postmarketing Adverse Event Reporting for Medical Products and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ... Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic; Availability AGENCY... for Medical Products and Dietary Supplements During an Influenza Pandemic.'' The draft guidance..., biologics, medical devices, and dietary supplements during an influenza pandemic. The agency makes...

  2. 77 FR 11134 - Guidance for Industry on Postmarketing Adverse Event Reporting for Medical Products and Dietary...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic; Availability AGENCY... Medical Products and Dietary Supplements During an Influenza Pandemic.'' The guidance discusses FDA's... devices, and dietary supplements during an influenza pandemic. The Agency makes recommendations to...

  3. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey

    PubMed Central

    Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

    2015-01-01

    Background In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA’s pre-market approval (PMA) pathway. Methods and results We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Conclusion Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives. PMID:26060416

  4. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

    PubMed

    Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

    2015-01-01

    In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

  5. Medical product safety surveillance: how many databases to use?

    PubMed

    Maro, Judith C; Brown, Jeffrey S; Kulldorff, Martin

    2013-09-01

    Large linked database networks, like the US Food and Drug Administration's Sentinel System, are being built for medical product surveillance. One use of these networks is for "near real-time" sequential database surveillance of prespecified medical product-adverse event pairs, which may result in a "safety signal" when a statistical excess risk is detected. Sequential database surveillance requires the investigator to manage surveillance in both information time (ie, how sample size accrues) and calendar time. Calendar time is important because people external to the surveillance population may be affected by the speed with which a safety signal is detected or ruled out. Optimal design and analysis aspects of sequential database surveillance are not well developed, but are gaining in importance as observational database networks grow. Using information time concepts, we show how to calculate sample sizes when performing sequential database surveillance, illustrating the relationships between statistical power, the time to detect a signal, and the maximum sample size for various true effect sizes. Then, using a vaccine example, we demonstrate a four-step planning process that allows investigators to translate information time into calendar time. Given the calendar time for surveillance, the process focuses on choosing observational database configurations consistent with the investigator's preferences for timeliness and statistical power. Although the planning process emphasizes sample size considerations, the influence of secondary database attributes such as delay times, measurement error, and cost are also discussed. Appropriate planning allows the most efficient use of public health dollars dedicated to medical product surveillance efforts.

  6. Closing the information gap: informing better medical decisionmaking through the use of post-market safety and comparative effectiveness information.

    PubMed

    Fox, Bethany

    2012-01-01

    While FDA gathers vast amounts of data about prescription drugs prior to their marketing approval, important information about the relative effectiveness and long term safety of products is not required for approval, and often is never collected. Increased postmarket research on the safety and comparative effectiveness of products would improve medical decisionmaking and lead to better clinical outcomes. Fortunately, Congress has recognized the value of this information for healthcare professionals. In response to a congressional mandate in the FDA Amendments Act (FDAAA), FDA is developing the Sentinel Initiative, an active surveillance system for monitoring postmarket drug safety issues. FDAAA also authorized FDA to require a drug sponsor to conduct postmarket safety studies or clinical trials to address a specific safety concern. To increase the repository of comparative effectiveness information, Congress established the Patient-Centered Outcomes Research Institute (PCORI) in the Patient Protection and Affordable Care Act (PPACA), directing it to manage comparative effectiveness research (CER). This article discusses the need for better safety and comparative effectiveness information and outlines methods to efficiently conduct the research and communicate it effectively to healthcare professionals. Coordination between FDA and the PCORI in gathering and communicating postmarket information is recommended. Medical source data collected by the Sentinel Initiative should be used for CER in addition to postmarket safety surveillance, and FDA and the PCORI should adopt identical standards for the distribution and communication of CER. Coordination between the two entities is recommended to save costs, reduce duplication of efforts, and to generate and communicate more information on prescription drugs for medical decisionmakers.

  7. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

    PubMed

    Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

    2017-09-01

    To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

  8. Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study.

    PubMed

    Yokote, Koutaro; Terauchi, Yasuo; Nakamura, Ichiro; Sugamori, Haruko

    2016-10-01

    To investigate the real-world safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (T2DM). Japanese patients (≥65 years old) who were first prescribed ipragliflozin within 3 months after its launch in April 2014 were registered in this post-marketing surveillance (PMS). Final data collection was in July 2015. Survey items included demographics, treatments, adverse drug reactions (ADRs), vital signs, and laboratory variables. The PMS included 8505 patients (4181 males/4324 females). The mean age and diabetes duration were 72.3 years and 10.6 years, respectively. In 84.3% of patients, ipragliflozin was prescribed at 50 mg/day, which was continued unchanged. Overall, 16.91% of patients experienced 1880 ADRs, and 165 ADRs were classified as serious in 127 patients (1.49%). ADRs of special interest included skin complications, volume depletion, polyuria/pollakiuria, genital infection, urinary tract infection, renal disorders, hypoglycemia, cerebrovascular disease, cardiovascular disease, malignant tumor, fracture, and ketone body-related events. This 1-year PMS revealed probable ADRs in elderly Japanese patients with T2DM prescribed ipragliflozin in real-world settings, with no new safety concerns. The risk factors for ADRs varied but could be rationalized. The results should help physicians to identify possible treatment-emergent ADRs in ipragliflozin-treated patients.

  9. Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis.

    PubMed

    Koike, Takao; Harigai, Masayoshi; Inokuma, Shigeko; Ishiguro, Naoki; Ryu, Junnosuke; Takeuchi, Tsutomu; Tanaka, Yoshiya; Yamanaka, Hisashi; Fujii, Koichi; Yoshinaga, Takunari; Freundlich, Bruce; Suzukawa, Michio

    2012-06-01

    The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2-5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs.

  10. Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

    PubMed

    Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

    2016-11-23

    Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Safety and efficacy of a novel drug elores (ceftriaxone+sulbactam+disodium edetate) in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study.

    PubMed

    Chaudhary, Manu; Mir, Mohd Amin; Ayub, Shiekh Gazalla

    In India, Elores (CSE-1034: ceftriaxone+sulbactam+disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded. A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR) bacterial infections under routine ward settings. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. Safety and tolerability of Peg-grafeel(™), a pegfilgrastim, for the prophylactic treatment of chemotherapy-induced neutropenia and febrile neutropenia: A prospective, observational, postmarketing surveillance study in India.

    PubMed

    Talwar, Vineet; Nirni, Sharanabasappa S; Mallavarapu, Krishna Mohan; Ramkumar, Anupama; Sinha, Nitu

    2017-01-01

    A granulocyte colony-stimulating factor, pegfilgrastim, is efficacious though expensive for prophylactic treatment of chemotherapy-induced neutropenia and febrile neutropenia. Biologics available and accessible today, having acceptable safety-efficacy profiles, require postapproval studies for better understanding of such drugs in clinical settings. This postmarketing surveillance study evaluated the safety of prophylactic Peg-grafeel(™) (pegfilgrastim) in cancer patients with chemotherapy-induced neutropenia. This prospective, noninterventional, single-arm, open-label study was conducted at 10 study sites in India. Patients received subcutaneous 6 mg Peg-grafeel(™) approximately 24 h following chemotherapy as part of routine patient care. Data were summarized descriptively. The study included 250 patients (male: female = 36.4%:63.6%; median age, 54 [16-80] years). Most patients had Stage III (33.2%) or IV (41.6%) cancers and received cyclophosphamide (37.2%) and doxorubicin (31.6%) as chemotherapy. On an average, 4 Peg-grafeel(™) doses were administered per patient. Treatment-emergent adverse events (AEs) were reported in 115 (46%) patients, the most common being vomiting (11.6%), pain (11.2%), nausea (8.4%), and constipation (8.4%). Peg-grafeel(™)-related AEs included pain (3.2%), asthenia (2.4%), and arthralgia (1.2%). Bone pain (0.4%) and extremity pain (1.2%) were rare. Grade 3/4 neutropenia and febrile neutropenia occurred in 4 (1.6%) and 3 (1.2%) patients, respectively. Serious AEs included vomiting (2.8%) and pyrexia (2%). No new safety concerns were identified. None of the five deaths was considered related to Peg-grafeel(™). The overall safety profile of Peg-grafeel(™) was consistent with the expected safety profile of pegfilgrastim in patients with advanced malignancies in a clinical setting.

  13. A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance

    PubMed Central

    Akaza, Hideyuki; Oya, Mototsugu; Iijima, Masafumi; Hyodo, Ichinosuke; Gemma, Akihiko; Itoh, Hiroshi; Adachi, Masatoshi; Okayama, Yutaka; Sunaya, Toshiyuki; Inuyama, Lyo

    2015-01-01

    Objective Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. Methods All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Results Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand–foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7–8.1), and the overall survival rate at 1 year was 75.4% (73.5–77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. Conclusions Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials. PMID:26206897

  14. Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post-Marketing Surveillance Study.

    PubMed

    Won, Ji Eon; Chu, Ji Yeon; Choi, Hyunah Caroline; Chen, Yun; Park, Hyun Jun; Dueñas, Héctor José

    2017-09-06

    The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, mean the IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.

  15. Incidence and predictors of hypoglycemia in Japanese patients with type 2 diabetes treated by insulin glargine and oral antidiabetic drugs in real-life: ALOHA post-marketing surveillance study sub-analysis.

    PubMed

    Odawara, Masato; Kadowaki, Takashi; Naito, Yusuke

    2014-02-15

    Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA), an observational, non-interventional, 24-week post-marketing surveillance study in Japanese patients with type 2 diabetes (T2DM) having uncontrolled glycemic control, demonstrated that basal supported oral therapy (BOT) with insulin glargine was an effective and safe treatment in real-life clinical practice. We performed subgroup analysis to identify incidence and predictors associated with risk of hypoglycemia. Among 4219 patients with T2DM, 3732 patients were insulin-naïve and 487 patients were insulin non-naïve who switched from other insulin to insulin glargine. All hypoglycemic episodes were counted by physicians' documentation based on patients' reports. Relationships between baseline patient characteristics and glargine-related hypoglycemic episodes were examined by univariate and multivariate analysis. Among 4219 patients, 44 (1.0%) patients experienced hypoglycemic episodes (41 insulin-naïve patients; 3 insulin non-naïve patients), with a rate of incidence 0.035 episodes/patient-years. Majority of patients with hypoglycemia (37 of 44) had just one hypoglycemic episode during study period. Among insulin-naïve patients, incidence of hypoglycemia differed significantly depending on age, diabetic complications, estimated glomerular filtration rate (eGFR), and postprandial plasma glucose (P <0.05). In a multivariate adjusted model, poor renal function (eGFR <60 mL/min/1.73 m2) was a statistically significant risk factor (P < 0.05). Our results suggest that BOT using insulin glargine is an option of insulin therapy with 1% risk of hypoglycemia in patients with T2DM with inadequate glycemic control. Patients with low renal function might need a careful follow-up.

  16. A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance.

    PubMed

    Akaza, Hideyuki; Oya, Mototsugu; Iijima, Masafumi; Hyodo, Ichinosuke; Gemma, Akihiko; Itoh, Hiroshi; Adachi, Masatoshi; Okayama, Yutaka; Sunaya, Toshiyuki; Inuyama, Lyo

    2015-10-01

    Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand-foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5-77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials. © The Author 2015. Published by Oxford University Press.

  17. A post-marketing surveillance study of a human live-virus pandemic influenza A (H1N1) vaccine (Nasovac (®) ) in India.

    PubMed

    Kulkarni, Prasad S; Raut, Sidram K; Dhere, Rajeev M

    2013-01-01

    A live attenuated pandemic H1N1 influenza vaccine was developed in India. A post marketing surveillance was conducted retrospectively in healthy individuals (³ 3 years) who were vaccinated intranasally around one year before. After consent, the subjects recorded adverse events developing within 42 days. Among 7565 individuals (3 - 85 years), a total of 81 solicited adverse reactions (1%) were reported in 49 subjects (0.65%). The reactions included mild to moderate respiratory symptoms. No H1N1 case was encountered during one year postvaccination. The data show the safety of the live attenuated influenza vaccine platform developed in India.

  18. Manufacturer's drug interaction and postmarketing adverse event data: what are appropriate uses?

    PubMed

    Kraft, W K; Waldman, S A

    2001-01-01

    Governmental agencies overseeing pharmaceutical products use a risk/benefit approach to analyse data and make regulatory decisions. Comprehensive public dissemination of the safety profile of pharmaceutical products is part of an overall strategy for reducing risk associated with the use of any medical product. In the US, reports of postmarketing surveillance of approved drugs are in the public domain. Some, but not all, of the information in drug interaction studies is available to the public through the Freedom of Information Act (FOIA). However, there are concerns over the misuse of these data for commercial or other gain. The need to protect intellectual property and foster innovation in drug development, and concerns of legal liability are often cited as reasons to limit full public access to data from drug development studies. In contrast, intellectual freedom. public safety, and a mandate for transparent decision-making processes by regulatory agencies are issues that support open access to these data. Ultimately. concern for the public safety justifies open access to postmarketing surveillance data, and to a lesser degree, data regarding drug interactions in marketed products, and should outweigh the potential loss of competitive advantage by pharmaceutical companies.

  19. Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance.

    PubMed

    Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Suzuki, Nahoko; Murakami, Masahiro

    2017-07-20

    To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

  20. Design and analysis of post-marketing research.

    PubMed

    Zhou, Xiao-Hua Andrew; Yang, Wei

    2013-07-01

    A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine (TCM) products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.

  1. Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015

    PubMed Central

    Moro, Pedro L.; Woo, Emily Jane; Paul, Wendy; Lewis, Paige; Petersen, Brett W.; Cano, Maria

    2016-01-01

    Background In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States. Objective To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. Methods We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990–July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV. Results VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination. Conclusions This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies. PMID:27410239

  2. Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry

    PubMed Central

    Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

    2016-01-01

    Objective Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. Methods A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. Results A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Conclusions Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. PMID:27881517

  3. Stent thrombosis and bleeding complications after implantation of sirolimus-eluting coronary stents in an unselected worldwide population: a report from the e-SELECT (Multi-Center Post-Market Surveillance) registry.

    PubMed

    Urban, Philip; Abizaid, Alexandre; Banning, Adrian; Bartorelli, Antonio L; Baux, Ana Cebrian; Džavík, Vladimír; Ellis, Stephen; Gao, Runlin; Holmes, David; Jeong, Myung Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Spaulding, Christian; Worthley, Stephen

    2011-03-29

    The aim of this study was to ascertain the 1-year incidence of stent thrombosis (ST) and major bleeding (MB) in a large, unselected population treated with sirolimus-eluting stents (SES). Stent thrombosis and MB are major potential complications of drug-eluting stent implantation. Their relative incidence and predisposing factors among large populations treated worldwide are unclear. The SES were implanted in 15,147 patients who were entered in a multinational registry. We analyzed the incidence of: 1) definite and probable ST as defined by the Academic Research Consortium; and 2) MB, with the STEEPLE (Safety and efficacy of Enoxaparin in PCI) definition, together with their relation to dual antiplatelet therapy (DAPT) and to 1-year clinical outcomes. The mean age of the sample was 62 ± 11 years, 30.4% were diabetic, 10% had a Charlson comorbidity index ≥3, and 44% presented with acute coronary syndrome or myocardial infarction. At 1 year, the reported compliance with DAPT as recommended by the European Society of Cardiology guidelines was 86.3%. Adverse event rates were: ST 1.0%, MB 1.0%, mortality 1.7%, myocardial infarction 1.9%, and target lesion revascularization 2.3%. Multivariate analysis identified 9 correlates of ST and 4 correlates of MB. Advanced age and a high Charlson index were associated with an increased risk of both ST and MB. After ST, the 7-day and 1-year all-cause mortality was 30% and 35%, respectively, versus 1.5% and 10% after MB. Only 2 of 13,749 patients (0.015%) experienced both MB and ST during the entire 1-year follow-up period. In this worldwide population treated with ≥1 SES, the reported compliance with DAPT was good, and the incidence of ST and MB was low. Stent thrombosis and MB very rarely occurred in the same patient. (The e-SELECT Registry: a Multicenter Post-Market Surveillance; NCT00438919). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. The sirolimus-eluting Cypher Select coronary stent for the treatment of bare-metal and drug-eluting stent restenosis: insights from the e-SELECT (Multicenter Post-Market Surveillance) registry.

    PubMed

    Abizaid, Alexandre; Costa, J Ribamar; Banning, Adrian; Bartorelli, Antonio L; Dzavik, Vladimir; Ellis, Stephen; Gao, Runlin; Holmes, David R; Jeong, Muyng Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Orlick, Amy; Spaulding, Christian; Worthley, Stephen; Urban, Philip M

    2012-01-01

    This study sought to compare the 1-year safety and efficacy of Cypher Select or Cypher Select Plus (Cordis Corporation, Bridgewater, New Jersey) sirolimus-eluting stents (SES) with the treatment of bare-metal stents (BMS) and drug-eluting stent (DES) in-stent restenosis (ISR) in nonselected, real-world patients. There is paucity of consistent data on DES for the treatment of ISR, especially, DES ISR. The e-SELECT (Multicenter Post-Market Surveillance) registry is a Web-based, multicenter and international registry encompassing virtually all subsets of patients and lesions treated with at least 1 SES during the period from 2006 to 2008. We enrolled in this pre-specified subanalysis all patients with at least 1 clinically relevant BMS or DES ISR treated with SES. Primary endpoint was major adverse cardiac events and stent thrombosis rate at 1 year. Of 15,147 patients enrolled, 1,590 (10.5%) presented at least 1 ISR (BMS group, n = 1,235, DES group, n = 355). Patients with DES ISR had higher incidence of diabetes (39.4% vs. 26.9%, p < 0.001), renal insufficiency (5.8% vs. 2.3%, p = 0.003), and prior coronary artery bypass graft (20.5% vs. 11.8%, p < 0.001). At 1 year, death (1.4% for BMS vs. 2.1% for DES, p = 0.3) and myocardial infarction (2.4% for BMS and 3.3% for DES, p = 0.3) rates were similar, whereas ischemia-driven target lesion revascularization and definite/probable late stent thrombosis were higher in patients with DES ISR (6.9% vs. 3.1%, p = 0.003, and 1.8% vs. 0.5%, p = 0.04, respectively). Use of SES for either BMS or DES ISR treatment is safe and associated with low target lesion revascularization recurrence and no apparent safety concern. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. 21 CFR 822.20 - What are the consequences if I fail to submit a postmarket surveillance plan, my plan is...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... your device would be misbranded under section 502(t)(3) of the act. We have the authority to initiate actions against products that are adulterated or misbranded, and against persons who commit prohibited acts. Adulterated or misbranded devices can be seized. Persons who commit prohibited acts can...

  6. 21 CFR 822.20 - What are the consequences if I fail to submit a postmarket surveillance plan, my plan is...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... your device would be misbranded under section 502(t)(3) of the act. We have the authority to initiate actions against products that are adulterated or misbranded, and against persons who commit prohibited acts. Adulterated or misbranded devices can be seized. Persons who commit prohibited acts can...

  7. 21 CFR 822.20 - What are the consequences if I fail to submit a postmarket surveillance plan, my plan is...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... your device would be misbranded under section 502(t)(3) of the act. We have the authority to initiate actions against products that are adulterated or misbranded, and against persons who commit prohibited acts. Adulterated or misbranded devices can be seized. Persons who commit prohibited acts can...

  8. 21 CFR 822.20 - What are the consequences if I fail to submit a postmarket surveillance plan, my plan is...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... your device would be misbranded under section 502(t)(3) of the act. We have the authority to initiate actions against products that are adulterated or misbranded, and against persons who commit prohibited acts. Adulterated or misbranded devices can be seized. Persons who commit prohibited acts can...

  9. 21 CFR 822.20 - What are the consequences if I fail to submit a postmarket surveillance plan, my plan is...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... your device would be misbranded under section 502(t)(3) of the act. We have the authority to initiate actions against products that are adulterated or misbranded, and against persons who commit prohibited acts. Adulterated or misbranded devices can be seized. Persons who commit prohibited acts can...

  10. 21 CFR 26.33 - Product coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... surveillance/postmarket and initial/preapproval inspection reports and European Community (EC)-type quality system evaluation reports will be exchanged with regard to all products regulated under both U.S. and EC... reports and EC-type-testing reports will be exchanged only with regard to those products classified...

  11. Monitoring risk: post marketing surveillance and signal detection.

    PubMed

    Dart, Richard C

    2009-12-01

    The primary goal of postmarketing surveillance is to provide information for risk assessment of a drug. Drugs affecting the central nervous system form a unique group of products for surveillance because they are often misused, abused, and diverted. These medications include opioid analgesics, stimulants, sedative-hypnotics, muscle relaxants, anticonvulsants and other drug classes. Their adverse events are difficult to monitor because the perpetrator often attempts to conceal the misuse, abuse and diversion of the product. A postmarketing surveillance system for prescription drugs of abuse in the U.S. should include product specific information that is accurate, immediately available, geographically specific and includes all areas of the country. Most producers of branded opioid analgesic products have created systems that measure abuse from multiple vantage points: criminal justice, treatment professionals, susceptible patient populations and acute health events. In the past, the U.S. government has not established similar requirements for the same products produced by generic manufacturers. However, the Food and Drug Administration Amendments Act of 2007 includes generic opioid analgesic products by requiring that all products containing potent opioid drugs perform rigorous surveillance and risk management. While general risk management guidance has been developed by FDA, more specific analyses and guidance are needed to improve surveillance methodology for drugs which are misused, abused, diverted.

  12. Efficacy and tolerability of sequential intravenous/oral moxifloxacin therapy in pneumonia: results of the first post-marketing surveillance study with intravenous moxifloxacin in hospital practice.

    PubMed

    Barth, J; Stauch, K; Landen, H

    2005-01-01

    This study aimed to investigate the efficacy, safety and tolerability of sequential intravenous (IV)/oral therapy with moxifloxacin in pneumonia under general hospital treatment conditions. Patients with pneumonia were documented in this non-interventional multicentre study. The patients were treated with IV moxifloxacin or moxifloxacin sequential therapy (IV and oral) in hospitals throughout Germany. Exclusion criteria were limited to the contraindications mentioned in the summary of product characteristics. The participating hospital-based physicians documented the patients' demography, anamnesis, antibiotic pretreatment, concomitant diseases and medications. Moxifloxacin therapy and symptom status were recorded daily up to the ninth day and on the last day of treatment. The physicians assessed the efficacy and tolerability of IV moxifloxacin therapy and reported all adverse events observed within the treatment period. The 1749 documented patients had a mean age of 66.2 (SD 15.5) years; 56.4% were males and 43.5% females. The majority (99.3%) were treated with moxifloxacin 400mg once daily. On average, moxifloxacin was given for 7.6 days (SD 3.2). In cases of sequential therapy (78.9% of patients), IV moxifloxacin was switched to oral moxifloxacin after a mean of 4.1 days (SD 1.8). Moxifloxacin produced a significant clinical improvement in 58.2% of patients by day 3 of therapy, in 84.2% by day 5 and in 89.4% by day 7. Recovery occurred in 27.0% of patients by day 5, in 54.0% by day 7 and in 87.0% by day 14. It took a mean of 3.4 days (SD 1.9) until improvement and 7.2 days (SD 3.0) until cure. Overall efficacy of IV moxifloxacin therapy was rated by the physicians as 'very good' or 'good' in 82.9% of patients. Tolerability was rated in 94.3% of patients as 'very good' or 'good'. Adverse events were recorded for 92 (5.3%) patients, but events were considered by the attending physician to be related to moxifloxacin therapy for only 45 patients (2.6%). IV

  13. Signal detection using change point analysis in postmarket surveillance†

    PubMed Central

    Xu, Zhiheng; Kass-Hout, Taha; Anderson-Smits, Colin; Gray, Gerry

    2015-01-01

    Purpose Signal detection methods have been used extensively in postmarket surveillance to identify elevated risks of adverse events associated with medical products (drugs, vaccines, and devices). However, current popular disproportionality methods ignore useful information such as trends when the data are aggregated over time for signal detection. Methods In this paper, we applied change point analysis (CPA) to trend analysis of medical products in a spontaneous adverse event reporting system. CPA was used to detect the time point at which statistical properties of a sequence of observations change over time. Two CPA approaches, change in mean and change in variance, were demonstrated by an example using neurostimulator adverse event dataset. Results Two significant change points associated with upward trends were detected in June 2008 (n = 20, p < 0.001) and May 2011 (n = 51, p = 0.003). Further investigation confirmed battery issues and expansion of the indication for use could be possible causes for the occurrence of these change points. Two time points showed extremely low number of loss of therapy events, two cases in October 2009 and three in November 2009, which could be the result of reporting issues such as underreporting. Conclusion As a complimentary tool to current signal detection efforts at FDA, CPA can be used to detect changes in the association between medical products and adverse events over time. Detecting these changes could be critical for public health regulation, adverse events surveillance, product recalls, and regulators’ understanding of the connection between adverse events and other events regarding regulated products. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:25903221

  14. Magnetic Resonance Based Diagnostics for Polymer Production and Surveillance

    SciTech Connect

    Chinn, S; Herberg, J; Gjersing, E; Cook, A; Sawvel, A M; Maxwell, R; Wheeler, H; Wilson, M

    2006-09-27

    In an effort to develop a magnetic resonance based diagnostic tool to be used for polymer production and surveillance, we have investigated the use of magnetic resonance imaging (MRI) and unilateral relaxometry. MRI provides a spatial map of the polymer, which can be correlated to the structure heterogeneity. Though highly detailed information can be obtained with MRI, the high equipment cost and expertise required to operate the system makes it a poor choice for a production setting. Unilateral relaxometry via the NMR MOUSE provides rapid, inexpensive polymer screening, useful in the development in new polymer parts or to identify potentially defective components. The NMR ProFiler (originally called the NMR MOUSE) was procured by Kansas City originally for production support of the W80 LEP with future applications as a surveillance diagnostic. A robotic autosampler has been designed allowing the detection of several components without the need for any human interaction. A summary of the qualification experiments and results to date from the ProFiler and the robotic unit will be presented.

  15. Pediatric post-marketing safety systems in North America: assessment of the current status.

    PubMed

    McMahon, Ann W; Wharton, Gerold T; Bonnel, Renan; DeCelle, Mary; Swank, Kimberley; Testoni, Daniela; Cope, Judith U; Smith, Phillip Brian; Wu, Eileen; Murphy, Mary Dianne

    2015-08-01

    It is critical to have pediatric post-marketing safety systems that contain enough clinical and epidemiological detail to draw regulatory, public health, and clinical conclusions. The pediatric safety surveillance workshop (PSSW), coordinated by the Food and Drug Administration (FDA), identified these pediatric systems as of 2010. This manuscript aims to update the information from the PSSW and look critically at the systems currently in use. We reviewed North American pediatric post-marketing safety systems such as databases, networks, and research consortiums found in peer-reviewed journals and other online sources. We detail clinical examples from three systems that FDA used to assess pediatric medical product safety. Of the 59 systems reviewed for pediatric content, only nine were pediatric-focused and met the inclusion criteria. Brief descriptions are provided for these nine. The strengths and weaknesses of three systems (two of the nine pediatric-focused and one including both children and adults) are illustrated with clinical examples. Systems reviewed in this manuscript have strengths such as clinical detail, a large enough sample size to capture rare adverse events, and/or a patient denominator internal to the database. Few systems include all of these attributes. Pediatric drug safety would be better informed by utilizing multiple systems to take advantage of their individual characteristics. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Postmarketing studies: benefits and risks.

    PubMed

    Garfield, F B; Caro, J J

    1999-01-01

    To consider the benefits and risks of large postmarketing outcomes studies, as demonstrated by studies of the statin drugs. Literature review. The risks were that the statin studies had a strong coat-tail effect. Each new study was beneficial to all statins as well as the one studied. Economic analyses based on the results of the postmarketing studies concluded that the drugs were not cost-effective. Long-term postmarketing studies were slow to be put into perspective and did not immediately influence other researchers or clinicians. During that time, the sponsoring companies shouldered opportunity costs as well as the actual costs of the studies. The risk that one drug company would use another company's results instead of investing in their own research did not materialize. The benefits were that the studies definitively showed that the drugs and the lowering of lipids were safe and efficacious. The studies also expanded the indications for the drugs, generated goodwill in the medical and research communities for the sponsors, allowed sponsors to include specific claims in their advertisements, generated follow-up studies, spawned economic analyses that sparked interest in the medical and lay press, and had a major impact on clinicians' use of the drug. The risks and benefits of postmarketing studies may depend on the company's time perspective. In the short term, the risks may outweigh the benefits. Only companies that have a longer perspective may find it beneficial to undertake large postmarketing studies.

  17. Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated With Severe Adverse Postmarketing Events.

    PubMed

    Kotarek, Joseph; Stuart, Christine; De Paoli, Silvia H; Simak, Jan; Lin, Tsai-Lien; Gao, Yamei; Ovanesov, Mikhail; Liang, Yideng; Scott, Dorothy; Brown, Janice; Bai, Yun; Metcalfe, Dean D; Marszal, Ewa; Ragheb, Jack A

    2016-03-01

    Peginesatide (Omontys(®); Affymax, Inc., Cupertino, CA) was voluntarily withdrawn from the market less than a year after the product launch. Although clinical trials had demonstrated the drug to be safe and efficacious, 49 cases of anaphylaxis, including 7 fatalities, were reported not long after market introduction. Commercialization was initiated with a multiuse vial presentation, which differs in formulation from the single-use vial presentation used in phase 3 studies. Standard physical and chemical testing did not indicate any deviation from product specifications in either formulation. However, an analysis of subvisible particulates using nanoparticle tracking analysis and flow imaging revealed a significantly higher concentration of subvisible particles in the multiuse vial presentation linked to the hypersensitivity cases. Although it is unknown whether the elevated particulate content is causally related to these serious adverse events, this report illustrates the utility of characterizing subvisible particulates not captured by conventional light obscuration. Copyright © 2016. Published by Elsevier Inc.

  18. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

    PubMed Central

    Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-01-01

    Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are

  19. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies.

    PubMed

    Spelsberg, Angela; Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-02-07

     To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.  Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.  Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.  Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.  Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.  Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the

  20. [Technical specifications for intensive hospital safety monitoring of post-marketing Chinese medicine (draft version for comments)].

    PubMed

    Xie, Yan-Ming; Liao, Xing; Zhao, Yu-Bin; Li, Ming-Quan; Zhang, Yun-Ling; Ma, Rong; Xian, Shao-Xiang; Liu, Jian; Li, Su-Yun; Wen, Ze-Huai; Yang, Zhong-Qi; Zou, Jian-Dong; Sun, Hong-Sheng; He, Yan; Li, Xue-Lin; Jiang, Jun-Jie; Wang, Zhi-Fei; Li, Yuan-Yuan; Wang, Lian-Xin; Chang, Yan-Peng; Yang, Wei; Zhang, Wen

    2013-09-01

    It is of vital significance to conduct active post-marketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China food and drug administration. The standards for technological specifications based on expert consensus have been drafted. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The technological specifications for post-marketing surveillance focus on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.

  1. Surveillance methods for identifying, characterizing, and monitoring tobacco products: potential reduced exposure products as an example

    PubMed Central

    O’Connor, Richard J.; Cummings, K. Michael; Rees, Vaughan W.; Connolly, Gregory N.; Norton, Kaila J.; Sweanor, David; Parascandola, Mark; Hatsukami, Dorothy K.; Shields, Peter G.

    2015-01-01

    Tobacco products are widely sold and marketed, yet integrated data systems for identifying, tracking, and characterizing products are lacking. Tobacco manufacturers recently have developed potential reduction exposure products (PREPs) with implied or explicit health claims. Currently, a systematic approach for identifying, defining, and evaluating PREPs sold at the local, state or national levels in the US has not been developed. Identifying, characterizing, and monitoring new tobacco products could be greatly enhanced with a responsive surveillance system. This paper critically reviews available surveillance data sources for identifying and tracking tobacco products, including PREPs, evaluating strengths and weaknesses of potential data sources in light of their reliability and validity. Absent regulations mandating disclosure of product-specific information, it is likely that public health officials will need to rely on a variety of imperfect data sources to help identify, characterize, and monitor tobacco products, including PREPs. PMID:19959680

  2. 21 CFR 314.81 - Other postmarketing reports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Other postmarketing reports. 314.81 Section 314.81... affect the safety, effectiveness, or labeling of the drug product. The report is also required to contain... drug, a copy of that portion of the annual report must be sent to the Food and Drug Administration...

  3. 21 CFR 314.81 - Other postmarketing reports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Other postmarketing reports. 314.81 Section 314.81... affect the safety, effectiveness, or labeling of the drug product. The report is also required to contain... drug, a copy of that portion of the annual report must be sent to the Food and Drug Administration...

