Section outline

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  • Thursday, January 7, 2016 8:45 AM – 10:15 AM

    Lecture: Design, Subjects and Randomization

    Definition and importance of randomized controlled trials (RCT); examples of RCTs; disadvantages; alternatives; reasons for doing RCTs; randomization; inclusion/exclusion criteria; study designs including classical RCT, factorial designs, cross-over designs, matched pairs, cluster or grouped randomization.

    Faculty:  Dennis Black

    Location:      Mission Hall 1400

    • Prospectus:

    • 2016CTCoursePlan 12.15.2015 File

    • Session Slides:

    • CT Lecture 1 01.07.2016 File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 10, pages 142-147 and Chapter 11, pages 151-158.

    • Lippman S, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers. JAMA. 2009;301(1):(doi:10.1001/jama.2008.864) [Note: read abstract and comment sections, review the tables and figures and skim the rest] File
      Not available unless: Your ID number contains 02
    • Gaziano J, et al. Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians' Health Study II randomized controlled trial. JAMA 2009;301(1):(doi:10.1001/jama.2008.862) File
      Not available unless: Your ID number contains 02
    • Black DM, et al. PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003:349:1207-15. [Note: read abstract] File
      Not available unless: Your ID number contains 02
    • Section from PaTH Protocol File
      Not available unless: Your ID number contains 02

    • Optional Reading:

      Fundamentals of Clinical Trials (4th Edition), Chapters 4, 5, and 6.

    • Assignment:

              Email your research question(s) to your Section Leader on Friday, January 8,

              2016 by 5pm.

    • AssignL1 2016 File
    • Protocol Assignment 1 File

    • Assignment Due Date: 

      Exercises from Lecture 1 are due Monday, January 11, 2016 by 5pm: email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com

    • Assignment Answer Key (Access restricted to registered students):

  • Thursday, January 14, 2016; 8:45 AM – 10:15 AM

    Lecture: Blinding, Intervention and Controls

    Definition and importance of blinding; strategies if the study can’t be blinded; strategies to evaluate blinding; considerations when choosing the intervention; multiple interventions; importance of the control or placebo; advantages and disadvantages of equivalence trials.

    Faculty: Deborah Grady

    Location:  Mission Hall 1400

    • Session Slides:

    • blinding plus intervention 2016 dg db File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 10, pages 147-149.
      Fundamentals of Clinical Trials (4th Edition), Chapter 7.

    • Noseworthy H, et al. The impact of blinding on the results of a randomized, placebo-controlled multiple sclerosis clinical trial. Neurology 1994 44: 16-20. [Note: PDF doc is poor quality] File
      Not available unless: Your ID number contains 02
    • Kirkley A, et al. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2008 Sep 11;359(11):1097-107. File
      Not available unless: Your ID number contains 02

    • Assignment:

      Exercises from Lecture 2 are due Tuesday, January 19, 2016 by 5pm: email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com

    • AssignL2 2016 File

    • Assignment Due Date: 

      Email your protocol to your Section Leader by 12pm (noon) on Tuesday, January 19, 2016; bring a copy to Section I.

      Protocol assignment due for Section I:
      Draft the following sections of a protocol for a randomized trial to address your own research question (2 pages max).
      1. Research question(s)
      2. Type of randomized trial design
      3. Subjects (target and accessible populations) and inclusion/exclusion criteria.
      4. Outcome measures
      You may summarize, but do not copy from other protocols.

            

    • Assignment Answer Key (Access restricted to registered students):

  • Thursday, January 21, 2016; 8:45 AM – 10:15 AM

    Small Group Discussion Section

    Faculty:  Andy Avins, Mary Beattie, Trisha Hue, Anne Schafer, Ann Schwartz, Jeff Tice

    Location:  Avins MH-1105, Beattie MH-1106, Hue MH-1107, Schafer MH-1108 , Schwartz MH-1109, Tice MH-2500 2:30pm - 4:00pm

    • Required Reading:

      The following studies are examples of various clinical trial designs. Focus only on the methods described in each paper:

    • Dobscha SK, et al.,Collaborative care for chronic pain in primary care: a cluster randomized trial. JAMA. 2009 Mar 25;301(12):1242-52. File
      Not available unless: Your ID number contains 02
    • Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C, Ullmer L, Gallagher A, Cullen J, Gehan E, Hayes DF, Isaacs C. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005 File
      Not available unless: Your ID number contains 02

    • Resources:

    • Sample Protocol 1 File
    • Sample Protocol 2 File
    • Sample Protocol 3 File

    • Assignment: Email your protocol to your section leader by 12pm (noon) on Tuesday, January 19, 2016; bring a copy to section meeting.

      Bring your Lecture 1 & 2 homework for review.

    • Protocol Assignment 2 File

  • Thursday, January 28, 2016; 8:45 AM – 10:15 AM

    Lecture: Statistical Issues in Randomized Trials

    Pervasiveness of multiple comparisons in randomized trials; the general problem of multiple comparisons and statistical adjustments; multiple endpoints; statistical concerns about subgroup analyses; what to do with an unexpected subgroup finding; adverse experience categorization; multivariate adjustment.

