Improving Adverse Drug Reaction Information in Product Labels. EFSPI IDA Webinar 28 th Sept 2017 Sally Lettis

Size: px
Start display at page:

Download "Improving Adverse Drug Reaction Information in Product Labels. EFSPI IDA Webinar 28 th Sept 2017 Sally Lettis"

Transcription

1 Improving Adverse Drug Reaction Information in Product Labels EFSPI IDA Webinar 28 th Sept 2017 Sally Lettis

2 Improving Adverse Drug Reaction Information in Product Labels 2

3 Outline Current Labelling Practice Current Labelling Limitations The problem to solve The proposed solution Improving Adverse Drug Reaction Information in Product Labels 3

4 Current Labelling Practice Product labels are intended to provide health care professionals with clear and concise prescribing information that will enhance the safe and effective use of drug products. Improving Adverse Drug Reaction Information in Product Labels 4

5 Current Labelling Practice: US Product Label Quantitative approach used in the Adverse Reactions section Incidence of common ADRs presented Common defined as an ADR that occurs at or above a specified incidence e.g. >=3% A comparator must be provided, except in exceptional circumstances. Typically, a single ADR table is included; however, more than 1 can be included when the ADR profile differs substantially from one setting or population to another Improving Adverse Drug Reaction Information in Product Labels 5

6 Current Labelling Practice: EU SPc ADRs (from RCTs) placed into frequency categories Convention for classification: very common (1/10), common (1/100 to <1/10), uncommon (1/1,000 to <1/100), rare (1/10,000 to <1/1,000), and very rare (<1/10,000); (CIOMS III and V) Comparator typically not included Category based on crude incidence on drug. Studies included don t need common comparator For drugs for long-term use, there is no representative duration; in practice, studies of differing durations are combined together Only in exceptional cases is more than 1 table included for different populations Improving Adverse Drug Reaction Information in Product Labels 6

7 Current Labelling Limitations: The issue with no comparator data in label Disease Severity Duration Incidence on drug In label it is an ADR and is common Category X Moderate 3 months 0.6% Uncommon - X Moderate 6 months 1.5% Common 1.7% X Severe 12 months 6.3% Common 3.3% X Pooled 3.0% Common 2.6% Heterogeneity? Appropriate to combine? Helpful for patient? If two similar drugs tested in different populations very different incidences with no comparator data to contextualise Incidence on Comparator Y Pooled 0.5% Uncommon Different X+Y Pooled 1.0% Common Multiple Improving Adverse Drug Reaction Information in Product Labels 7

8 Current Labelling Limitations: The issue with crude pooling Data presented is based on crude pooling of data across multiple studies: pooling data as if from a single study Can lead to Simpson s Paradox : When studies combined, trend seen in the individual studies either disappears or is reversed Why? Can result in an overall baseline risk that is different among treatment groups due to differing randomization allocations within a study and different study populations across studies Differences that could affect the incidence include age, sex, race, medical practice, differing time on study Common for reporting proportions with an ADR in labels Not a new issue (Chuang-Stein and Beltangady (2010)) E.g. Cochran-Mantel-Haenszel to produce a common odds ratio across strata If used, applied in Integrated Summaries of Safety Too complicated for Product Labels which revert to crude incidences Improving Adverse Drug Reaction Information in Product Labels 8

9 Current Labelling Limitations: Example showing misleading incidence proportion from crude pooling New treatment, Placebo, Total patients in study Phase 2 study 30/300 (10%) 10/100 (10%) 400 Phase 3 study 133/700 (19%) 67/350 (19%) 1050 Phase 3 study in refractory patients Incidence proportion: crude pooling 200/500 (40%) 200/500 (40%) /1500 (24%) 277/950 (29%) 2450 N = total number of patients in the group; n = the number in the group that experienced the event The last row gives the impression the new drug has a beneficial effect, though the AE incidences are equal in each study. If you were to do a statistical test -> p=0.007 Improving Adverse Drug Reaction Information in Product Labels 9

10 Current Labelling Limitations: Why did crude pooling go wrong? New treatment, Placebo, Total patients in study Allocation Ratio Phase 2 study 30/300 (10%) 10/100 (10%) 400 3:1 Phase 3 study 133/700 (19%) 67/350 (19%) :1 Phase 3 study in refractory patients Incidence proportion: crude pooling 200/500 (40%) 200/500 (40%) :1 363/1500 (24%) 277/950 (29%) 2450 N = total number of patients in the group; n = the number in the group that experienced the event Studies with uniformly lower ADR proportions (e.g. Phase 2) have more subjects on new treatment than placebo Improving Adverse Drug Reaction Information in Product Labels 10

11 The problem to solve: So what do we do? We can see what the issue is How should we present adjusted proportions? Conclusions from crude pooling misleading Meta-analytic techniques: e.g. Cochran-Mantel-Haenszel weights Not easy for non-statistician to understand Improving Adverse Drug Reaction Information in Product Labels 11

12 The Proposed Solution: A better way to go Study-size Adjusted Percentages New treatment, Placebo, Total patients in study Proportion of total patients in study Phase 2 study 30/300 (10%) 10/100 (10%) 400 w 1 = 400/2450 (16%) Phase 3 study 133/700 (19%) 67/350 (19%) 1050 w 2 = 1050/2450 (43%) Phase 3 study in refractory patients Incidence proportion from crude pooling 200/500 (40%) 200/500 (40%) 1000 w 3 = 1000/2450 (41%) 363/1500 (24%) 277/950 (29%) 2450 Improving Adverse Drug Reaction Information in Product Labels 12

