Bayesian Benefit-Risk Assessment. Maria Costa GSK R&D
|
|
- Duane Russell
- 6 years ago
- Views:
Transcription
1 Assessment GSK R&D
2 Disclosure is an employee and shareholder of GSK Data presented is based on human research studies funded and sponsored by GSK 2
3 Outline 1. Motivation 2. GSK s Approach to Benefit-Risk Assessment 3. Bayesian Joint Modelling of Mixed Outcomes 4. A GSK Case Study 5. Summary 3
4 Motivation Growing industry and regulator awareness that more quantitative methods can contribute to transparency of benefit-risk assessment Efficacy and safety signals could be linked via exposure to active drug Joint modelling of efficacy and safety endpoints enables data driven quantitative assessment of the benefit-risk profile Bayesian inference provides a direct framework to build relevant and intuitive probability statements in the context of benefit-risk 4
5 GSK s Approach to Benefit-Risk Assessment A 3 Step Process... Frame Model / Analyse / Graph Conclude The endpoints are important because and we met them or we didn t and this is why the drug will matter, or why it shouldn t continue. Value Tree Graph, effects table, others BENEFIT-RISK PROFILE Based on this evidence, we believe the benefit outweighs the risk because 5
6 Subjects GSK s Approach to Benefit-Risk Assessment Graphical Methods Separate analysis of benefits and risks Results presented jointly Forest Plot Norton Heatmap Active Benefit and Risk Comparison Placebo Weeks Benefit Only Benefit +AE Neither AE only Withdrew 6
7 GSK s Approach to Benefit-Risk Assessment More Complex Methods Joint analysis of benefits and risks Results presented jointly Utility Index Contour Plots 7
8 Bayesian Joint Modelling of Mixed Outcomes Motivation Strength of efficacy and safety signals likely to be linked at subject level via exposure to active drug: Higher exposure Higher efficacy Higher risk of AE continuous, count, binary, etc binary, count, continuous, etc E.g., antibody drugs for diabetes mellitus, increases in C-peptide (efficacy) and cytokine releases (safety) Approach that accounts for observed correlation at subject level between efficacy and safety signals is desirable Often efficacy and safety endpoints modelled using different distributions Further development conditional on magnitude of efficacy and safety effect 8
9 Bayesian Joint Modelling of Mixed Outcomes Approaches to Linking Mixed Outcomes Option 1: Use generalised linear mixed models Assume J different observations on same subject (each following some distribution) For subject i with mean response mu i, g(mu i ) = X i b + Z i u i, u i ~ N(0, G(X i )) Random effect u i is shared across all J observations for subject i thus modelling potential correlation When g j (.) is not identity function then fixed effects b are conditional on random effects u i Monte Carlo integration can be used to obtain marginal population effects Constraints may be necessary to ensure identifiability for certain distributions 9
10 Bayesian Joint Modelling of Mixed Outcomes Approaches to Linking Mixed Outcomes Option 2: Use copulas Copulas - distribution functions used to form new multivariate distributions given set of marginal distributions of interest (which are preserved) E.g., H(y 1,y 2 ) = C(F(y 1 ), G(y 2 ) θ), F(.) and G(.) CDF of marginal distribution of rv y 1 and y 2 C(.,. θ) is the copula function (e.g., Gaussian CDF) θ measures association between y 1 and y 2 Directly obtain marginal population effects for parameters of interest Choice of copula C(.) may impact results through different dependency assumptions Difficult to interpret beyond 3 dimensions (non-unique model definition) 10
11 A GSK Case Study Compound X in Adults With Schizophrenia Antipsychotic drugs can cause extra pyramidal side effects (EPS) Dystonia (involuntary muscle contractions) Akathisia (extreme, uncontrollable restlessness) risk of suicide Tardive dyskinesia (involuntary, repetitive movements)... Compound X novel antipsychotic - antagonist dopamine D2/D3 and 5HT2 receptors However, D2/D3 receptor antagonism is associated with EPS Clinical trial to evaluate safety and efficacy of compound X in acute schizophrenia Placebo and active comparator (Olanzapine ) In this talk, focus on compound X 120mg (54 subjects) vs placebo (52 subjects) Development of compound X was stopped due to preclinical finding of phospholipidosis 11