    Faculty:  Dennis Black

    Location:  Mission Hall 1400

    • Session Slides:

    • stat issues L3 2016 File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 11, pages 164-166

    • Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine--reporting of subgroup analyses in clinical trials. N Engl J Med. 2007 Nov 22;357(21):2189-94. File
      Not available unless: Your ID number contains 02

    • The following 2 articles were read for Lecture 1.  For this lecture, review how statistical issues for multiple treatments, multiple outcomes and subgroups were handled.

    • Lippman S, et al. Effect of selenium and vitamin E of risk on prostate cancer and other cancers. JAMA. 2009;301(1):(doi:10.1001/jama.2008.864) File
      Not available unless: Your ID number contains 02
    • Gaziano J, et al. Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians' Health Study II randomized controlled trial. JAMA 2009;301(1):(doi:10.1001/jama.2008.862 File
      Not available unless: Your ID number contains 02

    • Optional Reading:

      Fundamentals of Clinical Trials (4th Edition), Chapter 17

    • Assignment: There is no homework assignment for Lecture 3

  • Thursday, February 4, 2016; 8:45 AM – 10:15 AM

    Lecture: Measuring Outcomes and Adverse Effects

    Defining adverse events; elicited vs. volunteered; nuisance adverse events; pitfalls of attribution of cause; FDA adverse events classifications.

    Faculty:  Steve Cummings

    Location:  Mission Hall 1400

    • Session Slides:

    • Outcomes AEs 2 2016 File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 10, pages 140-142, Chapter 11 page 162

    • Psaty BM, Lumley T. Surrogate end points and FDA approval: a tale of 2 lipid-altering drugs. JAMA. 2008 Mar 26;299(12):1474-6. File
      Not available unless: Your ID number contains 02
    • Bent S, et al. Brief communication: Better ways to question patients about adverse medical events: a randomized, controlled trial. Ann Intern Med. 2006 Feb 21;144(4):257-61. File
      Not available unless: Your ID number contains 02

    • Assignment:

      Exercises from Lecture 4 are due Monday, February 8, 2016 by 5pm: email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com.  Bring a copy to Section II.

      Email your cumulative protocol to your Section Leader by 12pm (noon) on Monday, February 8, 2016; bring a copy to Section II.

      Protocol Assignment due for Section II:

      Continue to revise the protocol sections developed for Section I. Add the following sections (4 pages total max):

      1. Control group(s)

      2. Intervention(s)

      3. Methods for randomization and blinding

      4. Methods for maximizing adherence

    • AssignL4 2016 File

    • Assignment Answer Key (Access restricted to registered students):

  • Thursday, February 11, 2016; 8:45 AM – 10:15 AM

    Small Group Discussion Section

    Faculty:  Andy Avins, Mary Beattie, Trisha Hue, Anne Schafer, Ann Schwartz, Jeff Tice

    Location:  Avins MH-1105, Beattie MH-1106, Hue MH 1107, Schafer MH-1108 , Schwartz MH-1109, Tice MH-2500 2:30pm - 4:00pm

    • Required Reading:

    • Sackett DL. Superiority trials, noninferiority trials, and prisoners of the 2-sided null hypothesis. ACP Journal Club. March/April 2004; A-11. File
      Not available unless: Your ID number contains 02
    • Granger CB, et al; Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. File
      Not available unless: Your ID number contains 02

    • Optional Reading:

    • Olanow CW, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol. 2003 Sep;54(3):403-14. File
      Not available unless: Your ID number contains 02
    • Freeman TB, et al. Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson’s disease. NEJM 341:988-91 File
      Not available unless: Your ID number contains 02
    • Macklin, R. The ethical problems with sham surgery in clinical research. NEJM 341:992-6. File
      Not available unless: Your ID number contains 02

    • Assignment: Optional narrative description

    • Protocol Assignment 3 File

  • Thursday, February 18, 2016; 8:45 AM – 10:15 AM

    Lecture: Follow-up, Adherence to the Protocol, and Post-Randomization and Introduction to Sample Size Planning

    Follow-up in RCTs; what happens after randomization; patient compliance or adherence; effect of incomplete follow-up; strategies to enhance compliance; intention-to- treat and per-protocol analyses; analysis based on post-randomization; subgroup analysis.

    Faculty:  Dennis Black

    Location:      Mission Hall 1400

    • Session Slides:

    • follow up 2016 draft 10 pm File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 6, pages 55-59 and Chapter 11, pages 160-162.

      Fundamentals of Clinical Trials (4th Edition), Chapter 14.