13 The Proposed Solution: A better way to go Study-size Adjusted Percentages New treatment, Placebo, Total patients in study Proportion of total patients in study Phase 2 study 30/300 (10%) 10/100 (10%) 400 w 1 = 400/2450 (16%) Phase 3 study 133/700 (19%) 67/350 (19%) 1050 w 2 = 1050/2450 (43%) Phase 3 study in refractory patients Incidence proportion from crude pooling Study-sizeadjusted incidence proportions 200/500 (40%) 200/500 (40%) 1000 w 3 = 1000/2450 (41%) 363/1500 (24%) 277/950 (29%) 2450 w 1 x (30/300) + w 2 x (133/700) + w 3 x (200/500) = 26% w 1 x (10/100) + w 2 x (67/350) + w 3 x (200/500) = 26% Improving Adverse Drug Reaction Information in Product Labels 13

14 Comparison of Weights for New Treatment New treatment Study Size Weights in Crude Pooling = Proportion of total patients on new drug Weights in Study sized pooling = Proportion of patients in study Weights using CMH a j = (n 1j n 2j )/ (n 1j +n 2j ) Study 1 30/300 (10%) Study 2 133/700 (19%) Study 3 200/500 (40%) N w 1 = 300/ % 1050 w 2 = 700/ % 1000 w 3 = 500/ % w 1 = 400/ % w 2 = 1050/ % w 3 = 1000/ % w 1 = a 1 / a j 13% w 2 = a 2 / a j 42% w 3 = a 3 / a j 45% w 1 x (30/300) + w 2 x (133/700) + w 3 x (200/500) = 24% w 1 x (30/300) + w 2 x (133/700) + w 3 x (200/500) = 26% w 1 x (30/300) + w 2 x (133/700) + w 3 x (200/500) = 27% Study Adjusted Size and CMH weights same for each treatment; Crude pooling weights are not 14

15 Comparison of Weights for Placebo Placebo Study Size Weights in Crude Pooling = Proportion of total patients on placebo Weights in Study sized pooling = Proportion of patients in study Weights using CMH a j = (n 1j n 2j )/ (n 1j +n 2j ) Study 1 10/100 (10%) Study 2 67/350 (19%) Study 3 200/500 (40%) N w 1 = 100/950 11% 1050 w 2 = 350/950 37% 1000 w 3 = 500/950 53% w 1 = 400/ % w 2 = 1050/ % w 3 = 1000/ % w 1 = a 1 / a j 13% w 2 = a 2 / a j 42% w 3 = a 3 / a j 45% w 1 x (10/300) + w 2 x (67/350) + w 3 x (200/500) = 29% w 1 x (10/100) + w 2 x (67/350) + w 3 x (200/500) = 26% w 1 x (10/100) + w 2 x (67/350) + w 3 x (200/500) = 27% Study Adjusted Size and CMH weights same for each treatment; Crude pooling weights are not 15

16 Current labelling limitations: The Issue with Rule of 3 If ADR not observed in clinical trials but determined to be causally related post authorization based on spontaneous reports, Rule of 3 used to estimate category using sample sizes from clinical trials If X is number of patients exposed to drug in all relevant clinical trials, then frequency category would be 3/X, the upper limit of a 95% CI for the true incidence proportion of the event in question This method estimates the incidence proportion by the upper end of a range of plausible values for the incidence proportion. By doing so, ADRs that were never reported in clinical trials can be assigned to a frequency category that is higher than the category for ADRs that were reported in clinical trials. Anomalies arise when AE was observed in clinical trials at same or lower incidence than placebo and so not considered ADR. Subsequently included as ADR based on spontaneous reports. Frequency? Improving Adverse Drug Reaction Information in Product Labels 16

17 Recommendations That product labels that include comparator data be changed to include adjusted incidence proportions (or rates) when needed for adverse drug reactions (ADR) that are somewhat common. Product labels better reflect the risk of a drug relative to a comparator Not needed if: The ratio of patients receiving the new drug to that receiving the comparator is approximately the same across all the studies included or Incidences of AEs in the comparator group are nearly the same across the studies If crude pooling be sure to look at the individual study results to check that pooled results are consistent with the individual studies Including comparator incidence in product labels gives health care providers and patients appropriate information to put the absolute risks in perspective Move from reporting extremely rare events using Rule of 3. Suggest using a separate table for ADRs from PM Reports Improving Adverse Drug Reaction Information in Product Labels 17

18 References Crowe, B., Chuang-Stein, C., Lettis, S., & Brueckner, A. (2016). Reporting Adverse Drug Reactions in Product Labels. Therapeutic Innovation & Regulatory Science, 50(4), Chuang-Stein, C., and Beltangady, M. (2010). Reporting Cumulative Proportion of Subjects With an Adverse Event Based on Data From Multiple Studies. Pharmaceutical Statistics, 10, 3 7. Improving Adverse Drug Reaction Information in Product Labels 18

Pacira v. FDA: Summary of Declaration by Lee Jen Wei, PhD Concluding that the Pivotal Hemorrhoidectomy Study for EXPAREL Demonstrated a Treatment

Pacira v. FDA: Summary of Declaration by Lee Jen Wei, PhD Concluding that the Pivotal Hemorrhoidectomy Study for EXPAREL Demonstrated a Treatment Pacira v. FDA: Summary of Declaration by Lee Jen Wei, PhD Concluding that the Pivotal Hemorrhoidectomy Study for EXPAREL Demonstrated a Treatment Effect for Up To 72 Hours After Surgery Lee Jen Wei, PhD

