DOCSLIB.ORG

COHERENCE In-Vitro.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
COHERENCE In-Vitro.Pdf International Journal of Antimicrobial Agents 57 (2021) 106344 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag Review Systematic review and meta-analysis of in vitro efficacy of antibiotic combination therapy against carbapenem-resistant Gram-negative bacilli ∗ Luigia Scudeller a,1, Elda Righi b,1, , Margherita Chiamenti b, Damiano Bragantini b, Giulia Menchinelli c,d, Paolo Cattaneo b, Christian G. Giske e, Thomas Lodise f, Maurizio Sanguinetti c,d, Laura J.V. Piddock g, François Franceschi g, Sally Ellis g, ∗ Elena Carrara b, Alessia Savoldi b, Evelina Tacconelli b,h,i, a Clinical Epidemiology and Biostatistics, IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano Foundation, Milan, Italy b Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, P.Le L.A. Scuro 10, 37134 Verona, Italy c Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy d Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy e Clinical Microbiology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden f Albany College of Pharmacy and Health Sciences, Albany, New York, USA g Global Antibiotic Research & Development Partnership (GARDP), 15 Chemin Louis-Dunant, Geneva, Switzerland h Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Otfried Müller Straße 12, 72074 Tübingen, Germany i German Centre for Infection Research (DZIF), Clinical Research Unit for Healthcare Associated Infections, Tübingen, Germany a r t i c l e i n f o a b s t r a c t Article history: The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) in- Received 20 January 2021 fections remains controversial. In vitro models may predict the efficacy of antibiotic regimens Accepted 3 April 2021 against CR-GNB. A systematic review and meta-analysis was performed including pharmacoki- netic/pharmacodynamic (PK/PD) and time–kill (TK) studies examining the in vitro efficacy of antibi- Editor: Dr Jim Gray otic combinations against CR-GNB [PROSPERO registration no. CRD42019128104]. The primary out- come was in vitro synergy based on the effect size (ES): high, ES ≥ 0.75, moderate, 0.35 < ES < Keywords: 0.75; low, ES ≤ 0.35; and absent, ES = 0). A network meta-analysis assessed the bactericidal ef- In vitro synergy Antibiotic combination fect and re-growth rate (secondary outcomes). An adapted version of the ToxRTool was used for PK/PD risk-of-bias assessment. Over 180 combination regimens from 136 studies were included. The most Time–kill frequently analysed classes were polymyxins and carbapenems. Limited data were available for cef- Carbapenem-resistant bacteria tazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. High or moderate synergism was shown for polymyxin/rifampicin against Acinetobacter baumannii [ES = 0.91, 95% confidence in- terval (CI) 0.44–1.00], polymyxin/fosfomycin against Klebsiella pneumoniae (ES = 1.00, 95% CI 0.66– 1.00) and imipenem/amikacin against Pseudomonas aeruginosa (ES = 1.00, 95% CI 0.21–1.00). Com- pared with monotherapy, increased bactericidal activity and lower re-growth rates were reported for colistin/fosfomycin and polymyxin/rifampicin in K. pneumoniae and for imipenem/amikacin or imipenem/tobramycin against P. aeruginosa. High quality was documented for 65% and 53% of PK/PD and TK studies, respectively. Well-designed in vitro studies should be encouraged to guide the selection of combination therapies in clinical trials and to improve the armamentarium against carbapenem-resistant bacteria. ©2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) 1. Introduction ∗ Corresponding authors. Tel.: + 39 045 812 8284. The rapid emergence and dissemination of multidrug-resistant E-mail address: [email protected] (E. Tacconelli). 1 These two authors contributed equally to this study. (MDR) Gram-negative bacilli (GNB) is recognised as a major public https://doi.org/10.1016/j.ijantimicag.2021.106344 0924-8579/© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) L. Scudeller, E. Righi, M. Chiamenti et al. International Journal of Antimicrobial Agents 57 (2021) 106344 health issue [ 1 , 2 ]. Treatment options against carbapenem-resistant 2018. All search strings were discussed with a qualified librarian. (CR) GNB remain limited [3] . To direct research and development Details of the bibliographic search strategy are listed in the Sup- of new antibiotics, in 2017 the World Health Organization (WHO) plementary methods. Bibliographies of reviews and original pub- published a list of pathogens prioritising CR Acinetobacter bau- lications were hand-searched for further studies. To reduce publi- mannii , CR Pseudomonas aeruginosa and CR Enterobacteriaceae [4] . cation bias, the Infectious Diseases Society of America (IDSA) and