12 A GSK Case Study The Value Tree Symptoms Decrease in PANSS TS Benefits Benefit-Risk Balance Individual Risks Weight Gain Glucose Intolerance / Insulin Resistance High Dyslipidemia Identified Benefit or Risk Category Identified benefit/ risk Outcome Akathisia Risks Nervous System Disorders / EPS Tremor Dystonia Dyskinesia AIMS Scale Barnes Akathisia Scale Simpsons Angus Scale 12
13 A GSK Case Study Efficacy and Safety Endpoints and Prior Distributions PANSS Total Score (TS) = Positive and Negative Syndrome Scale measures symptom severity in patients with schizophrenia Highest possible score is 210 = most severe measure of schizophrenia Lowest possible score is 30 = subject not suffering from schizophrenia Change from baseline (CFB) in PANSS TS at week 6 ~ N(µ, σ 2 ) Efficacy threshold for further development: treatment difference (TD) = -8 pt, but clinically meaningful TD is ~ -15 Adverse events (AEs) associated with Nervous System Disorders I AE = 1 if subject has an AE, 0 otherwise, I AE ~ Bernoulli(p), p = Prob(AE) Safety threshold for further development : odds ratio (OR) = 1.5, huge level of unmet need, large number co-morbidities, top 5 causes of disability in individuals < 25* Non-informative priors assumed for all parameters in the model Covariates in the model include age, baseline PANSS TS and treatment Hermes et al, 2012 * Nasrallah et al,
14 A GSK Case Study Exploratory Analysis Correlation between efficacy and safety All outcomes: the subjects who had a nervous system Corr X = -0.18, and Corr Placebo = AE and took drug X had an improvement from baseline in PANSS TS by week 6 - Improvement in score associated with AEs? 14
15 A GSK Case Study Estimated Joint Posterior Distribution of Treatment Difference and Odds Ratio How much evidence exists from the data to support the Benefit-Risk profile: TD < - 8pt AND OR < 1.5? Joint Posterior Median Parameter Median (95% Crd.I.) TD (-15.91, 1.90) OR 2.65 (0.76, 12.39) Corr X (-0.38, 0) Corr Placebo (-0.30, 0) Safety Threshold: OR = 1.5 Efficacy Threshold: TD = -8 Prob(+ BR Profile) = 7% 15
16 A GSK Case Study Benefit-Risk Evaluation and Decision-Making How much evidence (probability) exists to support a chosen Benefit-Risk profile? Higher probabilities for lower benefit thresholds and/or higher risk thresholds 16
17 A GSK Case Study Predicting Response and AE event for a New Subject A new patient, aged 50, is diagnosed with schizophrenia (baseline PANSS score of 119) and the GP is considering whether to prescribe compound X......will compound X be effective, do nothing, or harm this patient? We can predict both the efficacy and safety responses for this new subject given what we have learned from the study data Predicted CFB in PANSS TS after 6 weeks = (95% CI [-58.46, 19.91]) Predicted probability of AE of nervous system disorder =
18 A GSK Case Study Predicting Response and AE event for a New Subject Use predictive distribution for CFB PANSS TS to make predictive probabilistic statements around particular levels of efficacy Prob (Observed CFB PANSS TS at week 6 < 0 NAA Data) = 84% Prob (Observed CFB PANSS TS at week 6 < -15 NAA Data) = 58% Although this patient has a high probability of benefitting from drug X, it has just over 50% chance of achieving a clinically meaningful improvement, whilst having a 30% chance of experiencing an AE The GP may still choose to prescribe drug X if no alternative therapies are available 18
19 Summary Benefit-Risk assessment is both qualitative and quantitative Bayesian inference based on joint models of mixed outcomes is a powerful tool for Benefit-Risk assessment Explore dependency between benefit and risk thresholds for decision-making Joint (and conditional) probabilistic statements Predicting responses for a new subject conditional on what was learned from study data Benefit-Risk profile is a combination of two different quantities: Set of thresholds for efficacy and safety define Benefit-Risk profile Level of evidence (posterior probability) to support Benefit-Risk profile 19
20 Acknowledgements Thomas Drury (Integral Statistics Limited) GSK: Susan Duke Colleen Russell John Krauss 20
21 Thank you
Bayesian Joint Modelling of Benefit and Risk in Drug Development
Bayesian Joint Modelling of Benefit and Risk in Drug Development EFSPI/PSDM Safety Statistics Meeting Leiden 2017 Disclosure is an employee and shareholder of GSK Data presented is based on human research
More informationMethod. NeuRA Paliperidone August 2016
Introduction Second generation antipsychotics (sometimes referred to as atypical antipsychotics) are a newer class of antipsychotic medication than first generation typical antipsychotics. Second generation
More informationPaliperidone: Clinical Protocol R076477SCH4012, CR Amendment INT-1