  4. Influenza Vaccines: From Surveillance Through Production to Protection

    PubMed Central

    Tosh, Pritish K.; Jacobson, Robert M.; Poland, Gregory A.

    2010-01-01

    Influenza is an important contributor to population and individual morbidity and mortality. The current influenza pandemic with novel H1N1 has highlighted the need for health care professionals to better understand the processes involved in creating influenza vaccines, both for pandemic as well as for seasonal influenza. This review presents an overview of influenza-related topics to help meet this need and includes a discussion of the burden of disease, virology, epidemiology, viral surveillance, and vaccine strain selection. We then present an overview of influenza vaccine—related topics, including vaccine production, vaccine efficacy and effectiveness, influenza vaccine misperceptions, and populations that are recommended to receive vaccination. English-language articles in PubMed published between January 1, 1970, and October 7, 2009, were searched using key words human influenza, influenza vaccines, influenza A, and influenza B. PMID:20118381

  5. Thirty years of medical surveillance in perfluooctanoic acid production workers.

    PubMed

    Costa, Giovanni; Sartori, Samantha; Consonni, Dario

    2009-03-01

    To report health outcomes of 30 years (1978-2007) of medical surveillance of workers engaged in a perfluooctanoic acid (PFOA) production plant. Fifty-three males workers (20 to 63 years) were submitted every year to medical examination and blood chemical chemistry tests, and serum PFOA dosage. In the latest survey PFOA serum levels ranged from 0.20 to 47.04 microg/mL in currently exposed workers, and from 0.53 to 18.66 microg/mL in those formerly exposed. No clinical evidence of any specific trouble or disease has been recorded over the 30 years, and all the biochemical parameters, including liver, kidney and hormonal functions, turned out to be within the reference ranges, but a significant association of total cholesterol and uric acid with and PFOA serum level was evidenced. A probable interference of PFOA on intermediate metabolism deserves further investigations.

  6. To establish a body of evidence on safety for postmarketing Chinese medicine: A new research paradigm.

    PubMed

    Liao, Xing; Xie, Yan-Ming; Robinson, Nicola; Wang, Yong-Yan

    2017-03-01

    The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in mainland China recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for effificacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this fifield both in China and abroad are urgently needed.

  7. FDA's expanding postmarket authority to monitor and publicize food and consumer health product risks: the need for procedural safeguards to reduce "transparency" policy harms in the post-9/11 regulatory environment.

    PubMed

    Roller, Sarah Taylor; Pippins, Raqiyyah R; Ngai, Jennifer W

    2009-01-01

    This article provides a summary of the expansion of FDA's discretionary authority in the post-9/11 period, particularly with respect to FDA's authority to monitor and publicize potential health risks linked to food, dietary supplements, nonprescription drugs, and other consumer health products. In addition, this article evaluates the need for FDA to establish procedural safeguards to reduce the significant risks of unintended and undue harm to people and regulated companies that can result from adverse publicity in the more "transparent" post 9/11 FDA regulatory environment. Specifically, Part I summarizes the amendments to the FDCA enacted during the post-9/11 period that have expanded FDA's postmarket authority to monitor, evaluate, and publicize potential health risks linked to food, dietary supplements, nonprescription drugs and other consumer health products marketed in the United States, in conjunction with FDA's Sentinel Initiative, Reportable Food Registry, and other adverse event reporting requirements. Part II discusses the convergence of FDA's expanded postmarket authority to publicize product-related risks with President Obama's transparency initiative aimed at fostering "open government" through increased public access to government information. In addition, Part II considers the nature of the procedural safeguards needed in the post-9/11 FDA regulatory environment, in view of FDA's historical record and illustrative cases that help expose how adverse "transparency" surrounding FDA warning letters, recalls and safety alerts concerning products in the marketplace can have undue and unintended prejudicial and harmful effects for the people and companies that are legally responsible for such products. Finally, based on these analysis, this article concludes with some observations concerning the nature of the procedural safeguards needed to reduce the significant risks of "transparency" policy harms in the pos-9/11 regulatory environment.

  8. A conceptual framework for economic optimization of single hazard surveillance in livestock production chains.

    PubMed

    Guo, Xuezhen; Claassen, G D H; Oude Lansink, A G J M; Saatkamp, H W

    2014-06-01

    Economic analysis of hazard surveillance in livestock production chains is essential for surveillance organizations (such as food safety authorities) when making scientifically based decisions on optimization of resource allocation. To enable this, quantitative decision support tools are required at two levels of analysis: (1) single-hazard surveillance system and (2) surveillance portfolio. This paper addresses the first level by presenting a conceptual approach for the economic analysis of single-hazard surveillance systems. The concept includes objective and subjective aspects of single-hazard surveillance system analysis: (1) a simulation part to derive an efficient set of surveillance setups based on the technical surveillance performance parameters (TSPPs) and the corresponding surveillance costs, i.e., objective analysis, and (2) a multi-criteria decision making model to evaluate the impacts of the hazard surveillance, i.e., subjective analysis. The conceptual approach was checked for (1) conceptual validity and (2) data validity. Issues regarding the practical use of the approach, particularly the data requirement, were discussed. We concluded that the conceptual approach is scientifically credible for economic analysis of single-hazard surveillance systems and that the practicability of the approach depends on data availability. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. [Literature review on premarketing and postmarketing evidence of xiyanping injection].

    PubMed

    Wang, Zhi-Fei; Chen, Xiao; Zhang, Wen; Xie, Yan-Ming

    2014-09-01

    This article systematically summarizes the non-clinical safety studies, pharmacological studies and postmarketing safety studies of Xiyanping injection based on literature. These studies include acute toxicity test, long-term toxicity test, reproductive toxicity test, active and passive anaphylaxis test, curative mechanism study, clinical trials of effectiveness, active surveillance, security analysis of passive monitoring data, the real world analysis of hospital information system (HIS) data, literature analysis, etcetera This article also analysis the relationship of the different evidence, summarizes the strategy of the researches, in order to make it to be a reference for making a systemic research program of traditional Chinese medicine injection.

  10. Efficacy and safety of botulinum toxin type A (Dysport) for the treatment of post-stroke arm spasticity: results of the German-Austrian open-label post-marketing surveillance prospective study.

    PubMed

    Jost, Wolfgang H; Hefter, Harald; Reissig, Andrea; Kollewe, Katja; Wissel, Joerg

    2014-02-15

    The current practice in Germany and Austria, and the safety and efficacy of botulinum toxin type A (BoNT-A; Dysport) in the treatment of patients with post-stroke arm spasticity (with no fixed upper-limb contractures), were assessed in this observational prospective non-interventional study. One treatment cycle was documented with assessments at baseline, approximately week 4 (optional), and approximately week 12. Pattern of spasticity, treatment goal, safety and efficacy were recorded. Overall response and goal achievement was rated on a 4-point scale ('no goal achievement', 'goal achievement', 'good goal achievement', 'best goal achievement'). In total, 409 patients were included and 99% assigned to one of five arm-spasticity patterns. Therapy goals included reduced muscle tone (92.6%), physiotherapy or occupational therapy support (63.8%), increased range of motion (61.8%), pain reduction (58.9%), facilitation of care or hygiene (55.7%), and functional improvement (17.0%). Goals were achieved in 84% of patients. The following factors had the most potential as predictors of treatment outcome: pre-treatment; time since onset of spasticity; pattern of arm spasticity. Mean Dysport dose was 728 U and an inverse dose-response relationship was observed. Treatment was well tolerated. 500-1000 U was a safe and effective treatment for post-stroke arm spasticity in this post-marketing evaluation. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Impact of insulin-treated diabetes and hemodialysis on long-term clinical outcomes following sirolimus-eluting stent deployment. Insights from a sub-study of the Cypher Stent Japan Post-Marketing Surveillance(Cypher J-PMS) Registry.

    PubMed

    Nakamura, Masato; Yokoi, Hiroyoshi; Hamazaki, Yuji; Watarai, Masato; Kijima, Mikihiro; Mitsudo, Kazuaki

    2010-11-01

    Long-term clinical outcomes of diabetes mellitus (DM) patients who underwent drug-eluting stent deployment has not well investigated. A total of 2,050 cases were enrolled consecutively from 50 sites in Japan into the Cypher stent Japan Post-Marketing Surveillance (Cypher J-PMS) registry, and the 3-year outcomes of DM patients were analyzed. Subjects were divided into 2 groups based on the treatment of DM (insulin-treated diabetes (IT) group, n=207; and non insulin-treated diabetes (NIT) group, n=682). Major adverse cardiac event (MACE) rates in the IT group and the NIT group were 26.0% and 14.5% at 3 years, respectively (P<0.001). There were no significant differences in stent thrombosis rates (definite and probable by Academic Research Consortium (ARC) definition) (0% and 1.08%, respectively). Multivariate analysis suggested that hemodialysis and insulin-treated DM were independent predictors for MACE, and insulin-treated DM, hemodialysis and long lesions were strong independent predictors for target-lesion revascularization (TLR). Hemodialysis and insulin-treated DM were strong independent predictors of mortality and TLR in DM patients. These results might suggest that special attention to patients with hemodialysis and insulin-treated DM is warranted in the setting of sirolimus-eluting stent deployment for DM patients.

  12. Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

    PubMed

    Schick, Andreas; Miller, Kathleen L; Lanthier, Michael; Dal Pan, Gerald; Nardinelli, Clark

    2017-06-01

    An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing

  13. The FDA's sentinel initiative--A comprehensive approach to medical product surveillance.

    PubMed

    Ball, R; Robb, M; Anderson, S A; Dal Pan, G

    2016-03-01

    In May 2008, the Department of Health and Human Services announced the launch of the Sentinel Initiative by the US Food and Drug Administration (FDA) to create the Sentinel System, a national electronic system for medical product safety surveillance. This system complements existing FDA surveillance capabilities that track adverse events reported after the use of FDA regulated products by allowing the FDA to proactively assess the safety of these products.

  14. Review of Transporter-Related Postmarketing Requirement or Postmarketing Commitment Studies.

    PubMed

    Fan, Ying; Sun, Bo; Agarwal, Sheetal; Zhang, Lei

    2016-07-01

    The objectives of this report are to summarize the content and status of transporter-related postmarketing requirement (PMR)/postmarketing commitment (PMC) studies in new drug applications (NDAs) approved by the U.S. Food and Drug Administration (FDA) and to discuss the reasons for requesting such studies and the impact of PMR/PMC study results on labeling to guide the optimal use of the drugs. Multiple data sources were searched to collect information on transporter-related PMR/PMC studies between January 1999 and May 2015. A total of 40 transporter-related PMR/PMC study requests were issued for 35 NDAs. Among these PMR/PMC studies, 27 requested studies related to P-glycoprotein. As of May 31, 2015, 34 transporter-related PMR/PMC studies (85%) are considered "fulfilled" (per the FDA's PMR/PMC website), and 22 (65%) resulted in labeling updates. The majority of the PMR/PMC studies are for drugs in the therapeutic areas of anti-infectives, oncology, and neurology. The results from PMR/PMC studies are important for dosing optimization and are often included in the updated labeling. Because a significant lag time is anticipated between drug approval and PMR/PMC fulfillment, NDA applicants are encouraged to include transporter-related assessments in clinical drug development programs for drug products.

  15. Production data reporting and how it aids surveillance in thermal recovery fields

    SciTech Connect

    Dever, R.E.; Womack, F.A.

    1983-03-01

    Modern surveillance requirements in large thermal recovery oil fields overwhelm manual efforts at collection, retrieval, and reporting of operations and production data. The introduction of a customized data base management and reporting system for this purpose can benefit Operations and Engineering through increased production from timelier awareness of field operating conditions, reduced operating expenses, better steam utilization, and significant manpower productivity increases.

  16. Guideline for postmarketing Chinese medicine pharmacoeconomic evaluation.

    PubMed

    Wang, Xin; Wang, Zhi-Fei; Xie, Yan-Ming; Zhang, Wen; Liao, Xing; Chang, Yan-Peng

    2015-06-01

    Pharmacoeconomics is an important part of the postmarketing Chinese medicine (CM) evaluation, and postmarketing pharmacoeconomic evaluation can reveal the clinical and market value of CM. The purpose of establishing the guideline for pharmacoeconomic evaluation is to make the evaluation process and results regarding Chinese patent medicines both scientific and fair. Every country's guidelines for pharmacoeconomic evaluation act as reference guidelines, we have already drawn up the guideline that takes into account the special characteristics of CM; and these are in preparation for the postmarketing CM pharmacoeconomic evaluation.

  17. Global Tobacco Surveillance System (GTSS): purpose, production, and potential.

    PubMed

    2005-01-01

    The World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and Canadian Public Health Association (CPHA) developed the Global Tobacco Surveillance System (GTSS) to assist all 192 WHO Member States in collecting data on youth and adult tobacco use. The flexible GTSS system includes common data items but allows countries to include important unique information at their discretion. It uses a common survey methodology, similar field procedures for data collection, and similar data management and processing techniques. The GTSS includes collection of data through three surveys: the Global Youth Tobacco Survey (GYTS) for youth, and the Global School Personnel Survey (GSPS) and the Global Health Professional Survey (GHPS) for adults. GTSS data potentially can be applied in four ways. First, countries and research partners can disseminate data through publications, presentations, and an active GTSS web site. Second, countries can use GTSS data to inform politicians about the tobacco problem in their country, leading to new policy decisions to prevent and control tobacco use. Third, GTSS can provide countries with valuable feedback to evaluate and improve Country National Action Plans or develop new plans. Fourth, in response to the WHO FCTC call for countries to use consistent methods and procedures in their surveillance efforts, GTSS offers such consistency in sampling procedures, core questionnaire items, training infield procedures, and analysis of data across all survey sites. The GTSS represents the most comprehensive tobacco surveillance system ever developed and implemented. As an example, this paper describes development of the GYTS and discusses potential uses of the data. Sample data were drawn from 38 sites in 24 countries in the African Region, 82 sites in 35 countries in the Americas Region, 20 sites in 17 countries and the Gaza Strip/West Bank region in the Eastern Mediterranean Region, 25 sites in 22 countries in the European

  18. Marriage of military and commercial RECCE products for surveillance applications

    NASA Astrophysics Data System (ADS)

    Regan, Brendan P.

    1994-10-01

    During recent years, in order to meet increased demands for aerial surveillance data and due to decreased availability of support from military tactical reconnaissance organizations, many state and federal agencies have begun to expand their organic reconnaissance capabilities. Agencies have attempted to minimize system costs by procuring excess military sensors, only to find that adaptation of existing military sensor control and data annotation systems, or development of application specific systems, is cost prohibitive. One proposed solution to this dilemma, as presented within this paper, is user integrated reconnaissance systems which can include excess military sensors, but which also make extensive use of cost effective commercially procurable reconnaissance management system (RMS) components.

  19. Postmarketing study of timolol-hydrochlorothiazide antihypertensive therapy.

    PubMed

    Bannon, J A; Stewart, K A; Schrogie, J J; Delisser, O

    1985-01-01

    A postmarketing surveillance study was conducted to determine the safety and efficacy of a fixed-ratio combination containing 10 mg of timolol maleate and 25 mg of hydrochlorothiazide, administered twice daily for one month to hypertensive patients. Data on 9,037 patients were collected by 1,455 participating physicians. Mean systolic blood pressure decreased 25 mmHg and mean diastolic blood pressure declined 15 mmHg after one month of timolol-hydrochlorothiazide therapy (P less than 0.01, both comparisons). Age, race, and sex appeared to have no influence on the decrease in blood pressure. The antihypertensive effect of the drug was greater in patients with more severe hypertension. Overall, 1,453 patients experienced a total of 2,658 adverse events, the most common being fatigue, dizziness, and weakness. Treatment in 590 patients was discontinued because of adverse events.

  20. Regulations and guidelines should be strengthened urgently for re-evaluation on post-marketing medicines in China.

    PubMed

    Xie, Yan-Ming; Tian, Feng

    2013-07-01

    This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and techniques on postmarketing surveillance (also named pharmacovigilance), therefore, their regulation systems are nearly perfect. In China, the regulations on post-marketing re-evaluation and relative technical guidelines do not cover the whole aspects, even lack in some important aspects, and long-term risk management mechanisms have not been established. So it is urgent to establish new regulations and improve the regulatory system in China based on the existing regulations and guidelines, by learning from the ideas of foreign advanced regulations, then fully integrating them with China's actual conditions, and cooperating with multidisciplinary researchers.

  1. [The scientific production and research groups on sanitary surveillance at CNPq].

    PubMed

    Pepe, Vera Lúcia Edais; de Noronha, Ana Beatriz Marinho; Figueiredo, Tatiana Aragão; de Souza, Adriana de Alvarenga Linhares; Oliveira, Catia Veronica dos Santos; Pontes Júnior, Durval Martins

    2010-11-01

    Sanitary surveillance is an intersectorial and multidisciplinary practice of health regulation. The aim was to describe the scientific research on sanitary surveillance and its research groups in Brazil during the period of 1997 to 2003, through the Census of 2000, 2002 and 2004 of Directory of Research Groups of the Scientific and Technological Development National Council (CNPq). The term "sanitary surveillance" was used to search the production and the research groups in the Lattes Platform of CNPq. There were 1,194 items, 913 in bibliographic production and 281 in post-graduated production, with an increment of 540% on the period. There were 735 research groups, created mostly from 2000 to 2003 and 6,263 researchers concentrated in the Southeast Region and in CNPq sub area of Public Health. The great increase of the production lead to the conclusion that sanitary surveillance have been a locus of production only in the last decade, presented in scientific events of Public Health and until now concentrated just like others areas in Health.

  2. Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

    PubMed

    Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

    2017-08-01

    To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

  3. A proposal for financing postmarketing drug safety studies by augmenting FDA user fees.

    PubMed

    Carpenter, Daniel

    2005-01-01

    I propose to raise funds for postapproval studies of long-term drug safety by augmenting the existing "user-fee" system. Fees would be raised by an amount deemed optimal for revenue collection, and the U.S. Food and Drug Administration (FDA) would direct the incremental funds to a combination of randomized controlled trials, epidemiological studies, and postmarketing surveillance. User-fee augmentation is an achievable, incremental reform that would subsidize information that is now undersupplied in the U.S. health care system; spread the burden of funding postmarketing safety studies among pharmaceutical sponsors; and help restore public, scientific, and professional confidence in the FDA and its user-fee system.

  4. 76 FR 52669 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ...The Food and Drug Administration (FDA) is correcting a notice of availability that appeared in the Federal Register of August 4, 2011 (76 FR 47211). The Agency is required to report annually in the Federal Register on the status of postmarketing requirements and commitments required of, or agreed upon by, holders of approved drug and biological products. The August 4, 2011, notice is the......

  5. 21 CFR 822.12 - Do you have any information that will help me prepare my submission or design my postmarket...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... plan are available on the Center for Devices and Radiological Health's Web site and from the Food and... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Do you have any information that will help me prepare my submission or design my postmarket surveillance plan? 822.12 Section 822.12 Food and Drugs...

  6. 21 CFR 822.12 - Do you have any information that will help me prepare my submission or design my postmarket...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... plan are available on the Center for Devices and Radiological Health's Web site and from the Food and... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Do you have any information that will help me prepare my submission or design my postmarket surveillance plan? 822.12 Section 822.12 Food and Drugs...

  7. 21 CFR 822.12 - Do you have any information that will help me prepare my submission or design my postmarket...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Do you have any information that will help me prepare my submission or design my postmarket surveillance plan? 822.12 Section 822.12 Food and Drugs FOOD... plan are available on the Center for Devices and Radiological Health's Web site and from the Center...

  8. 21 CFR 822.12 - Do you have any information that will help me prepare my submission or design my postmarket...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... plan are available on the Center for Devices and Radiological Health's Web site and from the Food and... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Do you have any information that will help me prepare my submission or design my postmarket surveillance plan? 822.12 Section 822.12 Food and Drugs...

  9. 21 CFR 822.12 - Do you have any information that will help me prepare my submission or design my postmarket...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... plan are available on the Center for Devices and Radiological Health's Web site and from the Food and... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Do you have any information that will help me prepare my submission or design my postmarket surveillance plan? 822.12 Section 822.12 Food and Drugs...

  10. The New Product Watch: Successes and Challenges of Crowdsourcing as a Method of Surveillance.

    PubMed

    Nyman, Amy L; Biener, Lois

    2016-01-01

    New smokeless tobacco (eg, snus and dissolvable tobacco products) and nontobacco nicotine products (eg, e-cigarettes) have emerged in recent years amid widespread speculation about locations of test marketing, toxic constituents, and consumer targeting. The New Product Watch was a pilot online monitoring system aimed at filling these information gaps by using a form of crowdsourcing: recruiting volunteers to visit local retailers and report their findings. With very little funding, the New Product Watch gathered county-specific data on new product availability in 19 states as well as trend data on product marketing and demand, and completed 2 rounds of product purchases and subsequent toxic constituent analyses. Data were collected over a 2-year period, between 2009 and 2011. Despite the successes, we found that this small-scale, volunteer effort was not a sustainable method for ensuring continuous, systematic surveillance of new product availability, marketing, and toxicity.

  11. International standards for monoclonal antibodies to support pre- and post-marketing product consistency: Evaluation of a candidate international standard for the bioactivities of rituximab.

    PubMed

    Prior, Sandra; Hufton, Simon E; Fox, Bernard; Dougall, Thomas; Rigsby, Peter; Bristow, Adrian

    2017-10-06

    The intrinsic complexity and heterogeneity of therapeutic monoclonal antibodies is built into the biosimilarity paradigm where critical quality attributes are controlled in exhaustive comparability studies with the reference medicinal product. The long-term success of biosimilars will depend on reassuring healthcare professionals and patients of consistent product quality, safety and efficacy. With this aim, the World Health Organization has endorsed the need for public bioactivity standards for therapeutic monoclonal antibodies in support of current controls. We have developed a candidate international potency standard for rituximab that was evaluated in a multi-center collaborative study using participants' own qualified Fc-effector function and cell-based binding bioassays. Dose-response curve model parameters were shown to reflect similar behavior amongst rituximab preparations, albeit with some differences in potency. In the absence of a common reference standard, potency estimates were in poor agreement amongst laboratories, but the use of the candidate preparation significantly reduced this variability. Our results suggest that the candidate rituximab standard can support bioassay performance and improve data harmonization, which when implemented will promote consistency of rituximab products over their life-cycles. This data provides the first scientific evidence that a classical standardization exercise allowing traceability of bioassay data to an international standard is also applicable to rituximab. However, we submit that this new type of international standard needs to be used appropriately and its role not to be mistaken with that of the reference medicinal product.

  12. 76 FR 47211 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ... Conducting Postmarketing Requirements and Commitments; Availability AGENCY: Food and Drug Administration, HHS... Register on the status of postmarketing requirements and commitments required of, or agreed upon by.... Under the Modernization Act, commitments to conduct postmarketing studies or clinical trials...

  13. Postmarketing pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol in Egypt.

    PubMed

    Badawi, M A; Wagdy, E; Nasr, M; Etman, M A; El-Khordagui, L K; Khalil, S A H

    2014-01-09

    Concerns have been raised regarding the postmarketing quality of generic drugs. This study assessed the pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol tablets in 24 healthy male volunteers in a single-dose, open, randomized, two-period crossover study under fasting conditions. Blood samples were collected for 24 h post dosing and assayed for atenolol using HPLC. Blood pressure and heart rate were measured at baseline and throughout blood sampling. The mean plasma concentration-time curves for both products were similar. Pharmacokinetic and statistical analysis indicated bioequivalence based on the mean ratios of log-transformed Cmax and AUC values. Both products had similar time courses of pharmacodynamic activity with a significant fall in blood pressure and heart rate (maximum after ~5 h) followed by a gradual increase towards baseline. Both products were well tolerated. Both atenolol products were bioequivalent in the postmarketing setting and can be used interchangeably in clinical practice.

  14. A distributed research network model for post-marketing safety studies: the Meningococcal Vaccine Study.

    PubMed

    Velentgas, Priscilla; Bohn, Rhonda L; Brown, Jeffrey S; Chan, K Arnold; Gladowski, Patricia; Holick, Crystal N; Kramer, Judith M; Nakasato, Cynthia; Spettell, Claire M; Walker, Alexander M; Zhang, Fang; Platt, Richard

    2008-12-01

    We describe a multi-center post-marketing safety study that uses distributed data methods to minimize the need for covered entities to share protected health information (PHI). Implementation has addressed several issues relevant to creation of a large scale post-marketing drug safety surveillance system envisioned by the FDA's Sentinel Initiative. This retrospective cohort study of Guillain-Barré syndrome (GBS) following meningococcal conjugate vaccination incorporates the data and analytic expertise of five research organizations closely affiliated with US health insurers. The study uses administrative claims data, plus review of full text medical records to adjudicate the status of individuals with a diagnosis code for GBS (ICD9 357.0). A distributed network approach is used to create the analysis files and to perform most aspects of the analysis, allowing nearly all of the data to remain behind institutional firewalls. Pooled analysis files transferred to a central site will contain one record per person for approximately 0.2% of the study population, and contain PHI limited to the month and year of GBS onset for cases or the index date for matched controls. The first planned data extraction identified over 9 million eligible adolescents in the target age range of 11-21 years. They contributed an average of 14 months of eligible time on study over 27 months of calendar time. MCV4 vaccination coverage levels exceeded 20% among 17-18-year olds and 16% among 11-13 and 14-16-year-old age groups by the second quarter of 2007. This study demonstrates the feasibility of using a distributed data network approach to perform large scale post-marketing safety analyses and is scalable to include additional organizations and data sources. We believe these results can inform the development of a large national surveillance system. Copyright (c) 2008 John Wiley & Sons, Ltd.

  15. Preclinical, Clinical, and Over-the-Counter Postmarketing Experience with a New Vaginal Cup: Menstrual Collection

    PubMed Central

    North, Barbara B.

    2011-01-01

    Abstract Background Menstrual cups have been available for decades, but their use is limited by bulky design and the need for multiple sizes. The Softcup® (Instead, Inc., San Diego, CA) is a simple single-size disposable over-the-counter (OTC) menstrual cup that compresses to tampon shape to facilitate insertion and can be worn during coitus. This report describes preclinical evaluation, clinical testing, and postmarketing monitoring of the Softcup. Methods Preclinical testing complied with U.S. Food and Drug Administration (FDA) guidelines and used standard United States Pharmacopoeia methodologies for assessment of potential toxicity. Clinical testing enrolled 406 women in seven U.S. centers. A detailed written questionnaire assessed safety, acceptability, and effectiveness for menstrual collection. Study safety parameters included pelvic examinations, Pap smears, colposcopy, urinalysis, vaginal pH, wet mounts, gram stain, and vaginal microflora cultures. Postmarketing surveillance of over 100 million Softcups has been conducted by the manufacturer and by the FDA Medwatch system. Results No toxicity or mutagenicity was observed in preclinical evaluations. In clinical testing, after three cycles of cup use, 37% of subjects rated the cup as better than, 29% as worse than, and 34% as equal to pads or tampons. The cup was preferred for comfort, dryness, and less odor. Cups received lower ratings for disposal and convenience. Eighty-one percent of enrolled women were able to insert and remove their first cup using only written instructions. Use difficulties resulting in study discontinuations included cramping (1%), leakage (1%), and improper fit (3%). No safety parameters were adversely affected. No significant health risks were reported during postmarketing surveillance. Conclusions These results demonstrate that a single-size vaginal device has no significant health risks and is acceptable to many women without the need for fitting or other medical services. PMID

  16. Monitoring biomedical literature for post-market safety purposes by analyzing networks of text-based coded information.

    PubMed

    Botsis, Taxiarchis; Foster, Matthew; Kreimeyer, Kory; Pandey, Abhishek; Forshee, Richard

    2017-01-01

    Literature review is critical but time-consuming in the post-market surveillance of medical products. We focused on the safety signal of intussusception after the vaccination of infants with the Rotashield Vaccine in 1999 and retrieved all PubMed abstracts for rotavirus vaccines published after January 1, 1998. We used the Event-based Text-mining of Health Electronic Records system, the MetaMap tool, and the National Center for Biomedical Ontologies Annotator to process the abstracts and generate coded terms stamped with the date of publication. Data were analyzed in the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment to evaluate the intussusception-related findings before and after the release of the new rotavirus vaccines in 2006. The tight connection of intussusception with the historical signal in the first period and the absence of any safety concern for the new vaccines in the second period were verified. We demonstrated the feasibility for semi-automated solutions that may assist medical reviewers in monitoring biomedical literature.

  17. Poison control centers' role in glow product-related outbreak detection: implications for comprehensive surveillance system.

    PubMed

    Chu, Alvin F; Marcus, Steven M; Ruck, Bruce

    2009-01-01

    The development of syndromic surveillance systems to detect bioterrorist attacks and emerging infectious diseases has become an important and challenging goal to many governmental agencies and healthcare authorities. This study utilized the sharp increase of glow product-related calls to demonstrate the utility of poison control data for early detection of potential outbreaks during the week of Halloween in 2007. A review was conducted of the electronic records of exposures reported to the New Jersey Poison Information and Education System (NJPIES) Poison Control Hotline from 2002 through 2007 with generic code number 0201027 (glow products) set by the American Association of Poison Control Centers (AAPCC). Key information such as age, gender, time of the call, exposure reason, clinical effects, and medical outcomes along with telephone number, zip code, and county location were used in the analyses to determine the extent of the outbreak. Analyses included a total of 139 glow product-related calls during the week of Halloween in 2007 with a single-day high of 59 calls on Halloween Day. More than 90% of the glow product exposures were in children 1-10 years of age. The glow product-related calls on Halloween Day increased from 14 calls in 2002 to 59 calls in 2007, a 321% increase during a six-year period. Poison control centers in the United States are equipped with a unique and uniform input data collection system -- the National Poison Data System -- that provides an important data source in the development of a comprehensive surveillance system for early outbreak detection.

  18. Analysis of postmarket complaints database for the iFuse SI Joint Fusion System®: a minimally invasive treatment for degenerative sacroiliitis and sacroiliac joint disruption.

    PubMed

    Miller, Larry E; Reckling, W Carlton; Block, Jon E

    2013-01-01

    The sacroiliac joint is a common but under-recognized source of low back and gluteal pain. Patients with degenerative sacroiliitis or sacroiliac joint disruption resistant to nonsurgical treatments may undergo open surgery with sacroiliac joint arthrodesis, although outcomes are mixed and risks are significant. Minimally invasive sacroiliac joint arthrodesis was developed to minimize the risk of iatrogenic injury and to improve patient outcomes compared with open surgery. Between April 2009 and January 2013, 5319 patients were treated with the iFuse SI Joint Fusion System® for conditions including sacroiliac joint disruption and degenerative sacroiliitis. A database was prospectively developed to record all complaints reported to the manufacturer in patients treated with the iFuse device. Complaints were collected through spontaneous reporting mechanisms in support of ongoing mandatory postmarket surveillance efforts. Complaints were reported in 204 (3.8%) patients treated with the iFuse system. Pain was the most commonly reported clinical complaint (n = 119, 2.2%), with nerve impingement (n = 48, 0.9%) and recurrent sacroiliac joint pain (n = 43, 0.8%) most frequently cited. All other clinical complaints were rare (≤0.2%). Ninety-six revision surgeries were performed in 94 (1.8%) patients at a median follow-up of four (range 0-30) months. Revisions were typically performed in the early postoperative period for treatment of a symptomatic malpositioned implant (n = 46, 0.9%) or to correct an improperly sized implant in an asymptomatic patient (n = 10, 0.2%). Revisions in the late postoperative period were performed to treat symptom recurrence (n = 34, 0.6%) or for continued pain of undetermined etiology (n = 6, 0.1%). Analysis of a postmarket product complaints database demonstrates an overall low risk of complaints with the iFuse SI Joint Fusion System in patients with degenerative sacroiliitis or sacroiliac joint disruption.

  19. Postmarketing monitoring of intussusception after RotaTeq vaccination--United States, February 1, 2006-February 15, 2007.