More information

Meta-analysis of safety thoughts from CIOMS X

Meta-analysis of safety thoughts from CIOMS X CIOMS Working Group X Meta-analysis of safety thoughts from CIOMS X Stephen.Evans@Lshtm.ac.uk Improving health worldwide www.lshtm.ac.uk Evans: ENCePP CIOMS Meta Analysis 1 Acknowledgements, conflicts,

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-USA-232 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. 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 information

GLOSSARY OF GENERAL TERMS

GLOSSARY OF GENERAL TERMS GLOSSARY OF GENERAL TERMS Absolute risk reduction Absolute risk reduction (ARR) is the difference between the event rate in the control group (CER) and the event rate in the treated group (EER). ARR =

More information

GRADE. Grading of Recommendations Assessment, Development and Evaluation. British Association of Dermatologists April 2018

GRADE. Grading of Recommendations Assessment, Development and Evaluation. British Association of Dermatologists April 2018 GRADE Grading of Recommendations Assessment, Development and Evaluation British Association of Dermatologists April 2018 Previous grading system Level of evidence Strength of recommendation Level of evidence

More information

Stratified Tables. Example: Effect of seat belt use on accident fatality

Stratified Tables. Example: Effect of seat belt use on accident fatality Stratified Tables Often, a third measure influences the relationship between the two primary measures (i.e. disease and exposure). How do we remove or control for the effect of the third measure? Issues

More information

UPDATE April 5, 2006 BRIEFING DOCUMENT. Paroxetine Adult Suicidality Analysis: Major Depressive Disorder and Non- Major Depressive Disorder

UPDATE April 5, 2006 BRIEFING DOCUMENT. Paroxetine Adult Suicidality Analysis: Major Depressive Disorder and Non- Major Depressive Disorder UPDATE April 5, 2006 BRIEFING DOCUMENT Paroxetine Adult Suicidality Analysis: Major Depressive Disorder and Non- Major Depressive Disorder 1. Introduction Selective serotonin reuptake inhibitors (SSRIs)

More information

Cost-effectiveness of mepolizumab (Nucala ) as an add-on treatment for severe refractory eosinophilic asthma in adult patients.

Cost-effectiveness of mepolizumab (Nucala ) as an add-on treatment for severe refractory eosinophilic asthma in adult patients. Cost-effectiveness of mepolizumab (Nucala ) as an add-on treatment for severe refractory eosinophilic asthma in adult patients. The NCPE has issued a recommendation regarding the cost-effectiveness of

More information

Critical Appraisal of a Meta-Analysis: Rosiglitazone and CV Death. Debra Moy Faculty of Pharmacy University of Toronto

Critical Appraisal of a Meta-Analysis: Rosiglitazone and CV Death. Debra Moy Faculty of Pharmacy University of Toronto Critical Appraisal of a Meta-Analysis: Rosiglitazone and CV Death Debra Moy Faculty of Pharmacy University of Toronto Goal To provide practitioners with a systematic approach to evaluating a meta analysis

More information

ACR OA Guideline Development Process Knee and Hip

ACR OA Guideline Development Process Knee and Hip ACR OA Guideline Development Process Knee and Hip 1. Literature searching frame work Literature searches were developed based on the scenarios. A comprehensive search strategy was used to guide the process

More information

Risk Management Plans Review of Experience

Risk Management Plans Review of Experience Risk Management Plans Review of Experience Dr Stella Blackburn Risk Management Plans November 05 till September 06 Positive CHMP Opinions RMP MAA 31 29 Extensions of Indication 27 13 Line Extensions 3

More information

GRADE. Grading of Recommendations Assessment, Development and Evaluation. British Association of Dermatologists April 2014

GRADE. Grading of Recommendations Assessment, Development and Evaluation. British Association of Dermatologists April 2014 GRADE Grading of Recommendations Assessment, Development and Evaluation British Association of Dermatologists April 2014 Previous grading system Level of evidence Strength of recommendation Level of evidence

More information

Safeguarding public health CHMP's view on multiplicity; through assessment, advice and guidelines

Safeguarding public health CHMP's view on multiplicity; through assessment, advice and guidelines Safeguarding public health CHMP's view on multiplicity; through assessment, advice and guidelines Rob Hemmings Statistics Unit Manager, MHRA CHMP member Chair, CHMP Scientific Advice Working Party Biostatistics

More information

Regina Louie, Syntex Research, Palo Alto, California Alex Y aroshinsky, Syntex Research, Palo Alto, California

Regina Louie, Syntex Research, Palo Alto, California Alex Y aroshinsky, Syntex Research, Palo Alto, California APPLICATION OF RANDOM EFFECTS MODEL FOR CATEGORICAL DATA TO ANTIEMETIC CLINICAL TRIALS IN CANCER PATIENTS Regina Louie, Syntex Research, Palo Alto, California Alex Y aroshinsky, Syntex Research, Palo Alto,

More information

Comparing the Cochrane review of electronic cigarettes to other meta-analyses

Comparing the Cochrane review of electronic cigarettes to other meta-analyses Comparing the Cochrane review of electronic cigarettes to other meta-analyses Jamie Hartmann-Boyce Cochrane Tobacco Addiction Group, Nuffield Department of Primary Care Health Sciences, University of Oxford.