Paliperidone: Clinical Protocol R076477SCH4012, CR013771 Amendment INT-1 A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Fixed
More informationSYNOPSIS. ER OROS Paliperidone: Clinical Study Report R SCH-301
SYNOPSIS Protocol No.: R076477-SCH-301 Title of Study: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study With an Open-Label Extension Evaluating Extended Release OROS Paliperidone in
More information) and serotonin Type 2 (5-HT 2A
Latuda (lurasidone HCl) Fact Sheet Schizophrenia FREQUENTLY ASKED QUESTIONS What type of patient with schizophrenia is appropriate for LATUDA? LATUDA is an atypical antipsychotic agent indicated for the
More informationFundamental Clinical Trial Design
Design, Monitoring, and Analysis of Clinical Trials Session 1 Overview and Introduction Overview Scott S. Emerson, M.D., Ph.D. Professor of Biostatistics, University of Washington February 17-19, 2003
More informationPharmacotherapy of psychosis and schizophrenia in youth
Pharmacotherapy of psychosis and schizophrenia in youth Benedetto Vitiello Pavia, 2 December 2017 Disclosure Benedetto Vitiello, M.D. Professor of Child and Adolescent Neuropsychiatry University of Turin,
More informationTechnology appraisal guidance Published: 26 January 2011 nice.org.uk/guidance/ta213
Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years Technology appraisal guidance Published: 26 January 2011 nice.org.uk/guidance/ta213 NICE 2018. All rights reserved. Subject
More informationBayesians methods in system identification: equivalences, differences, and misunderstandings
Bayesians methods in system identification: equivalences, differences, and misunderstandings Johan Schoukens and Carl Edward Rasmussen ERNSI 217 Workshop on System Identification Lyon, September 24-27,
More informationType of intervention Secondary prevention and treatment. Economic study type Cost-effectiveness analysis.
Modelling the treated course of schizophrenia: development of a discrete event simulation model Heeg B M, Buskens E, Knapp M, van Aalst G, Dries P J, de Haan L, van Hout B A Record Status This is a critical
More informationSummary ID#7029. Clinical Study Summary: Study F1D-MC-HGKQ
CT Registry ID# 7029 Page 1 Summary ID#7029 Clinical Study Summary: Study F1D-MC-HGKQ Clinical Study Report: Versus Divalproex and Placebo in the Treatment of Mild to Moderate Mania Associated with Bipolar
More informationHierarchical Bayesian Modeling of Individual Differences in Texture Discrimination
Hierarchical Bayesian Modeling of Individual Differences in Texture Discrimination Timothy N. Rubin (trubin@uci.edu) Michael D. Lee (mdlee@uci.edu) Charles F. Chubb (cchubb@uci.edu) Department of Cognitive
More informationDecision Making in Confirmatory Multipopulation Tailoring Trials
Biopharmaceutical Applied Statistics Symposium (BASS) XX 6-Nov-2013, Orlando, FL Decision Making in Confirmatory Multipopulation Tailoring Trials Brian A. Millen, Ph.D. Acknowledgments Alex Dmitrienko
More informationSiGMA/ MMHSCT GUIDELINES FOR ANTIPSYCHOTIC DRUG TREATMENT OF SCHIZOPHRENIA. [compatible with NICE guidance]
SiGMA/ MMHSCT GUIDELINES FOR ANTIPSYCHOTIC DRUG TREATMENT OF SCHIZOPHRENIA [compatible with NICE guidance] Medicines Management Committee August 2002 For review August 2003 Rationale The SiGMA algorithm
More informationStatistical Tolerance Regions: Theory, Applications and Computation
Statistical Tolerance Regions: Theory, Applications and Computation K. KRISHNAMOORTHY University of Louisiana at Lafayette THOMAS MATHEW University of Maryland Baltimore County Contents List of Tables
More informationXenazine. Xenazine (tetrabenazine) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Xenazine Page: 1 of 5 Last Review Date: November 30, 2018 Xenazine Description Xenazine (tetrabenazine)
More informationINDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER Volume: Page:
SYNOPSIS Protocol No.: CR004357 Title of Study: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of 50 and 100 mg eq. of Paliperidone Palmitate in Subjects With
More informationPROVIDED IN RESPONSE TO YOUR UNSOLICITED REQUEST FOR INFORMATION
KINECT 2 NCT01733121 Baseline Week 2 Week 4 Week 6 Valbenazine 25-75 mg Valbenazine 40 mg KINECT 3 NCT02274558 Valbenazine 80 mg a KINECT 2 and KINECT 3 were 6-week, double-blind placebo-controlled trials
More informationIngrezza (valbenazine)
Ingrezza (valbenazine) Policy Number: 5.01.635 Last Review: 7/2018 Origination: 07/2017 Next Review: 7/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Ingrezza