Novel compounds displaying in vitro activity against CR-GNB have European Congress of Clinical Microbiology and Infectious Diseases been mainly tested in clinical trials, often including carbapenem- (ECCMID) conference proceedings for the years 2016–2018 were susceptible bacteria [3] . Other antibiotic classes (e.g. polymyxins, also reviewed. carbapenems, aminoglycosides) have been used against CR-GNB alone or in combination in observational studies [ 5 , 6 ]. The ra- tionale for combining two or more antibiotics against CR-GNB is 2.2. Selection criteria based on the possibility to achieve a higher rate of bacterial killing and to reduce the development of resistance. Despite promising re- Reports including data of bacterial killing curves from PK/PD sults highlighted by some studies, pooled data from meta-analyses and TK studies analysing combination therapies against CR-GNB have not shown clear evidence to support the use of antibiotic were included. Any type of study except reviews, editorials and combinations in the treatment of CR-GNB infections [5–8] . More- protocol papers was eligible for inclusion, and all antibiotic dosage over, results from well-designed clinical trials including infections schedules and frequencies were considered. Standard inoculum × 5 by MDR-GNB are lacking, limiting the evidence on the effectiveness sizes (4 10 CFU/mL or the nearest available value) were selected of older compared with novel compounds. [14]. Gold-standard broth microdilution was considered as the sus- The COHERENCE project (COmbination tHErapy to treat sepsis ceptibility testing method. due to carbapenem-Resistant bacteria in adult and pediatric popu- lations: EvideNCE and common practice) aimed to coherently and 2.3. Data extraction comprehensively analyse data on the use of antibiotic combina- tions for treating severe infections caused by CR-GNB. The project Two investigators (MC and DB) independently assessed each was commissioned by the Global Antibiotic Research and Develop- potentially relevant study for eligibility. Disagreements were re- ment Partnership (GARDP) and was intended to have a global per- solved by consultation with a third party (ER). If eligibility could spective from real-world clinical practice assessment of published not be determined, the full article was retrieved. evidence from in vitro and clinical studies. The present article re- A standardised data extraction method was used to record rel- ports data deriving from the meta-analyses performed on in vitro evant features of each study in a database, including study char- studies. acteristics (year of publication, country, type of in vitro combina- In vitro assessments of bacterial killing and antibiotic synergism tion testing), bacterial characteristics (type of bacterial strain and can be used to support the effectiveness of antibiotic combinations number of isolated tested, method of antimicrobial susceptibility against MDR-GNB [9]. A recent meta-analysis including 26 clinical testing and carbapenemase identification) and antimicrobial ther- cases from 11 reports showed that synergy-guided antibiotic com- apy (type and dose of antibiotic administration, treatment dura- bination therapy against MDR-GNB (54% P. aeruginosa, 27% Enter- tion). Bacterial isolates were considered resistant to carbapenems obacteriaceae and 19% A. baumannii) was significantly associated according to the local interpretive criteria. Unless otherwise speci- = with survival [odds ratio (OR) 0.44, 95% confidence interval (CI) fied, resistance was determined according to European Committee 0.20–0.98] [10]. on Antimicrobial Susceptibility Testing (EUCAST) 2019 breakpoints There are currently only two meta-analyses assessing the ef- [15] . Combination therapy was defined as the association of at least fectiveness of antibiotic combinations against CR GNB, including two or more antibiotics used to treat CR-GNB. in vitro studies up to March 2013 and July 2014, respectively Primary outcome assessed was in vitro synergy or antagonism [11,12]. These reviews, however, restricted the search only to se- > of combination therapy defined as a 2 log10 reduction or increase, lected pathogens and to a limited number of antibiotic dosages and respectively, in CFU/mL
Load more

Recommended publications
  • In Vitro Susceptibilities of Escherichia Coli and Klebsiella Spp. To
