FDA Briefing Document: Moderna COVID-19 Vaccine
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Exclusions Granted December 17, 2019
69012 Federal Register / Vol. 84, No. 242 / Tuesday, December 17, 2019 / Notices notice setting out the process for the of the HTSUS, as set out in the Annex printed in various colors, valued at product exclusions, and opened a of the notice published at 84 FR 49600 $0.88 or more but not over $2.42 per kg’’ public docket. See 83 FR 47236 (the (September 20, 2019). in lieu thereof. September 18 notice). Subparagraphs A(2–7) of the Annex 7. U.S. note 20(v)(37) to subchapter III Under the September 18 notice, correct errors in U.S. notes 20(v)(21), of chapter 99 of the Harmonized Tariff requests for exclusion had to identify 20(v)(22), 20(v)(36), 20(v)(71), 20(v)(72), Schedule of the United States is the product subject to the request in and 20(v)(87) to subchapter III of modified by deleting ‘‘plastic sheeting terms of the physical characteristics that chapter 99 of the HTSUS, as set out in made of plain-woven, high-density distinguish it from other products the Annex of the notice published at 84 polyethylene fabric coated on both sides within the relevant 8-digit subheading FR 49600 (September 20, 2019). with low-density polyethylene, in rolls covered by the $16 billion action. In order to conform to the U.S. Trade measuring 5 m in width’’ and inserting Requestors also had to provide the 10- Representative’s intent to grant certain ‘‘plastic sheeting, core/scrim woven digit subheading of the HTSUS most exclusion requests, Subparagraphs A(8– layer of high-density polyethylene applicable to the particular product 9) of the Annex make amendments to (HDPE) textile strip, coated on both requested for exclusion, and could U.S. -
FDA Oncology Experience in Innovative Adaptive Trial Designs
Innovative Adaptive Trial Designs Rajeshwari Sridhara, Ph.D. Director, Division of Biometrics V Office of Biostatistics, CDER, FDA 9/3/2015 Sridhara - Ovarian cancer workshop 1 Fixed Sample Designs • Patient population, disease assessments, treatment, sample size, hypothesis to be tested, primary outcome measure - all fixed • No change in the design features during the study Adaptive Designs • A study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data (interim data) from subjects in the study 9/3/2015 Sridhara - Ovarian cancer workshop 2 Bayesian Designs • In the Bayesian paradigm, the parameter measuring treatment effect is regarded as a random variable • Bayesian inference is based on the posterior distribution (Bayes’ Rule – updated based on observed data) – Outcome adaptive • By definition adaptive design 9/3/2015 Sridhara - Ovarian cancer workshop 3 Adaptive Designs (Frequentist or Bayesian) • Allows for planned design modifications • Modifications based on data accrued in the trial up to the interim time • Unblinded or blinded interim results • Control probability of false positive rate for multiple options • Control operational bias • Assumes independent increments of information 9/3/2015 Sridhara - Ovarian cancer workshop 4 Enrichment Designs – Prognostic or Predictive • Untargeted or All comers design: – post-hoc enrichment, prospective-retrospective designs – Marker evaluation after randomization (example: KRAS in cetuximab -
FORMULAS from EPIDEMIOLOGY KEPT SIMPLE (3E) Chapter 3: Epidemiologic Measures
FORMULAS FROM EPIDEMIOLOGY KEPT SIMPLE (3e) Chapter 3: Epidemiologic Measures Basic epidemiologic measures used to quantify: • frequency of occurrence • the effect of an exposure • the potential impact of an intervention. Epidemiologic Measures Measures of disease Measures of Measures of potential frequency association impact (“Measures of Effect”) Incidence Prevalence Absolute measures of Relative measures of Attributable Fraction Attributable Fraction effect effect in exposed cases in the Population Incidence proportion Incidence rate Risk difference Risk Ratio (Cumulative (incidence density, (Incidence proportion (Incidence Incidence, Incidence hazard rate, person- difference) Proportion Ratio) Risk) time rate) Incidence odds Rate Difference Rate Ratio (Incidence density (Incidence density difference) ratio) Prevalence Odds Ratio Difference