More informationJNJ AAA; paliperidone palmitate Clinical Study Report R SCH-4009
SYNOPSIS Name of Sponsor/Company Name of Finished Product Name of Active Ingredient(s) Janssen Asia Pacific Medical Affairs, a Division of Johnson and Johnson Pte Ltd* INVEGA SUSTENNA * The legal entity
More informationAustedo. Austedo (deutetrabenazine) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.60.15 Subject: Austedo Page: 1 of 6 Last Review Date: September 15, 2017 Austedo Description Austedo
More informationXenazine. Xenazine (tetrabenazine) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.60.12 Subject: Xenazine Page: 1 of 5 Last Review Date: December 8, 2017 Xenazine Description Xenazine
More informationEffectiveness and Cost of Olanzapine and Haloperidol in the Treatment of Schizophrenia: A Randomized Controlled Trial
Effectiveness and Cost of Olanzapine and Haloperidol in the Treatment of Schizophrenia: A Randomized Controlled Trial R. Rosenheck et al., JAMA. 2003;290(20):2693-2702 Philipp Kainz Michael Mayrhofer-Reinhartshuber
More informationSYNOPSIS. Clinical Study Report CN138002: Addendum 1. Individual Study Table Referring to the Dossier
Name of Sponsor/Company: Bristol-Myers Squibb Name of Finished Product: Abilify Name of Active Ingredient: aripiprazole Individual Study Table Referring to the Dossier (For National Authority Use Only)
More informationIs Aristada (Aripiprazole Lauroxil) a Safe and Effective Treatment For Schizophrenia In Adult Patients?
Philadelphia College of Osteopathic Medicine DigitalCommons@PCOM PCOM Physician Assistant Studies Student Scholarship Student Dissertations, Theses and Papers 12-2016 Is Aristada (Aripiprazole Lauroxil)
More information(+)-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]- 6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyridol[1,2-a]pyrimidin-4- one
SYNOPSIS Issue Date: 18 November 2008 Document No.: EDMS-PSDB-9006510:2.0 Name of Sponsor/Company Name of Finished Product Name of Active Ingredient(s) Ortho-McNeil Janssen Scientific Affairs, L.L.C. Paliperidone
More informationCLINICAL STUDY REPORT SYNOPSIS
CLINICAL STUDY REPORT SYNOPSIS Document No.: EDMS-PSDB-7176909:2.0 Name of Sponsor/Company Name of Finished Product Name of Active Ingredient Protocol No.: CR002350 Johnson & Johnson Pharmaceutical Research
More informationMaking comparisons. Previous sessions looked at how to describe a single group of subjects However, we are often interested in comparing two groups
Making comparisons Previous sessions looked at how to describe a single group of subjects However, we are often interested in comparing two groups Data can be interpreted using the following fundamental
More informationDynamic borrowing of historical data: Performance and comparison of existing methods based on a case study
Introduction Methods Simulations Discussion Dynamic borrowing of historical data: Performance and comparison of existing methods based on a case study D. Dejardin 1, P. Delmar 1, K. Patel 1, C. Warne 1,
More informationFor Tardive Dyskinesia
A LOOK AT VMAT2 INHIBITORS DECEMBER 2017 For Tardive Dyskinesia Tardive dyskinesia (TD) is a repetitive, involuntary movement disorder caused by prolonged use of medications that block the dopamine receptor,
More informationCHAPTER 3. Schizophrenia and Antipsychotic Treatment
CHAPTER 3 Schizophrenia and Antipsychotic Treatment What is it? It is a severe, chronic, disabling brain disease Considered to have biological origins but exact unknown 1% of population affected Schizophrenia
More informationDBSA Survey Center Less Common Medication Side Effects Survey
Summary Report: March, 2017 BACKGROUND From 10/19/16-11/21/16, DBSA administered a survey to gather information on the experiences people living with mood disorders have had with a variety of medication
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Page 1 of 5 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Prime Therapeutics will review Prior Authorization requests Prior Authorization Form: https://www.bcbsks.com/customerservice/forms/pdf/priorauth-6514ks-ingr.pdf
More informationImproving the specificity and precision of PANSS factors:
Improving the specificity and precision of PANSS factors: One approach to facilitate development of novel treatments in schizophrenia Seth C. Hopkins, PhD Executive Director Translational Medicine Sunovion
More informationGSK Medicine: Study Number: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationPresented at the American Psychiatric Association Annual Meeting May 20 24, 2017 San Diego, CA.