    Jpn. J. Infect. Dis., 60, 227-229, 2007 Short Communication In Vitro Susceptibilities of Escherichia coli and Klebsiella Spp. to Ampicillin-Sulbactam and Amoxicillin-Clavulanic Acid Birgul Kacmaz* and Nedim Sultan1 Department of Central Microbiology and 1Department of Microbiology, Faculty of Medicine, Gazi University, Ankara, Turkey (Received January 30, 2007. Accepted April 13, 2007) SUMMARY: Ampicillin-sulbactam (A/S) and amoxicillin-clavulanic acid (AUG) are thought to be equally efficacious clinically against the Enterobacteriaceae family. In this study, the in vitro activities of the A/S and AUG were evaluated and compared against Escherichia coli and Klebsiella spp. Antimicrobial susceptibility tests were performed by standard agar dilution and disc diffusion techniques according to the Clinical and Laboratory Standards Institute (CLSI). During the study period, 973 strains were isolated. Of the 973 bacteria isolated, 823 were E. coli and 150 Klebsiella spp. More organisms were found to be susceptible to AUG than A/S, regardless of the susceptibility testing methodology. The agar dilution results of the isolates that were found to be sensitive or resistant were also compatible with the disc diffusion results. However, some differences were seen in the agar dilution results of some isolates that were found to be intermediately resistant with disc diffusion. In E. coli isolates, 17 of the 76 AUG intermediately resistant isolates (by disc diffusion), and 17 of the 63 A/S intermediately resistant isolates (by disc diffusion) showed different resistant patterns by agar dilution. When the CLSI breakpoint criteria are applied it should be considered that AUG and A/S sensitivity in E. coli and Klebsiella spp.
    [Show full text]
  • Optimizing Product Lifecycle Management with Real World
    1/17/2019 Optimizing Product Lifecycle Management With Real-World Evidence :: Medtech Insight This copy is for your personal, non-commercial use. For high-quality copies or electronic reprints for distribution to colleagues or customers, please call +44 (0) 20 3377 3183 Printed By Optimizing Product Lifecycle Management With Real- World Evidence 27 Dec 2018 SPONSORED Executive Summary Thought Leadership In Association With IQVIA An increasingly data-rich healthcare sector presents both opportunities and challenges for the MedTech industry, just as it does for the health systems and patients served by MedTech products. Used intelligently and appropriately, the vast quantities of real-world data emanating from multiple healthcare sources, such as electronic medical records (EMRs), claims databases, products and disease registries, provide the raw material for real-world evidence (RWE) that can inform strategy and decision- making throughout the MedTech-product lifecycle. An increasingly data-rich healthcare sector presents both opportunities and challenges for the MedTech industry, just as it does for the health systems and patients served by MedTech products. Used intelligently and appropriately, the vast quantities of real-world data emanating from multiple healthcare sources, such as electronic medical records (EMRs), claims databases, products and disease registries, provide the raw material for real-world evidence (RWE) that can inform strategy and decision-making throughout the MedTech-product lifecycle. “What we’re seeing in the industry
    [Show full text]
  • Ampicillin (Ampicillin Sodium) INJECTION, POWDER, FOR
    Ampicillin for Injection, USP Rx Only (For Intramuscular or Intravenous Injection) To reduce the development of drug-resistant bacteria and maintain the effectiveness of ampicillin and other antibacterial drugs, ampicillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. DESCRIPTION Ampicillin for injection, USP the monosodium salt of [2S-[2α,5α,6β(S*)]]-6- [(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, is a synthetic penicillin. It is an antibacterial agent with a broad spectrum of bactericidal activity against both penicillin-susceptible Gram-positive organisms and many common Gram-negative pathogens. Ampicillin for injection, USP is a white to cream-tinged, crystalline powder. The reconstituted solution is clear, colorless and free from visible particulates. Each vial of Ampicillin for injection, USP contains ampicillin sodium equivalent to 250 mg, 500 mg, 1 gram or 2 grams ampicillin. Ampicillin for injection, USP contains 65.8 mg [2.9 mEq] sodium per gram ampicillin. It has the following molecular structure: The molecular formula is C16H18N3NaO4S, and the molecular weight is 371.39. The pH range of the reconstituted solution is 8 to 10. CLINICAL PHARMACOLOGY Ampicillin for injection diffuses readily into most body tissues and fluids. However, penetration into the cerebrospinal fluid and brain occurs only when the meninges are inflamed. Ampicillin is excreted largely unchanged in the urine and its excretion can be delayed by concurrent administration of probenecid. Due to maturational changes in renal function, ampicillin half-life decreases as postmenstrual age (a sum of gestational age and postnatal age) increases for infants with postnatal age of less than 28 days.