Macintosh HD:Users:buddygerstman:Dropbox:eks:formula_sheet.doc Page 1 of 7 3.1 Measures of Disease Frequency No. of onsets Incidence Proportion = No. at risk at beginning of follow-up • Also called risk, average risk, and cumulative incidence. • Can be measured in cohorts (closed populations) only. • Requires follow-up of individuals. No. of onsets Incidence Rate = ∑person-time • Also called incidence density and average hazard. • When disease is rare (incidence proportion < 5%), incidence rate ≈ incidence proportion. • In cohorts (closed populations), it is best to sum individual person-time longitudinally. It can also be estimated as Σperson-time ≈ (average population size) × (duration of follow-up). Actuarial adjustments may be needed when the disease outcome is not rare. • In an open populations, Σperson-time ≈ (average population size) × (duration of follow-up). Examples of incidence rates in open populations include: births Crude birth rate (per m) = × m mid-year population size deaths Crude mortality rate (per m) = × m mid-year population size deaths < 1 year of age Infant mortality rate (per m) = × m live births No. -
Incidence and Secondary Transmission of SARS-Cov-2 Infections in Schools
Prepublication Release Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools Kanecia O. Zimmerman, MD; Ibukunoluwa C. Akinboyo, MD; M. Alan Brookhart, PhD; Angelique E. Boutzoukas, MD; Kathleen McGann, MD; Michael J. Smith, MD, MSCE; Gabriela Maradiaga Panayotti, MD; Sarah C. Armstrong, MD; Helen Bristow, MPH; Donna Parker, MPH; Sabrina Zadrozny, PhD; David J. Weber, MD, MPH; Daniel K. Benjamin, Jr., MD, PhD; for The ABC Science Collaborative DOI: 10.1542/peds.2020-048090 Journal: Pediatrics Article Type: Regular Article Citation: Zimmerman KO, Akinboyo IC, Brookhart A, et al. Incidence and secondary transmission of SARS-CoV-2 infections in schools. Pediatrics. 2021; doi: 10.1542/peds.2020- 048090 This is a prepublication version of an article that has undergone peer review and been accepted for publication but is not the final version of record. This paper may be cited using the DOI and date of access. This paper may contain information that has errors in facts, figures, and statements, and will be corrected in the final published version. The journal is providing an early version of this article to expedite access to this information. The American Academy of Pediatrics, the editors, and authors are not responsible for inaccurate information and data described in this version. Downloaded from©2021 www.aappublications.org/news American Academy by of guest Pediatrics on September 27, 2021 Prepublication Release Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools Kanecia O. Zimmerman, MD1,2,3; Ibukunoluwa C. Akinboyo, MD1,2; M. Alan Brookhart, PhD4; Angelique E. Boutzoukas, MD1,2; Kathleen McGann, MD2; Michael J. -
CALENDAR Updated 12.04.20
2020-2021 ACADEMIC YEAR CALENDAR updated 12.04.20 QUARTER 1: Monday August 17 9am-1pm Admin/Faculty Orientation Wednesday August 19 5pm-7pm Orientation: ALL COMMUNITY Wednesday August 26 First day of classes: 2pm dismissal Monday September 7 Labor Day: no school Thursday-Friday September 17–18 all day Parent/teacher conferences (no school for students) Thursday September 17 9am-1pm UVA Library Research (11, 12 students) Monday – Friday Sept. 28-Oct. 2 Student portrait week Monday - Friday October 5-9 Ninth Week: ALL STUDENTS Monday October 12 all day Faculty Work Day, no school Wednesday October 14 morning PSAT Testing (9,10, 11); SAT Testing (12) 2pm-4pm All School field trip Wednesday October 21 2pm Early dismissal/optional Focused Study Wednesday October 21 End of first quarter Thursday October 22 Faculty Work Day, no school Friday October 23 9am-3pm Faculty development (mandatory for all faculty) 9am Grades Due QUARTER 2: Monday October 26 Start 2nd quarter Monday November 2 all day Remote Learning Day, Bring-A-Friend Tuesday November 3, 4 Election, No School Monday November 9 all day Zoom Open House Wednesday November 11 10:30am Sixth Day, all school meet at remote assembly Thursday pending Shakespeare Theater Competition Friday pending all day TEDX Charlottesville (11) Mon. - Fri. November 23 – 27 Fall Break Tuesday December 1 10:30am Sixth Day, all school meet at remote assembly Wednesday December 9 10:30am Sixth Day, all school meet at remote assembly Thursday December 17 10:30am Sixth Day, all school meet at remote assembly Friday December 18 TBA Winter Talent Show Dec. -