Original Presentations Key Words: amines, antipsychotic agents, double-blind method, mood disorders, psychopharmacology, psychotic disorders, schizophrenia, tardive dyskinesia, valbenazine Efficacy of
More informationBayesian Dose Escalation Study Design with Consideration of Late Onset Toxicity. Li Liu, Glen Laird, Lei Gao Biostatistics Sanofi
Bayesian Dose Escalation Study Design with Consideration of Late Onset Toxicity Li Liu, Glen Laird, Lei Gao Biostatistics Sanofi 1 Outline Introduction Methods EWOC EWOC-PH Modifications to account for
More informationNew Medications in Early Psychosis
New Medications in Early Psychosis Jean Starling Department of Psychological Medicine, the Children s Hospital at Westmead Department of Psychological Medicine and Department of Paediatrics and Child Health,
More informationThe safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis
Nasrallah et al. BMC Psychiatry (2017) 17:305 DOI 10.1186/s12888-017-1459-z RESEARCH ARTICLE The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis
More informationChapter 161 Antipsychotics
Chapter 161 Antipsychotics Episode Overview Extrapyramidal syndromes are a common complication of antipsychotic medications. First line treatment is benztropine or diphenhydramine. Lorazepam is used in
More informationPharmaceutical Statistics Journal Club 15 th October Missing data sensitivity analysis for recurrent event data using controlled imputation
Pharmaceutical Statistics Journal Club 15 th October 2015 Missing data sensitivity analysis for recurrent event data using controlled imputation Authors: Oliver Keene, James Roger, Ben Hartley and Mike
More information7/16/2009. Cost-benefit, QALYs and the Value of a Statistical Life
7/16/29 Cost-benefit, QALYs and the Value of a Statistical Life Alan McKenzie, Bristol The benefits of many developments in radiotherapy may be obvious for instance, replacing hand planning by computer
More informationCDEC FINAL RECOMMENDATION
CDEC FINAL RECOMMENDATION ARIPIPRAZOLE LONG-ACTING INJECTION (Abilify Maintena Otsuka Pharmaceuticals Co. & Lundbeck Canada Inc.) Indication: Schizophrenia Recommendation: The Canadian Drug Expert Committee
More informationLecture Outline. Biost 590: Statistical Consulting. Stages of Scientific Studies. Scientific Method
Biost 590: Statistical Consulting Statistical Classification of Scientific Studies; Approach to Consulting Lecture Outline Statistical Classification of Scientific Studies Statistical Tasks Approach to
More informationWhat Team Members Other Than Prescribers Need To Know About Antipsychotics
What Team Members Other Than Prescribers Need To Know About Antipsychotics The Care Transitions Network National Council for Behavioral Health Montefiore Medical Center Northwell Health New York State
More informationExtrapyramidal Symptoms Associated with Antipsychotic Use
Extrapyramidal Symptoms Associated with Antipsychotic Use Tamara Pringsheim, MD, FRCPC, FAAN Associate Professor, University of Calgary Department of Clinical Neurosciences, Psychiatry, Pediatrics and
More informationCENTENE PHARMACY AND THERAPEUTICS DRUG REVIEW 1Q18 January February
BRAND NAME Austedo TM GENERIC NAME Deutetrabenazine MANUFACTURER Teva Pharmaceuticals USA, Inc. DATE OF APPROVAL August 30, 2017 PRODUCT LAUNCH DATE Currently commercially available REVIEW TYPE Review
More informationObjectives. Epidemiology. Diagnosis 3/27/2013. Identify positive and negative symptoms used for diagnosis of schizophrenia
Objectives Identify positive and negative symptoms used for diagnosis of schizophrenia Mohamed Sallout, Pharm D. Pharmacist Resident St. Luke s Magic Valley Regional Medical Center List medications used
More informationPractical Bayesian Optimization of Machine Learning Algorithms. Jasper Snoek, Ryan Adams, Hugo LaRochelle NIPS 2012
Practical Bayesian Optimization of Machine Learning Algorithms Jasper Snoek, Ryan Adams, Hugo LaRochelle NIPS 2012 ... (Gaussian Processes) are inadequate for doing speech and vision. I still think they're
More informationSchizophrenia Pharmacology UNIVERSITY OF HAWAI I HILO PRE -NURSING PROGRAM
Schizophrenia Pharmacology UNIVERSITY OF HAWAI I HILO PRE -NURSING PROGRAM NURS 203 GENERAL PHARMACOLOGY DANITA NARCISO PHARM D Learning Objectives Understand the result of dopamine binding to D2 receptors
More informationN e w s R e l e a s e
Sunovion Pharmaceuticals Inc. 84 Waterford Drive, Marlborough, MA 01752-7010 Tel 508-481-6700 N e w s R e l e a s e Contact: Susan Adler Alesina Vice President, Corporate Communications Sunovion Pharmaceuticals
