Section outline

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  • Thursday, January 10, 2019 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:

    • 2019CTCoursePlan 12.27.2018 File

    • Session Slides:

    • CT Lecture 1 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:

              1) Email your research question(s) to your section leader on Friday, January 11, 2019 by 5pm.

              2) Complete homework assignment #1 and submit to TAs by Monday, January 14, 2019, 5pm at UCSFClinicalTrials2019@gmail.com

              3) Work on protocol assignment #1 and submit to your section leader by Tuesday, January 22, 2019, 12pm. Please scroll down to section 1 (January 24, 2019) for sample protocols.

    • AssignL1 2019 File
    • Protocol Assignment 1 File

    • Assignment Due Date: 

      Exercises from Lecture 1 are due Monday, January 14, 2019 by 5pm: email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com

      Protocol assignment #1 due to section leaders on Tuesday, January 22, 2019 at 12pm. 

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

  • Thursday, January 17, 2019; 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:

    • Blind + Inter 2019 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. 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:

    • AssignL2 2019 File

    • Assignment Due Date: 

      Homework for lecture 2 is due on Tuesday, January 22, 2019 at 5pm. Please email to TAs at UCSFClinicalTrials2019@gmail.com

      Email your protocol assignment #1 to your Section Leader by 12pm (noon) on Tuesday , January 22, 2019; 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):

    • AnswerAssignL2 2019 File

  • Thursday, January 24, 2019; 8:45 AM – 10:15 AM

    Small Group Discussion Section

    Faculty:  Andy Avins, Trisha Hue, Patrick Phillips, Alice Pressman, Anne Schafer

    Location:  Avins MH-1105, Hue MH-1106, Phillips MH-1107, Pressman MH-1108, Schafer MH-1109

    • 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

    • Sample Protocols

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

    • Notes & Assignment:

      Please bring the following to section #1:

      1) Protocol assignment #1 (emailed to your section leader by January 22, 2019)

      2) Lecture 1 & 2 homework for review

      Assignment: Work on protocol assignment #2

    • Protocol Assignment 2 File

    • Assignment Due Date:  Protocol assignment #2 due to section leaders by February 11, 2019 @ 12pm (noon)

  • Thursday, January 31, 2019; 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 2019 db 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 7, 2019; 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:  Dennis Black

    Location:  Mission Hall 1400

    • Session Slides:

    • outcomes and events vers 2-8-19 final 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
    • Miller, PD., et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis a randomized clinical trial. Jama 316.7 (2016) 722-733. File
      Not available unless: Your ID number contains 02
    • Black, DM., et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New England Journal of Medicine 356.18 (2007) 1809-1822. File
      Not available unless: Your ID number contains 02

    • Homework Assignment: Exercises from Lecture 4 are due Monday, February 11, 2019 by 5pm: email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com.  Bring a copy to Section II.

      Protocol Assignment due for Section II: Email your cumulative protocol to your Section Leader by 12pm (noon) on Monday, February 11, 2019; bring a copy to Section II.

      Continue to revise the protocol sections developed for Section I. Please see protocol assignment #2 for instructions.

    • AssignL4 2019 File
    • Protocol Assignment 2 File

    • Assignment Due Date:  

      Protocol assignment #2 is due Monday, February 11, 2019 by 12pm; email to Section Leader.

      Homework exercises from Lecture 4 are due Monday, February 11, 2019 by 5pm; email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com.

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

  • Thursday, February 14, 2019; 8:45 AM – 10:15 AM

    Small Group Discussion Section

    Faculty:  Andy Avins, Trisha Hue, Patrick Phillips, Alice Pressman, Anne Schafer

    Location:  Avins MH-1105, Hue MH-1106, Phillips MH-1107, Pressman MH-1108, Schafer MH-1109

    • 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

    • Section reminders: Email your cumulative protocol to your section leader by 12pm (noon) on Monday, February 11, 2019; bring a copy to section.

      Bring your Lecture 4 homework for review.

    • Assignment: Work on protocol assignment #3.

    • Protocol Assignment #3 File

    • Protocol Assignment Due Date: Email your cumulative protocol assignment to your section leader by 12pm (noon) on March 18, 2019. Bring a copy to section #3.

  • Thursday, February 21, 2019; 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 and adherence 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 25, 2019 by 5pm; email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com

    • AssignL5 2019 File

    • Assignment Due Date:  February 25, 2019 by 5pm

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

  • Thursday, February 28, 2019; 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:  Dennis Black 

    Location:      Mission Hall 1400

    • Session Slides:

    • Multictr-Industry 2-27-19 9 pm File
    • UCSF public data methods forum 2-25-19 File

    • 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 6.

  • Thursday, March 7, 2019; 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:  Alison Huang

    Location:     Mission Hall 1400

    • Session Slides:

    • Trial Ethics and Interim Monitoring 2019 3-7-19 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

    • Homework Assignment: Exercises from Lecture 7 are due March 11, 2019 by 5pm; email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com

      Protocol Assignment: Email your cumulative protocol to your section leader by 12pm (noon) on March 18, 2019; bring a copy to section #3.

      Assignment due for Section III:

      Continue to develop and finalize sections of your protocol started in prior sections. Draft the following sections stated in protocol assignment #3

    • AssignL7 2019 File
    • Protocol Assignment 3 File
    • Sample Protocol 1 File
    • Sample Protocol 2 File
    • Sample Protocol 3 File

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

  • Thursday, March 14, 2019; 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 2019 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 8.

    • Final Exam: Take Home Final Exam to be posted on course website on March 15, 2019; and is due by 10am on Friday, March 22, 2019. Email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com

    • EPI 205 Final File
      Not available unless: You belong to a group in Registered Students Only

  • Thursday, March 21, 2019; 8:45 AM – 10:15 AM

    Small Group Discussion Section

    Faculty:  Andy Avins, Trisha Hue, Patrick Phillips, Alice Pressman, Anne Schafer

    Location:  Avins MH-1105, Hue MH-1106, Phillips MH-1107, Pressman MH-1108, Schafer MH-1109

    • 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 15, 2019; and is due by 10am on Friday, March 22, 2019. Email to Teaching Assistants at UCSFClinicalTrials2019@gmail.com

    • Final Exam Due Date:  Friday, March 22, 2019, 10am.