COVID-19 Vaccines: Update on Allergic Reactions, Contraindications, and Precautions
Centers for Disease Control and Prevention Center for Preparedness and Response COVID-19 Vaccines: Update on Allergic Reactions, Contraindications, and Precautions Clinician Outreach and Communication Activity (COCA) Webinar Wednesday, December 30, 2020 Continuing Education Continuing education will not be offered for this COCA Call. To Ask a Question ▪ All participants joining us today are in listen-only mode. ▪ Using the Webinar System – Click the “Q&A” button. – Type your question in the “Q&A” box. – Submit your question. ▪ The video recording of this COCA Call will be posted at https://emergency.cdc.gov/coca/calls/2020/callinfo_123020.asp and available to view on-demand a few hours after the call ends. ▪ If you are a patient, please refer your questions to your healthcare provider. ▪ For media questions, please contact CDC Media Relations at 404-639-3286, or send an email to [email protected]. Centers for Disease Control and Prevention Center for Preparedness and Response Today’s First Presenter Tom Shimabukuro, MD, MPH, MBA CAPT, U.S. Public Health Service Vaccine Safety Team Lead COVID-19 Response Centers for Disease Control and Prevention Centers for Disease Control and Prevention Center for Preparedness and Response Today’s Second Presenter Sarah Mbaeyi, MD, MPH CDR, U.S. Public Health Service Clinical Guidelines Team COVID-19 Response Centers for Disease Control and Prevention National Center for Immunization & Respiratory Diseases Anaphylaxis following mRNA COVID-19 vaccination Tom Shimabukuro, MD, MPH, MBA CDC COVID-19 Vaccine -
Version Gdsv27/Ipiv21
Version GDSv27/IPIv21 Interactions Use with Other Vaccines CERVARIX can be given concomitantly with any of the following vaccines: reduced antigen diphtheria-tetanus- acellular pertussis vaccine (dTpa), inactivated poliovirus vaccine (IPV) and the combined dTpa-IPV vaccine; meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (MenACWY-TT); hepatitis A (inactivated) vaccine (HepA), hepatitis B (rDNA) vaccine (HepB) and the combined HepA-HepB vaccine. Administration of CERVARIX at the same time as Twinrix (combined HepA-HepB vaccine) has shown no clinically relevant interference in the antibody response to the HPV and hepatitis A antigens. Anti-HBs geometric mean Human Papillomavirus Vaccine Types 16 and 18 antibody titres were lower on co-administration, but the clinical significance of this observation is not known since the seroprotection rates remain unaffected. The proportion of subjects reaching anti-HBs 10mIU/ml was 98.3% (Recombinant, AS04 adjuvanted) for concomitant vaccination and 100% for Twinrix alone. If CERVARIX is to be given at the same time as another injectable vaccine, the vaccines should always be Qualitative and Quantitative Composition administered at different injection sites. Suspension for injection. Use with Hormonal Contraceptive In clinical efficacy studies, approximately 60% of women who received CERVARIX used hormonal contraceptives. 1 dose (0.5 ml) contains: There is no evidence that the use of hormonal contraceptives has an impact on the efficacy of CERVARIX. Human Papillomavirus type 16 L1 protein1 20 micrograms Human Papillomavirus type 18 L1 protein1 20 micrograms Use with Systemic Immunosuppressive Medications 3-O-desacyl-4’- monophosphoryl lipid A (MPL)2 50 micrograms Aluminium hydroxide, hydrated2 0.5 milligrams Al3+ As with other vaccines it may be expected that in patients receiving immunosuppressive treatment an adequate 1 L1 protein in the form of non-infectious virus-like particles (VLPs) produced by recombinant DNA technology response may not be elicited. -
Pricing*, Pool and Payment** Due Dates January - December 2021 Mideast Marketing Area Federal Order No