    PubMed

    2007-03-16

    Rotavirus is the leading cause of severe gastroenteritis in children aged <5 years worldwide. In February 2006, a new rotavirus vaccine, RotaTeq (Merck and Co., West Point, Pennsylvania), was licensed in the United States, and the Advisory Committee on Immunization Practices (ACIP) recommended it for routine vaccination of U.S. infants with 3 doses, administered orally at ages 2, 4, and 6 months. Because a previous rotavirus vaccine, Rotashield (Wyeth Laboratories, Marietta, Pennsylvania), was withdrawn from the U.S. market in 1999 after postmarketing surveillance identified an association with intussusception (a rare type of bowel obstruction), the safety of RotaTeq was evaluated in a prelicensure clinical trial involving 71,725 infants who received either vaccine or placebo. In this controlled trial, no statistically significant elevated risk for intussusception was observed within a 42-day period after RotaTeq vaccination. However, postmarketing monitoring for intussusception after RotaTeq vaccination is necessary because of possible differences in the characteristics of infants who received the vaccine in routine use compared with the infants in the clinical trials. Also, the large numbers of infants being vaccinated provides an opportunity to detect intussusception occurring at a low rate after vaccination. This report presents data from the first year of postmarketing monitoring for intussusception after RotaTeq vaccination in the United States, with particular focus on all intussusception reports received by the Vaccine Adverse Event Reporting System (VAERS) during February 1, 2006-February 15, 2007. As of February 15, 2007, postmarketing surveillance did not suggest association of RotaTeq vaccination with intussusception. CDC reaffirms vaccine policy recommendations to routinely vaccinate U.S. infants with RotaTeq at ages 2, 4, and 6 months.

  20. The role of the Pharmaceuticals and Medical Devices Agency and healthcare professionals in post-marketing safety.

    PubMed

    Mori, Kazuhiko; Watanabe, Meguru; Horiuchi, Naoya; Tamura, Atsushi; Kutsumi, Hiromu

    2014-04-01

    The development of drugs and medical devices is necessary for medical progress; however, safety measures need to be put in place to protect the health of the population. In order to ensure the safety of drugs and medical devices, it is important to determine measures for appropriate management of risks at any time during the development phase, the regulatory review and the post-marketing phase. Adverse events detected in clinical trials are limited due to the restricted numbers of patients enrolled in the trials. Therefore, it is almost impossible to predict rare serious adverse events during the post-marketing phase. The revised Pharmaceutical Affairs Act was established in Japan in November 20, 2013. The new act focuses on increased safety of drugs and medical devices. The Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory authority in Japan that promotes safety measures from the development phase through to the post-marketing phase. In the post-marketing phase, the PMDA collects information from the medical product companies and healthcare professionals, as well as instructing and advising them with regard to post-marketing safety measures for each drug and medical device. Since Japan has a national health insurance system, a new drug or a medical device is available throughout the country when the drug price or medical fee is listed in the National Health Insurance price list. Healthcare professionals in medical institutions must learn about the drugs and medical devices they handle, and should make an effort to maintain patient safety. The PMDA medi-navi is a very useful electronic mail delivery service that provides critical information for protecting patients from health hazards caused by adverse events. The 'risk management plan' is also important as it contains important information about safety profile and post-marketing measures of a new drug.

  1. Surveillance of suspected adverse reactions to natural health products: the case of propolis.

    PubMed

    Menniti-Ippolito, Francesca; Mazzanti, Gabriela; Vitalone, Annabella; Firenzuoli, Fabio; Santuccio, Carmela

    2008-01-01

    Natural health products are promoted to the public as equally or more effective and less toxic than conventional drugs. However, some 'natural' medicines are known to have adverse effects. From April 2002 to August 2007, 18 suspected adverse reactions associated with propolis-containing products were reported to the national surveillance system of natural health products, coordinated by the Italian National Health Institute. Sixteen reports concerned allergic reactions (with dermatological or respiratory symptoms), while two concerned the digestive tract. Some of the reactions were serious: six patients were admitted to hospital or visited an emergency department and in two of these a life-threatening event was reported. In seven patients (four of whom were children), an allergic predisposition was indicated. Propolis, a resinous substance collected by honeybees from the buds of living plants, has been used for several purposes (dermatitis, laryngitis, oral ulcers) because of its wide range of suggested activities (antibacterial, antiviral, antifungal, anti-inflammatory, antioxidant and chemopreventive actions). However, propolis is also a potent sensitizer and should not be used in patients with an allergic predisposition, in particular an allergy to pollen. In Italy, products containing bee derivatives (bee pollen, royal jelly or propolis) are available to the public as food supplements. No label warning of possible adverse reactions is found on the packaging, although it is well known that atopic and asthmatic individuals may be at an increased risk of allergic reactions after using these products. The public and healthcare practitioners should be aware of the risk of allergic reactions to products derived from bees and a warning should be added to the packaging of these products.

  2. The Use of Bioaerosol Sampling for Airborne Virus Surveillance in Swine Production Facilities: A Mini Review.

    PubMed

    Anderson, Benjamin D; Lednicky, John A; Torremorell, Montserrat; Gray, Gregory C

    2017-01-01

    Modern swine production facilities typically house dense populations of pigs and may harbor a variety of potentially zoonotic viruses that can pass from one pig generation to another and periodically infect human caretakers. Bioaerosol sampling is a common technique that has been used to conduct microbial risk assessments in swine production, and other similar settings, for a number of years. However, much of this work seems to have been focused on the detection of non-viral microbial agents (i.e., bacteria, fungi, endotoxins, etc.), and efforts to detect viral aerosols in pig farms seem sparse. Data generated by such studies would be particularly useful for assessments of virus transmission and ecology. Here, we summarize the results of a literature review conducted to identify published articles related to bioaerosol generation and detection within swine production facilities, with a focus on airborne viruses. We identified 73 scientific reports, published between 1991 and 2017, which were included in this review. Of these, 19 (26.7%) used sampling methodology for the detection of viruses. Our findings show that bioaerosol sampling methodologies in swine production settings have predominately focused on the detection of bacteria and fungi, with no apparent standardization between different approaches. Information, specifically regarding virus aerosol burden in swine production settings, appears to be limited. However, the number of viral aerosol studies has markedly increased in the past 5 years. With the advent of new sampling technologies and improved diagnostics, viral bioaerosol sampling could be a promising way to conduct non-invasive viral surveillance among swine farms.

  3. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Epidemiology (HFM-210) for an acceptable alternative reporting format. (e) Postmarketing studies. (1) Licensed..., for alternatives to the VAERS Form, by the Division of Biostatistics and Epidemiology. (4) Copies of...

  4. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Epidemiology (HFM-210) for an acceptable alternative reporting format. (e) Postmarketing studies. (1) Licensed..., for alternatives to the VAERS Form, by the Division of Biostatistics and Epidemiology. (4) Copies of...

  5. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Epidemiology (HFM-210) for an acceptable alternative reporting format. (e) Postmarketing studies. (1) Licensed..., for alternatives to the VAERS Form, by the Division of Biostatistics and Epidemiology. (4) Copies of...

  6. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Epidemiology (HFM-210) for an acceptable alternative reporting format. (e) Postmarketing studies. (1) Licensed..., for alternatives to the VAERS Form, by the Division of Biostatistics and Epidemiology. (4) Copies of...

  7. 21 CFR 600.80 - Postmarketing reporting of adverse experiences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Epidemiology (HFM-210) for an acceptable alternative reporting format. (e) Postmarketing studies. (1) Licensed..., for alternatives to the VAERS Form, by the Division of Biostatistics and Epidemiology. (4) Copies of...

  8. Surveillance of tobacco industry retail marketing activities of reduced harm products.

    PubMed

    Slater, Sandy; Giovino, Gary; Chaloupka, Frank

    2008-01-01

    With the introduction of potential reduced exposure products (PREPs) and the interest in studying tobacco harm reduction, sound research and surveillance are needed to examine and understand the distribution and availability of PREPs in communities, as well as the tobacco industry's marketing practices surrounding these products. We examined the availability and marketing of PREPs in a national sample of tobacco retail stores. We also compared the price of PREPs to those of premium brand cigarettes and examined the distribution of PREPs in comparison with premium brand cigarettes by store type, urbanization, region, and race/ethnicity. We found that PREPs are not widely available, are priced similarly to leading cigarette brands, and have few promotional offers. We also found some significant differences in the distribution of PREPs and cigarettes, as well as in the distribution of Ariva and Omni, by store type and community demographics. The fact that this study used data collected nationally emphasizes the importance of these findings and helps shed some light on the tobacco industry's PREP marketing strategies. This study's national sample provides a unique perspective that needs to be replicated if and when other PREPs are widely marketed.

  9. Potential metal impurities in active pharmaceutical substances and finished medicinal products - A market surveillance study.

    PubMed

    Wollein, Uwe; Bauer, Bettina; Habernegg, Renate; Schramek, Nicholas

    2015-09-18

    A market surveillance study has been established by using different atomic spectrometric methods for the determination of selected elemental impurities of particular interest, to gain an overview about the quality of presently marketed drug products and their bulk drug substances. The limit tests were carried out with respect to the existing EMA guideline on the specification limits for residuals of metal catalysts or metal reagents. Also attention was given to the future implementation of two new chapters of the United States Pharmacopoeia (USP) stating limit concentrations of elemental impurities. The methods used for determination of metal residues were inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and atomic absorption spectrometry technologies (GFAAS, CVAAS, HGAAS). This article presents the development and validation of the methods used for the determination of 21 selected metals in 113 samples from drug products and their active pharmaceutical ingredients. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk.

    PubMed

    Raschi, Emanuel; De Ponti, Fabrizio

    2015-07-08

    Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities.

  11. Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk

    PubMed Central

    Raschi, Emanuel; De Ponti, Fabrizio

    2015-01-01

    Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent’s management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as “signals”), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities. PMID:26167249

  12. [Establishment of model of traditional Chinese medicine injections post-marketing safety monitoring].

    PubMed

    Guo, Xin-E; Zhao, Yu-Bin; Xie, Yan-Ming; Zhao, Li-Cai; Li, Yan-Feng; Hao, Zhe

    2013-09-01

    To establish a nurse based post-marketing safety surveillance model for traditional Chinese medicine injections (TCMIs). A TCMIs safety monitoring team and a research hospital team engaged in the research, monitoring processes, and quality control processes were established, in order to achieve comprehensive, timely, accurate and real-time access to research data, to eliminate errors in data collection. A triage system involving a study nurse, as the first point of contact, clinicians and clinical pharmacists was set up in a TCM hospital. Following the specified workflow involving labeling of TCM injections and using improved monitoring forms it was found that there were no missing reports at the ratio of error was zero. A research nurse as the first and main point of contact in post-marketing safety monitoring of TCM as part of a triage model, ensures that research data collected has the characteristics of authenticity, accuracy, timeliness, integrity, and eliminate errors during the process of data collection. Hospital based monitoring is a robust and operable process.

  13. Postmarketing Safety Profile of Subcutaneous Interferon Beta-1a Given 3 Times Weekly: A Retrospective Administrative Claims Analysis.

    PubMed

    Smith, Meredith Y; Sabidó-Espin, Meritxell; Trochanov, Anton; Samuelson, Mark; Guedes, Sandra; Corvino, Frank A; Richy, Florent F

    2015-08-01

    criteria. Descriptive analyses of patient demographic, health status, health care utilization, and adherence status were performed, and incidence rates (IRs) per 100 person-years of labeled AEs with corresponding 95% CIs were calculated. The IR calculation was based on events that presented after therapy initiation and that were not present in the 90-day pre-index period. The top 6 AEs included influenza-like symptoms (IR = 15.65, 95% CI = 14.96-16.36); malaise (IR = 15.33, 95% CI = 14.65-16.04; fatigue (IR = 15.02, 95% CI = 14.35-15.72); abdominal pain (IR = 10.18, 95% CI = 9.67-10.70); chest pain (IR = 8.48, 95% CI = 8.03-8.95); and depression (IR = 7.75, 95% CI = 7.32-8.20). In contrast, the 6 lowest IRs were for maculo-papular rash (IR = 0.01, 95% CI = 0.00-0.04; injection-site necrosis (IR = 0.01, 95% CI = 0.00-0.03); erythema multiforme (IR = 0.01, 95% CI = 0.00-0.04); hypoesthesia (IR = 0.00, 95% CI = 0.00-0.02); Stevens-Johnson Syndrome (IR = 0.00, 95% CI = 0.00-0.02); and xerophthalmia (IR = 0.00, 95% CI = 0.00-0.02). Study results show strong convergence between the real-world safety profile of IFN β-1a SC tiw and its U.S. label. Our findings demonstrate the value of using real-world evidence obtained from administrative claims to complement clinical trial and postmarketing surveillance data in order to characterize the safety profile of established products, such as IFN β-1a SC tiw, in the postmarketing context.

  14. Decision support methods for the detection of adverse events in post-marketing data.

    PubMed

    Hauben, M; Bate, A

    2009-04-01

    Spontaneous reporting is a crucial component of post-marketing drug safety surveillance despite its significant limitations. The size and complexity of some spontaneous reporting system databases represent a challenge for drug safety professionals who traditionally have relied heavily on the scientific and clinical acumen of the prepared mind. Computer algorithms that calculate statistical measures of reporting frequency for huge numbers of drug-event combinations are increasingly used to support pharamcovigilance analysts screening large spontaneous reporting system databases. After an overview of pharmacovigilance and spontaneous reporting systems, we discuss the theory and application of contemporary computer algorithms in regular use, those under development, and the practical considerations involved in the implementation of computer algorithms within a comprehensive and holistic drug safety signal detection program.

  15. 21 CFR 601.70 - Annual progress reports of postmarketing studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Clinical pharmacology; and (4) Nonclinical toxicology. (b)What to report. Each applicant of a licensed... postmarketing studies. (a) General requirements. This section applies to all required postmarketing studies (e.g...

  16. 21 CFR 601.70 - Annual progress reports of postmarketing studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Clinical pharmacology; and (4) Nonclinical toxicology. (b)What to report. Each applicant of a licensed... postmarketing studies. (a) General requirements. This section applies to all required postmarketing studies (e.g...

  17. 21 CFR 601.70 - Annual progress reports of postmarketing studies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Clinical pharmacology; and (4) Nonclinical toxicology. (b)What to report. Each applicant of a licensed... postmarketing studies. (a) General requirements. This section applies to all required postmarketing studies (e.g...

  18. 21 CFR 601.70 - Annual progress reports of postmarketing studies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Clinical pharmacology; and (4) Nonclinical toxicology. (b)What to report. Each applicant of a licensed... postmarketing studies. (a) General requirements. This section applies to all required postmarketing studies (e.g...

  19. Methodological approaches to developing and establishing the body of evidence on post-marketing Chinese medicine safety.

    PubMed

    Liao, Xing; Robinson, Nicola

    2013-07-01

    Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, postmarketing surveillance (PMS) has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions (ADRs). Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detect ADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.

  20. Post-marketing drug withdrawals: Pharmacovigilance success, regulatory problems.

    PubMed

    Aronson, Jeffrey K

    2017-03-30

    Modern pharmacovigilance began in the 1960s, since when the subject has grown markedly, interest having particularly increased since 2010. One index of its success is the increasing speed with which serious adverse drug reactions are discovered after marketing of a medicinal product. However, the speed with which products have subsequently been withdrawn as a result of the discovery of serious adverse reactions has not consistently changed. This highlights problems that regulators and manufacturers face when serious reactions are discovered, with difficulties in deciding which of several consequent actions to take: to add specific warnings (cautions) or contraindications to the product label; to issue a Direct Healthcare Professional Communication; to allow informed patients to decide whether they will take the drug; or, in the most serious cases, to withdraw the product or revoke the licence. Conflicts of interest may inhibit decision-making. Recommendations that arise from these observations are that: health professionals and patients should be more vigorously encouraged to report suspected adverse drug reactions; regulatory authorities and drug manufacturers should take quicker confirmatory action when serious suspected adverse drug reactions are reported, even anecdotally, with formal studies to test for causality conducted sooner rather than later, applying lower than usual thresholds for suspicion; temporary suspensions or restrictions could be considered during such assessments; universal guidelines are needed for determining when a drug should be withdrawn if serious adverse drug reactions are suspected; there should be more rigorous monitoring and verification of deaths and reporting of reasons for drop-outs during clinical trials, with more transparency in reporting adverse events and ready access to premarketing clinical study reports; post-marketing drug monitoring systems and medicines regulation in low-to-middle income economies, especially in Africa

  1. The Japanese Postmarketing Adverse Event Relief System: A Confluence of Regulatory Science, the Legal System, and Clinical Pharmacology.

    PubMed

    Tominaga, T; Miyazaki, S; Oniyama, Y; Weber, A D; Kondo, T

    2016-10-13

    The Japanese Postmarketing Relief System provides for compensation to patients with adverse reactions, based on the acknowledgment that unpredicted adverse events occur inevitably once a drug is marketed. The system also provides new knowledge about the benefit-risk profile of a drug that may be incorporated into product labeling. The system relies on causality assessments that are based on sound clinical pharmacology principles. The system may serve as a model for other countries' healthcare systems.

  2. Important statistical considerations in the evaluation of post-market studies to assess whether opioids with abuse-deterrent properties result in reduced abuse in the community.

    PubMed

    By, Kunthel; McAninch, Jana K; Keeton, Stephine L; Secora, Alex; Kornegay, Cynthia J; Hwang, Catherine S; Ly, Thomas; Levenson, Mark S

    2017-08-23

    Abuse, misuse, addiction, overdose, and death associated with non-medical use of prescription opioids have become a serious public health concern. Reformulation of these products with abuse-deterrent properties is one approach for addressing this problem. FDA has approved several extended-release opioid analgesics with abuse-deterrent labeling, the bases of which come from pre-market studies. As all opioid analgesics must be capable of delivering the opioid in order to reduce pain, abuse-deterrent properties do not prevent abuse, nor do pre-market evaluations ensure that there will be reduced abuse in the community. Utilizing data from various surveillance systems, some recent post-market studies suggest a decline in abuse of extended-release oxycodone after reformulation with abuse-deterrent properties. We discuss challenges stemming from the use of such data. We quantify the relationship between the sample, the population, and the underlying sampling mechanism and identify the necessary conditions if valid statements about the population are to be made. The presence of other interventions in the community necessitates the use of comparators. We discuss the principles under which the use of comparators can be meaningful. Results based on surveillance data need to be interpreted with caution as the underlying sampling mechanisms can bias the results in unpredictable ways. The use of comparators has the potential to disentangle the effect due to the abuse-deterrence properties from those due to other interventions. However, identifying a comparator that is meaningful can be very difficult. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  3. 48 CFR 42.1104 - Surveillance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Production Surveillance and Reporting 42... surveillance, contract administration office personnel shall avoid any action that may (1) be inconsistent with...

  4. An evaluation of computer-aided disproportionality analysis for post-marketing signal detection.

    PubMed

    Lehman, H P; Chen, J; Gould, A L; Kassekert, R; Beninger, P R; Carney, R; Goldberg, M; Goss, M A; Kidos, K; Sharrar, R G; Shields, K; Sweet, A; Wiholm, B E; Honig, P K

    2007-08-01

    To understand the value of computer-aided disproportionality analysis (DA) in relation to current pharmacovigilance signal detection methods, four products were retrospectively evaluated by applying an empirical Bayes method to Merck's post-marketing safety database. Findings were compared with the prior detection of labeled post-marketing adverse events. Disproportionality ratios (empirical Bayes geometric mean lower 95% bounds for the posterior distribution (EBGM05)) were generated for product-event pairs. Overall (1993-2004 data, EBGM05> or =2, individual terms) results of signal detection using DA compared to standard methods were sensitivity, 31.1%; specificity, 95.3%; and positive predictive value, 19.9%. Using groupings of synonymous labeled terms, sensitivity improved (40.9%). More of the adverse events detected by both methods were detected earlier using DA and grouped (versus individual) terms. With 1939-2004 data, diagnostic properties were similar to those from 1993 to 2004. DA methods using Merck's safety database demonstrate sufficient sensitivity and specificity to be considered for use as an adjunct to conventional signal detection methods.

  5. Surveillance as cultural practice.

    PubMed

    Monahan, Torin

    2011-01-01

    This special section of The Sociological Quarterly explores research on “surveillance as cultural practice,” which indicates an orientation to surveillance that views it as embedded within, brought about by, and generative of social practices in specific cultural contexts. Such an approach is more likely to include elements of popular culture, media, art, and narrative; it is also more likely to try to comprehend people's engagement with surveillance on their own terms, stressing the production of emic over etic forms of knowledge. This introduction sketches some key developments in this area and discusses their implications for the field of “surveillance studies” as a whole.

  6. Estratest and Estratest HS (esterified estrogens and methyltestosterone) therapy: a summary of safety surveillance data, January 1989 to August 2002.

    PubMed

    Phillips, Eric H; Ryan, Suzanne; Ferrari, Rob; Green, Clarice

    2003-12-01

    The use of hormone-replacement therapy (HRT) to treat menopausal symptoms has been influenced over the years by various safety concerns. These concerns include endometrial cancer, breast cancer, and cardiovascular disease, and have altered how HRT is prescribed. Evaluating postmarketing surveillance data for a product can help pharmaceutical manufactures and health care providers detect early safety signals that may call for further investigation of the product for safety risks. This review summarizes the safety surveillance data for Estratest and Estratest HS from January 1989 to August 2002. All adverse-event (AE) data reported to Solvay Pharmaceuticals, Inc., on this brand from January 1989 to August 2002 were accessed from a database system that uses a comprehensive software package for reporting and tracking clinical and postmarketing AEs. Exposure to the Estratest brand during the 13-year assessment period is estimated at >3.0 million patient-years. A total of 1372 unique case reports containing 2556 AEs were found. Assessment of the 43 (3.1%) serious AE cases reported did not generate any signals that might raise concern on the part of the medical community or consumers. Nonserious events comprising >4% of total AEs were all labeled events and included alopecia (8.8%), acne (5.6%), and hirsutism (4.5%). The relatively small number of serious AE reports compared with the significant patient exposure did not generate any signals that might raise concern on the part of the medical community or consumers. The safety profile suggests that continued use at the lowest effective dose is acceptable in menopausal women whose symptoms are not improved by estrogen alone.

  7. RNA cleavage products generated by antisense oligonucleotides and siRNAs are processed by the RNA surveillance machinery

    PubMed Central

    Lima, Walt F.; De Hoyos, Cheryl L.; Liang, Xue-hai; Crooke, Stanley T.

    2016-01-01

    DNA-based antisense oligonucleotides (ASOs) elicit cleavage of the targeted RNA by the endoribonuclease RNase H1, whereas siRNAs mediate cleavage through the RNAi pathway. To determine the fates of the cleaved RNA in cells, we lowered the levels of the factors involved in RNA surveillance prior to treating cells with ASOs or siRNA and analyzed cleavage products by RACE. The cytoplasmic 5′ to 3′ exoribonuclease XRN1 was responsible for the degradation of the downstream cleavage products generated by ASOs or siRNA targeting mRNAs. In contrast, downstream cleavage products generated by ASOs targeting nuclear long non-coding RNA Malat 1 and pre-mRNA were degraded by nuclear XRN2. The downstream cleavage products did not appear to be degraded in the 3′ to 5′ direction as the majority of these products contained intact poly(A) tails and were bound by the poly(A) binding protein. The upstream cleavage products of Malat1 were degraded in the 3′ to 5′ direction by the exosome complex containing the nuclear exoribonuclease Dis3. The exosome complex containing Dis3 or cytoplasmic Dis3L1 degraded mRNA upstream cleavage products, which were not bound by the 5′-cap binding complex and, consequently, were susceptible to degradation in the 5′ to 3′ direction by the XRN exoribonucleases. PMID:26843429

  8. Regulatory Oversight of Gene Therapy and Cell Therapy Products in Korea.

    PubMed

    Choi, Minjoung; Han, Euiri; Lee, Sunmi; Kim, Taegyun; Shin, Won

    2015-01-01

    The Ministry of Food and Drug Safety regulates gene therapy and cell therapy products as biological products under the authority of the Pharmaceutical Affairs Act. As with other medicinal products, gene therapy and cell therapy products are subject to approval for use in clinical trials and for a subsequent marketing authorization and to post-market surveillance. Research and development of gene therapy and cell therapy products have been progressing rapidly in Korea with extensive investment, offering great potential for the treatment of various serious diseases. To facilitate development of safe and effective products and provide more opportunities to patients suffering from severe diseases, several regulatory programs, such as the use of investigational products for emergency situations, fast-track approval, prereview of application packages, and intensive regulatory consultation, can be applied to these products. The regulatory approach for these innovative products is case by case and founded on science-based review that is flexible and balances the risks and benefits.

  9. Spontaneous adverse event signaling methods: classification and use with health care treatment products.

    PubMed

    Clark, J A; Klincewicz, S L; Stang, P E

    2001-01-01

    AE signal detection and its techniques are part of the continuum of public health surveillance, borrowing from both its theory and application (171). Like public health surveillance networks, whose major goals are to identify early signs of new outbreaks, pinpoint new organisms, and monitor designated illnesses, AE signaling and surveillance systems attempt to provide early warnings of previously unsuspected product-AE pairs, hypothesize potential drug-event relations, identify populations "at risk," and facilitate case ascertainment and definition. In both examples, definitive research is often subsequently undertaken to quantify the strength of relations that may be proposed. As with any public health surveillance effort, AE surveillance provides an infrastructure for the ongoing collection of health data and its direct integration into the health regulatory policy (172), including its keystone role in risk assessment and management. However, unlike many surveillance systems, postmarketing AE systems collect case information that is often relatively incomplete and imperfect, estimate exposure based on surrogate values (e.g., sales data), and are used by both governmental and the private sector for preventive planning. These factors make AE signaling and surveillance more ambiguous, regulatory oriented, and complex than its disease counterparts (173). Despite such issues, AE signaling methods continue to evolve in extent, complexity, and acceptance (4, 131, 174). Undoubtedly, this is largely due to the widespread practical experience that has been gained with spontaneous reporting systems over the past 4 decades and the cumulative usefulness that has been demonstrated.

  10. Hazards of Illicit Methamphetamine Production and Efforts at Reduction: Data from the Hazardous Substances Emergency Events Surveillance System

    PubMed Central

    Melnikova, Natalia; Welles, Wanda Lizak; Wilburn, Rebecca E.; Rice, Nancy; Wu, Jennifer; Stanbury, Martha

    2011-01-01

    Objectives. Methamphetamine (meth) is a highly addictive drug of abuse that can easily be made in small illegal laboratories from household chemicals that are highly toxic and dangerous. Meth labs have been found in locations such as homes, outbuildings, motels, and cars. Its production endangers the “cook,” neighbors, responders, and the environment. This article describes surveillance data used to examine the emergence and public health impacts of illicit clandestine meth labs, as well as two states' efforts to thwart lab operations and prevent responder injuries. Methods. We analyzed data collected from 2001 to 2008 by 18 states participating in the Agency for Toxic Substances and Disease Registry's Hazardous Substances Emergency Events Surveillance (HSEES) Program to examine the occurrence and public health impacts of clandestine meth production. Results. HSEES data indicate that the majority of clandestine meth lab events occurred in residential areas. About 15% of meth lab events required evacuation. Nearly one-fourth of these events resulted in injuries, with 902 reported victims. Most victims (61%) were official responders, and one-third were members of the general public. Since 2004, with the implementation of local and federal laws and prevention activities, the number of meth lab events has declined. Increased education and training of first responders has led to decreased injuries among police officers, firefighters, and emergency medical personnel. Conclusions. HSEES data provided a good data source for monitoring the emergence of domestic clandestine meth production, the associated public health effects, and the results of state and federal efforts to promote actions to address the problem. PMID:21563719

  11. Postmarketing evidence of disease-modifying drugs in multiple sclerosis.

    PubMed

    Trojano, Maria; Paolicelli, Damiano; Fuiani, Aurora; Pellegrini, Fabio; Iaffaldano, Pietro; Direnzo, Vita; D'Onghia, Mariangela

    2008-09-01

    There is growing interest in the use of observational data to estimate treatment effects in chronic diseases such as multiple sclerosis (MS). The main results derived from postmarketing evaluations, in the last 2 years, of short-and long-term disease modifying drugs (DMDs) effectiveness will be reported in this Review. Moreover, some of the methodological improvements that may be useful to enhance the quality of observational studies will also be discussed.

  12. Analysis of "Seven Year Surveillance of the Clinical Performance of a Blood Glucose Test-Strip Product".

    PubMed

    Krouwer, Jan S

    2017-09-01

    The article titled "Seven Year Surveillance of the Clinical Performance of a Blood Glucose Test-Strip Product" by Setford and coworkers in this issue of Journal of Diabetes Science and Technology is an impressive study showing that over 7 years in three clinics, using multiple reagent lots, a total of 73 600 samples met the ISO 15197 2015 standard with no results in the D or E zones of a Parkes glucose meter error grid. Three requirements are suggested for a clinically acceptable glucose meter. The authors provide strong evidence for meeting two requirements but fail to provide summarized data about the number of nonnumeric results. Finally, the authors overstate some results, called "spin" by some which is not necessary. The superb results should stand on their own.

  13. Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

    PubMed

    Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

    2017-07-27

    Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

  14. A Synthesis of Current Surveillance Planning Methods for the Sequential Monitoring of Drug and Vaccine Adverse Effects Using Electronic Health Care Data

    PubMed Central

    Nelson, Jennifer C.; Wellman, Robert; Yu, Onchee; Cook, Andrea J.; Maro, Judith C.; Ouellet-Hellstrom, Rita; Boudreau, Denise; Floyd, James S.; Heckbert, Susan R.; Pinheiro, Simone; Reichman, Marsha; Shoaibi, Azadeh

    2016-01-01

    Introduction: The large-scale assembly of electronic health care data combined with the use of sequential monitoring has made proactive postmarket drug- and vaccine-safety surveillance possible. Although sequential designs have been used extensively in randomized trials, less attention has been given to methods for applying them in observational electronic health care database settings. Existing Methods: We review current sequential-surveillance planning methods from randomized trials, and the Vaccine Safety Datalink (VSD) and Mini-Sentinel Pilot projects—two national observational electronic health care database safety monitoring programs. Future Surveillance Planning: Based on this examination, we suggest three steps for future surveillance planning in health care databases: (1) prespecify the sequential design and analysis plan, using available feasibility data to reduce assumptions and minimize later changes to initial plans; (2) assess existing drug or vaccine uptake, to determine if there is adequate information to proceed with surveillance, before conducting more resource-intensive planning; and (3) statistically evaluate and clearly communicate the sequential design with all those designing and interpreting the safety-surveillance results prior to implementation. Plans should also be flexible enough to accommodate dynamic and often unpredictable changes to the database information made by the health plans for administrative purposes. Conclusions: This paper is intended to encourage dialogue about establishing a more systematic, scalable, and transparent sequential design-planning process for medical-product safety-surveillance systems utilizing observational electronic health care databases. Creating such a framework could yield improvements over existing practices, such as designs with increased power to assess serious adverse events. PMID:27713904

  15. Systems pharmacology augments drug safety surveillance.

    PubMed

    Lorberbaum, T; Nasir, M; Keiser, M J; Vilar, S; Hripcsak, G; Tatonetti, N P

    2015-02-01

    Small molecule drugs are the foundation of modern medical practice, yet their use is limited by the onset of unexpected and severe adverse events (AEs). Regulatory agencies rely on postmarketing surveillance to monitor safety once drugs are approved for clinical use. Despite advances in pharmacovigilance methods that address issues of confounding bias, clinical data of AEs are inherently noisy. Systems pharmacology-the integration of systems biology and chemical genomics-can illuminate drug mechanisms of action. We hypothesize that these data can improve drug safety surveillance by highlighting drugs with a mechanistic connection to the target phenotype (enriching true positives) and filtering those that do not (depleting false positives). We present an algorithm, the modular assembly of drug safety subnetworks (MADSS), to combine systems pharmacology and pharmacovigilance data and significantly improve drug safety monitoring for four clinically relevant adverse drug reactions.

  16. A Mobile Sensing Approach for Regional Surveillance of Fugitive Methane Emissions in Oil and Gas Production.

    PubMed

    Albertson, John D; Harvey, Tierney; Foderaro, Greg; Zhu, Pingping; Zhou, Xiaochi; Ferrari, Silvia; Amin, M Shahrooz; Modrak, Mark; Brantley, Halley; Thoma, Eben D

    2016-03-01

    This paper addresses the need for surveillance of fugitive methane emissions over broad geographical regions. Most existing techniques suffer from being either extensive (but qualitative) or quantitative (but intensive with poor scalability). A total of two novel advancements are made here. First, a recursive Bayesian method is presented for probabilistically characterizing fugitive point-sources from mobile sensor data. This approach is made possible by a new cross-plume integrated dispersion formulation that overcomes much of the need for time-averaging concentration data. The method is tested here against a limited data set of controlled methane release and shown to perform well. We then present an information-theoretic approach to plan the paths of the sensor-equipped vehicle, where the path is chosen so as to maximize expected reduction in integrated target source rate uncertainty in the region, subject to given starting and ending positions and prevailing meteorological conditions. The information-driven sensor path planning algorithm is tested and shown to provide robust results across a wide range of conditions. An overall system concept is presented for optionally piggybacking of these techniques onto normal industry maintenance operations using sensor-equipped work trucks.