More information

Clinical Study Synopsis

Clinical Study Synopsis Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace

More information

To open a CMA file > Download and Save file Start CMA Open file from within CMA

To open a CMA file > Download and Save file Start CMA Open file from within CMA Example name Effect size Analysis type Level Tamiflu Hospitalized Risk ratio Basic Basic Synopsis The US government has spent 1.4 billion dollars to stockpile Tamiflu, in anticipation of a possible flu

More information

Helmut Schütz. Satellite Short Course Budapest, 5 October

Helmut Schütz. Satellite Short Course Budapest, 5 October Multi-Group and Multi-Site Studies. To pool or not to pool? Helmut Schütz Satellite Short Course Budapest, 5 October 2017 1 Group Effect Sometimes subjects are split into two or more groups Reasons Lacking

More information

Types of Data. Systematic Reviews: Data Synthesis Professor Jodie Dodd 4/12/2014. Acknowledgements: Emily Bain Australasian Cochrane Centre

Types of Data. Systematic Reviews: Data Synthesis Professor Jodie Dodd 4/12/2014. Acknowledgements: Emily Bain Australasian Cochrane Centre Early Nutrition Workshop, December 2014 Systematic Reviews: Data Synthesis Professor Jodie Dodd 1 Types of Data Acknowledgements: Emily Bain Australasian Cochrane Centre 2 1 What are dichotomous outcomes?

More information

Assessing risk of bias

Assessing risk of bias Assessing risk of bias Norwegian Research School for Global Health Atle Fretheim Research Director, Norwegian Institute of Public Health Professor II, Uiniversity of Oslo Goal for the day We all have an

More information

CLINICAL REGISTRIES Use and Emerging Best Practices

CLINICAL REGISTRIES Use and Emerging Best Practices CLINICAL REGISTRIES Use and Emerging Best Practices Tim Friede Department of Medical Statistics University Medical Center Göttingen DZHK (German Center for Cardiovascular Research) OUTLINE Background:

More information

Summary of Findings tables

Summary of Findings tables Cochrane Pain, Palliative & Supportive Care Review Group Pain Research Unit The Churchill Hospital Headington, Oxford, OX3 7LE, UK Tel: +44 (0)1865 225762 Fax: +44 (0)1865 225400 PaPaS Summary of Findings

More information

STAT362 Homework Assignment 5

STAT362 Homework Assignment 5 STAT362 Homework Assignment 5 Sharon O Boyle Problem 1, Problem 3.6, p. 117 SAS Program * Sharon O'Boyle; * Stat 362; * Homework Assignment 5; * Problem 3.6, p. 117; * Program to compute Odds Ratio and

More information

Introduction to meta-analysis

Introduction to meta-analysis Introduction to meta-analysis Steps of a Cochrane review 1. define the question 2. plan eligibility criteria 3. plan methods 4. search for studies 5. apply eligibility criteria 6. collect data 7. assess

More information

Epidemiologic Methods I & II Epidem 201AB Winter & Spring 2002

Epidemiologic Methods I & II Epidem 201AB Winter & Spring 2002 DETAILED COURSE OUTLINE Epidemiologic Methods I & II Epidem 201AB Winter & Spring 2002 Hal Morgenstern, Ph.D. Department of Epidemiology UCLA School of Public Health Page 1 I. THE NATURE OF EPIDEMIOLOGIC

More information

Epidemiologic study designs

Epidemiologic study designs Epidemiologic study designs and critical appraisal of scientific papers Rolf H.H. Groenwold, MD, PhD Bio sketch MD, PhD in epidemiology Associate professor of Epidemiology at UMC Utrecht Research focus

More information

115 remained abstinent. 140 remained abstinent. Relapsed Remained abstinent Total

115 remained abstinent. 140 remained abstinent. Relapsed Remained abstinent Total Chapter 10 Exercises 1. Intent-to-treat analysis: Example 1 In a randomized controlled trial to determine whether the nicotine patch reduces the risk of relapse among smokers who have committed to quit,

More information

Cardiovascular Risk of Celecoxib in 6 Randomized Placebo-controlled Trials: The Cross Trial Safety Analysis

Cardiovascular Risk of Celecoxib in 6 Randomized Placebo-controlled Trials: The Cross Trial Safety Analysis Cardiovascular Risk of Celecoxib in 6 Randomized Placebo-controlled Trials: The Cross Trial Safety Analysis Scott D. Solomon, MD, Janet Wittes, PhD, Ernest Hawk, MD, MPH for the Celecoxib Cross Trials

More information

How to do a meta-analysis. Orestis Efthimiou Dpt. Of Hygiene and Epidemiology, School of Medicine University of Ioannina, Greece

How to do a meta-analysis. Orestis Efthimiou Dpt. Of Hygiene and Epidemiology, School of Medicine University of Ioannina, Greece How to do a meta-analysis Orestis Efthimiou Dpt. Of Hygiene and Epidemiology, School of Medicine University of Ioannina, Greece 1 Overview (A brief reminder of ) What is a Randomized Controlled Trial (RCT)

More information

Is There An Association?

Is There An Association? Is There An Association? Exposure (Risk Factor) Outcome Exposures Risk factors Preventive measures Management strategy Independent variables Outcomes Dependent variable Disease occurrence Lack of exercise

More information

How Causal Heterogeneity Can Influence Statistical Significance in Clinical Trials

How Causal Heterogeneity Can Influence Statistical Significance in Clinical Trials How Causal Heterogeneity Can Influence Statistical Significance in Clinical Trials Milo Schield, W. M. Keck Statistical Literacy Project. Minneapolis, MN. Abstract: Finding that an association is statistically

More information

INDUSTRY PERSPECTIVE ON DRUG DEVELOPMENT FOR TYPE 1 SMA

INDUSTRY PERSPECTIVE ON DRUG DEVELOPMENT FOR TYPE 1 SMA INDUSTRY PERSPECTIVE ON DRUG DEVELOPMENT FOR TYPE 1 SMA Kathie M. Bishop, PhD Disclosures: Currently, CSO of Tioga Pharmaceuticals, no activities in SMA; 2009-2015, full-time employee of Ionis Pharmaceuticals,