Pricing*, Pool and Payment** Due Dates January - December 2021 Mideast Marketing Area Federal Order No. 33 Class & Market Administrator Payment Dates for Producer Milk Component Final Pool Producer Advance Prices Payment Dates Final Payment Due Partial Payment Due Pool Month Prices Release Date Payrolls Due & Pricing Factors PSF, Admin., MS Cooperative Nonmember Cooperative Nonmember January February 3 * February 13 February 22 December 23, 2020 February 16 ** February 16 February 17 Janaury 25 January 26 February March 3 * March 13 March 22 January 21 * March 15 March 16 March 17 February 25 February 26 March March 31 * April 13 April 22 February 18 * April 15 April 16 April 19 ** March 25 March 26 April May 5 May 13 May 22 March 17 * May 17 ** May 17 ** May 17 April 26 ** April 26 May June 3 * June 13 June 22 April 21 * June 15 June 16 June 17 May 25 May 26 June June 30 * July 13 July 22 May 19 * July 15 July 16 July 19 ** June 25 June 28 ** July August 4 * August 13 August 22 June 23 August 16 ** August 16 August 17 July 26 ** July 26 August September 1 * September 13 September 22 July 21 * September 15 September 16 September 17 August 25 August 26 September September 29 * October 13 October 22 August 18 * October 15 October 18 ** October 18 ** September 27 ** September 27 ** October November 3 * November 13 November 22 September 22 * November 15 November 16 November 17 October 25 October 26 November December 1 * December 13 December 22 October 20 * December 15 December 16 December 17 November 26 ** November 26 December January 5, 2022 January 13, 2022 January 22, 2022 November 17 * January 18, 2022 ** January 18, 2022 ** January 18, 2022 ** December 27 ** December 27 ** * If the release date does not fall on the 5th (Class & Component Prices) or 23rd (Advance Prices & Pricing Factors), the most current release preceding will be used in the price calculation. -
Considerations for Causality Assessment of Neurological And
Occasional essay J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2021-326924 on 6 August 2021. Downloaded from Considerations for causality assessment of neurological and neuropsychiatric complications of SARS- CoV-2 vaccines: from cerebral venous sinus thrombosis to functional neurological disorder Matt Butler ,1 Arina Tamborska,2,3 Greta K Wood,2,3 Mark Ellul,4 Rhys H Thomas,5,6 Ian Galea ,7 Sarah Pett,8 Bhagteshwar Singh,3 Tom Solomon,4 Thomas Arthur Pollak,9 Benedict D Michael,2,3 Timothy R Nicholson10 For numbered affiliations see INTRODUCTION More severe potential adverse effects in the open- end of article. The scientific community rapidly responded to label phase of vaccine roll- outs are being collected the COVID-19 pandemic by developing novel through national surveillance systems. In the USA, Correspondence to SARS- CoV-2 vaccines (table 1). As of early June Dr Timothy R Nicholson, King’s roughly 372 adverse events have been reported per College London, London WC2R 2021, an estimated 2 billion doses have been million doses, which is a lower rate than expected 1 2LS, UK; timothy. nicholson@ administered worldwide. Neurological adverse based on the clinical trials.6 kcl. ac. uk events following immunisation (AEFI), such as In the UK, adverse events are reported via the cerebral venous sinus thrombosis and demyelin- MB and AT are joint first Coronavirus Yellow Card reporting website. As of ating episodes, have been reported. In some coun- authors. early June 2021, approximately 250 000 Yellow tries, these have led to the temporary halting of BDM and TRN are joint senior Cards have been submitted, equating to around authors. -
Outcome Reporting Bias in COVID-19 Mrna Vaccine Clinical Trials
medicina Perspective Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials Ronald B. Brown School of Public Health and Health Systems, University of Waterloo, Waterloo, ON N2L3G1, Canada; [email protected] Abstract: Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. The present article uses clinical epidemiologic tools to critically appraise reports of efficacy in Pfzier/BioNTech and Moderna COVID-19 mRNA vaccine clinical trials. Based on data reported by the manufacturer for Pfzier/BioNTech vaccine BNT162b2, this critical appraisal shows: relative risk reduction, 95.1%; 95% CI, 90.0% to 97.6%; p = 0.016; absolute risk reduction, 0.7%; 95% CI, 0.59% to 0.83%; p < 0.000. For the Moderna vaccine mRNA-1273, the appraisal shows: relative