  17. The use of existing environmental networks for the post-market monitoring of GM crop cultivation in the EU.

    PubMed

    Smets, G; Alcalde, E; Andres, D; Carron, D; Delzenne, P; Heise, A; Legris, G; Martinez Parrilla, M; Verhaert, J; Wandelt, C; Ilegems, M; Rüdelsheim, P

    2014-07-01

    The European Union (EU) Directive 2001/18/EC on the deliberate release of genetically modified organisms (GMOs) into the environment requires that both Case-Specific Monitoring (CSM) and General Surveillance (GS) are considered as post-market implementing measures. Whereas CSM is directed to monitor potential adverse effects of GMOs or their use identified in the environmental risk assessment, GS aims to detect un-intended adverse effects of GMOs or their use on human and animal health or the environment. Guidance documents on the monitoring of genetically modified (GM) plants from the Commission and EFSA clarify that, as appropriate, GS can make use of established routine surveillance practices. Networks involved in routine surveillance offer recognised expertise in a particular domain and are designed to collect information on important environmental aspects over a large geographical area. However, as the suitability of existing monitoring networks to provide relevant data for monitoring impacts of GMOs is not known, plant biotechnology companies developed an approach to describe the processes and criteria that will be used for selecting and evaluating existing monitoring systems. In this paper, the availability of existing monitoring networks for this purpose is evaluated. By cataloguing the existing environmental monitoring networks in the EU, it can be concluded that they can only be used, in the context of GMO cultivation monitoring, as secondary tools to collect baseline information.

  18. An Evaluation of a Distributed Medical Device Safety Surveillance System: The DELTA Network Study

    PubMed Central

    Vidi, Venkatesan D.; Matheny, Michael E.; Donnelly, Sharon; Resnic, Frederic S.

    2011-01-01

    Background Post-market medical product safety surveillance is a complex task requiring standardized data collection, prompt adverse event reporting mechanisms and appropriate methodologies to identify low frequency safety threats and risk communication. Purpose To review the design of the DELTA (Data Extraction and Longitudinal Trend Analysis) network study of the medical device safety surveillance. Methods This is a multicenter prospective observational study designed to evaluate the safety of new cardiovascular devices used during percutaneous coronary intervention (PCI) performed through continuous analysis of the routinely collected American College of Cardiology- National Cardiovascular Data Registry (ACC-NCDR) data elements. The primary endpoint of the study is detection of adverse event rates specific to several classes of new medical devices, including drug eluting coronary stents, embolic protection devices, and vascular closure devices in patients undergoing PCI. Secondary endpoints include the time-savings between the DELTA network detection of a true device safety alert and the time taken to detect the same outcome using conventional retrospective data analysis, overall sensitivity, specificity, positive predictive value and negative predictive value of the DELTA network surveillance system. Results The details of the study are described including system design, eligibility criteria, methods and components of data collection, data security and statistical methods. In addition, the methods of adjudication and verification following an adverse event alert, overall study outcomes, end points, limitations and potential advantages are discussed. Conclusion This report describes the first multicenter prospective study of a computerized safety surveillance system to monitor and evaluate the safety of new cardiovascular devices. PMID:21356331

  19. 78 FR 44573 - Guidance for Industry on Providing Submissions in Electronic Format-Postmarket Non-Expedited...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ... Format--Postmarket Non-Expedited Individual Case Safety Reports; Technical Questions and Answers... Electronic Format--Postmarket Non-Expedited ICSRs; Technical Questions and Answers.'' The guidance provides... to FDA postmarket non-expedited individual case safety reports (ICSRs) on adverse drug...

  20. Use of Carabids for the Post-Market Environmental Monitoring of Genetically Modified Crops.

    PubMed

    Skoková Habuštová, Oxana; Svobodová, Zdeňka; Cagáň, Ľudovít; Sehnal, František

    2017-03-29

    Post-market environmental monitoring (PMEM) of genetically modified (GM) crops is required by EU legislation and has been a subject of debate for many years; however, no consensus on the methodology to be used has been reached. We explored the suitability of carabid beetles as surrogates for the detection of unintended effects of GM crops in general PMEM surveillance. Our study combines data on carabid communities from five maize field trials in Central Europe. Altogether, 86 species and 58,304 individuals were collected. Modeling based on the gradual elimination of the least abundant species, or of the fewest categories of functional traits, showed that a trait-based analysis of the most common species may be suitable for PMEM. Species represented by fewer than 230 individuals (all localities combined) should be excluded and species with an abundance higher than 600 should be preserved for statistical analyses. Sixteen species, representing 15 categories of functional traits fulfill these criteria, are typical dominant inhabitants of agroecocoenoses in Central Europe, are easy to determine, and their functional classification is well known. The effect of sampling year is negligible when at least four samples are collected during maize development beginning from 1 April. The recommended methodology fulfills PMEM requirements, including applicability to large-scale use. However, suggested thresholds of carabid comparability should be verified before definitive conclusions are drawn.

  1. Use of Carabids for the Post-Market Environmental Monitoring of Genetically Modified Crops

    PubMed Central

    Skoková Habuštová, Oxana; Svobodová, Zdeňka; Cagáň, Ľudovít; Sehnal, František

    2017-01-01

    Post-market environmental monitoring (PMEM) of genetically modified (GM) crops is required by EU legislation and has been a subject of debate for many years; however, no consensus on the methodology to be used has been reached. We explored the suitability of carabid beetles as surrogates for the detection of unintended effects of GM crops in general PMEM surveillance. Our study combines data on carabid communities from five maize field trials in Central Europe. Altogether, 86 species and 58,304 individuals were collected. Modeling based on the gradual elimination of the least abundant species, or of the fewest categories of functional traits, showed that a trait-based analysis of the most common species may be suitable for PMEM. Species represented by fewer than 230 individuals (all localities combined) should be excluded and species with an abundance higher than 600 should be preserved for statistical analyses. Sixteen species, representing 15 categories of functional traits fulfill these criteria, are typical dominant inhabitants of agroecocoenoses in Central Europe, are easy to determine, and their functional classification is well known. The effect of sampling year is negligible when at least four samples are collected during maize development beginning from 1 April. The recommended methodology fulfills PMEM requirements, including applicability to large-scale use. However, suggested thresholds of carabid comparability should be verified before definitive conclusions are drawn. PMID:28353663

  2. Special surveillance list of chemicals, products, materials and equipment used in the clandestine production of controlled substances or listed chemicals. Drug Enforcement Administration (DEA), Justice. Final notice.

    PubMed

    1999-05-13

    On October 3, 1996, the Comprehensive Methamphetamine Control Act of 1996 (MCA) was signed into law. The MCA makes it unlawful for any person to distribute a laboratory supply to a person who uses, or attempts to use, that laboratory supply to manufacture a controlled substance or a listed chemical, with reckless disregard for the illegal uses to which such laboratory supply will be put. Individuals who violate this provision are subject to a civil penalty of not more than $25,000; businesses which violate this provision are subject to a civil penalty of not more than $250,000. The term "laboratory supply" is defined as "a listed chemical or any chemical, substance, or item on a special surveillance list published by the Attorney General, which contains chemicals, products, materials, or equipment used in the manufacture of controlled substances and listed chemicals." This final notice contains the list of "laboratory supplies" which constitutes the Special Surveillance List that was required to be published by the Attorney General pursuant to Title 21, United States Code, Section 842(a).

  3. Measles, mumps, and rubella virus vaccine (M-M-R™II): a review of 32 years of clinical and postmarketing experience.

    PubMed

    Lievano, Fabio; Galea, Susan A; Thornton, Michele; Wiedmann, Richard T; Manoff, Susan B; Tran, Trung N; Amin, Manisha A; Seminack, Margaret M; Vagie, Kristen A; Dana, Adrian; Plotkin, Stanley A

    2012-11-06

    M-M-R™II (measles, mumps, and rubella virus vaccine live; Merck, Sharp, & Dohme Corp.) is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals ≥ 12 months of age. Before the vaccine era, these viruses infected most exposed individuals, with subsequent morbidity and mortality. One of the greatest achievements of public health has been to eliminate these 3 diseases in large geographic areas. The safety profile of M-M-R™II is described using data from routine global postmarketing surveillance. Postmarketing surveillance has limitations (including incomplete reporting of case data), but allows collection of real-world information on large numbers of individuals, who may have concurrent medical problems excluding them from clinical trials. It can also identify rare adverse experiences (AEs). Over its 32-year history, ≈ 575 million doses of M-M-R™II have been distributed worldwide, with 17,536 AEs voluntarily reported for an overall rate of 30.5 AEs/1,000,000 doses distributed. This review provides evidence that the vaccine is safe and well-tolerated.

  4. [Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

    PubMed

    Li, Yuanyuan; Xie, Yanming

    2011-10-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

  5. Ballistic Testing and Product Quality Surveillance for the Interceptor Body Armor - Vest Components Need Improvement

    DTIC Science & Technology

    2011-01-03

    Acronyms and Abbreviations AQL Acceptance Quality Limit COPD Contract Purchase Description DAP Deltoid and Axillary Protector DCMA...and other measures. The IBA contract purchase description ( COPD ) provides the requirements for the material, design, ballistic performance, and...inspections for the IBA products. The COPD divides the Quality Assurance requirements into four categories; see Table 1 for details

  6. Post-market drug evaluation research training capacity in Canada: an environmental scan of Canadian educational institutions.

    PubMed

    Wiens, Matthew O; Soon, Judith A; MacLeod, Stuart M; Sharma, Sunaina; Patel, Anik

    2014-01-01

    Ongoing efforts by Health Canada intended to modernize the legislation and regulation of pharmaceuticals will help improve the safety and effectiveness of drug products. It will be imperative to ensure that comprehensive and specialized training sites are available to train researchers to support the regulation of therapeutic products. The objective of this educational institution inventory was to conduct an environmental scan of educational institutions in Canada able to train students in areas of post-market drug evaluation research. A systematic web-based environmental scan of Canadian institutions was conducted. The website of each university was examined for potential academic programs. Six core programmatic areas were determined a priori as necessary to train competent post-market drug evaluation researchers. These included biostatistics, epidemiology, pharmacoepidemiology, health economics or pharmacoeconomics, pharmacogenetics or pharmacogenomics and patient safety/pharmacovigilance. Twenty-three academic institutions were identified that had the potential to train students in post-market drug evaluation research. Overall, 23 institutions taught courses in epidemiology, 22 in biostatistics, 17 in health economics/pharmacoeconomics, 5 in pharmacoepidemiology, 5 in pharmacogenetics/pharmacogenomics, and 3 in patient safety/pharmacovigilance. Of the 23 institutions, only the University of Ottawa offered six core courses. Two institutions offered five, seven offered four and the remaining 14 offered three or fewer. It is clear that some institutions may offer programs not entirely reflected in the nomenclature used for this review. As Heath Canada moves towards a more progressive licensing framework, augmented training to increase research capacity and expertise in drug safety and effectiveness is timely and necessary.

  7. Rethinking Research Ethics: The Case of Postmarketing Trials

    PubMed Central

    London, Alex John; Carlisle, Benjamin

    2015-01-01

    Phase IV studies are often criticized for poor scientific standards. Yet they provide an important resource for addressing evidence shortfalls in drug safety, comparative effectiveness, and real-world utility. Current research ethics policies, and contemplated revisions to them, do not provide an adequate framework for preventing social harms that result from poor post-marketing research practice. Rather than focus exclusively on the welfare and interests of human volunteers, research policies and ethics should also safeguard the integrity of the research enterprise as a system for producing reliable medical evidence. We close by briefly describing how an integrity framework might be implemented for phase IV studies. PMID:22556237

  8. Embedding 'speaking up' into systems for safe healthcare product development and marketing surveillance.

    PubMed

    Edwards, Brian; Hugman, Bruce; Tobin, Mary; Whalen, Matthew

    2012-04-01

    Robust, active cooperation, and effective, open communication between all stakeholders is essential for ensuring regulatory compliance and healthcare product safety; avoiding the necessity for whistle-blowing; and, most essentially, meeting the transparency requirements of public trust.The focus here is on what can be done within a healthcare product organization (HPO) to achieve actionable, sustainable policies and practices such as leadership, management, and supervision role-modelling of best practice; ongoing process review and improvements in every department; protection of those who report concerns through robust policies endorsed at Board level throughout an organization to eliminate the fear of retaliation; training in open, non-defensive team-working principles; and mediation structure and process for resolution of differences of opinion or interpretation of contradictory and volatile data.Based on analyses of other safety systems, workplace silence and interpersonal breakdowns are warning signs of defective systems underlying poor compliance and compromising safety. Remedying the situation requires attention to the root causes underlying such symptoms of dysfunction, especially the human factor, i.e. those factors that influence human performance. It is essential that leadership and management listen to employees' concerns about systems and processes, assess them impartially and reward contributions that improve safety.Fundamentally, the safety, transparency, and trustworthiness of HPOs, both commercial and regulatory, can be judged by the extent of the freedom of their staff to 'speak up' when the time is right. This, in turn, consolidates the trust of external stakeholders in the safety of a system and its products. The promotion of 'speaking up' in an organization provides an important safeguard against the risk of poor compliance and the undermining of societal confidence in the safety of healthcare products.

  9. Application of syndromic surveillance on routinely collected cattle reproduction and milk production data for the early detection of outbreaks of Bluetongue and Schmallenberg viruses.

    PubMed

    Veldhuis, Anouk; Brouwer-Middelesch, Henriëtte; Marceau, Alexis; Madouasse, Aurélien; Van der Stede, Yves; Fourichon, Christine; Welby, Sarah; Wever, Paul; van Schaik, Gerdien

    2016-02-01

    This study aimed to evaluate the use of routinely collected reproductive and milk production data for the early detection of emerging vector-borne diseases in cattle in the Netherlands and the Flanders region of Belgium (i.e., the northern part of Belgium). Prospective space-time cluster analyses on residuals from a model on milk production were carried out to detect clusters of reduced milk yield. A CUSUM algorithm was used to detect temporal aberrations in model residuals of reproductive performance models on two indicators of gestation length. The Bluetongue serotype-8 (BTV-8) epidemics of 2006 and 2007 and the Schmallenberg virus (SBV) epidemic of 2011 were used as case studies to evaluate the sensitivity and timeliness of these methods. The methods investigated in this study did not result in a more timely detection of BTV-8 and SBV in the Netherlands and BTV-8 in Belgium given the surveillance systems in place when these viruses emerged. This could be due to (i) the large geographical units used in the analyses (country, region and province level), and (ii) the high level of sensitivity of the surveillance systems in place when these viruses emerged. Nevertheless, it might be worthwhile to use a syndromic surveillance system based on non-specific animal health data in real-time alongside regular surveillance, to increase the sense of urgency and to provide valuable quantitative information for decision makers in the initial phase of an emerging disease outbreak. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Moored Surveillance System Field Validation Test Sensor Performance Analysis. Volume 2. Standard Resolution Data Products

    DTIC Science & Technology

    1978-12-31

    calibration nignal intervals. .?.e third )ortion contains the estimated ambient sowid fi•ld (ASF) levels in dgt /lU•[1H2 The o=dire-ctic-nal (0) and vertic-al...loss than the total received SPL technique , such as was used in Ref. 2. This difference is discussed in Volume IV. (C) Data products of the next type...earlier, a simple technique wos used to partially debias the S/N results. (C) The results which appear most anomalous, i.e., those at 55 Hz, were

  11. The respective roles of controlled clinical trials and cohort monitoring studies in the pre- and postmarketing assessment of drugs.

    PubMed

    Vray, Muriel; Hamelin, Bernard; Jaillon, Patrice

    2005-01-01

    The respective roles of controlled clinical trials and observational studies (cohort or case-control studies) in evaluating the efficacy, safety and usefulness of a drug were analysed. A randomised, controlled, double-blind study is the best method of estimating the efficacy of a treatment. It provides the least biased and most robust estimate of the causal relationship. In certain situations and on the basis of certain criteria, observational studies can have a proof-of-efficacy value. Randomised, controlled, pre- and postmarketing authorisation (MA) clinical studies identify the rarer adverse effects and compare them with those resulting from the reference treatment. Before the MA, the pooled safety data from different controlled trials can provide an estimation of relatively frequent adverse events and subjects at risk. However, an observational study is the most appropriate method of evaluating the safety of a drug in the currently used conditions. By definition, a drug influences the health of a population if it directly or indirectly improves its health. A drug would have a major role in public health if it reduced mortality or morbidity related to a particular disease or if it improved the quality of life of patients with this disease. Prior to marketing a product, modelling is the approach of choice to quantify the expected effect. Pragmatic, postmarketing trials and observational studies are the reference methods used to define the population affected, the efficacy and safety of the drug in a real situation and its usefulness for public health. In conclusion, randomised clinical trials remain the reference approach for evaluating efficacy, while observational studies have a confirmatory value. Observational studies are the most appropriate way of evaluating safety in the currently used conditions, as the clinical trial has limited indications. In the interests of public health, modelling is the pre-marketing approach of choice, while pragmatic trials and

  12. Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data

    PubMed Central

    D’Urzo, Anthony D; Kerwin, Edward M; Chapman, Kenneth R; Decramer, Marc; DiGiovanni, Robert; D’Andrea, Peter; Hu, Huilin; Goyal, Pankaj; Altman, Pablo

    2015-01-01

    Background Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents. Methods We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50μg, placebo (both delivered via the Breezhaler® device), or tiotropium 18 μg (delivered via the HandiHaler® device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA™. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated. Results The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data. Conclusion The overall safety profile of glycopyrronium was

  13. Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

    PubMed

    Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

    2017-01-01

    Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

  14. Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data.

    PubMed

    D'Urzo, Anthony D; Kerwin, Edward M; Chapman, Kenneth R; Decramer, Marc; DiGiovanni, Robert; D'Andrea, Peter; Hu, Huilin; Goyal, Pankaj; Altman, Pablo

    2015-01-01

    Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents. We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50 μg, placebo (both delivered via the Breezhaler device), or tiotropium 18 μg (delivered via the HandiHaler device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated. The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data. The overall safety profile of glycopyrronium was similar to its comparators indicating no

  15. [Application of Markov model in post-marketing pharmacoeconomic evaluation of traditional Chinese medicine].

    PubMed

    Wang, Xin; Su, Xia; Sun, Wentao; Xie, Yanming; Wang, Yongyan

    2011-10-01

    In post-marketing study of traditional Chinese medicine (TCM), pharmacoeconomic evaluation has an important applied significance. However, the economic literatures of TCM have been unable to fully and accurately reflect the unique overall outcomes of treatment with TCM. For the special nature of TCM itself, we recommend that Markov model could be introduced into post-marketing pharmacoeconomic evaluation of TCM, and also explore the feasibility of model application. Markov model can extrapolate the study time horizon, suit with effectiveness indicators of TCM, and provide measurable comprehensive outcome. In addition, Markov model can promote the development of TCM quality of life scale and the methodology of post-marketing pharmacoeconomic evaluation.

  16. [Technical specifications for post-marketing pharmacoeconomic evaluation of Chinese medicine (draft version for comments)].

    PubMed

    Xie, Yan-Ming; Wang, Xin; Wang, Nuo; Chang, Yan-Peng

    2013-09-01

    Pharmacoeconomics is an important part of the post-marketing evaluation of Chinese medicine, post-marketing pharmacoeconomic evaluation can better reflect the clinical and market value of Chinese medicine, the purpose of establishing the technical specifications for pharmacoeconomic evaluation is to make the evaluation process and results regarding Chinese patent medicines more scientific and fair. Every country's technical specifications for pharmacoeconomic evaluation act as reference guidelines, we have already drawn up the technical specifications which take into account the special characteristics of Chinese medicine; these are in preparation for post-marketing pharmacoeconomic evaluation Chinese medicine.

  17. Environmental surveillance master sampling schedule

    SciTech Connect

    Bisping, L.E.

    1993-01-01

    Environmental surveillance of the Hanford Site and surrounding areas is conducted by the Pacific Northwest Laboratory (PNL) for the US Department of Energy (DOE). Samples are routinely collected and analyzed to determine the quality of air, surface water, ground water, soil, sediment, wildlife, vegetation, foodstuffs, and farm products at Hanford Site and surrounding communities. This document contains the planned schedule for routine sample collection for the Surface Environmental Surveillance Project (SESP) and Drinking Water Project, and Ground-Water Surveillance Project.

  18. 48 CFR 42.1104 - Surveillance requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... use of any reliable contractor production control or data management systems. (d) In performing... CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Production Surveillance and Reporting...

  19. 48 CFR 42.1104 - Surveillance requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... use of any reliable contractor production control or data management systems. (d) In performing... CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Production Surveillance and Reporting...

  20. 48 CFR 42.1104 - Surveillance requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... use of any reliable contractor production control or data management systems. (d) In performing... CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Production Surveillance and Reporting...

  1. 48 CFR 42.1104 - Surveillance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... use of any reliable contractor production control or data management systems. (d) In performing... CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Production Surveillance and Reporting...

  2. Indicators of drug-seeking aberrant behaviours: the feasibility of use in observational post-marketing cohort studies for risk management.

    PubMed

    Layton, Deborah; Osborne, Vicki; Al-Shukri, Mohammad; Shakir, Saad A W

    2014-08-01

    Problematic prescription drug use is reflected by or associated with drug-seeking aberrant behaviours. Research gaps include lack of post-marketing evidence and instruments. As part of the pharmacovigilance requirements, a risk management plan was developed for fentanyl buccal tablets (FEBT) by the manufacturer, with an additional pharmacovigilance activity requested by the regulatory authority, to investigate the risks of misuse, abuse, criminal use, off-label use and accidental exposure to FEBT after the product became commercially available. A Modified Prescription-Event Monitoring (M-PEM), observational, post-authorisation safety surveillance (PASS) study was conducted, with an overall aim to examine the use of FEBT in relation to their safety as prescribed in primary care in England. One of the exploratory objectives included estimating the prevalence of aberrant behaviours during FEBT treatment. To determine the feasibility of estimating the prevalence of risk factors associated with dependence on starting treatment and aberrant behaviours in patients during treatment with a prototypical abuse liable substance (fentanyl), as based on the application of an existing index (the Chabal criteria). Data were collected as part of the M-PEM PASS study; exposure and outcome data (including risk factors for dependence and aberrant behaviours based on behavioural not clinical manifestations) were derived from questionnaires sent to primary care physicians in England during April 2008 to June 2011. For the exploratory objective of interest, descriptive statistics and simple (non-weighted) risk scores were constructed on aggregate counts (score ≥3 considered 'high-risk'). Supplementary analyses explored the relationship between the two indices and the characteristics of patients with aberrant behaviours and those without (crude odds ratios plus 95% confidence interval (CI) were calculated). In a cohort of 551 patients, the prevalence of at least one pre-existing risk

  3. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China.

    PubMed

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe.

  4. [Arthroplasty registers as post-marketing surveillance systems: the Catalan Arthroplasty Register].

    PubMed

    Allepuz, A; Serra-Sutton, V; Martínez, O; Tebé, C; Nardi, J; Portabella, F; Espallargues, M

    2013-01-01

    The aim is to present the functioning and results of the Catalan Arthroplasty Registry (RACat). The RACat arose by the initiative of the Catalan Society of Orthopaedic Surgery and Traumatology, the Catalan Health Service (CHS) and the Catalan Agency for Health Information Assessment and Quality. Publicly funded hospitals sent information through the Internet (CHS Applications website) on knee and hip arthroplasties: patient identification, hospital, joint (hip/knee), type (primary/revision), side of operation, date of surgery and prosthesis (manufacturer's name and reference number). The quality of the data is analysed regularly. We estimate the risk of replacement by the Kaplan-Meier method. A total of 52 hospitals out of 62 send data to RACat, and information on 36,951 knee and 26,477 hip arthroplasties is available. Data quality improved between 2005 and 2010. In 2010 coverage exceeded 70%, with side of operation 97%, and prostheses identification of 80%. The risk of replacement at three years was 3.3% (95% CI:3.1-3.6) for knee, 2.9% (95% CI:2.5-3.3) for total hip, and 2.5% (95% CI:2.0-3.1) for partial hip. Risk of replacement is higher than that observed in other registers, although data quality and its improvement over time should be taken into account. The information available in the RACat will help to establish a standard that will enable hospitals to compare results. Copyright © 2012 SECOT. Published by Elsevier Espana. All rights reserved.

  5. Post-marketing surveillance of Norplant((R)) contraceptive implants: II. Non-reproductive health(1).

    PubMed

    2001-04-01

    This controlled cohort study aimed to evaluate the safety and efficacy of Norplant contraceptive implants in developing countries. Women initiating Norplant implants were index subjects and women initiating intrauterine devices (IUDs) or surgical sterilization were controls. Consenting participants at 32 clinics in eight developing countries were admitted and followed-up every 6 months for 5 years. Major and less serious health events during follow-up were recorded. Incidence rate ratios of health events adjusted for clinic were estimated for initial and current method use. This paper reports non-reproductive health events. The study involved 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of sterilization. Five years follow-up was completed for 94.6% of the women. The study accumulated 78,323 woman-years of observation. The initial method chosen accounted for 84.4% or more of observed woman-years in users of Norplant, IUD, or sterilization. Twenty-two of the recorded 34 deaths were due to accidents, suicide or homicide. Few deaths or major health events were due to cancer or acute cardiovascular diseases and were not associated with the contraceptive method used. The incidence rates of major health events were low and with two exceptions, there was no significant excess risk of serious morbidity for Norplant users compared with controls; among Norplant initiators gallbladder disease occurred at an incidence rate of 1.5 per 1,000 woman-years and was weakly associated with use of Norplant (rate ratio 1.52 [95% C.I. 1.02, 2.27]). For current Norplant users compared to controls, the rate ratio of a combined variable of hypertension and borderline hypertension was significantly elevated (1.81, [1.12, 2.92]). The occurrence of less serious health events was also low and several of them were significantly more often reported among Norplant users. Headache-migraine, weight gain, mood disturbances, pruritus, eczema, and acne had incidence rates among Norplant users of 11.5, 4.5, 2.8, 1.5, 1.4, and 0.9 per 1,000 woman-years, respectively, and were significantly higher than in controls. Respiratory health problems, nonspecific symptoms, and several ill-defined conditions were also significantly more often reported for Norplant users, but some of the excess incidence may be attributable to reporting and detection bias. The study confirms the safety with respect to serious disease of Norplant, IUDs, and sterilization.

  6. Role of the post-marketing authorisation studies in drug risk surveillance: specifications and methodologies.

    PubMed

    Tubach, Florence; Lamarque-Garnier, Véronique; Castot, Anne

    2011-01-01

    Studies conducted after the marketing authorisation with the objective of identification, characterization or quantification of one or more risks (called PASS "Post-Authorisation Safety Studies"), have been strengthened in the past years with the implementation of the concept of risk management plans (RMPs), established in 2005 in the European regulatory framework and recently amended as part of the community revision. These safety studies, interventional or not, are related to a marketed drug, whether or not the drug is used within the market authorisation conditions. Apart from these safety studies, other studies whose primary objective is not risk assessment, including assessment of efficacy, description of prescription data and use in real life, pharmacokinetics, public health impact ... can complete available safety data.The Giens Round Table examined PASS from the risk management plans of a sample of marketing authorisation holders (participants to the Round Table) and identified the main characteristics of proposed actions. Concerning the specifications and the choice of methodology, only a general outline has been sketched in view of the complexity and diversity of drug risks situations.

  7. An analysis of implantable cardiac device reliability. The case for improved postmarketing risk assessment and surveillance.

    PubMed

    Laskey, Warren; Awad, Khaled; Lum, Jeremy; Skodacek, Ken; Zimmerman, Barbara; Selzman, Kimberly; Zuckerman, Bram

    2012-07-01

    Implantable cardiac devices have become the mainstay of the treatment of patients with heart disease. However, data regarding their reliability and, inferentially, safety have been called into question. We reviewed annual reports submitted to the Food and Drug Administration Office of Device Evaluation by device manufacturers from 2003 to 2007. The annual number of implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillator (CRT-D) implants, explants, and returned devices were tabulated along with the cumulative (Cum) number of implants for each device. We derived an annual explantation rate (AER) defined as the ratio of the annual number of explants less the number of normal battery depletions/Cum (×1000). From 2003 to 2007, 256,392 CRT-D and 459,300 ICD devices were implanted in the United States. The overall mean (±SD) AERs for ICD and CRT-D devices were, respectively, 49.5 (15.6) per 1000 ICD devices and 82.6 (35.5) per 1000 CRT-D devices. The AER for each device type significantly decreased over the study period (P for trend <0.001) although the AER for CRT-D devices was 38% higher than that for ICD devices (P < 0.001). On average, 20.3% of CRT-D devices and 22.6% of ICD devices were returned to the manufacturer for analysis after explantation. The rates of explanted CRT-D and ICD devices decreased from 2003 to 2007. Notwithstanding this favorable trend, the AER for CRT-D devices was higher than that for ICD devices. Improved methods for tracking individual device histories are needed for more precise estimates of the risk of device explantation for suspected malfunction. The proportion of devices returned to the manufacturer is suboptimal and needs to be improved to better understand the mechanisms of device malfunction.

  8. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China

    PubMed Central

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe. PMID:28192490

  9. A postmarketing surveillance study of dexrabeprazole in the treatment of acid peptic disorders.

    PubMed

    Jain, S C

    2009-02-01

    Dexrabeprazole [R(+) rabeprazole] is a novel proton-pump inhibitor which has recently become available in India for the treatment of acid peptic diseases. Experimental and clinical studies have shown superiority of dexrabeprazole (at half the recommended rabeprazole dose) over rabeprazole in terms of favourable pharmacokinetics, better efficacy and faster and greater healing activity. Results of present study in a large population of 4931 patients of acid peptic disorders, reconfirmed safety and efficacy of dexrabeprazole 10 mg once daily in the treatment of gastro-oesophageal reflux disease and also showed its effectiveness in the treatment of patients with peptic ulcers (gastric/duodenal).

  10. Safety and Efficacy of Zonisamide in Patients with Epilepsy: A Post-Marketing Surveillance Study

    PubMed Central

    Lee, Hye Jin; Son, Jeong Min; Mun, Jihee; Kim, Dong Wook

    2015-01-01

    Background and Purpose: Zonisamide (ZNS) is one of new antiepileptic drug, which is known to inhibit seizure through multiple mechanisms of action. In Korea, ZNS was approved as an antiepileptic drug in 1992 and has been used for epilepsy patients with partial and generalized seizures. The objective of this study was to investigate the efficacy and tolerability of ZNS in patients with epilepsy and to identify the incidence of adverse events in real clinical setting. Methods: This study was carried out in patients who received ZNS for epilepsy. Patients who were observed for at least 12 weeks after treatment with ZNS were included as evaluable subjects. Information regarding the status and type of adverse events occurring during the course of treatment with ZNS was obtained regardless of causal relationship to ZNS and efficacy was assessed by the study physicians and patients at 12 weeks post dose of ZNS. Results: A total of 1,948 patients were included in the study, and ZNS efficacy was evaluated in 1,744 patients. ZNS was used as a monotherapy in 1,095 patients and as an adjunctive drug in 853 patients. Of the total patients, 1,345 (69.1%) patients had partial seizure, 563 patients had generalized seizure, and 40 patients were undetermined. Adverse events were reported in 65 patients (3.34%) including 1 case of Stevens-Johnson syndrome, but no incidence of serious unexpected adverse drug reactions were reported. 755 patients (43.29%) became seizure free with ZNS treatment, and additional 322 patients (18.41%) experienced marked improvement with ZNS treatment. Conclusions: Our study shows the safety and tolerability of ZNS treatment in patients with epilepsy in real clinical setting. In addition, ZNS was found to be an effective option as a monotherapy or in patients with generalized seizure. PMID:26819941

  11. 77 FR 52742 - Public Meeting-Strengthening the National Medical Device Postmarket Surveillance System; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... Greenbelt Marriott Hotel, 6400 Ivy Lane, Greenbelt, MD 20770, 301-441-3700. FOR FURTHER INFORMATION CONTACT... optimally structured to meet the challenges of rapidly evolving medical devices and the changing nature of health care delivery and information technology. In their report entitled ``Medical Devices and the...

  12. [Post-marketing surveillance of Tanreqing injection in children: a real world study].