    [Show full text]
  • Use of in Vivo and in Vitro Models to Guide Dose Selection for Neonatal Infections
    Use of In Vivo and In Vitro Models to Guide Dose Selection for Neonatal Infections Professor William Hope Antimicrobial Pharmacodynamics & Therapeutics University of Liverpool September 2016 Disclosures • William Hope has received research funding from Pfizer, Gilead, Astellas, AiCuris, Amplyx, Spero Therapeutics and F2G, and acted as a consultant and/or given talks for Pfizer, Basilea, Astellas, F2G, Nordic Pharma, Medicines Company, Amplyx, Mayne Pharma, Spero Therapeutics, Auspherix, Cardeas and Pulmocide. First of all BIOMARKER OUTCOME OF CLINICAL DOSE INTEREST/IMPORTANCE •Decline in Log10CFU/mL •Linked to an outcome of clinical interest •Survival 7 6 5 4 CFU/g) CNS 10 3 Effect (log 2 1 0 0.01 0.1 1 10 100 1000 Total doseDose 5FC (mg/kg) PHARMACOKINETICS PHARMACODYNAMICS Concept of Expensive Failure COST Derisking White Powder Preclinical Program Clinical Program Concept from Trevor Mundell & Gates Foundation And this… Normal Therapeutics Drug A, Dose A1 versus Drug B, Dose B1 Pharmacodynamics is the Bedrock of ALL Therapeutics…it sits here without being seen One of the reasons simple scaling does not work is the fact pharmacodynamics are different Which means the conditions that govern exposure response relationships in neonates need to be carefully considered …Ignore these at your peril Summary of Preclinical Pharmacodynamic Studies for Neonates** • Hope el al JID 2008 – Micafungin for neonates – Primary question of HCME – Rabbit model with hematogenous dissemination • Warn et al AAC 2010 – Anidulafungin for neonates – Primary question
    [Show full text]
  • In Vitro–In Vivo Correlation (IVIVC): a Strategic Tool in Drug Development
    alenc uiv e & eq B io io B a f v o a Sakore and Chakraborty, J Bioequiv Availab 2011, S3 i l l a a b n r i l i u DOI: 10.4172/jbb.S3-001 t y o J Journal of Bioequivalence & Bioavailability ISSN: 0975-0851 Review Article OpenOpen Access Access In Vitro–In Vivo Correlation (IVIVC): A Strategic Tool in Drug Development Somnath Sakore* and Bhaswat Chakraborty Cadila Pharmaceuticals Ltd, Research & Development, 1389, Trasad Road, Dholka, Ahmedabad 387810, Gujarat, India Abstract In Vitro–In Vivo Correlation (IVIVC) plays a key role in pharmaceutical development of dosage forms. This tool hastens the drug development process and leads to improve the product quality. It is an integral part of the immediate release as well as modified release dosage forms development process. IVIVC is a tool used in quality control for scale up and post-approval changes e.g. to improve formulations or to change production processes & ultimately to reduce the number of human studies during development of new pharmaceuticals and also to support the biowaivers. This article provides the information on the various guidances, evaluation, validation, BCS application in IVIVC, levels of IVIVC, applications of IVIVC in mapping, novel drug delivery systems and prediction of IVIVC from the dissolution profile characteristics of product. Keywords: IVIVC definitions; Predictions; BCS classification; IVIVC definitions IVIVC Levels; Applications, Guidance United state pharmacopoeia (USP) definition of IVIVC Abbreviations: IVIVC: In Vitro In Vivo correlation; FDA: Food and Drug Administration; AUC: Area Under Curve; MDT vitro: The establishment of a rational relationship between a biological Mean in vitro Dissolution Time; MRT: Mean Residence Time; BCS: property, or a parameter derived from a biological property produced Biopharmaceutical Classification System by a dosage form, and a physicochemical property or characteristic of the same dosage form [2].