risk reduction, 94.1%; 95% CI, 89.1% to 96.8%; p = 0.004; absolute risk reduction, 1.1%; 95% CI, 0.97% to 1.32%; p < 0.000. Unreported absolute risk reduction measures of 0.7% and 1.1% for the Pfzier/BioNTech and Moderna vaccines, respectively, are very much lower than the reported relative risk reduction measures. Reporting absolute risk reduction measures is essential to prevent outcome reporting bias in evaluation of COVID-19 vaccine efficacy. Keywords: mRNA vaccine; COVID-19 vaccine; vaccine efficacy; relative risk reduction; absolute risk reduction; number needed to vaccinate; outcome reporting bias; clinical epidemiology; critical appraisal; evidence-based medicine Citation: Brown, R.B. -
Ethics of Vaccine Research
COMMENTARY Ethics of vaccine research Christine Grady Vaccination has attracted controversy at every stage of its development and use. Ethical debates should consider its basic goal, which is to benefit the community at large rather than the individual. accines truly represent one of the mira- include value, validity, fair subject selection, the context in which it will be used and Vcles of modern science. Responsible for favorable risk/benefit ratio, independent acceptable to those who will use it. This reducing morbidity and mortality from sev- review, informed consent and respect for assessment considers details about the pub- eral formidable diseases, vaccines have made enrolled participants. Applying these princi- lic health need (such as the prevalence, bur- substantial contributions to global public ples to vaccine research allows consideration den and natural history of the disease, as health. Generally very safe and effective, vac- of some of the particular challenges inherent well as existing strategies to prevent or con- cines are also an efficient and cost-effective in testing vaccines (Box 1). trol it), the scientific data and possibilities way of preventing disease. Yet, despite their Ethically salient features of clinical vac- (preclinical and clinical data, expected brilliant successes, vaccines have always been cine research include the fact that it involves mechanism of action and immune corre- controversial. Concerns about the safety and healthy subjects, often (or ultimately) chil- lates) and the likely use of the vaccine (who untoward effects of vaccines, about disturb- dren and usually (at least when testing effi- will use and benefit from it, safety, cost, dis- ing the natural order, about compelling indi- cacy) in very large numbers. -
Intramuscular and Intradermal Electroporation of HIV-1 PENNVAX-GP® DNA Vaccine and IL-12 Is Safe, Tolerable, Acceptable in Healthy Adults
Article Intramuscular and Intradermal Electroporation of HIV-1 PENNVAX-GP® DNA Vaccine and IL-12 Is Safe, Tolerable, Acceptable in Healthy Adults Srilatha Edupuganti 1,*, Stephen C. De Rosa 2,3, Marnie Elizaga 2 , Yiwen Lu 2, Xue Han 2, Yunda Huang 2,4, Edith Swann 5, Laura Polakowski 5, Spyros A. Kalams 6, Michael Keefer 7, 2,8 9, 9 9 9, Janine Maenza , Megan C. Wise y, Jian Yan , Matthew P. Morrow , Amir S. Khan y, 9 9 9 9, 9,§ Jean D. Boyer , Laurent Humeau , Scott White , Niranjan Y. Sardesai z, Mark L. Bagarazzi , Peter B. Gilbert 2, James G. Kublin 2, Lawrence Corey 2, David B. Weiner 10, on behalf of the HVTN 098 Study Team k and the NIAID-Funded HIV Vaccine Trials Network 1 Division of Infectious Disease, Department of Medicine, Emory University, Atlanta, GA 30322, USA 2 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; [email protected] (S.C.D.R.); [email protected] (M.E.); [email protected] (Y.L.); [email protected] (X.H.); [email protected] (Y.H.); [email protected] (J.M.); [email protected] (P.B.G.); [email protected] (J.G.K.); [email protected] (L.C.) 3 Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA 4 Department of Global Health, University of Washington, Seattle, WA 98195, USA 5 Division of AIDS, NIH, Bethesda, MD 20892, USA; [email protected] (E.S.); [email protected] (L.P.) 6 Vanderbilt University Medical Center, Nashville, TN 37232, USA; [email protected] 7 Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY 14642, USA; [email protected] 8 Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98195, USA 9 Inovio Pharmaceuticals Inc.