    PubMed

    Li, X X; Zhuo, L; Yang, Y H; Zhan, S Y; Zhai, S D

    2017-02-10

    Objective: To evaluate the safety of Tanreqing injection among children in the real world. Methods: A multicenter, large sample, ambispective cohort study, with registration-type clinical safety monitoring. A total of 6 188 inpatients and patients from the emergency units, aged ≤ 14 years who all had been using Tanreqing injection in 59 secondary and tertiary hospitals in China, were recruited between January, 2014 and May, 2015. The main outcomes would include incidence and severity of adverse drug reaction (ADR)/adverse drug event (ADE) of Tanreqing injection. Univariate analysis was used to explain the risk factors of ADR. Results: The overall incidence of ADE was 4.20‰ (26 cases), including 4 serious ones. The incidence of ADR was 3.07‰ (19 cases), including 17 cases of general ADR and 2 cases of new ADR. All the ADR cases were mild or moderate, mostly showing damages in skin and appendages. The onset of disease happened in 24 hours after the Tanreqing injection but all the ADR cases got improved or cured. Having histories of allergies to drugs or foods would increase the incidence of ADR. Conclusion:Tanreqing injection caused low incidence of ADR in children. Progams as stratifying high-risk patients and improving administrative management could further increase the safety level of Tanreqing injection.

  13. 76 FR 43691 - Unique Device Identification for Postmarket Surveillance and Enforcement; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ...-mail, and telephone number. For those without Internet access, please contact Jay Crowley (see Contact..., information about lodging, and other relevant information on the Internet at http://www.fda.gov/UDI . Comments... Sentinel Initiative, on the Internet at...

  14. Safety and Efficacy of Zonisamide in Patients with Epilepsy: A Post-Marketing Surveillance Study.

    PubMed

    Lee, Hye Jin; Son, Jeong Min; Mun, Jihee; Kim, Dong Wook

    2015-12-01

    Zonisamide (ZNS) is one of new antiepileptic drug, which is known to inhibit seizure through multiple mechanisms of action. In Korea, ZNS was approved as an antiepileptic drug in 1992 and has been used for epilepsy patients with partial and generalized seizures. The objective of this study was to investigate the efficacy and tolerability of ZNS in patients with epilepsy and to identify the incidence of adverse events in real clinical setting. This study was carried out in patients who received ZNS for epilepsy. Patients who were observed for at least 12 weeks after treatment with ZNS were included as evaluable subjects. Information regarding the status and type of adverse events occurring during the course of treatment with ZNS was obtained regardless of causal relationship to ZNS and efficacy was assessed by the study physicians and patients at 12 weeks post dose of ZNS. A total of 1,948 patients were included in the study, and ZNS efficacy was evaluated in 1,744 patients. ZNS was used as a monotherapy in 1,095 patients and as an adjunctive drug in 853 patients. Of the total patients, 1,345 (69.1%) patients had partial seizure, 563 patients had generalized seizure, and 40 patients were undetermined. Adverse events were reported in 65 patients (3.34%) including 1 case of Stevens-Johnson syndrome, but no incidence of serious unexpected adverse drug reactions were reported. 755 patients (43.29%) became seizure free with ZNS treatment, and additional 322 patients (18.41%) experienced marked improvement with ZNS treatment. Our study shows the safety and tolerability of ZNS treatment in patients with epilepsy in real clinical setting. In addition, ZNS was found to be an effective option as a monotherapy or in patients with generalized seizure.

  15. Surface Environmental Surveillance Project: Locations Manual Volume 1 – Air and Water Volume 2 – Farm Products, Soil & Vegetation, and Wildlife

    SciTech Connect

    Fritz, Brad G.; Patton, Gregory W.; Stegen, Amanda; Poston, Ted M.

    2009-01-01

    This report describes all environmental monitoring locations associated with the Surface Environmental Surveillance Project. Environmental surveillance of the Hanford site and surrounding areas is conducted by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy (DOE). Sampling is conducted to evaluate levels of radioactive and nonradioactive pollutants in the Hanford environs, as required in DOE Order 450.1, Environmental Protection Program, and DOE Order 5400.5, Radiation Protection of the Public and the Environment. The environmental surveillance sampling design is described in the Hanford Site Environmental Monitoring Plan, United States Department of Energy, Richland Operation Office (DOE/RL-91-50). This document contains the locations of sites used to collect samples for the Surface Environmental Surveillance Project (SESP). Each section includes directions, maps, and pictures of the locations. A general knowledge of roads and highways on and around the Hanford Site is necessary to successfully use this manual. Supplemental information (Maps, Gazetteer, etc.) may be necessary if user is unfamiliar with local routes. The SESP is a multimedia environmental surveillance effort to measure the concentrations of radionuclides and chemicals in environmental media to demonstrate compliance with applicable environmental quality standards and public exposure limits, and assessing environmental impacts. Project personnel annually collect selected samples of ambient air, surface water, agricultural products, fish, wildlife, and sediments. Soil and vegetation samples are collected approximately every 5 years. Analytical capabilities include the measurement of radionuclides at very low environmental concentrations and, in selected media, nonradiological chemicals including metals, anions, volatile organic compounds, and total organic carbon.

  16. Citicoline for acute ischemic stroke in Mexican hospitals: a retrospective postmarketing analysis.

    PubMed

    Leon-Jimenez, C; Chiquete, E; Cantu, C; Miramontes-Saldana, M J; Andrade-Ramos, M A; Ruiz-Sandoval, J L

    2010-06-01

    Some neuroprotective agents have shown benefits in animal models, but disappointing results in humans. Citicoline is used in several countries as coadjuvant treatment in acute ischemic stroke (AIS) patients; however, there are no retrospective postmarketing surveillances on the experience of citicoline in Mexico. The aim of this study was to evaluate the correlation between citicoline exposure and functional outcome at discharge and at 30 and 90 days post-stroke, in a retrospective case-control design on systematic descriptive databases from three referral hospitals. Clinical records of 173 consecutively registered patients were analyzed, 86 of whom were treated with citicoline within the first 48 h after AIS and the remaining 87 were untreated, randomly selected controls matched for age (+/- 5 years), gender and NIHSS (+/- 1 point) at hospital admission. Pretreatment conditions were similar between groups. Compared with controls, exposure to citicoline was associated with a significantly lower 30-day mean and median modified Rankin score (in both, P < 0.05). After paired multivariate analyses (controlled for NIHSS, age, gender, hospital arrival in < 24 h, thrombolysis and comorbidities) citicoline was independently associated with a lower 90-day mortality risk (P = 0.047) and with fewer in-hospital complications (mainly infections and sepsis, P = 0.001). In this observational study, citicoline use was associated with a better functional status and lower rates of short-term mortality, possibly due to fewer in-hospital systemic complications. The putative benefits should be interpreted as clinical associations, since this is not a randomized, controlled clinical trial.

  17. Safety surveillance of esterified estrogens-methyltestosterone (Estratest and Estratest HS) replacement therapy in the United States.

    PubMed

    Phillips, E; Bauman, C

    1997-01-01

    This paper summarizes all postmarketing safety surveillance data collected by Solvay Pharmaceuticals, Inc. (Marietta, Georgia), between 1989 and 1996 for Estratest and Estratest HS (half-strength). These oral esterified estrogens--methyltestosterone combination products have been marketed in the United States since 1964 for the treatment of moderate-to-severe vasomotor symptoms associated with menopause in patients whose symptoms have not been relieved by estrogens alone. Between 1989 and 1996, more than 1 million woman-years of exposure occurred. The safety profile contained in this paper is based on a cumulative total of 568 individual cases comprising 863 adverse events (AEs). The proportions of AEs associated with the use of Estratest (575 events; 66.6%) and Estratest HS (288 events; 33.4%) were commensurate with the proportions of individual reports of adverse experiences for the two formulations (369 reports [65.0%] and 199 reports [35.0%], respectively). The rank order and percentage of types of AEs reported were also similar. The cumulative volume of reports was relatively low given the extent of exposure. Despite the limitations inherent in spontaneous postmarketing surveillance, the safety profile derived from this assessment does not indicate a significant safety concern with Estratest or Estratest HS. No deaths were reported, and no adverse findings indicative of the need for more comprehensive surveillance or concern on the part of the medical community or consumers were observed. Reports of cancer, cardiovascular disease, thromboembolic phenomena, and hepatic dysfunction were few and were assessed as not related to treatment with Estratest or Estratest HS; reports of drug overdose, drug-drug interaction, and birth defects were rare (4 of 863 events; 0.5%). The most commonly reported AEs were those known to be associated with estrogen therapy (weight gain, headache, nausea, and vasodilatation) and androgen treatment (alopecia, acne, and hirsutism

  18. A pre-marketing ALT signal predicts post-marketing liver safety.

    PubMed

    Moylan, Cynthia A; Suzuki, Ayako; Papay, Julie I; Yuen, Nancy A; Ames, Michael; Hunt, Christine M

    2012-08-01

    Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety.

  19. Surveillance Metrics Sensitivity Study

    SciTech Connect

    Bierbaum, R; Hamada, M; Robertson, A

    2011-11-01

    In September of 2009, a Tri-Lab team was formed to develop a set of metrics relating to the NNSA nuclear weapon surveillance program. The purpose of the metrics was to develop a more quantitative and/or qualitative metric(s) describing the results of realized or non-realized surveillance activities on our confidence in reporting reliability and assessing the stockpile. As a part of this effort, a statistical sub-team investigated various techniques and developed a complementary set of statistical metrics that could serve as a foundation for characterizing aspects of meeting the surveillance program objectives. The metrics are a combination of tolerance limit calculations and power calculations, intending to answer level-of-confidence type questions with respect to the ability to detect certain undesirable behaviors (catastrophic defects, margin insufficiency defects, and deviations from a model). Note that the metrics are not intended to gauge product performance but instead the adequacy of surveillance. This report gives a short description of four metrics types that were explored and the results of a sensitivity study conducted to investigate their behavior for various inputs. The results of the sensitivity study can be used to set the risk parameters that specify the level of stockpile problem that the surveillance program should be addressing.

  20. Surveillance metrics sensitivity study.

    SciTech Connect

    Hamada, Michael S.; Bierbaum, Rene Lynn; Robertson, Alix A.

    2011-09-01

    In September of 2009, a Tri-Lab team was formed to develop a set of metrics relating to the NNSA nuclear weapon surveillance program. The purpose of the metrics was to develop a more quantitative and/or qualitative metric(s) describing the results of realized or non-realized surveillance activities on our confidence in reporting reliability and assessing the stockpile. As a part of this effort, a statistical sub-team investigated various techniques and developed a complementary set of statistical metrics that could serve as a foundation for characterizing aspects of meeting the surveillance program objectives. The metrics are a combination of tolerance limit calculations and power calculations, intending to answer level-of-confidence type questions with respect to the ability to detect certain undesirable behaviors (catastrophic defects, margin insufficiency defects, and deviations from a model). Note that the metrics are not intended to gauge product performance but instead the adequacy of surveillance. This report gives a short description of four metrics types that were explored and the results of a sensitivity study conducted to investigate their behavior for various inputs. The results of the sensitivity study can be used to set the risk parameters that specify the level of stockpile problem that the surveillance program should be addressing.

  1. Surveillance of Autism.

    ERIC Educational Resources Information Center

    Boyle, Coleen A.; Bertrand, Jacquelyn; Yeargin-Allsopp, Marshalyn

    1999-01-01

    This article describes the autism surveillance activities of the Center for Disease Control and Prevention. It considers why surveillance to track prevalence of autistic disorders is needed, how such surveillance is conducted, and the special challenges of autism surveillance. (DB)

  2. "Insuring" the continued solvency of pharmaceutical companies in the face of product liability class actions.

    PubMed

    Chodock, Rochelle; Yolkut, David; Connolly, Dennis R

    2005-01-01

    Costly product liability lawsuits continue to plague the pharmaceutical industry, and insurance to cover these losses is severely inadequate. Furthermore, questionable regulation of drugs exists once a pharmaceutical has passed FDA approval. This article describes a plan that uses a capitalistic, rather than a governmental, approach to solve both the insurance and the quality control problems. Although the proposed plan has never been used to insure pharmaceutical companies, different permutations of it have been used to insure other litigation-prone industries. Success from the proposed insurance entity results from the combined knowledge of scientists and actuaries to provide both protection from product liability lawsuits for the pharmaceutical industry and enhanced post-market surveillance of pharmaceuticals.

  3. Collaborative Point Paper on Border Surveillance Technology

    DTIC Science & Technology

    2007-12-01

    technologies. Section 2 identifies 22 US and Canadian companies, a brief description of their border surveillance systems/ products and the applicable...surveillance company data including: company name hyperlinked to its About Us/Profile page, a brief description of its systems/ products , and the...This section identifies foreign border surveillance companies a brief description of their systems/ products and the applicable environment(s) for each

  4. Post-marketing safety monitoring of shenqifuzheng injection: a solution made of dangshen (Radix Codonopsis) and huangqi (Radix Astragali Mongolici).

    PubMed

    Ai, Qinghua; Zhang, Wen; Xie, Yanming; Huang, Wenhua; Liang, Hong; Cao, Hui

    2014-08-01

    To identify the potential risk factors associated with Shenqifuzheng injection (SFI), a solution made of Dangshen (Radix Codonopsis) and Huangqi (Radix Astragali Mongolici), for the timely provision of information to regulatory authorities. A comprehensive analysis of the production process, quality standards, pharmacology, post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions (ADR), case analyses, and systematic reviews, intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital information system (HIS). Sub-acute toxicity tests suggesting that a dose of 15 mL/kg (concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85 per thousand. From March to November 2013, of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI at a dosage and a treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash, chills, feeling cold, palpitation, dyspnea, edema of a lower extremity, palpebral edema, and superficial vein inflammation, among others. This study introduces "get full access" to the flow of information on

  5. The European Post-marketing Observational Serdolect (EPOS) Project: increasing our understanding of schizophrenia therapy.

    PubMed

    Wehnert, A

    1998-03-01

    Well-controlled clinical trials, although essential for registration purposes, often fail to reflect the real-life usage of a drug. Ultimately, it is how a new medicinal product is used in clinical practice, how it performs in everyday life and how the patient who takes it feels and functions that determine the real benefit: risk ratio of the drug. Such a prospective, referenced, cohort study of sertindole (Serdolect, H. Lundbeck A/S, Copenhagen, Denmark) in schizophrenia was initiated in 1997. Sertindole is a new limbic-selective antipsychotic agent which has recently received marketing authorization in several countries across Europe for the treatment of schizophrenia. The experience gained in around 2200 sertindole-treated patients in controlled clinical trials has enabled an optimal targeting of sertindole to those patient groups who will benefit most and who are least likely to experience adverse effects. The European Post-marketing Observational Serdolect (EPOS) project plans to recruit over 12000 patients in two cohorts in centres throughout Europe. The aims are to provide a full safety evaluation of sertindole under marketed conditions at the relevant clinical dosage and, further, to provide epidemiological data on the treatment of schizophrenia in Europe under usual clinical conditions. The study is currently the only one of its kind to be undertaken in schizophrenia, and will provide important new data for psychiatrists around the world.

  6. Postmarketing Safety Events Relating to New Drugs Approved in Brazil Between 2003 and 2013: A Retrospective Cohort Study.

    PubMed

    Botelho, Stephanie Ferreira; Martins, Maria Auxiliadora Parreiras; Vieira, Liliana Batista; Reis, Adriano Max Moreira

    2017-04-01

    This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. The existence of risk evaluation and mitigation strategies (REMS) by the US Food and Drug Administration (FDA) and Brazil were recorded. A Kaplan-Meier survival curve of the period between the date of ANVISA registration and the PMSE was calculated. We found a statistically significant difference between the time to PMSE for drugs with an FDA REMS compared with those without a REMS, with a log rank value (Mantel Cox) of 0.002. There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs.

  7. Air surveillance

    SciTech Connect

    Patton, G.W.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the air surveillance and monitoring programs currently in operation at that Hanford Site. Atmospheric releases of pollutants from Hanford to the surrounding region are a potential source of human exposure. For that reason, both radioactive and nonradioactive materials in air are monitored at a number of locations. The influence of Hanford emissions on local radionuclide concentrations was evaluated by comparing concentrations measured at distant locations within the region to concentrations measured at the Site perimeter. This section discusses sample collection, analytical methods, and the results of the Hanford air surveillance program. A complete listing of all analytical results summarized in this section is reported separately by Bisping (1995).

  8. Post-Marketing Survey of Adverse Events Following Ocriplasmin.

    PubMed

    Shah, Sumit P; Jeng-Miller, Karen W; Fine, Howard F; Wheatley, H Matthew; Roth, Daniel B; Prenner, Jonathan L

    2016-02-01

    To study the post-marketing safety profile of ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) as experienced by retinal physicians in the United States. Two thousand four hundred sixty-five retinal physicians were surveyed regarding their frequency of use of ocriplasmin and reports of ocular adverse events. There were 270 respondents (11%) who reported treating 1,056 eyes with ocriplasmin. The reports of adverse events (AE) were as follows: acute decline in visual acuity (16.95%), development of submacular fluid or serous retinal detachment (10.23%), dyschromatopsia (9.09%), progression of vitreomacular traction to macular hole (8.71%), development of retinal detachment (2.65%), development of retinal tear (1.99%), development of afferent pupillary defect (1.80%), electroretinography abnormalities (0.57%), crystalline lens instability (0.38%), and vasculitis (0.28%). Although the frequency of some ocular AEs reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology and clinical relevance of ocular AEs of ocriplasmin. Copyright 2016, SLACK Incorporated.

  9. [Postmarketing herbs clinical evaluation should concern about re-evaluating symptoms].

    PubMed

    He, Wei; Xie, Yanming; Wang, Yongyan

    2010-06-01

    Re-evaluation of premarketing medicine is a important supplementary of clinical and elementary research. It is a basement that establish the medicine administration supervisition , found and integrity postmarketing washing out mechanism and define reasonable using drug. After drug marketing, we must not only concern on the re-evaluation of herbs security but also focus on evaluating herbs suitable symptom, as well as its dosage and course of treatment, ect. The re-evaluation of symptoms were seen as the core and feature of traditional Chinese medicine's clinical evaluation. It is also seen as hot spot and difficulty of the research . This article try to focus on simply illustrating the necessity and research thinking of re-evaluation symptoms of postmarketing herbs. So we can define the re-evaluation of postmarketing drug's objection, method, and basement. It will provide beneficial experience and reference to re-evaluation symptom of marketed herbs.

  10. [Clinical orientation and thought on several problems in post-marketed reassessment of traditional Chinese medicine].

    PubMed

    Wang, Xin; Su, Xia; Yu, Jie; Xie, Yanming; Wang, Yongyan

    2011-10-01

    The post-marketed reassessment is an important link to ensure the safety and effectiveness of traditional chinese medicine. It is also the expansion and stretch of new drug evaluation. Through the systematic, standard, rigorous post-marketed reassessment, the enterprise can full access to drugs after listing the efficacy and safety information, evaluate the interests and risk of the drug and provide the scientific basis for the drug use. It can also provide timely, scientific technology basis for government health decisions, the enterprise marketing decision and public health security. This paper mainly discussed the thought on clinical orientation of traditional chinese medicine in the post-marketed reassessment and how to reach the goal through systematic consideration and overall plan.

  11. A comparison of active adverse event surveillance systems worldwide.

    PubMed

    Huang, Yu-Lin; Moon, Jinhee; Segal, Jodi B

    2014-08-01

    Post-marketing drug surveillance for adverse drug events (ADEs) has typically relied on spontaneous reporting. Recently, regulatory agencies have turned their attention to more preemptive approaches that use existing data for surveillance. We conducted an environmental scan to identify active surveillance systems worldwide that use existing data for the detection of ADEs. We extracted data about the systems' structures, data, and functions. We synthesized the information across systems to identify common features of these systems. We identified nine active surveillance systems. Two systems are US based-the FDA Sentinel Initiative (including both the Mini-Sentinel Initiative and the Federal Partner Collaboration) and the Vaccine Safety Datalink (VSD); two are Canadian-the Canadian Network for Observational Drug Effect Studies (CNODES) and the Vaccine and Immunization Surveillance in Ontario (VISION); and two are European-the Exploring and Understanding Adverse Drug Reactions by Integrative Mining of Clinical Records and Biomedical Knowledge (EU-ADR) Alliance and the Vaccine Adverse Event Surveillance and Communication (VAESCO). Additionally, there is the Asian Pharmacoepidemiology Network (AsPEN) and the Shanghai Drug Monitoring and Evaluative System (SDMES). We identified two systems in the UK-the Vigilance and Risk Management of Medicines (VRMM) Division and the Drug Safety Research Unit (DSRU), an independent academic unit. These surveillance systems mostly use administrative claims or electronic medical records; most conduct pharmacovigilance on behalf of a regulatory agency. Either a common data model or a centralized model is used to access existing data. The systems have been built using national data alone or via partnership with other countries. However, active surveillance systems using existing data remain rare. North America and Europe have the most population coverage; with Asian countries making good advances.

  12. [Active surveillance of adverse drug reaction in the era of big data: challenge and opportunity for control selection].

    PubMed

    Wang, S F; Zhan, S Y

    2016-07-01

    Electronic healthcare databases have become an important source for active surveillance of drug safety in the era of big data. The traditional epidemiology research designs are needed to confirm the association between drug use and adverse events based on these datasets, and the selection of the comparative control is essential to each design. This article aims to explain the principle and application of each type of control selection, introduce the methods and parameters for method comparison, and describe the latest achievements in the batch processing of control selection, which would provide important methodological reference for the use of electronic healthcare databases to conduct post-marketing drug safety surveillance in China.

  13. Characteristics and follow-up of postmarketing studies of conditionally authorized medicines in the EU.

    PubMed

    Hoekman, Jarno; Klamer, Thea T; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; De Bruin, Marie L

    2016-07-01

    The aim of the present study was to provide an insight into the characteristics and follow-up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU). We compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time. A total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were 'long-term follow-up' and 'increase data on subpopulations'. Of the 34 studies eligible for follow-up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (-121 to 556) days longer than expected. Our results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA. © 2016 The British Pharmacological Society.

  14. Characteristics and follow‐up of postmarketing studies of conditionally authorized medicines in the EU

    PubMed Central

    Klamer, Thea T.; Mantel‐Teeuwisse, Aukje K.; Leufkens, Hubert G. M.; De Bruin, Marie L.

    2016-01-01

    Aim The aim of the present study was to provide an insight into the characteristics and follow‐up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU). Methods We compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time. Results A total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were ‘long‐term follow‐up’ and ‘increase data on subpopulations’. Of the 34 studies eligible for follow‐up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (−121 to 556) days longer than expected. Conclusions Our results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA. PMID:26992001

  15. [Study on method on post-marketing traditonal Chinese medicine safety assessment].

    PubMed

    Kou, Qiuai; Zhao, Suping; Feng, Guoshuang; Xie, Yanming

    2011-10-01

    Traditional Chinese medicine (TCM) safety assessment is an important content of post-marketing Chinese herbal medicine assessment and the primary question. It includes safety monitoring and safety evaluation. China has established the elementary system for the TCM safety monitoring, but did few things on safety evaluation. People have knew that the methods of pharmacoepidemiology have good practicability on drug safety assessment in recent years. This article analyzed three methods of pharmacoepidemiology used in post-marketing Chinese herbal medicine safety assessment. There are three examples that may give some suggestions to fellow doctors working for safety monitoring and evaluation of TCM.

  16. [Necessity of applying pharmacovigilance in post-marketing safety monitoring of traditional Chinese medicine injections].

    PubMed

    Wang, Hai-Nan; Chen, Wen; Fu, Zheng; Du, Wen-min; He, Jia

    2008-03-01

    Traditional Chinese medicine (TCM) injection has become one of the hotspots in the new TCM research and development. The serious adverse drug reactions happened in clinical have arosed attention widely in the whole society. It's very urgent to monitor the post-marketing safety of TCM injections. This paper elucidated the pharmacovigilance's necessity in the post-marketing safety monitoring of TCM injections, basing on the reason of safety problem of TCM injections and the future developing trend of adverse drug reaction monitoring. Also, this paper introduced the rapid signal detection method of spontaneous reporting system database by data mining technology.

  17. [Thought on several problems of post-marketing herbs clinical evaluation in special populations].

    PubMed

    Zhou, Ai; Lian, Fengmei

    2011-10-01

    The re-evaluation of clinical post-marketing herbs in special populations, such as children, the aged, pregnant women, lactating women, has attracted attention in our country. The media is drug adverse reaction reports and package insert. The safety of combined administration in aged and children's growth should have been taken long-term follow-up study. Perfecting traditional chinese medicine FDA system will be beneficial to the re-evaluation of clinical postmarketing herbs in pregnant women. Dose-effect study in children also should cause the concern of researchers.

  18. Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation.

    PubMed

    Babiskin, Andrew H; Zhang, Xinyuan

    2015-09-01

    Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used for the treatment of attention deficit hyperactivity disorder. We developed physiologically based absorption models for mixed AMP salts ER capsules and dextroamphetamine sulfate ER capsules to address specific questions raised during generic drug postmarketing surveillance and bioequivalence (BE) guidance development. The models were verified against several data sets. Virtual BE simulations were conducted to assess BE in various populations other than normal healthy subjects where BE studies are generally conducted for approval. The models were also used to predict pharmacokinetics (PK) for hypothetical formulations having dissolution profiles falling within specification after the development of in vitro-in vivo relation. Finally, we demonstrated how to use the models to test sensitivity of PK metrics to the changes in formulation variables. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  19. 48 CFR 242.1104 - Surveillance requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... production surveillance is required, shall— (A) Conduct a periodic risk assessment of the contractor to... risk assessment shall consider information provided by the contractor and the contracting officer; (B) Develop a production surveillance plan based on the risk level determined during a risk assessment;...

  20. 48 CFR 242.1104 - Surveillance requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... production surveillance is required, shall— (A) Conduct a periodic risk assessment of the contractor to... risk assessment shall consider information provided by the contractor and the contracting officer; (B) Develop a production surveillance plan based on the risk level determined during a risk assessment;...

  1. 48 CFR 242.1104 - Surveillance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... production surveillance is required, shall— (A) Conduct a periodic risk assessment of the contractor to... risk assessment shall consider information provided by the contractor and the contracting officer; (B) Develop a production surveillance plan based on the risk level determined during a risk assessment;...

  2. 48 CFR 242.1104 - Surveillance requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... production surveillance is required, shall— (A) Conduct a periodic risk assessment of the contractor to... risk assessment shall consider information provided by the contractor and the contracting officer; (B) Develop a production surveillance plan based on the risk level determined during a risk assessment;...

  3. 48 CFR 242.1104 - Surveillance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... production surveillance is required, shall— (A) Conduct a periodic risk assessment of the contractor to... risk assessment shall consider information provided by the contractor and the contracting officer; (B) Develop a production surveillance plan based on the risk level determined during a risk assessment;...

  4. Public involvement in environmental surveillance at Hanford

    SciTech Connect

    Hanf, R.W. Jr.; Patton, G.W.; Woodruff, R.K.; Poston, T.M.

    1994-08-01

    Environmental surveillance at the Hanford Site began during the mid-1940s following the construction and start-up of the nation`s first plutonium production reactor. Over the past approximately 45 years, surveillance operations on and off the Site have continued, with virtually all sampling being conducted by Hanford Site workers. Recently, the US Department of Energy Richland Operations Office directed that public involvement in Hanford environmental surveillance operations be initiated. Accordingly, three special radiological air monitoring stations were constructed offsite, near hanford`s perimeter. Each station is managed and operated by two local school teaches. These three stations are the beginning of a community-operated environmental surveillance program that will ultimately involve the public in most surveillance operations around the Site. The program was designed to stimulate interest in Hanford environmental surveillance operations, and to help the public better understand surveillance results. The program has also been used to enhance educational opportunities at local schools.

  5. National surveillance for radiological exposures and intentional potassium iodide and iodine product ingestions in the United States associated with the 2011 Japan radiological incident.

    PubMed

    Law, Royal K; Schier, Josh G; Martin, Colleen A; Olivares, Dagny E; Thomas, Richard G; Bronstein, Alvin C; Chang, Arthur S

    2013-01-01

    In March of 2011, an earthquake struck Japan causing a tsunami that resulted in a radiological release from the damaged Fukushima Daiichi nuclear power plant. Surveillance for potential radiological and any iodine/iodide product exposures was initiated on the National Poison Data System (NPDS) to target public health messaging needs within the United States (US). Our objectives are to describe self-reported exposures to radiation, potassium iodide (KI) and other iodine/iodide products which occurred during the US federal response and discuss its public health impact. All calls to poison centers associated with the Japan incident were identified from March 11, 2011 to April 18, 2011 in NPDS. Exposure, demographic and health outcome information were collected. Calls about reported radiation exposures and KI or other iodine/iodide product ingestions were then categorized with regard to exposure likelihood based on follow-up information obtained from the PC where each call originated. Reported exposures were subsequently classified as probable exposures (high likelihood of exposure), probable non-exposures (low likelihood of exposure), and suspect exposure (unknown likelihood of exposure). We identified 400 calls to PCs associated with the incident, with 340 information requests (no exposure reported) and 60 reported exposures. The majority (n = 194; 57%) of the information requests mentioned one or more substances. Radiation was inquired about most frequently (n = 88; 45%), followed by KI (n = 86; 44%) and other iodine/iodide products (n = 47; 24%). Of the 60 reported exposures, KI was reported most frequently (n = 25; 42%), followed by radiation (n = 22; 37%) and other iodine/iodide products (n = 13; 22%). Among reported KI exposures, most were classified as probable exposures (n = 24; 96%); one was a probable non-exposure. Among reported other iodine/iodide product exposures, most were probable exposures (n = 10, 77%) and the rest were suspect exposures (n = 3; 23

  6. National surveillance for radiological exposures and intentional potassium iodide and iodine product ingestions in the United States associated with the 2011 Japan radiological incident

    PubMed Central

    LAW, ROYAL K.; SCHIER, JOSH G.; MARTIN, COLLEEN A.; OLIVARES, DAGNY E.; THOMAS, RICHARD G.; BRONSTEIN, ALVIN C.; CHANG, ARTHUR S.

    2015-01-01

    Background In March of 2011, an earthquake struck Japan causing a tsunami that resulted in a radiological release from the damaged Fukushima Daiichi nuclear power plant. Surveillance for potential radiological and any iodine/iodide product exposures was initiated on the National Poison Data System (NPDS) to target public health messaging needs within the United States (US). Our objectives are to describe self-reported exposures to radiation, potassium iodide (KI) and other iodine/iodide products which occurred during the US federal response and discuss its public health impact. Methods All calls to poison centers associated with the Japan incident were identified from March 11, 2011 to April 18, 2011 in NPDS. Exposure, demographic and health outcome information were collected. Calls about reported radiation exposures and KI or other iodine/iodide product ingestions were then categorized with regard to exposure likelihood based on follow-up information obtained from the PC where each call originated. Reported exposures were subsequently classified as probable exposures (high likelihood of exposure), probable non-exposures (low likelihood of exposure), and suspect exposure (unknown likelihood of exposure). Results We identified 400 calls to PCs associated with the incident, with 340 information requests (no exposure reported) and 60 reported exposures. The majority (n = 194; 57%) of the information requests mentioned one or more substances. Radiation was inquired about most frequently (n = 88; 45%), followed by KI (n = 86; 44%) and other iodine/iodide products (n = 47; 24%). Of the 60 reported exposures, KI was reported most frequently (n = 25; 42%), followed by radiation (n = 22; 37%) and other iodine/iodide products (n = 13; 22%). Among reported KI exposures, most were classified as probable exposures (n = 24; 96%); one was a probable non-exposure. Among reported other iodine/iodide product exposures, most were probable exposures (n = 10, 77%) and the rest were

  7. Collaborative Point Paper on Border Surveillance Technology

    DTIC Science & Technology

    2007-06-01

    Canadian companies, a brief description of their border surveillance systems/ products and the applicable environment(s) for each system/ product and/or...page, a brief description of its systems/ products , and the applicable nvironment(s) for each. The environments are labeled and color coe is green...SYSTEM/ PRODUCT MANUFACTURERS This section identifies foreign border surveillance companies a brief description of their systems/ products and the

  8. Bridge the gap: The need for harmonized regulatory and ethical standards for postmarketing observational studies.

    PubMed

    Urushihara, Hisashi; Parmenter, Louise; Tashiro, Shimon; Matsui, Kenji; Dreyer, Nancy

    2017-08-16

    Drug safety issues do not respect national borders. Hence, addressing a safety question may necessitate globally coordinated efforts between regulatory authorities and market authorization holders (MAHs) to draw reliable conclusions. Regulatory authorities have shared responsibility with MAHs sponsoring postmarketing nonintervention studies in determining study goals and design. Their shared accountabilities include what will be investigated and how the data will be retrieved to ensure appropriate study quality required for regulatory decision making. The need for a harmonized framework and ethical standards for postmarketing observational studies is well recognized but has been lacking even among the United States, European Union, and Japan, which are so-called International Conference on Harmonisation (ICH) regions. A recent update of the Council for International Organizations of Medical Sciences International Ethical Guidelines for Health-Related Research Involving Humans provides further clarification on provisions for informed consent and the role of research ethics committees. However, without incorporation into legislative structures, the future impact of these guidelines is uncertain. This lack of harmonization leads to a complex and uncertain framework for ethical review and for participant informed consent, resulting in numerous inefficiencies in the regulatory postmarketing observational studies. The regulatory frameworks for postmarketing observational studies conducted under the auspices of regulatory agencies in the 3 regions are reviewed, with a focus on ethical requirements and opportunities for efficiencies. Copyright © 2017 John Wiley & Sons, Ltd.