More information

Deep vein thrombosis and its prevention in critically ill adults Attia J, Ray J G, Cook D J, Douketis J, Ginsberg J S, Geerts W H

Deep vein thrombosis and its prevention in critically ill adults Attia J, Ray J G, Cook D J, Douketis J, Ginsberg J S, Geerts W H Deep vein thrombosis and its prevention in critically ill adults Attia J, Ray J G, Cook D J, Douketis J, Ginsberg J S, Geerts W H Authors' objectives To systematically review the incidence of deep vein

More information

Per the study design and a limitation of this analysis, swabs were not tested for HPV types 6

Per the study design and a limitation of this analysis, swabs were not tested for HPV types 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 SUPPLEMENTARY MATERIAL Progression, regression, and clearance of HPV6/11 infections Per the study design and a limitation of this analysis, swabs

More information

Lecture 4. Confounding

Lecture 4. Confounding Lecture 4 Confounding Learning Objectives In this set of lectures we will: - Formally define confounding and give explicit examples of it s impact - Define adjustment and adjusted estimates conceptually

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-INT-24 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral disturbances in demented patients: an international, multicenter,

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of

More information

Do the sample size assumptions for a trial. addressing the following question: Among couples with unexplained infertility does

Do the sample size assumptions for a trial. addressing the following question: Among couples with unexplained infertility does Exercise 4 Do the sample size assumptions for a trial addressing the following question: Among couples with unexplained infertility does a program of up to three IVF cycles compared with up to three FSH

More information

Can erythropoietin treatment during antiviral drug treatment for hepatitis C be cost effective?

Can erythropoietin treatment during antiviral drug treatment for hepatitis C be cost effective? Below Are Selected Good Abstracts from Digestive Disease Week 2006 Meeting Published in Gut. 2006 April; 55(Suppl 2): A1 A119. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1859999/?tool=pmcentrez Can erythropoietin

More information

Evidence-Based Medicine Journal Club. A Primer in Statistics, Study Design, and Epidemiology. August, 2013

Evidence-Based Medicine Journal Club. A Primer in Statistics, Study Design, and Epidemiology. August, 2013 Evidence-Based Medicine Journal Club A Primer in Statistics, Study Design, and Epidemiology August, 2013 Rationale for EBM Conscientious, explicit, and judicious use Beyond clinical experience and physiologic

More information

Adverse Events Following Immunisation

Adverse Events Following Immunisation Adverse Events Following Immunisation (common, uncommon, shockin rare, and how do we know their likely cause?) Kevin Connolly Portiuncula Hospital, Sept. 18, 2017 Definitions Adverse Event (AE).. untoward

More information

Adalimumab M Clinical Study Report Final R&D/16/0603

Adalimumab M Clinical Study Report Final R&D/16/0603 Methodology (Continued): The 70-day safety follow-up period started from the last dose of study drug, but was not required for any subject who initiated commercial Humira after study completion. Additional

More information

Observational Studies and PCOR: What are the right questions?

Observational Studies and PCOR: What are the right questions? Observational Studies and PCOR: What are the right questions? Steven Goodman, MD, MHS, PhD Stanford University PCORI MC Steve.goodman@stanford.edu A tale of two cities? "It was the best of times, it was

More information

Statistical challenges of meta-analyses of randomised clinical trials in a regulatory setting

Statistical challenges of meta-analyses of randomised clinical trials in a regulatory setting Statistical challenges of meta-analyses of randomised clinical trials in a regulatory setting Frank Pétavy ISCTM 14th Annual Scientific Meeting, Washington D.C. Presented by Frank Pétavy on 21 February

More information

Varenicline and cardiovascular and neuropsychiatric events: Do Benefits outweigh risks?

Varenicline and cardiovascular and neuropsychiatric events: Do Benefits outweigh risks? Varenicline and cardiovascular and neuropsychiatric events: Do Benefits outweigh risks? Sonal Singh M.D., M.P.H, Johns Hopkins University Presented by: Sonal Singh, MD MPH September 19, 2012 1 CONFLICTS

More information

Paliperidone: Clinical Protocol R076477SCH4012, CR Amendment INT-1

Paliperidone: 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 information

Live WebEx meeting agenda

Live WebEx meeting agenda 10:00am 10:30am Using OpenMeta[Analyst] to extract quantitative data from published literature Live WebEx meeting agenda August 25, 10:00am-12:00pm ET 10:30am 11:20am Lecture (this will be recorded) 11:20am

More information

Using Statistical Principles to Implement FDA Guidance on Cardiovascular Risk Assessment for Diabetes Drugs

Using Statistical Principles to Implement FDA Guidance on Cardiovascular Risk Assessment for Diabetes Drugs Using Statistical Principles to Implement FDA Guidance on Cardiovascular Risk Assessment for Diabetes Drugs David Manner, Brenda Crowe and Linda Shurzinske BASS XVI November 9-13, 2009 Acknowledgements

More information

Answer keys for Assignment 4: Measures of disease frequency

Answer keys for Assignment 4: Measures of disease frequency Answer keys for Assignment 4: Measures of disease frequency (The correct answer is underlined in bold text) 1. This statistic is used to estimate the risk of acquiring a disease. It may be measured as

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-AUS-5 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-AUS-5 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-AUS-5 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral and psychological symptoms in dementia: a multicenter, double-blind,

More information

JAMA. 2011;305(24): Nora A. Kalagi, MSc

JAMA. 2011;305(24): Nora A. Kalagi, MSc JAMA. 2011;305(24):2556-2564 By Nora A. Kalagi, MSc Cardiovascular disease (CVD) is the number one cause of mortality and morbidity world wide Reducing high blood cholesterol which is a risk factor for