More informationpaliperidone palmitate 50mg, 75mg, 100mg and 150mg prolonged release suspension for injection (Xeplion) SMC No. (713/11) Janssen-Cilag Ltd
Re-Submission paliperidone palmitate 50mg, 75mg, 100mg and 150mg prolonged release suspension for injection (Xeplion) SMC No. (713/11) Janssen-Cilag Ltd 07 October 2011 The Scottish Medicines Consortium
More informationPractical and ethical advantages of Bayesian approaches in adaptive clinical trial designs. Kristian Thorlund
Practical and ethical advantages of Bayesian approaches in adaptive clinical trial designs Kristian Thorlund Background This talk was previously given as an invited talk at a DSEN sponsored meeting on
More informationClinical Trial Database Analyses to Inform Regulatory Guidances: Improving the Efficiency of Schizophrenia Clinical Trials
Clinical Trial Database Analyses to Inform Regulatory Guidances: Improving the Efficiency of Schizophrenia Clinical Trials Islam R. Younis, Ph.D. Team Leader Office of Clinical Pharmacology Office of Translational
More informationDosing & Administration
Dosing & Administration REAL LIFE. REAL RESULTS. INDICATION INVEGA SUSTENNA (paliperidone palmitate) is indicated for the treatment of: Schizophrenia. Schizoaffective disorder as monotherapy and as an
More informationFile NDA SE5 046/047, NDA SE5 036/037, NDA SE5 020/021
M E M O R A N D U M DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH DATE: 18 June 2007 FROM: TO: SUBJECT: Mitchell V.
More informationManaging Behavioural Problems in Patients with Learning Disabilities
Managing Behavioural Problems in Patients with Learning Disabilities Some people with a learning disability display behaviour that challenges. Although such behaviour is a challenge to services, family
More informationLecture 9 Internal Validity
Lecture 9 Internal Validity Objectives Internal Validity Threats to Internal Validity Causality Bayesian Networks Internal validity The extent to which the hypothesized relationship between 2 or more variables
More informationSYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-USA-232 (FOR NATIONAL AUTHORITY USE ONLY)
SYNOPSIS Protocol No.: RIS-USA-232 Title of Study: Efficacy and Safety of a Flexible Dose of Risperidone Versus Placebo in the Treatment of Psychosis of Alzheimer's Disease Principal Investigator: M.D.
More informationXenazine. Xenazine (tetrabenazine) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Xenazine Page: 1 of 5 Last Review Date: June 12, 2014 Xenazine Description Xenazine (tetrabenazine)
More informationSchizophrenia. Class Objectives. Can someone be psychotic without having schizophrenia? 12/7/2011. Other psychotic disorders and causes
Schizophrenia Other psychotic disorders and causes Class Objectives What are Delusional Disorders? What causes Schizophrenia? How can Schizophrenia be treated? Can someone be psychotic without having schizophrenia?
More informationHEALTH PROFESSIONAL v SANOFI
CASE AUTH/3062/8/18 HEALTH PROFESSIONAL v SANOFI Toujeo leaflet A consultant physician complained about a six-page A5 gate-folded leavepiece produced by Sanofi. The leavepiece related to Toujeo (insulin
More informationSECTION 9 : MANAGEMENT OF MOVEMENT DISORDERS AND EXTRAPYRAMIDAL SIDE EFFECTS
SECTION 9 : MANAGEMENT OF MOVEMENT DISORDERS AND EXTRAPYRAMIDAL SIDE EFFECTS Formulary and Prescribing Guidelines 9.1 Introduction Movement disorders and extrapyramidal side effects can manifest in the
More information- The safety and efficacy of oral, once-daily VRAYLAR was established in a clinical trial program involving more than 2,700 patients
Allergan and Gedeon Richter Plc. Receive FDA Approval of VRAYLAR TM (cariprazine) for Treatment of Manic or Mixed Episodes of Bipolar I Disorder and Schizophrenia in Adults - The safety and efficacy of
More informationBayesian Nonparametric Methods for Precision Medicine
Bayesian Nonparametric Methods for Precision Medicine Brian Reich, NC State Collaborators: Qian Guan (NCSU), Eric Laber (NCSU) and Dipankar Bandyopadhyay (VCU) University of Illinois at Urbana-Champaign
More informationAn Introduction to Multiple Imputation for Missing Items in Complex Surveys
An Introduction to Multiple Imputation for Missing Items in Complex Surveys October 17, 2014 Joe Schafer Center for Statistical Research and Methodology (CSRM) United States Census Bureau Views expressed
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationUS Tardive Dyskinesia Market: Size, Trends & Forecasts ( ) December 2016
US Tardive Dyskinesia Market: Size, Trends & Forecasts (2016-2025) December 2016 US Tardive Dyskinesia Market Report Scope of the Report The report entitled US Tardive Dyskinesia Market: Size, Trends &