  9. 21 CFR 601.70 - Annual progress reports of postmarketing studies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Annual progress reports of postmarketing studies. 601.70 Section 601.70 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... revised schedule, as well as the reason(s) for the revision, if the schedule under paragraph (b)(7)...

  10. 77 FR 14402 - Draft Guidance on Classifying Significant Postmarket Drug Safety Issues; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ... to classifying a significant postmarket drug safety issue as a ``priority'' tracked safety issue (TSI) or a ``standard'' TSI, with the capability of elevating some priority TSIs to an ``emergency'' status... CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it...

  11. [Sample size calculation in clinical post-marketing evaluation of traditional Chinese medicine].

    PubMed

    Fu, Yingkun; Xie, Yanming

    2011-10-01

    In recent years, as the Chinese government and people pay more attention on the post-marketing research of Chinese Medicine, part of traditional Chinese medicine breed has or is about to begin after the listing of post-marketing evaluation study. In the post-marketing evaluation design, sample size calculation plays a decisive role. It not only ensures the accuracy and reliability of post-marketing evaluation. but also assures that the intended trials will have a desired power for correctly detecting a clinically meaningful difference of different medicine under study if such a difference truly exists. Up to now, there is no systemic method of sample size calculation in view of the traditional Chinese medicine. In this paper, according to the basic method of sample size calculation and the characteristic of the traditional Chinese medicine clinical evaluation, the sample size calculation methods of the Chinese medicine efficacy and safety are discussed respectively. We hope the paper would be beneficial to medical researchers, and pharmaceutical scientists who are engaged in the areas of Chinese medicine research.

  12. [Thinking on risk assessment and risk management of post-marketing Chinese medicine].

    PubMed

    Yu, Xueqing; Xie, Yanming; Wang, Yongyan

    2012-01-01

    Drug risk assessment and management is an important measure for reducing the adverse drug reaction and enhancing medication safety of the patient. Based on the concepts of drug risk assessment and risk management, and domestic and international drug risk management situation, this paper discusses the risk management of post-marketing Chinese medicine.

  13. 78 FR 20926 - Draft Guidance for Industry on Providing Postmarket Periodic Safety Reports in the International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-08

    ... Safety Reports in the International Conference on Harmonisation E2C(R2) Format (Periodic Benefit-Risk... ``Providing Postmarket Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report).'' This guidance is intended to inform applicants of the conditions under which FDA will...

  14. [Post-marketing drug safety-risk management plan(RMP)].

    PubMed

    Ezaki, Asami; Hori, Akiko

    2013-03-01

    The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

  15. 21 CFR 26.50 - Alert system and exchange of postmarket vigilance reports.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Alert system and exchange of postmarket vigilance reports. 26.50 Section 26.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL...

  16. 21 CFR 26.50 - Alert system and exchange of postmarket vigilance reports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Alert system and exchange of postmarket vigilance reports. 26.50 Section 26.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE...

  17. 21 CFR 26.50 - Alert system and exchange of postmarket vigilance reports.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Alert system and exchange of postmarket vigilance reports. 26.50 Section 26.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE...

  18. 21 CFR 26.50 - Alert system and exchange of postmarket vigilance reports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Alert system and exchange of postmarket vigilance reports. 26.50 Section 26.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE...

  19. 21 CFR 26.50 - Alert system and exchange of postmarket vigilance reports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Alert system and exchange of postmarket vigilance reports. 26.50 Section 26.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE...

  20. Deriving meaningful insights from clinical trial and postmarketing safety data: Perspectives from India.

    PubMed

    Harugeri, Anand; Shastri, Vineet; Patel, Chanakya

    2017-01-01

    Today, drug safety data collection in India is both manual and electronic with reporting of potential overlapping and duplicate data, which is likely incomplete for further review and analysis. Furthermore, standardized data collection and timelines are not aligned with international standards. Complete coverage of safety data from all sources throughout the life of the drug cannot be ensured. There is no requirement to submit periodic safety data in clinical trials to regulatory authority. There is clearly a lack of emphasis on deriving meaningful safety data insights for ensuring patient safety. Efforts toward the early detection of drug safety issues are minimal. There is no mandate to publicly disclose drug safety findings. Benefit-risk evaluation of investigational and marketed products cannot be assured merely through annual status reports and periodic safety update reports, respectively. Focused initiatives involving stakeholders from regulatory, health-care, and pharmaceutical industries are required to change the current situation and enable derivation of meaningful insights from safety data. Equal emphasis on assessing real-time safety of the drugs and protection of patients' rights, safety, and well-being is required. Periodic safety data reporting in clinical trials, proactive safety data collection related to potential safety concerns, electronic medical records, electronic expedited reporting, collection of targeted data from stakeholders, and standardized and harmonized data collection aligned to the International Council for Harmonization guidelines are required. The Central Drugs Standard Control Organization should implement requirements to submit Development Safety Update Reports, Periodic Benefit-Risk Evaluation Reports, and Risk Management Plans. Access to clinical trials and postmarketing safety data through central repository would enable researchers to explore the data for application in clinical practice.

  1. Deriving meaningful insights from clinical trial and postmarketing safety data: Perspectives from India

    PubMed Central

    Harugeri, Anand; Shastri, Vineet; Patel, Chanakya

    2017-01-01

    Today, drug safety data collection in India is both manual and electronic with reporting of potential overlapping and duplicate data, which is likely incomplete for further review and analysis. Furthermore, standardized data collection and timelines are not aligned with international standards. Complete coverage of safety data from all sources throughout the life of the drug cannot be ensured. There is no requirement to submit periodic safety data in clinical trials to regulatory authority. There is clearly a lack of emphasis on deriving meaningful safety data insights for ensuring patient safety. Efforts toward the early detection of drug safety issues are minimal. There is no mandate to publicly disclose drug safety findings. Benefit-risk evaluation of investigational and marketed products cannot be assured merely through annual status reports and periodic safety update reports, respectively. Focused initiatives involving stakeholders from regulatory, health-care, and pharmaceutical industries are required to change the current situation and enable derivation of meaningful insights from safety data. Equal emphasis on assessing real-time safety of the drugs and protection of patients' rights, safety, and well-being is required. Periodic safety data reporting in clinical trials, proactive safety data collection related to potential safety concerns, electronic medical records, electronic expedited reporting, collection of targeted data from stakeholders, and standardized and harmonized data collection aligned to the International Council for Harmonization guidelines are required. The Central Drugs Standard Control Organization should implement requirements to submit Development Safety Update Reports, Periodic Benefit-Risk Evaluation Reports, and Risk Management Plans. Access to clinical trials and postmarketing safety data through central repository would enable researchers to explore the data for application in clinical practice. PMID:28447016

  2. Market surveillance on non-halal additives incorporated in surimi based products using polymerase chain reaction (PCR)-southern hybridization analysis

    NASA Astrophysics Data System (ADS)

    Aravindran, S.; Sahilah, A. M.; Aminah, A.

    2014-09-01

    Halal surveillance on halal ingredients incorporated in surimi based products were studied using polymerase chain reaction (PCR)-southern hybridization on chip analysis. The primers used in this technique were targeted on mitochondria DNA (mtDNA) of cytochrome b (cyt b) gene sequence which able to differentiate 7 type (beef, chicken, duck, goat, buffalo, lamb and pork) of species on a single chip. 17 (n = 17*3) different brands of surimi-based product were purchased randomly from Selangor local market in January 2013. Of 17 brands, 3 (n = 3*3) brands were positive for chicken DNA, 1 (n = 1*3) brand was positive for goat DNA, and the remainder 13 brands (n = 13*3) have no DNA species detected. The sensitivity of PCR-southern hybridization primers to detect each meat species was 0.1 ng. In the present study, it is evidence that PCR-Southern Hybridization analysis offered a reliable result due to its highly specific and sensitive properties in detecting non-halal additive such as plasma protein incorporation in surimi-based product.

  3. Correlation of β-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program

    PubMed Central

    Bradford, Patricia A.; Biedenbach, Douglas J.; Wise, Mark G.; Hackel, Meredith; Sahm, Daniel F.

    2015-01-01

    The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of Enterobacteriaceae (excluding Proteeae and Serratia spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum β-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC90, 2 to 4 μg/ml) and aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml) consistently tested with low MIC values against colistin-resistant, ESBL-positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin-resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were Klebsiella pneumoniae. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of Enterobacteriaceae demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning. PMID:26666920

  4. Quality assessment of nonanthrax vaccination data in the Defense Medical Surveillance System (DMSS), 1998-2004.

    PubMed

    Davila, Jill C; Payne, Daniel C; Zhang, Yujia; Rose, Charles E; Aranas, Aaron; Hill, Andrew N; Ruscio, Bruce; McNeil, Michael M

    2008-03-17

    We assessed nonanthrax vaccination data quality in the Defense Medical Surveillance System (DMSS) during 1998-2004. We sampled servicemembers' medical charts at 28 Military Treatment Facilities and estimated the agreement between DMSS electronic and medical chart vaccination data, conditional on the data in the medical charts. Our analysis included 3831 individuals who received 39,305 nonanthrax vaccine doses. Yellow fever vaccine category had the highest conditional sensitivity for exact date match (83.4%; 95% CI = 80.1, 86.3); most vaccine categories' conditional sensitivities improved over time. Our study suggests DMSS vaccination data may be acceptable for post-marketing vaccine safety studies for certain vaccines and timeframes.

  5. Influenza surveillance

    PubMed Central

    Pereira, M.; Assaad, F. A.; Delon, P. J.

    1978-01-01

    The main objectives of influenza surveillance are: to measure the impact of the disease by collection and analysis of epidemiological information on morbidity and mortality, and to anticipate future epidemics and pandemics by the collection and analysis of influenza viruses. The World Health Organization's influenza programme is based on the collaboration of 98 national influenza centres in 70 countries and the 2 WHO Collaborating Centres in Atlanta and London. Epidemiological information may be based on morbidity figures derived from a variety of sources such as returns from physicians or hospitals; mortality statistics or new claims for sickness benefit; school or industrial absenteeism, etc. The laboratory aspects of influenza epidemiology are certainly more uniformly covered than the statistical aspects. Since the advent of the A/Hong Kong/1/68 (H3N2) influenza virus A subtype there have been a number of variants with antigenic ”drift” but only three succeeded in causing widespread epidemics: A/England/42/72, A/Port Chalmers/1/73, and A/Victoria/3/75. In 1972, the influenza B virus also showed some antigenic ”drift”, the new variants being characterized by B/Hong Kong/5/72. Whenever a new variant appears, the degree of protection afforded to the population by the available vaccine is assessed. In the light of these data, WHO publishes annually in the Weekly epidemiological record recommendations formulated by the WHO Collaborating Centres on vaccine composition. PMID:78771

  6. The surveillant assemblage.

    PubMed

    Haggerty, K D; Ericson, R V

    2000-12-01

    George Orwell's 'Big Brother' and Michel Foucault's 'panopticon' have dominated discussion of contemporary developments in surveillance. While such metaphors draw our attention to important attributes of surveillance, they also miss some recent dynamics in its operation. The work of Gilles Deleuze and Felix Guattari is used to analyse the convergence of once discrete surveillance systems. The resultant 'surveillant assemblage' operates by abstracting human bodies from their territorial settings, and separating them into a series of discrete flows. These flows are then reassembled in different locations as discrete and virtual 'data doubles'. The surveillant assemblage transforms the purposes of surveillance and the hierarchies of surveillance, as well as the institution of privacy.

  7. Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004.

    PubMed

    Nakayama, Tetsuo; Onoda, Kazumasa

    2007-01-05

    General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain-Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1-0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in

  8. The out-of-focus bias in drug surveillance.

    PubMed

    Gnädinger, Markus; Mellinghoff, Hans-Ulrich

    2013-03-01

    Existing drug safety systems with phase II and III studies and post-marketing surveillance by principle do not allow for the recognition of an important class of adverse drug reactions (ADRs). ADRs that are resistant to being detected reliably may a) appear as if they are age-related chronic diseases, which also manifest themselves in a high degree without drug treatment, b) arise in "old" drugs, c) arise during long-term application, and d) arise with the administration to frail and aged populations. "Silent" and multi-factorial health problems evolving from long-term drug treatment must therefore be addressed with a systematic search strategy, as a third track along with the phase II and III studies and spontaneous reporting systems which still exist.

  9. Non-clinical Post-Marketing Commitments for newly licenced pharmaceuticals.

    PubMed

    Reeve, Lesley M

    2009-11-01

    There are clear minimum requirements for non-clinical (toxicology) studies which are needed prior to human exposure to a potential new pharmaceutical and additional studies are needed in an ongoing manner to support clinical development and marketing [ICH, 2009. ICH M3(R2) Non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals (CPMP/ICH/286/95). Adopted June 2009, effective December 2009.] The pharmaceutical industry is under increasing pressure to reduce costs and reduce, refine and replace the use of animals, as far as possible. Hence any increase in regulatory requirements for non-clinical safety data could have a significant impact both on the economic and ethical considerations of drug development. It is, therefore, of interest that further non-clinical studies are required by the Regulatory Authorities for a small but increasing proportion of drug product applications at the marketing approval/data review stage. These studies are known as Post-Marketing Commitments (PMCs). Available information on non-clinical PMCs was collated using drug product information from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA), resulting in a combined data set of 162 studies. Non-clinical PMCs comprised 9.8% and 6.5% of total PMCs for products authorised by the EMEA (Centralised Procedure) and FDA, respectively. Non-clinical PMCs increased with increasing date of approval, despite increased regulatory information available to guide Applicants. Furthermore, the increase reflected an increased proportion of applications with non-clinical PMCs, not an increase in overall numbers of applications. There was no clear correspondence between the publication dates of relevant guidelines and increases in specific non-clinical PMC study types, when the data were analysed by non-clinical study category, target population/indication or compound class. Possible exceptions were some

  10. Public participation in radiological surveillance.

    PubMed

    Hanf, R W; Schreckhise, R G; Patton, G W; Poston, T M; Jaquish, R E

    1997-10-01

    In 1989, Pacific Northwest National Laboratory developed a program, for the U.S. Department of Energy, to involve local citizens in environmental surveillance at the Hanford Site. The Community-Operated Environmental Surveillance Program was patterned after similar community-involvement efforts at the Nevada Test Site and the Three Mile Island nuclear facility. Its purpose is to increase the flow of information to the public, thereby enhancing the public's awareness and understanding of surveillance activities. The program consists of two components: radiological air monitoring at nine offsite locations and agricultural product sampling at selected locations near the site. At each air-monitoring station, two local school teachers collect air particulate samples and operate equipment to monitor ambient radiation levels. Atmospheric tritium samples (as water vapor) are also collected at some locations. Four of the air-monitoring stations include large, colorful informational displays for public viewing. These displays provide details on station equipment, sample types, and sampling purposes. Instruments in the displays also monitor, record, and show real-time ambient radiation readings (measured with a pressurized ionization chamber) and meteorological conditions. Agricultural products, grown primarily by middle-school-aged students, are obtained from areas downwind of the site. Following analysis of these samples, environmental surveillance staff visit the schools to discuss the results with the students and their teachers. The data collected by these air and agricultural sampling efforts are summarized with other routinely collected sitewide surveillance data and reported annually in the Hanford Site environmental report.

  11. Time Series Analysis of the Effectiveness and Safety of Capsule Endoscopy between the Premarketing and Postmarketing Settings: A Meta-Analysis

    PubMed Central

    Iijima, Kazuo; Umezu, Mitsuo; Iwasaki, Kiyotaka

    2016-01-01

    Background Clinical studies for assessing the effectiveness and safety in a premarketing setting are conducted under time and cost constraints. In recent years, postmarketing data analysis has been given more attention. However, to our knowledge, no studies have compared the effectiveness and the safety between the pre- and postmarketing settings. In this study, we aimed to investigate the importance of the postmarketing data analysis using clinical data. Methods and Findings Studies on capsule endoscopy with rich clinical data in both pre- and postmarketing settings were selected for the analysis. For effectiveness, clinical studies published before October 10, 2015 comparing capsule endoscopy and conventional flexible endoscopy measuring the detection ratio of obscure gastrointestinal bleeding were selected (premarketing: 4 studies and postmarketing: 8 studies) from PubMed (MEDLINE), Cochrane Library, EMBASE and Web of Science. Among the 12 studies, 5 were blinded and 7 were non-blinded. A time series meta-analysis was conducted. Effectiveness (odds ratio) decreased in the postmarketing setting (premarketing: 5.19 [95% confidence interval: 3.07–8.76] vs. postmarketing: 1.48 [0.81–2.69]). The change in odds ratio was caused by the increase in the detection ratio with flexible endoscopy as the control group. The efficacy of capsule endoscopy did not change between pre- and postmarketing settings. Heterogeneity (I2) increased in the postmarketing setting because of one study. For safety, in terms of endoscope retention in the body, data from the approval summary and adverse event reports were analyzed. The incidence of retention decreased in the postmarketing setting (premarketing: 0.75% vs postmarketing: 0.095%). The introduction of the new patency capsule for checking the patency of the digestive tract might contribute to the decrease. Conclusions Effectiveness and safety could change in the postmarketing setting. Therefore, time series meta-analyses could be

  12. Time Series Analysis of the Effectiveness and Safety of Capsule Endoscopy between the Premarketing and Postmarketing Settings: A Meta-Analysis.

    PubMed

    Iijima, Kazuo; Umezu, Mitsuo; Iwasaki, Kiyotaka

    2016-01-01

    Clinical studies for assessing the effectiveness and safety in a premarketing setting are conducted under time and cost constraints. In recent years, postmarketing data analysis has been given more attention. However, to our knowledge, no studies have compared the effectiveness and the safety between the pre- and postmarketing settings. In this study, we aimed to investigate the importance of the postmarketing data analysis using clinical data. Studies on capsule endoscopy with rich clinical data in both pre- and postmarketing settings were selected for the analysis. For effectiveness, clinical studies published before October 10, 2015 comparing capsule endoscopy and conventional flexible endoscopy measuring the detection ratio of obscure gastrointestinal bleeding were selected (premarketing: 4 studies and postmarketing: 8 studies) from PubMed (MEDLINE), Cochrane Library, EMBASE and Web of Science. Among the 12 studies, 5 were blinded and 7 were non-blinded. A time series meta-analysis was conducted. Effectiveness (odds ratio) decreased in the postmarketing setting (premarketing: 5.19 [95% confidence interval: 3.07-8.76] vs. postmarketing: 1.48 [0.81-2.69]). The change in odds ratio was caused by the increase in the detection ratio with flexible endoscopy as the control group. The efficacy of capsule endoscopy did not change between pre- and postmarketing settings. Heterogeneity (I2) increased in the postmarketing setting because of one study. For safety, in terms of endoscope retention in the body, data from the approval summary and adverse event reports were analyzed. The incidence of retention decreased in the postmarketing setting (premarketing: 0.75% vs postmarketing: 0.095%). The introduction of the new patency capsule for checking the patency of the digestive tract might contribute to the decrease. Effectiveness and safety could change in the postmarketing setting. Therefore, time series meta-analyses could be useful to continuously monitor the effectiveness

  13. USE OF MAILBOX APPROACH, VIDEO SURVEILLANCE, AND SHORT-NOTICE RANDOM INSPECTIONS TO ENHANCE DETECTION OF UNDECLARED LEU PRODUCTION AT GAS CENTRIFUGE ENRICHMENT PLANTS.

    SciTech Connect

    BOYER, B.D.; GORDON, D.M.; JO, J.

    2006-07-16

    Current safeguards approaches used by the IAEA at gas centrifuge enrichment plants (GCEPs) need enhancement in order to detect undeclared LEU production with adequate detection probability. ''Mailbox'' declarations have been used in the last two decades to verify receipts, production, and shipments at some bulk-handling facilities (e.g., fuel-fabrication plants). The operator declares the status of his plant to the IAEA on a daily basis using a secure ''Mailbox'' system such as a secure tamper-resistant computer. The operator agrees to hold receipts and shipments for a specified period of time, along with a specified number of annual inspections, to enable inspector access to a statistically large enough population of UF{sub 6} cylinders and fuel assemblies to achieve the desired detection probability. The inspectors can access the ''Mailbox'' during randomly timed inspections and then verify the operator's declarations for that day. Previously, this type of inspection regime was considered mainly for verifying the material balance at fuel-fabrication, enrichment, and conversion plants. Brookhaven National Laboratory has expanded the ''Mailbox'' concept with short-notice random inspections (SNRIs), coupled with enhanced video surveillance, to include declaration and verification of UF{sub 6} cylinder operational data to detect activities associated with undeclared LEU production at GCEPs. Since the ''Mailbox'' declarations would also include data relevant to material-balance verification, these randomized inspections would replace the scheduled monthly interim inspections for material-balance purposes; in addition, the inspectors could simultaneously perform the required number of Limited-Frequency Unannounced Access (LFUA) inspections used for HEU detection. This approach would provide improved detection capabilities for a wider range of diversion activities with not much more inspection effort than at present.

  14. [Process and key points of clinical literature evaluation of post-marketing traditional Chinese medicine].

    PubMed

    Liu, Huan; Xie, Yanming

    2011-10-01

    The clinical literature evaluation of the post-marketing traditional Chinese medicine is a comprehensive evaluation by the comprehensive gain, analysis of the drug, literature of drug efficacy, safety, economy, based on the literature evidence and is part of the evaluation of evidence-based medicine. The literature evaluation in the post-marketing Chinese medicine clinical evaluation is in the foundation and the key position. Through the literature evaluation, it can fully grasp the information, grasp listed drug variety of traditional Chinese medicines second development orientation, make clear further clinical indications, perfect the medicines, etc. This paper discusses the main steps and emphasis of the clinical literature evaluation. Emphasizing security literature evaluation should attach importance to the security of a comprehensive collection drug information. Safety assessment should notice traditional Chinese medicine validity evaluation in improving syndrome, improveing the living quality of patients with special advantage. The economics literature evaluation should pay attention to reliability, sensitivity and practicability of the conclusion.

  15. [Discussion on development of four diagnostic information scale for clinical re-evaluation of postmarketing herbs].

    PubMed

    He, Wei; Xie, Yanming; Wang, Yongyan

    2011-12-01

    Post-marketing re-evaluation of Chinese herbs can well reflect Chinese medicine characteristics, which is the most easily overlooked the clinical re-evaluation content. Since little attention has been paid to this, study on the clinical trial design method was lost. It is difficult to improving the effectiveness and safety of traditional Chinese medicine. Therefore, more attention should be paid on re-evaluation of the clinical trial design method point about tcm syndrome such as the type of research program design, the study of Chinese medical information collection scale and statistical analysis methods, so as to improve the clinical trial design method study about tcm syndrome of Chinese herbs postmarketing re-evalutation status.

  16. [Opportunity and challenge of post-marketing evaluation of traditional Chinese medicine].

    PubMed

    Du, Xiao-Xi; Song, Hai-Bo; Ren, Jing-Tian; Yang, Le; Guo, Xiao-Xin; Pang, Yu

    2014-09-01

    Post-marketing evaluation is a process which evaluate the risks and benefits of drug clinical application comprehensively and systematically, scientific and systematic results of post-marketing evaluation not only can provide data support for clinical application of traditional Chinese medicine, but also can be a reliable basis for the supervision department to develop risk control measures. With the increasing demands for treatment and prevention of disease, traditional Chinese medicine has been widely used, and security issues are also exposed. How to find risk signal of traditional Chinese medicine in the early stages, carry out targeted evaluation work and control risk timely have become challenges in the development of traditional Chinese medicine industry.

  17. Investigation of an outbreak of anemia cases at an Army trinitrotoluene munitions production plant from 2004 to 2005 and subsequent surveillance 2005-2013.

    PubMed

    Mallon, Timothy M; Ortiz, Jose M; Candler, William H; Rogers, Gregory; Hillburn, Richard

    2014-11-01

    Investigate an outbreak of anemia that occurred at an Army trinitrotoluene (TNT) munitions production facility in 2004-2005 and describe subsequent medical surveillance efforts between 2005 and 2013. A retrospective, cross-sectional investigation of anemia cases and exposure levels was conducted to target corrective engineering and administrative changes needed to reduce TNT levels and anemia cases. Mean TNT exposure levels decreased from 1.2 to 0.08 mg/m(3) between 2004 and 2012, but the trend was not statistically significant. Anemia cases rose from 17 to 38 between 2004 and 2011 and cases declined from 4 to 0 between 2012 and 2013. The overall trend in cases was not statistically significant. TNT levels rose at a munitions plant until ventilation changes reduced exposures. Despite this, anemia cases continued to rise until the commander held workers accountable for failing to wear PPE and motivated them to wear respirators to avoid a loss in pay. The case definition of anemia was revised to be consistent with the case definition used by private physicians who practiced in the community. Better coveralls are needed, which are easy to wear, reduce static discharge, and prevent TNT skin absorption. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  18. Using high-dimensional propensity scores to automate confounding control in a distributed medical product safety surveillance system.

    PubMed

    Rassen, Jeremy A; Schneeweiss, Sebastian

    2012-01-01

    Distributed medical product safety monitoring systems such as the Sentinel System, to be developed as a part of Food and Drug Administration's Sentinel Initiative, will require automation of large parts of the safety evaluation process to achieve the necessary speed and scale at reasonable cost without sacrificing validity. Although certain functions will require investigator intervention, confounding control is one area that can largely be automated. The high-dimensional propensity score (hd-PS) algorithm is one option for automated confounding control in longitudinal healthcare databases. In this article, we discuss the use of hd-PS for automating confounding control in sequential database cohort studies, as applied to safety monitoring systems. In particular, we discuss the robustness of the covariate selection process, the potential for over- or under-selection of variables including the possibilities of M-bias and Z-bias, the computation requirements, the practical considerations in a federated database network, and the cases where automated confounding adjustment may not function optimally. We also outline recent improvements to the algorithm and show how the algorithm has performed in several published studies. We conclude that despite certain limitations, hd-PS offers substantial advantages over non-automated alternatives in active product safety monitoring systems.

  19. Safety Overview of Postmarketing and Clinical Experience of Sodium Oxybate (Xyrem): Abuse, Misuse, Dependence, and Diversion

    PubMed Central

    Wang, Y. Grace; Swick, Todd J.; Carter, Lawrence P.; Thorpy, Michael J.; Benowitz, Neal L.

    2009-01-01

    Study Objectives: This study reviewed the cumulative postmarketing and clinical safety experience with sodium oxybate (Xyrem®), a treatment approved for cataplexy and excessive daytime sleepiness in narcolepsy. Study objectives were to investigate the occurrence of abuse/misuse of sodium oxybate since first market introduction in 2002, classify cases using DSM-IV criteria for substance abuse and dependence, and describe specific characteristics of these cases. Methods: We retrospectively reviewed postmarketing spontaneous adverse event (AE) reports from 15 countries for all cases containing reporting terminology related to abuse/misuse to determine its occurrence. All death cases independent of causality were reviewed to identify associated risk factors. Results: Approximately 26,000 patients worldwide received sodium oxybate from first market introduction in 2002 through March 2008. Of those 26,000 patients, 0.2% reported ≥ 1 of the events studied. These included 10 cases (0.039%) meeting DSM-IV abuse criteria, 4 cases (0.016%) meeting DSM-IV dependence criteria, 8 cases (0.031%, including 3 of the previous 4) with withdrawal symptoms reported after discontinuation of sodium oxybate, 2 confirmed cases (0.008%) of sodium oxybate–facilitated sexual assault, 8 cases (0.031%) of overdose with suicidal intent, 21 deaths (0.08%) in patients receiving sodium oxybate treatment with 1 death known to be related to sodium oxybate, and 3 cases (0.01%) of traffic accidents involving drivers taking sodium oxybate. During this period, approximately 600,000 bottles of sodium oxybate were distributed, and 5 incidents (0.0009%) of diversion were reported. Conclusion: Cumulative postmarketing and clinical experience indicates a very low risk of abuse/misuse of sodium oxybate. Citation: Wang YG; Swick TJ; Carter LP; Thorpy MJ; Benowitz NL. Safety overview of postmarketing and clinical experience of sodium oxybate (xyrem): abuse, misuse, dependence, and diversion. J Clin Sleep

  20. Community pharmacist surveillance of hypertension in pregnancy

    PubMed Central

    Tsao, Nicole W.; Lynd, Larry D.; Thomas, Jamie M.; Ferreira, Ema

    2014-01-01

    Background: Hypertensive disorders of pregnancy (HDP) are associated with serious maternal and perinatal complications. For nonsevere hypertension, there is a lack of consensus regarding treatment during pregnancy and while breastfeeding. Further, there is considerable variability in guidelines for antihypertensive drug choices. As part of a Drug Safety and Effectiveness Network (DSEN)–funded project, we piloted a novel surveillance strategy in which community pharmacists recruited pregnant and breastfeeding women to monitor their blood pressure and medication use and to provide education on HDP. Methods: Participating pharmacists were required to complete a certified training program, identify and recruit patients who were pregnant or breastfeeding, obtain informed consent, administer a patient questionnaire and complete an initial case report form for enrolled patients. Study outcomes included the feasibility of community pharmacists to enroll patients and carry out study-related documentation and follow-up. The criteria for success in this pilot study included the ability of pharmacists to recruit 10 participants per pharmacy. Results: 178 community pharmacies across British Columbia agreed to participate in this feasibility study, of which 63 pharmacists completed the study training. Of these, only 21 pharmacists recruited at least 1 patient and 1 pharmacist met the success criteria. Overall, 51 patients were enrolled, 2 withdrew from the study and 7 patients were diagnosed with HDP. Antihypertensive medications used by patients included methyldopa and labetalol. Conclusions: While postmarketing surveillance is an important tool for the assessment of drug safety in the pregnant and breastfeeding patient population, the feasibility of community pharmacists taking on this role was not successfully demonstrated. PMID:25364340

  1. Dissolution Failure of Solid Oral Drug Products in Field Alert Reports.

    PubMed

    Sun, Dajun; Hu, Meng; Browning, Mark; Friedman, Rick L; Jiang, Wenlei; Zhao, Liang; Wen, Hong

    2017-01-17

    From 2005 to 2014, 370 data entries of dissolution failures of solid oral drug products were assessed with respect to the solubility of drug substances, dosage forms [immediate release (IR) vs. modified release (MR)], and manufacturers (brand name vs. generic). The study results show that the solubility of drug substances does not play a significant role in dissolution failures; however, MR drug products fail dissolution tests more frequently than IR drug products. When multiple variables were analyzed simultaneously, poorly water-soluble IR drug products failed the most dissolution tests, followed by poorly soluble MR drug products and very soluble MR drug products. Interestingly, the generic drug products fail dissolution tests at an earlier time point during a stability study than the brand name drug products. Whether the dissolution failure of these solid oral drug products has any in vivo implication will require further pharmacokinetic, pharmacodynamic, clinical, and drug safety evaluation. Food and Drug Administration is currently conducting risk-based assessment using in-house dissolution testing, physiologically based pharmacokinetic modeling and simulation, and post-market surveillance tools. At the meantime, this interim report will outline a general scheme of monitoring dissolution failures of solid oral dosage forms as a pharmaceutical quality indicator.

  2. General Medical Surveillance Program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background on the General Medical Surveillance Program at LeRC is presented. The purpose of the General Medical Surveillance Program at LeRC is outlined, and the specifics of the program are discussed.

  3. Respiratory health surveillance in a toluene di-isocyanate production unit, 1967-97: clinical observations and lung function analyses

    PubMed Central

    Ott, M; Klees, J.; Poche, S.