More information

Alcohol interventions in secondary and further education

Alcohol interventions in secondary and further education National Institute for Health and Care Excellence Guideline version (Draft for Consultation) Alcohol interventions in secondary and further education NICE guideline: methods NICE guideline Methods

More information

To open a CMA file > Download and Save file Start CMA Open file from within CMA

To open a CMA file > Download and Save file Start CMA Open file from within CMA Example name Effect size Analysis type Level Tamiflu Symptom relief Mean difference (Hours to relief) Basic Basic Reference Cochrane Figure 4 Synopsis We have a series of studies that evaluated the effect

More information

Making 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 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 information

Controlling Bias & Confounding

Controlling Bias & Confounding Controlling Bias & Confounding Chihaya Koriyama August 5 th, 2015 QUESTIONS FOR BIAS Key concepts Bias Should be minimized at the designing stage. Random errors We can do nothing at Is the nature the of

More information

SYNOPSIS 2/198 CSR_BDY-EFC5825-EN-E02. Name of company: TABULAR FORMAT (For National Authority Use only)

SYNOPSIS 2/198 CSR_BDY-EFC5825-EN-E02. Name of company: TABULAR FORMAT (For National Authority Use only) SYNOPSIS Title of the study: A randomized, double-blind, placebo-controlled, parallel-group, fixed-dose (rimonabant 20 mg) multicenter study of long-term glycemic control with rimonabant in treatment-naïve

More information

Meta Analysis. David R Urbach MD MSc Outcomes Research Course December 4, 2014

Meta Analysis. David R Urbach MD MSc Outcomes Research Course December 4, 2014 Meta Analysis David R Urbach MD MSc Outcomes Research Course December 4, 2014 Overview Definitions Identifying studies Appraising studies Quantitative synthesis Presentation of results Examining heterogeneity

More information

Evidence Based Medicine

Evidence Based Medicine Course Goals Goals 1. Understand basic concepts of evidence based medicine (EBM) and how EBM facilitates optimal patient care. 2. Develop a basic understanding of how clinical research studies are designed

More information

Identifying Susceptibility in Epidemiology Studies: Implications for Risk Assessment. Joel Schwartz Harvard TH Chan School of Public Health

Identifying Susceptibility in Epidemiology Studies: Implications for Risk Assessment. Joel Schwartz Harvard TH Chan School of Public Health Identifying Susceptibility in Epidemiology Studies: Implications for Risk Assessment Joel Schwartz Harvard TH Chan School of Public Health Risk Assessment and Susceptibility Typically we do risk assessments

More information

GATE: Graphic Appraisal Tool for Epidemiology picture, 2 formulas & 3 acronyms

GATE: Graphic Appraisal Tool for Epidemiology picture, 2 formulas & 3 acronyms GATE: Graphic Appraisal Tool for Epidemiology 1991-2015 1 picture, 2 formulas & 3 acronyms 1 GATE: Graphic Appraisal Tool for Epidemiology Graphic Architectural Tool for Epidemiology Graphic Approach To

More information

Cochrane Pregnancy and Childbirth Group Methodological Guidelines

Cochrane Pregnancy and Childbirth Group Methodological Guidelines Cochrane Pregnancy and Childbirth Group Methodological Guidelines [Prepared by Simon Gates: July 2009, updated July 2012] These guidelines are intended to aid quality and consistency across the reviews

More information

Background. Population/Intervention(s)/Comparison/Outcome(s) (PICO) Role of antidepressants in people with dementia and associated depression

Background. Population/Intervention(s)/Comparison/Outcome(s) (PICO) Role of antidepressants in people with dementia and associated depression updated 2012 Role of antidepressants in people with dementia and associated depression Q4: For people with dementia with associated depression, do antidepressants when compared to placebo/comparator produce

More information

Use of Subgroups to Rescue a Trial or Improve Benefit-Risk

Use of Subgroups to Rescue a Trial or Improve Benefit-Risk 1 Use of Subgroups to Rescue a Trial or Improve Benefit-Risk Martin King, Ph.D. Director, Statistics Global Pharmaceutical R&D, Abbott Abbott Park, IL USA 2 Disclaimer The opinions in this presentation

More information

The role of MTM in Overviews of Reviews

The role of MTM in Overviews of Reviews Deborah Caldwell The role of MTM in Overviews of Reviews d.m.caldwell@bristol.ac.uk Comparing Multiple Interventions Methods Group Keystone, 2010 Why we need overviews of reviews Explosion in RCTs necessitated

More information

How to Conduct a Meta-Analysis

How to Conduct a Meta-Analysis How to Conduct a Meta-Analysis Faculty Development and Diversity Seminar ludovic@bu.edu Dec 11th, 2017 Periodontal disease treatment and preterm birth We conducted a metaanalysis of randomized controlled

More information

Sponsor / Company: Sanofi Drug substance(s): AMARYL M (1/250 mg) / HOE490

Sponsor / Company: Sanofi Drug substance(s): AMARYL M (1/250 mg) / HOE490 These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert in the country of prescription. Sponsor / Company: Sanofi Drug substance(s):

More information

2.0 Synopsis. ABT-711 M Clinical Study Report R&D/06/054. (For National Authority Use Only) Referring to Part of Dossier: Volume: Page:

2.0 Synopsis. ABT-711 M Clinical Study Report R&D/06/054. (For National Authority Use Only) Referring to Part of Dossier: Volume: Page: 2.0 Synopsis Abbott Laboratories Name of Study Drug: Depakote ER Name of Active Ingredient: Divalproex Sodium Individual Study Table Referring to Part of Dossier: Volume: Page: (For National Authority

More information

What is indirect comparison?