    [Show full text]
  • Opportunities and Gaps in Real-World Evidence for Medical Devices 1201 Pennsylvania Ave
    Robert J. Margolis, MD Center for Health Policy Duke Opportunities and Gaps in Real-World Evidence for Medical Devices 1201 Pennsylvania Ave. NW Suite 500 ● Washington, DC 20004 April 26, 2017 Meeting Summary Purpose Medical devices have substantially improved our ability to manage and treat a wide variety of conditions. Given the extent of their use, it is important that there be an effective system for monitoring medical device performance and the associated patient outcomes. Although significant steps have been takento enable evaluation and safety surveillance of medical products, critical gaps remain in capturingreal-world data(RWD) to evaluate medical devices before and afterFDA approval. As the collection and use of RWD advances, real-world evidence (RWE) will be able to incorporate data captured throughout the total medical device lifecycle, informing and improving the next iteration of devices. 1 The recently launched National Evaluation System for health Technology CoordinatingCenter(NESTcc) is compilingalandscape analysis report to facilitate conversation and encourage the increased and improved use of RWD with stakeholders across the medical device ecosystem. The analysis will build on the work ofFDA,thePlanning Board, the Registry Taskforce, and many stakeholders and experts. The long-term goal is forthelandscape analysis to become a living document and a NESTcc-maintained resource that encourages communication and collaboration. This workshop convened a broad range of experts and stakeholders to provide input on the analysis, including highlighting some of the current uses of RWD/RWEand identifying where gaps still remain.2 For overadecade, there have been increasing concerns that the post-market surveillance system in the United States was not fully meeting the demands of a constantly evolving medical device ecosystem.
    [Show full text]
  • Meta-Analysis of Randomized Trials of Ivermectin to Treat SARS-Cov-2 Infection
    Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection Andrew Hill ( [email protected] ) University of Liverpool Ahmed Abdulamir College of Medicine, Alnahrain University, Baghdad, Iraq Sabeena Ahmed International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh, Asma Asghar Department of Medicine, Combined Military Hospital, Lahore, Pakistan Olufemi Emmanuel Babalola Bingham University / Lagos University, Nigeria Rabia Basri Fatima Memorial Hospital, Lahore, Pakistan Carlos Chaccour Barcelona Institute for Global Health, Clinica Universidad de Navarra, Spain Aijaz Zeeshan Khan Chachar Fatima Memorial Hospital, Lahore, Pakistan Abu Tauib Mohammed Chowdhury Xi'an Jiaotong University Medical College First Aliated Hospital, Shaannxi, China Ahmed Elgazzar Faculty of Medicine, Benha University, Benha, Egypt Leah Ellis Faculty of Medicine, Imperial College, London, UK Jonathan Falconer Department of Infectious Diseases, Chelsea and Westminster Hospital, London, UK Anna Garratt Department of Infectious Diseases, University Hospital of Wales, Cardiff and Vale University Health Board, UK Basma Hany Faculty of Medicine, Benha University, Benha, Egypt Hashim A Hashim Alkarkh Hospital, Alateya, Baghdad, Iraq Wasim Ul Haque Department of Nephrology, BIRDEM General Hospital, Dhaka, Bangladesh Arshad Hayat Department of Medicine, Combined Military Hospital, Lahore, Pakistan Shuixiang He Xi'an Jiaotong University Medical College First Aliated Hospital, Shaanxi, China Ramin Jamshidian Jundishapur University School
    [Show full text]
  • In Vitro Diagnostic Medical Devices
    In vitro diagnostic medical devices SUMMARY In vitro diagnostic medical devices are tests used on biological samples to determine the status of a person's health. The industry employs about 75 000 people in Europe, and generates some €11 billion in revenue per year. In September 2012, the European Commission (EC) published a proposal for a new regulation on in vitro diagnostic medical devices, as part of a larger legislative package on medical devices. The proposed legislation aims at enhancing safety, traceability and transparency without inhibiting innovation. In April 2014, the European Parliament (EP) amended the legislative proposals to strengthen the rights of patients and consumers and take better into