    • Hollis and Campbell. What is meant by intention to treat analysis? Survey of published randomized controlled trials. BMJ 1999:319;670-4. File
      Not available unless: Your ID number contains 02

    • Assignment:

      Exercises from Lecture 5 are due February 22, 2016 by 5pm; email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com

    • AssignL5 2016 File

    • Assignment Due Date:  February 22, 2016 by 5pm

    • Assignment Answer Key (Access restricted to registered students):

    • AnswerAssignL5 2016 File
      Available until end of March 30, 2016

  • Thursday, February 25, 2016; 8:45 AM – 10:15 AM

    Lecture:  Ethics in Clinical Trials and Interim Monitoring
    Ethical issues in clinical trials, including choice of interventions in control and intervention groups, randomization, selection of subjects, and interim analyses

    Why alter/stop a clinical trial early; who should decide to stop the trial; what parameters should be monitored and how often; what statistical methods should be used; statistical approaches

    Faculty:  Deborah Grady

    Location:     Mission Hall 1400

    • Session Slides:

    • Ethics and Interim Monitoring 2016 File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 11, pages 163-164 and 168-169.

    • Lo B. Ethical issues in clinical trials, pages 1-7. File
      Not available unless: Your ID number contains 02
    • Dixon D, Freedman R et al.. Guidelines for data and safety monitoring for clinical trials not requiring traditional data monitoring committees. Clinical Trials 2006. Nov 3: 314-19. File
      Not available unless: Your ID number contains 02
    • Bryant J and Wolmark N. Letrozole after tamoxifen for breast cancer--what is the price of success? N Engl J Med. 2003 Nov 6;349(19):1855-7. File
      Not available unless: Your ID number contains 02

    • Optional Reading:

    • DeMets DL, Pocock SJ, Julian DG. The agonizing negative trend in monitoring of clinical trials. Lancet 1999:354:1983-88. File
      Not available unless: Your ID number contains 02

    • Assignment:

      Exercises from Lecture 6 are due February 29, 2016 by 5pm; email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com

      Email your cumulative protocol to your section leader by 12pm (noon) on Monday, February 29, 2016; bring a copy to section.

      Assignment due for Section III:

      Continue to develop and finalize sections of your protocol started in prior sections. Draft the following sections (6-7 pages total max):

      1. Adverse event and side effect measures

      2. Plans for interim monitoring

      3. List one or two ethical issues related to your protocol and how you plan to manage them.

    • AssignL6 2016 File
    • Sample Protocol 1 File
    • Sample Protocol 2 File
    • Sample Protocol 3 File

    • Assignment Answer Key (Access restricted to registered students):

    • AnswerAssignL6 2016 File
      Available until end of March 30, 2016

  • Thursday, March 3, 2016; 8:45 AM – 10:15 AM

    Small Group Discussion Section

    Faculty:  Andy Avins, Mary Beattie, Trisha Hue, Anne Schafer, Ann Schwartz, Jeff Tice

    Location:  Avins MH-1105, Beattie MH-1106, Hue MH 1107, Schafer MH-1108 , Schwartz MH-1109, Tice MH-2500 2:30pm - 4:00pm

    • Required Reading:

    • Montori VM, Devereaux PJ, Adhikari NK, et al. Randomized trials stopped early for benefit: a systematic review .JAMA. 2005 Nov 2;294(17):2203-9. Note: read abstract only File
      Not available unless: Your ID number contains 02
    • Pocock SJ. When (not) to stop a clinical trial for benefit. JAMA. 2005 Nov 2:294(17):2228-30. File
      Not available unless: Your ID number contains 02

    • Final Exam: 

      Take Home Final Exam to be posted on course website on March 3, 2016; and is due by 10am on Friday, March 11, 2016. Email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com

    • CT Course Final Exam 2016. doc File

    • Final Exam Due Date: 10am on Friday, March 11, 2016.

  • Thursday, March 10, 2016; 8:45 AM – 10:15 AM

    Lecture:  Nuts and Bolts  - Conducting a Trial

    Should one do a trial; pilot studies; funding sources; contracts; budgets; the study team; team management; space; recruitment of study subjects; starting the protocol; forms; compliance and follow-up; final visit and post-trial.

    Faculty:  Deborah Grady

    Location:      Mission Hall 1400

    • Session Slides:

    • Pilot Studies and N+B 2016 File

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Designing Clinical Research (4th Edition), Chapter 11, pages 158-159 and Chapter 17.

    • Assignment: There is no homework assignment for Lecture 7.

    • Final Exam: 

      Take Home Final Exam due March 11, 2016 by 10am, email to Teaching Assistants at UCSFClinicalTrials2016@gmail.com

  • Thursday, March 17, 2016; 8:45 AM – 10:15 AM

    Lecture: Multicenter Studies and Industry-sponsored trials
    The anatomy and physiology of multicenter trials. How to work effectively and make use of data from such trials. How industry trials operate. Pros and cons of participation in industry sponsored trials and principles that may minimize bias.

    Faculty:  Steve Cummings

    Location:      Mission Hall 1400

    • Session Slides:

    • Session Audio/Video Recording (Access restricted to registered students):

    • Required Reading:

      Fundamentals of Clinical Trials (4th Edition), Chapter 8, pages 159-161.

      (Other readings may be distributed before the lecture)

    • Assignment: There is no homework assignment for Lecture 8