What is indirect comparison? ...? series New title Statistics Supported by sanofi-aventis What is indirect comparison? Fujian Song BMed MMed PhD Reader in Research Synthesis, Faculty of Health, University of East Anglia Indirect comparison

More information

Study No: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:

Study 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 information

Reflection paper on assessment of cardiovascular safety profile of medicinal products

Reflection paper on assessment of cardiovascular safety profile of medicinal products 25 February 2016 EMA/CHMP/50549/2015 Committee for Medicinal Products for Human Use (CHMP) Reflection paper on assessment of cardiovascular safety profile of medicinal products Draft agreed by Cardiovascular

More information

Confounding and Bias

Confounding and Bias 28 th International Conference on Pharmacoepidemiology and Therapeutic Risk Management Barcelona, Spain August 22, 2012 Confounding and Bias Tobias Gerhard, PhD Assistant Professor, Ernest Mario School

More information

Summary ID#7029. Clinical Study Summary: Study F1D-MC-HGKQ

Summary 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 information

Outline. What is Evidence-Based Practice? EVIDENCE-BASED PRACTICE. What EBP is Not:

Outline. What is Evidence-Based Practice? EVIDENCE-BASED PRACTICE. What EBP is Not: Evidence Based Practice Primer Outline Evidence Based Practice (EBP) EBP overview and process Formulating clinical questions (PICO) Searching for EB answers Trial design Critical appraisal Assessing the

More information

Transcranial Direct-Current Stimulation

Transcranial Direct-Current Stimulation Introduction (tdcs) is a non-invasive form of brain stimulation similar to transcranial magnetic stimulation, but instead of using magnets, it uses a lowintensity, constant current applied through scalp

More information

A Guide to Reading a Clinical or Research Publication

A Guide to Reading a Clinical or Research Publication A Guide to Reading a Clinical or Research Publication For people living with a rare disease, being able to read and understand the information found in a clinical or research publication can be especially

More information

SYNOPSIS (FOR NATIONAL AUTHORITY USE ONLY) INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER

SYNOPSIS (FOR NATIONAL AUTHORITY USE ONLY) INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER SYNOPSIS Protocol No.: RIS-USA-63 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: A randomized, double-blind, placebo controlled study of risperidone for treatment of behavioral disturbances

More information

Tuning Epidemiological Study Design Methods for Exploratory Data Analysis in Real World Data

Tuning Epidemiological Study Design Methods for Exploratory Data Analysis in Real World Data Tuning Epidemiological Study Design Methods for Exploratory Data Analysis in Real World Data Andrew Bate Senior Director, Epidemiology Group Lead, Analytics 15th Annual Meeting of the International Society

More information

Part 1. For each of the following questions fill-in the blanks. Each question is worth 2 points.

Part 1. For each of the following questions fill-in the blanks. Each question is worth 2 points. Part 1. For each of the following questions fill-in the blanks. Each question is worth 2 points. 1. The bell-shaped frequency curve is so common that if a population has this shape, the measurements are

More information

Progesterone support of the luteal phase and in the first trimester

Progesterone support of the luteal phase and in the first trimester Progesterone support of the luteal phase and in the first trimester This statement has been developed and reviewed by the Women s Health Committee and approved by the RANZCOG Board and Council. A list

More information

The role of Randomized Controlled Trials

The role of Randomized Controlled Trials The role of Randomized Controlled Trials Dr. Georgia Salanti Lecturer in Epidemiology University of Ioannina School of Medicine Outline Understanding study designs and the role of confounding Observational

More information

Leaning objectives. Outline. 13-Jun-16 BASIC EXPERIMENTAL DESIGNS

Leaning objectives. Outline. 13-Jun-16 BASIC EXPERIMENTAL DESIGNS BASIC EXPERIMENTAL DESIGNS John I. Anetor Chemical Pathology Department University of Ibadan Nigeria MEDICAL EDUCATION PATNERSHIP INITIATIVE NIGERIA [MEPIN] JUNIOR FACULTY WORKSHOP 10-13 th May, 2014 @

More information

Index. Springer International Publishing Switzerland 2017 T.J. Cleophas, A.H. Zwinderman, Modern Meta-Analysis, DOI /

Index. Springer International Publishing Switzerland 2017 T.J. Cleophas, A.H. Zwinderman, Modern Meta-Analysis, DOI / Index A Adjusted Heterogeneity without Overdispersion, 63 Agenda-driven bias, 40 Agenda-Driven Meta-Analyses, 306 307 Alternative Methods for diagnostic meta-analyses, 133 Antihypertensive effect of potassium,

More information

Clinical Trial Report Synopsis

Clinical Trial Report Synopsis This document has been do\vnloaded from \v ww.leo-pharma.com subject to the terms of use state on the website. It contains data and results regarding approved and non-approved uses, formulations or treatment

More information

Chapter 5: Field experimental designs in agriculture

Chapter 5: Field experimental designs in agriculture Chapter 5: Field experimental designs in agriculture Jose Crossa Biometrics and Statistics Unit Crop Research Informatics Lab (CRIL) CIMMYT. Int. Apdo. Postal 6-641, 06600 Mexico, DF, Mexico Introduction

More information

Systematic Reviews and Meta- Analysis in Kidney Transplantation

Systematic Reviews and Meta- Analysis in Kidney Transplantation Systematic Reviews and Meta- Analysis in Kidney Transplantation Greg Knoll MD MSc Associate Professor of Medicine Medical Director, Kidney Transplantation University of Ottawa and The Ottawa Hospital KRESCENT

