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Clinical Trials Clinical Trials: Highlights from Design to Conduct Masha Kocherginsky, PhD Biostascs Collaboraon Center Department of Prevenve Medicine Stascally Speaking … What’s next? Clinical Trials: Highlights from Design to Conduct Masha KocherginsKy, Friday, October 21 PhD, Associate Professor, Division of BiostaOsOcs, Department of Prevenve Medicine Finding Signals in Big Data Kwang-Youn A. Kim, PhD, Assistant Tuesday, October 25 Professor, Division of Biostascs, Department of Prevenve Medicine Enhancing Rigor and Transparency in Research: Adopng Tools Friday, October 28 that Support Reproducible Research Leah J. Welty, PhD, BCC Director, Associate Professor, Division of BiostaOsOcs, Department of Prevenve Medicine All lectures will be held from noon to 1 pm in Hughes Auditorium, Robert H. Lurie Medical Research Center, 303 E. Superior St. 2 BCC: Biostascs Collaboraon Center Who We Are Leah J. Welty, PhD Joan S. Chmiel, PhD Jody D. Ciolino, PhD Kwang-Youn A. Kim, PhD Assoc. Professor Professor Asst. Professor Asst. Professor BCC Director Alfred W. Rademaker, PhD Masha Kocherginsky, PhD Mary J. Kwasny, ScD Julia Lee, PhD, MPH Professor Assoc. Professor Assoc. Professor Assoc. Professor Not Pictured: 1. David A. Aaby, MS Senior Stat. Analyst 2. Tameka L. Brannon Financial | Research Hannah L. Palac, MS Gerald W. Rouleau, MS Amy Yang, MS Administrator Senior Stat. Analyst Stat. Analyst Senior Stat. Analyst Biostascs Collaboraon Center |680 N. Lake Shore Drive, Suite 1400 |Chicago, IL 60611 3 BCC: Biostascs Collaboraon Center What We Do Our mission is to support FSM inves>gators in the conduct of high- quality, innovave health-related research by providing exper>se in biostas>cs, stas>cal programming, and data management. 4 BCC: Biostascs Collaboraon Center How We Do It Stas>cal support for Cancer-related projects or The BCC recommends Lurie Children’s should be reques>ng grant triaged through their support at least 6 -8 available resources. weeks before submission deadline We provide: Study Design BCC faculty serve as Co- YES Inves>gators; analysts Analysis Plan serve as Biostas>cians. Power Sample Size Are you wri*ng a Recharge Model grant? (hourly rate) Short Short or long term NO collaboraon? Long Subscrip>on Model Every inves>gator is (salary support) provided a FREE ini>al consultaon of up to 2 hours with BCC faculty of staff 5 BCC: Biostascs Collaboraon Center How We Do It Stas>cal support for Cancer-related projects or The BCC recommends Lurie Children’s should be reques>ng grant triaged through their support at least 6 -8 available resources. weeks before submission deadline We provide: Study Design BCC faculty serve as Co- YES Inves>gators; analysts Analysis Plan serve as Biostas>cians. Power Sample Size Are you wri*ng a Recharge Model grant? (hourly rate) Short Short or long term NO collaboraon? Long Subscrip>on Model Every inves>gator is (salary support) provided a FREE ini>al consultaon of up to 2 hours with BCC faculty of staff 6 BCC: Biostascs Collaboraon Center How can you contact us? • Request an Appointment - hp://www.feinberg.northwestern.edu/sites/bcc/contact-us/request- form.html • General Inquiries - [email protected] - 312.503.2288 • Visit Our Website - hp://www.feinberg.northwestern.edu/sites/bcc/index.html Biostascs Collaboraon Center |680 N. Lake Shore Drive, Suite 1400 |Chicago, IL 60611 7 What we’ll be talking about today 8 Outline • What is a clinical trial? • Why a clinical trial? • What do we think of when we hear “clinical trial”? • Highlights of clinical trial design and conduct: - What’s the big ques>on? - Choosing endpoints - Clinical trial phases and designs - Logiscs • Conclusions 9 What is a clinical trial? 10 What Is a Clinical Trial? NIH Definion (October 23, 2014, NOT-OD-15-015) A research study1 in which one or more human subjects2 are prospecvely assigned3 to one or more intervenons4 (which may include placebo or other control) to evaluate the effects of those intervenons on health- related biomedical or behavioral outcomes.5 11 What Is a Clinical Trial? NIH Definion (October 23, 2014, NOT-OD-15-015) A research study1 in which one or more human subjects2 are prospecvely assigned3 to one or more intervenons4 (which may include placebo or other control) to evaluate the effects of those intervenons on health- related biomedical or behavioral outcomes.5 - Research means a systemac invesgaon, including research development, tesng and evaluaon, designed to develop or contribute to generalizable knowledge. 