    2000-01-01

    OBJECTIVES—To characterise irritant and allergic airway responses and assess changes in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) relative to exposure to toluene di-isocyanate (TDI).
METHODS—Employees (n=313) ever assigned to a TDI production unit for ⩾3 months (1967-92) were identified from personnel records along with 158 frequency matched referents without known exposure to TDI. Reports made during visits to the occupational clinic of incidents related to exposure to TDI and annual periodic examination results (questionnaire, physical findings, and spirometry) were abstracted and assessed relative to industrial hygiene estimates of exposure to TDI.
RESULTS—Mean 8 hour time weighted average estimates of TDI concentrations ranged from 9.9 ppb in jobs with potentially high exposure during the early years of plant operations to 0.5 ppb in jobs with potentially low exposure in more recent years. The corresponding rates of visits to the clinic due to incidents of exposure to TDI (including both irritant and allergic airway responses) declined from 20.5 to 1.0 visits per 100 years of employment at the unit. The annual incidence of asthma induced by TDI declined from 1.8% before 1980 to 0.7% afterwards. Neither cross sectional nor longitudinal analyses of FVC and FEV1 showed significant dose-response findings relative to exposure to TDI across the total exposed population. Among cases of occupational asthma there was an apparent initial decline in FEV1 within 2 years of first reporting symptoms, but not an accelerated rate of decline in follow up tests from 4-30 years after induction of asthma.
CONCLUSIONS—Occurrences of both asthma induced by TDI and irritant airway responses due to exposure to TDI were found in this cohort, but there was no relation between cumulative exposure to TDI and irreversible airflow obstruction as assessed by spirometry.


Keywords: toluene di-isocyanate; lung function

  4. Post-marketing safety evaluation of S-1 in patients with inoperable or recurrent breast cancer: especially in patients treated with S-1 + trastuzumab.

    PubMed

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-09-01

    The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. At least one adverse drug reaction was encountered by 858 patients, with an overall incidence of 63.0% (858/1361). The incidence of Grade 3 or higher adverse drug reactions in a descending order was 14.7% (200/1361). In this study, the most common combination drug was trastuzumab. The overall incidence of adverse drug reactions was 63.5% (431/679 patients) in patients treated with S-1 alone, and 55.9% (66/118 patients) in patients treated with S-1 + trastuzumab. Monotherapy with S-1 or combination therapy with S-1 + trastuzumab was well tolerated for inoperable or recurrent breast cancer patients.

  5. Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study.

    PubMed

    Yan, Ying-Ying; Yang, Yi-Heng; Wang, Wei-Wei; Pan, Yu-Ting; Zhan, Si-Yan; Sun, Ming-Yang; Zhang, Hong; Zhai, Suo-Di

    2017-01-01

    Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed. To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice. This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520. Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50-73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the approved indication (RR = 0.655, P<0.001, 95%CI [0.532~0.807]) was associated with lower incidence of ADEs. SMDS was well tolerated in the general population. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. Several risk factors of its ADEs have been identified. It is recommended to follow the instructions when prescribing and administrating SMDS in the real world clinical practice.

  6. ABSORB: Postmarketing Surveillance Registry to Monitor the Everolimus-eluting Bioresorbable Vascular Scaffold in Patients With Coronary Artery Disease

    ClinicalTrials.gov

    2016-12-08

    Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Coronary Restenosis; Heart Diseases; Coronary Stenosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

  7. Comparing the strengths and weaknesses of observational and experimental studies using a postmarketing surveillance study as a protypic example.

    PubMed

    Furst, D E

    1993-10-01

    A recent prospective, observational study in rheumatoid arthritis patients indicated that the addition of hydroxychloroquine to either aspirin or methotrexate therapy decreased the incidence of hepatic enzyme abnormalities. This interesting finding is of potential clinical importance, but its validity needs to be examined in terms of the potential confounders inherent in observational studies. Although one of the study's strengths is its derivation from "real-life" data, some potential confounders that might weaken the data include a need to examine whether any scientific rationale can be discerned for the observation; examination of control-case matching (issues of randomization and baseline disease characteristics); the potential for attribution bias; data-collection methods (prospective versus retrospective, uniform versus chart review); and equivalency of treatment protocols, dosing regimens, and concomitant medications. Potential scientific rationale exists for the observed interaction, and data collection is both uniform and prospective. These strengths are confounded by the inevitable lack of randomization in observational studies, the potential for differences in baseline disease characteristics, attribution bias, a lack of controlled dosing regimens and treatment protocols, and an assumption that all nonsteroid antiinflammatory drugs are alike (which is not true). On balance, the hypothesis generated by these data is compelling enough to deserve further testing in both observational and experimental settings.

  8. Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study

    PubMed Central

    Yan, Ying-Ying; Yang, Yi-Heng; Wang, Wei-Wei; Pan, Yu-Ting; Zhan, Si-Yan; Sun, Ming-Yang; Zhang, Hong; Zhai, Suo-Di

    2017-01-01

    Background Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed. Objective To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice. Methods This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520. Results Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50–73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the approved indication (RR = 0.655, P<0.001, 95%CI [0.532~0.807]) was associated with lower incidence of ADEs. Conclusions SMDS was well tolerated in the general population. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. Several risk factors of its ADEs have been identified. It is recommended to follow the instructions when prescribing and administrating SMDS in the real world clinical practice. PMID:28125608

  9. 77 FR 9256 - Design and Methodology for Postmarket Surveillance Studies Under Section 522 of the Federal Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-16

    ... stakeholders with experience in epidemiology, statistics, and biomedical research to advance the design and... epidemiology, statistics, and biomedical research in the scientific community to advance the design and...

  10. Evaluation of Aryoseven Safety (Recombinant Activated Factor VII) in Patients with Bleeding Disorders (An Observational Post-Marketing Surveillance Study)

    PubMed Central

    Toogeh, Gholamreza; Abolghasemi, Hassan; Eshghi, Peyman; Managhchi, Mohammadreza; Shaverdi-niasari, Mohammadreza; Karimi, Katayoon; Roostaei, Samin; Emran, Neda; Abdollahi, Alireza

    2016-01-01

    Background: Recombinant activated factor VII induces hemostasis in patients with coagulopathy disorders. AryoSeven™ as a safe Iranian Recombinant activated factor VII has been available on our market. This study was performed to establish the safety of AryoSeven on patients with coagulopathy disorder. Methods: This single-center, descriptive, cross sectional study was carried out in Thrombus and Homeostasis Research Center ValiAsr Hospital during 2013-2014. Fifty one patients with bleeding disorders who received at least one dose of Aryoseven were enrolled. Patients’ demographic data and adverse effect of drug and reaction related to Aryoseven or previous usage of Recombinant activated FVII were recorded in questionnaires. Finally data were analyzed to compare side effects of Aryoseven and other Recombinant activated FVII brands. Results: Aryoseven was prescribed for 51 Patients. Of all participants with mean age 57.18+21.38 yr, 31 cases were male and 26 subjects had past history of recombinant activated FVII usage. Glanzman was the most frequent disorder followed by congenital FVII deficiency, hemophilia with inhibitors, factor 5 deficiency, acquired hemophilia, hemophilia A with inhibitor, and hemophilia A or B with inhibitor. The majority of bleeding episodes had occurred in joints. Three patients (5.9%) complained about adverse effects of Aryoseven vs. 11.5 % about adverse effects of other brands. However this difference was not significant, statistically. Conclusion: Based on monitor patients closely for any adverse events, we concluded that Aryoseven administration under careful weighing of benefit versus potential harm may comparable with other counterpart drugs. PMID:27799968

  11. Italian post-marketing surveillance for adverse event reports after MF59-adjuvanted H1N1v vaccination.

    PubMed

    Parretta, Elisabetta; Ianniello, Benedetta; Ferrazin, Fernanda; Rossi, Francesco; Capuano, Annalisa

    2011-05-09

    According to European recommendations, the Italian Medicines Agency (AIFA) required close monitoring of the safety of the MF59-adjuvanted H1N1v vaccine, which was the only vaccine available in Italy for prophylaxis of the A/H1N1 (2009) pandemic influenza. From October 2009 to June 2010, the Italian Pharmacovigilance Adverse Event (AE) Spontaneous Reporting System [Rete Nazionale Farmacovigilanza] (RNF) received 1330 reports of AEs temporally related with the pandemic influenza vaccination out of a total of 924,057 doses administered. Among these, 1,162 (87.37%) AE reports were classified 'non serious', 91 (6.84%) 'serious', 3 (0.23%) had a fatal outcome and 74 (5.56%) did not include the degree of seriousness. Among the serious AE reports, some unexpected AEs emerged. Even though some typical vaccine safety issues which emerged should be further explored, such as vaccination in pregnancy, the analysis of all AE reports sent to RNF shows that the vaccine has a well-tolerated safety profile which resembles that of the already available seasonal influenza vaccines. This contrasts with the widespread public concern about its safety, which has been one of the major causes of the low vaccination rate observed in Italy, as well as in other countries.

  12. Safety of Japanese encephalitis live attenuated vaccination in post-marketing surveillance in Guangdong, China, 2005-2012.

    PubMed

    Liu, Yu; Lin, Hualiang; Zhu, Qi; Wu, Chenggang; Zhao, Zhanjie; Zheng, Huizhen

    2014-03-26

    We reviewed the adverse events following immunization of live attenuated Japanese encephalitis vaccine in Guangdong Province, China. During the period of 2005-2012, 23 million doses of live attenuated Japanese encephalitis vaccine were used and 1426 adverse events were reported (61.24 per million doses); of which, 570 (40%) were classified as allergic reactions (24.48 per million doses), 31 (2%) were neurologic events (1.33 per million doses), and 36 (2.5%) were diagnosed as serious adverse events (1.55 per million doses). This study suggests that the JEV-L has a reasonable safety profile, most adverse events are relatively mild, with relatively rare neurologic events being observed.

  13. Post-marketing surveillance study to assess the safety and tolerability of an Inactivated Poliomyelitis Vaccine in Indian children.

    PubMed

    Sharma, Hitt; Dhere, Rajeev; Parekh, Sameer; Shewale, Sunil

    2017-08-28

    To evaluate the incidence of adverse events following administration of an Inactivated poliomyelitis vaccine (IPV) manufactured by Serum Institute of India Pvt. Ltd., Pune, India. A single 0.5 ml dose of the IPV was administered intramuscularly to children attending private clinics or out-patient department of hospitals for routine immunization across different cities in India. They were observed over a period of 30 days for local or systemic adverse events and rare case of anaphylaxis, if any. A total of 2210 children were enrolled of which 2120 children received the vaccine within primary immunization series and 90 children received booster dose. The common adverse events reported were pain, erythema, swelling and fever. No serious adverse event was reported during the study period. Poliomyelitis vaccine (Inactivated) manufactured by Serum Institute of India Pvt. Ltd., Pune can be safely administered to children following the Expanded Programme on Immunization or World Health Organization recommended immunization schedule.

  14. Food and farm products surveillance

    SciTech Connect

    Poston, T.M.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the radiological analyses performed on food and farm samples collected during 1994. The food and farm sampling design addresses the potential influence of Hanford Site releases. Details of the sampling design and radionuclides analyzed are included in this section.

  15. [Basic requirements on post-marketing clinical re-evaluation of chinese medicine and phase IV clinical trials].

    PubMed

    Xie, Yanming; Wang, Yanping; Tian, Feng; Wang, Yongyan

    2011-10-01

    As information on safety and effectiveness is not comprehensive, gained from the researches for listing approval of Chinese medicine, it is very necessary to conduct post-marketing clinical re-evaluation of Chinese medicine. Effectiveness, safety and economic evaluation are three main aspects of post-marketing clinical re-evaluation. In this paper, the difference and relations between the post-marketing clinical re-evaluation and the phase IV clinical trials were discussed, and the basic requests and suggestions were proposed, according to the domestic and foreign relevant regulations and experts' suggestions, and discussed the requirements of the phase IV clinical trials on indications, design methods, inclusion and exclusion criteria, sample size, etc.

  16. [Research about re-evaluation of screening of traditonal Chinese medicine symptoms item of post-marketing medicine Xuezhikang].

    PubMed

    He, Wei; Xie, Yanming; Wang, Yongyan

    2011-10-01

    The purpose of post-marketing Chinese medicine re-evaluation is to identify Chinese medicine clinical indications, while designing scientific and rational of Chinese medicine symptoms items are important to the result of symptoms re-evaluation. This study give screening of traditional Chinese medicine(TCM) symptoms item of post-marketing medicine Xuezhikang re-evaluation as example that reference to principle dyslipidemia clinical research, academic dissertations, Xuezhikang directions, clinical expert practice experience etc. while standardization those symptom names and screening 41 dyslipidemia common symptoms. Furthermore, this paper discuss about the accoerdance and announcements when screening symptoms item, so as to providing a research thread to manufacture PRO chart for post-marketing medicine re-evaluation.

  17. [Post-marketing clinical study of traditional Chinese medicine--lessons learned from comprehensive evaluation of Fufang Zaoren capsule].

    PubMed

    Qing, Shan; Gao, Lin; Zhang, Li; Jia, Jian-Ping; Liu, Xin-Min; Ji, Shao-Liang; Yang, Xiao-Hui

    2013-11-01

    By comprehensive review and analysis of post-marketing clinical research on the efficacy and safety,we concluded that Fufang Zaoren capsule has certain therapeutic effects for insomnia, although current clinical research design needs improving. The post-marketing clinical studies also showed that it causes several adverse reactions at the recommended doses, such as chills, fever, dizziness, nausea, shortness of breath, chest tightness and palpitations, whereas high doses of Fufang Zaoren capsule can cause delayed extrapyramidal symptoms. Health Canada government website also prompted the L-tetrahydropalmatine in Fufang Zaoren capsule caused liver damage in pregnant women. The authors summarized the risk points, factors and risk control in the clinical use of Fufang Zaoren capsule and also present their perspective on the research status, existing problems and corresponding countermeasures in the post-marketing clinical re-evaluation of traditional Chinese medicine.

  18. Audits and surveillance: A functional quality surveillance system

    SciTech Connect

    Smart, R.J.; Duda, J.E.

    1987-03-01

    The implementation of a quality surveillance program can be painless and productive. The system described in this report has been in use at the Fast Flux Test Facility (FFTF) for more than a year and effectively fills the void between audits and inspections. Recognized benefits of this system include: minimum administrative overhead; excellent management overview; ease of implementing trending efforts; audit supplement; fully computerization; lower cost than traditional methods; early problem detection, adaptability to other projects and facilities.

  19. Environmental surveillance master sampling schedule

    SciTech Connect

    Bisping, L E

    1992-01-01

    Environmental surveillance of the Hanford Site and surrounding areas is conducted by the Pacific Northwest Laboratory (PNL) for the US Department of Energy (DOE). This document contains the planned schedule for routine sample collection for the Surface Environmental Surveillance Project (SESP) and Ground-Water Monitoring Project. Samples for radiological analyses include Air-Particulate Filter, gases and vapor; Water/Columbia River, Onsite Pond, Spring, Irrigation, and Drinking; Foodstuffs/Animal Products including Whole Milk, Poultry and Eggs, and Beef; Foodstuffs/Produce including Leafy Vegetables, Vegetables, and Fruit; Foodstuffs/Farm Products including Wine, Wheat and Alfalfa; Wildlife; Soil; Vegetation; and Sediment. Direct Radiation Measurements include Terrestrial Locations, Columbia River Shoreline Locations, and Onsite Roadway, Railway and Aerial, Radiation Surveys.

  20. [Clinical orientation of post-marketing Chinese patent drugs: an evidence-based practice].

    PubMed

    Shang, Hong-Cai; Zhang, Bo-Li; Li, You-Ping

    2008-09-01

    Unclear clinical orientation in practice has become one of the common problems with the effective application of famous and excellent Chinese herbal drugs, consequently restricting their development. The authors suggest that there are three aspects to be considered in dealing with this problem. Clinical evaluation and orientation of the famous and excellent Chinese herbal drugs is an important task, and it is also a requirement for the internationalization of traditional Chinese medicine. Literature evaluation-pharmacology research-clinical expertise analysis method will establish a theoretical basis and method for post-marketing development of famous and excellent Chinese patent drugs.

  1. The surveillance error grid.

    PubMed

    Klonoff, David C; Lias, Courtney; Vigersky, Robert; Clarke, William; Parkes, Joan Lee; Sacks, David B; Kirkman, M Sue; Kovatchev, Boris

    2014-07-01

    Currently used error grids for assessing clinical accuracy of blood glucose monitors are based on out-of-date medical practices. Error grids have not been widely embraced by regulatory agencies for clearance of monitors, but this type of tool could be useful for surveillance of the performance of cleared products. Diabetes Technology Society together with representatives from the Food and Drug Administration, the American Diabetes Association, the Endocrine Society, and the Association for the Advancement of Medical Instrumentation, and representatives of academia, industry, and government, have developed a new error grid, called the surveillance error grid (SEG) as a tool to assess the degree of clinical risk from inaccurate blood glucose (BG) monitors. A total of 206 diabetes clinicians were surveyed about the clinical risk of errors of measured BG levels by a monitor. The impact of such errors on 4 patient scenarios was surveyed. Each monitor/reference data pair was scored and color-coded on a graph per its average risk rating. Using modeled data representative of the accuracy of contemporary meters, the relationships between clinical risk and monitor error were calculated for the Clarke error grid (CEG), Parkes error grid (PEG), and SEG. SEG action boundaries were consistent across scenarios, regardless of whether the patient was type 1 or type 2 or using insulin or not. No significant differences were noted between responses of adult/pediatric or 4 types of clinicians. Although small specific differences in risk boundaries between US and non-US clinicians were noted, the panel felt they did not justify separate grids for these 2 types of clinicians. The data points of the SEG were classified in 15 zones according to their assigned level of risk, which allowed for comparisons with the classic CEG and PEG. Modeled glucose monitor data with realistic self-monitoring of blood glucose errors derived from meter testing experiments plotted on the SEG when compared to

  2. Efficacy and safety of recombinant factor VIII products in patients with hemophilia A.

    PubMed

    Musso, Robert

    2008-10-01

    The introduction of recombinant factor VIII (rFVIII) clotting factor concentrates nearly 20 years ago represented a significant advance in the treatment of hemophilia A. The major advantage of rFVIII products compared with plasma-derived FVIII products is related to product safety, with rFVIII products virtually eliminating bloodborne pathogen transmission. The most challenging aspect of hemophilia A management today is the development of FVIII inhibitors; previously untreated patients are at the highest risk for inhibitor formation. Presented in this article are results of clinical trials in previously treated and untreated patients and postmarketing surveillance studies for the four commercially available rFVIII products (Recombinate, ReFacto, Kogenate FS/Kogenate Bayer and Advate). Recombinant FVIII therapies are highly efficacious when used ondemand and prophylactically, and they have excellent safety profiles; there have been no reports of viral- or prion-based disease transmission associated with rFVIII administration. The incidence rate of inhibitors in previously untreated patients ranges from 15% to approximately 30%. Because rFVIII concentrates have proven efficacy and safety profiles, a number of hemophilia treatment groups recommend rFVIII products as first-line therapy in the management of hemophilia A.

  3. 21 CFR 314.81 - Other postmarketing reports.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... whether new studies in the pediatric population to support appropriate labeling for the pediatric population have been initiated. Where possible, an estimate of patient exposure to the drug product, with special reference to the pediatric population (neonates, infants, children, and adolescents) shall be...

  4. 21 CFR 314.81 - Other postmarketing reports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... whether new studies in the pediatric population to support appropriate labeling for the pediatric population have been initiated. Where possible, an estimate of patient exposure to the drug product, with special reference to the pediatric population (neonates, infants, children, and adolescents) shall be...

  5. Performance of health product risk management and surveillance conducted by health personnel at sub-district health promotion hospitals in the northeast region of Thailand

    PubMed Central

    Kanjanarach, Tipaporn; Jaisa-ard, Raksaworn; Poonaovarat, Nantawan

    2014-01-01

    Background Health personnel at sub-district health promotion hospitals (SD-HPHs) are assigned to take responsibility for 15 activities related to health product risk management and surveillance (HP-RM&S). This cross-sectional survey aimed to identify factors that determined their job performance and to record their expressed needs to support HP-RM&S operation. In this study, job performance was defined as completion of all 15 activities. Methods Self-administered postal questionnaires were used to collect data from 380 randomly selected health personnel who were in charge of HP-RM&S at SD-HPHs in the northeast of Thailand. Results Thirty-six point one percent (n=137) of the respondents were able to perform all 15 of the HP-RM&S activities assigned to SD-HPHs. A logistic regression model identified three factors that statistically significantly determined the completion of all 15 HP-RM&S activities. These were: receiving a high or very high level of support from the community (adjusted odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.5, 4.1), the responsible persons for HP-RM&S did not hold an administrative position (adjusted OR: 1.7; 95% CI: 1.1, 2.7), and having at least one training session related to HP-RM&S per year (adjusted OR: 1.7; 95% CI 1.1, 2.6). There were 1,536 expressed needs which can be classified into four major categories, ie, training needs (41.6%, n=639), resource support (28.3%, n=435), mechanisms that facilitate HP-RM&S operation (24.1%, n=370) and adjusting of the scope of HP-RM&S (6.0%, n=92). The topics most frequently referred to in training needs were drug law, food law, and cosmetics law. Conclusion A strategy for improvement of the job performance in HP-RM&S of health personnel in SD-HPHs should target identifying schemes to encourage the community to proactively participate in HP-RM&S. The district health office as the organization directly controlling and supervising SD-HPHs should also regularly update knowledge base and skills

  6. Redefining syndromic surveillance.

    PubMed

    Katz, Rebecca; May, Larissa; Baker, Julia; Test, Elisa

    2011-12-01

    With growing concerns about international spread of disease and expanding use of early disease detection surveillance methods, the field of syndromic surveillance has received increased attention over the last decade. The purpose of this article is to clarify the various meanings that have been assigned to the term syndromic surveillance and to propose a refined categorization of the characteristics of these systems. Existing literature and conference proceedings were examined on syndromic surveillance from 1998 to 2010, focusing on low- and middle-income settings. Based on the 36 unique definitions of syndromic surveillance found in the literature, five commonly accepted principles of syndromic surveillance systems were identified, as well as two fundamental categories: specific and non-specific disease detection. Ultimately, the proposed categorization of syndromic surveillance distinguishes between systems that focus on detecting defined syndromes or outcomes of interest and those that aim to uncover non-specific trends that suggest an outbreak may be occurring. By providing an accurate and comprehensive picture of this field's capabilities, and differentiating among system types, a unified understanding of the syndromic surveillance field can be developed, encouraging the adoption, investment in, and implementation of these systems in settings that need bolstered surveillance capacity, particularly low- and middle-income countries. Copyright © 2011 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  7. Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post-marketing clinical study on healthy volunteers

    PubMed Central

    Del Tacca, Mario; Pasqualetti, Giuseppe; Di Paolo, Antonello; Virdis, Agostino; Massimetti, Gabriele; Gori, Giovanni; Versari, Daniele; Taddei, Stefano; Blandizzi, Corrado

    2009-01-01

    AIMS There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug. METHODS Two generic amoxicillin products (generic A and B) were selected among four fast-release tablet formulations available on the Italian market. Twenty-four healthy adult volunteers of either sex participated to a single-dose, randomized, three-treatment, crossover, single-blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high-performance liquid chromatography. RESULTS Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of Cmax ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation. CONCLUSIONS These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for Cmax on the basis of single-dose pharmacokinetic assessment. PMID:19660001

  8. Environmental surveillance master sampling schedule

    SciTech Connect

    Bisping, L.E.

    1995-02-01

    Environmental surveillance of the Hanford Site and surrounding areas is conducted by the Pacific Northwest Laboratory (PNL) for the U.S. Department of Energy (DOE). This document contains the planned 1994 schedules for routine collection of samples for the Surface Environmental Surveillance Project (SESP), Drinking Water Project, and Ground-Water Surveillance Project. Samples are routinely collected for the SESP and analyzed to determine the quality of air, surface water, soil, sediment, wildlife, vegetation, foodstuffs, and farm products at Hanford Site and surrounding communities. The responsibility for monitoring onsite drinking water falls outside the scope of the SESP. PNL conducts the drinking water monitoring project concurrent with the SESP to promote efficiency and consistency, utilize expertise developed over the years, and reduce costs associated with management, procedure development, data management, quality control, and reporting. The ground-water sampling schedule identifies ground-water sampling .events used by PNL for environmental surveillance of the Hanford Site. Sampling is indicated as annual, semi-annual, quarterly, or monthly in the sampling schedule. Some samples are collected and analyzed as part of ground-water monitoring and characterization programs at Hanford (e.g. Resources Conservation and Recovery Act (RCRA), Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), or Operational). The number of samples planned by other programs are identified in the sampling schedule by a number in the analysis column and a project designation in the Cosample column. Well sampling events may be merged to avoid redundancy in cases where sampling is planned by both-environmental surveillance and another program.

  9. Pharmacy study of natural health product adverse reactions (SONAR): a cross-sectional study using active surveillance in community pharmacies to detect adverse events associated with natural health products and assess causality.

    PubMed

    Necyk, Candace; Tsuyuki, Ross T; Boon, Heather; Foster, Brian C; Legatt, Don; Cembrowski, George; Murty, Mano; Barnes, Joanne; Charrois, Theresa L; Arnason, John T; Ware, Mark A; Rosychuk, Rhonda J; Vohra, Sunita

    2014-03-28

    To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies. Cross-sectional study of screened patients. 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July 2011. The participating pharmacy staff screened consecutive patients, or agents of patients, who were dropping or picking up prescription medications. Patients were screened to determine the proportions of them using prescription drugs and/or NHPs, as well as their respective AE rates. All AEs reported by the screened patients who took a NHP, consented to, and were available for, a detailed telephone interview (14%) were adjudicated fully to assess for causality. Over a total of 105 pharmacy weeks and 1118 patients screened, 410 patients reported taking prescription drugs only (36.7%; 95% CI 33.9% to 39.5%), 37 reported taking NHPs only (3.3%; 95% CI 2.4% to 4.5%) and 657 reported taking prescription drugs and NHPs concurrently (58.8%; 95% CI 55.9% to 61.6%). In total, 54 patients reported an AE, representing 1.2% (95% CI 0.51% to 2.9%), 2.7% (95% CI 0.4% to 16.9%) and 7.3% (95% CI 5.6% to 9.6%) of each population, respectively. Compared with patients who reported using prescription drugs, the patients who reported using prescription drugs and NHPs concurrently were 6.4 times more likely to experience an AE (OR; 95% CI 2.52 to 16.17; p<0.001). Combined with data from Ontario, Canada, a national proportion was calculated, which found that 45.4% (95% CI 43.8% to 47.0%) of Canadians who visit community pharmacies take NHPs and prescription drugs concurrently, and of those, 7.4% (95% CI 6.3% to 8.8%) report an AE. A substantial proportion of community pharmacy patients use prescription drugs and NHPs concurrently; these patients are at a greater risk of experiencing an AE. Active surveillance provides a means of

  10. Pharmacy study of natural health product adverse reactions (SONAR): a cross-sectional study using active surveillance in community pharmacies to detect adverse events associated with natural health products and assess causality

    PubMed Central

    Necyk, Candace; Tsuyuki, Ross T; Boon, Heather; Foster, Brian C; LeGatt, Don; Cembrowski, George; Murty, Mano; Barnes, Joanne; Charrois, Theresa L; Arnason, John T; Ware, Mark A; Rosychuk, Rhonda J; Vohra, Sunita

    2014-01-01

    Objectives To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies. Design Cross-sectional study of screened patients. Setting 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July 2011. Participants The participating pharmacy staff screened consecutive patients, or agents of patients, who were dropping or picking up prescription medications. Primary outcome measures Patients were screened to determine the proportions of them using prescription drugs and/or NHPs, as well as their respective AE rates. All AEs reported by the screened patients who took a NHP, consented to, and were available for, a detailed telephone interview (14%) were adjudicated fully to assess for causality. Results Over a total of 105 pharmacy weeks and 1118 patients screened, 410 patients reported taking prescription drugs only (36.7%; 95% CI 33.9% to 39.5%), 37 reported taking NHPs only (3.3%; 95% CI 2.4% to 4.5%) and 657 reported taking prescription drugs and NHPs concurrently (58.8%; 95% CI 55.9% to 61.6%). In total, 54 patients reported an AE, representing 1.2% (95% CI 0.51% to 2.9%), 2.7% (95% CI 0.4% to 16.9%) and 7.3% (95% CI 5.6% to 9.6%) of each population, respectively. Compared with patients who reported using prescription drugs, the patients who reported using prescription drugs and NHPs concurrently were 6.4 times more likely to experience an AE (OR; 95% CI 2.52 to 16.17; p<0.001). Combined with data from Ontario, Canada, a national proportion was calculated, which found that 45.4% (95% CI 43.8% to 47.0%) of Canadians who visit community pharmacies take NHPs and prescription drugs concurrently, and of those, 7.4% (95% CI 6.3% to 8.8%) report an AE. Conclusions A substantial proportion of community pharmacy patients use prescription drugs and NHPs concurrently; these patients are at a

  11. Pinimenthol ointment in patients suffering from upper respiratory tract infections - a post-marketing observational study.

    PubMed

    Kamin, Wolfgang; Kieser, Meinhard

    2007-12-01

    In order to gain further experience regarding the tolerability of Pinimenthol ointment(1) in adolescents (> or = 12 years) and adults suffering from upper respiratory tract infections, a post-marketing observational study was performed. In this study, data of 3060 patients were collected (64.9% prospectively over an individual observation period of 5-14 days, 35.1% retrospectively). The prospective documentation also comprised data concerning treatment effects. Sample size of the post-marketing observational study was calculated in the way that adverse drug reactions with an event probability of at least 1:1000 would occur within the study at least once with a probability of 95%. Most patients suffered from cold, acute or chronic bronchitis, bronchial catarrh or hoarseness. Pinimenthol ointment was prescribed to inunction (29.6%), inhalation (17.3%) or inunction and inhalation (53.1%), respectively. The mean duration of study participation was 8.0 +/- 3.4 days. The tolerability was rated as excellent or good by 96.7% of physicians and 95.7% of patients. A total of 22 patients (0.7%) reported adverse drug reactions which mostly affected the skin or mucus membrane and therefore correspond to the expected adverse effects profile of Pinimenthol ointment. The treatment effect was mostly judged as excellent or good (physicians: 88.3%; patients: 88.1%). In conclusion, the study confirms Pinimenthol ointment as a well tolerated therapy option for upper respiratory tract infections in both adolescents and adults.

  12. [Establish research model of post-marketing clinical safety evaluation for Chinese patent medicine].

    PubMed

    Zheng, Wen-ke; Liu, Zhi; Lei, Xiang; Tian, Ran; Zheng, Rui; Li, Nan; Ren, Jing-tian; Du, Xiao-xi; Shang, Hong-cai

    2015-09-01

    The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.

  13. Post-marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross-sectional study.

    PubMed

    Zeitoun, Jean-David; Baron, Gabriel; Vivot, Alexandre; Atal, Ignacio; Downing, Nicholas S; Ross, Joseph S; Ravaud, Philippe

    2017-09-20

    Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2345 post-marketing trials; 1362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials [range 8-530] and overall population to be enrolled per trial [1-8381]. Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3% to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low. This article is protected by copyright. All rights reserved. © 2017 UICC.

  14. Mercury Surveillance Program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background on mercury exposure is presented including forms, sources, permissible exposure limits, and physiological effects. The purpose of the Mercury Surveillance Program at LeRC is outlined, and the specifics of the Medical Surveillance Program for Mercury Exposure at LeRC are discussed.

  15. Soil and vegetation surveillance

    SciTech Connect

    Antonio, E.J.

    1995-06-01

    Soil sampling and analysis evaluates long-term contamination trends and monitors environmental radionuclide inventories. This section of the 1994 Hanford Site Environmental Report summarizes the soil and vegetation surveillance programs which were conducted during 1994. Vegetation surveillance is conducted offsite to monitor atmospheric deposition of radioactive materials in areas not under cultivation and onsite at locations adjacent to potential sources of radioactivity.

  16. Arsenic surveillance program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background information about arsenic is presented including forms, common sources, and clinical symptoms of arsenic exposure. The purpose of the Arsenic Surveillance Program and LeRC is outlined, and the specifics of the Medical Surveillance Program for Arsenic Exposure at LeRC are discussed.

  17. Asbestos Surveillance Program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background on asbestos is presented including the different types and the important medical distinctions between those different types. The four diseases associated with asbestos exposure are discussed: mesothelioma, lung cancer, asbestosis, and benign pleural disorders. The purpose of the LeRC Asbestos Surveillance Program is outlined, and the specifics of the Medical Surveillance Program for Asbestos Monitoring at LeRC are discussed.

  18. Lead Surveillance Program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background on lead exposure is presented including forms of lead, sources, hematologic effects, neurologic effects, endocrine effects, renal effects, and reproductive and developmental effects. The purpose of the Lead Surveillance Program at LeRC is outlined, and the specifics of the Medical Surveillance Program for Lead Exposure at LeRC are discussed.