More informationAntipsychotic Medications
TRAIL: Team Review of EVIDENCE REVIEW & RECOMMENDATIONS FOR LTC Behavioural and psychological symptoms of dementia (BPSD) refer to the non-cognitive symptoms of disturbed perception, thought content, mood
More informationSignal Detection Theory and Bayesian Modeling
Signal Detection Theory and Bayesian Modeling COGS 202: Computational Modeling of Cognition Omar Shanta, Shuai Tang, Gautam Reddy, Reina Mizrahi, Mehul Shah Detection Theory and Psychophysics: A Review
More informationAn application of a pattern-mixture model with multiple imputation for the analysis of longitudinal trials with protocol deviations
Iddrisu and Gumedze BMC Medical Research Methodology (2019) 19:10 https://doi.org/10.1186/s12874-018-0639-y RESEARCH ARTICLE Open Access An application of a pattern-mixture model with multiple imputation
More informationTHERAPEUTIC AND EVOLUTIVE ASPECTS IN SCHIZOPHRENIA
UNIVERSITY OF MEDICINE AND PHARMACY OF CRAIOVA THERAPEUTIC AND EVOLUTIVE ASPECTS IN SCHIZOPHRENIA ABSTRACT Ph.D. Coordinator Professor Dragoș MARINESCU PhD Student: Mihai MUTICĂ Craiova 2016 TABLE OF CONTENTS
More informationQuantitative benefit-risk assessment: An analytical framework for a shared understanding of the effects of medicines. Patrick Ryan 21 April 2010
Quantitative benefit-risk assessment: An analytical framework for a shared understanding of the effects of medicines Patrick Ryan 21 April 2010 Challenges in understanding the effects of medicines Benefit
More informationVisualization of Study Data to Evaluate UDU Capability. Presented at IFPAC 28 Jan 2015 Thomas Parks, Jeff Hofer, Adam Rauk (Inventive Clinical, LLC)
Visualization of Study Data to Evaluate UDU Capability Presented at IFPAC 28 Jan 2015 Thomas Parks, Jeff Hofer, Adam Rauk (Inventive Clinical, LLC) 1 Motivation Increased expectations to demonstrate acceptable
More informationClinical trials with incomplete daily diary data
Clinical trials with incomplete daily diary data N. Thomas 1, O. Harel 2, and R. Little 3 1 Pfizer Inc 2 University of Connecticut 3 University of Michigan BASS, 2015 Thomas, Harel, Little (Pfizer) Clinical
More informationGuidance Document for Claims Based on Non-Inferiority Trials
Guidance Document for Claims Based on Non-Inferiority Trials February 2013 1 Non-Inferiority Trials Checklist Item No Checklist Item (clients can use this tool to help make decisions regarding use of non-inferiority
More informationPsychosis and Agitation in Dementia
Psychosis and Agitation in Dementia Dilip V. Jeste, MD Estelle & Edgar Levi Chair in Aging, Director, Stein Institute for Research on Aging, Distinguished Professor of Psychiatry & Neurosciences, University
More informationEcological Statistics
A Primer of Ecological Statistics Second Edition Nicholas J. Gotelli University of Vermont Aaron M. Ellison Harvard Forest Sinauer Associates, Inc. Publishers Sunderland, Massachusetts U.S.A. Brief Contents
More informationAssessing & Management of side effects: Part 1. medicationmanagement
Assessing & Management of side effects: Part 1 medicationmanagement What side effects of antipsychotic medication do you see in you clinical practice? How do you routinely assess for side effects of medication?
More informationStudy No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationSymbyax (Zyprexa [olanzapine] and Prozac [fluoxetine] combination)
Symbyax (Zyprexa [olanzapine] and Prozac [fluoxetine] combination) Generic name: Olanzapine and fluoxetine combination Available strengths: 6 mg/25 mg, 6 mg/50 mg, 12 mg/25 mg, 12 mg/50 mg (Zyprexa/Prozac)
More informationBayesian Hierarchical Models for Fitting Dose-Response Relationships
Bayesian Hierarchical Models for Fitting Dose-Response Relationships Ketra A. Schmitt Battelle Memorial Institute Mitchell J. Small and Kan Shao Carnegie Mellon University Dose Response Estimates using
More informationMeta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ
Tutorial in Biostatistics Received: 11 March 2016, Accepted: 13 September 2016 Published online 16 October 2016 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/sim.7141 Meta-analysis using
More informationIf You Are Serious About Benefit:Risk Assessment
If You Are Serious About Benefit:Risk Assessment Christy Chuang-Stein, PhD Statistics, Pfizer Inc MRHA/EFSPI Joint Meeting 29 March 2010 1 Basic & Well-Accepted Facts All pharmaceutical products have side
More informationRecent Advances in the Antipsychotic Treatment of People with schizophrenia. Robert W. Buchanan, M.D.