account the needs of small and medium-sized enterprises (SMEs). Some stakeholders consider that a provision for mandatory genetic counselling interferes with the practice of medicine in Member States and violates the subsidiarity principle. Device manufacturers warn that the proposed three-year transition period may be too tight. In this briefing: Introduction EU legislation Commission proposal for a new Regulation European Parliament Expert analysis and stakeholder positions Further reading EPRS In vitro diagnostic medical devices Glossary Companion diagnostic: (in vitro) medical device which provides information that is essential for the safe and effective use of a corresponding drug or biological product. In vitro diagnostic medical device: test performed outside the human body on biological samples to detect diseases, conditions, or infections. Notified body: (private-sector) organisation appointed by an EU Member State to assess whether a product meets certain standards, for example those set out in the Medical Devices Directive.
    [Show full text]
  • (GIVIMP) for the Development and Implementation of in Vitro Methods for 829 Regulatory Use in Human Safety Assessment
    1 2 Draft GUIDANCE DOCUMENT ON GOOD IN VITRO METHOD PRACTICES (GIVIMP) 3 FOR THE DEVELOPMENT AND IMPLEMENTATION OF IN VITRO METHODS FOR 4 REGULATORY USE IN HUMAN SAFETY ASSESSMENT 5 6 FOREWORD 7 8 A guidance document on Good In Vitro Method Practices (GIVIMP) for the development and 9 implementation of in vitro methods for regulatory use in human safety assessment was 10 identified as a high priority requirement. The aim is to reduce the uncertainties in cell and 11 tissue-based in vitro method derived predictions by applying all necessary good scientific, 12 technical and quality practices from in vitro method development to in vitro method 13 implementation for regulatory use. 14 The draft guidance is coordinated by the European validation body EURL ECVAM and has 15 been accepted on the work plan of the OECD test guideline programme since April 2015 as a 16 joint activity between the Working Group on Good Laboratory Practice (GLP) and the 17 Working Group of the National Coordinators of the Test Guidelines Programme (WNT). 18 The draft document prepared by the principal co-authors has been sent in September 2016 to 19 all 37 members of the European Union Network of Laboratories for the Validation of 20 Alternative Methods (EU-NETVAL1) and has been subsequently discussed at the EU- 21 NETVAL meeting on the 10th of October 2016. 22 By November/December 2016 the comments of the OECD Working Group on GLP and 23 nominated experts of the OECD WNT will be forwarded to EURL ECVAM who will 24 incorporate these and prepare an updated version.
    [Show full text]
  • Guidance for Industry and FDA Staff: in Vitro Diagnostic (IVD) Device Studies
    1 Guidance for Industry and FDA Staff In Vitro Diagnostic (IVD) Device Studies -Frequently Asked Questions Document issued on: June 25, 2010 The draft of this document was issued on October 25, 2007. This document supersedes "Guidance for FDA Staff: Regulating In Vitro Diagnostic Device (IVD) Studies," issued December 17, 1999. For questions regarding this document, contact Sally Hojvat, Ph.D. in CDRH at 301-796-5455 or the Office of Communication, Outreach and Development in CBER at 1-800-835-4709 or 301- 827-1800. U.S. Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health Center for Biologics Evaluation and Research 2 Preface Additional Copies Additional copies are available from the Internet at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu ments/ucm071230.pdf, Or, contact: Office of Communication, Outreach and Development, HFM-40 Center for Biologics Evaluation and Research Food and Drug Administration 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448 Internet: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/defaul t.htm Tel: 800-835-4709 or 301-827-1800 3 Table of Contents I. Background................................................................................................................................4 II. Introduction.............................................................................................................................. 5 III. General Regulatory Issues....................................................................................................