  19. Economic Analysis of Classical Swine Fever Surveillance in the Netherlands.

    PubMed

    Guo, X; Claassen, G D H; Oude Lansink, A G J M; Loeffen, W; Saatkamp, H W

    2016-06-01

    Classical swine fever (CSF) is a highly contagious pig disease that causes economic losses and impaired animal welfare. Improving the surveillance system for CSF can help to ensure early detection of the virus, thereby providing a better initial situation for controlling the disease. Economic analysis is required to compare the benefits of improved surveillance with the costs of implementing a more intensive system. This study presents a comprehensive economic analysis of CSF surveillance in the Netherlands, taking into account the specialized structure of Dutch pig production, differences in virulence of CSF strains and a complete list of possible surveillance activities. The starting point of the analysis is the current Dutch surveillance system (i.e. the default surveillance-setup scenario), including the surveillance activities 'daily clinical observation by the farmer', 'veterinarian inspection after a call', 'routine veterinarian inspection', 'pathology in AHS', 'PCR on tonsil in AHS', 'PCR on grouped animals in CVI' and 'confirmatory PCR by NVWA'. Alternative surveillance-setup scenarios were proposed by adding 'routine serology in slaughterhouses', 'routine serology on sow farms' and 'PCR on rendered animals'. The costs and benefits for applying the alternative surveillance-setup scenarios were evaluated by comparing the annual mitigated economic losses because of intensified CSF surveillance with the annual additional surveillance costs. The results of the cost-effectiveness analysis show that the alternative surveillance-setup scenarios with 'PCR on rendered animals' are effective for the moderately virulent CSF strain, whereas the scenarios with 'routine serology in slaughterhouses' or 'routine serology on sow farms' are effective for the low virulent strain. Moreover, the current CSF surveillance system in the Netherlands is cost-effective for both moderately virulent and low virulent CSF strains. The results of the cost-benefit analysis for the

  20. [Post-marketing reevaluation for potential quality risk and quality control in clinical application of traditional Chinese medicines].

    PubMed

    Li, Hong-jiao; He, Li-yun; Liu, Bao-yan

    2015-06-01

    The effective quality control in clinical practices is an effective guarantee for the authenticity and scientificity of the findings. The post-marketing reevaluation for traditional Chinese medicines (TCM) focuses on the efficacy, adverse reaction, combined medication and effective dose of drugs in the market by expanded clinical trials, and requires a larger sample size and a wider range of patients. Therefore, this increases the difficulty of quality control in clinical practices. With the experience in quality control in clinical practices for the post-marketing reevaluation for Kangbingdu oral for cold, researchers in this study reviewed the study purpose, project, scheme design and clinical practice process from an overall point of view, analyzed the study characteristics of the post-marketing reevaluation for TCMs and the quality control risks, designed the quality control contents with quality impacting factors, defined key review contents and summarized the precautions in clinical practices, with the aim to improve the efficiency of quality control of clinical practices. This study can provide reference to clinical units and quality control-related personnel in the post-marketing reevaluation for TCMs.

  1. 76 FR 18226 - Guidance for Industry on Postmarketing Studies and Clinical Trials-Implementation of Section 505...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... Trials--Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act; Availability... Clinical Trials--Implementation of Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act.'' The..., Drug, and Cosmetic Act (the FD&C Act) authorizing FDA to require certain postmarketing studies and...

  2. [Importance of Post-Marketing Studies in Gathering of Clinical Evidences for Proper Usage of Anti-Cancer Drugs, and the StudyRequirements for Their Credibility].

    PubMed

    Inagaki, Osamu

    2016-04-01

    Pharmaceutical companies recognize the importance of post-marketing studies because they are crucial in the generation of clinical evidences for the usage of new medicines. To generate clinical evidences, quality of post-marketing studies should be well controlled from view point of "ethical conduction" and "reliability of results". In addition, control of conflict of interest (COI) between researchers and industries is also indispensable and is requested for the transparency of the studies. Japan Pharmaceutical Manufacturers Association(JPMA)stresses its commitment to the progressof transparency in post-marketing studies.

  3. Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

    PubMed

    Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

    2017-07-03

    Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

  4. BP goal achievement in patients with uncontrolled hypertension : results of the treat-to-target post-marketing survey with irbesartan.

    PubMed

    Schrader, Joachim; Bramlage, Peter; Lüders, Stephan; Thoenes, Martin; Schirmer, Andreas; Paar, Dieter W

    2007-01-01

    Despite the fact that high BP is a leading risk factor for cardiovascular morbidity and mortality, BP goals are achieved in less than 10-30% of hypertensive patients. Irbesartan alone or in combination with hydrochlorothiazide has been shown to control BP in >70% of hypertensive patients in clinical trials. We set out to investigate the role in clinical practice of irbesartan in improving BP in uncontrolled hypertensive patients with a particular focus on patients with the metabolic syndrome through analysis of data from a post-marketing surveillance study. A multicentre, prospective, post-marketing surveillance study was conducted over 9 months in 14 200 patients aged > or =18 years with previously uncontrolled hypertension (either receiving therapy or newly diagnosed), paying particular attention to a subgroup of patients receiving irbesartan/hydrochlorothiazide as first-line combination therapy. BP was measured by a sphygmomanometer. The main outcome measures were systolic BP (SBP) and diastolic BP (DBP) reduction, response rate (DBP reduction of > or =10mm Hg or to <90 mm Hg), and BP normalisation (SBP <140 and DBP <90 mm Hg) in patients treated with irbesartan alone or in combination with hydrochlorothiazide. Analyses per patient subgroup, previous medication and whether treatment was initiated by the treating physician as first-line combination therapy were conducted. The number and nature of adverse events were documented. Use of irbesartan 300 mg/day as monotherapy in previously uncontrolled patients resulted in a significant reduction in SBP/DBP (-26.8/-13.3mm Hg, p < 0.0001), which was comparable to the subgroup of patients with the metabolic syndrome (-26.3/-13.0mm Hg, p < 0.0001 vs baseline). Combination therapy (irbesartan 300 mg/hydrochlorothiazide 12.5mg once daily) lowered BP by -27.9/-14.2mm Hg (p < 0.0001) in previously uncontrolled patients; again the subgroup of patients with the metabolic syndrome achieved a comparable BP reduction (-27

  5. Environmental surveillance master sampling schedule

    SciTech Connect

    Bisping, L.E.

    1994-02-01

    This document contains the planned 1994 schedules for routine collection of samples for the Surface Environmental Surveillance Project (SESP), Drinking Water Project, and Ground-Water Surveillance Project. Samples are routinely collected for the SESP and analyzed to determine the quality of air, surface water, soil, sediment, wildlife, vegetation, foodstuffs, and farm products at Hanford Site and surrounding communities. The responsibility for monitoring the onsite drinking water falls outside the scope of the SESP. The Hanford Environmental Health Foundation is responsible for monitoring the nonradiological parameters as defined in the National Drinking Water Standards while PNL conducts the radiological monitoring of the onsite drinking water. PNL conducts the drinking water monitoring project concurrent with the SESP to promote efficiency and consistency, utilize the expertise developed over the years, and reduce costs associated with management, procedure development, data management, quality control and reporting. The ground-water sampling schedule identifies ground-water sampling events used by PNL for environmental surveillance of the Hanford Site.

  6. Safety and effectiveness of daily teriparatide for osteoporosis in patients with severe stages of chronic kidney disease: post hoc analysis of a postmarketing observational study

    PubMed Central

    Nishikawa, Atsushi; Yoshiki, Fumito; Taketsuna, Masanori; Kajimoto, Kenta; Enomoto, Hiroyuki

    2016-01-01

    Teriparatide (recombinant 1–34 N-terminal sequence of human parathyroid hormone) for the treatment of osteoporosis should be prescribed with caution in patients with severe stages of chronic kidney disease (CKD). However, in clinical settings, physicians and surgeons who treat such patients have few available options. We sought to further explore the safety and effectiveness of teriparatide for the treatment of osteoporosis in Japanese patients with severe stages of CKD. This was a post hoc analysis of a postmarketing surveillance study that included patients with osteoporosis at high risk of fracture and stage 4 or 5 CKD. Patients received subcutaneous teriparatide 20 μg daily for up to 24 months. Safety profiles were assessed by physician-reported adverse drug reactions (ADRs). Effectiveness was assessed by measuring bone formation (via procollagen type 1 N-terminal propeptide [P1NP]), bone mineral density (BMD), and the incidence of clinical vertebral or nonvertebral fragility fractures. A total of 33 patients with severe stages of CKD (stage 4, n=30; stage 5, n=3) were included. All patients were female, and 81.8% had a history of previous fracture. No serious ADRs were recorded; a total of 4 ADRs were recorded for 4 of 33 patients. Increases in BMD and P1NP levels were observed both overall and in most individual patients. New fractures occurred in 1 patient with stage 5 CKD, but not in patients with stage 4 CKD. In this post hoc analysis conducted in Japan, teriparatide appeared to be effective for the treatment of osteoporosis in elderly female patients with severe stages of CKD, and no new safety concerns were observed. PMID:27895472

  7. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection

    PubMed Central

    2014-01-01

    Background Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. Results The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. Conclusions We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance. PMID:24428898

  8. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection.

    PubMed

    Xu, Rong; Wang, QuanQiu

    2014-01-15

    Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance.

  9. Automatic signal extraction, prioritizing and filtering approaches in detecting post-marketing cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS).

    PubMed

    Xu, Rong; Wang, Quanqiu

    2014-02-01

    Targeted drugs dramatically improve the treatment outcomes in cancer patients; however, these innovative drugs are often associated with unexpectedly high cardiovascular toxicity. Currently, cardiovascular safety represents both a challenging issue for drug developers, regulators, researchers, and clinicians and a concern for patients. While FDA drug labels have captured many of these events, spontaneous reporting systems are a main source for post-marketing drug safety surveillance in 'real-world' (outside of clinical trials) cancer patients. In this study, we present approaches to extracting, prioritizing, filtering, and confirming cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). The dataset includes records of 4,285,097 patients from FAERS. We first extracted drug-cardiovascular event (drug-CV) pairs from FAERS through named entity recognition and mapping processes. We then compared six ranking algorithms in prioritizing true positive signals among extracted pairs using known drug-CV pairs derived from FDA drug labels. We also developed three filtering algorithms to further improve precision. Finally, we manually validated extracted drug-CV pairs using 21 million published MEDLINE records. We extracted a total of 11,173 drug-CV pairs from FAERS. We showed that ranking by frequency is significantly more effective than by the five standard signal detection methods (246% improvement in precision for top-ranked pairs). The filtering algorithm we developed further improved overall precision by 91.3%. By manual curation using literature evidence, we show that about 51.9% of the 617 drug-CV pairs that appeared in both FAERS and MEDLINE sentences are true positives. In addition, 80.6% of these positive pairs have not been captured by FDA drug labeling. The unique drug-CV association dataset that we created based on FAERS could facilitate our understanding and prediction of cardiotoxic events associated with

  10. Circuits of Surveillance

    PubMed Central

    Williams, Robin; Johnson, Paul

    2005-01-01

    This paper examines the increasing police use of DNA profiling and databasing as a developing instrumentality of modern state surveillance. It briefly notes previously published work on a variety of surveillance technologies and their role in the governance of social action and social order. It then argues that there are important differences amongst the ways in which several such technologies construct and use identificatory artefacts, their orientations to human subjectivity, and their role in the governmentality of citizens and others. The paper then describes the novel and powerful form of bio-surveillance offered by DNA profiling and illustrates this by reference to an ongoing empirical study of the police uses of the UK National DNA Database for the investigation of crime. It is argued that DNA profiling and databasing enable the construction of a ‘closed circuit’ of surveillance of a defined population. PMID:16467920

  11. IMPROVING WATERBORNE DISEASE SURVEILLANCE

    EPA Science Inventory

    Public health surveillance has played a key role in controlling the spread of communicable disease and identifying the need for specific publich health practices, such as the filteration and chlorination of drinking water supplies. However, the characteristics of waterborne ou...

  12. Autonomous surveillance for biosecurity.

    PubMed

    Jurdak, Raja; Elfes, Alberto; Kusy, Branislav; Tews, Ashley; Hu, Wen; Hernandez, Emili; Kottege, Navinda; Sikka, Pavan

    2015-04-01

    The global movement of people and goods has increased the risk of biosecurity threats and their potential to incur large economic, social, and environmental costs. Conventional manual biosecurity surveillance methods are limited by their scalability in space and time. This article focuses on autonomous surveillance systems, comprising sensor networks, robots, and intelligent algorithms, and their applicability to biosecurity threats. We discuss the spatial and temporal attributes of autonomous surveillance technologies and map them to three broad categories of biosecurity threat: (i) vector-borne diseases; (ii) plant pests; and (iii) aquatic pests. Our discussion reveals a broad range of opportunities to serve biosecurity needs through autonomous surveillance. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  13. A GIS-driven integrated real-time surveillance pilot system for national West Nile virus dead bird surveillance in Canada.

    PubMed

    Shuai, Jiangping; Buck, Peter; Sockett, Paul; Aramini, Jeff; Pollari, Frank

    2006-04-20

    An extensive West Nile virus surveillance program of dead birds, mosquitoes, horses, and human infection has been launched as a result of West Nile virus first being reported in Canada in 2001. Some desktop and web GIS have been applied to West Nile virus dead bird surveillance. There have been urgent needs for a comprehensive GIS services and real-time surveillance. A pilot system was developed to integrate real-time surveillance, real-time GIS, and Open GIS technology in order to enhance West Nile virus dead bird surveillance in Canada. Driven and linked by the newly developed real-time web GIS technology, this integrated real-time surveillance system includes conventional real-time web-based surveillance components, integrated real-time GIS components, and integrated Open GIS components. The pilot system identified the major GIS functions and capacities that may be important to public health surveillance. The six web GIS clients provide a wide range of GIS tools for public health surveillance. The pilot system has been serving Canadian national West Nile virus dead bird surveillance since 2005 and is adaptable to serve other disease surveillance. This pilot system has streamlined, enriched and enhanced national West Nile virus dead bird surveillance in Canada, improved productivity, and reduced operation cost. Its real-time GIS technology, static map technology, WMS integration, and its integration with non-GIS real-time surveillance system made this pilot system unique in surveillance and public health GIS.

  14. A GIS-driven integrated real-time surveillance pilot system for national West Nile virus dead bird surveillance in Canada

    PubMed Central

    Shuai, Jiangping; Buck, Peter; Sockett, Paul; Aramini, Jeff; Pollari, Frank

    2006-01-01

    Background An extensive West Nile virus surveillance program of dead birds, mosquitoes, horses, and human infection has been launched as a result of West Nile virus first being reported in Canada in 2001. Some desktop and web GIS have been applied to West Nile virus dead bird surveillance. There have been urgent needs for a comprehensive GIS services and real-time surveillance. Results A pilot system was developed to integrate real-time surveillance, real-time GIS, and Open GIS technology in order to enhance West Nile virus dead bird surveillance in Canada. Driven and linked by the newly developed real-time web GIS technology, this integrated real-time surveillance system includes conventional real-time web-based surveillance components, integrated real-time GIS components, and integrated Open GIS components. The pilot system identified the major GIS functions and capacities that may be important to public health surveillance. The six web GIS clients provide a wide range of GIS tools for public health surveillance. The pilot system has been serving Canadian national West Nile virus dead bird surveillance since 2005 and is adaptable to serve other disease surveillance. Conclusion This pilot system has streamlined, enriched and enhanced national West Nile virus dead bird surveillance in Canada, improved productivity, and reduced operation cost. Its real-time GIS technology, static map technology, WMS integration, and its integration with non-GIS real-time surveillance system made this pilot system unique in surveillance and public health GIS. PMID:16626490

  15. Radio spectrum surveillance station

    NASA Technical Reports Server (NTRS)

    Hersey, D. R.

    1979-01-01

    The paper presents a general and functional description of a low-cost surveillance station designed as the first phase of NASA's program to develop a radio spectrum surveillance capability for deep space stations for identifying radio frequency interference sources. The station described has identified several particular interferences and is yielding spectral signature data which, after cataloging, will serve as a library for rapid identification of frequently observed interference. Findings from the use of the station are discussed.

  16. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

    PubMed

    Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

    2012-01-01

    Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

  17. Technical success from endovascular aneurysm repair in the post-marketing era: a multicenter prospective trial.

    PubMed

    Naslund, Thomas C; Becker, Stacey Y

    2003-01-01

    Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was accomplished by review of a multicenter, prospective trial involving 46 centers and 163 patients. A second cohort of patients (n = 350) treated with the AEG under a controlled-use interval prior to the prospective trial was simultaneously evaluated. Technical success in both groups of patients (96.9% and 97.4%, respectively) was similar to what was reported in pre-market clinical trials. Operative implantation complications unique to the AEG included graft limb stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%, jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8 and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract jacket in 1.8 and 0.5% of patients involved in the multicenter trial and controlled-use interval, respectively. One of four patients undergoing conversion in the prospective trial had graft misdeployment as a mode of failure. Three were converted for access failure. The 30-day mortality rate in the prospective trial was 3.7%. Interventions to resolve implantation-related events included stenting, guide catheter manipulations, wire exchanges, and delivery catheter disassembly. These interventions were successful in virtually every case. Open surgical procedures were not needed to correct these operative problems. Results from this study demonstrate excellent technical success with the AEG in the post-market era. Interventions to resolve implantation complications, when utilized, are highly successful in facilitating AEG implantation and providing technical success.

  18. Postmarketing pharmacovigilance of adverse drug reactions: the case of rosiglitazone in Mexico.

    PubMed

    Reyes-Morales, Hortensia; Mino-León, Dolores; Doubova, Svetlana V; Flores-Hernández, Sergio

    2012-01-01

    Commercialization of rosiglitazone, an oral blood glucose-lowering drug of the thiazolidinedione class, was recently suspended in Europe and significantly restricted in the United States due to a possibly increased risk of ischemic heart disease; the drug is still being marketed in Mexico. This study was aimed to analyze the post-marketing occurrence of adverse drug reactions (ADRs) with rosiglitazone when used in combination therapy in Mexican Type 2 Diabetes patients. A prospective observational study was conducted at a primary health-care clinic in Mexico City. Eligible subjects were adult patients with Type 2 diabetes inadequately controlled with maximal doses of oral monotherapy, in which one of two combined therapeutic schemes was prescribed: rosiglitazone/glibenclamide (R/G), or rosiglitazone/metformin (R/M). Patients' blood pressure, weight, treatment adherence and occurrence of ADRs were monitored during a 6-month follow-up period. 174 patients received treatment with R/M or R/G (112 and 62 patients, respectively). At least one ADR was observed in about 75%, of patients. Prior to the end of the follow-up period, moderate ADRs leading to discontinuation of the treatment occurred in 29.5% and 14.5% of patients treated with R/M and R/G, respectively. The ADRs most frequently observed were peripheral edema and moderate weight gain. The use of rosiglitazone in combination with other oral anti-diabetic drugs was associated with a high frequency of ADRs in Mexican patients with Type 2 diabetes. Post-marketing studies are relevant to identify drug-associated risks to patients in clinical practice.

  19. Geospatial Intelligence (GEOINT) and Intelligence Surveillance and Reconnaissance (ISR) convergence

    NASA Astrophysics Data System (ADS)

    Lee, Michael G.

    2013-05-01

    An examination of the potentialities, benefits and challenges of the confluence, integration and operation of Geospatial Intelligence (GEOINT) capabilities, products and techniques within the larger context of the Intelligence, Surveillance and Reconnaissance (ISR) arena, particularly in regards to persistent surveillance and Full Motion Video (FMV).

  20. [Biosimilars : Current state of the build up to series production].

    PubMed

    Aringer, M; Dörner, T

    2013-11-01

    When patents expire, usually after 10 years in Germany, generic medicines routinely enter the market in place of conventional medications leading to significant reductions in prices. Currently the first biologicals are approaching patent expiry. Because of the biochemical complexities truly identical imitators are unrealistic. On the other hand, there is high socioeconomic pressure towards reduced cost of biologicals. In response to this situation the European Medicines Agency (EMA) has released a highly differentiated guidance document for the approval process of biosimilars. Biosimilars, which are already reality in other areas have to remain within a narrow biochemical variability corridor and are subsequently required to show bioequivalence to the reference product in both efficacy and safety in at least one large clinical phase III trial. In addition, post-marketing surveillance programs are mandatory in order to identify potential low frequency safety issues. In contrast to the "intended copies" used in some third world countries without such rigorous clinical testing the EMA-approved biosimilars are expected to have almost identical efficacy and safety as the reference medications. It is not yet clear how the use of specific biosimilars can be tracked and how uncontrolled exchange can be avoided. Nevertheless, biosimilars in rheumatology are likely to be available in the near future.

  1. Innovative postmarket device evaluation using a quality registry to monitor thoracic endovascular aortic repair in the treatment of aortic dissection.

    PubMed

    Beck, Adam W; Lombardi, Joseph V; Abel, Dorothy B; Morales, J Pablo; Marinac-Dabic, Danica; Wang, Grace; Azizzadeh, Ali; Kern, John; Fillinger, Mark; White, Rodney; Cronenwett, Jack L; Cambria, Richard P

    2017-05-01

    United States Food and Drug Administration (FDA)-mandated postapproval studies have long been a mainstay of the continued evaluation of high-risk medical devices after initial marketing approval; however, these studies often present challenges related to patient/physician recruitment and retention. Retrospective single-center studies also do not fully represent the spectrum of real-world performance nor are they likely to have a sufficiently large enough sample size to detect important signals. In recent years, The FDA Center for Devices and Radiological Health has been promoting the development and use of patient registries to advance infrastructure and methodologies for medical device investigation. The FDA 2012 document, "Strengthening the National System for Medical Device Post-market Surveillance," highlighted registries as a core foundational infrastructure when linked to other complementary data sources, including embedded unique device identification. The Vascular Quality Initiative (VQI) thoracic endovascular aortic repair for type B aortic dissection project is an innovative method of using quality improvement registries to meet the needs of device evaluation after market approval. Here we report the organization and background of this project and highlight the innovation facilitated by collaboration of physicians, the FDA, and device manufacturers. This effort used an existing national network of VQI participants to capture patients undergoing thoracic endovascular aortic repair for acute type B aortic dissection within a registry that aligns with standard practice and existing quality efforts. The VQI captures detailed patient, device, and procedural data for consecutive eligible cases under the auspices of a Patient Safety Organization (PSO). Patients were divided into a 5-year follow-up group (200 acute; 200 chronic dissections) and a 1-year follow-up group (100 acute; 100 chronic). The 5-year cohort required additional imaging details, and the 1-year

  2. [Application of nested case-control study on safe evaluation of post-marketing traditional Chinese medicine injection].

    PubMed

    Xiao, Ying; Zhao, Yubin; Xie, Yanming

    2011-10-01

    The nested case-control study design (or the case-control in a cohort study) is described here as a new study design used in safe evaluation of post-marketing traditional Chinese medicine injection. In the nested case-control study, cases of a disease that occur in a defined cohort are identified and, for each, a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case. For many research questions, the nested case-control design potentially offers impressive reductions in costs and efforts of data collection and analysis compared with the full cohort approach, with relatively minor loss in statistical efficiency. The nested case-control design is particularly advantageous for studies in safe evaluation of post-marketing traditional Chinese medicine injection. Some examples of the application of nested case-control study were given.

  3. Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

    PubMed

    Downing, Nicholas S; Shah, Nilay D; Aminawung, Jenerius A; Pease, Alison M; Zeitoun, Jean-David; Krumholz, Harlan M; Ross, Joseph S

    2017-05-09

    Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001

  4. Surveillance of antibiotic resistance

    PubMed Central

    Johnson, Alan P.

    2015-01-01

    Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

  5. Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

    PubMed

    Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

    2017-07-20

    This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79-653). The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

  6. Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies.

    PubMed

    Balassy, Csilla; Roberts, Donna; Miller, Stephen F

    2015-11-01

    Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children.

  7. Nationwide survey on informed consent and ethical review at hospitals conducting post-marketing studies sponsored by pharmaceutical companies.

    PubMed

    Urushihara, Hisashi; Murakami, Yuka; Matsui, Kenji; Tashiro, Shimon

    2017-09-25

      Under the Japanese drug regulatory system, post-marketing studies (PMS) must be in compliance with Good Post-marketing Study Practice (GPSP). The GPSP Ordinance lacks standards for the ethical conduct of PMSs; although only post-marketing clinical trials are subject to Good Clinical Practice.   We conducted a web-based questionnaire survey on the ethical conduct of PMSs in collaboration with the Japanese Society of Hospital Pharmacists and pharmacists belonging to the Society. 1819 hospitals around Japan answered the questionnaire, of which 503 hospitals had conducted company-sponsored PMSs in 2015. 40.2% of the hospitals had obtained informed consent from participating patients in at least one PMS conducted in 2015, the majority of which was in written form. The first and second most frequent reasons for seeking informed consent in PMSs were to meet protocol requirements, followed by the requirement to meet institutional standard operational procedures and the request of the ethical review board of the hospital. Ethical review of PMSs was conducted in 251 hospitals. Despite a lack of standards for informed consent and ethical review in PMSs, a considerable number of study sites employed informed consent and ethical review for PMSs. While company policies and protocols are likely to be major determinants of the ethical conduct of PMSs, the governmental regulatory agency should also play a significant role in implementing a standardized ethical code for the conduct of PMSs.

  8. [Worker's Health Surveillance

    PubMed

    Machado

    1997-01-01

    This paper is part of a broader discussion on the need for more in-depth study of workers' health surveillance practices, which are most often developed empirically, without well-defined theoretical or technical foundations. The paper presents a concept of surveillance in workers' health as a fulcrum for actions in the relationship between the work process and health. It emphasizes the exposure-based perspective involved in the epidemiological approach. Risk situations and effects are placed in spatial and technological context. The model provides an interdisciplinary approach with a technological, social, and epidemiological basis in a three-dimensional structure. A matrix for planning actions in workers' health surveillance is also presented, focusing on the connections between effects, risks, territory, and activities.

  9. Viral surveillance and discovery.

    PubMed

    Lipkin, Walter Ian; Firth, Cadhla

    2013-04-01

    The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Application of PGNAA to plutonium surveillance

    SciTech Connect

    Prettyman, T.H.; Foster, L.A.; Staples, P.

    1997-12-01

    Prompt gamma-ray neutron activation analysis (PGNAA) is a well-established tool for nondestructive elemental analysis of bulk samples. At Los Alamos National Laboratory we are investigating the use of PGNAA as a diagnostic tool for a number of applications, particularly matrix characterization for nondestructive assay and plutonium surveillance. Surveillance is an essential feature of most plutonium facility operations, including routine material processing and research, short-term storage, and processing operations prior to disposal or long-term storage. The ability to identify and assay specific elements from gamma-ray-produced active neutron interrogation (e.g., by neutron capture, nonelastic scattering, and the decay of activation products) makes PGNAA an ideal tool for surveillance. For example, PGNAA can help confirm item descriptions (for example, plutonium chloride versus plutonium oxide). This feature is particularly important in operations involving poorly characterized legacy materials where the material form could adversely impact plutonium-processing operations.

  11. MARGINAL EXPENSE OIL WELL WIRELESS SURVEILLANCE MEOWS

    SciTech Connect

    Mason M. Medizade; John R. Ridgely; Donald G. Nelson

    2004-11-01

    A marginal expense oil well wireless surveillance system to monitor system performance and production from rod-pumped wells in real time from wells operated by Vaquero Energy in the Edison Field, Main Area of Kern County in California has been successfully designed and field tested. The surveillance system includes a proprietary flow sensor, a programmable transmitting unit, a base receiver and receiving antenna, and a base station computer equipped with software to interpret the data. First, the system design is presented. Second, field data obtained from three wells is shown. Results of the study show that an effective, cost competitive, real-time wireless surveillance system can be introduced to oil fields across the United States and the world.

  12. Outbreaks of H5N1 in poultry in Thailand: the relative role of poultry production types in sustaining transmission and the impact of active surveillance in control.

    PubMed

    Walker, Patrick; Cauchemez, Simon; Hartemink, Nienke; Tiensin, Thanawat; Ghani, Azra C

    2012-08-07

    H5N1, highly pathogenic avian influenza, continues to pose a public health risk in the countries of southeast Asia where it has become endemic. However, in Thailand, which experienced two of the largest recorded epidemics in 2004-2005, the disease has been successfully reduced to very low levels. We fitted a spatio-temporal model of the spread of infection to outbreak data collected during the second wave of outbreaks to assess the extent to which different poultry types were responsible for propagating infection. Our estimates suggest that the wave of outbreaks would not have been possible without the contribution of backyard flocks to the susceptibility of a sub-district. However, we also estimated that outbreaks involving commercial poultry, a much larger sector in Thailand than in neighbouring countries, were disproportionately infectious, a factor which was also crucial in sustaining the wave. As a result, implemented measures that aim to reduce the role of commercial farms in the spread of infection, such as the drive to bring aspects of the supply chain 'in house', may help to explain the subsequent success in controlling H5N1 in Thailand. We also found that periods of active surveillance substantially improved the rate of outbreak detection.

  13. Intussusception in southern India: comparison of retrospective analysis and active surveillance.

    PubMed

    Jehangir, Susan; John, Jacob; Rajkumar, Sangeeth; Mani, Betty; Srinivasan, Rajan; Kang, Gagandeep

    2014-08-11

    through active monitoring in the trial. The WHO recommendation of sentinel hospital based surveillance for post-marketing surveillance after rotavirus vaccine introduction is likely to a better approach than active surveillance. Copyright © 2014. Published by Elsevier Ltd.

  14. Number needed to harm in the post-marketing safety evaluation: results for rosiglitazone and pioglitazone.

    PubMed

    Mendes, Diogo; Alves, Carlos; Batel-Marques, Francisco

    2015-12-01

    Our aim is to investigate the usefulness of metric indices in post-marketing safety evaluations by estimating number needed to harm (NNH) values for cardiovascular (CV) adverse outcomes for rosiglitazone and pioglitazone. Reports from regulatory authorities (RAs) were consulted, and Medline searches were performed to identify studies assessing CV risks [all-cause death, CV death, myocardial infarction (MI), stroke, or congestive heart failure (CHF)] for thiazolidinediones. Meta-analyses were performed to pool evidence from randomized controlled trials (RCTs) and observational studies (OS). NNHs [with 95% confidence intervals (CI)] per year were estimated for CV adverse events. Reports from RAs included two meta-analyses of short-term RCTs, two long-term RCTs (RECORD and PROACTIVE), and a systematic review of OS (n = 29). The Medline search identified six additional OS. Statistically significant NNH values were obtained for the following: (i) rosiglitazone versus control on MI and CHF in the meta-analysis of RCTs (NNH = 16; 95%CI = 10-255; and NNH = 7; 95%CI = 5-16, respectively) and meta-analysis of OS (NNH = 12; 95%CI = 9-20; and NNH = 5; 95%CI = 32-131, respectively) and on CHF in the RECORD (NNH = 6; 95%CI = 4-14); (ii) pioglitazone versus control on CHF (NNH = 11; 95%CI = 6, 403) in the meta-analysis of RCTs and PROACTIVE (NNH = 12; 95%CI = 8-43); and (iii) rosiglitazone versus pioglitazone on MI (NNH = 69; 95%CI = 32-379), stroke (NNH = 36; 95%CI = 20-225), CHF (NNH = 33; 95%CI = 19-47), and all-cause death (NNH = 63; 95%CI = 49-100) in the meta-analysis of OS. The NNH values suggested an increased CV risk with rosiglitazone versus pioglitazone across several sources of information. The inclusion of objective metrics in post-marketing drug's benefit-risk assessments could be of increased value and help RAs to make consistent decisions on drug safety. Copyright © 2015

  15. Sensing Surveillance & Navigation

    DTIC Science & Technology

    2012-03-07

    Fully Adaptive Radar” Sensor Processing including MIMO Sensing for Object Identification: Analysis and Synthesis of Invariants Integrated...Operators are overwhelmed by massive volumes of high dimensional multi-sensor data • Challenges -Efficiently process data to extract inherent...Sensing & Surveillance Systems • Develop toolkit for matrix treatment of MIMO radar wave-forms • Multiple-Input/Multiple-Output • enable performance

  16. Diagnostics and surveillance methods

    USDA-ARS?s Scientific Manuscript database

    Detection and diagnosis of influenza A virus (IAV) infection in animals requires a laboratory test since disease from IAV presents no pathognomonic signs. Diagnosis and surveillance of animal influenza focuses on the detection of virus or type specific antibodies. Whether one targets the virus or ...

  17. A Population Health Surveillance Theory

    PubMed Central

    Bigras-Poulin, Michel; Michel, Pascal; Ra