Recent Advances in the Antipsychotic Treatment of People with schizophrenia Robert W. Buchanan, M.D. Antipsychotic medications are the primary class of drugs used in the pharmacological treatment of schizophrenia.
More informationUse of Psychotherapeutic Medications in Children and Adolescents with ASD and ID
Use of Psychotherapeutic Medications in Children and Adolescents with ASD and ID Although not considered first line treatment in children with ASD and ID, depending on the severity of symptoms, some medications
More informationIndividualized Treatment Effects Using a Non-parametric Bayesian Approach
Individualized Treatment Effects Using a Non-parametric Bayesian Approach Ravi Varadhan Nicholas C. Henderson Division of Biostatistics & Bioinformatics Department of Oncology Johns Hopkins University
More informationIntroduction to Bayesian Analysis 1
Biostats VHM 801/802 Courses Fall 2005, Atlantic Veterinary College, PEI Henrik Stryhn Introduction to Bayesian Analysis 1 Little known outside the statistical science, there exist two different approaches
More informationAddressing multiple treatments II: multiple-treatments meta-analysis basic methods
Deborah Caldwell and Georgia Salanti d.m.caldwell@bristol.ac.uk Addressing multiple treatments II: multiple-treatments meta-analysis basic methods Keystone, 2010 18 th Cochrane Colloquium, 18 th to 22
More informationAppendix D: Included Studies adverse effects review
DELIRIUM APPENDICES (Draft for Consultation) Appendix D: Included Studies adverse effects review Table D1: Studies directly comparing two antipsychotic agents in delirium Author Study design Setting Age
More informationQuantitative challenges of extrapolation
Quantitative challenges of extrapolation Michael Looby, Frank Bretz (Novartis) EMA workshop on extrapolation of efficacy and safety in medicine development across age groups May 17-18, 2016 Extrapolation
More informationBehavioural and Psychological Symptoms and Medications Presentation
1 2 Vover s research indicated that antipsychotic med are frequently used for individual presenting with disruptive behaviours. This often combined with physical restraints Efficacy of use not justify
More informationIngrezza. (valbenazine) New Product Slideshow
Ingrezza (valbenazine) New Product Slideshow Introduction Brand name: Ingrezza Generic name: Valbenazine Pharmacological class: Vesicular monoamine transporter 2 (VMAT2) inhibitor Strength and Formulation:
More informationCould your uncontrollable movements be tardive dyskinesia (TD)? There s a treatment with INGREZZA.
Lip smacking, eye blinking, dancing hands and fingers, hip jerking... Could your uncontrollable movements be tardive dyskinesia (TD)? There s a treatment with INGREZZA. Approved for adults with TD TD can
More informationA Case Study: Two-sample categorical data
A Case Study: Two-sample categorical data Patrick Breheny January 31 Patrick Breheny BST 701: Bayesian Modeling in Biostatistics 1/43 Introduction Model specification Continuous vs. mixture priors Choice
More informationPromoting and Monitoring Evidenced-Based Antipsychotic Prescribing Practices in Children and Adolescents: Florida Medicaid Initiatives
Promoting and Monitoring Evidenced-Based Antipsychotic Prescribing Practices in Children and Adolescents: Florida Medicaid Initiatives Mary Elizabeth Jones, Pharm BSc, RPh Senior Pharmacist AHCA Pharmacy
More informationA Treatment for Acute Manic or Mixed Episodes of Bipolar I Disorder in Adults
Transcript Details This is a transcript of an educational program accessible on the ReachMD network. Details about the program and additional media formats for the program are accessible by visiting: https://reachmd.com/industry-feature/psychiatry-and-mental-health/treatment-acute-manic-mixedepisodes-bipolar-i-disorder-adults/7534/
More informationINSTRUCTIONS FOR USE Please read complete instructions prior to use
INSTRUCTIONS FOR USE Please read complete instructions prior to use For deltoid or gluteal intramuscular injection only 3 MONTHS Administer every 3 months 1 With the syringe tip pointing up, shake syringe
More information