More information

Benefit - Risk Analysis for Oncology Clinical Trials

Benefit - Risk Analysis for Oncology Clinical Trials PhUSE 2012 PP14 Benefit - Risk Analysis for Oncology Clinical Trials Waseem Jugon, Lovemore Gakava, Littish Dominic and Jayantha Ratnayake Roche Products Ltd, UK ABSTRACT The conventional analysis of safety

More information

Estimands. EFPIA webinar Rob Hemmings, Frank Bretz October 2017

Estimands. EFPIA webinar Rob Hemmings, Frank Bretz October 2017 Estimands EFPIA webinar Rob Hemmings, Frank Bretz October 2017 Why estimands? To explain which treatment effect is described to prescribers and other stakeholders. To align objectives with (design and)

More information

EFFECTIVE MEDICAL WRITING Michelle Biros, MS, MD Editor-in -Chief Academic Emergency Medicine

EFFECTIVE MEDICAL WRITING Michelle Biros, MS, MD Editor-in -Chief Academic Emergency Medicine EFFECTIVE MEDICAL WRITING Michelle Biros, MS, MD Editor-in -Chief Academic Emergency Medicine Why We Write To disseminate information To share ideas, discoveries, and perspectives to a broader audience

More information

1/25/2018 ARE CGRP ANTAGONISTS ANY BETTER THAN CURRENT EVIDENCE BASED TREATMENTS? Disclosures: Objectives: Headache Division

1/25/2018 ARE CGRP ANTAGONISTS ANY BETTER THAN CURRENT EVIDENCE BASED TREATMENTS? Disclosures: Objectives: Headache Division ARE CGRP ANTAGONISTS ANY BETTER THAN CURRENT EVIDENCE BASED TREATMENTS? Lawrence C Newman, MD, FAHS, FAAN Clinical Professor of Neurology Disclosures: Advisory Board: Alder, Allergan, Amgen, Lilly, Supernus,

More information

Chapter 2 Methodology: How Social Psychologists Do Research

Chapter 2 Methodology: How Social Psychologists Do Research Chapter 2 Methodology: How Social Psychologists Do Research Methodology Social Psychology: An Empirical Science Empirical research allows us to test the validity of personal observations and folk wisdom.

More information

CLINICAL STUDY REPORT SYNOPSIS

CLINICAL STUDY REPORT SYNOPSIS CLINICAL STUDY REPORT SYNOPSIS Document No.: EDMS-PSDB-5412862:2.0 Research & Development, L.L.C. Protocol No.: R115777-AML-301 Title of Study: A Randomized Study of Tipifarnib Versus Best Supportive Care

More information

Cardiovascular Disease and Commercial Motor Vehicle Driver Safety. Physical Qualifications Division April 10, 2007

Cardiovascular Disease and Commercial Motor Vehicle Driver Safety. Physical Qualifications Division April 10, 2007 Federal Motor Carrier Safety Administration Executive Summary Cardiovascular Disease and Commercial Motor Vehicle Driver Safety Presented to Physical Qualifications Division April 10, 2007 Prepared by:

More information

Confounding and Effect Modification. John McGready Johns Hopkins University

Confounding and Effect Modification. John McGready Johns Hopkins University This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this

More information

European Federation of Statisticians in the Pharmaceutical Industry (EFSPI)

European Federation of Statisticians in the Pharmaceutical Industry (EFSPI) Page 1 of 14 European Federation of Statisticians in the Pharmaceutical Industry (EFSPI) COMMENTS ON DRAFT FDA Guidance for Industry - Non-Inferiority Clinical Trials Rapporteur: Bernhard Huitfeldt (bernhard.huitfeldt@astrazeneca.com)

More information

Confounding, Effect modification, and Stratification

Confounding, Effect modification, and Stratification Confounding, Effect modification, and Stratification Tunisia, 30th October 2014 Acknowledgment: Kostas Danis Takis Panagiotopoulos National Schoool of Public Health, Athens, Greece takis.panagiotopoulos@gmail.com

More information

Meta-analyses: analyses:

Meta-analyses: analyses: Meta-analyses: analyses: how do they help, and when can they not? Lee Hooper Senior Lecturer in research synthesis & nutrition l.hooper@uea.ac.uk 01603 591268 Aims Systematic Reviews Discuss the scientific

More information

MSc Programme in International Health Epidemiology and Statistics. Before lecture exercise. Aims of the lecture

MSc Programme in International Health Epidemiology and Statistics. Before lecture exercise. Aims of the lecture MSc Programme in International Health Epidemiology and Statistics Why was the advert for Actimel banned by the ASA? Lecture 9 1 Before lecture exercise Select 10 red tiles and 10 blue tiles at random from

More information

Journal Club. 1. Develop a PICO (Population, Intervention, Comparison, Outcome) question for this study

Journal Club. 1. Develop a PICO (Population, Intervention, Comparison, Outcome) question for this study Journal Club Articles for Discussion Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-pa Stroke Study Group. N Engl J Med. 1995 Dec

More information

Risk Study. Section for Clinical Epidemiology and Biostatistics. Definition

Risk Study. Section for Clinical Epidemiology and Biostatistics. Definition Risk Study Section for Clinical Epidemiology and Biostatistics What is Risk? Definition The probability of some untoward event The likelihood that people who are exposed to certain factors (risk factors)

More information

Database of Abstracts of Reviews of Effects (DARE) Produced by the Centre for Reviews and Dissemination Copyright 2017 University of York.

Database of Abstracts of Reviews of Effects (DARE) Produced by the Centre for Reviews and Dissemination Copyright 2017 University of York. A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling Brown

More information