45 CFR 46.102(d) 12 What Is a Clinical Trial? NIH Definion (October 23, 2014, NOT-OD-15-015) A research study1 in which one or more human subjects2 are prospecvely assigned3 to one or more intervenons4 (which may include placebo or other control) to evaluate the effects of those intervenons on health- related biomedical or behavioral outcomes.5 - Human subject means a living individual about whom an invesgator (whether professional or student) conducng research obtains (1) data through intervenon or interacon with the individual, or (2) idenfiable private informaon 45 CFR 46.102(d) 13 What Is a Clinical Trial? NIH Definion (October 23, 2014, NOT-OD-15-015) A research study1 in which one or more human subjects2 are prospecvely assigned3 to one or more intervenons4 (which may include placebo or other control) to evaluate the effects of those intervenons on health- related biomedical or behavioral outcomes.5 - Prospecvely assigned refers to a pre-defined process (e.g., randomizaon) specified in an approved protocol that s>pulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervenon, placebo, or other control) of a clinical trial. - Note: all subjects in a trial could be assigned to the same interven?on (single arm trials) 14 What Is a Clinical Trial? NIH Definion (October 23, 2014, NOT-OD-15-015) A research study1 in which one or more human subjects2 are prospecvely assigned3 to one or more intervenons4 (which may include placebo or other control) to evaluate the effects of those intervenons on health- related biomedical or behavioral outcomes.5 - Intervenon - a manipulaon of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: • drugs behavior (e.g., diet, cognive • biologics therapy, exercise) • devices • prevenon strategies • procedures (e.g., surgical techniques) • diagnosc strategies • delivery systems (e.g., telemedicine, face-to-face interviews) • strategies to change health-related 15 What Is a Clinical Trial? NIH Definion (October 23, 2014, NOT-OD-15-015) A research study1 in which one or more human subjects2 are prospecvely assigned3 to one or more intervenons4 (which may include placebo or other control) to evaluate the effects of those intervenons on health-related biomedical or behavioral outcomes.5 - Health-related biomedical or behavioral outcome - pre-specified goal(s) or condion(s) that reflect the effect of the intervenon on human subjects’ biomedical or behavioral status or quality of life. - Examples include changes in: • physiological or biological parameters (e.g., improvement of lung capacity, gene expression) • psychological outcomes (e.g. mood management intervenon in smokers) • neurodevelopmental outcomes (e.g. school performance in children) • disease processes • health-related behaviors • quality of life 16 Classificaon of clinical research Grimes, D. A, & Schulz, K. F. (2002). Epidemiology 1: An overview of clinical research: the lay of the land. Lancet, 359(9300), 57–61 17 Why a clinical trial? 18 Clinical Trials vs. Other Study Designs • Other types of studies include: - Case reports and anecdotal evidence - Case series and observaonal studies - Database analyses - Case-control studies - Prospecve cohort studies • A variety of limitaons: - selecon bias - lack of appropriate controls - recall bias (retrospecve assessment) - confounding • Clinical trials: - prospecve and planned - assign treatment by design - eliminate many biases via randomiza>on, blinding, and appropriate controls Example: Women’s Health Iniave (WHI) trials • Leading causes of mortality and morbidity among postmenopausal women: - osteoporosis - cardiovascular disease (CHD) - cancer • Age-related estrogen deficiency believed to play a role • Based on observaonal studies, hormone replacement therapy (HRT) was widely used for disease prevenon via treatment of postmenopausal estrogen deficiency • 1991: NIH policy to require inclusion of women in clinical research 20 Example: Women’s Health Iniave (WHI) trials • Women’s Health Ini>ave (WHI) was ini>ated by NIH, and conducted three large randomized controlled prevenon clinical trials - Postmenopausal women, age 50-79, 40 clinical centers - 15 years, $625M funding, >112,000 women enrolled - Findings: • HRT increased risk of CHD, stroke and demena, breast cancer • No effect on overall mortality • Many of the original hypotheses were not supported by the clinical trials • Overall risks far outweigh the benefits - Dramac reducon in HRT use, followed by reducon in breast cancer rates - $37.1B return on investment (reducon in health expenditure and beer quality adjusted life-years) 21 What do we think of when we hear “clinical trial”? 22 What do we think of when we hear “clinical trial”? • Clinical trials frequently get reported in the news - Large trials - Expensive trials - Or when things go wrong 23 Drug Development Cycle Time in years 0 1 2 3 4 5 6 7 8 9 10 11 hp://www.phrma.org/advocacy/research-development/clinical-trials 24 Drug Development Cycle Time in years 0 1 2 3 4 5 6 7 8 9 10 11 • Drug development is expensive and me-consuming (10-12 years) • Clinical trials are the longest and most expensive component • Most drugs fail in larger clinical trials “The average R&D cost required to bring a new, FDA-approved medicine to paents is esmated to be $2.6 billion over the past decade (in 2013 dollars), including the cost of the many potenal medicines that do not make it through to the FDA approval.
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