BMTRY 781

Methods in Clinical Cancer Research

Spring 2015

 

Description: Didactic lectures will cover the following areas: (1) clinical and statistical design of phase I, II and III trials; (2) incorporation of correlative and biomarkers in clinical trials, (3) considerations in chemotherapy, surgery, radiation and multimodality trials, (4) quality of life and other patient reported outcomes in cancer research, (5) the protocol review and IRB process, (6) informed consent, (7) data collection, trial monitoring and investigator responsibilities, (8) the grants process and mentoring. Other topics are incorporated as well, (e.g., disparities research). In addition to the didactic portions of the training, each trainee will have a clinical research proposal which will be developed into a “letter of intent” (LOI) for a clinical trial. In addition to the didactic sessions , contact hours will take the form of a journal club where clinical research papers from journals such as Clinical Cancer Research or Journal of Clinical Oncology are discussed, and protocols that are being undertaken at HCC are reviewed and discussed.  Lastly, trainees will also be required to attend and take part in the HCC Protocol Review Committee’s monthly meetings (meetings occur every 3 weeks). This will allow the trainees to be exposed to a variety of studies ranging from Phase I to III cancer trials, in addition to observational, translational and qualitative research studies. Trainees will also be encouraged to attend one or more of the HCC Data Safety and Monitoring Board meetings to gain exposure to issues of trial review and monitoring.

 

Course Organization: This course is organized by Dr. Elizabeth Garrett-Mayer who is also the primary instructor. Some lectures are given by other faculty members and senior students or fellows as appropriate.

 

Textbooks: No textbook. Reading material (primarily found on the web) will be provided as necessary. This will include journal articles in clinical trial and cancer research journals.  Suggested textbooks for reference include:

o   Clinical Trials: A Methodologic Perspective (Piantadosi)

o   Oncology Clinical Trials (Kelly & Halabi)

o   Principles of Anti-Cancer Drug Development (Hidalgo, Eckhardt, Garrett-Mayer, Clendennin)

 

Prerequisites: eligible students must satisfy at least one of the following criteria:

(1)  The student is enrolled in the MSCR program,

(2)  The student is a Paul Calabresi K-12 training grant scholar.

(3)  The student is enrolled in a masters or PhD program in the Dept. of Public Health Sciences

(4)   The student has received consent of the instructor.

 

 

Assessment of Students: Students will be graded based on the following components where each assignment is given numeric score, according to the Merit Grades for the MUSC grading system.

1)    Written reviews of protocols, given as assignments. There will be 3-4 protocols assigned and the review will be structured with particular questions about appropriateness of study design, clarity of the study aims, incorporation of early stopping rules in the trial design, etc. (45% of grade)

2)    Oral presentation of journal article presenting results of a cancer clinical trial. The article will be selected by the student and Dr. Garrett-Mayer. The student will present to the class an overall summary of the trial and provide a critique of the methods employed. (25% of grade)

3)    Submitted LOI: The LOI will be submitted twice. First, a draft will be submitted about two-thirds through the course. Dr. Garrett-Mayer will provide feedback. This first draft will constitute 15% of the total grade. The final LOI will be submitted as the ‘final’ and will also count for 15% of the course grade. Total: 30% of grade

 

Homeworks Policy:  Homeworks are due by 5pm on the due date. All homeworks should be emailed to the primary instructor (garrettm@musc.edu) or turned in at lecture time. Asking for extensions on homeworks is strongly discouraged. However, it is expected that, on occasion, extenuating circumstances may arise. Therefore, the policy is that each student may request an extension on homework twice and the extension is to be no more than 2 days. You must notify the primary instructor that you are requesting an extension before the time the assignment is due. After using two extensions, no more extensions will be granted except with a medical note.

 

Office Hours: The primary instructor will have office hours by appointment.

 

Course Objectives: At the end of the course, students should be able to:

1)    Understand the key components required for designing, activating and implementing a cancer clinical trial.

2)    Write a proposal for a cancer clinical trial, including objectives, endpoints, trial design, patient population selection, and have some understanding of the required sample size and analytic techniques used to analyze the data at the end of the trial.

3)    Effectively review and critique clinical trial protocols and published cancer clinical trials research.

 

Primary Instructor:

 

Elizabeth Garrett-Mayer

Website:

 

http://people.musc.edu/~elg26/teaching/statcomputing.2014/statcomputingI.2014.htm

Contact Info:

 

Hollings Cancer Center, Rm 118G

garrettm@musc.edu (preferred mode of contact is email)

Time:

 

Tuesdays and Thursdays, 1:30-3:00pm

Location:

 

BSB 302

Office Hours:

 

By appointment. Contact via email.

 

 

 

Tentative Lecture Schedule:

 

Lecture number

Date

Topic

Instructor

Notes and links

1

Tu Jan 6

Introduction

EGM

Lecture1_Intro.pptx

LoRusso, et al.

