BIOE 301 Lecture Seventeen. Progression of Heart Disease High Blood Pressure High Cholesterol Levels Atherosclerosis Ischemia Heart Attack Heart Failure.

Slides:



Advertisements
Similar presentations
How would you explain the smoking paradox. Smokers fair better after an infarction in hospital than non-smokers. This apparently disagrees with the view.
Advertisements

Randomized Controlled Trial
Regulatory Clinical Trials Clinical Trials. Clinical Trials Definition: research studies to find ways to improve health Definition: research studies to.
Designing Clinical Research Studies An overview S.F. O’Brien.
LSU-HSC School of Public Health Biostatistics 1 Statistical Core Didactic Introduction to Biostatistics Donald E. Mercante, PhD.
Critical Appraisal: Epidemiology 101 POS Lecture Series April 28, 2004.
1 Health and Disease in Populations 2002 Week 9 – 2/5/02 Randomised controlled trials 2 Dr Jenny Kurinczuk.
天 津 医 科 大 学天 津 医 科 大 学 Clinical trail. 天 津 医 科 大 学天 津 医 科 大 学 1.Historical Background 1537: Treatment of battle wounds: 1741: Treatment of Scurvy 1948:
Clinical Trials Medical Interventions
Chapter 11: Sequential Clinical Trials Descriptive Exploratory Experimental Describe Find Cause Populations Relationships and Effect Sequential Clinical.
Clinical Trials Hanyan Yang
BS704 Class 7 Hypothesis Testing Procedures
Sample Size Determination
Cohort Studies Hanna E. Bloomfield, MD, MPH Professor of Medicine Associate Chief of Staff, Research Minneapolis VA Medical Center.
Experimental Study.
Clinical Trials The Way We Make Progress Against Disease.
RANDOMIZED CLINICAL TRIALS. What is a randomized clinical trial?  Scientific investigations: examine and evaluate the safety and efficacy of new drugs.
The Bahrain Branch of the UK Cochrane Centre In Collaboration with Reyada Training & Management Consultancy, Dubai-UAE Cochrane Collaboration and Systematic.
Adverse Events, Unanticipated Problems, Protocol Deviations & other Safety Information Which Form 4 to Use?
Clinical Trials. What is a clinical trial? Clinical trials are research studies involving people Used to find better ways to prevent, detect, and treat.
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 7: Gathering Evidence for Practice.
Testing People Scientifically.  Clinical trials are research studies in which people help doctors and researchers find ways to improve health care. Each.
How To Design a Clinical Trial This exercise will guide you through all the steps of your course project, in particular how to design a clinical trial.
BIOE 301 Lecture Seventeen. Guest Speaker Jay Brollier World Camp Malawi.
Epidemiology The Basics Only… Adapted with permission from a class presentation developed by Dr. Charles Lynch – University of Iowa, Iowa City.
Background to Adaptive Design Nigel Stallard Professor of Medical Statistics Director of Health Sciences Research Institute Warwick Medical School
Study design P.Olliaro Nov04. Study designs: observational vs. experimental studies What happened?  Case-control study What’s happening?  Cross-sectional.
Clinical Trial Designs An Overview. Identify: condition(s) of interest, intended population, planned treatment protocols Recruitment of volunteers: volunteers.
Placebo-Controls in Short-Term Clinical Trials of Hypertension Sana Al-Khatib, MD, MHS Assistant Professor of Medicine Division of Cardiology Duke University.
Sample Size And Power Warren Browner and Stephen Hulley  The ingredients for sample size planning, and how to design them  An example, with strategies.
1 An Interim Monitoring Approach for a Small Sample Size Incidence Density Problem By: Shane Rosanbalm Co-author: Dennis Wallace.
Lecture 5 Objective 14. Describe the elements of design of experimental studies: clinical trials and community intervention trials. Discuss the advantages.
1 Statistics in Drug Development Mark Rothmann, Ph. D.* Division of Biometrics I Food and Drug Administration * The views expressed here are those of the.
What is a non-inferiority trial, and what particular challenges do such trials present? Andrew Nunn MRC Clinical Trials Unit 20th February 2012.
통계적 추론 (Statistical Inference) 삼성생명과학연구소 통계지원팀 김선우 1.
How to read a paper D. Singh-Ranger. Academic viva 2 papers 1 hour to read both Viva on both papers Summary-what is the paper about.
بسم الله الرحمن الرحيم جامعة أم درمان الإسلامية كلية الطب و العلوم الصحية - قسم طب المجتمع مساق البحث العلمي / الدفعة 21 Basics of Clinical Trials.
Medical Statistics as a science
BME 301 Lecture Nineteen. Progression of Heart Disease High Blood Pressure High Cholesterol Levels Atherosclerosis Ischemia Heart Attack Heart Failure.
August 20, 2003FDA Antiviral Drugs Advisory Committee Meeting 1 Statistical Considerations for Topical Microbicide Phase 2 and 3 Trial Designs: A Regulatory.
Math 4030 – 9a Introduction to Hypothesis Testing
How To Design a Clinical Trial
Lecture Twenty: Clinical Trials Biomedical Engineering for Global Health.
June 23, 2005Abiomed, H DRAFT. CIRCULATORY SUPPORT DEVICES PANEL Thursday, June 23, 2005 Abiomed, Inc. Abiocor® Implantable Replacement Heart HDE.
Copyright © 2013, 2009, and 2007, Pearson Education, Inc. Chapter 10 Comparing Two Groups Section 10.1 Categorical Response: Comparing Two Proportions.
BIOE 301 Lecture Twenty: Clinical Trials Mike Cordray
Compliance Original Study Design Randomised Surgical care Medical care.
Safety of Albumin Revisited Blood Products Advisory Committee Meeting March 17, 2005 Laurence Landow MD, FRCPC.
Course: Research in Biomedicine and Health III Seminar 5: Critical assessment of evidence.
What about VIOXX?. Adenomatous Polyp Prevention on Vioxx (APPROVe) Vioxx (rofecoxib) versus Placebo Basic Clinical Trial Objective: Assess whether Vioxx.
بسم الله الرحمن الرحیم.
STA Lecture 231 STA 291 Lecture 23 Testing hypothesis about population proportion(s) Examples.
BME 301 Lecture Nineteen. Progression of Heart Disease High Blood Pressure High Cholesterol Levels Atherosclerosis Ischemia Heart Attack Heart Failure.
Introduction to Biostatistics, Harvard Extension School, Fall, 2005 © Scott Evans, Ph.D.1 Sample Size and Power Considerations.
Purpose of Clinical Trials Assess safety and efficacy of Experimental treatments New combinations of drugs New approaches to surgery or radiation therapies.
Chapter 10 Comparing Two Populations or Groups Sect 10.1 Comparing two proportions.
Critical Appraisal Course for Emergency Medicine Trainees Module 2 Statistics.
How To Design a Clinical Trial
CLINICAL PROTOCOL DEVELOPMENT
How many study subjects are required ? (Estimation of Sample size) By Dr.Shaik Shaffi Ahamed Associate Professor Dept. of Family & Community Medicine.
Statistical Core Didactic
How to read a paper D. Singh-Ranger.
Clinical Trials Medical Interventions
Randomized Trials: A Brief Overview
Observational Studies and Experiments
Clinical Trials.
Bioengineering and World Health
HEC508 Applied Epidemiology
Type I and Type II Errors
Finding a Balance of Synergy and Flexibility in Master Protocols
Presentation transcript:

BIOE 301 Lecture Seventeen

Progression of Heart Disease High Blood Pressure High Cholesterol Levels Atherosclerosis Ischemia Heart Attack Heart Failure

Review of Last Time What is heart failure? Occurs when left or right ventricle loses the ability to keep up with amount of blood flow How do we treat heart failure? Heart transplant Rejection, inadequate supply of donor hearts LVAD Can delay progression of heart failure Artificial heart

Artificial Heart - History First artificial heart implanted in 1969 No more human trials until the 1980s…

History of Artificial Heart com/stories/2004/05/ 27/earlyshow/contrib utors/emilysenay/mai n shtml com/stories/2004/05/ 27/earlyshow/contrib utors/emilysenay/mai n shtml June ures/feature.jhtml?wfId= ures/feature.jhtml?wfId= August ures/feature.jhtml?wfId= ures/feature.jhtml?wfId= November ures/feature.jhtml?wfId= ures/feature.jhtml?wfId=

AbioCor Artificial Heart eers.com/newsimages.html# eers.com/newsimages.html# Cost: $70-100k

Clinical Trial of AbioCor Goals of Initial Clinical Trial Determine whether AbioCor™ can extend life with acceptable quality for patients with less than 30 days to live and no other therapeutic alternative To learn what we need to know to deliver the next generation of AbioCor, to treat a broader patient population for longer life and improving quality of life.