    [Show full text]
  • Prevalence of Structural Birth Defects in IVF-ICSI Pregnancies Resulting from Autologous and Donor Oocytes in Indian Sub-Continent: Results from 2444 Births
    Received: 19 August 2018 | Revised: 9 January 2019 | Accepted: 11 January 2019 DOI: 10.1111/aogs.13541 ORIGINAL RESEARCH ARTICLE Prevalence of structural birth defects in IVF-ICSI pregnancies resulting from autologous and donor oocytes in Indian sub-continent: Results from 2444 births Manish Banker1 | Parul Arora1 | Jwal Banker2 | Hetal Benani1 | Sandeep Shah1 | Parmeswaran Grace Luther Lalitkumar3 1Nova‐IVI Fertility, Ahmedabad, India Abstract 2Srimati Bhikiben Kanjibhai Shah Medical Institute and Research Center, Vadodara, Introduction: This study was conducted to evaluate and compare the incidence of India birth defects in In‐Vitro Fertilization‐Intra Cytoplasmic Sperm Injection (IVF‐ICSI) 3Nova‐IVI Fertility, Bangalore, India pregnancies with autologous and donor oocytes. As a secondary outcome, the preva‐ Correspondence lence of birth defects in IVF‐ICSI pregnancies was compared with those from spon‐ Parul Arora, Nova IVI Fertility, 108, Swastik Society, Ahmedabad 380009, India. taneous conceptions in India. Email: [email protected] Material and methods: This retrospective study included 2444 births resulting from IVF‐ICSI cycles from autologous (n = 1743) and donor oocytes (n = 701) during a 3‐ year period in an Indian infertility center. Birth defects, if any, were noted antenatally and followed till the neonatal period, in case of live birth. Results: The overall prevalence of birth defects in IVF‐ICSI pregnancies in this study was 29/2444 (118.6/10 000 births) and the most common congenital anomaly was cardiac malformation (32.7/10 000 births) followed by genitourinary (28.6/10 000 births). The risks of birth defects resulting from autologous and donor oocytes did not differ (114.7/10 000 vs 128.38/10 000; P > 0.05).
    [Show full text]
  • Concordance of Functional in Vitro Data and Epidemiological Associations in Complex Disease Genetics John P
    September 2006 ⅐ Vol. 8 ⅐ No. 9 article Concordance of functional in vitro data and epidemiological associations in complex disease genetics John P. A. Ioannidis, MD,1,2,3and Fotini K. Kavvoura, MD1 Purpose: We aimed to assess whether epidemiological evidence on genetic associations for complex diseases concord with in vitro functional data. Methods: We examined 36 studies on bi-allelic markers and 23 studies on haplotypes where investigators had addressed both epidemiological associations and the functional effect of the same gene variants in luciferase reporter systems in vitro. Results: There was no correlation between epidemio- logical odds ratios and luciferase activity ratios (Ϫ0.09, P ϭ 0.60). Luciferase activity ratios could not tell whether a probed epidemiologic association would be significant or not (area under receiver operating characteristics curve, 0.52). Luciferase results usually were qualitatively similar across cell lines and experimental conditions, with some exceptions. A luciferase activity ratio of 1.44 adequately separated statistically significant from non-significant functional differences (area under receiver operating characteristics curve, 0.95). Binary and continuous disease outcomes usually gave concordant results; other in vitro methods, in particular EMSA, agreed with luciferase results. Selective reporting and use of different variants and contrasts between functional and epidemiological analyses were common in these studies. Conclusions: In vitro biological data and epidemiology provide indepen- dent lines of evidence on complex diseases. We provide suggestions for improving the design and reporting of studies addressing both in vitro and epidemiological effects. Genet Med 2006:8(9):583–593. Key Words: function, gene-disease association, polymorphism, gene, luciferase Variability in the human genome amounts to over 5 million challenge to evaluate their impact on gene transcription, let polymorphisms, but only a fraction of them has biological and alone protein levels and activity.
    [Show full text]