Seymour, et al

Sullivan

2

Th Jan 8

Intro (continued)

EGM

PhaseIPart1.pptx

Weberetal.pdf

3

Tu Jan 13

Phase I trials: practical considerations

EGM

Ivyetal.pdf

4

Th Jan 15

No class

 

 

5

Tu Jan 20

Phase I trial designs

EGM

Phase1trials_part2.pptx

6

Th Jan 22

Phase I in practice: current topics/controversies

EGM

Phase1trials_part3.pptx

Dahlberg.pdf

IasonosOQuigley.pdf

Nivolumumab.Design.pdf

Nivolumumab.PhaseII.pdf

Nivolumumab.protocol.pdf

Pembrolizumab_keytruda.pdf

PressAnouncement.keytruda.pdf

PressAnnouncement.nivolumumb.pdf

Ratain.pdf

Weberetal.pdf

 

7

Tu Jan 27

Phase II trials: practical considerations

EGM

StdPhaseIIDesignIssues.ppt

Rubinsteinetal.pdf

Ratainsargent.pdf

8

Th Jan 29

No class

EGM

9

Tu Feb 3

Phase II trial designs

EGM

phaseII_part2.ppt

Bayesmovie.wmv

10

Th Feb 5

Phase II trials: challenges for the future (and present)

EGM

Improving Phase II Designs.pptx

Adjei, Christian, Ivy

Dhani et al.

Note: Phase I trial review due

11

Tu Feb 10

Quality of Life and patient reported outcomes

Katie Sterba

Sterba PROMS for Methods Class021015.pptx

12

Th Feb 12

Biomarker clinical trial designs       

EGM

Biomarkers in Phase II designs in cancer clinical.pptx

McShane et al.

Freidlin et al.

Lopez-Chaves et al.

Redig & Janne

13

Tu Feb 17

Phase III trial designs

EGM

Phase III trials in oncology.pptx

Ellis et al

14

Th Feb 19

Other designs: phase 0, window of opportunity, Bayesian adaptive.

EGM

OtherDesigns.pptx

BattleDesign1.pdf

BattleResults1.pdf

Battle_sorafenib.pdf

Battle_vandetanib.pdf

Phase0.pdf

Ispy.pdf

Yoga.pdf

Cranialirrad.pdf

Ellis.pdf (Matthew Ellis’ slides)

L-3.02-J.Jack-Lee.pdf (jack lee’s slides)

15

Tu Feb 24

 

EGM

 

16

Th Feb 26

Data safety and monitoring

EGM

SAE Reporting and Data Safety Monitoring Boards.ppt

Corkery.pdf

Whitehead.pdf

17

Tu Mar 3

Endpoint selection issues /Power calculations

EGM

Power_endpoints.pptx

18

Th Mar 5

The IRB process: part 1

Susan Sonne

HCC Presentation Slides.pptx

Note: phase II trial assignment due

19

Tu Mar 10

Spring break (no class)

 

Obsnlstudies.pptx

Jansenetal.pdf

Pundole.pdf

Rebbeck.pdf

Fitzgerald.pdf

 

Th Mar 12

Spring break (no class)

 

 

 

Tu Mar 17

Observational studies

EGM

Obsnlstudies.pptx

Rebbeck et al.

Jansen et al.

Pundole et al.

Fitzgerald et al.

20

Th Mar 19

The IRB process: part 2

Susan Sonne

(see slides from 3/5/15)

21

Tu Mar 24

Local protocol process and the CTO

Terri Matson

Methods in Clinical Cancer Research Class_CTO issues March 2015.pptx

22

Th Mar 26

Grants and grant writing

Anita Harrison

Grants101.ppt

23

Tu Mar 31

Disparities research

Ford

Ford lecture.pdf

24

Th Apr 2

Prevention and Control studies

Kristin Wallace

METHODS_4.2.2015.pdf

25

Tu Apr 7

Correlative studies

EGM

Regan_correlatives.pptx

JCO1.pdf

JCO_letter.pdf

26

Th Apr 9

Tobacco Cessation in Clinical Cancer Trials

Graham Warren

 

27

Tu Apr 14

Radiation and Multimodality Trials

Graham Warren

 

28

Th Apr 16

Imaging Endpoints

James Ravenel

 

29

Tu Apr 21

Informed Consent Process

EGM

InformedConsent(StacyBerg).pdf

NCItemplate.doc

SimplificationofIC.doc

Tips.doc

SimpleWords&Phrases.doc

StanfordGlosary.pdf

StateLaws.doc

30

Th Apr 23

Tissue testing methods

Laura Spruill

 

31

Tu Apr 28

Work-Life Balance

EGM

WLB.pptx

Work-Life_Balance_R-Harrison.pdf

·      Kuerer etal. Career Satisfaction, Practice Patterns and Burnout among Surgical Oncologists.

·      Shanafelt etal. Satisfaction with work-life balance and the career and retirement plans of US oncologists.

·      Balancing your life at work and home. Journal of Oncology Practice.

·      Shanafelt et al. Shaping your career to maximize personal satisfaction in the practice of oncology.

·      Shanafelt. A career in surgical oncology: finding meaning, balance, and personal satisfaction.

·      Shanafelt. Finding meaning, balance and personal satisfaction in the practice of oncology.

 

Homework Assignments:

 

1) Phase I trial review:  Select one of the following protocols (RTOG0017, RTOG0241, Nivolumumab (either final or initial).  Fill out review template: PhaseIReview.docx. 

Please submit by Thursday, Feb 5 @ 5pm to garrettm@musc.edu.

 

2) Phase II trial designs:

            For Biostatistics grad students:  TrialCharacteristics.PhaseII.docx

            For K-12 scholars/MDs: PhaseIIReview.docx

Please submit by Thursday, Mar 5 @ 5pm to garrettm@musc.edu

 

3) Phase III trial designs:

For Biostatistics grad students: HomeworkIII.docx

 

 

Tumor Boards Schedule

PRC and DSMB Schedule, Spring 2015