Clinical Trial of AbioCor Patient Inclusion Criteria (highlights) Bi-ventricular heart failure Greater than eighteen years old High likelihood of dying within the next thirty days Unresponsive to maximum existing therapies Ineligible for cardiac transplantation Successful AbioFit™ analysis Patient Exclusion Criteria (highlights) Heart failure with significant potential for reversibility Life expectancy >30 days Serious non-cardiac disease Pregnancy Psychiatric illness (including drug or alcohol abuse) Inadequate social support system

Clinical Trial of AbioCor Clinical Trial Endpoints All-cause mortality through sixty days Quality of Life measurements Repeat QOL assessments at 30-day intervals until death Number of patients Initial authorization for five (5) implants Expands to fifteen (15) patients in increments of five (5) if 60-day experience is satisfactory to FDA

Consent Form es/ABIOMED_1-Case.pdf es/ABIOMED_1-Case.pdf

Prevention of Heart Disease 1990s: Small series of trials suggested that high doses of Vitamin E might reduce risk of developing heart disease by 40% 1996: Randomized clinical trial: 1035 patients taking vitamin E 967 patients taking placebo Vitamin E provides a protective effect

Prevention of Heart Disease 2000: pivotal clinical trial 9,541 patients No benefit to Vitamin E Followed for 7 years: may increase risk of heart disease What happened?

Challenges: Clinical Research Early studies, small # patients: Generate hypotheses Larger studies Rigorously test hypotheses Due to biological variability: Larger studies often contradict early studies Recent study: 1/3 of highly cited studies - later contradicted! More frequent if patients aren’t randomized

Types of Clinical Studies Hypothesis Generation Case study, case series: examine patient or group of patients with similar illness Hypothesis Testing: Observational: Identify group of patients with and without disease. Collect data. Use to test our hypothesis. Advantage: Easy, cheap. Disadvantage: Bias. Can’t control the interventional to decisively show cause and effect.

Types of Clinical Studies Hypothesis Testing: Experimental: Clinical trial: Research study to evaluate effect of an intervention on patients. Isolate all but a single variable and measure the effect of the variable. Done prospectively: Plan, then execute. Single arm study: Take patients, give intervention, compare to baseline. Can suffer from placebo effect. Randomized clinical trials: Different subjects are randomly assigned to get the treatment or the control.

Planning a Randomized Clinical Trial Two arms: Treatment group Control group Outcome: Primary outcome Secondary outcomes Sample size: Want to ensure that any differences between treatment and control group are real Must consider $$ available

Example – Planning a Clinical Trial New drug eluting stent Treatment group: Control group: Primary Outcome: Secondary Outcomes:

Sample Size Calculation There will be some statistical uncertainty associated with the measured restenosis rate Goal: Uncertainty << Difference in primary outcome between control & treatment group Choose our sample size so that this is true

Types of Errors in Clinical Trial Type I Error: We mistakenly conclude that there is a difference between the two groups, when in reality there is no difference Type II Error: We mistakenly conclude that there is not a difference between the two, when in reality there is a difference Choose our sample size: Acceptable likelihood of Type I or II error Enough $$ to carry out the trial

Types of Errors in Clinical Trial Type I Error: We mistakenly conclude that there IS a difference between the two groups p-value – probability of making a Type I error Usually set p = 1% - 5% Type II Error: We mistakenly conclude that there IS NOT a difference between the two Beta – probability of making a Type II error Power = 1 – beta = 1 – probability of making a Type II error Usually set beta = %

How do we calculate n? Select primary outcome Estimate expected rate of primary outcome in: Treatment group Control group Set acceptable levels of Type I and II error Choose p-value Choose beta

How do we calculate n? Calculate standardized difference: SD = P 1 -P 2 /sqrt(p(1-p)) p = (P 1 +P 2 )/2 P 1 = fraction of patients in treatment group who experience primary outcome P 2 = fraction of patients in control group who experience primary outcome Use Altman’s nomogram to determine n

Drug Eluting Stent – Sample Size Treatment group: Receive stent Control group: Get angioplasty Primary Outcome: 1 year restenosis rate Expected Outcomes: Stent: 10% Angioplasty: 45% Error rates: p = 0.05 Beta = 0.2 SD = patients required in each arm

Data & Safety Monitoring Boards DSMB: Special committees to monitor interim results in clinical trials. Federal rules require all phase III trials be monitored by DSMBs. Can stop trial early: New treatment offered to both groups. Prevent additional harm.

DSMBs New treatment for sepsis: New drug Placebo n = 1500 Interim analysis after 722 patients: Mortality in placebo group: 38.9% Mortality in treatment group: 29.1% Significant at the p = level! Should the study be stopped?

DSMBs Decision: No Neither researchers nor subjects were informed Outcome: Mortality in placebo group: 33.9% Mortality in treatment group: 34.2% Difference was neither clinically nor statistically significant! Informed consents should be modified to indicate if a trial is monitored by a DSMB.

Assignments Due Next Time HW8: Chapter 13, problems 2, 3 and 5 Exam Two: November 18 th Can bring one 8.5 x 11” note sheet