Lecture 1: Design, Subjects and Randomization

Required Reading:

1. Designing Clinical Research (3rd Edition), Chapter 10, pages 152-157 and Chapter 11, pages 163-168 and 177.
2. 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]
3. 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) [Note: read abstract; skim the rest]
4. 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]
5. Section from PaTH Protocol

Optional Reading:

1. Friedman, Furberg and DeMets. Chapters 3, 4, and 5.

Note/Slide Files: 2010CTCoursePlan_010710.doc (95 KB) CT2010_calendar.doc (67 KB) Lecture_1.ppt (1537 KB)

Assignment:
Exercises from Lecture 1 are due Monday, January 11 by 5 PM: email to Vivek Jain at clinicaltrials2010@yahoo.com.

Assignment Files: AssignL1_2010.doc (37 KB)

Assignment Answer Files: L1_Homework_Answers_2010.doc (47 KB)

Lecture 2: Blinding, Intervention and Controls

Required Reading:

1. Designing Clinical Research (3rd Edition), Chapter 10, pages 157-159
2. Friedman, Furberg and DeMets Chapter 6
3. 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
4. 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.

Note/Slide Files: Lecture_2.ppt (137 KB)

Assignment:
Exercises from Lecture 2 are due Tuesday, January 19 by 5 PM clinicaltrials2010@yahoo.com.

Assignment Files: AssignL2_2010.doc (33 KB)

Assignment Answer Files: L2_Homework_Answers_2010.doc (48 KB)

Lecture 3: Measuring Outcomes and Adverse Effects

Required Reading:

1. Designing Clinical Research (3rd Edition), Chapter 10, pages 150-151, Chapter 11 pages 173-174.
2. 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.
3. 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.

Optional Reading:

1. Guidance for clinical investigators, sponsors and IRBS: Adverse Event Reporting to IRBs – Improving Human Subject Protection. January 2009 Procedural

Note/Slide Files: Lecture_3.pdf (860 KB)

Assignment:
Exercises from Lecture 3 are due Monday, January 25 by 5 PM. clinicaltrials2010@yahoo.com

Assignment Files: AssignL3_2010.doc (47 KB)

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Required Reading:

1. 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.
2. 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 Oct 1;23(28):6919-30.

Assignment:
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. Email your protocol to your section leader by noon on Monday, January 18; bring a copy to section. Bring your homework for review: Lectures 1 and 2.

Assignment Files: AssignS1_2010.doc (32 KB)

Lecture 4: Statistical Issues in Randomized Trials

Required Reading:

1. Designing Clinical Research (3rd Edition), Chapter 11, pages 177-179
2. 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.
3. 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.
4. 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)
5. 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)

Optional Reading:

1. Friedman, Furberg and DeMets, Chapter 16

Note/Slide Files: Lecture_4_2010.ppt (2142 KB)

Lecture 5: Follow-up, Adherence to the Protocol and Post-Randomization

Required Reading:

1. Designing Clinical Research (3rd Edition), Chapter 11, pages 170-173.
2. Friedman, Furberg and DeMets, Chapter 13.
3. Hollis and Campbell. What is meant by intention to treat analysis? Survey of published randomized controlled trials. BMJ 1999:319;670-4.

Note/Slide Files: Lecture_5_2010.ppt (2379 KB)

Assignment:
Exercises from Lecture 5 are due Monday, February 8 by 5 PM. clinicaltrials2010@yahoo.com.

Assignment Files: AssignL5_2010rev.doc (35 KB)

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Required Reading:

1. Sackett DL. Superiority trials, noninferiority trials, and prisoners of the 2-sided null hypothesis. ACP Journal Club. March/April 2004; A-11.
2. Parienti, JJ, et al. Hand-rubbing with an aqueous alcoholic solution vs. traditional surgical hand-scrubbing and 30-day surgical site infection rates. A randomized equivalence study. JAMA 2002;288:722-7. [Note: focus on equivalence study design, randomization process and “blinding” issue.]

Optional Reading:

1. [Note: this study provides a very interesting example regarding choosing a proper control for an invasive intervention.] 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.
2. Freeman TB, et al. Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson’s disease. NEJM 341:988-91.
3. Macklin, R. The ethical problems with sham surgery in clinical research. NEJM 341:992-6.

Assignment:
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
Email your cumulative protocol to your section leader by noon on Monday, February 1; bring a copy to section. Bring your homework for review: Lecture 3

Assignment Files: AssignS2_2010.doc (24 KB)

Lecture 6: Ethics in Clinical Trials and Interim Monitoring

Required Reading:

1. Designing Clinical Research, Chapter 11 page 174-176 and 180-181.
2. Lo B. Ethical issues in clinical trials.
3. 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.
4. 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.

Optional Reading:

1. DeMets DL, Pocock SJ, Julian DG. The agonizing negative trend in monitoring of clinical trials. Lancet 1999:354:1983-88

Assignment:
Exercises from Lecture 6 are due Tuesday, February 16 by 5 PM. clinicaltrials2010@yahoo.com

Assignment Files: AssignL6_2010rev.doc (32 KB)

Lecture 7: Nuts and Bolts-Conducting a Trial

Required Reading:

1. Designing Clinical Research (3rd Edition), Chapter 11, pages 168-170 and Chapter 17.

Assignment:
Take Home Final Exam to be distributed; due Thursday, March 4 by 5 PM

Lecture 8: Multicenter Studies and Industry-sponsored trials

Required Reading:

1. Friedman, Furberg and DeMets, Chapter 7, pages122-123.

Optional Reading:

1. Psaty BM, Furberg CD, Ray WA, Weiss NS. Potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis. JAMA. 2004 Dec 1;292(21):2622-31.

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Required Reading:

1. 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
2. Pocock SJ. When (not) to stop a clinical trial for benefit. JAMA. 2005 Nov 2;294(17):2228-30.

Assignment:
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.
Email your cumulative protocol to your section leader by noon on Monday, February 22; bring a copy to section. Bring your homework for review: Lectures 5 and 6

Assignment Files: AssignS3_2010.doc (25 KB)